Abstract Supplement: 2017 ACR/ARHP Annual Meeting November 3-8, 2017 San Diego, CA

Volume 69 • Number S10 • October 2017
ABSTRACT SUPPLEMENT
2017 ACR/ARHP Annual Meeting
November 3–8, 2017
San Diego, CA
None: Has no relevant financial relationship to
disclose.
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None: Has no relevant financial relationship to
disclose.
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Abstract Number: 1L
Efficacy and Safety of Intra-Articular Sprifermin in

Symptomatic Radiographic Knee Osteoarthritis:
Results of the 2-Year Primary Analysis from a 5-Year
Randomised, Placebo-Controlled, Phase II Study
Marc C. Hochberg1, Ali Guermazi2, Hans Guehring3, Aida Aydemir4, Stephen Wax5,
Patricia Fleuranceau-Morel4, Asger Reinstrup Bihlet6, Inger Byrjalsen6, Jeppe Ragnar
Andersen6 and Felix Eckstein7, 1University of Maryland School of Medicine, Baltimore,
MD, 2Boston Imaging Core Lab, LLC, and Boston University School of Medicine,
Boston, MA, 3Merck KGaA, Darmstadt, Germany, 4EMD Serono Research &
Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica,
MA, 5EMD Serono Research & Development Institute, Inc. (a business of Merck KGaA,
Darmstadt, Germany), BIllerica, MA, 6Nordic Bioscience, Herlev, Denmark, 7Institute of
Anatomy, Paracelsus Medical University, Salzburg, Austria
First publication: October 13, 2017
SESSION INFORMATION
Session Date: Tuesday, November 7, 2017
Session Title: ACR Late-Breaking Abstract Session
Session Type: ACR Late-breaking Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Sprifermin, anovel recombinant human fibroblast growth

factor‑18 is currentlyinvestigated as a potential disease-modifying osteoarthritis (OA)
drug. Two-year primary data from a 5-year PhaseII trial (FORWARD) is presented.
Methods: Patients (pts) aged 40–85 years with symptomaticradiographic knee OA, KLG
2 or 3, and medial mJSW ≥2.5 mm in the targetknee were randomized (1:1:1:1:1) to
receive 3 weekly intra-articular injectionswith double-blinded placebo (PBO) or
sprifermin, administered in cycles every 6or 12 months (Fig 1). The primary endpoint was
the change in total tibiofemoraljoint (TFJ) cartilage thickness from baseline (BL) to Year
2. The ITTpopulation (all randomized pts) was used for non-MRI endpoints; and the
mITT(all ITT pts with BL and ≥1 post-treatment MRI up to Year 2) for MRIendpoints.
Results: The ITT population included 549 pts:median age 65 years, 69% women, 80%
white, and 69% KLG2. Of these, 12.2% (sprifermin)and 19.4% (PBO) discontinued
treatment within 2 years. The primary endpoint wasmet (Fig 2); there was a dose-
dependent increase in total TFJ cartilagethickness, with significant differences for
sprifermin 100µg q6 mo (Group 1)and 100µg q12 mo (Group 2) vs PBO (+0.03 vs -0.02
mm; p<0.001, and +0.02 vs ‑0.02mm; p<0.001, respectively). Furthermore, significant
differences in changeof cartilage thickness were observed between sprifermin vs PBO in
medial (Group1: +0.02 vs -0.03 mm; p=0.003) and lateral TFJ compartments (Group 1
and 2:both +0.04 vs -0.01 mm; p<0.001), and in central medial TFJ sub-regions (Group1:
+0.054 vs -0.11; p<0.001). Changes in mJSW observed with X-ray weresignificantly
different between sprifermin Group 1 and PBO in the lateral butnot the medial
compartment. Total WOMAC scores improved by ~50% in all treatmentgroups including
PBO. AEs and serious AEs were balanced between groups, and anoverall acceptable
safety profile was observed.
Conclusion: To our knowledge, sprifermin is thefirst investigational agent to show

prevention of cartilage loss in both thelateral and medial (including central medial)
femorotibial compartments. Thesestructural benefits associated with sprifermin suggest
that it may beefficacious for disease-modifying treatment of OA, and should be
furtherevaluated in clinical trials.
Disclosure: M. C. Hochberg, Bioiberica SA, Bristol Myers Squibb, EMD Serono,
Galapagos, IBSA SA, Eli Lilly, Novartis Pharma AG, Pfizer Inc., Plexxikon, Samumed
LLC, Theralogix LLC and TissueGene, 5; A. Guermazi, BICL, LLC, 1,Merck Serono,
TissueGene, OrthoTrophix, AstraZeneca and Genzyme, 5; H. Guehring, Merck KGaA, 3;
A. Aydemir, EMD Serono, Inc, 3; S. Wax, EMD Serono, Inc., 3; P. Fleuranceau-Morel,
EMD Serono, Inc, 3; A. R. Bihlet, None; I. Byrjalsen, None; J. R. Andersen, None; F.
Eckstein, Chondrometrics GmbH, 1.
View Abstract and Citation Information Online -

http://acrabstracts.org/abstract/efficacy-and-safety-of-intra-articular-sprifermin-in-
symptomatic-radiographic-knee-osteoarthritis-results-of-the-2-year-primary-analysis-
from-a-5-year-randomised-placebo-controlled-phase-ii-study
Abstract Number: 2L
Efficacy and Safety Results from a Phase 2 Trial of

Risankizumab, a Selective IL-23p19 Inhibitor, in
Patients with Active Psoriatic Arthritis
Philip J Mease1, Herbert Kellner2, Akimichi Morita3, Alan J. Kivitz4, Kim A. Papp5,
Stella Aslanyan6, Beate Berner7, Kun Chen8, Ann Eldred8 and Frank Behrens9, 1Swedish
Medical Center and University of Washington School of Medicine, Seattle, WA, 2Private
Practice and Division of Rheumatology KHI Neuwittelsbach, München, Germany, 3Dept
of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of
Medical Sciences, Nagoya, Japan, 4Altoona Center for Clinical Research, Duncansville,
PA, 5K Papp Clinical Research and Probity Medical Research Inc, Waterloo, ON, Canada,
6Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, 7Boehringer Ingelheim
Pharma GmbH & Co. KG, Biberach, Germany, 8AbbVie Inc., North Chicago, IL,
9CIRI/Rheumatology and Fraunhofer Institute IME, Translational Medicine and
Pharmacology, Goethe University, Frankfurt, Germany
SESSION INFORMATION
Background/Purpose: Interleukin-23(IL-23), a key regulator of multiple effector

cytokines (including IL-17,IL-22, and TNF), has been implicated in psoriatic lesions,
synovitis, enthesitis,and bone erosion. Risankizumab (RZB) is a potent humanized IgG1
mAb thatinhibits IL-23 by specifically binding its p19 subunit. The purpose of thisPhase 2
study was to investigate the safety and efficacy of RZB in patients(pts) with active
psoriatic arthritis (PsA).
Methods: Ptswith active PsA were randomized in a 2:2:2:1:2 ratio to receive RZB (150
mg atweeks [Wks] 0, 4, 8, 12, and 16 [Arm 1], 150 mg at Wks 0, 4, and 16 [Arm 2],150
mg at Wks 0 and 12 [Arm 3], 75 mg single dose at Wk 0 [Arm 4]) or matching
placebo(PBO, Arm 5) in this ongoing double-blind, parallel-design, dose-ranging Phase2
study. Pts were stratified at randomization by prior TNFi use and concurrentMTX use.
The primary efficacy endpoint was ACR20 response at Wk 16. Additional
efficacyendpoints included ACR50/70, minimal disease activity (MDA), DAS28(CRP),
dactylitiscount, SPARCC enthesitis index, pain on visual analog scale (VAS), and HAQ-
DI;PASI responses were assessed only in pts with psoriasis (PsO) affecting ≥3%body
surface area (BSA) at baseline (BL).
Results: Amongthe 185 pts who were randomized and received the study drug, 172
(93.0%)completed 16 wks of treatment. BL demographics and disease characteristics
weresimilar across treatment arms. The median age was 51 years; 80 (43.2%) pts
werefemale and 89 (49.4%) pts had PsO ≥3% BSA. At BL, dactylitis orenthesitis was
present in 56 (30.4%) and 119 (64.7%) pts, respectively; 45(24.3%) pts had prior TNFi
exposure and 106 (57.3%) pts were receiving concomitantMTX. At Wk 16, ACR20
responses were significantly greater in pts receiving RZB (acrossall arms, 57.1–65.0%)
compared with PBO (37.5%, Table 1). PASI75/90/100responses at Wk 16 were
significantly higher in RZB-treated pts compared withPBO. ACR50 responses were
numerically higher and improvements in HAQ-DI andenthesitis from BL were
numerically greater in RZB arms. At Wk 16, RZB-treated ptsachieved significantly higher
ACR70 and MDA responses as well as greaterimprovements in DAS28(CRP) and Pain–
VAS.Treatment-emergent adverse events (TEAEs) were comparable across treatment
arms(Table 2); the most common TEAE was infection. There were no deaths orcases of
tuberculosis in RZB-treated pts; 1 adjudicated major adverse cardiovascularevent was
reported in RZB arm.
Conclusion: Inthis Phase 2 study, RZB significantly improved joint and skin symptoms in
ptswith active PsA. RZB was well-tolerated with no new or unexpected safetyfindings.
Disclosure: P. J. Mease, AbbVie, Amgen, Bristol Myers, Celgene, Genentech, Janssen,
Lilly, Merck, Novartis, Pfizer, Sun Pharma, and UCB, 2,AbbVie, Amgen, Bristol Myers,
Celgene, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, Sun Pharma, and UCB,
5,AbbVie, Amgen, Bristol Myers, Celgene, Genentech, Janssen, Lilly, Merck, Novartis,
Pfizer, Sun Pharma, and UCB, 8; H. Kellner, AbbVie, BMS, MSD, Novartis, Pfizer,
Roche and UCB, 2,AbbVie, BMS, MSD, Novartis, Pfizer, Roche and UCB, 5,AbbVie,
BMS, MSD, Novartis, Pfizer, Roche and UCB, 8; A. Morita, AbbVie, Eli Lilly Japan
K.K., Janssen Pharmaceutical K. K., Kyowa Hakko Kirin Co., Ltd, Leo Pharma, Maruho
Co, Ltd, Mitsubishi-Tanabe Pharma, and Novartis, 2,AbbVie, Eli Lilly Japan K.K.,
Janssen Pharmaceutical K. K., Kyowa Hakko Kirin Co., Ltd, Leo Pharma, Maruho Co,
Ltd, Mitsubishi-Tanabe Pharma, and Novartis, 5,AbbVie, Eli Lilly Japan K.K., Janssen
Pharmaceutical K. K., Kyowa Hakko Kirin Co., Ltd, Leo Pharma, Maruho Co, Ltd,
Mitsubishi-Tanabe Pharma, and Novartis, 8; A. J. Kivitz, AbbVie, Amgen, Boehringer
Ingelheim, Celgene, Genentech, Genzyme, Horizon, Janssen, Merck, Novartis, Pfizer,
Sanofi, Sun Pharma Advanced Research, Regeneron, UCB, and Vertex, 5,AbbVie,
Amgen, Boehringer Ingelheim, Celgene, Genentech, Genzyme, Horizon, Janssen, Merck,
Novartis, Pfizer, Sanofi, Regeneron, UCB, and Vertex, 8; K. A. Papp, AbbVie, Amgen,
Astellas, Baxalta, Baxter, BI, BMS, Celgene, Dermira, Lilly, Forward, Galderma,
Genentech, GSK, Janssen, Kyowa-Hakko Kirin, Leo, MedImmune, Merck, Novartis,
Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Sun, Takeda, UCB, and Valeant,
2,AbbVie, Amgen, Astellas, Baxalta, Baxter, BI, BMS, Celgene, Dermira, Lilly, Forward,
Galderma, Genentech, GSK, Janssen, Kyowa-Hakko Kirin, Leo, MedImmune, Merck,
Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Sun, Takeda, UCB, and
Valeant, 5,AbbVie, Amgen, Astellas, Baxalta, Baxter, BI, BMS, Celgene, Dermira, Lilly,
Forward, Galderma, Genentech, GSK, Janssen, Kyowa-Hakko Kirin, Leo, MedImmune,
Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Sun, Takeda, UCB,
and Valeant, 8; S. Aslanyan, Boehringer Ingelheim, 3; B. Berner, Boehringer Ingelheim,
3; K. Chen, AbbVie Inc, 1,AbbVie Inc, 3; A. Eldred, AbbVie, 1,AbbVie, 3; F. Behrens,
AbbVie, Amgen, Celgene, Chugai, Eli Lilly, Genzyme Janssen, Novartis, Pfizer, Roche,
Sandoz, and Sanofi, 2,AbbVie, Amgen, Celgene, Chugai, Eli Lilly, Genzyme Janssen,
Novartis, Pfizer, Roche, Sandoz, and Sanofi, 5,AbbVie, Amgen, Celgene, Chugai, Eli
Lilly, Genzyme Janssen, Novartis, Pfizer, Roche, Sandoz, and Sanofi, 8.

http://acrabstracts.org/abstract/efficacy-and-safety-results-from-a-phase-2-trial-of-
risankizumab-a-selective-il-23p19-inhibitor-in-patients-with-active-psoriatic-arthritis
Abstract Number: 3L
Secukinumab Demonstrates Low Radiographic

Progression and Sustained Efficacy through 4 Years in
Patients with Active Ankylosing Spondylitis
Jürgen Braun1, Xenofon Baraliakos1, Atul A. Deodhar2, Denis Poddubnyy3, Paul
Emery4, Evie Maria Delicha5, Zsolt Talloczy6 and Brian Porter6, 1Rheumazentrum
Ruhrgebiet, Herne, and Ruhr University Bochum, Herne, Germany, 2Division of Arthritis
& Rheumatic Diseases, Oregon Health & Science University, Portland, OR, 3Department
of Rheumatology, Charité Universitätsmedizin Berlin, Berlin, Germany, 4Leeds
Musculoskeletal Biomedical Research Unit/Institute Rheumatic and Musculoskeletal
Medicine, Leeds, United Kingdom, 5Novartis Pharma AG, Basel, Switzerland, 6Novartis
Pharmaceuticals Corporation, East Hanover, NJ
SESSION INFORMATION
Background/Purpose: Secukinumab, a fully human anti–interleukin-17A monoclonal

antibody, reported improved signs and symptoms of ankylosing spondylitis (AS) in the
MEASURE 1 trial.1 Here, we report efficacy, including imaging outcomes, and safety
from the MEASURE 1 extension trial (NCT01863732) out to 4 years (208 weeks [wks]).
Methods: In the core study, 371 patients (pts) with active AS were randomized to
secukinumab or placebo (PBO). Pts on secukinumab had a 10 mg/kg iv loading dose at
baseline (BL), Wks 2 and 4, and then 150 mg sc (IV→150 mg) or 75 mg sc (IV→75 mg)
every 4 wks from Wk 8 (same schedule for PBO). Based on ASAS20 response at Wk 16,
PBO pts were re-randomized to secukinumab 150 or 75 mg sc at Wk 16 (non-responders)
or Wk 24 (responders). Efficacy data at Wk 208 are reported for pts originally
randomized to secukinumab 150 mg (approved dose with sc loading). Lateral radiographs
of the cervical and lumbar spine at BL, Wk 104 and Wk 208 were read centrally by 2
independent readers, blinded to treatment arm and radiograph sequence, using the
modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). For this analysis,
radiographs performed at BL and Wk 104 were re-read for pts who completed 208 wks of
treatment. Descriptive statistics on observed or imputed data are provided.
Results: Of the 274 patients in this extension study, 89.7% (78/87) originally assigned to
secukinumab 150 mg completed 208 wks. Mean (±SD) change in mSASSS from BL to
Wk 208 was lower with secukinumab 150 mg (1.2±3.91) vs 75 mg (1.7±4.70). No
radiographic progression was seen in 73% (mSASSS change from BL ≤0) and 79%
(mSASSS change from BL <2) of pts with secukinumab over 208 wks (Figure). Mean
mSASSS changes at Wk 208 were numerically higher in males vs females, pts with
elevated vs normal BL hsCRP, and pts with vs without BL syndesmophytes. Sustained
efficacy in signs/symptoms was seen through Wk 208, evidenced by ASAS 20/40,
BASDAI, BASFI, BASMI and ASDAS inactive disease (Table). Efficacy responses were
numerically lower with secukinumab 75 mg vs 150 mg. Across the entire treatment period
(secukinumab exposure [mean±SD]: 3.4±1.44 years), exposure-adjusted incidence rates
for serious infections, Crohn's disease, uveitis and malignant/unspecified tumors were 1.0,
0.6, 1.8 and 0.5 per 100 pt-years, respectively.
Conclusion: Secukinumab 150 mg demonstrates lower radiographic progression vs 75

mg at 4 years. These 4-year results confirm the sustained efficacy and known safety
profile of secukinumab.1
References: 1. Braun J et al. Ann Rheum Dis 2016;0:1‒8
Table. Summary of efficacy data at Wk 208

Secukinumab
IV→150mg (N=87)
Radiographic outcomesa,b
mSASSS at BL, mean±SD 8.8±16.23 (n=71)
Change in mSASSS from BL to Wk 208,
mean±SD 1.2±3.91 (n=71)
Change in mSASSS from BL to Wk 104,
mean±SD 0.6±1.84 (n=57)
Change in mSASSS from Wk 104 to Wk
208, mean±SD 0.6±2.61 (n=58)
Other efficacy outcomes

ASAS20 / 40,c % 76.4 / 58.0
BASDAI,d change from BL, LS mean±SE –3.3±0.23
ASDAS inactive disease,c % 11.6
BASFI,b change from BL, mean±SD –2.9±2.39 (n=80)
BASMI,b change from BL, mean±SD –0.52±1.12 (n=76)
BL, baseline; LS, least squares; n, number of pts meeting criteria; N,
total number of pts in the extension trial; SD, standard deviation; SE,
standard error aRadiographs performed at BL and Wk 104 were re-
read for pts who completed 208 wks of treatment; bObserved data;
cEstimated using multiple imputation; dMMRM estimates
Disclosure: J. Braun, Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion,
Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma,
Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB, 2,Abbvie (Abbott), Amgen,
BMS, Boehringer, Celgene, Celltrion, Cetocor, Chugai, EBEWE Pharma, Medac, MSD
(Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and
UCB, 5,Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor,
Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis,
Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB, 8; X. Baraliakos, AbbVie, Merck,
Pfizer, UCB, Novartis, and Chugai, 2,AbbVie, Merck, Pfizer, UCB, Novartis, and Chugai,
5,AbbVie, Merck, Pfizer, UCB, Novartis, and Chugai, 8; A. A. Deodhar, AbbVie,
Amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, 2,AbbVie, Amgen, Janssen,
Novartis, Pfizer, UCB, 5; D. Poddubnyy, AbbVie, MSD, Novartis, 2,AbbVie, BMS,
MSD, Novartis, Pfizer, UCB, 5,AbbVie, BMS, Janssen, MSD, Novartis, Pfizer, UCB, 8;
P. Emery, AbbVie, BMS, Merck, Novartis, Pfizer, Roche, UCB, 5; E. M. Delicha,
Norartis Pharma AG, 3; Z. Talloczy, Novartis Pharmaceutical Corporation, 1,Novartis
Pharmaceutical Corporation, 3; B. Porter, Novartis Pharmaceutical Corporation,
1,Novartis Pharmaceutical Corporation, 3.

http://acrabstracts.org/abstract/secukinumab-demonstrates-low-radiographic-progression-
and-sustained-efficacy-through-4-years-in-patients-with-active-ankylosing-spondylitis
Abstract Number: 4L
Final Results of an Open Label Phase 2 Study of a

Reversible B Cell Inhibitor, Xmab®5871, in IgG4-
Related Disease
John H. Stone1, Zachary S. Wallace2, Cory A. Perugino3, Ana D. Fernandes4, Payal
Patel5, Paul A. Foster6 and Debra J. Zack6, 1Massachusetts General Hospital
Rheumatology Unit, Harvard Medical School, Boston, MA, 2Division of Rheumatology,
Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School,
Boston, MA, 3Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 4Division of
Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA,
5Rheumatology, Harvard, Boston, MA, 6Xencor, Inc., San Diego, CA
SESSION INFORMATION
Background/Purpose: IgG4-related disease (IgG4-RD) is an immune-mediated

condition causing fibro-inflammatory lesions that can lead to irreversible organ damage
and death. No approved therapies exist. A novel monoclonal antibody, XmAb5871, is a
humanized anti-CD19 antibody with an Fc engineered for increased affinity to Fc RIIb.
Co-ligation of CD19 and Fc RIIb leads to inhibition of B lineage cells. Because of the
importance of B cells and plasmablasts (PB) in IgG4-RD pathogenesis, an open label pilot
of XmAb5871 in IgG4-RD was performed.
Methods: IgG4-RD patients with active disease defined by an IgG4-RD Responder Index
(RI) of ≥ 3 were administered XmAb5871 (5 mg/kg) IV every 14 days for 12 doses. The
primary outcome measure was the proportion of patients on Day 169 with a decrease in
the IgG4-RD RI of ≥2 points compared to baseline. Secondary endpoints included the
proportion of patients achieving an IgG4-RD RI of 0 with no corticosteroids (CS) after
month 2. Other immunosuppressive medications were not allowed. Mechanistic studies
were performed at baseline and at selected intervals.
Results: 15 patients enrolled between March 2016 and January 2017. The median age of
the 15 patients was 63 years (43 to 77 years). Two-thirds were male. 12 of 15 patients had
elevated baseline serum IgG4 concentrations (median IgG4: 220 mg/dL; 25 – 2415). 10
had undergone treatment with other therapy before entry. The median baseline IgG4-RD
RI was 12 (2 – 30), with active inflammatory disease in a median of 5 organ systems (1-
10). The organs most commonly affected were lymph nodes (73% of patients),
submandibular glands (60%), parotid glands (53%), and lacrimal glands (47%). 5 patients
(33%) had kidney involvement, 4 (27%) had lung findings and 3 each (20%) had orbital
lesions, nasal cavity involvement or heart/pericardium findings. 12 patients (80%)
completed the study and all 12 achieved the primary endpoint of at least a 2-point
reduction in the IgG4-RD RI on Day 169. None of the 12 required CS after month 2. 8
patients (53%) achieved remission (IgG4-RD RI of 0 and no CS after 2 months) and the
other 4 achieved IgG4-RD RI scores of ≤4 at Day 169. 14 of 15 patients (93%) achieved a
decrease of ≥ 2 in the IgG4-RD RI, most within 2 weeks. One patient had been on
baseline CS for 2 years (15 mg/day) and was able to discontinue CS within 2 months. 4
others received CS at the start of the trial and tapered off within 2 months. 3 patients had
minor, transient GI side-effects during the 1st infusion; all completed the study. Two
SAEs of pneumonia and recurrence of pneumonia due to lack of compliance were seen in
1 patient (who completed). 3 patients discontinued early. One was an atypical patient with
laryngeal involvement only who did not respond to XmAb5871 or to subsequent
rituximab. A 2nd responded well, but flared at 12 weeks and did not respond to
subsequent rituximab therapy. The 3rd responded well but developed infusion-related
symptoms including transient rash and arthralgias following the 5th infusion. She
concurrently developed anti-drug antibodies.
Mean B cell counts decreased to ~40-55% of baseline and circulating PBs decreased by
~70% following XmAb5871.
Conclusion: XmAb5871 is tolerated well in patients with active IgG4-RD and is a

promising treatment approach for IgG4-RD.
Disclosure: J. H. Stone, Xencor, 2; Z. S. Wallace, None; C. A. Perugino, None; A. D.

Fernandes, None; P. Patel, None; P. A. Foster, Xencor Inc, 1,Xencor Inc, 3; D. J. Zack,
Xencor Inc, 1,Xencor Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/final-

results-of-an-open-label-phase-2-study-of-a-reversible-b-cell-inhibitor-xmab5871-in-
igg4-related-disease
Abstract Number: 5L
Rapamycin Vs. Placebo for the Treatment of Inclusion
Body Myositis: Improvement of the 6 Min Walking
Distance, a Functional Scale, the FVC and Muscle
Quantitative MRI
Olivier Benveniste1, Jean-Yves Hogrel2, Melanie Annoussamy2, Damien Bachasson2,
Aude Rigolet3, Laurent Servais2, Joe-Elie Salem4, Baptiste Hervier3, Oceane Landon
Cardinal5, Kuberaka Mariampillai1, Jean-Sebastien hulot4, Pierre Carlier2 and Yves
Allenbach6, 1Assistance Publique - Hôpitaux de Paris, Pitié-Salpêtrière University
Hospital, Department of Internal Medicine and Clinical Immunology, Hospital University
Department: inflammation, immunopathology and biotherapy (DHU i2B), Paris, France,
Paris, France, 2Institute of Myology, Paris, France, 3Internal Medicine, Pitié-Salpêtrière
University Hospital, Paris, France, 4INSERM, CIC-1421, Paris, France, 5Internal
Medicine, Assistance Public - Hopitaux de Paris, Pitié-Salpêtrire University Hospital,
Paris, France, 6Internal Medicine, Assistance Public - Hopitaux de Paris, Pitié-Salpêtrière
University Hospital, Paris, France
SESSION INFORMATION
Background/Purpose:
Inclusion body Myositis (IBM) is the most frequent myositis in patients over 50 years old.
Conventional immunosuppressive drugs are today ineffective or even aggravate muscle
deficits. Rapamycin is a mTOR inhibitor used in organ transplantation. Potentially,
rapamycin can deplete T effector cells, preserve T regulatory cells and induce autophagy
(protein degradation), all parameters impaired during IBM.
Methods:
RAPAMI is a prospective, randomized, controlled, double blind, monocentric, phase IIb

trial evaluating the efficacy of rapamycin against placebo (NCT02481453). The primary
endpoint was stabilization of maximal voluntary quadriceps isometric strength assessed
with a dynamometer (Biodex System3 pro). Secondary endpoints included safety, other
muscle groups strength, distance walked in 6 minutes (6MWD), pulmonary functional
tests, functional scales, and muscle quality assessed by quantitative nuclear resonance
magnetic exams (NRM).
Results:
Forty-four patients were treated by oral rapamycin (2 mg/d, n=22) or placebo (n=22)
during 12 months (M12). Twelve months after the initiation of the treatment, the
quadriceps strength decreased significantly and similarly in both groups (mean relative
change: -11.07% vs. -12.36 %). Nevertheless, in comparison to the placebo group, 6MWD
was unchanged (mean change: -4.1 m vs. -38.5 m, p=0.035), IBM weakness composite
index was less degraded (11.91% vs. 24.26%, p=0.038) and forced vital capacity
significantly improved (mean relative change: +12.3% vs. 1.6%, p=0.016). Additionally,
NRM showed significant less fat muscle replacement (difference between M12 and
baseline in %) in quadriceps (1.7 vs. 4.4, p=0.025) or hamstrings (0.9 vs. 7.3, p=0.027).
Finally in NRM, the loss between M12 and baseline of contractile cross-sectional area
(mm²) was less pronounced in quadriceps (-3.7 vs. -10.7, p=0.005).
Conclusion: Even if the primary endpoint was not reached, these first results showed
coherent data in favor of rapamycin. Notably for the first time in a RCT, an improvement
of the 6MWD is observed during IBM.
Disclosure: O. Benveniste, None; J. Y. Hogrel, None; M. Annoussamy, None; D.

Bachasson, None; A. Rigolet, None; L. Servais, None; J. E. Salem, None; B. Hervier,
None; O. Landon Cardinal, None; K. Mariampillai, None; J. S. hulot, None; P.
Carlier, None; Y. Allenbach, None.

http://acrabstracts.org/abstract/rapamycin-vs-placebo-for-the-treatment-of-inclusion-body-
myositis-improvement-of-the-6-min-walking-distance-a-functional-scale-the-fvc-and-
muscle-quantitative-mri
Abstract Number: 6L
Efficacy and Safety of Ustekinumab, an Interleukin

12/23 Inhibitor, in Patients with Active Systemic Lupus
Erythematosus: Results of a Phase 2, Randomized
Placebo-Controlled Study
Ronald van Vollenhoven1, Bevra H. Hahn2, George C. Tsokos3, Carrie Wagner4, Peter
Lipsky5, Benjamin Hsu4, Marc Chevrier4, Robert Gordon4, Manon Triebel6 and Shawn
Rose4, 1Amsterdam Rheumatology and Immunology Center ARC, Amsterdam,
Netherlands, 2UCLA David Geffen School of Medicine, Los Angeles, CA, 3Division of
Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard
Medical School, Boston, MA, 4Janssen Research & Development, LLC, Spring House,
PA, 5Ampel BioSolutions LLC, Charlottesville, VA, 6Janssen Biologics Europe, Leiden,
Netherlands
SESSION INFORMATION
Background/Purpose: TheIL-12/23 pathway has been implicated in the pathogenesis of

SLE. Theanti-IL12/23 monoclonal antibody ustekinumab (UST) is efficacious in
thetreatment of psoriasis, psoriatic arthritis, and Crohn’s disease. Here, weevaluated the
safety and efficacy of UST in patients (pts) with active SLE.
Methods: Weconducted a phase 2, placebo (PBO)-controlled study in 102 adults with

seropositive(ANA, anti-dsDNA, and/or anti-Smith antibodies) SLE by SLICC criteria and
activedisease (SLEDAI score ≥6 and ≥1 BILAG A and/or ≥2 BILAG B scores)
despitestandard-of-care therapy. Pts (n=102) were randomized (3:2) to receive UST IV
~6mg/kg or PBO at wk0, followed by SC injections of UST 90mg q8w or PBO,
bothadded to standard care; stratification factors were consent for skin biopsy(y/n),
disease features, (eg, presence of lupus nephritis, baseline concomitantSLE medications,
SLEDAI score), site/region, and race. The primary endpointwas the proportion of
patients achieving SLE response index (SRI)-4 response atwk24. Major secondary
endpoints at wk24 included change from baseline in SLEDAI-2K,change from baseline in
Physician’s Global Assessment (PGA), and proportion ofpts with BICLA response.
Endpoint analyses included all pts who received≥1 dose of study agent, had ≥1
measurement prior to administration,and had ≥1 post-baseline measurement. Patients
with missing data andtreatment failures were imputed as nonresponders.
Results: Baselinept demographic and disease characteristics were well-balanced between

treatmentgroups (female=91%; mean age=41 (18-66) years; mean SLEDAI-2K= 10.9). At
wk24,60% of pts in the UST group had an SRI-4 response vs 31% in the PBO group
(p=0.0046),with a treatment effect favoring UST beginning at wk12. Pts in the UST
grouphad greater median change from wk0 to wk24 in SLEDAI-2K and PGA vs PBO
(Table).No difference was observed in the proportion of pts achieving a BICLA
compositeresponse at wk24, although among BICLA nonresponders, a greater proportion
ofUST pts had no BILAG worsening vs PBO. The risk of a new BILAG flare (≥1new
BILAG A or ≥2 new BILAG B) was significantly lower in the UST groupvs. PBO (HR
0.11 [95% CI 0.01-0.94]; p=0.0078). UST demonstrated improvement inmusculoskeletal
and mucocutaneous disease features vs PBO. Improvements in anti-dsDNAand C3 levels
were also noted through wk24 with UST. Through wk24, 78% of UST ptsand 67% of
PBO pts had ≥1 adverse event; 8.3% and 9.5%, respectively, had≥1 serious adverse event
(Table). There were no deaths in the study. Safetyevents were consistent with the UST
safety profile in other studied indications.
Conclusion: USTshowed significantly better efficacy in clinical and laboratory

parameters in thetreatment of active SLE compared with placebo, while demonstrating a
comparablesafety profile. UST may be an effective therapy with a novel mechanism
ofaction in the treatment of SLE.
Table. Efficacy and safety results at Week 24.
Placebo Ustekinumab
Patients randomized, n 42 60
Efficacy
Patients with SRI-4 response,
n (%) 13 (31.0) 36 (60.0)
P value 0.0046a
Change from baseline in
SLEDAI-2K, median (range) -2.0 (-20; 10) -6.0 (-10; 3)
P value 0.0265a,b
PGA, median (range) -1.6 (-5.6; 2.7) -2.5 (-6.6; 2.8)
P value 0.2110a,b
Patients with BICLA
response, n (%) 14 (33.3) 21 (35.0)
P value 0.9939a
Proportion of BICLA
nonresponders with no
BILAG worsening, n/N (%) 11/28 (39.2) 29/39 (74.4)
P value 0.0043
Patients with 50%
improvement from baseline
joint disease activityc, % (95%
CI) 63.2 (61.7-64.6) 87.7 (86.8-88.6)
P value 0.0208d
Patients with 50%
improvement from baseline
CLASI activity scored, %
(95% CI) 25.2 (23.1-27.4) 58.7 (57.4-60.1)
P value 0.0429e
Change from baseline in anti-
dsDNA (kIU/L)f, median
(range) -12.6 (-168.8; 233.1) -30.7 (-2919.6; 132.9)
P value 0.1073h
Complement C3 (mg/dL)g,
median (range) 0.15 (-12.4; 21.8) 6.60 (-17; 50.8)
P value 0.0636h
Adverse events
Patients with ≥1 TEAE, n (%) 28 (66.7) 47 (78.3)
Most Common TEAEs, n (%)
Upper respiratory tract
infection 9 (21.4) 5 (8.3)
Urinary tract infection 5 (11.9) 6 (10.0)
Nasopharyngitis 3 (7.1) 6 (10.0)
Headache 5 (11.9) 4 (6.7)
Patients with ≥1 SAE, n (%) 4 (9.5) 5 (8.3)
aPrespecified analyses; all other analyses shown here were post-hoc.
bOne-sidedtest for no difference between two treatment groups based upon a

Wilcoxon non-parametric median test for difference of location
cPatientsubpopulation (67% of total population) with at least 4 joints with pain
and signs of inflammation at baseline
dPatient subpopulation (58% of total population) with CLASI activity score of
at least 4 at baseline
eProportions of responders and p values based on a modified intention to treat
analysis using a multiple imputation model for missing data from weeks 16 to
24
fPatientsubpopulation (42% of total population) with anti-dsDNA
autoantibodies present at baseline
gPatient subpopulation (41% of total population) with low Complement C3
levels present at baseline
hOne-sidedtest for no difference between two treatment groups based upon a
Wilcoxon non-parametric median test for difference of location
BICLA, BILAG-based Combined Lupus Assessment; BILAG, British Isles

Lupus Assessment Group; CLASI, Cutaneous Lupus Erythematosus Disease
Area and Severity Index; SLEDAI-2K, Systemic Lupus Erythematosus Disease
Activity Index 2000; ; PGA, physician’s global assessment; SRI-4, SLE
Response Index TEAE, treatment emergent adverse event
Disclosure: R. van Vollenhoven, Janssen Research & Development, LLC, 5; B. H.
Hahn, BMS, Squibb, Janssen, 5; G. C. Tsokos, Janssen Research & Development, LLC,
5; C. Wagner, Janssen Research & Development, LLC, 3,Johnson & Johnson, 1; P.
Lipsky, Janssen Research & Development, LLC, 5; B. Hsu, Johnson & Johnson,
1,Johnson & Johnson, 3; M. Chevrier, Johnson & Johnson, 1,Janssen Research
Development LLC, 3; R. Gordon, Janssen Research & Development, LLC, 3,Johnson &
Johnson, 1; M. Triebel, Janssen Biologics Europe, 3; S. Rose, Janssen Research &
Development, LLC, 3,Johnson & Johnson, 1.

http://acrabstracts.org/abstract/efficacy-and-safety-of-ustekinumab-an-interleukin-1223-
inhibitor-in-patients-with-active-systemic-lupus-erythematosus-results-of-a-phase-2-
randomized-placebo-controlled-study
Abstract Number: 7L
A Phase 2 Study of Safety and Efficacy of Anabasum

(JBT-101), a Cannabinoid Receptor Type 2 Agonist, in
Refractory Skin-Predominant Dermatomyositis
Victoria P. Werth1, Emily Hejazi2, Sandra M. Pena1, Jessica S. Haber3, Joyce Okawa1,
Rui Feng4, Kirubel Gabre2, Josef Concha2, Caitlin Cornwall5, Nancy Dgetluck6, Scott
Constantine5 and Barbara White5, 1Department of Dermatology, Perelman School of
Medicine at the University of Pennsylvania, Philadelphia, PA, 2University of
Pennsylvania, Philadelphia, PA, 3Department of Dermatology, University of
Pennsylvania, Philadelphia, PA, 4Department of Biostatistics and Epidemiology at the
Hospital of the University of Pennsylvania, Philadelphia, PA, 5Corbus Pharmaceuticals,
Inc., Norwood, MA, 6Biostatistics, Corbus Pharmaceuticals, Inc., Norwood, MA
SESSION INFORMATION
Session Title: ACR Late-Breaking Abstract Poster
Session Time: 9:00AM-11:00AM
Background/Purpose: Effective treatment options are limited for refractory skindisease
in dermatomyositis (DM). Anabasum is a non-immunosuppressive,synthetic, oral
preferential CB2 agonist that triggers resolution of innateimmune responses and reduces
cytokine production by PBMC from DM patients. Thispurpose of this study was to test
safety and efficacy of anabasum in DMsubjects with refractory, moderate-to-severely
active skin disease.
Methods: A double-blind, randomized placebo-controlled16-week Phase 2 trial

(JBT101-DM-001) enrolled adults with documented DM and a Cutaneous
Dermatomyositis Disease Area and Severity Index (CDASI)activity score ≥ 14, minimal
active muscle involvement and failure orintolerance to hydroxychloroquine and stable
DM medications including immunosuppressants. Subjects received 2 escalating doses of
anabasum (20 mg QD X 4 weeks, then 20mg BID X 8 weeks) or PBO X 12 weeks.
Subjects were followed off study drug X 4weeks. Safety and efficacy outcomes were
assessed from Day 1 through end ofstudy at Week 16. The primary efficacy objective was
to assess efficacy ofanabasum using CDASI activity score.
Results: 11 adults eachreceived anabasum and PBO (N = 22). Demographic and disease
characteristicswere similar in both cohorts. Both cohorts had mean CDASI activity scores
inthe severe range (33-35) despite immunosuppressants (19/22 subjects). Anabasum
subjects had clinically meaningful improvement inCDASI activity scores with mean
reduction ≥ 5 points at all visits after4 weeks. Improvement had statistical significance at
end of study (Fig. 1, P =0.02, 2-sided MMRM) that first became apparent after 4 weeks.
Anabasum provided greater improvement than placebo in CDAIdamage index, patient-
reported global skin disease and overall diseaseassessments, skin symptoms including
photosensitivity and itch, fatigue, sleep,pain interference with activities, pain, and
physical function (examples in Fig.1). Improvements in secondary efficacy outcomes
reached statisticalsignificance (P ≤ 0.1, 1-sided MMRM) at multiple visits after week
4(Fig. 1). There were no serious, severe or unexpected adverse events (AEs)related to
anabasum. Tolerability of anabasum was excellent with no studydrop-outs. Subjects in
the anabasum cohort had numerically more mild AEs thanplacebo subjects (29 vs. 19) and
fewer moderate AEs (4 vs. 7). AEs in ≥3 subjects in any cohort were diarrhea, dizziness
(lightheadedness), fatigueand dry mouth.
Conclusion: Anabasum demonstrated consistentevidence of clinical benefit across
multiple efficacy outcomes and had acceptablesafety and tolerability in this Phase 2 trial
in refractory skin disease in DM. Further evaluation of anabasum in the treatment of DM
is warranted.
Disclosure: V. P. Werth, None; E. Hejazi, None; S. M. Pena, None; J. S. Haber, None;

J. Okawa, None; R. Feng, None; K. Gabre, None; J. Concha, None; C. Cornwall,
Corbus Pharmaceuticals, Inc., 1,Corbus Pharmaceuticals, Inc., 3; N. Dgetluck, Corbus
Pharmaceuticals, Inc., 1,Corbus Pharmaceuticals, Inc., 3; S. Constantine, Corbus
Pharmaceuticals, Inc., 1,Corbus Pharmaceuticals, Inc., 3; B. White, Corbus
Pharmaceuticals, 1,Corbus Pharmaceuticals, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-

phase-2-study-of-safety-and-efficacy-of-anabasum-jbt-101-a-cannabinoid-receptor-type-
2-agonist-in-refractory-skin-predominant-dermatomyositis
Abstract Number: 8L
Prevalence of Blindness in a Cohort of Rheumatologic

Patients Treated with Hydroxychloroquine
Dilpreet Singh1, Leila Muhieddine2, Douglas Einstadter3 and Stanley Ballou4,
1Rheumatology, Case Western Reserve University School of Medicine at MetroHealth
Medical Center, Cleveland, OH, 2Internal Medicine, Case Western Reserve University,
MetroHealth Medical Center, Cleveland, OH, 3Case Western Reserve University at
MetroHealth Medical Center, Cleveland, OH, 4Rheumatology, Case Western Reserve
University/MetroHealth Medical Center, Cleveland, OH
SESSION INFORMATION
Background/Purpose: Hydroxychloroquine (HCQ) is widely used in the treatment of

chronic rheumatic diseases. Its long-standing use has been associated with retinopathy in
a daily and cumulative dose dependent manner by weight. Less frequently, ‘bull’s eye
maculopathy’ may be found, which is irreversible and can result in blindness. We
examined the prevalence of ocular toxicity in a large cohort of patients in a tertiary center
in the United States treated with HCQ for inflammatory arthritis and systemic lupus
erythematosus (SLE).
Methods: Our retrospective cohort study identified 2898 patient from 1999 to August
2017 with diagnoses of rheumatoid arthritis (RA), inflammatory polyarthritis, SLE,
subacute cutaneous lupus and discoid lupus erythematosus who had a prescription written
for HCQ. 31 patients were identified as having a diagnosis of ‘blindness’ or ‘toxic
maculopathy’ in their electronic medical record (Epic) and were chart reviewed. Patient
weight and dose of HCQ at initiation and discontinuation, dose of HCQ at the time of any
ocular symptoms, duration of HCQ use, rheumatologic diagnosis, reason for blindness or
vision impairment, comorbidities and the use of tamoxifen were extracted into REDCap
database.
Results:
Of our 31 patients with a diagnosis of ‘blindness’ or ‘toxic maculopathy’, 11 had

documented blindness of one or both eyes. In each of these cases, a diagnosis other than
HCQ ocular toxicity was confirmed as the cause of blindness: stroke (27%), pre-existing
macular disease (18%), diabetic retinopathy (18%), hypertensive retinopathy (9%) and
cataracts (9%).
Three out of the 31 patents in our cohort had HCQ retinal toxicity, each without blindness
or change in vision.
Two cases were identified with bull’s eye maculopathy attributed to HCQ, diagnosed on
fundus and macular optical coherence tomography (OCT) exam. Case one was a 51 year
old female who had been treated for SLE with HCQ 400 mg daily for over 20 years at
7.1-8.2 mg/kg dose based on documented weight over 15 years. Case two was a 66 year
old female who had been treated for SLE on HCQ 400 mg daily for at least 18 years at
7.3-8.2 mg/kg dose based on documented weight over 13 years. Comorbidity of case one
was chronic kidney disease, whereas case two had hypertension and cataracts (not
visually significant), both without prior use of tamoxifen.
One patient had HCQ toxicity without bull’s eye maculopathy but with pigmentary
changes on fundus exam and loss of photoreceptor inner segment and outer segment
junction in mid periphery on OCT exam. She was 57 years old with 25 years use of HCQ
400 mg daily at 6.3 mg/kg dose based on documented weight over 11 years. She had
underlying myopia controlled with glasses without vision complaints.
Conclusion: There were no cases of blindness attributable to toxic maculopathy from

HCQ use in our cohort of 2868 patients. We identified two patients with bull’s eye
maculopathy (0.10%) and one with HCQ toxic maculopathy (0.07%) in this cohort; all 3
patients received HCQ for greater than 18 years, and none had functional vision loss at
diagnosis. Our findings suggest that comorbid conditions that are common in RA and
SLE contribute substantially to vision loss and blindness and should not be ignored.
Disclosure: D. Singh, None; L. Muhieddine, None; D. Einstadter, None; S. Ballou,

None.

http://acrabstracts.org/abstract/prevalence-of-blindness-in-a-cohort-of-rheumatologic-
patients-treated-with-hydroxychloroquine
Abstract Number: 9L
Circulating Type I, II and III Interferons (IFNs)

Associate with IFN-Scores, but Define Distinct Subsets
of Active SLE
Vilija Oke1, Iva Gunnarsson1, Jessica M. Dorschner2, Agneta Zickert1, Timothy B.
Niewold3 and Elisabet Svenungsson1, 1Department of Medicine, Rheumatology Unit,
Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, Stockholm,
Sweden, 2Division of Rheumatology and Department of Immunology, Mayo Clinic,
Rochester, MN, 3Colton Center for Autoimmunity, New York University, New York, NY
SESSION INFORMATION
Background/Purpose:
Serum induced IFN gene expression (IFN-score) is considered a golden standard to assess
IFN activity in SLE. So far, IFN-scores have not been compared to serum levels of type I,
II and III IFNs. The study aimed to investigate how IFN-scores and SLE manifestations
relate to serum levels of IFNs type I(αs), II(γ) and III(λ1).
Methods:
461 SLE patients and 322 controls were included. IFN-score was measured by WISH cell
assay. INF-αs and IFN-λ1 were measured by ELISA. IFN-γ was measured by MSD 30-
plex assay.
Results:
SLE patients had higher IFN-scores and higher levels of IFN-αs, IFN-γ and IFN-λ1
(p<0.001). IFN-scores correlated with levels of IFN-γ and IFN-α (ρ=0.39, and ρ=0.25,
p<0.0001). Further, patients were grouped according to the high levels (≥3rd quartile) of
each IFN/IFN-score. The group with high IFN-scores had higher disease activity (SLAM,
SLEDAI): weight loss (41%), fatigue (33%), fever (39%), rash (44%), lymphadenopathy
(45%), arthritis (40%), nephritis (55%)(p<0.01). Interestingly, incidence of
neuropsychiatric SLE, antiphospholipid (aPL) antibodies (abs), and also damage score
was lower (p<0.05).
The characteristics of IFN-γ high group included higher disease activity (SLAM,
SLEDAI), and specifically: active nephritis (52%), lymphadenopathy (40%), arthritis
(42%), lymphopenia (37%), anemia (35%) and positivity for Sm (41%), SmRNP (36%)
and RNP68 (45%), Ro52 (35%) and Ro60 (33%)(p<0.03).
The common features of IFN-α high group included younger age, shorter disease
duration, active rash (34%), lymphadenopathy (43%), Ro52 (38%) and La (43%)(p=0.01).
Presence of aPL abs and previous vascular events were lower and renal affection was
uncommon (p<0.01).
In general, high IFN-scores reflected SLE manifestations that could be further stratified
by high IFN-γ levels and to a lesser extent by high IFN-α. High IFN-λ1 did not define any
phenotype of active SLE, except presence of anti-nucleosome abs.
Conclusion:
We demonstrate that high IFN-score associate more strongly with type II rather than type
I IFNs. Importantly, major manifestations of SLE: active nephritis and arthritis, and also
anti-Sm/SmRNP antibodies associate with IFN-γ; while rash associate with IFN-α.
Our findings are of major importance while tailoring clinical trials with anti-IFN therapies
and demonstrate that importance of IFN-γ has so far been underscored.
Disclosure: V. Oke, None; I. Gunnarsson, None; J. M. Dorschner, None; A. Zickert,

None; T. B. Niewold, None; E. Svenungsson, None.

http://acrabstracts.org/abstract/circulating-type-i-ii-and-iii-interferons-ifns-associate-with-
ifn-scores-but-define-distinct-subsets-of-active-sle
Abstract Number: 10L
Upadacitinib (ABT-494) in Patients with Active

Rheumatoid Arthritis and Inadequate Response or
Intolerance to Biological Dmards: A Phase 3
Randomized, Placebo-Controlled, Double-Blind Study
of a Selective JAK-1 Inhibitor
Mark C. Genovese1, Roy Fleischmann2, Bernard Combe3, Stephen Hall4, Ying Zhang5,
Yijie Zhou5, Mohamed-Eslam F. Mohamed6, Sebastian Meerwein7 and Aileen L.
Pangan5, 1Stanford University Medical Center, Palo Alto, CA, 2University of Texas
Southwestern Medical Center at Dallas, Dallas, TX, 3Rheumatology, CHU Lapeyronie
and Montpellier University, Montpellier, France, 4Department of Medicine, Monash
University, Cabrini Health and Emeritus Research, Malvern, Australia, 5AbbVie Inc.,
North Chicago, IL, 6Clinical Pharmacology and Pharmacometrics, AbbVie Inc., North
Chicago, IL, 7AbbVie Deutschland GmbH & Co, Ludwigshafen, Germany
SESSION INFORMATION
Background/Purpose: Upadacitinib (ABT-494, UPA), an oral,selective JAK-1 inhibitor

was effective in 2 ph2 trials in rheumatoid arthritis(RA) pts with inadequate response
(IR)/intolerance to csDMARDs/ bDMARDs.
Methods: Pts with active RA (TJC≥6, SJC≥6;hsCRP≥3 mg/L) on stable csDMARDs

were randomized 2:2:1:1 to receive UPA15 mg or 30 mg once daily (QD) or PBO for 12
wks followed by UPA 15 mg or UPA30 mg QD starting at Wk 12. The primary endpoints
were the proportion of ptswho achieved ACR20 and the proportion who achieved
DAS28-CRP ≤3.2 at Wk12 (NRI).
Results: Of 499 randomized pts, 498 receivedstudy drug; 451 (90.6%) and 419 (84.1%)
completed Wks 12 and 24 respectively. Baselinedisease characteristics indicated long-
standing severe, refractory disease:(means) duration since diagnosis 13 yrs; DAS28CRP,
5.8; TJC68, 27.9; SJC66,16.8; 53% experienced ≥2 prior bDMARDs. At Wk 12,
significantly more pts(p<.001) on UPA 15 and 30 vs PBO achieved the primary endpoints
(ACR20: 64.6%and 56.4% vs 28.4%; DAS28-CRP≤3.2: 43.3% and 42.4% vs 14.2%) and
othersecondary endpoints (Table 1). By Wk 1, significantly more pts achievedACR20 on
UPA 15 and 30 vs PBO (27.4% and 24.8% vs 10.7%, p<.001). At Wk 12,significant
improvements were observed on UPA 15 and 30 vs PBO for HAQ-DI (LSmean change
-0.39 and -0.42 vs -0.17, p<.001). At Wk 24, responseswere similar or greater for pts
originally on UPA and comparable for pts whoswitched to UPA after 12 wks of PBO.
In the first12 wks, frequency of AEs was comparable for PBO and UPA 15, but higher for
UPA30 (Table 2). Overall AE rates (E/100 PY) through Wk 24 for UPA 30 weresimilar
or slightly higher than UPA15; more AEs led to study drugdiscontinuation in UPA 30.
Occurrence of infections was similar in all arms,but there were more serious infections
and herpes zoster cases in UPA 30. Malignancieswere observed in 4 pts over 12 wks with
1 additional case through Wk 24.Through Wk 12, pulmonary embolism (PE) was reported
in 2 pts (1 each on UPA 15and 30), none with DVT; through Wk 24, PE were reported in
4 more pts (UPA 15:3, 1 of whom also had a DVT; UPA 30:1). All had risk factors for
DVT/PE. Twodeaths were reported (UPA 30: 1 prior to Wk 12; UPA 15:1 after Wk12).
Conclusion: In this treatment-refractory, bDMARD-IRRA population, rapid, significant

improvements in signs and symptoms wereobserved with UPA at both doses vs PBO
during 12 wks of treatment, andmaintained through 24 wks. No new safety signals were
identified vs previousph2 studies. PE and DVT cases observed in this study have not been
reported forthe only other ph3 study with unblinded data to date. Overall data from the
ph3program will allow a comprehensive evaluation of the benefit:risk profile ofUPA in
RA.
Disclosure: M. C. Genovese, AbbVie, Lilly, Pfizer, Galapagos, Gilead, 2,AbbVie, Lilly,
Pfizer, Galapagos, Gilead, 5; R. Fleischmann, AbbVie, 2,AbbVie, 5; B. Combe, Abbvie,
BMS, Jansen, Lilly, MSD, Pfizer, Roche Chugai, UCB, 5; S. Hall, None; Y. Zhang,
AbbVie Inc, 3,AbbVie Inc, 1; Y. Zhou, Abbvie, 1,AbbVie, 3; M. E. F. Mohamed,
AbbVie, 1,AbbVie, 3; S. Meerwein, AbbVie, 1,AbbVie, 3; A. L. Pangan, AbbVie,
1,AbbVie, 3.

http://acrabstracts.org/abstract/upadacitinib-abt-494-in-patients-with-active-rheumatoid-
arthritis-and-inadequate-response-or-intolerance-to-biological-dmards-a-phase-3-
randomized-placebo-controlled-double-blind-study-of-a-selec
Risk of Second Malignant Neoplasm and Mortality in

Rheumatoid Arthritis Patients Treated with Biological
Dmards: A Danish Population-Based Cohort Study
Lene Dreyer1, René Cordtz2, Inger Marie J. Hansen3, Lars Erik Kristensen4, Merete
Lund Hetland5 and Lene Mellemkjær6, 1Center for Rheumatology and Spine Diseases,
Gentofte University Hospital,Rigshospitalet, Hellerup, Denmark, 2Center for
Rheumatology and Spine Diseases, Gentofte University Hospital, Rigshospitalet,
Hellerup, Denmark, 3Department of Reumatology, OUH, Svendborg Hospital, Svendborg,
Denmark, 4The Parker Institute, Copenhagen University Hospital, Bispebjerg and
Frederiksberg, Copenhagen F, Denmark, 5DANBIO, Glostrup Hospital.On behalf of all
Depts of Rheumatology in Denmark.Copenhagen Center for Arthritis Research, Center
for Rheumatology and Spine Diseases, Rigshospitalet, Denmark, Glostrup, Denmark,
6Danish Cancer Society Research Center, Copenhagen, Denmark, Copenhagen, Egypt
SESSION INFORMATION
Background/Purpose:
The safety of treatment with biological DMARDs (bDMARDs) hasbeen carefully studied
for the past 15 years, however, it is still largelyunknown whether this treatment is safe in
arthritis patients with a history ofcancer. We studied the risk of a second malignant
neoplasm (SMN)and mortality in rheumatoid arthritis (RA) patients with a history of a
primarycancer diagnosis and treated with bDMARDs.
Methods:
In total, 1678 RA patients registered in the DANBIO Register during 2000-2011, had a
primary cancer according to the Danish Cancer Registry. Hazard Ratios (HR) forSMN
and death were calculated.
Results:
There were 190 RA patients who had received bDMARDs beforetheir primary cancer
diagnosis only, 220 only after, 92 both before andafter, while 1176 arthritis patients with
cancer had never receivedbDMARDs. Among 502 patients ever treated withbDMARDs,
the HR (cancer site adjusted) for developing a SMN was 1.11 (95% Confidence interval
(CI) 0.74-1.67) compared with nevertreated, Table 1. The HR for death amongpatients
treated with bDMARDs before theprimary cancer diagnosis only, was 1.53 (95%CI 1.13-
2.09). After further adjustment for extent of the primary cancer, the HR for death was 1.20
(95% CI 0.88-1.63) among patients treated with bDMARDsbefore the primary cancer
diagnosis only, 1.36 (95% CI 0.78-2.39)among patients treated only after the cancer and
1.22 (95% CI 0.70-2.13) among patients treated both beforeand after the cancer.
Conclusion:
RA patients with a history of cancer and treated with bDMARDshad no increased risk of
a SMN compared with never treated. No clear conclusioncan be drawn regarding
mortality in bDMARD-treated patients.
Table 1. Risk of a second malignant neoplasm
(SMN) in rheumatoid arthritis patients according
to biological DMARD treatment
Treatment SMN, Person- HR1
N years (95% CI)
Never bDMARDs 70 2461 1 (ref.)
(N=1176)
Ever bDMARDs 38 1225 1.11 (0.74-
(N=502) 1.67)
bDMARDs only 11 272 1.06 (0.52-
before first cancer 2.14)
bDMARDs after first 27 953 1.13 (0.71-
cancer 1.80)
bDMARDs only 21 760 1.15 (0.68-
after first cancer 1.95)
bDMARDs both 6 193 1.09 (0.46-
before and after first 2.57)
cancer
TNF-I after 21 723 1.21 (0.73-
2.03)
Rituximab after 7 235 1.05 (0.47-
2.34)
Abbreviations: DMARD, Disease modifying anti-
rheumatic drug; HR, Hazard Ratio; TNF-I,
tumour necrosis factor-alpha inhibitor.
1 Adjusted for age, gender, calendar time and
cancer site
Table 2 Observed number of deaths (Obs) and overall mortality in rheumatoid
arthritis patients with cancer according to biological DMARD treatment
All Extent of disease recorded
N=1678 N= 1326
Treatment DeathsPerson- Adjusted1 Deaths Person- Adjusted1 Further
years adjusted2
Obs HR (95% Obs years HR (95%
CI) CI) HR (95%
CI)
Never 207 2461 1 (ref.) 150 2022 1 (ref.) 1 (ref.)
bDMARDs
Ever bDMARDs135 1225 1.25 (0.99- 110 982 1.35 1.23
1.57) (1.04- (0.94-
1.76) 1.60)
bDMARDs 93 272 1.50 (1.15- 75 214 1.53 1.20
only before first 1.97) (1.13- (0.88-
cancer 2.09) 1.63)
bDMARDs 42 953 0.92 (0.64- 35 767 1.08 1.29
after first cancer 1.31) (0.73- (0.86-
1.61) 1.94)
bDMARDs 23 760 1.01 (0.62- 20 640 1.19 1.36
only after first 1.65) (0.69- (0.78-
cancer 2.04) 2.39)
bDMARDs 19 193 0.85 (0.52- 15 128 0.99 1.22
both before and 1.38) (0.57- (0.70-
after 1.73) 2.13)
first cancer
TNF-I after 35 723 0.96 (0.66- 29 568 1.13 1.42
1.41) (0.73- (0.91-
1.74) 2.20)
Rituximab 9 235 0.86 (0.43- 8 205 1.13 1.11
after 1.72) (0.54- (0.53-
2.40) 2.35)
Abbreviations: DMARD, Disease modifying anti-rheumatic drug; HR, Hazard
Ratio; TNF-I, tumour necrosis factor-alpha inhibitor.
1Adjusted for age, gender, calendar time, cancer site 2 Further adjusted for extent
of disease
Disclosure: L. Dreyer, MSD, UCB and Janssen Pharmaceutical, 8; R. Cordtz, None; I.
M. J. Hansen, Roche Pharmaceuticals, 2; L. E. Kristensen, Pfizer, AbbVie, Amgen,
UCB, Celgene, BMS, Biogen, Forward Pharma, MSD, Novartis, Eli Lilly, and Janssen
pharmaceuticals, 8; M. Lund Hetland, AbbVie, BMS, MSD, Pfizer, Orion, Novartis,
Biogen, Eli Lilly, Celltrion, 2; L. Mellemkjær, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/risk-

of-second-malignant-neoplasm-and-mortality-in-rheumatoid-arthritis-patients-treated-
with-biological-dmards-a-danish-population-based-cohort-study
Evaluation of Intravenous Injection of Tc 99m

Tilmanocept in Static Planar Gamma Emission Imaging
and Fused SPECT/CT Imaging for Rheumatoid
Arthritis
Arash Kardan1, Bonnie Abbruzzese2, James Sanders2, Allison Kissling2, David Ralph2,
Joanna Shuping2, Michael Blue2, Carley Hartings2, Rachael Hershey2, Ahmad Ismail2,
Izabela Gierach2, Hannah Bailey2, Amelia Spaulding2, Matthew Haynam2, George
Zubal3 and Frederick Cope2, 1Charles F. Kettering Memorial Hospital and Wright State
University Boonshoft School of Medicine, Dayton, ND, 2Navidea Biopharmaceuticals,
Inc., Dublin, OH, 3Z-Concepts, LLC, East Haven, CT
SESSION INFORMATION
Background/Purpose:Activatedmacrophages play a critical role in RA by perpetuating

inflammation via TNFαrelease and participating in the destruction of bone and cartilage.
Notably,macrophages are the dominant cell type in the synovial sublining of RA-
affectedjoints. Thus, specific detection of activated macrophageinfiltration in RA patients
may provide valuable immunodiagnostic insight towardsjoint inflammation, destruction
and overall disease progression.
Tc 99m Tilmanocept is asynthetic radiopharmaceutical imaging agent that binds to the

activated macrophagemannose receptor (CD206) with high affinity. It is currently under
investigationfor intravenous (IV) administration in subjects with RA in a dose escalation
study.The purpose of this report is to communicate safety and imaging findings fromRA
subjects who received the maximum study dose of 400 µg tilmanocept/10 mCi Tc99m.
Methods: Nine subjects with clinically diagnosed RA were enrolled in the trial.
Allsubjects received IV administration of 400 µg of tilmanocept radiolabeled with
either10 mCi (n=3), 5mCi (n=3), or 1 mCi (n=3) Tc 99m. Static planar gamma
emissionimages of the whole body and affected joints were acquired at 60 and 180
minpost injection with additional SPECT/CT imaging of affected joints.
Results: Noadverse events were observed after IV administration of 400 µg Tc 99m

tilmanoceptradiolabeled with 1, 5, or 10 mCi of Tc 99m. There was strong correlation
ofradiotracer localization to affected joints observed in gamma emission
imaging.SPECT/CT imaging further demonstrated that Tc 99m tilmanocept localization
isspecific to the PIP, MCP, knees, ankle, shoulder, elbow, and periarticularsynovial spaces
and not in cortical bone or osseous marrow spaces.
Conclusion: Overt joint-specific localization of Tc 99m tilmanocept activity was

visualizedin affected joints of all subjects who had undergone multiple RA flares
despiteprevious successful treatments, which demonstrates macrophage infiltration
ofthese joints as a key component of disease. IV injection of Tc 99m tilmanoceptat the
maximum study dose was well-tolerated with no adverse events. These findings,in
addition to prior biopsy evaluations from other subjects, confirm activatedCD206
macrophage infiltration to be a key component of RA pathology which canbe safely and
effectively visualized on gamma emission imaging with Tc 99mtilmanocept.
Disclosure: A. Kardan, None; B. Abbruzzese, None; J. Sanders, None; A. Kissling,
None; D. Ralph, None; J. Shuping, None; M. Blue, None; C. Hartings, None; R.
Hershey, None; A. Ismail, None; I. Gierach, None; H. Bailey, None; A. Spaulding,
None; M. Haynam, None; G. Zubal, None; F. Cope, None.

http://acrabstracts.org/abstract/evaluation-of-intravenous-injection-of-tc-99m-
tilmanocept-in-static-planar-gamma-emission-imaging-and-fused-spectct-imaging-for-
rheumatoid-arthritis
Significant, Sustained Improvement in Knee Function

after Intra-Articular TPX-100: A Double-Blind,
Randomized, Multi-Center, Placebo-Controlled Phase 2
Trial
Dawn McGuire1, Nancy E Lane2, Neil Segal3, Samy Metyas4, Hans Richard Barthel5,
Meghan Miller1, David Rosen1 and Yoshi Kumagai1, 1OrthoTrophix, Inc, Oakland, CA,
2UC Davis Medical Center, Sacramento, CA, 3University of Kansas, Shawnee, KS,
4Medvin Clinical Research, Covina, CA, 5Barthel Clinic, Santa Barbara, CA
SESSION INFORMATION
Background/Purpose: The current Phase 2 study was designed to evaluate safety,

tolerability and preliminary efficacy of TPX-100 by IA administration in subjects with
mild to moderate patellofemoral osteoarthritis (PFOA) involving both knees. TPX-100, a
23-amino acid peptide derived from Matrix Extracellular Phosphoglycoprotein (MEPE),
has been shown to induce articular cartilage proliferation and improve healing after
experimental injury in large and small animal models after IA administration. A unique
feature of this clinical trial was the use of each subject as his/her own control, intended to
minimize effects of age, sex, genetic factors, and activity levels that can complicate inter-
subject comparisons. Knee-specific patient-reported outcomes (PROs) used in this study,
including the Knee Osteoarthritis Outcome Score (KOOS), were recorded separately for
left and right knees.
Methods: Adult men and women with bilateral PFOA (ICRS grade 1-3, confirmed by
screening MRI) were enrolled at 15 sites. One knee was randomly assigned to receive
TPX-100 for 4 weekly injections, while the contralateral knee (control) received identical
placebo (saline) injections. Investigator, subject, site and sponsor were blinded as to
treatment assignment. The study had two parts: in Part A, 4 dose cohorts (n=6-9
subjects/cohort; 20, 50, 100 and 200mg/injection) were enrolled. Safety/tolerability of
each cohort was evaluated by a Safety Review Committee (SRC) before the next cohort
was enrolled. There were no dose-limiting toxicities or safety concerns at any dose, and
the 200 mg dose was selected dose for Part B of the study.
Results: A total of 118 subjects (236 knees) were enrolled, 29 in Part A and 89 in Part B.
The study population was fairly representative of the knee OA population in the U.S.
regarding age (median 60 years) and Body Mass Index (29.2). There were no drug-related
SAEs and no dose-limiting toxicities across doses from 20-200 mg/injection. Common
adverse events such as knee pain had virtually identical incidences in control and TPX-
100-treated knees. Efficacy results were based on the “per-protocol” population of 93
subjects (186 knees) who received 4 weekly injections of 200mg TPX-100 (from Part A
or Part B) in the knee randomly assigned to active drug and had at least one MRI after
baseline. Quantitative MRI revealed no measurable between-knee differences in cartilage
thickness or volume at 6 or 12 months. However, statistically significant (P<.05) and
clinically meaningful differences, per literature criteria, in knee function were
demonstrated in favor of TPX-100-treated knees compared with controls at 6 and 12
months, including activities of daily living, sports activities, and knee-related quality of
life, and a significant reduction in pain going up or down stairs. Subjects’ use of
analgesics, including non-steroidal anti-inflammatory medications, declined markedly
during the study. Results will be provided in detail.
Conclusion: Improving the functional status of patients with knee OA is a central

therapeutic goal of OA treatment. In the present proof-of-concept study, TPX-100,
administered in 4 weekly intra-articular injections, was safe and associated with robust
functional benefits for up to 12 months.
Disclosure: D. McGuire, OrthoTrophix, Inc, 3; N. E. Lane, OrthoTrophix, 9; N. Segal,

OrthoTrophix, 9; S. Metyas, OrthoTrophix, 9; H. R. Barthel, OrthoTrophix, 9; M.
Miller, OrthoTrophix, Inc, 3; D. Rosen, OrthoTrophix, Inc, 3; Y. Kumagai, Ortho rophix,
Inc, 3.

http://acrabstracts.org/abstract/significant-sustained-improvement-in-knee-function-after-
intra-articular-tpx-100-a-double-blind-randomized-multi-center-placebo-controlled-phase-
2-trial
Miv-711, a Novel Cathepsin K Inhibitor Demonstrates

Evidence of Osteoarthritis Structure Modification:
Results from a 6 Month Randomized Double-Blind
Placebo-Controlled Phase IIA Trial
Philip G. Conaghan1, Michael A Bowes2, Sarah R. Kingsbury1, Alan Brett2, Gwenael
Guillard2, Åsa Jansson3, Cecilia Wadell3, Richard Bethell3 and John Öhd3, 1University of
Leeds, Leeds, United Kingdom, 2Imorphics Ltd, Manchester, United Kingdom, 3Medivir
AB, Huddinge, Sweden
SESSION INFORMATION
Background/Purpose:
The need for drugsthat achieve structure modification in OA is imminent but their
development hasbeen burdened by the need for large, long term studies. New imaging
biomarkersusing structured machine learning offer opportunity for shorter duration
andsmaller DMOAD trials. MIV-711, a potent and selective cathepsin K inhibitor
reducedCTX-I and CTX-II after once-daily administration for up to 28 days in
healthyvolunteers. Our aim was to examine the efficacy (symptoms and structure)
andsafety of MIV-711 in knee OA patients.
Methods:
Patients with ACR knee OA, KL2-3 and pain≥4 & <10 on 0-10 NRS were enrolled at one
of 6 European sites andrandomised to receive MIV-711 100mg or 200mg or matched
placebo qd. Participantsremained on usual analgesic medication. Clinical (pain, function,
QoL) andsafety data were recorded serially and MRI was performed at baseline and
wk26. Primaryoutcome was change in NRS pain score with the key secondary endpoint of
changein MRI bone area (medial femur). The main analyses were conducted using
linearmixed models.
Results:
244 participants were enrolled (100mg n=82,200mg n=82, placebo n=80), 69% women,
mean age 62, mean BMI ~32. NRS pain scores;function and QoL measures were not
statistically significantly reduced comparedto placebo. However, there was a trend to
reduction for MIV-711 on the NRS (Figure1) and across the majority of patient-reported
outcomes. Significant reductionin medial femur bone area change for both MIV-711 doses
(unadjusted p-values =0.002and 0.004) were observed at wk26, with no evident
differences between the 2doses (Figure 2A). MIV-711 treated participants demonstrated
reduced loss ofcartilage thickness on the medial femur versus placebo (unadjusted
p=0.023 for100mg dose, 0.125 for 200mg dose, Figure 2B); medial tibia cartilage loss
wasnot significant. The reductions observed for the biomarkers CTX-I and –II
weresubstantial and of a similar magnitude, indicating strong target engagement forboth
doses. There was generally good tolerability and safety, with infrequent
musculoskeletalsymptoms, infections and rashes.
Conclusion:
MIV-711 demonstrated significant reductionin OA bone disease progression, and also

reduced cartilage progression, in thefemur. Although there was no statistically significant
reduction in pain, thestudy duration required to fully realize the symptom benefits
expected fromstructure modification is unclear. Further evaluation of this novel agent
isnow warranted.
Disclosure: P. G. Conaghan, Novartis Pharmaceutical Corporation, 5,Flexion
Therapeutics, 5,AbbVie, 5,Infirst, 5,Medivir, 5,Merck Serono, 5,ONO Pharmaceutical
Co., 5; M. A. Bowes, Imorphics Ltd, 3; S. R. Kingsbury, Medivir AB, 5; A. Brett,
Imorphics Ltd, 3; G. Guillard, Imorphics Ltd, 3; Å. Jansson, Medivir AB, 3,Medivir
AB, 1; C. Wadell, Medivir AB, 3; R. Bethell, Medivir AB, 3,Medivir AB, 1; J. Öhd,
Medivir AB, 3,Medivir AB, 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/miv-

711-a-novel-cathepsin-k-inhibitor-demonstrates-evidence-of-osteoarthritis-structure-
modification-results-from-a-6-month-randomized-double-blind-placebo-controlled-phase-
iia-trial
A Phase 2, Randomized, Double-Blind, Placebo-

Controlled, Titration-to-Effect Study of Orally
Administered CR845 in Patients with Osteoarthritis of
the Hip or Knee
Sukirti Bagal, Catherine Munera, Patricia Brady and Joseph Stauffer, Cara Therapeutics,
Stamford, CT
SESSION INFORMATION
Background/Purpose: CR845 is a selective kappa opioid receptor agonist with a

peripheral mechanism of action. Here we report preliminary results from a Phase 2b study
designed to characterize the analgesic efficacy of orally administered CR845 in patients
with osteoarthritis (OA) of the hip or knee (ClinicalTrials.gov NCT02944448).
Methods: 476 male and female patients (ages ≥25 years) with moderate to severe pain
(numeric rating scale [NRS] ≥5) associated with hip or knee OA were enrolled at 33 sites
in the US. Following a 14-day screening period, patients were randomized 2:1 to CR845
or placebo, respectively. CR845 (1.0, 2.5, or 5.0 mg) or placebo were administered BID
for a total of 8 weeks, with doses administered at least 2 hours before or after a meal.
Patients started on 1.0 mg or placebo, then during the 4-week post-randomization period,
titrated upward to 2.5 or 5.0 mg to effect in a double-blind fashion and maintained for 4
weeks on the final individualized effective dose. The primary outcome measure was
change from baseline in the weekly mean pain intensity score (0-10, NRS) at the index
joint with CR845 compared to placebo at Week 8/Day 57. Secondary outcome measures
included differences between CR845 and placebo in the Western Ontario and McMaster
Osteoarthritis Index (WOMAC) total and sub-scores and in the Patient Global Impression
of Change (PGIC) scale. Safety and tolerability measures were also captured over the 8-
week treatment period.
Results: Efficacy was assessed in 118 hip OA patients (CR845, n=78; placebo, n=40) and
358 patients with knee OA (CR845, n=238; placebo, n=120). The primary efficacy results
comparing CR845 (all doses) vs placebo were not statistically significant. However,
patients with hip OA maintained on 5.0 mg (n=66) exhibited a statistically significant
69% reduction in mean joint pain score over placebo (p=0.043) accompanied by a 41%
reduction over placebo in use of rescue medication at Week 8. The proportion of patients
who titrated to the 5.0 mg dose and reported a PGIC score of "very much improved" or
"much improved" was statistically higher in patients with knee OA (p<0.005 vs placebo)
and hip OA (p<0.006 vs placebo). Patients maintained on the 1.0 and 2.5 mg doses did
not exhibit statistically significant reductions in mean joint pain scores compared to
placebo nor did patients with knee OA at any dose. Doses were generally well tolerated
with no drug-related serious AEs. The most common AEs with ≥5% incidence were
constipation (13%), dizziness (8%), and dry mouth (6%). There were no clinically
significant changes in serum sodium levels during the 8-week treatment period for any
dose group.
Conclusion: Post-hoc analyses demonstrated that hip OA patients receiving CR845 5.0
mg had significant pain reduction compared to placebo patients. The PGIC measure of
pain in hip and knee patients combined also showed significant benefit of 5.0 mg CR845
while other pain measures showed improvement but not statistical significance. These
beneficial effects and a positive safety profile warrant further clinical study.
Disclosure: S. Bagal, Cara Therapeutics, 3; C. Munera, Cara Therapeutics, 3; P. Brady,

Cara Therapeutics, 3; J. Stauffer, Cara Therapeutics, 3,Cara Therapeutics, 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-

phase-2-randomized-double-blind-placebo-controlled-titration-to-effect-study-of-orally-
administered-cr845-in-patients-with-osteoarthritis-of-the-hip-or-knee

Incidence of Thromboembolic Events in the Tofacitinib
Rheumatoid Arthritis, Psoriasis, Psoriatic Arthritis and
Ulcerative Colitis Development Programs
Philip J Mease1, Joel Kremer2, Stanley Cohen3, Jeffrey R Curtis4, Christina Charles-
Schoeman5, Edward V Loftus6, Jeffrey D Greenberg7, Niki Palmetto8, Keith S Kanik9,
Daniela Graham9, Cunshan Wang9, Pinaki Biswas8, Gary Chan10, Ryan DeMasi10,
Hernan Valdez8, Thijs Hendrikx10 and Thomas V Jones10, 1Swedish Medical Center and
University of Washington, Seattle, WA, 2Medicine, Albany Medical College and the
Center for Rheumatology, Albany, NY, 3Metroplex Clinical Research Center, Dallas, TX,
4University of Alabama, Birmingham, AL, 5University of California, Los Angeles, CA,
6Mayo Clinic, Rochester, MN, 7Corrona, LLC, Southborough, MA, 8Pfizer Inc, New
York, NY, 9Pfizer Inc, Groton, CT, 10Pfizer Inc, Collegeville, PA

SESSION INFORMATION
Background/Purpose: Tofacitinib is an oral Janus kinase(JAK) inhibitor that

preferentially inhibits signaling by JAK3 and JAK1, with functionalselectivity over
JAK2. Potential increased risk of venous thromboembolic events(VTE) in patients (pts)
with rheumatoid arthritis (RA) has been reported for a JAK1/2 inhibitor.1 To assess VTE
risk with tofacitinib, data werereviewed from the tofacitinib development program in RA,
psoriasis (PsO),psoriatic arthritis (PsA), and ulcerative colitis (UC).
Methods: Data from Phase (P) 2 (RA, PsO, UC) and P3 (RA, PsO, PsA, UC) randomized
clinical studies oftofacitinib as monotherapy or in combination with conventional
synthetic(cs)DMARDs were included. Two cohorts were defined; 1) the placebo (PBO)-
controlledcohort: pts randomized to tofacitinib 5 or 10 mg BID, or PBO up to Month (M)
3 inRA, PsO, and PsA studies, and pts randomized to tofacitinib 10 mg BID or PBOfor
the 9-week induction period in UC studies; 2) the dose-comparison cohort: ptsrandomized
to tofacitinib 5 or 10 mg BID, adalimumab (ADA) 40 mg SC Q2W (RA andPSA only) or
methotrexate (MTX) 20 mg QW (RA only) throughout the P2/3 studies forRA (up to
M24), PsO (up to M12), and PsA (up to M12), and for the 12-month P3UC maintenance
study. First deep vein thrombosis (DVT) and pulmonary embolism(PE) events were
identified using the MedDRA embolic and thrombotic SMQ preferredterms restricted to
the respiratory, thoracic, mediastinal, and vasculardisorder System Organ Classes;
incidence rates (IRs; pts with events/100 pt-years)were based on single events occurring
during treatment or ≤28 days afterthe last dose or up to the cohort cut-off date. IRs for PE
in pts with RA werecompared with Corrona Registry data.
Results: Up to M3 in the PBO-controlled cohort, DVT and PEwere both independently

reported in 1 pt with RA and 1 with UC, who bothreceived PBO; no pts receiving
tofacitinib had DVT or PE events (Table).In the dose-comparison cohort there were 2
DVT events in tofacitinib-treated ptswith RA (5 mg BID, n=1; 10 mg BID n=1) and 1
DVT event in a pt with PsA(tofacitinib 10 mg BID) (Table). IRs were 0.1 (95% CI: 0.0,
0.3) for bothtofacitinib doses in RA, and 0.5 (95% CI: 0.0, 2.8) for tofacitinib 10 mg
BIDin PsA. Five PE events occurred in the dose‑comparison cohort, all in RA(5 mg BID,
n=2; 10 mg BID, n=3). IRs were 0.1 (95% CI: 0.0, 0.4) fortofacitinib 5 mg BID and 0.2
(95% CI: 0.0, 0.4) for 10 mg BID. IRs for PE with tofacitinib in RA weresimilar to those
reported by the Corrona Registry in pts with RA treated withtofacitinib (0.1 [95% CI: 0.0,
0.4]), biologic DMARDs (0.2 [95% CI: 0.1, 0.3]), and csDMARDs (0.2 [95% CI: 0.0,
0.5]). DVT were reported twice with MTX, and nonewith ADA.
Conclusion: Analysis of DVT and PE across randomized clinical studiesfor RA, PsO,
PsA, and UC showed no evidence of an increased risk of events withtofacitinib.
1. Kremer K, et al.EULAR 2017 Abstract, FRI0090.

Disclosure: P. J. Mease, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly,
Janssen, Novartis, Pfizer Inc, Sun Pharmaceutical, UCB, 2,AbbVie, Amgen, Bristol-
Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, Sun Pharmaceutical,
UCB, 5,AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis,
Pfizer Inc, UCB, 8; J. Kremer, Corrona, LLC, 1,Corrona, LLC, 3,AbbVie, Amgen, BMS,
Genentech, Lilly, Regeneron, Sanofi, Pfizer, 5,AbbVie, Genentech, Lilly, Novartis, Pfizer,
2; S. Cohen, AbbVie, Amgen, Boehringer Ingelheim, Gilead, Merck, Pfizer Inc,
5,AbbVie, Amgen, Boehringer Ingelheim, Gilead, Merck, Pfizer Inc, 9; J. R. Curtis,
Amgen, 2,Corrona, 2,Crescendo Bio, 2,Pfizer Inc, 2,AbbVie, 5,Amgen, 5,Bristol-Myers
Squibb, 5,Corrona, 5,Eli Lilly and Company, 5,Janssen Pharmaceutica Product, L.P.,
5,Myriad, 5,Pfizer Inc, 5,Roche Pharmaceuticals, 5,UCB, 5; C. Charles-Schoeman,
AbbVie, Bristol-Myers Squibb, Pfizer Inc, 2,Amgen, Pfizer Inc, Regeneron-Sanofi, 3; E.
V. Loftus, AbbVie, 5,Amgen, 5,CVS Caremark, 5,Eli Lilly and Company, 5,Janssen
Pharmaceutica Product, L.P., 5,Mesoblast, 5,Pfizer Inc, 5,Salix, 5,Takeda, 5,UCB,
5,AbbVie, 2,Amgen, 2,Celgene, 2,Genentech and Biogen IDEC Inc., 2,Gilead, 2,Janssen
Pharmaceutica Product, L.P., 2,MedImmune, 2,Pfizer Inc, 2,Receptos, 2,Robarts Clinical
Trials, 2,Seres, 2,Takeda, 2,UCB, 2; J. D. Greenberg, Corrona, LLC, 1,Corrona, LLC,
3,Eli Lilly, Genentech, Janssen, Novartis, Pfizer, 5; N. Palmetto, Pfizer Inc, 1,Pfizer Inc,
3; K. S. Kanik, Pfizer Inc, 1,Pfizer Inc, 3; D. Graham, Pfizer Inc, 1,Pfizer Inc, 3; C.
Wang, Pfizer Inc, 1,Pfizer Inc, 3; P. Biswas, Pfizer Inc, 1,Pfizer Inc, 3; G. Chan, Pfizer
Inc, 1,Pfizer Inc, 3; R. DeMasi, Pfizer Inc, 1,Pfizer Inc, 3; H. Valdez, Pfizer Inc, 1,Pfizer
Inc, 3; T. Hendrikx, Pfizer Inc, 1,Pfizer Inc, 3; T. V. Jones, Pfizer Inc, 1,Pfizer Inc, 3.
http://acrabstracts.org/abstract/incidence-of-thromboembolic-events-in-the-tofacitinib-
rheumatoid-arthritis-psoriasis-psoriatic-arthritis-and-ulcerative-colitis-development-
programs
Subcutaneous Secukinumab Inhibits Radiographic

Progression in Psoriatic Arthritis: Primary Results from
a Large Randomized, Controlled, Double-Blind Phase 3
Study
Philip J Mease1, Désirée van der Heijde2, Robert B.M. Landewé3, Shephard Mpofu4,
Proton Rahman5, Hasan Tahir6, Atul Singhal7, Elke Böttcher8, Sandra V. Navarra9, Karin
Meiser4, Aimee Readie10, Luminita Pricop10 and Ken Abrams10, 1Swedish Medical
Center and University of Washington, Seattle, WA, 2Leiden University Medical Center,
Leiden, Netherlands, 3Academic Medical Center, Amsterdam and Atrium Medical Center,
Heerlen, Netherlands, 4Novartis Pharma AG, Basel, Switzerland, 5Rheumatology,
Memorial University of Newfoundland, St Johns, NF, Canada, 6Whipps Cross Hospital,
London, United Kingdom, 7Southwest Rheumatology, Dallas, TX, 8Rheumazentrum
Favoriten, Vienna, Austria, 9Rheumatology, University of Santo Tomas Hospital, Manila,
Philippines, 10Novartis Pharmaceuticals Corporation, East Hanover, NJ
SESSION INFORMATION
Background/Purpose: Secukinumab, a fullyhuman monoclonal antibody that

selectivelyneutralizes IL-17A, has shownsignificant and rapid efficacy in psoriatic
arthritis (PsA). We present primaryresults of FUTURE 5 (NCT02404350),the largest
randomized controlled trial (RCT) of a biologic conducted to date inPsA, assessing
efficacy of subcutaneous (sc) secukinumab 300 mg and 150 mg, includingradiographic
inhibition of structural damage, and safety.
Methods: Adults (n =996) with active PsA, stratified by previous anti-TNFuse, were
randomized 2:2:2:3 to sc secukinumab 300 mg with loading dosage (LD),150 mg with
LD, 150 mg without LD, or placebo (PBO). All groups receivedsecukinumab or PBO at
baseline (BL), Wks 1, 2, 3, and 4, and then every 4 wks. At Wk 16, PBO non-responders
(patients [pts] with <20% improvement from BL intender or swollen joint counts) were
switched to secukinumab 300 mg or 150 mg;remaining PBO pts were switched at Wk 24.
The primary endpoint was ACR20 at Wk 16. The key secondary endpoint was
radiographic structural progression,as measured by modified total van der Heijde Sharp
score (mTSS), assessed by two blinded readers, based on hand/wrist/foot X-rays obtained
at BL, Wk16 (non-responders), and Wk 24. Statistical analyses used non-
responderimputation for binary variables, linear extrapolation for radiographic data,and
missing at random assumption for continuous endpoints. Testing results useda pre-defined
hierarchical hypothesis testing strategy to adjust formultiplicity.
Results: BL characteristics werebalanced across arms. Approximately30% of pts had

experienced an inadequate response or intolerance to previousanti-TNF therapy.
Secukinumabsignificantly improved ACR20 at Wk 16 vs. PBO. Radiographic progression
(mTSS) wassignificantly inhibited at Wk 24 in all secukinumab arms vs. PBO (Table).A
greater proportion of pts had no radiographic progression (change from BL in mTSS≤0.5)
with secukinumab vs. PBO: 88% (300 mg), 79% (150 mg), 83% (150 mgwithout LD),
and 73% (PBO). All hierarchical endpoints were significant forsecukinumab vs. PBO at
Wk 16, except for enthesitis and dactylitis resolutionfor 150 mg without LD (Table).
Table. Summary of hierarchical primary endpoints
Week 16 Data‡ Secukinumab Secukinumab Secukinumab Placebo
300 mg sc 150 mg sc 150 mg sc
without LD (n=332)
(n=222) (n=220)
(n=222)
ACR20 62.6* 55.5* 59.5* 27.4
(% responders)
mTSS 0.08¥ 0.17∞ –0.09¥ 0.50
structural
progression
(mean change
from BL to
week 24)
PASI 75/90 70.0*/53.6* 60.0*/36.8* 58.1*/31.6* 12.3/9.3
(% responders)
ACR50 39.6* 35.9* 32.0* 8.1
(% responders)
HAQ-DI score –0.55* –0.44* –0.45* –0.21
(LS mean
change from
BL)
DAS28-CRP –1.49* –1.29* –1.29* –0.63
score (LS mean
change from
BL)
Enthesitis 55.7† 54.6† 41.9 35.4
resolution (%)
Dactylitis 65.9* 57.5† 56.3 32.3
resolution (%)
*P < 0.0001; †P < 0.001; ¥ P < 0.01; ∞P < 0.05 un-adjusted p-values
vs. placebo. ‡Week 24 data for mTSS. ACR, American College of
Rheumatology response criteria; BL, baseline; DAS28-CRP, Disease
Activity Score-28-joint count C-reactive protein; HAQ-DI, Health
Assessment Questionnaire – Disability Index; LD, loading dosage; LS,
least squares; mTSS, modified total van der Heijde Sharp score; PASI,
Psoriasis Area and Severity Index; sc, subcutaneous
Efficacyacross all endpoints was greater in pts who were anti-TNF-naïve. The 300 mg
and150 mg groups had an earlier onset of response vs. pts who received 150 mg
withoutLD. Adverse event (AE) ratesat Wk 16 were 51.8% (300 mg), 52.7% (150 mg),
52.7% (150 mg without LD) and58.7% (PBO); non-fatal serious AE rates were 2.3%,
3.2%, 1.4%, and 3.0%,respectively. No deaths were reported.
Conclusion: Subcutaneous secukinumab300 mg with LD and 150 mg with and without

LD, inhibited radiographic structuralprogression and provided rapid and clinically
significant improvements in thesigns, symptoms and physical function of pts with PsA.
The safety profile wasconsistent with that previously reported with no new safety signals
identified.
Disclosure: P. J. Mease, AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer,
Sun, UCB, 2,AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Corrona, Demira,
Janssen, Lilly, Novartis, Pfizer, Sun, UCB, Zynerba, 5,AbbVie, Amgen, BMS, Celgene,
Crescendo Bioscience, Genentech, Janssen, Novartis, Pfizer, UCB, 8; D. van der Heijde,
AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi,
Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer,
Regeneron, Roche, Sanofi, Takeda, UCBAbbVie, Amgen, Astellas, AstraZeneca, BMS,
Boehringe, 5,Director: Imaging Rheumatology bv, 9; R. B. M. Landewé, Abbott/AbbVie,
Ablynx, Amgen, Astra-Zeneca, Bristol Myers Squibb, Celgene, Janssen (formerly
Centocor), Galapagos, GlaxoSmithKline, Novartis, Novo-Nordisk, Merck, Pfizer, Roche,
Schering-Plough, TiGenix, UCB, and Wyeth, 5,Abbott, Amgen, Centocor, Novartis,
Pfizer, Roche, Schering-Plough, UCB, and Wyeth, 2,Abbott/AbbVie, Amgen, Bristol
Myers Squibb, Janssen (formerly Centocor), Merck, Pfizer, Roche, Schering-Plough,
UCB, and Wyeth, 8; S. Mpofu, Novartis, 1,Novartis, 3; P. Rahman, Janssen
Pharmaceutica Product, L.P., 8,Amgen, AbbVie, BMS, Celgene, Pfizer, Janssen, Wyeth,
EliLiiy, Novartis, 8,Amgen, AbbVie, BMS, Celgene, Pfizer, Janssen, Wyeth, EliLiiy,
Novartis, 5; H. Tahir, Abbvie, 5,Novartis Pharmaceutical Corporation, 5,Pfizer Inc,
5,UCB, 5,Eli-Lily, 5,Janssen Pharmaceutica Product, L.P., 5,Novartis Pharmaceutical
Corporation, 2,Pfizer Inc, 2; A. Singhal, Abbvie, 2,Gilead, 2,Sanofi, 2,Regeneron,
2,Amgen, 2,Roche Pharmaceuticals, 2,BMS, 2,Janssen Pharmaceutica Product, L.P.,
2,Lilly, 2,Novartis Pharmaceutical Corporation, 2,Pfizer Inc, 2,UCB, 2,AstraZeneca,
2,MedImmune, 2,FujiFilm, 2,Nichi-Iko, 2,Mallinckrodt, 2,Abbvie, 8; E. Böttcher,
Amgen, 5,Roche Pharmaceuticals, 5,Eli-Lily, 5,Pfizer Inc, 5,MSD, 5,Novartis
Pharmaceutical Corporation, 5,Amgen, 8,Roche Pharmaceuticals, 8,Eli-Lily, 8,Pfizer Inc,
8,MSD, 8,Novartis Pharmaceutical Corporation, 8; S. V. Navarra, Pfizer Inc, 5,Novartis
Pharmaceutical Corporation, 5,AstraZeneca, 5,Janssen Pharmaceutica Product, L.P.,
5,Astellas, 5,Roche Pharmaceuticals, 5,Pfizer Inc, 8,Novartis Pharmaceutical Corporation,
8,AstraZeneca, 8,Janssen Pharmaceutica Product, L.P., 8,Astellas, 8,Roche
Pharmaceuticals, 8; K. Meiser, Novartis, 3; A. Readie, Novartis Pharmaceutical
Corporation, 3,Novartis Pharmaceutical Corporation, 1; L. Pricop, Novartis
Pharmaceutical Corporation, 1,Novartis Pharmaceutical Corporation, 3; K. Abrams,
Novartis Pharmaceutical Corporation, 3,Novartis Pharmaceutical Corporation, 1.

http://acrabstracts.org/abstract/subcutaneous-secukinumab-inhibits-radiographic-
progression-in-psoriatic-arthritis-primary-results-from-a-large-randomized-controlled-
double-blind-phase-3-study
Rituximab As Re-Induction Therapy in Relapsing

ANCA-Associated Vasculitis
Rona Smith1, Rachel Jones2, Ulrich Specks3, Carol A McAlear4, Kim Mynard2, Simon
Bond2, David Jayne5 and Peter A. Merkel6, 1Department of Medicine, University of
Cambridge, Department of Medicine, University of Cambridge, Cambridge, United
Kingdom, 2Cambridge University Hospitals NHS Foundation Trust, Cambridge, United
Kingdom, 3Mayo Clinic College of Medicine, Rochester, MN, 4University of
Pennsylvania, Philadelphia, PA, 5Vasculitis and Lupus Clinic, Department of Medicine,
University of Cambridge, Cambridge, United Kingdom, 6Division of Rheumatology,
University of Pennsylvania, Philadelphia, PA
SESSION INFORMATION
Background/Purpose:
RITAZAREM (ClinicalTrials.gov: NCT01697267) is an international,

randomized,controlled trial comparing rituximab with azathioprine as maintenance
therapy afterinduction of remission with rituximab and glucocorticoids for
relapsingANCA-associated vasculitis (AAV). Since all patients receive rituximab for
induction, the RITAZAREM trial isalso the largest prospective study of the use of
rituximab in patients with relapsingAAV.
Methods:
188 patients with granulomatosis withpolyangiitis (GPA) or microscopic polyangiitis

(MPA) were enrolled and receivedremission-induction therapy with rituximab (4 x 375
mg/m2) and ahigher- or lower-dose glucocorticoid regimen, depending on physician
choice:reducing from either prednisone (or prednisolone) 1 mg/kg/day or 0.5 mg/kg/dayto
10 mg/day by 4 months. Severe diseasewas defined as an organ- or life-threatening
manifestation. Patients who achieved remission (BVAS/WG≤1 and prednisone ≤10 mg
daily) by month 4 were randomized toeither repeat dose rituximab (1 g every 4 months) or
azathioprine (2 mg/kg/day)for a total treatment period of 24 months. Preliminary results
of the 4-month induction phase are reported.
Results:
95/188 (51%) subjects were male, median age 59years (interquartile range (IQR) 47.5-
68.0), disease duration of 5.0 years (IQR1.85-10.15). 149/188 (79%) hadpreviously
received cyclophosphamide and 67/188 (36%) had previously received
rituximab. 137/188 (73%) had PR3-ANCA positivedisease, and 51/188 (37%) MPO-
ANCA positive disease. 118/188 (63%) of relapses were severe, 56/188(30%) received
the higher-dose glucocorticoid regimen and 132/188 (70%)received the lower-dose
glucocorticoid regimen (Table 1). The median BVAS/WG at enrollment was 5,maximum
14.
Data on responses at month 4 was available on181 patients. 165/181 (91.2%) ofpatients
achieved remission. 11/181 (6.0%)patients failed to achieve remission: 9/11 had PR3-
ANCA positive disease; 9/11had ear, nose, and throat involvement at baseline; 7/11 had
severe disease atenrollment; and 9/11 received the lower (0.5 mg/kg) glucocorticoid
dosingregimen. 5 (2.8%) patients died in theinduction phase; causes of death included:
pneumonia (2), cerebrovascularaccident (1), alveolar hemorrhage/respiratory failure (1),
and colon cancer(1).
53 severe adverse events (SAEs) occurred in 30patients during the induction phase; 15/53
(28%) SAEs were severe infections. 52/188 (28%) patients developed an IgG level<5g/l
in the induction phase.
Conclusion:
Data from the first phase of RITAZAREM, thelargest reported cohort of patients with
relapsing AAV, demonstrates that rituximab,in conjunction with glucocorticoids, is highly
effective at re-inducing remissionin patients with AAV who have relapsed, with an
acceptable safety profile. The maintenance phase of the RITAZAREM trialis ongoing.
Table 1. Distribution of study subjects based on severity of relapse at

enrollment and glucocorticoid induction regimen
Glucocorticoid induction Relapse Severity at Totals
regimen Enrollment (%) (%)
(oral
prednisone/prednisolone) Severe Non-Severe
High-dose (starting at 45 / 188 (24%) 11 / 188 (6%) 56 / 188 (30%)
1mg/kg/day)
Low-dose (starting at 73 / 188 (39%) 59 / 188 (31%) 132 / 188 (70%)
0.5mg/kg/day)
Totals (%) 118 / 188 70 / 188 (37%)
(63%)
Disclosure: R. Smith, Roche Pharmaceuticals, 2; R. Jones, Roche Pharmaceuticals, 2; U.

Specks, Genentech and Biogen IDEC Inc., 2; C. A. McAlear, Genentech and Biogen
IDEC Inc., 2; K. Mynard, Roche Pharmaceuticals, 2; S. Bond, Roche Pharmaceuticals,
2; D. Jayne, Roche Pharmaceuticals, 2; P. A. Merkel, Genentech and Biogen IDEC Inc.,
2.

http://acrabstracts.org/abstract/rituximab-as-re-induction-therapy-in-relapsing-anca-
associated-vasculitis
Abstract Number: 1
Anti-Phosphatidylserine/Prothrombin Antibodies (aPS/PT) As Potential Diagnostic

Markers and Risk Predictors of Venous Thrombosis and Obstetric Complications in
Antiphospholipid Syndrome
Hui Shi1, Qiongyi Hu2, Hui Zheng2, Jialin Teng2, Gary Norman3, Jinfeng Zhou4 and Chengde Yang2, 1Department of Rheumatology and
Immunology, Ruijin Hospital,Shanghai Jiao Tong University School of Medicine, Shanghai, China, Shanghai, China, 2Ruijin
Hospital,Shanghai Jiao Tong University School of Medicine, Shanghai, China, Shanghai, China, 3INOVA Diagnostics, Inc, San Diego, China,
4Werfen China, Shanghai, China
First publication: September 18, 2017
SESSION INFORMATION
Session Date: Sunday, November 5, 2017
Session Title: Antiphospholipid Syndrome Poster
Session Type: ACR Poster Session A
Background/Purpose: , Methods: , Results: and Conclusion:
Background/Purpose:
The antiphospholipid syndrome (APS) is a thrombophilic disorder characterized by clinical manifestations of vascular thrombosis and
obstetric complications associated with the presence of specific antiphospholipid antibodies (aPLs). Most patients with APS can be
identified using the conventional laboratory assays for LAC, IgG/IgM anti-cardiolipin (aCL), and IgG/IgM anti-ß2glycoprotein I (ß2GPI)
antibodies. Some patients with clinical manifestations highly suggestive of APS however are negative for these classic biomarkers and
new biomarkers are needed to identify these “seronegative APS or SNAPS) patients. Anti-Phosphatidylserine/Prothrombin (aPS/PT)
antibodies are positive in many SNAPS patients. In the present study we assessed the prevalence and significance of aPS/PT, as well
conventional APS biomarkers, in a large cohort of well-characterized patients with APS from the Shanghai region of China.
Methods:
186 Chinese patients meeting the criteria for the classification of APS using the Sydney criteria (67 primary and119 secondary APS), 48
with SNAPS, 176 disease controls ((79 systemic lupus erythematosus (SLE), 29 Sjogren’s syndrome (SS), 30 ankylosing spondylitis
(AS), 38 rheumatoid arthritis (RA)), and 90 healthy donors were examined. IgG and IgM aPS/PT, IgG, IgM, IgA anticardiolipin (aCL),
and IgG, IgM, IgA anti-ß2-glycoprotein I (anti-ß2GPI) antibodies were tested by QUANTA Lite® ELISA kits (Inova Diagnostics, San
Diego, CA). Statistical analyses were performed using SPSS 23.0 (IBM, Chicago, IL, USA) or Analyze-it ver 4.6 (Analyze-it Software,
LTD). T-test, Mann-Whitney U test, Kappa test, Fisher’s exact or Chi-square tests were applied.
Results:
160(86.0%) of APS patients were positive for at least one aPS/PT isotype. 135(72.6%) were positive for IgG aPS/PT, 124/186(66.7%)
positive for IgM aPS/PT, and 99(53.2%) positive for both. Approximately half of the SNAPS patients were positive for IgG and/or IgM
aPS/PT. Highly significant associations between IgG aPS/PT and venous thrombotic events (OR 6.72) and IgG/IgM aPS/PT and
pregnancy loss (OR 9.44) were found. Levels of IgM aPS/PT were significantly different in APS patients with thrombotic manifestations
and those with fetal loss (p=0.014). The association between IgG/IgM aPS/PT and LAC was highly significant (p<0.001), when both
were positive the OR for APS was 101.6. Notably, 91.95%(80/87) of LAC positive specimens were positive for IgG and/or IgM aPS/PT
suggesting aPS/PT is an effective option when LAC testing is not available.
Conclusions:
Anti-PS/PT antibody assays demonstrated high diagnostic performance for Chinese patients with APS, detected some APS patients
negative for criteria markers, and may serve as potential risk predictors for venous thrombosis and obstetric complications.
Disclosure: H. Shi, None; Q. Hu, None; H. Zheng, None; J. Teng, None; G. Norman, None; J. Zhou, None; C. Yang, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/anti-phosphatidylserineprothrombin-antibodies-apspt-as-

potential-diagnostic-markers-and-risk-predictors-of-venous-thrombosis-and-obstetric-complications-in-antiphospholipid-syndrome
Abstract Number: 2
Identifying “Second Hit” Risk Factor(s) Associated with Thrombosis and Pregnancy
Morbidity in Ethnically Diverse Antiphospholipid Antibodies Positive Patients
Yu Zuo1, Jennifer Fan2, Ravi Sarode1, Song Zhang2, Una E. Makris1, David Karp3 and Yu-min Shen2, 1University of Texas Southwestern
Medical Center, Dallas, TX, 2University of Texas Southwestern Medical Center, dallas, TX, 3Rheumatology, UT Southwestern Med Ctr,
Dallas, TX
SESSION INFORMATION
Background/Purpose: The evaluation of thrombotic and pregnancy risks associated with antiphospholipid antibodies (aPL) in individual
patients without APS clinical manifestation is challenging. Our aim is to identify potential predictors of thrombosis and pregnancy
morbidities among aPL positive patients.
Methods: This study included 229 consecutive persistent aPL positive patients who attended clinic at University of Texas Southwestern
Medical Center. All patients had persistent high titer (99 percentiles) aPL. The aPL profiles were assessed with commercial assay.
Hypertension (HTN) was classified based on 8th Joint National Committee guidelines. Hyperlipidemia (HLD) was defined as fasting total
cholesterol >200 mg/dl. When assessing risk factors associated with pregnancy morbidities, only reproductive age (age<45) female controls
were used. Pearson Chi-squared analysis and multivariable logistic regression were used to evaluate correlation between different risk
factors and clinical manifestations.
Results: Of the 229 aPL positive patients, 130 (56.8%) patients had criteria APS clinical manifestations and 99 patients did not. 46% were
Caucasian, 26% of African descent, 18% Hispanic, 2% Asian, and 8% were unspecified. Among traditional risk factors and signs of
endothelial injury, only hypertension demonstrated an independent association with arterial thrombosis (OR=3.826, 95%CI 1.597 – 9.167,
P=0.0026), and LA demonstrated an independent association with venous thrombosis (OR=3.308, 95%CI 1.544 – 7.085, P=0.0021). Fisher’s
exact test showed a marginally significant association between Caucasian race and thrombosis (P=0.045); however, multivariable analysis
did not confirm an independent association. Age, diabetes, hypercholesterolemia, smoking, Raynaud’s phenomenon, livedo reticularis, and
triple positive aPLs were not significantly associated with either arterial or venous thrombosis. None of the evaluated risk factors
demonstrated a significant association with pregnancy morbidity.
Conclusion: HTN is a potential predictor of arterial thrombosis and the presence of LA is a potential predictor of venous thrombosis in aPL
positive patients.
Disclosure: Y. Zuo, None; J. Fan, None; R. Sarode, None; S. Zhang, None; U. E. Makris, None; D. Karp, None; Y. M. Shen, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/identifying-second-hit-risk-factors-associated-with-

thrombosis-and-pregnancy-morbidity-in-ethnically-diverse-antiphospholipid-antibodies-positive-patients
Abstract Number: 3
Burden of Antiphospholipid Syndrome in a Thromboembolic Disease Registry

Aurelia Luissi1, Marina Scolnik1, Maria Florencia Grande Ratti2, Maria Lourdes Posadas Martinez2 and Enrique R. Soriano3,
1Rheumatology Unit, Internal Medicine Service, Hospital Italiano de Buenos Aires, CABA, Argentina, 2Research Unit, Internal Medicine
Service, Hospital Italiano de Buenos Aires, CABA, Argentina, 3Rheumatology Unit, Internal Mecine Service, Hospital Italiano de Buenos
Aires, Buenos Aires, Argentina
SESSION INFORMATION
Background/Purpose: Prevalence of antiphospholipid antibodies in general population has been reported in about 5%. Impact of different
thrombophilias in clinical thromboembolic disease is difficult to estimate. Our objective was to assess prevalence (global and in patients <
40 years) of Antiphospholipid Syndrome (APS) in a prospective Institutional Registry of Thromboembolic Disease at a tertiary university
hospital
Methods: A prospective cohort study evaluated all consecutive incident cases of pulmonary thromboembolism (PTE) and deep vein
thrombosis (DVT) confirmed in patients over the age of 18 between january 1st 2011 and December 31st 2014 at a university hospital. All
patients with venous thromboembolic disease (VTED), confirmed by venous doppler ultrasound and/or multislice computed tomographic
angiography and/or angioMRI and/or ventilation/perfusión scan and/or angiography, were included in the registry after given informed
consent. A personal interview was performed and clinical (risk factors, comorbidities, etc) and laboratory data were collected. Patients
were contacted annually after incident event in order to assess clinical status, treatments, adverse events, recurrence or death. Electronic
medical records of all patients included in the registry were reviewed. APS prevalence was estimated and patients’ characteristics were
compared with other VTED etiologies
Results: 1294 patients with VTED were included in the registry in this period [females 54.9%, mean age 68.8 years (SD 15.7)]. VTED was
attributed to APS in 23 patients [females 73.9%, mean age 59.6 (SD 18.2)], representing 1.8% of all patients and 3.8% of patients <= 40
years (Table 1). APS was associated with other autoimmune diseases in 7 patients (30.4%) (4 SLE, 2 RA, 1 overlap). Patients with APS and
other thrombophilias were younger than patients with other etiologies (p<0.001) (Table 2). Type of event and event mortality were similar
across groups (Table 2). Having a prior/recurrent event was more frequent in patients with APS and other thrombophilias. In a multivariate
logistic regression analysis, younger age (OR 1.03, CI 1.01-1.06), female sex (OR 1.64, CI 1.06-1.86) and a prior VTED event (OR 6.3, CI
2.5-16.1), were significantly associated with APS as the cause of the event.
Table 1. Registry patients’ characteristics

All patients (n=1294) Patients <= 40 years (n=79)
Females, n (%) 713 (54.9) 46 (58.2)
Mean age at diagnosis, years(SD) 68.8 (15.7) 30.2 (6.6)
Main cause of DVT/PTE, % (CI 95%)
- Cancer 34.2 (31.6-36.8) 22.8 (14.8-33.4)
- Immobility 15.6 (13.7- 17.6) 5.1 (1.9-12.8)
- Major surgery 14.8 (13-16.8) 20.2 (12.7-30.6)
- Thrombophilias (other than APS) 5.6 (4.5-7) 12.7 (6.9-22)
- Antiphospholipid syndrome 1.8 (1.2-2.6) 3.8 (1.2-11.2)
- Recent journey 1.3 (0.8-2.1) 2.5 (0.6-9.6)
- Oral contraceptives/hormonal replacement 1.2 (0.7-1.9) 10.1 (5.1-19)
- Pregnancy/puerperium 0.5 (0.2-1) 6.3 (2.6-14.4)
- Thrombocytosis 0.4 (0.2-0.9) 0
- Multiple causes 10.3 (8.7-12) 7.6 (3.4-16)
- Unknown 14.5 (12.7-16.5) 8.9 (0.4-17.5)
Table 2. APS patients’ characteristics in comparison with other etiologies

APS patients (n=23) Other Thrombophilias Other causes of VTED P value
(n=73) (n=1201)
Female, n (%) 17 (73.9) 42 (57.5) 654 (54.5) 0.2
Mean age at diagnosis, 59.6 (18.2) 61.3 (17.6) 69.4 (15.4) <0.001
years (SD)
Event type, n (%)
- DVT 12 (52.2) 46 (63.1) 687 (57.3) 0.55
- PTE 6 (26.1) 16 (21.9) 344 (28.7) 0.44
- DVT + PTE 5 (21.7) 11 (15.1) 167 (13.9) 0.55
Event mortality, n (%) 0 (0) 4 (5.5) 110 (9.2) 0.18
On anticoagulation at event 7 (30.4) 14 (19.2) 129 (10.8) 0.002
time, n (%)
Prior event, n (%) 11 (47.8) 24 (32.9) 140 (11.7) <0.001
Type of prior event, n (%)
- DVT 6 (26.1) 18 (24.7) 105 (8.8) <0.001
- PTE 2 (8.7) 3 (4.1) 12 (1) 0.001
- DVT + PTE 3 (13.1) 3 (4.1) 23 (1.9) 0.001
Follow-up after event , 1.9 (0.1-4.5) 3.2 (0.8-4.5) 1.1 (0.1-3.1) <0.001
years, median (IQR)
Recurrence of any 4 (17.4) 14 (19.2) 40 (3.3) <0.001
thrombotic event during
follow up, n (%)
Comorbidities, n (%)
- Hypertension 15 (65.2) 36 (49.3) 780 (65.1) 0.02
- Diabetes 5 (21.7) 10 (13.7) 190 (15.9) 0.6
- Dyslipidemia 12 (52.2) 27 (36.9) 483 (40.3) 0.4
- Active Smoker 6 (26.1) 28 (38.4) 379 (31.6) 0.4
- Major cardiovascular 5 (21.7) 6 (8.2) 144 (12.1) 0.2
event
- Heart failure 2 (8.7) 3 (4.1) 93 (7.8) 0.5
Conclusion: APS- related VTED events represented 1.8% of total events in this registry. Younger age, female sex and having had a prior
event were significantly associated with APS
Disclosure: A. Luissi, None; M. Scolnik, None; M. F. Grande Ratti, None; M. L. Posadas Martinez, None; E. R. Soriano, Abbvie, BMS,
Novartis, Janssen, Pfizer, Roche, UCB, 2,Abbvie, BMS, Novartis, Janssen, Pfizer, Roche, UCB, 5,Abbvie, BMS, Novartis, Janssen, Pfizer,
Roche, UCB, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/burden-of-antiphospholipid-syndrome-in-a-

thromboembolic-disease-registry
Abstract Number: 4
Downregulation of microRNAs in Plasmacytoid Dendritic Cells Is Associated with a

Type I Interferon Signature in Systemic Lupus Erythematosus and Antiphospholipid
Syndrome
Lucas L. van den Hoogen1, Joel A.G. van Roon2,3, Ruth D.E. Fritsch-Stork4, Cornelis P.J. Bekker1, Aridaman Pandit1, Marzia Rossato5
and Timothy R.D.J. Radstake1, 1Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, University Medical
Center Utrecht, Utrecht, Netherlands, 2Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht,
Netherlands, 3Laboratory for Translational immunology, University Medical Center Utrecht, Utrecht, Netherlands, 4Department of
Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, Netherlands, 5Department of Rheumatology & Clinical
Immunology, Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands
SESSION INFORMATION
Background/Purpose:
The most prominent alteration in the immune system of patients with SLE is a type I interferon (IFN) signature, which we recently also
reported in patients with primary APS (PAPS). In SLE and APS, this signature is related to disease activity and vascular disease.
Plasmacytoid dendritic cells (pDC) are considered key players in the pathogenesis of SLE and APS as they are major producers of type I
IFN. MicroRNAs (miRNAs) are short non-coding RNAs that modulate gene expression through RNA interference and have been implicated
in the dysregulation of immune cells in autoimmune diseases. Here we investigated miRNA expression in pDC of patients with SLE and APS
in relation to the IFN signature.
Methods:
RNA was extracted from pDCs isolated from the peripheral blood of patients with SLE (n=20), SLE+APS (n=10), PAPS (n=10) and HC
(n=12). pDC miRNA and transcriptome profiles were assessed by RT-qPCR by OpenArray and RNA-sequencing (RNAseq) respectively.
Patients were stratified by the presence (IFN-high) or absence (IFN-low) of an IFN signature on the basis of RNAseq. pDC stimulated with
TLR7 agonists were analyzed for changes in miRNA expression. The frequency of circulating pDC was determined by flow cytometry in
patients with SLE (n=49), SLE+APS (n=34) and PAPS (n=27) and healthy controls (HC, n=22)
Results:
Among 131 expressed miRNAs, 36, 17 and 21 miRNAs were differentially expressed (p<0.05) in patients with SLE, SLE+APS and PAPS,
respectively, as compared with HC. All but one of these miRNAs were downregulated in the patients versus HC. Only 1 miRNA was
differentially expressed when comparing between SLE and SLE+APS patients and between SLE+APS and PAPS patients. No changes in
expression of genes related to the biogenesis of miRNAs were observed in the pDC of the patient groups. RNAseq data revealed an IFN
signature in pDC, which was strongest in SLE and SLE+APS patients. IFN-high (n=23) patients showed a stronger downregulation of
miRNAs as compared with IFN-low (n=17) patients. Activation of pDCs by TLR7 agonists induced a downregulation of miRNAs in pDC,
resembling the miRNA expression pattern seen in patients, in particular those with a high type I IFN signature. Pathway enrichment on the
overlap of the targets of the top three miRNA (p<0.001) and differentially expressed genes from RNAseq between IFN-high and –low
patients indicated that these miRNAs are potentially regulating pathways relevant for pDC function such as TLR signaling, endocytosis and
pDC survival. In line with that, the numbers of circulating pDC were reduced in peripheral blood of patients with SLE, SLE+APS and PAPS,
in particular in patients with a high type I IFN signature.
Conclusion:
Reduced numbers of circulating pDC and downregulation of miRNAs in pDC are shared between SLE, SLE+APS and PAPS patients and are
related to the IFN signature. Our data suggest that the reduced expression of a subset of miRNA underlies pDC dysregulation in SLE,
SLE+APS and PAPS patients.
Disclosure: L. L. van den Hoogen, None; J. A. G. van Roon, None; R. D. E. Fritsch-Stork, None; C. P. J. Bekker, None; A. Pandit,
None; M. Rossato, None; T. R. D. J. Radstake, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/downregulation-of-micrornas-in-plasmacytoid-dendritic-

cells-is-associated-with-a-type-i-interferon-signature-in-systemic-lupus-erythematosus-and-antiphospholipid-syndrome
Abstract Number: 5
Clinical Utility of the Global Antiphospholipid Syndrome Score (GAPSS) for Risk
Stratification: A Pooled Analysisfrom 2273 Patients
Savino Sciascia1, Massimo Radin2, Giovanni Sanna3, Irene Cecchi4, Dario Roccatello5 and Maria Laura Bertolaccini6, 1Center of Research
of Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, Department of
Clinical and Biological Sciences, University of Turin, Italy, Center of Research of Immunopathology and Rare Diseases- Coordinating Center
of Piemonte and Valle d’Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, University of Turin, Italy,
Torino, Italy, 2Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases- Coordinating
Center of Piemonte and Valle d’Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, University of Turin,
Italy, Turin, Italy, 3Louise Coote Lupus Unit, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom, London, United
Kingdom, 4Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Valle d’Aosta Network for
Rare Diseases, Department of Clinical and Biological Sciences, University of Turin, Italy, Turin, Italy, 5Center of Research of
Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, Department of
Clinical and Biological Sciences, University of Turin and S. Giovanni Bo, Turin, Italy, 6Academic Department of Vascular Surgery,
Cardiovascular Division, King's College London, United Kingdom, London, United Kingdom
SESSION INFORMATION
Background/Purpose:
Recently, our group conceived a risk score for clinical manifestations of APS [the global APS score or GAPSS] that takes into account the
combination of independent cardiovascular risk factors and the aPL positivity profile. These include hyperlipidemia, arterial hypertension,
aCL, anti-b2GPI, aPS/PT and the LA. A complementary version, the adjusted GAPSS or aGAPSS, which excludes aPS/PT, was also
designed.
Methods:
We pooled data from available cohort studies, including a total of 10 studies, counting for a total of 2273 patients in which the GAPSS score
has been applied. A search strategy was developed a priori to identify available cohort that reported findings that investigated the clinical
utility of GAPSS or aGAPSS score.
Results:
When pooling together available data, GAPSS/aGAPSS was applied in a total of 2273 patients. Studies characteristics and patients enrolled
are summarized in Table 1.
Seven studies used the GAPSS in their cohort, whether three studies used the aGAPSS. In brief, we found a statistically significant difference
in the cumulative GAPSS and aGAPSS scores between patients that experienced arterial and/or venous thrombotic event (Cumulative
GAPSS 10.6±4.74 and aGAPSS 7.6±3.95), patients without any thrombotic manifestation (Cumulative GAPSS 7.01±5.46 and aGAPSS
4.9±4.33) and patients with pregnancy morbidity (Cumulative GAPSS 8.79±2.59 and aGAPSS 6.7±2.8).
The highest levels of GAPSS were found in patients that experienced arterial thrombosis (mean GAPSS 12.2±5.2) and patients that
experienced any recurrences of clinical manifestations of APS (mean GAPSS 13.7±3.1).
Conclusion:
GAPSS may represent a useful tool to assess the thrombosis or pregnancy loss risk in aPL positive patient, switching from the concept of aPL
as a sole diagnostic antibody to aPL as risk factors for clinical events. A risk assessment, using appropriate tools as GAPSS, should be
implemented to identify and monitor those patients at a higher risk of recurrences and those needing a strict control of all modifiable risk
factor for cardiovascular events; in agreement with the above, in the future the management of APS should also modulate according to the
GAPSS values.
Table 1. Demographic, clinical and laboratory characteristics of the cohort

NUMBER
STUDY PATIENTS'
STUDY YEAR AIM OF
DESIGN CHARACTERISTICS
PATIENTS
Sciascia et
al. Cross- To validate the first GAPSS score with a validation
2013 105 SLE
Sectional cohort
Sciascia et To prospectively and independently validate

al.
2014 Prospective GAPSS, with a follow-up of mean 32.94 (SD 51 SLE aPL positive patients
12.06) months
To investigate the validity of the global APS score
Zuily et al.
(GAPSS) to predict thrombosis in patients
2015 Prospective 137 patients with aPL and/or SLE
with autoimmune diseases, followed up
for a mean duration of 43.1 (S.D. 20.7) months
41 APS (17 PAPS) patients, 88
SLE without APS, 50 rheumatoid
Oku et al. arthritis, 16 Sjögren’s syndrome,
2015 Retrospective To validate the GAPSS independently 282 21 systemic sclerosis, 10
polymyositis/ dermatomyositis
and 56 other autoimmune
diseases
Sciascia et To evaluate the clinical relevance of the global
al.
2015 Retrospective APS score (GAPSS) in a cohort of primary APS 62 PAPS patients
patients
Zigon et al. To evaluate association of different risk factors
2016 Retrospective with thrombosis; and b) to apply GAPSS on a large 585 Systemic Autoimmune Diseases
cohort of unselected Slovenian patients
Sciascia et
al. To evaluate the clinical utility of the GAPSS with
2016 Retrospective 550 APS Patients
the help of APS ACTION Registry
Zu et al. To evaluate the clinical revalence of aGAPSS in a

2016 Retrospective 89 89 APS Patients
chinese cohort
Fernandez PAPS diagnosed in 130 patients
Mosteirin et To independently validate the aGAPSS to predict
and 89 SAPS patients, and 100
al. 2017 Retrospective thrombosis in a cohort of patients with APS and/or 319
patients with autoimmune disease
autoimmune disease
without APS
Radin et al. To investigate the validity of aGAPSS in young
2017 Retrospective 83 APS Patients
patients with myocardial infarction
Table 2. GAPSS and aGAPSS between groups
Oku Zu
SciasciaSciascia Zuily SciasciaSciasciaCUMULATIVE RadinFernandez CUMULATIVE
et et
et al. et al. et al. et al. et al. GAPSS et al. Mosteirin aGAPPS
al. al.
2013 2014 2015 2015 2016 mean(±SD) 2017 et al. 2017 mean(±SD)
2015 2016
Total N 105 51 137 282 62 550 1187 98 83 319 500
Thrombotic
37 4 16 N/A 39 N/A 96 53 70 201 324
N
GAPSS 9.6 10.88 11.5 9.4 9.2
10 (5.4) N/A N/A 10.6 (4.74) 6.58 (3.36) 7.6 (3.95)
mean(± SD) (4.8) (5.06) (4.6) (3.2) (5.1)
Non
Thrombotic 68 47 121 N/A N/A N/A 236 N/A N/A 118 118
N
GAPSS 7.13 8.15
4.9 (5) N/A N/A N/A 7.01 (5.46) N/A N/A 4.9 (4.33) 4.9 (4.33)
mean(±SD) (5.75) (5.31)
PM N 22 N/A N/A 11 44 419 496 38 N/A N/A 38
GAPSS 8.7 6.7
7.3 (5) N/A N/A 4 9 8.78 N/A N/A 6.7 (2.8)
mean(±SD) (3.2) (2.8)
Graph 1. Cumulative GAPSS values between groups
Disclosure: S. Sciascia, None; M. Radin, None; G. Sanna, None; I. Cecchi, None; D. Roccatello, None; M. L. Bertolaccini, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/clinical-utility-of-the-global-antiphospholipid-syndrome-

score-gapss-for-risk-stratification-a-pooled-analysisfrom-2273-patients
Abstract Number: 6
Pregnancy Outcomes in a Cohort of Women with Antiphospholipid Syndrome. 25-

Years Long-Term Observation
Dana Tegzova1, Katerina Andelova2, Iva Kucerova2, Vera Vlasakova3, Stejskal Jan4, Putova Ivana5, Marta Olejarova6 and Ctibor Dostál7,
1Clinical Department, Institute of Rheumatology and Rheumatological Clinic of 1st Medical Faculty, Charles University, Prague, Czech
Republic, 2Institute of Mother and Child Care, Prague, Prague, Czech Republic, 3Dept.of Internal Medicine, City Hospital Ceske Budejovice,
Ceske Budejovice, Czech Republic, 41st Medical Faculty, Dpt. of Pathology, Charles University, Prague, Czech Republic, 5Institute of
Rheumatology, Dpt. of Immunology, Prague, Czech Republic, 6Clinical, Institute of Rheumatology and Rheumatological Clinic of 1st Medical
Faculty, Charles University, Prague, Czech Republic, 7Institute of Rheumatology and Rheumatological Clinic of 1st Medical Faculty, Charles
University, Prague, Czech Republic
SESSION INFORMATION
Background/Purpose: The goal of this long-term project was to investigate the course of pregnancy in patients with APS (primary or
secondary with SLE) in 1993-2017, to describe the type and severity of it and to explore their relationship with disease-related
characteristics. To find specific histological changes in maternal tissue in a subgroup of patients.
Methods: During more than 25 years of systematic observation 80 pregnant women with APS were observed and examined. Secondary APS
was in our cohort common with systemic lupus erythematosus (SLE). Patients were evaluated every 3 months by a rheumatologist and
gynaecologist. Basic demographic data were assessed, as well as the duration and type of therapy, autoantibodies, organ involvement and its
activity, the number and type of disease flares, thrombosis, the number of abortions and premature labours, new-born weight and presence of
complications such as gestational diabetes, hypertension and preeclampsia. In a subgroup of 13 patients (5 with primary APS, 7 with
sec.APS/SLE a macroscopic and histological examination of maternal tissue was performed in comparison with a healthy control group.
Results: The group comprised 65 pregnant women with APS, out of which 57% had secondary APS/SLE and 33% primary APS. In the group
of primary APS 90% pts were treated with low molecular heparin and/or salicylates. In pts. with sec.APS/SLE 90 % of patients were treated
with oral corticosteroids, 8% with cyclosporine A and 16% with azathioprine and 95% with low molecular weight heparin and/or
salicylates. 7% of pregnancies were terminated in the first trimester due to missed abortion. 6% of abortions in patients with sec. APS/SLE
in second trimester were observed. 57 APS patients delivered 58 newborns, 16% of them before the 37th week of pregnancy and 7% before
the 34th week. Out of this group 75% patients delivered prematurely due to hypertension or preeclampsia, 10% due to growth retardation of
fetus. Newborn weight was 3020g on average. AV heart block of 3rd degree was observed in 1 newborn with sec.APS/SLE. No congenital
malformations were observed in our group. In the group sec.APS/SLE higher number of gestational diabetes was found: 38% of patients, all
of which were treated with corticosteroids. Hypertension was found in 33% patients, preeclampsia in 12 % and 60% of patients with
preeclampsia had a history of lupus nephritis. Higher score of maternal infarcts and decidual pathological changes with deposits of
immunocomplexes were found in microscopic examination in patients with APS in comparison with healthy controles. Rate of weight
placenta/fetus was lower. Signs of accelerate aging, nodules and inflammatory infiltration was found in light microscopy and higher score of
deposits of immunecomplexes were found.
Conclusion: In spite of the fact that women with APS have a high risk during the course of pregnancy, the results of our long terms study
showed a good outcome of pregnancy. Higher rate of complications was found in the group with sec. APS with SLE.
Supported by Research Project Ministry of Health of Czech Republic NO: 000 000 23728
Disclosure: D. Tegzova, None; K. Andelova, None; I. Kucerova, None; V. Vlasakova, None; S. Jan, None; P. Ivana, None; M.
Olejarova, None; C. Dostál, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/pregnancy-outcomes-in-a-cohort-of-women-with-

antiphospholipid-syndrome-25-years-long-term-observation
Abstract Number: 7
Predictive Value for Thrombosis of Double or Triple Positivity in Secondary APS

Depends on the Component Assays and the Type of Thrombosis
Michelle Petri1, Daniel Goldman2 and Laurence S Magder3, 1Medicine (Rheumatology), Division of Rheumatology, Johns Hopkins
University School of Medicine, MD, USA, Baltimore, MD, 2Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD,
3Epidemiology and Public health, University of Maryland School of Medicine, Baltimore, MD
SESSION INFORMATION
Background/Purpose: The lupus anticoagulant (LAC) is individually the antiphospholipid antibody (aPL) most associated with thrombotic
risk in both primary and secondary APS. Anticardiolipin (aCL) and anti-beta2 glycoprotein 1 may further increase the risk. We investigated
the risk for thrombosis in SLE of double or triple positivity for these different aPLs.
Methods: The analysis is based on 1508 SLE patients, (92% female, 51% white, 40% black, and with a mean age at end of follow-up of
46.4 [SD=14.2]). Thrombosis was defined as: arterial thrombosis (CVA, MI, other arterial thrombosis or digital gangrene); and venous
thrombosis (DVT, PE or other venous thrombosis).
Results: We looked at the risk of lifetime occurrence of thrombosis as a function of the history of LAC (RVVT confirm), aCL, or anti-beta2
glycoprotein 1 (anti-Beta2). The OR’s in the tables are adjusted for age.
Table 1. History of thrombosis by history of APS.

Specific Proportion (%) Odds Ratio P-value
Components of patients with (relative to
a history of any those without
thrombosis any APS
components)
Any Thrombosis
No aPL None 100/488 (20%) 1.0 (Ref Group)
aCL alone 66/369 (18%) 0.8 (0.6, 1.2) 0.31
Single
LAC alone 26/74 (35%) 2.1 (1.2, 3.6) 0.0063
Positive
anti-Beta2 alone 10/82 (12%) 0.6 (0.3, 1.1) 0.095
Any double 105/315 (33%) 1.9 (1.4, 2.6) 0.0002
positive
Double aCL + LAC 61/138 (44%) 2.9 (1.9, 4.4) <0.0001
Positive
aCL + anti-Beta2 29/147 (20%) 0.9 (0.6, 1.5) 0.71
LAC + anti-Beta2 15/30 (50%) 4.1 (1.9, 8.8) 0.0002
Triple All three 89/180 (49%) 3.7 (2.6, 5.4) <0.0001
positive
Arterial Thrombosis
No aPL None 55/488 (11%) 1.0 (Ref)
aCL alone 40/369 (11%) 0.9 (0.6, 1.5) 0.78
Single
LAC alone 12/74 (16%) 1.5 (0.7, 3.0) 0.26
Positive
anti-Beta2 alone 6/82 (7%) 0.6 (0.3, 1.5) 0.31
Any double 59/315 (19%) 1.7 (1.1, 2.5) 0.013
positive
Double aCL + LAC 37/138 (27%) 2.6 (1.6, 4.2) <0.0001
Positive
aCL + anti-Beta2 18/147 (12%) 1.0 (0.6, 1.9) 0.89
LAC + anti-Beta2 4/30 (13%) 1.3 (0.4, 3.8) 0.66
Triple All three 54/180 (30%) 3.2 (2.1, 5.0) <0.0001
positive
Venous Thrombosis
No aPL None 54/488 (11%) 1.0 (Ref)
aCL alone 39/369 (11%) 0.9 (0.6, 1.5) 0.79
Single
LAC alone 19/74 (26%) 2.8 (1.5, 5.1) 0.0008
Positive
anti-Beta2 alone 5/82 (6%) 0.5 (0.2, 1.4) 0.19
Any double 72/315 (23%) 2.4 (1.6, 3.5) <0.0001
positive
Double aCL + LAC 42/138 (31%) 3.5 (2.2, 5.6) <0.0001
Positive
aCL + anti-Beta2 17/147 (12%) 1.0 (0.6, 1.8) 0.93
LAC + anti-Beta2 12/30 (40%) 5.5 (2.5, 12.0) <0.0001
Triple All three 60/180 (33%) 3.9 (2.6, 6.0) <0.0001
positive
The findings in the table confirm that there can be an increase in the point estimate from single, to double positivity. However, it clearly
depends on which components are considered, and whether it is arterial or venous thrombosis. The strongest finding is that LAC is the most
important component. For arterial thrombosis, however, double positivity with LAC and aCL leads to increased risk.
Conclusion: In SLE, lupus anticoagulant is the most important single antiphospholipid test predictive of any thrombosis and venous
thrombosis. For arterial thrombosis, aCL and LAC together outperform single tests. For venous thrombosis, the point estimates increase for
double positives containing LAC, and for triple positive, although the confidence intervals overlap. In SLE, double, and possibly triple,
positivity show promising results. However, different combinations of “double positive” aPLs are important, and differ in arterial vs. venous
thrombosis.
Disclosure: M. Petri, Anthera Inc, 5,GlaxoSmithKline, 5,EMD Serono, 5,Eli Lilly and Company, 5,Bristol Meyer Squibb, 5,Amgen,
5,United Rheumatology, 5,Global Academy, 5,Exagen, 2; D. Goldman, None; L. S. Magder, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/predictive-value-for-thrombosis-of-double-or-triple-

positivity-in-secondary-aps-depends-on-the-component-assays-and-the-type-of-thrombosis
Abstract Number: 8
Antiphospholipid Syndrome Leukocytes Demonstrate Increased Adhesive Potential: a

Search for Novel Therapeutic Targets
Gautam Sule 1, William J. Kelley1, Srilakshmi Yalavarthi1, Alison Banka1, Omolola Eniola-Adefeso1 and Jason S. Knight2, 1University of
Michigan, Ann Arbor, MI, 2., University of Michigan, Ann Arbor, MI
SESSION INFORMATION
Background/Purpose: Adhesion of leukocytes to the endothelium is an initiating event in the thrombosis inherent to antiphospholipid
syndrome (APS). Over the years, a number of groups have demonstrated that antiphospholipid antibodies (aPL) upregulate both selectins and
integrin receptors on endothelial cells, thereby increasing the adhesive potential of the endothelium. Here, we posit that factors intrinsic to
leukocytes may also play a pivotal role in adhesive interactions. For example, transcriptome analysis of APS patient neutrophils has revealed
an activated, adhesive signature. Furthermore, leukocyte adhesion in our mouse model of aPL-mediated large vein thrombosis is regulated by
leukocyte (more so than endothelial) factors. In this study, we functionally characterize leukocyte adhesion in APS, with the goal of ultimately
testing the therapeutic potential of putative targets.
Methods: Patients had primary APS (classified by Sydney criteria), while healthy controls were matched for age and gender. Freshly-
isolated human umbilical vein endothelial cells (HUVECs) were used. Anticoagulated whole blood (or purified cellular components) was
introduced into a flow channel via a programmable syringe pump, and perfused across an unstimulated HUVEC monolayer in a pulsatile flow
profile with wall shear rate set to 1000 s-1. After 15 minutes of perfusion, the chamber was flushed to remove nonadherent cells, and images
were captured with an inverted microscope.
Results: Perfusion of APS blood across unstimulated HUVECs resulted in significantly more leukocyte adhesion as compared with control
blood (mean 5.0-fold increase; p<0.0001 with n=18 patients). To assess the role of leukocytes themselves (versus plasma factors that might
activate HUVECs), leukocytes were washed free of plasma, resuspended in buffer, and then perfused across HUVECs. In this plasma-free
context, there was still significantly more adhesion of APS leukocytes (mean 2.2-fold increase; p<0.01 with n=10 patients), suggesting an
intrinsic increase and/or activation of leukocyte adhesion factors. Furthermore, treating control leukocytes with APS patient plasma (which
was then washed away before perfusion) resulted in increased adhesion of the control leukocytes (mean 2.5-fold increase; p<0.0001 with
n=12 plasma samples). Experiments are underway to delineate the factors on the leukocyte surface that dictate the increased adhesive
potential (as well as the factors in APS plasma that mediate their upregulation). In particular, we are characterizing both selectin ligands and
beta-2 integrins on leukocytes, as even unstimulated HUVECs demonstrate baseline expression of potential binding partners (selectins and
ICAM-1, respectively). We are also determining the relative adhesive potential of different leukocyte subpopulations (i.e., monocytes versus
neutrophils).
Conclusion: While there is a known role for aPL in increasing the adhesive potential of endothelial cells, we now report that leukocytes
themselves have an intrinsic increase in their adhesive potential. The ultimate goal of this work is to identify the most relevant pharmacologic
targets on the leukocyte surface.
Disclosure: G. Sule, None; W. J. Kelley, None; S. Yalavarthi, None; A. Banka, None; O. Eniola-Adefeso, None; J. S. Knight, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/antiphospholipid-syndrome-leukocytes-demonstrate-

increased-adhesive-potential-a-search-for-novel-therapeutic-targets
Abstract Number: 9
Renal Protective Effect of Antiplatelet Therapy in Antiphospholipid Antibody-Positive

Lupus Nephritis Patients without the Antiphospholipid Syndrome
Hironari Hanaoka1, Tomofumi Kiyokawa1, Harunobu Iida1, Yukiko Takakuwa1, Takahiro Okazaki2, Hidehiro Yamada3, Shoichi Ozaki4
and Kimito Kawahata1, 1Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of
Medicine, Kawasaki, Japan, 2Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan, 3Rheumatology, Seirei
Yokohama Hospital, Yokohama, Japan, 4Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
SESSION INFORMATION
Background/Purpose: Lupus nephritis (LN) class III or IV is associated with a poor prognosis for both patient and renal survival. Since
antiphospholipid syndrome (APS) is reported to worsen the prognosis of LN, LN patients with APS should be treated with conventional
immunosuppressive treatment plus antiplatelet or anticoagulation therapy according to the recommendations for LN management. However it
has been unclear whether these therapies would benefit antiphospholipid antibodies (aPL)-positive LN patients not meeting the diagnostic
criteria. Here, we evaluated the effect of antiplatelet therapy in addition to conventional immunosuppressive therapy for LN patients positive
for aPL without definite APS.
Methods: Patients with biopsy-proven LN class III or IV who did not take hydroxychloriquine were retrospectively evaluated. We selected
patients positive for anticardiolipin antibody (aCL) or lupus anticoagulant (LA) who did not meet the criteria for a diagnosis of APS. The
patients were divided into two subgroups according to whether antiplatelet therapy was received. The cumulative complete renal response
(CR) rate, relapse-free rate, and change in estimated glomerular filtration rate (eGFR) over 3 years after induction therapy were calculated.
Results: We identified 17 patients who received antiplatelet therapy and 21 who did not. Baseline clinicopathological characteristics and
immunosuppressive therapy did not show a statistically significant difference between the two groups except for a significantly higher
incidence of LN class IV in the treatment group (p = 0.03). There was no significant difference in cumulative CR rate, relapse-free rate, or
eGFR change between these subgroups. However, when data on LA-positive patients were assessed, a significant improvement in eGFR was
found (p = 0.04) in patients receiving antiplatelet therapy (Figure 1).
Conclusion: Addition of anti-platelet therapy was associated with an improvement of eGFR in LA-positive patients with LN class III or IV.
There may be a wider indication for antiplatelet therapy in LN, in addition to its use in patients with a definite APS diagnosis.
Disclosure: H. Hanaoka, None; T. Kiyokawa, None; H. Iida, None; Y. Takakuwa, None; T. Okazaki, None; H. Yamada, None; S. Ozaki,
None; K. Kawahata, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/renal-protective-effect-of-antiplatelet-therapy-in-

antiphospholipid-antibody-positive-lupus-nephritis-patients-without-the-antiphospholipid-syndrome
Abstract Number: 10
Arterial Events in Primary Antiphospholipid Syndrome Are Associated with High

Values of the Adjusted Global Antiphospholipid Syndrome Score
Flavio Signorelli1, Gustavo G M Balbi2, Roger A. Levy2 and Savino Sciascia3, 1Universidade do Estado do Rio de Janeiro, Rio de
Janeiro, Brazil, 2Rheumatology, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil, 3Center of Research of Immunopathology
and Rare Diseases- Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, Department of Clinical and Biological
Sciences, University of Turin, Italy, Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Valle
d’Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, University of Turin, Italy, Torino, Italy
SESSION INFORMATION
Background/Purpose: The adjusted Global AntiPhospholipid Syndrome Score (aGAPSS) was described as a tool to estimate the risk of
thromboses in patients with APS. The aim of this study is to evaluate if higher values of aGAPSS correlate with the presence of arterial or
venous thromboses in thrombotic primary APS patients.
Methods: A cross-sectional study was performed in a group of 72 outpatients who fulfilled thrombotic pAPS classification criteria
(Sydney). Clinical and serologic features were collected during visits and by chart review. aGAPSS was calculated for each patient and
correlated to arterial and venous thromboses. Statistical analysis was performed using chi-square, Mann-Whitney U and Spearman’s R when
applicable. Multivariate regression analysis included age, sex, race and variables with p<0.10 in the bivariate analysis.
Results: Thirty-seven (51.4%) patients had arterial events and 51 (70.8%) had venous thromboses. The mean number of episodes of arterial
and venous thromboses was 1.65 and 1.4 per patient, respectively. The median aGAPSS of the 72 patients included in the analysis was 9 (7-
13); this was used to divide two groups of patients: low aGAPSS (<10) and high aGAPSS (≥10). Patients with or without arterial
thromboses were compared regarding the presence of high aGAPSS. In a bivariate analysis, higher aGAPSS correlated with the presence of
arterial thromboses (p=0.018). In a multivariate regression analysis, higher aGAPSS remained as a risk factor for the presence of arterial
thromboses (OR 3.4, 95%CI 1.26-9.2, p=0.016). Demographic and clinical characteristics of this group of patients are shown in Table 1.
Regarding venous thrombosis, there was a tendency towards higher levels of aGAPSS (p=0.063). To avoid contamination of data, a new
different analysis was performed. Patients who presented both arterial and venous thromboses were excluded, and 2 groups were created,
one with arterial exclusive events (N=19) and another with venous exclusive events (N=35). The group with arterial exclusive thromboses
had higher values of aGAPSS (p=0.007). In the multivariate analysis, high aGAPSS was associated with increased risk of arterial events
(OR 4.95, 95%CI 1.49-16.47). Patients with both arterial and venous thromboses did not have higher aGAPSS (p=0.677).
Conclusion: The presence of arterial events was associated with higher values of aGAPSS. aGAPSS seems to be a tool capable to detect
high risk thrombotic patients, particularly arterial events.
Table 1: Demographic and clinical characteristics (N=72).

Variable Arterial No arterial P
thromboses thromboses value
(N=37) (N=35)
Age 46.9±13.5 42.1±11.9 NS
Female gender 29 (78.4) 31 (88.6) NS
Caucasian 23 (62.2) 24 (68.6) NS
Time first 180 (96-240) 108 (69.5-192) NS
manifestation
(mo)
aGAPSS
High aGAPSS 20 (54.1) 9 (25.7) 0.013
(value≥10)
Hypertension 17 (45.9) 10 (28.6) NS
Dyslipidemia 20 (54.1) 9 (25.7) 0.018
Lupus 34 (91.9) 32 (91.4) NS
anticoagulant
Anticardiolipin 15 (40.5) 13 (37.1) NS
Anti-ß2- 24 (64.9) 15 (42.9) NS
glycoprotein I
Values showed as N(%) for categorical variables, Mean± SD for normal distribution and Median (interquartil range) for asymmetrical
distribution.
Disclosure: F. Signorelli, None; G. G M Balbi, None; R. A. Levy, None; S. Sciascia, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/arterial-events-in-primary-antiphospholipid-syndrome-

are-associated-with-high-values-of-the-adjusted-global-antiphospholipid-syndrome-score
Abstract Number: 11
Possible Therapeutics for Antiphospholipid Antibody Related Thrombocytopenia: A

Systemic Review and Meta-Analysis
Nobuya Abe 1, Kenji Oku1, Olga Amengual1, Yuichiro Fujieda1, Masaru Kato1, Toshiyuki Bohgaki1, Shinsuke Yasuda1, Rintaro Mori2,
Eriko Morishita3, Katsue Suzuki-Inoue4 and Tatsuya Atsumi1, 1Department of Rheumatology, Endocrinology and Nephrology, Faculty of
Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan, 2Department of Health Policy, National Center for Child
Health and Development, Tokyo, Japan, 3Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan, 4Department of
Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
SESSION INFORMATION
Background/Purpose: Despite the pro-thrombotic nature of antiphospholipid antibodies (aPL), thrombocytopenia is frequently observed in
patients with antiphospholipid syndrome (APS) or in non-APS patients with aPL. The management of the thrombocytopenia with aPL (aPL
related thrombocytopenia; APAT) is often deductive, due to the paradoxical risks of thrombosis and hemorrhage. We have been striving to
clarify the mechanisms of APAT and reported its high prevalence of arterial thrombotic events (Nakagawa I, et al. ACR 2014, Abstract #2).
In the present study, along with the reconfirmation of the clinical importance of APAT, we aimed to evaluate the efficacy of therapeutic
regimes in APAT through a systematic review of the literature with the objective of elaborating a clinical practice guideline for APAT on a
consignment project from the Japanese Ministry of Health, Labor and Welfare.
Methods: Four clinical questions were selected for systematic review and redefined using the PICO (Patient, Intervention, Comparison,
Outcome) format and prioritized. The four clinical questions were to evaluate the effects of possible therapeutics for APAT; antiplatelet
agents, glucocorticoids, splenectomy and thrombopoietin receptor agonists. Systematic reviews were performed using electronic databases
(MEDLINE, EMBASE and CENTRAL) by the Cochrane Japan Centre. Cochrane Collaboration Review Manager software was used to
manage and analyze the data collected.
Results: The initial search yielded 1407 citations of which nine were included in our final analysis. There was no randomized controlled
trial on treatment for APAT. We identified four case-controlled studies for splenectomy, one for antiplatelet agents and four observational
studies for glucocorticoids. Meta-analysis of quantitative data (17/23) showed evidence of an increase in platelet count in patients who
underwent splenectomy compared with the patients without splenectomy (mean difference 22.6~104 /mL, P = 0.007) (Figure). Complete
remissions of the thrombocytopenia were observed in 18/23 (78%) patients with splenectomy versus 0/23 (0%) without splenectomy. The
relapses were occurred in 3/23 (13%) patients with splenectomy. There was no complications due to splenectomy. None of the configured
outcomes were susceptible to the antiplatelet and glucocorticoid therapy.
Conclusion: Although splenectomy for APS was previously reported to be a risk of portal vein thrombosis, our systematic review and meta-
analysis revealed that it may be performed rather safely and effectively in APAT patients. However, there was no clear evidence to support
applications of antiplatelet agents, glucocorticoids, or thrombopoietin receptor agonists as therapeutics of APAT. Further clinical trials are
required to establish therapeutic recommendation for APAT.
Disclosure: N. Abe, None; K. Oku, None; O. Amengual, None; Y. Fujieda, None; M. Kato, None; T. Bohgaki, None; S. Yasuda, None; R.
Mori, None; E. Morishita, None; K. Suzuki-Inoue, None; T. Atsumi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/possible-therapeutics-for-antiphospholipid-antibody-

related-thrombocytopenia-a-systemic-review-and-meta-analysis
Abstract Number: 12
Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking

(APS ACTION) Clinical Database and Repository Analysis: Pregnancy Outcomes Since
Inception
Ecem Sevim1, Danieli Andrade2, Alessandra Banzato3, D. Ware Branch4, Ricard Cervera5, Guilherme Ramires de Jesus6, Jason S. Knight7,
Pier Luigi Meroni8, Maria Tektonidou9, Angela Tincani10, Amaia Ugarte11, Zhang Zhuoli12, Doruk Erkan13 and , on Behalf of APS
ACTION .14, 1Umraniye Research and Training Hospital, Istanbul Health Sciences University, Istanbul, Turkey, 2Rheumatology, Hospital
das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR., Sao Paulo, Brazil, 3Department of
Cardiac Thoracic and Vascular Sciences, Clinical Cardiology, Thrombosis Centre, University of Padova, Padova, Italy, 4Obstetrics and
Gynecology, University of Utah and Intermountain Healthcare, Salt Lake City, UT, 5Department of Autoimmune Diseases, Institut Clínic de
Medicina i Dermatologia, Hospital Clínic de Barcelona, Barcelona, Spain, 6Obstetrics, Universidade do Estado do Rio de Janeiro, Rio de
Janeiro, Brazil, 7., University of Michigan, Ann Arbor, MI, 8Istituto Ortopedico Gaetano Pini, University of Milan, Milano, Italy, 9First
Department of Internal Medicine, School of Medicine, National University of Athens, Athens, Greece, 10Rheumatology and Clinical
Immunology, Spedali Civili and University of Brescia, Brescia, Italy, 11Autoimmune Diseases Research Unit, Department of Internal
Medicine, BioCruces Health Research Institute, Hospital Universitario Cruces, University of the Basque Country, Biscay, Spain,
12Department of Rheumatology and Immunology,Peking University First Hospital, Peking University First Hospital, Beijing, China,
13Rheumatology, Hospital for Special Surgery- Weill Cornell Medicine, New York, NY, 14., New York, NY
SESSION INFORMATION
Background/Purpose: APS ACTION Clinical Database and Repository (‘‘Registry’’) was created to study the natural course of disease
over 10 years in persistently antiphospholipid antibody (aPL) positive patients with/without other systemic autoimmune diseases. Our
objective was to describe the new pregnancy outcomes of the aPL-positive patients since the inception of the registry.
Methods: A web-based data capture system is used to store patient demographics, history, and medications. The inclusion criteria are
positive aPL based on the Updated Sapporo Classification Criteria at least twice within one year prior to enrollment. Patients are followed
every 12±3 months with clinical data and blood collection. For this analysis, we identified all patients who were recorded as “pregnant”
during the prospective follow-up.
Results: Since the inception of the registry in 5/2012, 45 pregnancies were recorded in 36 aPL-positive patients (mean age 33.4 ± 4.9 y;
lupus: 5 [14%]; LA-positive alone: 16 [44%]; triple aPL-positive: 11 [31%]; double aPL-positive: 7 [19%]; obstetric APS [OAPS]: 5
[14%]; thrombotic APS [TAPS]: 10 [28%]; OAPS+TAPS: 12 [33%]; and no history of OAPS/TAPS: 9 [25%]). Of 45 pregnancies (28
patients had one pregnancy, seven had two, and one had three), 23 (51%) resulted in term live birth (preeclampsia [PEC]: 1; and small for
gestational age [SGA]: 2), eight (18%) preterm live birth (mean delivery week [w] 33.5 ± 1.7; PEC: 4; and SGA: 1), 12 (27%) (pre)
embryonic loss < 10w, one (2%) fetal death > 20w, and one was ongoing at the time of data lock (Table). Term live birth occurred in 12/21
(57%) of pregnancies of patients with history of OAPS (no treatment: 1; Aspirin [ASA]: 1; low-molecular-weight-heparin [LMWH]:2; and
ASA+LMWH: 8), compared to 11/24 (46%) of pregnancies of patients without history of OAPS (no treatment: 1; ASA:1; LMWH:2; and
ASA+LMWH: 7). (p: 0.38). Pre-term live birth occurred in 3/21 (14%) of pregnancies of patients with history of OAPS (no treatment: 1;
and ASA+LMWH: 2), compared to 5/24 (21%) of pregnancies of patients without history of OAPS (ASA+LMWH: 5) (p: 0.70). Similarly,
term and preterm live birth rates were not different between patients with and without TAPS.
Conclusion: Fifty percent and 20% of pregnancies in our multi-center international aPL-positive cohort resulted in term and preterm live
births, respectively. While 80% of the pregnancies were treated with low dose aspirin +/- LMWH, only 60% had had a history of pregnancy
morbidity fulfilling the Updated Sapporo Classification Criteria. Term and preterm live birth rates were similar between patients with and
without history of obstetric APS or thrombotic APS; no pregnancy was complicated with fetal loss between 10-20 weeks; and only one with
fetal loss after 20 weeks.
Term Preterm (Pre)Emb. Fetal
LB LB Lossa Lossb
(n: 23) (n: 8) (n: 12) (n:1)
History of Pregnancy 22 (96%) 6 (75%) 10 (83%) 1
History of Pregnancy . . . .
Morbidity
10 (45%) 1 (17%) 5 (50%) 0
- >1 Fetal Loss
4 (18%) 1 (17%) 3 (30%) 0
- >1 Preterm Delivery
2 (9%) 1 (17%) 0 0
- >3c (Pre)Embryonic
Loss 8 (35%) 2 (34%) 5 (50%) 1
- >1 (Pre) Embryonic 5 (23%) 0 1 (10%) 0

Loss
No History of Pregnancy
Morbidity
Treatment During . . . .
Pregnancy
4 (17%) 1 (13%) 4 (33%) 0
- No ASA/LMWH
8 (38%) 1 (13%) 2 (17%) 0
- ASA
2 (9%) 0 0 0
- LMWH
9 (39%) 6 (75%) 6 (50%) 1
- ASA + LMWH
13 (57%) 4 (50%) 6 (50%) 1
- Hydroxychloroquine
LB: live birth; ASA: low-dose aspirin; LMWH: low-molecular-weight-heparin; a: (pre)embryonic loss < 10 weeks of gestation; b: fetal
loss > 20 weeks of gestation; c: consecutive
Disclosure: E. Sevim, None; D. Andrade, None; A. Banzato, None; D. W. Branch, None; R. Cervera, None; G. Ramires de Jesus, None;
J. S. Knight, None; P. L. Meroni, None; M. Tektonidou, None; A. Tincani, None; A. Ugarte, None; Z. Zhuoli, None; D. Erkan, None; O.
B. O. A. A. ., None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/antiphospholipid-syndrome-alliance-for-clinical-trials-

and-international-networking-aps-action-clinical-database-and-repository-analysis-pregnancy-outcomes-since-inception
Abstract Number: 13
Epidemiology of Antiphospholipid Syndrome: A Population-Based Study

Ali Duarte-Garcia1, Michael Pham1, Cynthia S. Crowson2, Kevin Moder3, Rajiv Pruthi4 and Eric L. Matteson5, 1Mayo Clinic, Rochester,
MN, 2Health Sciences Research, Mayo Clinic College of Medicine and Science, Rochester, MN, 3Rheumatology, Mayo Clinic, Rochester,
MN, 4Mayo Clinic, R, MN, 5Rheumatology, Mayo Clinic College of Medicine and Science, Rochester, MN
SESSION INFORMATION
Background/Purpose: The epidemiology of definite antiphospholipid syndrome (APS) in the general population has not been described. A
recent meta-analysis (Andreoli L, et al. Arth Care Res 2013;65:1869-73) concluded that it was difficult to determine the frequency of a
“clinically significant antiphospholipid (aPL) profile” in patients with aPL-related clinical outcomes due to the lack of robust data; only 4%
of the studies had the current cutoff values for anticardiolipin antibodies (aCL) and less than one fifth of them had confirmation after 6-12
weeks. This study aimed to characterize the epidemiology of definite APS based on the 2006 updated international consensus (Sydney)
classification criteria.
Methods: An inception cohort of patients with incident APS in 2000-2015 in a geographically well-defined population were identified
based on comprehensive individual medical record review. All cases met the definite 2006 Sydney consensus APS criteria, including the
laboratory and clinical criteria as well as laboratory confirmation after 12 weeks. Lupus anticoagulant, IgM and IgG aCL and anti-β2
glycoprotein-1 antibodies were tested in a centralized lab (cutoff >40 GPL/MPL). Incidence rates were age and sex adjusted to the US white
2010 population. Prevalence estimates were obtained from the incidence rates assuming no increased mortality associated with APS and
assuming migration in/out of the area was independent of disease status.
Results: In 2000-2015, 33 cases of incident APS were identified (mean age 54.2 years, 55% female; 97% Caucasian). The annual incidence
of definite APS was 2.0 per 100,000 population aged ≥ 18 years (95% confidence interval [CI]: 1.1-3.1 per 100,000). Incidence rates were
similar in both sexes (2.1 per 100,000 population in females and 2.0 per 100,000 population in males). The peak incidence was observed in
those who were older than 75 years. Significant changes in incidence rates over time were not observed. Six (18%) of the patients had a
concurrent diagnosis of systemic lupus erythematosus. Three (17%) patients had obstetric manifestations. During a median follow-up of 8.8
years, 7 patients died (84% survival at 10 years after APS incidence; 95% CI: 69-100%). The overall mortality of patients with APS was not
significantly different from the general population (standardized mortality ratio: 1.14; 95% CI, 0.46-2.64). The estimated prevalence of APS
adjusted to the US white 2010 population was 50 per 100,000 (95% CI: 42-58) and was similar in both sexes (51/100,000 for females and
48/100,000 for males). Based on this and US census data, an estimated 119,300 persons in the US were affected by APS in 2015.
Conclusion: Results from this first ever population based study revealed that definite APS occurred in about 2 persons per 100,000 per year.
The estimated prevalence is 50 per 100,000. Overall mortality was not different from the general population. The prevalence of APS in the
same population was at least as common as SLE (Jarukitsopa, et al. Arth Care Res 2015;67:817-28).
Disclosure: A. Duarte-Garcia, None; M. Pham, None; C. S. Crowson, None; K. Moder, None; R. Pruthi, None; E. L. Matteson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/epidemiology-of-antiphospholipid-syndrome-a-

population-based-study
Abstract Number: 14
Abnormalities in Th1, Th2 and Th17 Lymphoid Subpopulations in Long-Term

Evolution Primary Antiphospholipid Syndrome
Gabriela Medina1, Oscar I Florez-Durante2, Laura Arcelia Montiel Cervantes3, Rubiraida Molina Aguilar2, Elba Reyes Maldonado2 and
Luis J. Jara4, 1Clinical Research Unit, Hospital de Especialidades Centro Medico La Raza,IMSS, Mexico City, Mexico, 2Escuela Nacional
de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico, 3Hematology Laboratory, Hospital de Especialidades Centro
Médico La Raza, IMSS, Mexico City, Mexico, 4Direction of Education and Research, Hospital de Especialidades Centro Médico La Raza,
IMSS, Mexico City, Mexico
SESSION INFORMATION
Background/Purpose: Primary antiphospholipid antibody syndrome (PAPS) is characterized by recurrent thrombosis and pregnancy
morbidity in the presence of antiphospholipid antibodies (aPL). Lymphoid subpopulations and innate and adaptive immune responses have
not been fully studied in long-term evolution PAPS.
OBJECTIVE: To analyze the lymphoid subpopulations, Th1, Th2 and Th17 immune response in long-term evolution PAPS patients.
Methods: Patients with PAPS >18 years of age, of both genders and a group of healthy blood donors matched for age and sex were included.
All patients were receiving oral anticoagulants (Coumadin type). No patient had a recent episode (six months) of thrombosis or other
manifestation of APS at the time of the study. Peripheral blood was obtained and lymphoid subpopulations were determined by flow
cytometry in order to identify with specific immunological markers, for Treg cells we used: CD4+/CD25+/FoxP3+ and
CD8+/CD25+/FoxP3+. The dendritic cells analyzed were: type 1: Lin1-/HLA-DR+/CD11c+; Type 2: Lin1-/HLA-DR+/CD123+; B
lymphocytes with CD19+; Monocytes with CD14+; NK: CD3-/CD16+/56+ and NKT: CD3+/CD16+/56+ lymphocytes. Th1 cells were
identified by IFN-g+ positivity; Th2: positivity for IL-4+; Th17: positivity for IL-17+. Parametric statistics and Mann-Whitney U-test were
used.
Results:
A total of 50 patients with PAPS were included, age: 51.9 ± 12.8, evolution time: 12.8 ± 8.9 years and 35 healthy controls. In patients with
PAPS there was a decrease in the total CD3 (p<0.001), CD4 (p<0.005) CD8 (p <0.05) count, Monocytes (p<0.03) B lymphocites (p<0.002),
iNKT (p <0.001), DC1 (p <0.001) and DC2 (p <0.001) count cells compared to the control group (Table 1). We found significant decrease
in Th1, Th2 and Th17 cytokines basal and after activation compared to healthy controls.
Patients Controls
N=50 N=35 p
Median Median
CD3/uL 962 1351 0.001
CD4/uL 587 786 0.005
CD8/uL 246 445 0.001
nk/uL 129 249 0.02
nkt/uL 33 58 0.02
14/uL
140 241 0.03
(Monocytes)
19/uL (B
41 104 0.002
Lymphocites)
Tgd/uL 29 45 0.3
iNKT/uL 8 20 0.001
DC1/uL 2 5 0.001
DC2/uL 1 5 0.001
Treg CD4/uL 17 13 0.5
Treg CD8/uL 11 13 0.5
Mann Whitney
U test
Conclusion:
This study shows profound alterations in innate and adaptive immunity in patients with long-term PAPS, characterized by a decrease in
lymphocyte subpopulations and Th1, Th2, and Th17 cytokines with a possible prevalence of other proinflammatory cytokines and
inflammasomes. These abnormalities can become new therapeutic targets in order to restore immune imbalance. Our findings may explain in
part, the development of thrombosis, accelerate atherosclerosis and other complications, in PAPS patients with long term disease evolution.
Disclosure: G. Medina, None; O. I. Florez-Durante, None; L. A. Montiel Cervantes, None; R. Molina Aguilar, None; E. Reyes
Maldonado, None; L. J. Jara, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/abnormalities-in-th1-th2-and-th17-lymphoid-

subpopulations-in-long-term-evolution-primary-antiphospholipid-syndrome
Abstract Number: 15
Methodology and Systematic Review of the Literature for the Mcmaster RARE-Best
Practice Clinical Practice Guideline on Diagnosis and Management of the Catastrophic
Kimberly Legault1, Christopher Hillis1, Cindy Yeung1, Elie Akl2, Marc Carrier3, Ricard Cervera4, Mark Crowther1, Francesco Dentali5,
Doruk Erkan6, Gerard Espinosa7, Munther A Khamashta8, Joerg Meerpohl9, Karen Moffatt10, Sarah O'Brien11, Vittorio Pengo12, Jacob
Rand13, Ignasi Rodriguez14, Lisa Thom15, Holger Schunemann1 and Alfonso Iorio1, 1McMaster University, Hamilton, ON, Canada,
2American University of Beirut, Beirut, Lebanon, 3University of Ottawa, Ottawa, ON, Canada, 4Department of Autoimmune Diseases, Institut
Clínic de Medicina i Dermatologia, Hospital Clínic de Barcelona, Barcelona, Spain, 5Insubria University, Insubria, Italy, 6Rheumatology,
Hospital for Special Surgery- Weill Cornell Medicine, New York, NY, 7Autoimmune Diseases Department. Hospital Clínic de Barcelona,
Barcelona, Spain, 8Graham Hughes Lupus Research Laboratory, The Rayne Institute, London, United Kingdom, 9University of Freiburg,
Freiburg, Germany, 10Hamilton Health Sciences, Hamilton, ON, Canada, 11Nationwide Children's, Columbus, OH, 12Azienda Ospedaliera
of Padova, University of Padova, Padova, Italy, 13NY Presbyterian Hospital, New York, NY, 14Rheumatology, Hospital Clinica, Barcelona,
Spain, 15None (patient representative), Oxford, United Kingdom
SESSION INFORMATION
Background/Purpose:
Catastrophic antiphospholipid syndrome (CAPS), a rare disease, is characterized by the rapid onset of widespread thrombosis associated
with multi-organ failure in patients meeting the serological criteria for antiphospholipid syndrome. To date, the diagnosis and treatment for
CAPS has been based on expert consensus and case-series, not evidence-based guidelines developed with rigorous methodology. One of the
main obstacles to guideline development in rare diseases is the sparsity and very low certainty (or quality) of the available evidence. As a
prototypical rare disease, CAPS was selected to pilot the application of a guideline development process to a rare disease.
Methods:
The RARE-BestPractices project group in partnership with McMaster University developed a clinical practice guideline on diagnosis and
management of patients with CAPS, bringing together a panel of international experts, and using the GIN-McMaster Guideline Development
checklist. The evidence for the CAPS guideline was summarized using the GRADE methodology framework. Two novel methods, systematic
observation reporting forms and ad hoc registry data analysis, were implemented to supplement the available evidence.
Systematic observation reporting involved collecting standardized contributions from each panel member prior to the panel meeting regarding
characteristics and clinical course of previous CAPS patients. The goal was to systematize the process of expert input based on actual
experience rather than opinions or anecdotes. Ad hoc analysis of registry data involved calculating raw data for survival estimates for each
therapy question from the ‘CAPS Registry’, an international database that has over 500 CAPS patients enrolled.
Results:
Question generation yielded 47 questions, which were prioritized. The top 10 questions were selected by the panel for the guideline process,
3 diagnosis and 7 therapy. The therapy search identified 671 references, of which 8 articles were included in the systematic reviews. The
diagnosis search identified 519 references, of which 1 article was included. All of the included studies were considered to be at high risk of
bias. Eleven of the 20 panel members submitted systematic observation forms, representing 55 patient cases. The CAPS registry was used to
calculate raw mortality for 7 recommendations and impacted the panel’s decision for a treatment recommendation related to rituximab.
Conclusion:
The CAPS guideline initiative met the objective of successful development of a clinical practice guideline in a rare disease using GRADE
methodology. The novel methodology was found to be useful for complementing literature-based evidence in informing the recommendations.
Disclosure: K. Legault, Bayer, 9; C. Hillis, None; C. Yeung, None; E. Akl, None; M. Carrier, Leo Pharma, 5,Bayer, 5,Pfizer Inc, 5,Leo
Pharma, 9,BMS, 9; R. Cervera, None; M. Crowther, Bayer, 2; F. Dentali, None; D. Erkan, Alexion Pharmaceuticals, Inc., 5; G. Espinosa,
None; M. A. Khamashta, None; J. Meerpohl, None; K. Moffatt, None; S. O'Brien, None; V. Pengo, None; J. Rand, None; I. Rodriguez,
None; L. Thom, None; H. Schunemann, None; A. Iorio, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/methodology-and-systematic-review-of-the-literature-for-

the-mcmaster-rare-best-practice-clinical-practice-guideline-on-diagnosis-and-management-of-the-catastrophic-antiphospholipid-syndrome
Abstract Number: 16
Anti-Phosphatidylserine/Prothrombin Antibodies in Primary

Paola Bermudez-Bermejo1, Gabriela Hernandez-Molina2, Diego Hernández-Ramírez3, Victor Zamora-Legoff2, Elizabeth Olivares-
Martínez3, Antonio R. Cabral4 and Carlos Núñez-Álvarez5, 1Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y
Nutricion SZ, Mexico City, Mexico, 2Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición SZ, mexico city,
Mexico, 3Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico,
4Department of Medicine. Division of Rheumatology, The Ottawa Hospital.University of Ottawa, Ottawa, ON, Canada, 5Immunology and
Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion S.Z., Mexico city, Mexico
SESSION INFORMATION
Background/Purpose: Several studies have showed conflicting results regarding the presence and meaning of anti-
phosphatidylserine/prothrombin (aPS/PT). However aPS/PT antibodies seem to be a risk factor for thrombosis. Nevertheless, most of the
studies have focused on patients with SLE and secondary antiphospholipid syndrome (APS). We assessed the prevalence of aPS/PT
antibodies, as well as their association with other antiphospholipid (aPL) antibodies (specially lupus anticoagulant [LA]) and thrombosis, in
a well-established cohort of primary APS from a single center.
Methods: We included 96 consecutive patients with primary APS according the Sydney classification criteria and/or patients with
hematological features (thrombocytopenia and hemolytic anemia) attending a referral center in Mexico City. Patients from both groups
fulfilled the Sydney laboratory criteria for APS. We registered demographics, disease duration and type of manifestation. aCL (IgG and IgM),
antibodies to purified human anti-β2GP-I (IgG and IgM) and aPS/PT antibodies (IgG and IgM) were assessed by ELISA (INOVA
Diagnostics). LA was determined by LA/1 screening reactant and a confirmatory test LA/2 according to published guidelines. We used chi-
square (χ2) test, Spearman correlation analysis and logistic regression.
Results: Most patients were females (69.7%), mean age 44.5 ± 14.6 and median disease duration 7.3 years. The main clinical features were
thrombosis (n=74, 77%), hematologic involvement (n=49 patients, 51%) and obstetric events (n=24, 25%) (non-exclusive groups). The
prevalence of LA was 69.8%, aCL-IgG 56.8%, anti-β2GP-l IgG 43.1%, aCL-IgM 31.5% and anti-β2GP-I IgM 21%. The frequency of
aPS/PT antibodies was 61.2% and 61.6% for IgG and IgM isotype, respectively. When we compared patients with LA+ (n=58) vs. LA-
(n=25), the first group had a higher prevalence of aPS/PT-IgG (79.3% vs.16%, p=0.0001) and aPS/PT-IgM antibody (81.5% vs. 31.8%,
p=0.001), as well as higher titers (aPS/PT-IgG 130.5 U vs. 8.2 U and aPS/PT-IgM 58.5 U vs. 16.6 U, p=0.0001). aPS/PT-IgG antibodies
correlated with aPS/PT-IgM (ρ=0.59, p=0.0001), aCL-IgG (ρ=0.62, p=0.0001), anti-β2GP-l IgG (ρ= 0.63, p=0.001) and anti-β2GP-l IgM
(ρ=0.35, p=0.001). On the other hand, aPS/PT IgM antibodies correlated with aCL-IgG (ρ=0.57, p=0.0001), aCL-IgM (ρ=0.42, p=0.001),
anti-β2GP-l IgG (ρ=0.48, p=0.001) and anti-β2GP-l IgM (ρ =0.59, p=0.0001). We found moderate agreement between the presence of LA
and both aPS/PT isotypes (k= 0.58 p=0.0001 for IgG, and k=0.47 p=0.001 for IgM). Thrombosis was associated with aPS/PT-IgG antibodies
(87.7% vs. 61.1%, p=0.003) but not with aPS/PT IgM (73.6% vs. 81.8%, p=0.37). At the logistic regression analysis, the aPS/PT IgG
antibodies remained associated with thrombosis after adjusting by all other aPL antibodies, OR 8.6 95% CI 2.1-33.8, p=0.002.
Conclusion: In this cohort of patients with primary APS, aPS/PT antibodies were highly prevalent, correlated with other aPL antibodies and
were associated independently with thrombosis.
Disclosure: P. Bermudez-Bermejo, None; G. Hernandez-Molina, None; D. Hernández-Ramírez, None; V. Zamora-Legoff, None; E.

Olivares-Martínez, None; A. R. Cabral, None; C. Núñez-Álvarez, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/anti-phosphatidylserineprothrombin-antibodies-in-

primary-antiphospholipid-syndrome
Abstract Number: 17
Thrombotic Events in Pediatric Systemic Lupus Erythematosus: A Preliminary Analysis

of a Large, Single-Center Cohort
Jennifer Rammel1, Martha Curry2 and Marietta M. de Guzman3, 1Department of Pediatrics, Division of Immunology, Allergy and
Rheumatology, Baylor College of Medicine, Houston, TX, 2Pediatric Immunology, Allergy and Rheumatology, Baylor College of Medicine,
Houston, TX, 3Immunology, Allergy and Rheumatology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
SESSION INFORMATION
Background/Purpose: While pediatric systemic lupus erythematosus (pSLE) represents only 20% of all SLE cases, pSLE patients often have
more aggressive disease with multi-organ involvement. These patients can be at significant risk for thrombotic events due to systemic
inflammation, vasculopathy, antiphospholipid antibodies (aPLs) and nephrotic features. Data detailing the timing and nature of thrombotic
events in pSLE patients are limited. The objective of this study was to further characterize thrombotic events in a pSLE patient cohort at a
large academic medical center.
Methods: A retrospective chart review was completed for patients with pSLE who had a documented thrombotic event. All patients fulfilled
the American College of Rheumatology (ACR) classification criteria for SLE. Descriptive statistics were utilized for this preliminary
analysis.
Results: Of the 402 patients in this pSLE cohort, there were a total of 45 thrombotic events in 28 patients. The cohort was 89% female, 50%
African American, Non-Hispanic and 43% Caucasian, Hispanic. Mean age at pSLE diagnosis was 12.9 years, range was from 6.7 to 17.8
years. 71% (20) had positive APLs at pSLE diagnosis: 60% lupus anticoagulant (LA), 70% anticardiolipin (aCL), and 45%
antiβ2glycoprotein1 (aβ2GP1). Mean age at first thrombotic event was 14.9 years, range was from 7.8 to 22.9 years. There was a mean
difference of 2.0 years from pSLE diagnosis to thrombotic event, with a range of -4.4 to 10.3 years. Fifteen patients (54%) were diagnosed
with pSLE at the time of the initial thrombotic event. Of the 45 thrombotic events, 33% (15) were arterial and 66% (30) were venous.
Arterial events included 10 cerebrovascular accidents and 4 transient ischemic attacks. Venous events included 16 deep vein thromboses
(DVT), 2 pulmonary emboli (PE) without radiographically identified DVT, and 3 combined DVT/PEs. Seven patients (25%) had multiple
thrombotic events. At the time of the thrombotic event, 56% were aPL positive (60% LA, 72% aCL, and 40% aβ2GP1), 11% were negative,
and 33% were either not tested or the data was not available.
Conclusion: The majority of the thrombotic events in this cohort were venous, and a single occurrence. More than half of the patients were
diagnosed with pSLE as a result of the presenting thrombotic event. Most patients had positive antiphospholipid antibodies both at pSLE
diagnosis and at the time of the thrombotic event. Further research plans for this dataset include further analysis of predictive factors for
thrombosis and characterizing the variation in establishing initial thrombotic risk, surveillance and management.
Disclosure: J. Rammel, None; M. Curry, None; M. M. de Guzman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/thrombotic-events-in-pediatric-systemic-lupus-

erythematosus-a-preliminary-analysis-of-a-large-single-center-cohort
Abstract Number: 18
Increased Frequency of Nailfold Videocapillaroscopy Abnormalities in

Primaryantiphospolipid (PAPS) Patients
Tatiana Sofia Rodriguez-Reyna1, Eduardo Martín Nares2, Paola Bermudez-Bermejo3, Victor Zamora-Legoff4 and Gabriela Hernandez-
Molina5, 1Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico,
2Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico,
3Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion SZ, Mexico City, Mexico, 4Rheumatology and
Immunology, Instituto Nacional de Ciencias Medicas y Nutricion SZ, Mexico D.F., Mexico, 5Immunology and Rheumatology, Instituto
Nacional de Ciencias Médicas y Nutrición SZ, mexico city, Mexico
SESSION INFORMATION
Background/Purpose: Primary antiphospholipid syndrome (PAPS) is characterized by venous and arterial thrombosis, obstetric morbidity
and the presence of antiphospholipid antibodies. The utility of nailfold videocapillaroscopy in conditions such as scleroderma (SSc) and
primary Raynaud´s phenomenon is well known. Whether patients with PAPS have specific findings in nailfold videocapillaroscopy is not
well stablished. Our aim was to evaluate nailfold videocapillaroscopy findings in PAPS patients and their association with clinical and
serological features.
Methods: Weincluded 32 PAPS patients according to the modified Sidney criteria and the Alarcón-Segovia criteria for haematologic
antiphospholipid syndrome, who regularly attend a tertiary referral center in Mexico City, and 17 healthy controls. We performed nailfold
videocapillaroscopy according to the Cutolo technique (Optilia 200x) and obtained: capillary morphology, abnormalities (tortuosity, crossed
and dilated capillaries, capillary haemorrhages, neo-angiogenesis) and mean vascular density on 32 images per patient. We collected
demographic, clinical (thrombosis, obstetric morbidity, non-criteria manifestations and comorbidities), serological (anticardiolipin
antibodies, anti-β2 glycoprotein 1 antibodies and lupus anticoagulant) and treatment information. Analysis was performed used SSPS v.22,
Chi square test was used to compare frequencies and Student´s t test was used to compare means.
Results: PAPS patients had higher frequency of at least 1 abnormal finding on videocapillaroscopy (78% vs 12%, p<0.009, OR=26,
95%CI=5-146), higher frequency of dilated capillaries (69% vs 0%, p=0.0001, OR=3.2, 95%CI=1.9-5.3), lower frequency of “perfect
normal” pattern (12% vs 59%, p=0.002, OR=0.1, 95%CI=0.02-0.4) than controls, and 8 patients (25%) showed changes compatible with the
“early” SSc Cutolo pattern (<4 dilated capillaries/mm, <4 haemorrhages/mm, preserved architecture and no avascular areas). In PAPS
patients, capillary haemorrhages were associated with neurologic manifestations (75% vs 14%, p=0.02, OR=19, 95%CI=1.4-248) and with
comorbidity with hypertension (75% vs 14%, p=0.02, OR=19, 95%CI=1.4-248), while alterations compatible with “early” pattern were not
associated to any clinical or serological variable.
Conclusion: PAPS patients frequently show at least one abnormality on videocapillaroscopy. The most frequent abnormalities are dilated
capillaries, microhaemorrhages and the presence of an “atypical normal” pattern. Capillary haemorrages are frequently found in patients with
neurologic involvement of PAPS. The coexistence of hypertension or other comorbidities may contribute to the development of capillary
abnormalities in PAPS patients.
Disclosure: T. S. Rodriguez-Reyna, None; E. Martín Nares, None; P. Bermudez-Bermejo, None; V. Zamora-Legoff, None; G.
Hernandez-Molina, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/increased-frequency-of-nailfold-videocapillaroscopy-

abnormalities-in-primaryantiphospolipid-paps-patients
Abstract Number: 19
The Transcription Factor Specificity Protein 1 up-Regulates IL-21 Receptor Expression

on B Cells in Rheumatoid Arthritis Leading to Altered Cytokine Production and
Maturation
Elizabeth Dam1, Alison Maier1, Anne Hocking1, Jeffrey Carlin2 and Jane H. Buckner1, 1Benaroya Research Institute at Virginia Mason,
Seattle, WA, 2Rheumatology, Virginia Mason Medical Center, Seattle, WA
SESSION INFORMATION
Session Title: B Cell Biology and Targets in Autoimmune Disease Poster
Background/Purpose: Growing evidence suggests that IL-21 has a role in B cell dysfunction in rheumatoid arthritis (RA). Previous studies
have reported that IL-21 levels are increased in the serum and synovial fluid of RA subjects and correlate with the 28-joint count disease
activity score. While an increase in the percent of IL-21R positive B cells in RA has been described, the significance of this finding in B
cells with respect to signaling, B cell differentiation and function has not been investigated. The goal of this study was to address this gap in
knowledge and determine the mechanism that leads to increased IL-21R expression on B cells in RA.
Methods: We analyzed IL-21 receptor expression in B cells isolated from whole blood and synovial fluid from a cohort of RA subjects and
healthy controls matched for age, gender and race. The RA subjects all met the ACR classification criteria and none of the subjects were on
biologics at the time of the draw. Flow cytometry was used to quantify protein and mRNA levels of IL-21R, specificity protein 1 (SP1) and
to determine cytokine production (IL-6) and maturation status of B cells. IL-21 signaling was assessed by measuring pSTAT3 levels
following IL-21 stimulation. IL-21R levels were correlated to serum levels of rheumatoid factor (RF) IgM which was assessed by ELISA.
SP1 binding to the IL21R promoter region in B cells was assessed with ChIP-qPCR.
Results: We demonstrate an increase in IL-21R expression in total and memory B cells from RA subjects, which correlated with
responsiveness to IL-21 as measured by phosphorylation of STAT3. IL-21R expression on memory B cell also correlated with serum
rheumatoid factor IgM levels. There was comparable levels of IL-21R expression between memory B cells from peripheral blood and those
from synovial fluid in the same subject. In addition, stimulation of naïve B cells from RA subjects with IL-21 and CD40L resulted in an
increase in differentiation into plasmablasts. Further investigation showed that IL-21R expression correlated with an increase in the level of
the SP1 transcription factor. Mechanistic experiments showed increased binding of SP1 to the IL21R promoter region in B cells in RA.
Conclusion: Our results suggest a mechanism by which IL-21 enhances B cell development and function in RA through an SP1 mediated
increase in IL-21R expression on B cells. This suggests that therapies for RA may be more efficacious if targeted to memory B cells and/or
target SP1.
Disclosure: E. Dam, None; A. Maier, None; A. Hocking, None; J. Carlin, None; J. H. Buckner, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-transcription-factor-specificity-protein-1-up-

regulates-il-21-receptor-expression-on-b-cells-in-rheumatoid-arthritis-leading-to-altered-cytokine-production-and-maturation
Abstract Number: 20
Low Molecular Weight BAFF Receptor Antagonists Restrain Infiltration of B Cells into
Organs of Autoimmune Model Mice By Suppressing B Cell Activation
Keiko Yoshimoto1, Noriyasu Seki2, Katsuya Suzuki3, Kunio Sugahara4 and Tsutomu Takeuchi1, 1Division of Rheumatology, Department of
Internal Medicine, Keio University School of Medicine, Tokyo, Japan, 23) Research Unit/Immunology & Inflammation, Mitsubishi Tanabe
Pharma Corporation, Yokohama, Japan, 3Division of Rheumatology, Department of Internal Medicine, Keio University School of Medcine,
Tokyo, Japan, 4Research Unit/Immunology & Inflammation, Mitsubishi Tanabe Pharma Corporation, Yokohama, Japan
SESSION INFORMATION
Background/Purpose: We have reported that soluble BAFF (sBAFF) robustly increased IL-6 production by peripheral monocytes of
patients with primary Sjögren’s syndrome (pSS) and that the expression level of a BAFF receptor (BR3) was significantly elevated in pSS
monocytes. In our previous study, we have also demonstrated that the proportion of BR3-positive monocytes to total monocytes was
positively and significantly correlated with the serum IgG level of pSS patients. These data collectively suggest that the elevated expression
of BR3 on monocytes is involved in IgG overproduction by B cells and that BAFF signaling via BR3 is a possible therapeutic target to treat
autoimmune diseases, such as pSS. In addition, we have successfully discovered two pyrrolopryimidine derivatives, which inhibit BAFF
binding to BR3, by a high throughput screening of a low molecular weight compound library. These compounds inhibited not only IL-6 and
IL-10 production by BAFF-stimulated monocytes, but also IgG production by B cells in vitro co-cultured with monocytes in the presence of
sBAFF possibly by impairing differentiation of B cells.Notably, these compounds suppressed the serum level of an anti-dsDNA antibody in
autoimmune disease model mice. In this study, we investigate the effects of these compounds on infiltration of B cells into organs of the
model mice.
Methods: A pyrrolopryimidine derivative, BIK-13, which inhibits BAFF binding to BR3, was administered intraperitoneally to MRL/lpr
mice three times a week at a dose of 0.2 mg/kg for 6 months. Serum levels of an anti-ds DNA antibody, IL-6 and IL-10 were measured by
ELISA. The proportion of B cell in peripheral blood of the mice was analyzed by FACS. Infiltration of lymphocytes into organs was analyzed
by immunohistochemistry.
Results: Administration of BIK13 to MRL/lpr mice for 16 weeks decreased the serum level of an anti-dsDNA antibody. Moreover, serum
levels of IL-6 and IL-10, both of which induce B cell activation, in the mice were concomitantly declined as compared to control mice.
Notably, immunohistochemistry revealed that infiltration of B lymphocytes was remarkably suppressed in salivary and lacrimal glands and
kidney of the mice. In addition, the proportion of B cells in peripheral blood was also decreased in BIK-13-treated mice as compared to the
control mice.
Conclusion: These data collectively suggest that BIK-13, a low molecular weight BR3 antagonist, suppress the B cell activation and resultant
infiltration into organs in vivo. Suppression of cytokine production by monocytes may be directly or indirectly involved in the molecular
mechanism of the suppression of the B cell activation. The compound may provide a novel therapeutic possibility to treat autoimmune
diseases.
Disclosure: K. Yoshimoto, None; N. Seki, Mitsubishi Tanabe Pharma Corporation, 3; K. Suzuki, None; K. Sugahara, Mitsubishi Tanabe
Pharma Corporation, 3; T. Takeuchi, Mitsubishi Tanabe Pharma Corporation, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/low-molecular-weight-baff-receptor-antagonists-restrain-

infiltration-of-b-cells-into-organs-of-autoimmune-model-mice-by-suppressing-b-cell-activation
Abstract Number: 21
Reciprocal Regulation of B Cells on Bleomycin-Induced Scleroderma Model: IL-6-

Producing Effector B Cells Play a Pathogenic Role, While IL-10-Producing Regulatory
B Cells Play a Protective Role
Takashi Matsushita1, Yasuhito Hamaguchi1, Minoru Hasegawa2, Manabu Fujimoto3 and Kazuhiko Takehara4, 1Department of
Dermatology, Kanazawa University, kanazawa, Japan, 2Department of Dermatology, University of Fukui, Fukui, Japan, 3Department of
Dermatology, University of Tsukuba, Tsukuba, Japan, 4Department of Dermatology, Kanazawa University, Kanazawa, Japan
SESSION INFORMATION
Background/Purpose: IL-10-producing regulatory B (Breg) cells negatively regulate autoimmune diseases. We reported that Breg cells play
a protective role in a mouse model of systemic sclerosis (SSc) and in patients. Recent studies indicate that IL-6-producing effector B (Beff)
cells have pathogenic effect in autoimmune diseases. IL-6 plays a critical role for the pathogenesis of SSc, and a phase III trial of anti-IL-6R
antibody (tocilizumab) is ongoing in patients with SSc. However, the phenotype and function of IL-6-producing Beff cells remains unclear. In
this study, we investigated the phenotype of IL-6-producing Beff cells and their role in SSc pathogenesis.
Methods: B cell subsets were sorted and cytokine production was measured by intracellular cytokine staining. We generated mixed bone
marrow chimeric mice with a B cell_specific deficiency in IL-6 or IL-10 production (B-IL-6-/- or B-IL-10-/-), together with control chimeras
(B-WT). Skin fibrosis was assessed 4 weeks after the initiation of bleomycin treatment in mixed bone marrow chimeric mice.
Results: Most splenic IL-6 producing Beff cells were detected within the marginal zone (MZ) B cell subset, while IL-10-producing Breg
cells were detected within the MZ B and B1 B cell subsets, but not within the follicular B cell subset (Fig 1). Serum IL-6 levels gradually
increased with the development of fibrosis in bleomycin-induced scleroderma mice, while serum IL-10 levels did not. In addition, the
frequency of splenic IL-6-producing Beff cells in bleomycin-treated mice was significantly increased. The bleomycin-induced skin fibrosis
was attenuated in B-IL-6-/- mice compared with that in B-WT mice. In contrast, B-IL-10-/- mice showed more severe skin fibrosis than B-WT
mice (Fig 2).
Conclusion: IL-6-producing Beff cells play a pathogenic role in bleomycin-induced scleroderma model, while IL-10-producing Breg cells
play a protective role (Fig 3). Thus, B cells have reciprocal roles in SSc pathogenesis, presenting pathogenic and protective functions.
Disclosure: T. Matsushita, None; Y. Hamaguchi, None; M. Hasegawa, None; M. Fujimoto, None; K. Takehara, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/reciprocal-regulation-of-b-cells-on-bleomycin-induced-

scleroderma-model-il-6-producing-effector-b-cells-play-a-pathogenic-role-while-il-10-producing-regulatory-b-cells-play-a-protective-role
Abstract Number: 22
Bone Regulatory Cytokine Production By B Cells in Rheumatoid Arthritis Is Dependent

on NF-κb Activation and Autophagy Pathways
Jason Glanzman1, Nida Meednu1, Victor Wang1, Wen Sun2, Lianping Xing3 and Jennifer H. Anolik1, 1Medicine- Allergy, Immunology and
Rheumatology, University of Rochester Medical Center, Rochester, NY, 2Nanjing Medical University, Nanjing, China, 3Pathology & Lab
Medicine, University of Rochester Medical Center, Rochester, NY
SESSION INFORMATION
Background/Purpose: Rheumatoid arthritis (RA) is a systemic autoimmune disease that often leads to joint damage, a process mediated by
an imbalance between bone resorption and bone formation. B cells play a role in bone homeostasis in RA, and evidence suggests that B cells
can affect function of both osteoblasts (OB) and osteoclasts (OC). In mouse models of RA, B cells were enriched in the subchondral bone
marrow (BM) and synovium, and were adjacent to the bone surface. These B cells produce the inflammatory cytokines TNFα and CCL3,
which drive dysregulation of bone homeostasis via their OB inhibitory and OC stimulatory effects. In vitro, synergistic production of these
cytokines results from co-activation of the B cell receptor (BCR) and toll-like receptor 9 (TLR9). Therefore, we investigated the mechanisms
underlying synergistic TNFα/CCL3 production by B cells in response to BCR and TLR9 co-activation.
Methods: Isolated B cells from peripheral blood of healthy controls (HC) were stimulated with 10 µg/mL anti-Ig (A+M+G) and CpG2006
for 4 hours, and production of TNFα and CCL3 was assessed by ELISA and qPCR. Multiple specific inhibitors were used to test the
involvement of BCR, TLR9, and NF-κB signaling, as well as autophagy. Data is presented as mean±SEM. Statistical significance was
determined by student’s t-test.
Results: Stimulation of B cells with α-Igs and CpG2006 induced significant production of TNFα and CCL3 compared to unstimulated B cells
at mRNA and protein levels. Furthermore, cytokine production was significantly higher than levels from α-Igs or CpG2006 stimulations
alone, suggesting a synergistic effect (CpG+α-Igs vs. CpG vs. α-Igs (ng/mL): TNFα: 2.71±0.42 vs. 0.33±0.04 (P<0.0001) vs. 0.70±0.23
(P=0.0008), CCL3: 3.69±1.00 vs. 0.77±0.29 (P=0.0031) vs. 0.64±0.18 (P=0.0037)). This synergistic production was dependent on TLR9
and BCR signaling, as blocking B cells with hydroxychloroquine (TLR inhibitor) or PP2 (Src kinase inhibitor) reduced cytokine production
to non-synergistic levels. Additionally, blocking BCR internalization with MDC also reduced TNFα and CCL3 production. To investigate
signaling downstream of BCR/TLR9 synergy, we tested inhibitors against classical NF-κB (TPCA-1), non-classical NF-κB (NIK inhibitor)
and AP-1. We found that BCR/TLR9 synergy was classical NF-κB dependent (CpG+α-Igs vs. CpG+α-Igs+TPCA-1 (ng/mL): TNFα:
2.5±0.44 vs. 0.33±0.14 (P=0.009), CCL3: 1.9±0.3 vs. 0.83±0.08 (P=0.027)). Finally, we inhibited autophagy using class III PI3K inhibitor
3-methyladenine which reduced TNFα and CCL3 production to non-synergistic levels, suggesting that BCR/TLR9 synergy depends on
autophagy (CpG+α-Igs vs. CpG+α-Igs+3-MA (ng/mL): TNFα: 1.5±0.25 vs. 0.4±0.04 (P=0.0058), CCL3: 4.1±1.15 vs. 0.82±0.35
(P=0.033)). Investigation of the specific autophagy pathway involved is currently underway.
Conclusion: Dual activation of B cells through the BCR and TLR9 synergistically enhanced TNFα and CCL3 production in a classical NF-
κB, and autophagy-dependent manner. These results characterize key mechanistic events in the synergistic production of bone regulatory
cytokines by B cells, a process that contributes to the dysregulation of bone homeostasis in RA.
Disclosure: J. Glanzman, None; N. Meednu, None; V. Wang, None; W. Sun, None; L. Xing, None; J. H. Anolik, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/bone-regulatory-cytokine-production-by-b-cells-in-

rheumatoid-arthritis-is-dependent-on-nf-%ce%bab-activation-and-autophagy-pathways
Abstract Number: 23
Auto-Reactive B Cells Escape Peripheral Tolerance Checkpoints in Patients with PR3-

ANCA Associated Vasculitis
Divi Cornec1, Alvise Berti2, Amber Hummel1, Tobias Peikert1, Jacques-Olivier Pers3 and Ulrich Specks4, 1Mayo Clinic, Rochester, MN,
2Department of Immunology, Rheumatology, Allergy and Rare Diseases, San Raffaele Scientific Institute, Milan, Italy, 3Immunology, Brest
University Medical School Hospital, Brest, France, 4Mayo Clinic College of Medicine, Rochester, MN
SESSION INFORMATION
Background/Purpose:
While extensive studies have been performed to characterize ANCA, little is known about the auto-reactive B cells that produce these
autoantibodies. Indirect evidence previously suggested the presence of circulating PR3-specific B cells in patients with PR3-ANCA-
associated vasculitis (AAV). Our objectives here were to develop a method to detect circulating PR3-specific B cells in patients with PR3-
AAV, to study their proportion among the different B-cell subsets and to assess their relationship with disease activity.
Methods:
A recombinant PR3 (rPR3) was tagged using FITC or biotin, and we studied its ability to bind specifically to two hybridoma cell lines,
MCPR3-2 (producing an anti-human PR3 monoclonal antibody) and MCPR3-13 (producing an anti-mouse PR3 monoclonal antibody, with no
cross-reactivity with human PR3). We measured the proportion of PR3-FITC positive B cells among PBMCs in 13 patients with PR3-AAV
and 14 healthy controls (HCs) by flow cytometry. We then developed a multi-color flow cytometry including CD19, IgD, CD27, CD38,
CD24 and biotinylated rPR3 to measure the proportion of PR3-specific B cells among different B-cell subsets in an independent group of 13
patients with PR3-AAV and 11 HCs.
Results:
rPR3 efficiently bound MCPR3-2 hybridoma cells but not MCPR3-13. Specificity of the staining was confirmed by competition experiments:
pre-incubation of MCPR3-2 cells with untagged human rPR3 totally abrogated rPR3-FITC staining, whereas pre-incubation with mouse rPR3
had no effect. Dose-ranging experiments defined the optimal concentration of rPR3 to stain cells expressing anti-PR3 immunoglobulin. The
mean (SEM) proportion of rPR3-FITC-stained B cells was higher in patients with PR3-AAV compared to HCs: 2.10% (2.33) vs 0.45%
(0.19) respectively, p<0.001. Patients with active disease had numerically higher proportions of PR3-specific B cells than patients in
remission: 3.66% (3.28) vs 1.10% (0.52), p=0.09. In HCs, the proportion of PR3-specific B cells was highest among the transitional B-cell
subset, and decreased along with the maturation of B cells (figure). Conversely, in patients, the proportion of PR3-specific B cells
progressively increased with the maturation of B cells (median 1.9% of naïve B cells, 2.30% of IgD+ memory B cells, 2.37% of IgD-
memory B cells, and 3.68% of plasmablasts, p<0.05 for all comparisons with the naïve subset).
Conclusion:
This study describes an original method to detect and study circulating auto-reactive B cells in patients with PR3-AAV, and suggests that
PR3-specific B cells are associated with disease activity and may represent a promising biomarker to predict relapse risk in patients in
clinical remission. The progressive enrichment in PR3-specific B cells during the B-cell maturation steps in patients suggest that auto-
reactive B cells are actively selected and escape peripheral tolerance checkpoints.
Disclosure: D. Cornec, None; A. Berti, None; A. Hummel, None; T. Peikert, None; J. O. Pers, None; U. Specks, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/auto-reactive-b-cells-escape-peripheral-tolerance-

checkpoints-in-patients-with-pr3-anca-associated-vasculitis
Abstract Number: 24
Trafficking of Innate B Cells to the Lungs As a Novel Mechanism in a Model of

Pulmonary Lupus and Vasculitis
Priti Prasad1, Michael Fishbein2, Rohan Sharma3, Ramesh Halder4, Isela Valera1 and Ram R. Singh5, 1Autoimmunity and Tolerance
Laboratory, Division of Rheumatology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles,
Los Angeles, CA, 2Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California Los
Angeles, Los ángeles, CA, 3Autoimmunity and Tolerance Laboratory, Division of Rheumatology, Department of Medicine, David Geffen
School of Medicine at University of California Los Angeles, Los angeles, CA, 4Autoimmunity and Tolerance Laboratory, Division of
Rheumatology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, Los ángeles, CA,
5Autoimmunity and Tolerance Laboratory, Department of Medicine/Rheumatology, David Geffen School of Medicine at University of
California Los Angeles, Los Angeles, CA
SESSION INFORMATION
Background/Purpose: Lung is involved in up to 50% patients with SLE. Among manifestations of pulmonary lupus, pneumonitis, vasculitis
and diffuse pulmonary hemorrhage (DPH) carry a high mortality rate, and are without any effective treatment. Advances in the pathogenesis of
pulmonary lupus have been hampered because of the heterogeneity of clinical findings, paucity of access to the affected tissue, and the lack of
suitable model systems. Hydrocarbon oils, such as 2,6,10,14-tetramethylpentadecane (TMPD), induce lupus-like autoantibodies, nephritis,
arthritis, pneumonitis, and DPH depending on the animals’ genetic background. Previous studies have used this model to show that animals
that lack B cells (Igμ-/-) have a reduced prevalence of DPH. Here, we examined the role of innate B1 B cells in the pathogenesis of
pulmonary lupus using the TMPD-DPH model.
Methods: We injected TMPD to induce pulmonary lupus in C57BL/6 (B6) mice and analyzed B cells and B cell subsets in the lungs and
peritoneal cavity. To determine the role of innate B cells, we injected CD19-/- mice (deficient in B1a B cells) and wild-type B6 mice with
500 μl TMPD intraperitoneally. Furthermore, we adoptively transferred wild-type peritoneal fluid cells which are enriched in B1 B cells
into CD19-/- and in Igμ-/- mice (have no B cells). We assessed disease using weight-loss, a semi quantitative scoring system for lung
inflammation and hemorrhage, and a quantitative measurement for lung hemorrhage.
Results: 73% of 62 TMPD-injected wild-type B6 mice exhibited weight-loss, pneumonitis, vasculitis, and/or DPH compared to none of
controls injected with control hydrocarbon oil hexadecane or with PBS or sham. Immunophenotyping revealed abnormalities of all immune
cells tested in the diseased lungs. At earlier timepoints prior to histopathological changes, while both hexadecane and TMPD caused myeloid
cell abnormalities, only TMPD caused lung-infiltration with B-cells that expressed B1 B cell subset markers: CD19+CD11b+/CD19+CD5+.
Such B1 B cells were simultaneously reduced in their usual location (peritoneal cavity). CD19-/- mice that have less B1a B cells developed
less DPH, and less B cell infiltration in the lungs than wildtype mice. The adoptive transfer of wildtype peritoneal fluid cells that are
abundant in B1 B cells into the peritoneum of CD19-/- or Igμ-/- mice induced more DPH/pneumonitis than the respective knockout recipients
reconstituted with CD19-/- B-cells. The adoptive transfer of CD45.1+ wildtype peritoneal fluid cells into the peritoneum of CD45.2+CD19-/-
recipients led to lung-infiltration with CD45.1+ B cells. Furthermore, TMPD induced in the lungs a differential expression of a set of
immune/inflammatory genes including chemokine Cxcl13 that are known to drive B1 B-cells’ migration.
Conclusion: Exposure to TMPD induces B1 B cells to traffic from the peritoneum into the lungs and cause pneumonitis/DPH. Our
observations have implications for pulmonary complications of lupus, vasculitis and other rheumatic diseases by identifying a specific B cell
subset as a potential target for therapy. Furthermore, humans can be exposed to hydrocarbon oils present in crude oil and in mineral oils used
in cosmetics, laxatives, and food-coatings.
Disclosure: P. Prasad, None; M. Fishbein, None; R. Sharma, None; R. Halder, None; I. Valera, None; R. R. Singh, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/trafficking-of-innate-b-cells-to-the-lungs-as-a-novel-

mechanism-in-a-model-of-pulmonary-lupus-and-vasculitis
Abstract Number: 25
A Novel Role for Galectin-3 Binding Protein in B Cell Biology and Antibody Secretion
Shinji Okitsu1, Melinda Genest1, Nuruddeen Lewis1, Evgeni Tzvetkov1, Yin Wu2, Andrew Bender1, Arnon Arazi3, Thomas Eisenhaure3,
Edward Browne4, Alex Rolfe5, Jonathan Derry6, William Pendergraft III7, Nir Hacohen8, Julie DeMartino5 and Jaromir Vlach5, 1TIP
Immunology, EMD Serono Research and Development Institute, Billerica, MA, 2TIP Immunology, EMD Serono Research & Development
Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica, MA, 3Broad Institute, Cambridge, MA, 4Massachusetts General
Hospital, Boston, MA, 5EMD Serono Research and Development Institute, Billerica, MA, 6Iris Bioconsulting, Bainbridge Island, WA,
7Kidney Center, University of North Carolina, Chapel Hill, NC, 8Harvard Medical School, Boston, MA
SESSION INFORMATION
Background/Purpose: Antibodies are important in protection against pathogens, but also harbor the potential to cause autoimmune disease
when directed against self-antigens. Systemic lupus erythematosus (SLE) is an autoimmune disease where antibodies recognizing nucleic
acids and associated proteins form immune complexes that drive inflammation and disease progression. Consequently, targeting B cells and
antibody production is a main focus in SLE drug development and we have endeavored to discover new targets in this pathway.
Methods: Here we show results from screening a secreted protein library for effects on Ig secretion by primary human B cells.
Results: We identified galectin-3 binding protein (G3BP) as a soluble factor that enhances antibody production induced by a variety of
stimuli in vitro. In an orthogonal translational study we found that the G3BP gene (LGALS3BP) was one of the most upregulated genes across
14 different immune cell types isolated from lupus nephritis (LN) patient blood. LGALS3BP contains an IRF7 binding site in its promoter and
we observed increased expression in TLR7-stimulated PBMCs. SLE is characterized by RNAs that induce type I interferon (IFN)
inflammation through the innate receptor TLR7. LGALS3BP expression in LN patients correlated with type I interferon-inducible genes
indicating that G3BP is part of this pathological process. Indeed, in support of this hypothesis, other investigators have documented
upregulated LGALS3BP in active IFN high SLE patients versus healthy controls (Merrill, J.T. et al., ACR abstract 1809, 2013). We found the
same LGALS3BP upregulation and correlation with type I IFN in a mouse model of LN. Moreover, upregulation in mouse kidneys correlated
with nephritis development. In in vitro studies we found that antibodies against G3BP led to defects in human B cell survival and loss of
antibody production.
Conclusion: We hypothesize that targeting G3BP may be a novel approach to inhibit autoantibody production and may benefit patients
suffering from antibody-mediated autoimmune diseases, including lupus nephritis.
Disclosure: S. Okitsu, EMD Serono Inc., 3,EMD Serono Inc, 1; M. Genest, EMD Serono Inc, 3; N. Lewis, EMD Serono Inc, 3; E.
Tzvetkov, EMD Serono Inc, 3; Y. Wu, EMD Serono, Inc, 3; A. Bender, EMD Serono, Inc, 3; A. Arazi, None; T. Eisenhaure, None; E.
Browne, None; A. Rolfe, EMD Serono Inc, 3; J. Derry, Amgen, Merck and Co, 1,EMD Serono, Inc; Curis, Inc; ITeos Therapeutics; Lumos
Pharma; Aptevo Therapeutics, 5; W. Pendergraft III, EMD Serono, Inc, 2; N. Hacohen, EMD Serono, Inc, 2; J. DeMartino, EMD Serono
Inc, 3,EMD Serono, Novartis, 1,Merck and Co, 1; J. Vlach, Jaromir Vlach, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-novel-role-for-galectin-3-binding-protein-in-b-cell-
biology-and-antibody-secretion
Abstract Number: 26
Single B Cell Analysis Revealed the Relationship Among the Cytokine Profile, Antibody
Affinity, and Pathogenic Roles of Autoantigen-Reactive B Cells in Systemic Sclerosis
Takemichi Fukasawa1, Ayumi Yoshizaki2, Satoshi Ebata1, Kouki Nakamura1, Ryosuke Saigusa1, Takashi Yamashita1, Yoshihide Asano3,
Yutaka Kazoe4, Kazuma Mawatari4, Takehiko Kitamori4 and Shinichi Sato5, 1Dermatology, University of Tokyo, Graduate School of
Medicine, Tokyo, Japan, 2Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan, 3Applied
Chemistry, University of Tokyo, Graduate School of Medicine, Tokyo, Japan, 4Applied Chemistry, University of Tokyo, Graduate School of
Engineering, Tokyo, Japan, 5Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan
SESSION INFORMATION
Background/Purpose:
Recent studies have indicated that B cells play critical roles in systemic autoimmunity and disease expression through various functions such
as induction of the activation of other immune cells in addition to autoantibody production. Indeed, rituximab, a B cell depleting antibody, can
ameliorate some autoimmune diseases including systemic sclerosis (SSc). However, the role of autoreactive B cells is still not clear,
because the number of autoreactive B cells is too small to study their functions directly. Although several studies have revealed that B cells
play crucial roles in SSc development, autoreactive B cell functions remain totally unclear. In this study, we investigated the role of
autoreactive B cells directly using our original micro-ELISA system, which integrates immunoassay into a microchip in order to detect
extremely small amounts of analytes and can study autoreactive B cells at a single cell level.
Methods:
Peripheral blood mononuclear cells (PBMCs) were obtained from topoisomerase (topo) I positive SSc patients and healthy controls. Each of
topo I-specific B cells was sorted into individual wells of 96 well plates. Their mRNA levels were assessed by single cell PCR. In addition,
their cytokine production was analyzed by the micro-ELISA system which realized the analysis of cytokine production in single cells. In
mouse studies, we assessed antibody affinities and cytokine production of topo I-specific B cells using topo I and complete Freund’s
adjuvant-induced SSc model mice. Furthermore, topo I-specific B cells from topo I and complete Freund’s adjuvant-induced SSc model mice
were adoptively transferred to these model mice and then skin and lung fibrosis was assessed.
Results:
Topo I-specific B cells from SSc patients produced higher amounts of IL-6 compared with topo I-non-specific B cells. In addition, IL-10
production of topo I-specific B cells was lower than those of topo I-non-specific B cells.
To reveal the relationship between B cell affinity to the autoantigen and their cytokine production, we analyzed single topo I-immunized SSc
model mice and fourth immunized SSc model mice. Single immunized mice had higher frequencies of IL-10-producing topo I-specific B cells
than fourth immunized mice, while fourth immunized mice had higher frequencies of IL-6-producing topo I-specific B cells than single
immunized mice. The affinity of topo I-specific B cells from fourth immunized mice was higher than those from single immunized mice.
Adoptive transfer with high-affinity topo I-specific B cells aggravated skin and lung fibrosis. By contrast, that with low-affinity topo I-
specific B cells ameliorated skin and lung fibrosis.
Conclusion:
These results suggest that distinct B cell cytokine production is determined by B cell autoantigen affinity. Autoantigen-reactive B cells with
higher autoantigen affinity can be a novel therapeutic target in SSc.
Disclosure: T. Fukasawa, None; A. Yoshizaki, None; S. Ebata, None; K. Nakamura, None; R. Saigusa, None; T. Yamashita, None; Y.
Asano, None; Y. Kazoe, None; K. Mawatari, None; T. Kitamori, None; S. Sato, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/single-b-cell-analysis-revealed-the-relationship-among-

the-cytokine-profile-antibody-affinity-and-pathogenic-roles-of-autoantigen-reactive-b-cells-in-systemic-sclerosis
Abstract Number: 27
Effects of High Titers of Anti-Chimeric Antibodies Following Rituximab

Roberta Fenoglio1, Laura Solfietti1, Savino Sciascia2 and Dario Roccatello1, 1Center of Research of Immunopathology and Rare Diseases-
Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, University
of Turin and S. Giovanni Bo, Turin, Italy, 2Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piemonte and
Valle d’Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, University of Turin, Italy, Center of Research of
Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, Department of
Clinical and Biological Sciences, University of Turin, Italy, Torino, Italy
SESSION INFORMATION
Background/Purpose:
Monoclonal antibodies (MoAbs) are highly successful in treating various immunological disorders. The development of anti-drug antibodies
(ADA) against the therapeutic MoAb is relatively common. In recent years, knowledge of how to assess immunogenicity of biological drugs
has improved. ADA are thought to form immune complexes with the MoAb, leading to accelerated MoAB clearance and low decrease levels
in the blood stream. Several reports showed an inverse relationship between MoAb levels and anti MoAb antibody formation. Further,
patients who develop ADA are more likely to present with infusion-related adverse effects. Acute infusion reactions, including anaphylaxis,
develop in a close temporal relationship to MoAb infusion.
Among the others MoAbs, Rituximab (RTX), an anti-CD20 monoclonal antibody, often results in the production of human anti-chimeric
antibodies (HACA).
In this study, we aimed to evaluate the presence of HACA in patients with poor response to treatment with RTX
Methods:
We assessed the incidence of anti-drug antibodies (ADA) in patients with autoimmune diseases treated with the RTX and determine the
potential relationship with trough drug concentration, efficacy, and patient-reported outcomes.
Results:
When investigating 37 patients treated with RTX, we found very high-titer of HACA (> 1,000 AU) in 5 patients (13.5%): 2 with Systemic
Lupus Erythematosus (SLE), 2 with Membranous Nephropathy (MN) and 1 patient with Mixed Cryoglobulinemia (MC). Details are given in
table 1. In 4 of them, high titers of HACA were clearly related to unresponsiveness to RTX treatment. In the other case the appearance of high
HACA titers was consonant with a severe hypersensitivity reaction during RTX re-treatment.
Conclusion:
HACA detection and monitoring, especially in the cases of RTX re-treatment, could not only assure a safer administration, but also support a
more rational strategy of treatment.
Case Disease # of steroid- HACA-Titer RTX-
cycles level
with RTX therapy (AU)
1 SLE 1 Yes 15,720 ND
2 SLE 1 Yes 3,719 ND
3 MC 3 No 14,670 0
4 MN 1 No 1,007 0
5* MN 2 No 10,363 0
Tab.I: Patient sample

Disclosure: R. Fenoglio, None; L. Solfietti, None; S. Sciascia, None; D. Roccatello, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effects-of-high-titers-of-anti-chimeric-antibodies-

following-rituximab
Abstract Number: 28
Sapril and Sbcma As Potential Biomarkers of B Cell Hyperactivation in Rheumatoid

Arthritis: A Cluster Analysis Approach
Javier Rodríguez-Carrio1, Mercedes Alperi-López2, Patricia López1, Francisco Javier Ballina-García3 and Ana Suárez1, 1Area of
Immunology, Department of Functional Biology, University of Oviedo, Oviedo, Spain, 2Department of Rheumatology, Hospital Universitario
Central de Asturias, Asturias, Spain, 3Department of Rheumatology, Hospital Universitario Central de Asturias, Oviedo, Spain
SESSION INFORMATION
Background/Purpose: B cell compartment plays a key role in the pathogenesis of rheumatoid arthritis (RA). Activation and survival of B
cell largely rely on the BLyS-APRIL system, including ligands and receptors, both expressed as membrane (m) and soluble (s) forms. The
main aim of this study was to analyze the role of the BLyS-APRIL system in RA, with a special focus on its clinical relevance.
Methods: sBLyS, sAPRIL, sBCMA, sTACI, IFNα, MIP1α, TNFα, IL-10, IFNγ, IL-8, IL-37 and GM-CSF levels were measured by
immunoassays in serum samples from 104 RA patients (EULAR/ACR 2010 criteria) and 33 healthy controls (HC). The membrane BLyS
(mBLyS) expression was assessed on B cells, monocytes (MØ), myeloid (mDC) and plasmacytoid (pDC) dendritic cells and neutrophils
(NØ) by flow cytometry in blood samples. A group of biological-naïve RA patients was prospectively followed for 3 months upon TNFα-
blockade.
Results: RA patients exhibited increased sAPRIL (p<0.001) and sBCMA serum levels (p=0.002) than HC. sBLyS was higher in patients
with early arthritis (recruited at onset) compared to those with long-standing disease (p=0.051) and HC (p=0.024). Levels of sTACI did not
differ between patients and controls (p=0.462). mBLyS expression was increased on B cells (p=0.002), MØ (p<0.001), mDC (p<0.001) and
NØ (p=0.014) in RA. By means of an unsupervised cluster analysis based on sBLyS, sAPRIL, sBCMA and sTACI, two clusters were
identified (clusters I and II), cluster II being hallmarked by increased sAPRIL and sBCMA serum levels. Cluster II was found in 26 (25.0%)
RA patients but was not observed in the HC group (p=0.001). Cluster II RA patients showed increased RF (p=0.002) and ACPA (p=0.001)
positivity and were less likely to be treated with methotrexate (p=0.028) but more likely with anti-TNFα agents (p=0.013) compared to their
cluster I counterparts. Cluster II was associated with higher DAS28 (p<0.050) but no difference in disease duration was observed (p=0.159).
Additionally, higher IL-10 (p=0.060), IFNα (p=0.005), MIP1α (p=0.042), TNFα (p=0.006) and GM-CSF (p=0.008) levels were registered
in cluster II. Further analyses revealed that sTACI was negatively associated with DAS28 score (r=-0.283, p=0.014) and positively with IL-
10 serum levels (r=0.233, p=0.040) in patients within cluster I. On the contrary, in cluster II, APRIL was positively correlated with mBLyS
expression on B cells (r=0.786, p=0.036), whereas sBLyS was associated with DAS28 (r=0.281, p=0.016). Also, IFNα serum levels
paralleled those of sTACI (r=-0.636, p<0.001) in these patients. Finally, increasing sBLyS (p=0.043) and sBCMA levels (p=0.019) upon
TNFα-blockade were associated with poor clinical outcome.
Conclusion: APRIL and sBCMA identify a subset of patients with a more severe disease, probably linked to a B cell hyperactivation status.
APRIL and sBCMA may be promising biomarkers for patient stratification to B-cell targeted therapy in RA.
Disclosure: J. Rodríguez-Carrio, None; M. Alperi-López, None; P. López, None; F. J. Ballina-García, None; A. Suárez, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/sapril-and-sbcma-as-potential-biomarkers-of-b-cell-

hyperactivation-in-rheumatoid-arthritis-a-cluster-analysis-approach
Abstract Number: 29
BTK Inhibition Ameliorates Lupus-Associated Neuropsychiatric and Skin Disease

Samantha Chalmers1, Jing Wen1, Jessica Doerner1, Ariel Stock2, Carla Cuda3, Hadijat Makinde3, Harris Perlman4, Todd Bosanac5,
Deborah Webb5, Gerald Nabozny6, Elliott Klein5, Jay S. Fine5, Meera Ramanujam5 and Chaim Putterman7, 1Albert Einstein College of
Medicine, Bronx, NY, 2Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, 3Northwestern University,
Chicago, IL, 4Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine, Northwestern
University Feinberg School of Medicine,, Chicago, IL, 5Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT,
6gerald.nabozny@boehringer-ingelheim.com, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, 7Division of Rheumatology, Albert
Einstein College of Medicine, Bronx, NY, USA, Bronx, NY
SESSION INFORMATION
Background/Purpose:
The importance of macrophages in the pathogenesis of cutaneous and neuropsychiatric systemic lupus erythematosus (SLE) is well
established. Additionally, autoantibodies produced by autoreactive B cells are implicated in both the skin and brain disease associated with
lupus. Bruton's tyrosine kinase (BTK) plays an important role in several key macrophage and B cell functions; therefore, we used a novel
BTK inhibitor, BI-BTK-1, to target both macrophage and B cell dependent disease pathways in the MRL/lpr murine model of SLE.
Methods:
Starting at 8-9 weeks of age, female MRL/MpJ-Faslpr/J (MRL/lpr) mice were treated with BI-BTK-1, a highly selective BTK inhibitor, via
medicated or control chow (Control mice, n=8; BI-BTK-1 treated, n=12). We quantified the development of skin lesions, and additionally
assessed neuropsychiatric disease manifestations via comprehensive behavioral testing and immunohistochemical analysis of brain tissue.
Results:
Treatment with BI-BTK-1 significantly attenuated the skin inflammation and cognitive deficits associated with disease in the MRL/lpr strain.
Specifically, BI-BTK-1 treated mice had less macroscopic (Fig. 1) and microscopic skin lesions, and reduced cutaneous cellular infiltration.
Furthermore, skin from treated mice had significantly diminished inflammatory cytokine expression, including reduced protein levels of TNF,
IL-6, IL-17, MCP-1, and GM-CSF. BTK inhibition also significantly improved memory function (p<0.05), and dramatically decreased
accumulation of T cells, B cells, and macrophages within the brain, specifically in the choroid plexus (Fig. 2).
Conclusion:
Targeted therapies may improve the response rate in lupus driven target organ involvement, and decrease the dangerous side effects
associated with more global immunosuppression. Overall, our results suggest that inhibition of BTK with BI-BTK-1 may be a promising
therapeutic option for cutaneous and neuropsychiatric disease associated with SLE.
FIGURE 1:
FIGURE 2:
Disclosure: S. Chalmers, None; J. Wen, None; J. Doerner, None; A. Stock, None; C. Cuda, None; H. Makinde, None; H. Perlman, None;
T. Bosanac, Boehringer Ingelheim, 3; D. Webb, Boehringer Ingelheim, 3; G. Nabozny, Boehringer Ingelheim, 3; E. Klein, Boehringer
Ingelheim, 3; J. S. Fine, Boehringer Ingelheim, 3; M. Ramanujam, Boehringer Ingelheim, 3; C. Putterman, Boehringer Ingelheim, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/btk-inhibition-ameliorates-lupus-associated-

neuropsychiatric-and-skin-disease
Abstract Number: 30
Specificity of Salivary Gland-Derived Monoclonal Antibodies from Sjogren’s Syndrome

Patients Using Human Proteome Arrays
Sherri Longobardi1, Christina Lawrence2, Kristi A. Koelsch3, Kenneth Smith2, Constantin Georgescu2, Michelle L. Joachims2, Lida
Radfar4, Astrid Rasmussen2, Kathy L. Sivils2, Jonathan Wren2, R. Hal Scofield2 and A. Darise Farris2, 1Graduate Program in Biological
Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 2Arthritis and Clinical Immunology Program, Oklahoma
Medical Research Foundation, Oklahoma City, OK, 3Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation,
Okalahoma City, OK, 4Department of Oral Diagnosis and Radiology, University of Oklahoma College of Dentistry, Oklahoma City, OK
SESSION INFORMATION
Background/Purpose: Sjögren’s syndrome (SS) is a rheumatic autoimmune disease characterized by focal lymphocytic infiltrations in the
lacrimal and salivary glands, autoantibodies to the ubiquitous Ro and La nuclear antigens, severe dry mouth and eyes, arthritis, fatigue, pain
and debilitation. In this project we used human proteome arrays to identify potential non-Ro/non-La autoantigens targeted by salivary gland
plasmablasts from SS patients.
Methods: Recombinant human monoclonal antibodies (mAbs) derived from minor salivary gland plasmablasts of five individuals meeting
the 2016 ACR/EULAR classification criteria for primary Sjögren’s syndrome were tested for binding to human proteome microarrays
containing >15,500 GST- and 6xhis-tagged recombinant human proteins representing >75% of the human proteome spotted in duplicate
(HuProt 3.0 arrays, CDI Laboratories). Each of six arrays was probed with a mAb pool (5 to 10 mAbs/pool) derived from one or two
subjects. As controls, separate arrays were probed with secondary antibody alone (AlexaFluor 647 Affinipure F(ab’)2 Goat Anti-Human IgG
(H+L)) and pools of mAbs specific for rabies, anthrax, and S. pneumoniae vaccines. The foreground to background ratio (F/B) was
calculated for each array spot then transformed to fit a normal distribution for analyses. Significant binding was defined as normalized F/B
ratios ≥ 2.0 SD above the mean value across all arrays and lack of binding by secondary antibody alone. Literature connectivity
(IRIDESCENT), interactome and pathways (Ingenuity) bioinformatics analyses were conducted to investigate relationships among the bound
antigens.
Results: A total of 201 proteins were found to be significantly bound by salivary gland mAbs, including Ro60, La, and Ro52 antigens. These
were bound by patient mAbs but not by irrelevant mAbs or secondary antibody alone. Furthermore, of 199 novel non-Ro/non-La antigens
identified, 16 were shared between 2 or more subjects on at least 2 arrays. Bioinformatics analyses revealed literature connectivity to the
terms “salivary gland” or “Sjögren’s syndrome” among many of the bound antigens. The interactome showed multiple connections between
several of the novel antigens; however, the most significant pathway among the shared antigen interactome was the proteasome/ubiquitination
pathway.
Conclusion: Sixteen novel, non-Ro/La antigens shared between two or more patients were identified as possible targets of autoantibodies in
SS. Pathway analysis of the shared interactome supports immune targeting of the proteasome/ubiquitination pathway by SG plasmablasts in
SS.
Funding: National Institutes of Health (1P50 AR060804) and Oklahoma Center for the Advancement of Science and Technology (HR 16-055-
01)
Disclosure: S. Longobardi, None; C. Lawrence, None; K. A. Koelsch, None; K. Smith, None; C. Georgescu, None; M. L. Joachims,
None; L. Radfar, None; A. Rasmussen, None; K. L. Sivils, None; J. Wren, None; R. H. Scofield, None; A. D. Farris, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/specificity-of-salivary-gland-derived-monoclonal-

antibodies-from-sjogrens-syndrome-patients-using-human-proteome-arrays
Abstract Number: 31
Single Cell Analysis Revealed That the Response to Cyclophosphamide Therapy Is

Regulated By B Cells in Systemic Sclerosis-Associated Interstitial Lung Disease
Satoshi Ebata1, Ayumi Yoshizaki2, Takemichi Fukasawa1, Kouki Nakamura1, Maiko Hirakawa1, Takashi Yamashita1, Shunsuke Miura3,
Ryosuke Saigusa1, Megumi Hirabayashi1, Asako Yoshizaki1, Kaname Akamata1, Yoshihide Asano4, Yutaka Kazoe5, Kazuma Mawatari5,
Takehiko Kitamori5 and Shinichi Sato6, 1Dermatology, University of Tokyo, Graduate School of Medicine, Tokyo, Japan, 2Department of
Dermatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan, 3University of Tokyo, Graduate School of Medicine,
Tokyo, Japan, 4Applied Chemistry, University of Tokyo, Graduate School of Medicine, Tokyo, Japan, 5Applied Chemistry, University of
Tokyo, Graduate School of Engineering, Tokyo, Japan, 6Department of Dermatology, Graduate School of Medicine, The University of Tokyo,
Bunkyo-ku, Japan
SESSION INFORMATION
Background/Purpose: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of several organs. SSc-associated
interstitial lung disease (ILD) is a frequent and severe complication of SSc. SSc-ILD declines the quality of patients' lives and sometimes
determines their prognosis. Despite the severeness of SSc-ILD, the treatment for SSc-ILD is still debated. The cyclophosphamide (CYC)
treatment is the only therapy found to be effective in stabilizing or improving lung function of SSc-ILD in randomized clinical trials, which
contained abundant numbers of patients. However, not every SSc-ILD patients treated with CYC recover. We need to know the difference
between the responders and the non-responders against CYC. Recent studies indicate that B cells play a critical role in SSc through their
function of cytokine production. Indeed, some studies have reported that the B cell depletion therapy with rituximab can be effective for SSc-
ILD. However, the relationship between response to CYC therapy and B cell function remains unknown in SSc-ILD. We hypothesized that
cytokine-producing effector B cells determine the effectiveness of the CYC treatment in SSc-ILD patients. In this study, we assessed the role
of interleukin (IL)-10-producing regulatory B cells and IL-6-producing pathogenic B cells in the responders or non-responders of the CYC
treatment.
Methods: We cultured human lung endothelial cells (LECs) in a microchannel. Sequentially, B cells from responders or non-responders
against the CYC treatment were loaded into the microchannel. After each of B cells which adhered to LECs had produced cytokines, we
measured IL-6 and IL-10 production from single B cells by our original micro fluidic-ELISA system. Similarly, we assessed B cells from
topoisomerase (topo) I and complete Freund’s adjuvant-induced SSc model mice.
Results: In SSc-ILD patients, the number of B cells adhering to LECs significantly increased relative to healthy controls. B cells adhering to
LECs from CYC-responders produced significantly higher amounts of IL-10 and lower amounts of IL-6 than those from CYC-non-responders.
After the CYC treatment, the frequency of B cells which adhered to LECs significantly decreased in responders but did not decrease in non-
responders. Regarding the cytokine profile of B cells adhering to LECs, the frequencies of IL-10 producing regulatory B cells after the CYC
treatment increased in responders and decreased in non-responders. Those of IL-6-producing pathogenic B cells after the CYC treatment
decreased in responders and increased in non-responders. In the mouse study, the number of topo I-specific B cells which adhere to LECs
significantly increased compared to non-specific conventional B cells. Topo I-specific B cells also showed significantly higher production of
IL-6 and lower production of IL-10 than conventional B cells.
Conclusion: These results suggested that the effectiveness of CYC to SSc-ILD patients is associated with the cytokine profile of B cells
which interact with LECs. It is likely that IL-6-producing pathogenic B cells which survived the CYC treatment damage the lung function of
non-responders.
Disclosure: S. Ebata, None; A. Yoshizaki, None; T. Fukasawa, None; K. Nakamura, None; M. Hirakawa, None; T. Yamashita, None; S.
Miura, None; R. Saigusa, None; M. Hirabayashi, None; A. Yoshizaki, None; K. Akamata, None; Y. Asano, None; Y. Kazoe, None; K.
Mawatari, None; T. Kitamori, None; S. Sato, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/single-cell-analysis-revealed-that-the-response-to-

cyclophosphamide-therapy-is-regulated-by-b-cells-in-systemic-sclerosis-associated-interstitial-lung-disease
Abstract Number: 32
Longitudinal Associations between Rheumatoid Factor and Ex Vivo Cytokine

Production Reveal Novel Mechanistic Insights into Rheumatoid Arthritis
John M. Davis III1, Cynthia S. Crowson2, Keith L. Knutson3, Sara J. Achenbach4, Terry M. Therneau5, Eric L. Matteson6, Sherine E.
Gabriel7 and Peter J. Wettstein8, 1Division of Rheumatology, Mayo Clinic, Rochester, MN, 2Health Sciences Research, Mayo Clinic
College of Medicine and Science, Rochester, MN, 3Immunology, Mayo Clinic, Jacksonville, FL, 4Mayo Clinic, Rochester, MN,
5Biostatistics, Mayo Clinic, Rochester, MN, 6Rheumatology, Mayo Clinic College of Medicine and Science, Rochester, MN, 7Rutgers
Robert Wood Johnson Medical School, New Brunswick, NJ, 8Immunology, Mayo Clinic, Rochester, MN
SESSION INFORMATION
Background/Purpose:
Positive rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA) identify a major rheumatoid arthritis (RA) subgroup,
characterized by greater propensity to erosive joint damage and extra-articular disease manifestations as compared to seronegative patients.
The purpose was to determine the associations between RF/ACPA and changes in functional immune response signatures over 5 years in
patients with RA.
Methods:
A longitudinal analysis was performed of baseline and 5-year follow-up data from a prospective study of adult RA patients in a population-
based incidence cohort. Data were available for 324 patients at baseline and for 155 patients at 5 years. Peripheral blood leukocytes (PBL)
were freshly collected from patients and isolated by Ficoll density gradient centrifugation at both time-points. PBLs were stimulated at 37°C
for 48 hrs under six separate conditions: anti-CD3/anti-CD28 monoclonal antibodies (CD3/CD28); phytohemagglutinin (PHA),
staphylococcal enterotoxins A and B (SEA/SEB); phorbol myristate acetate and ionomycin (PMA); CpG oligonucleotides (CpG ODN2006);
and medium alone. A panel of 17 cytokines and chemokines was analyzed using multiplexed immunoassays (Meso Scale Discovery). RF was
measured using the nephelometry (CSL Behring), and ACPA was measured by Quanta Lite CCP3 IgG (Inova Diagnostics). Factor analysis of
normalized data was performed using baseline data on 324 patients to make inferences about underlying cell types based on cytokine profiles.
Among the 155 patients with follow-up, Spearman methods were used to assess correlations between RF and/or ACPA seropositivity and
longitudinal changes in the factor scores for each stimulus, adjusting for age and sex.
Results:
A total of 109 (70%) of the 155 patients were seropositive at baseline (median age: 57.7 yrs; median disease duration: 9.7 yrs). RF/ACPA
positively associated with CpG factor 1 (r = 0.28, p <.001), factor 2 (r = 0.21, p =.011), and factor 3 (r = 0.20, p =.015). Based on loadings
>0.5, CpG factor 1 comprised IL-1β, G-CSF, TNF-α, MIP-1β, and IL-6; factor 2 comprised IFNγ, IL-2, and IL-13; and factor 3 comprised
IL-12, and IL-5. Previous studies have shown that the type of CpG used in this study mainly activates B cells. Responses to medium alone
paralleled those to CpG, as RF/ACPA positively correlated with medium alone factor 1 (r = 0.27, p <.001) and factor 3 (r = 0.29, p <.001)
responses. Medium alone factor 1 comprised GM-CSF, MCP-1, IL-17A, IL-6, MIP-1β, TNF-α, and G-CSF; factor 3 comprised IL-1β and
TNF-α. Based on this profile, multiple Toll-like receptor (TLR) ligands present in the medium fetal calf serum could have stimulated
monocytes or other antigen presenting cells. In contrast, RF/ACPA negatively correlated with CD3/CD28-induced IL-5 (r = -0.21, p =.008),
IL-17A (r = -0.22, p =.005), and GM-CSF (r = -0.20, p =.013).
Conclusion:
Our findings suggest that sustained stimulation of RF-containing immune complexes increases monocyte and B-cell activation states with
increased expression of TLR. This could inform the development of functional assays for CpG and other TLR immune responses as
predictors of response to B-cell directed therapy in RA.
Disclosure: J. M. Davis III, None; C. S. Crowson, None; K. L. Knutson, None; S. J. Achenbach, None; T. M. Therneau, None; E. L.
Matteson, None; S. E. Gabriel, None; P. J. Wettstein, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/longitudinal-associations-between-rheumatoid-factor-

and-ex-vivo-cytokine-production-reveal-novel-mechanistic-insights-into-rheumatoid-arthritis
Abstract Number: 33
B Cell Abnormalities in Patients with Chronic Cutaneous Lupus Erythematosus

Chungwen Wei1, Aisha Hill2, Kira Smith3, Ignacio Sanz1, S. Sam Lim4 and Cristina Drenkard4, 1Medicine, Emory University School of
Medicine, Atlanta, GA, 2Medicine, Emory University School of Medicine, atlanta, GA, 3Emory University School of Medicine, Atlanta, GA,
4Division of Rheumatology, Emory University School of Medicine, Atlanta, GA
SESSION INFORMATION
Background/Purpose: Lupus is a spectrum of disease with cutaneous lupus (CLE) without systemic features on one end and systemic lupus
erythematosus (SLE) on the other. Among CLE subtypes, chronic cutaneous lupus (CCLE) is deemed less likely to be associated with
systemic features. However, 10-20% CCLE will develop SLE throughout their disease course. Little is known regarding the immunological
correlates to the disease progression, which we postulate may be accompanied by the emergence of SLE-associated B cell abnormalities. As
an initial test for our hypothesis, we compared the B cell phenotypes in a cross-sectional analysis among patients with CCLE, SLE with or
without CCLE.
Methods: Patients met SLICC and ACR criteria for the classification of CCLE and SLE. Frozen PBMCs were analyzed by flow cytometry
from healthy controls (HC) (n=23) and patients with primary CCLE (n=60), SLE (n=58) or CCLE with SLE (n=42). B cell subsets were
identified using the following markers: CD19, IgD, CD27, CD38, CD24, CD21, CD11c, 9G4, in addition to CD3 and live/dead staining as
exclusion markers. Frequencies of the various B cell subsets were compared among the groups using ANOVA followed by Tukey’s multiple
comparison statistical tests. To gain a global view of the changes in B cell homeostasis, an unsupervised hierarchical clustering analysis of
the B cell profiles was carried out.
Results: Several B cell abnormalities have been shown in SLE patients compared to the healthy controls, including a contraction of
IgD+CD27+ unswitched memory (USM) and an expansion of IgD-CD27- double negative (DN) cells. These observations are replicated in
this study as well. Furthermore, within the DN population, a subset of cells with an activated phenotype (CD11c+CD21-, termed DN2) is
significantly expanded in SLE compared to HC. Its counterpart in the IgD+CD27- naïve and transitional (N+T) compartment – the
CD11c+CD21- activated naïve (aN) B cells – is also expanded in SLE, though not statistically different from HC. Interestingly, CCLE
patients share with SLE the characteristic contraction of USM also seen in Sjogren’s and other autoimmune diseases, yet they do not exhibit
the expansion of DN, activated DN2 and aN subsets. Instead, CCLE patients show an expansion of the early transitional (T1+T2) cells.
Globally, an unsupervised hierarchical clustering analysis demonstrates the segregation of HC from SLE (with or without CCLE) on the basis
of their B cell profiles. On the other hand, B cell profiles of CCLE patients are heterogeneous and interspersed between HC and SLE
patients.
Conclusion: Cross-sectional analysis at baseline reveals that CCLE patients share some SLE abnormalities including contracted USM and
expansion of early transitional B cells, but do not display expansions of activated mature B cells (both naïve and isotype switched DN cells),
a phenotype that is frequently observed in SLE patients. Moreover, our study demonstrates that from a B cell standpoint, CCLE is a
heterogeneous condition thereby opening the door to investigations of correlations between distinct B cell profiles and clinical variables and
in particular, with progression to systemic disease. Confirmation awaits the longitudinal follow-up of these patients over the next years.
Disclosure: C. Wei, None; A. Hill, None; K. Smith, None; I. Sanz, None; S. S. Lim, None; C. Drenkard, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/b-cell-abnormalities-in-patients-with-chronic-cutaneous-

lupus-erythematosus
Abstract Number: 34
IL-23 Regulates Development of Spontaneous Germinal Centers and Pathogenic

Autoantibody Production in BXD2 Mice
Huixian Hong1, Qi Wu2, PingAr Yang2, Bao Luo3, Jun Li4, Hao Li5, Daniel Cua6, Hui-Chen Hsu2 and John D. Mountz2,7, 1University of
Alabama at Birmingham， Division of Clinical Immunology and Rheumatology, Department of Medicine, Birmingham, AL, 2Division of
Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham， Division of Clinical Immunology
and Rheumatology, Department of Medicine, Birmingham, AL, 3DIvision of Clinical Immunology and Rheumatology, Department of
Medicine, University of Alabama at Birmingham， Division of Clinical Immunology and Rheumatology, Department of Medicine,
Birmingham, AL, 4Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham， Division of Clinical
Immunology and Rheumatology, Department of Medicine, Birmingham, AL, 5Division of Rheumatology, Department of Medicine, Beth Israel
Deaconess Medical Center, Harvard Medical School, Boston, MA, 6Discovery Research, Merck Research Laboratory, Palo Alto, CA,
7University of Alabama at Birmingham and Birmingham VA Medical center, Birmingham, AL
SESSION INFORMATION
Background/Purpose: Targeting IL-23 to treat autoimmune disease and chronic inflammation is currently in development based on its pro-
inflammatory function via regulating the activation of Th17 cells. IL-23 was previously shown to be important for promoting pathogenic
autoantibody production in Fas deficient B6-Faslpr/lpr mice, suggesting the positive role of IL-23 in mediating Fas-independent germinal
center (GC) responses. In contrast, the lack of IL-23 did not influence conventional GC formation and IgG anti-CII autoantibodies in type II
collagen immunized DBA/1 mice. We determined if IL-23 could regulate development of GCs and pathogenic autoantibody production in
BXD2 mice.
Methods: The BXD2-IL-23 p19–⁄– mice were generated by 10 generation crossing the B6-p19–⁄– with the BXD2 mice. Serum autoantibodies
were determined by ELISA. GC development was measured by FACS (GL-7 and Fas) and confocal imaging analyses. Autoantibody class
switching was enumerated by the percentage of (IgM–IgD–) in GL-7+ B cells. Immune complex deposition (IgM and IgG) in kidney was
detected by confocal imaging.
Results: There was lower induction of Il17a in subpopulations of spleen cells from BXD2-p19–⁄– mice compared to WT BXD2 mice.
However, unlike BXD2-Il17ra–⁄– mice, which developed lower levels of both IgM and IgG autoantibodies, BXD2-p19–⁄– mice exhibited
significantly elevated titer of total IgM and IgM anti-DNA and RF autoantibodies but significantly lower levels of total IgG and IgG anti-
histone, compared to WT BXD2 mice. Despite the lower circulating IgG autoantibodies, IgG staining was significantly increased in the
glomerulus of BXD2-p19–⁄– mice compared to BXD2 and normal B6 mice with both an immune complex and linear staining pattern. The
number and size of PNA+ GCs and the percent of GL-7+Fas+ GC B cells were increased in BXD2-p19–⁄– mice comparable to WT BXD2
mice. Abnormal GC development kinetics was confirmed by increased conventional isotype switched IgM–IgD– GL7+Fas+ B cells in
BXD2-p19–⁄– mice compared to BXD2 WT mice.
Conclusion: The present findings provide a potential link to consolidate previous findings on the importance of IL-23 in mediating IgG
autoantibody development in B6-Faslpr/lpr mice and the lack of effects in development of IgG anti-CII antibody in CII immunized IL-23
deficient mice. These results extend the paradigm of IL-23 disease beyond the classical IL23-Th17 axis and suggest IL-23 exhibits a negative
effect on development of classical GC B cells that produce highly pathogenic autoAbs.
effect on development of classical GC B cells that produce highly pathogenic autoAbs.
Disclosure: H. Hong, None; Q. Wu, None; P. Yang, None; B. Luo, None; J. Li, None; H. Li, None; D. Cua, Merck Pharmaceuticals, 3; H.
C. Hsu, NIH, 2; J. D. Mountz, NIH, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/il-23-regulates-development-of-spontaneous-germinal-

centers-and-pathogenic-autoantibody-production-in-bxd2-mice
Abstract Number: 35
B-Cell Subset Differences in Inflammatory Rheumatic Diseases

Joao Lagoas Gomes1,2, Dario Ligeiro3, Alice Lima3, Cristina Teixeira3, Alexandre Sepriano4,5, Sofia Ramiro6, Carina Lopes7, Tiago
Costa8, Manuela Costa8, Jaime Cunha Branco1,2 and Fernando Pimentel-Santos1,2, 1Rheumatology, Hospital Egas Moniz, Centro Hospitalar
de Lisboa Ocidental, Lisbon, Portugal, 2CEDOC, NOVA Medical School, Lisbon, Portugal, 3Centro de Sangue e Transplantação de Lisboa,
Instituto Português do Sangue e Transplantação (IPST), I.P, Lisbon, Portugal, 4CEDOC, NOVA Medical School, Lisboa, Portugal,
5Rheumatology, Leiden University Medical Center, Leiden, Netherlands, 6Rheumatology, Department of Rheumatology, LUMC, Leiden,
Netherlands, Leiden, Netherlands, 7Hospital de Egas Moniz-CHLO, Lisbon, Portugal, 8Rheumatology, Hospital de Egas Moniz, Centro
Hospitalar de Lisboa Ocidental, Lisbon, Portugal
SESSION INFORMATION
Background/Purpose: Targeting humoral immunity has been proved effective in several inflammatory rheumatic diseases (IRD). Though
clinical trials have shown some efficacy of B-cell depletion in ankylosing spondylitis (AS), results are less convincing. Other studies have
revealed an association between mutations and expression of immune regulatory genes suggesting a B-cell dysfunction in the development
and progression of AS. Yet, there is still lack of data describing B-cell subsets in AS. The study purpose is to assess and compare the
immature, naive and antigen differentiated subsets of peripheral B-cell compartment in AS with those in healthy controls (HC) and other IRD
Methods: Patients with AS, RA and SLE according to respective classification criteria were included. Patients under biologic DMARDS
were not included. Sociodemographic and clinical variables were recorded and blood samples were collected for quantification of
inflammatory markers, immunoglobulin levels and assessment of B-cell immature transitional stages and mature subsets by flow cytometry.
Mann-Whitney and Fisher´s exact test were used for statistical analysis
Results: Overall, 60 patients and 12 HC were included. All patient groups presented similar and rather low levels of inflammation, as
measured by CRP, ESR and immunoglobulins, in addition to a decreased lymphocyte count. There were no differences in the B-cell counts
between AS patients and HC, and both groups had higher B-cell counts than RA and SLE patients. Regarding B-cell subsets, the immature
transitional compartment of AS patients was found in normal range, but not in RA and SLE. The latter presented a significant decrease in all
transitional cell maturity stages (T1-T3). The next step in B-cell differentiation is mature naïve cells, also found to be normal in AS and
decreased in RA and SLE. AS patients presented slightly higher counts of CD27+IgD+ MZ-like and class able to switch memory cells with
reference to HC and these cell numbers were found to be low in RA and SLE patients. Switched memory CD27+IgD- B-cells were reduced
in all patient groups, however, only SLE patients presented highly decreased cell levels
Conclusion: We found that while a severe dysfunction is present in the homeostasis of the B-cell compartment in RA and in particular SLE
pts, which are lymphopenic in both immature and mature B-cell compartments, it appears that AS patients are not affected in the same way.
At this stage, functional studies appear to be necessary in order to identify differences in key mechanisms of B cell development and
differentiation that play a role in the aetiology and progression of these inflammatory rheumatic diseases. Our first results, however, establish
that pathophysiological mechanisms involving B-cells clearly differentiate AS from RA and SLE
AS RA SLE HC
(n=22) (n=20) (n=18) (n=12)

Male, Female; n (%) 11 (50); 11 9 (45); 11 5 (27.8); 3 (25); 9
(50) (55) 13 (72.2) (75)
Age; median (IQR) 56 (45.8- 55 (51- 44 (37.5- 56 (35.3-
65.5) 65.5) 52.5)* 63.3)
ESR mm/hour 14 (10- 21 (10.3- 23 (6-34.5) 11 (8-
29.3) 37.8) 22.5)
CRP mg/dL 1.1 (0.9- 0.98 (0.7- 0.6 (0.5- -
1.7) 3.2) 1.6)
HLA B27+: n (%) 11 (68.8) - - -
With csDMARS, n (%) 6 (30) 18 (90) 15 (83.3) 0
Ig seric levels, mg/dl; median (IQR)
IgG 1165 1021 1140 1033.5
(881.3- (830.3- (1003-1325 (823.3-
1247.5) 1265) 1235)
IgA 230 250.5 261 (205- 236.5
(158.8- (164.3- 323) (150.3-
340) 315.3) 339.8)
IgM 95.3 (65.6- 112 (67.7- 103 (60.6- 122
119.5) 164.8) 131.5 (71.5-
158.3)
Absolute cell counts/μl blood; median (IQR)
Lymphocytes 1685 1555 1250 (625- 2170
(1217- (1097.5- 1892.5) (1830-
2007.5) 2085) 2377)**
Total B-cells (CD20+) 186.3(111- 96.2 65.8 (20.9- 182.1
238.6) (50.3- 116.1)*** (100.9-
180.6)*** 269.7)
Immature Transitional B-cells (CD5+CD27-IgD+), median (IQR)
CD24+++CD38+++(T1) 2.8 (1.8- 0.6 (0.1- 1.5 (0.2- 4.3 (2.3-
3.9) 2.7)** 2.8)** 6.5)
++
CD24 CD38 (T2) ++ 8.3 (5.1- 2.6 (0.2- 3.0 (1.0- 13.7
14.9) 8.0)** 8.0)** (5.7-
18.8)
CD24+CD38+(T3) 9.0 (5.5- 2.2 (0.3- 1.9 (0.2- 7.7 (4.1-
17.7) 4.6)** 3.7)** 12.3)
Mature B-Cells, median (IQR)
CD27-IgD+ (naïve) 73.2 (49.7- 40.1(19.2- 27.2(11.9- 78.6
121.7) 76.9)** 57.1) † (48.4-
163.4)
CD27+IgD+(mem. MZ- 25.9 (13.6- 13.0 (3.5- 2.6 (1.8- 18.9
like) 39.9) 27.2)** 9.6) † (11.2-
27.1)
+ -
CD27 IgD (switch 18.8 (12.2- 13.5 (3.9- 4.9 (2.2- 29.3
mem.) 37.9) 37.6) 17.2)*** (14.51-
37.9)
CD27-IgD-(double 2.4 (1.8- 3.1 (2.0- 2.9 (1.0- 5.2 (2.6-
neg.) 5.2) 6.4) 5.0) 8.1)
Mann-Whitney and the Fisher´s exact test were used for comparison between AS and other groups
* p<0.05; **p<0.02; ***p<0.01; †p<0.0001;
Disclosure: J. Lagoas Gomes, None; D. Ligeiro, None; A. Lima, None; C. Teixeira, None; A. Sepriano, None; S. Ramiro, None; C.
Lopes, None; T. Costa, None; M. Costa, None; J. C. Branco, None; F. Pimentel-Santos, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/b-cell-subset-differences-in-inflammatory-rheumatic-

diseases
Abstract Number: 36
GM-CSF-Producing B Cells: A Novel B Cell Subset Involved in the Pathogenesis of

Systemic Sclerosis
Kazuhiko Higashioka1, Yuri Ota1, Tsuyoshi Nakayama1, Koji Mishima1, Masahiro Ayano1, Yasutaka Kimoto2, Hiroki Mitoma1, Mitsuteru
Akahoshi1, Yojiro Arinobu1, Koichi Akashi1, Takahiko Horiuchi3 and Hiroaki Niro4, 1Department of Medicine and Biosystemic Science,
Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, 2Department of Internal Medicine, Kyushu University Beppu
Hospital, Oita, Japan, 3Department of Internal Medicine, Kyushu University Beppu Hospital, Beppu, Japan, 4Department of Medical
Education, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
SESSION INFORMATION
Background/Purpose: Systemic sclerosis (SSc) is a T helper type 2 (Th2)-driven autoimmune disease characterized by vasculopathy and
fibrosis. There are still unmet needs in the management of SSc, however B-cell depletion therapy has recently been reported to be effective
for this disease. Intriguingly here there is no significant correlation between autoantibody titers and the improvement of clinical symptoms,
thus highlighting a novel antibody-independent function of B cells, particularly cytokine production, involved in the pathogenesis of
SSc.Granulocyte-macrophage colony-stimulating factor (GM-CSF) exerts a wide range of biological effects mainly on myeloid cells, and B
cells has recently been reported as another cellular source of GM-CSF that is induced by a Th2 cytokine IL-4. Given a pathological
relevance of Th2 cytokines in SSc and association of GM-CSF with fibrotic processes in various rodent models, in the present study we have
sought to elucidate a role of GM-CSF-producing B cells in this disease.
Methods: B cell subsets in peripheral blood from healthy donors and patients with SSc were enriched by cell sorting and subjected to the
analysis of GM-CSF transcripts and proteins (intracellular staining and ELISA). The relationship between GM-CSF-producing B cells and
the clinical features of SSc was also evaluated. To determine the functional impacts of GM-CSF-producing B cells on myeloid cells, B cells
cultured under Th2 conditions were co-cultured with CD14+ monocytes.
Results: Among a panel of CD4+ T cell-derived cytokines, Th2 cytokine IL-4 most significantly induced the generation of GM-CSF-
producing memory B cells, while T follicular helper (Tfh) cytokine IL-21 remarkably abrogated this process. Intriguingly TGF-b further
potentiated IL-4-induced GM-CSF production in memory B cells. GM-CSF-producing effector B cells were positive for CD30, a distinct
phenotype from Ab-producing cells induced by IL-21. GM-CSF production in B cells from patients with SSc was more pronounced than that
from healthy donors. This trend was also observed in both naïve and memory B cell subsets. A subpopulation of SSc patients with the diffuse
type and concomitant IP, in particular, represented enhanced GM-CSF production in memory B cells. Moreover, B cells cultured under Th2
conditions along with TGF-b facilitated the differentiation from CD14+ monocytes to DC-SIGN+CD1a+CD14-CD86+ cells, a novel DC
subset previously reported in skin of SSc patients and SSc model mice.
Conclusion: Together, these findings suggest that GM-CSF-producing effector B cells is a novel B cell subset and play a critical role in the
pathogenesis of SSc by Ab-independent mechanisms.
Disclosure: K. Higashioka, None; Y. Ota, None; T. Nakayama, None; K. Mishima, None; M. Ayano, None; Y. Kimoto, None; H. Mitoma,
None; M. Akahoshi, None; Y. Arinobu, None; K. Akashi, None; T. Horiuchi, None; H. Niro, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/gm-csf-producing-b-cells-a-novel-b-cell-subset-

involved-in-the-pathogenesis-of-systemic-sclerosis
Abstract Number: 37
β2-Glycoprotein I Binds to Necroptotic Cells and Serves As a Target for SLE

Autoantibodies
David Salem1, Rebecca Subang1, Maziar Divangahi1, Christian Pineau2, Sasha Bernatsky3, Jerrold S. Levine4 and Joyce Rauch5,
1Research Institute of the McGill University Health Centre, Montreal, QC, Canada, 2Division of Rheumatology, McGill University Health
Centre, Montreal, QC, Canada, 3Divisions of Rheumatology and Clinical Epidemiology, McGill University Health Centre, Montreal, QC,
Canada, 4Section of Nephrology, Department of Medicine, University of Illinois at Chicago and Jesse Brown Veterans Affairs Medical
Center, Chicago, IL, 5Division of Rheumatology, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
SESSION INFORMATION
Background/Purpose: β2-glycoprotein I (β2GPI), a phospholipid-binding protein, binds to apoptotic cells and serves as an antigenic target
for autoantibodies from patients with systemic lupus erythematosus (SLE). Here, we determine whether this paradigm can be extended to
necroptotic cells. Like apoptotic cells, necroptotic cells express phosphatidylserine on their surface and provide a “scaffold” of cellular self-
antigens. We hypothesized that β2GPI should bind to necroptotic cells and serve as a target for anti-β2GPI autoantibodies from patients with
SLE.
Methods: We established conditions for inducing necroptotic or apoptotic cell death in murine L929 fibroblast cells. L929 cells treated with
vehicle served as the viable cell control. Cells were incubated with human β2GPI and murine monoclonal anti-β2GPI IgG antibody (or
isotype control), and bound antibody detected with fluorescently conjugated anti-murine IgG. Similarly, binding of anti-β2GPI autoantibodies
from human sera (or IgG isolated from these sera) was detected using fluorescently conjugated anti-human IgG. Human sera were from
healthy controls and patients who satisfied the ACR classification criteria for SLE. Antibody binding was analyzed by flow cytometry and
confocal microscopy.
Results: Using murine monoclonal anti-β2GPI antibody, we demonstrate that β2GPI binds to necroptotic cells in a similar manner as to
apoptotic cells, but not to viable cells. Cells treated with an irrelevant antigen (serum albumin) or isotype control showed little or no
antibody binding. Confocal microscopy confirmed monoclonal anti-β2GPI antibody staining of the cell surface of both necroptotic and
apoptotic cells. SLE sera positive for anti-β2GPI autoantibodies bound to necroptotic cells and apoptotic cells. In contrast, sera negative for
anti-β2GPI autoantibodies behaved similarly to healthy control sera, and showed little or no binding to necroptotic or apoptotic cells.
Binding of purified IgG from the sera replicated the findings observed with sera.
Conclusion: Our data demonstrate that β2GPI binds to necroptotic cells and can serve as a target for SLE autoantibodies recognizing β2GPI.
Based on these findings, we propose that the paradigm of apoptotic cells serving as a “cellular scaffold” of self-antigens in SLE may be
extended to necroptotic cells.
Disclosure: D. Salem, None; R. Subang, None; M. Divangahi, None; C. Pineau, None; S. Bernatsky, None; J. S. Levine, None; J. Rauch,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/%ce%b22-glycoprotein-i-binds-to-necroptotic-cells-and-

serves-as-a-target-for-sle-autoantibodies
Abstract Number: 38
Cytokine Production By CpG-Activated B Cells Require Glutaminolysis to Drive mTOR

Activation, Aerobic Glycolysis and Mitochondrial Respiration
Matthew Cheung1, Dongyue Huang1, Emily Liu2, Jennifer Ra2 and Alfred Kim3, 1Rheumatology, Washington University School of Medicine,
Saint Louis, MO, 2IM/Rheumatology, Washington University School of Medicine, Saint Louis, MO, 3IM/Rheumatology, Washington
University School of Medicine, St. Louis, MO
SESSION INFORMATION
Background/Purpose: B cells contribute to disease pathophysiology through several mechanisms, including cytokine secretion. A wide
variety of stimuli can activate B cells to produce cytokines including B cell receptor and Toll-like receptor engagement. Recently, numerous
observations have established the role of metabolic pathways in the diverse array of immune cell functions. It is unknown though how these
metabolic pathways influence B cell cytokine production. We sought to elucidate the metabolic programs required for B cell cytokine
production
Methods: B cells were isolated from the spleens of C57Bl/6J mice and activated overnight individually by anti-μ antibody, anti-CD40
agonist antibody, poly(I:C), LPS, R484, and CpG. Supernatants were analyzed for the quantification of cytokines using the Milliplex cytokine
kit (EMD Millipore). Real-time analysis of extracellular acidification rates and oxygen consumption rates of activated B cells were
performed using the XF-96 Extracellular Flux Analyzer (Seahorse Bioscience). To assess 3-carbon sources for oxidative phosphorylation,
inhibitors to fatty acid oxidation (etomoxir), pyruvate transfer to mitochondria (UK-5099), and glutamine usage (BPTES) were used. Amino
acids, organic acids, and acylcarnitines were extracted using methanol for targeted metabolomics studies using mass spectroscopy.
Results: CpG stimulation of mouse splenic B cells increased both glycolysis and mitochondrial respiration to a larger extent that by other
stimuli such as LPS or B cell receptor alone. These processes are highly dependent on glutamine, as inhibition of glutaminolysis with BPTES
significantly reduced both processes. Furthermore, glutaminolysis activated mTOR, which was required for glycolysis, mitochondrial
respiration, and ATP production in CpG-activated B cells. Quantitative targeted metabolomic studies confirmed CpG-stimulation drove
increases in intracellular amino acid levels, aerobic glycolysis and TCA cycle intermediates, all of which were reversed in the presence of
BPTES. Production of TNF-α, IL-6, and IL-10 by CpG-stimulated B cells also relied on glutaminolysis and mTOR activation. Interesting,
inhibition of glycolysis alone selectively decreased IL-10 production.
Conclusion: B cells undergo metabolic reprogramming when stimulated with CpG, requiring glutaminolysis and mTOR activation, which
drove aerobic glycolysis, TCA cycling, and ATP production. Cytokine production is intrinsically linked with this reprogramming, although
glycolysis was required for B cell IL-10 production suggesting the possibility that various B cell cytokines differentially rely on specific
metabolic pathways. These data are the among first to demonstrate a relationship between B cell effector function and metabolic
reprogramming, and suggest that B cell cytokine secretion can be manipulated by altering the local metabolic environment. Manipulating
metabolic pathways may represent an interesting therapeutic approach for modulating B cells in autoimmune diseases.
Disclosure: M. Cheung, None; D. Huang, None; E. Liu, None; J. Ra, None; A. Kim, Kypha, Inc., 2,Exagen Diagnostics, 5,NIH/NIAMS,
2,Department of Defense, 2,Rheumatology Research Foundation, 2,Doris Duke Foundation, 2,Midwest Strategic Pharma-Academic Research
Consortium, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/cytokine-production-by-cpg-activated-b-cells-require-

glutaminolysis-to-drive-mtor-activation-aerobic-glycolysis-and-mitochondrial-respiration
Abstract Number: 39
Protein Array Technology Identifies Rituximab-Treated Non-Responder Rheumatoid

Arthritis Patients to Generate New Autoantibody Repertoires during Treatment
Zoltán Konthur1, Melvin Michael Wiemkes2, Thomas Häupl2, Gerd R. Burmester2 and Karl Skriner2, 1Department of Biomolecular
Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany, 2Department of Rheumatology and Clinical Immunology,
Charité - University Medicine Berlin, Free University and Humboldt University Berlin, Berlin, Germany
SESSION INFORMATION
Background/Purpose: Rituximab (RTX) has shown clinical efficacy but up to 40 % of RTX treated rheumatoid arthritis (RA) patients are
poor responders (Ann-Rheum-Dis. 2005 Feb;64(2):246-52) and the commonly used RA biomarkers (RF/ACPA) are poor predictors for
therapy response. In this study the autoantibody repertoire analysed on protein macorarrays from RA patients under RTX treatment was
correlated to clinical DAS28 response.
Methods: Screening of RA sera was conducted on 37.830 unique human proteins on protein marcoarrays with sera taken before and 24
weeks after treatment. The autoantibody response of different immunoglobulin classes IgD, IgA, and IgG was recorded and bioinformatically
evaluated. Response was determined according to DAS28 criteria. DAS 28 scores in the responder group before treatment was from 5.4 –
7.8 and in the non-responder group 5,6 – 6,8. We analyzed 26 RA patient sera (9 responder, 7 non-responder and 10 patients with blinded
response classification) investigated the data of found autoantigens in silico and by hierarchical clustering.
Results: In the cohort of 26 patients 1292 different autoantigens (IgD,IgA,IgG) were detected. Using protein array we investigated clusters of
autoantigen responses that disappeared or developed during RTX treatment of RA patients. RA autoantigenic patterns
before and 6 month after RTX treatment were patient-specific and no relevant autoantigenic cluster was found that was shared between
patients or associated with response. However, RTX reduced the repertoire of autoantibodies after 24 weeks of treatment in the tested RA
patient cohort on average by 60%. RA patients which do not respond are generating on average 63% new autoantibodies. In good responders
to RTX only 5,5% (+/-3%) new autoantibodies can be detected. The IgA and IgG autoantibody
repertoire in the serum after 24 weeks of RTX treatment is reduced (IgA: 41%, IgG :31%) in good responders whereas it is increased (IgA:
1,3%, IgG: 24%) in non responders to RTX.
Conclusion: After 6 month of RTX treatment the autoantibody repertoire in all good responding RA patients is reduced and non-responders
to RTX change their autoantibody repertoire directed against new but patient specific antigens. The fast rebuilding of functional B cells is
only detected in non-responders to rituximab.
Disclosure: Z. Konthur, None; M. M. Wiemkes, None; T. Häupl, None; G. R. Burmester, None; K. Skriner, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/protein-array-technology-identifies-rituximab-treated-

non-responder-rheumatoid-arthritis-patients-to-generate-new-autoantibody-repertoires-during-treatment
Abstract Number: 40
B-Cell Attracting Chemokine-1 (BCA-1) and Macrophage Inflammatory Protein-3

Alpha (MIP-3α) Act Synergistically in the Recruitment of B Cells in the Rheumatoid
Synovium
Estefanía Armas-González 1, María Jesús Domínguez-Luis2, María Teresa Arce-Franco3, Javier Castro-Hernández3, Vanesa Hernandez4,
Sagrario Bustabad5, Alberto Cantabrana-Alutiz6 and Federico Díaz-González7, 1Universidad de La Laguna, Departamento de Medicina
Física y Farmacología, Facultad de Medicina, La Laguna, Tenerife, Spain, 2Laboratorio de Reumatología. Hospital Universitario de
Canarias, La Laguna, Spain, 3Laboratorio de Reumatología. Hospital Universitario de Canarias, La Laguna, Tenerife, Spain, 4Rheumatology,
Servicio de Reumatología. Hospital Universitario de Canarias, S/C Tenerife, Spain, 5Rheumatology, Servicio de Reumatología. Hospital
Universitario de Canarias, La Laguna, Tenerife, Spain, 6Servicio de Reumatología. Hospital Universitario Nuestra Señora de Candelaria, La
Laguna, Tenerife, Spain, 7Servicio de Reumatología. Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
SESSION INFORMATION
Background/Purpose: B cells are recognized as key players in the pathogenesis of rheumatoid arthritis (AR) through the production of
autoantibodies, the local production of proinflammatory soluble factors and, when acting as antigen-presenting cells, the regulation of T-cell
functions. Experimental evidence suggests that B cells should migrate to and accumulate within the synovial microenvironment to exert their
pathogenic action in RA. However, little is known about the driving force responsible for the recruitment of B cells in the rheumatoid
synovium. Chemokines and their receptors expressed in leucocytes help to control the selective migration and activation of inflammatory
cells in the inflamed synovium. Objective: to determine the chemokine or chemokines responsible for the recruitment of B cells in the
rheumatoid synovium.
Methods: Surface expression levels of CD27, CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CXCR2, CXCR4, CXCR5 and CXCR7
were assessed by double- or triple-staining flow cytometry analysis in CD20+ mononuclear cells isolated by Ficoll-gradient from the
peripheral blood (PB) and synovial fluid (SF) of 15 RA patients. In a sample of patients, the total expression (intra- and extracellular) of
specific chemokine receptors was analyzed by flow cytometry in CD20+ cells PB and SF permeabilized mononuclear cells from PB and SF.
Transwell experiments were used to study the synergism and migration capabilities of negatively immunoselected PB B-cells from normal
donors or in CD20+ mononuclear cells from PB and SF of RA patients in response to a single chemokine or a mix of two chemokines.
Results: B cells from the SF of RA patients showed a significant increase in the surface expression of CCR1 (2.1± 0.1-fold), CCR2 (2.4±0.2
fold), CCR4 (6±2 fold), CCR5 (2±0.1 fold) and CXCR4 (2.5±0.8-fold) with respect to PB. Remarkably, SF B cells expressed consistently
lower amounts of CXCR5 (0.15±0.05 fold, p<0.01), CXCR7 (0.7±0.1 fold, p<0.05) and CCR6 (0.75±0.1 fold, p<0.05) with respect to PB.
This differential pattern of chemokine receptor expression was not modified by the previous contact of B cells with antigen, as assessed by
CD27 expression levels. Flow cytometry results showed a relative increase in the expression of CXCR5 and CCR6 in permeabilized CD20+
cells from SF compared to those from PB, which suggests that both receptors undergo cell internalization in B cells that migrate to the
rheumatoid synovium. In Transwell experiments, MIP-3α and BCA-1, ligands of CCR6 and CXCR5, respectively, caused a significantly
higher migration on B cells from PB than in those from the SF of RA patients. Together, the two chemokines synergistically increased B cells
migration from PB but not from SF.
Conclusion: B cells present in the synovial microenvironment of patients with RA down-regulate the surface expression of CXCR5, CCR6
and CXCR7 via an internalization mechanism. Individually, BCA-1 and MIP-3α show higher chemoattractant effects in B cells from PB
versus those from SF, while together they exert a synergistic effect in B cells from PB, but not from SF. These results suggest that BCA-1 and
MIP-3a might play major roles in RA pathogenesis by acting synergistically in the accumulation of B lymphocytes within the inflamed
synovium.
Disclosure: E. Armas-González, None; M. J. Domínguez-Luis, None; M. T. Arce-Franco, None; J. Castro-Hernández, None; V.

Hernandez, None; S. Bustabad, None; A. Cantabrana-Alutiz, None; F. Díaz-González, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/b-cell-attracting-chemokine-1-bca-1-and-macrophage-

inflammatory-protein-3-alpha-mip-3%ce%b1-act-synergistically-in-the-recruitment-of-b-cells-in-the-rheumatoid-synovium
Abstract Number: 41
A Fine Bioinformatical Analysis of Lymphocyte Distribution Predicts the Diagnosis of

Systemic Autoimmune Diseases
Quentin Simon1, Bénédicte Rouvière1, Tifenn Martin1, Lucas Le Lann1, Alain Saraux1, Valérie Devauchelle-Pensec1, Concepcion
Marañón2, Nieves Varela Hernández2, Aleksandra Dufour3, Carlo Chizzolini4, Ellen de Langhe5, Nuria Barbarroja6, Chary Lopez-Pedrera7,
Velia Gerl8, Aurelie Degroof9, Julie Ducreux10, Elena Trombetta11, Tianlu Li12, Marta Alarcón-Riquelme13, Christophe Jamin1 and
Jacques-Olivier Pers1, 1U1227, Université de Brest, Inserm, Labex IGO, CHU de Brest, Brest, France, 2GENYO, Centre for Genomics and
Oncological Research Pfizer, University of Granada, Andalusian Regional Government, Granada, Spain, 3Immunology & Allergy, University
Hospital and School of Medicine, Geneva, Switzerland, 4University hospital of Geneva, Geneva, Switzerland, 5Rheumatology, University
Hospital KU Leuven, Leuven, Belgium, 6Rheumatology service, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Spain,
7IMIBIC/Reina Sofia Hospital/ University of Cordoba, Cordoba, Spain, 8Department of Rheumatology and Clinical Immunology, Charité
University Hospital, Berlin, Germany, 9Pôle de Maladies Rhumatismales, Institut de Recherche Expérimentale et Clinique, Université
catholique de Louvain, Brussels, Belgium, 10Pôle de pathologies rhumatismales inflammatoires et systémiques, Institut de Recherche
Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium, 11Laboratorio di Analisi Chimico Cliniche e Microbiologia
- Servizio di Citofluorimetria, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milano, Italy, 12Bellvitge
Biomedical Research Institute (IDIBELL), Barcelona, Spain, 13GENYO. Center for Genomics and Oncological Research, Granada, Spain
SESSION INFORMATION
Background/Purpose : We investigated 194 individuals with SADs (38 primary Sjögren’s syndrome (pSS), 47 rheumatoid arthritis (RA), 46
systemic lupus erythematosus (SLE), 42 systemic sclerosis (SSc) and 21 undifferentiated connective tissue disease (UCTD) patients) and 53
healthy controls (HCs) to determine whether a fine flow cytometry analysis of T and B cell distribution in whole blood could cluster
individuals according to disease diagnosis.
Methods: Two flow cytometry panels were designed. The first panel was dedicated to T cells and combined CD57, CD45RA, CD62L,
CD27, CD38, CD3, CD4 and CD8 mAbs. The second panel was dedicated to B cells and combined IgD, TACI, CD27, CD5, CD38, CD19
and CD24 mAbs. A classical manual gating strategy and the Flow-clustering without K (FLOCK) investigation, a density-based clustering
approach to algorithmically identify relevant cell populations from multiple samples in an unbiased fashion, were used.
Results: The manual gating strategy allows the identification of 17 distinct lymphocyte subsets. The prediction of the different SADs was
determined by discriminant function analysis (DFA). No clustering was found. The FLOCK exploration of the merged HCs identifies 85
distinct subsets of lymphocytes used as reference when compared to SADs . The DFA analysis clearly clusters the HCs and the patients
according to each SAD (see figure below).
When compared to HCs, the pSS signature was discriminated by an increase in IgDhiCD24hiCD38hiCD27-TACI-CD5hi transitional B cells,
and an increase of CD45RA+CD27-CD62Llo/-CD57hi effector CD8+ T cells.
The SLE signature was discriminated by an increase in IgD-CD24loCD38-CD27-TACI+CD5- memory like B cells, an increase in
CD45RA-CD62L+CD38hi activated central memory CD4+ T cells.
The RA signature was discriminated by an increase in IgDhiCD24loCD38-CD27-TACI+CD5- unactivated mature naïve B cells and a
decrease in CD45RA+CD62L+CD38hi naïve CD8+ T cells.
The SSc signature was discriminated by a decrease in CD45RA+CD62L+CD38hi naïve CD8+ T cells.
Interestingly, patients with UCTD were distributed among the different clusters (28% with HC, 29% with SLE, 29% with SSc, 9% with RA
and 5% with pSS clusters).
Conclusion: A fine bioinformatical flow cytometry analysis of T and B cell subsets clusterizes patients and HCs suggesting that each SAD
can be associated with abnormal specific phenotypical distributions that could be helpful in the diagnosis.
This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking PRECISESADS grant n°
115565.www.precisesads.eu
Disclosure: Q. Simon, EFPIA, 2; B. Rouvière, None; T. Martin, None; L. Le Lann, EFPIA, 2; A. Saraux, None; V. Devauchelle-Pensec,
Roche-Chugai provided me tocilizumab for the SEMAPHORER study, 2; C. Marañón, EFPIA, 2; N. Varela Hernández, EFPIA, 2; A.
Dufour, EFPIA, 2; C. Chizzolini, EFPIA, 2; E. de Langhe, None; N. Barbarroja, None; C. Lopez-Pedrera, EFPIA, 2; V. Gerl, EFPIA, 2;
A. Degroof, EFPIA, 2; J. Ducreux, EFPIA, 2; E. Trombetta, EFPIA, 2; T. Li, EFPIA, 2; M. Alarcón-Riquelme, Genzyme/Sanofi
Corporation, 2; C. Jamin, EFPIA, 2; J. O. Pers, EFPIA, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-fine-bioinformatical-analysis-of-lymphocyte-

distribution-predicts-the-diagnosis-of-systemic-autoimmune-diseases
Abstract Number: 42
Resveratrol Regulates Sirt1 to Control B Cells Activation and Plasma B Cells

Differentiation
Ting Wang1, Xing Song2, Xiaofang Luo2, Mengtao Li2 and Xiaofeng Zeng1, 1Rheumatology, Peking Union Medical College and Chinese
Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China, 2Peking Union Medical College and Chinese
Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China
SESSION INFORMATION
Background/Purpose: Systemic lupus erythematosus (SLE) is a multi-systemic autoimmune disease characterized by B cell hyperactivation
and the production of autoantibodies. Histone deacetylase, Sirtuin1 (Sirt1) has been shown to play a role in regulation of inflammation. Sirt1
deficiency results in the development of lupus-like disease in mice, including the production of anti-nuclear antibody.Resveratrol (trans-
3,4′,5-trihydroxystilbene), a natural polyphenolic phytoalexins, is a potent activator of Sirt1. Our study was conducted to determine the
expression of Sirt1 in B cells in SLE patients and further test the effects of resveratrol on B cell activation and auto-Ab production in
pristane-induced mouse lupus model.
Methods: Flow cytometry and real-time PCR were used to analyze the expression of Sirt1. Sirt1 signaling was modulated with the Sirt1
agonist resveratrol. BALB/c mice were given 0.5 ml of pristane on day 1 by intraperitoneal injection to induce the lupus-like disease and on
day 2 the mice received various doses of resveratrol. CD19+ B cells were isolated from the spleen mononuclear cells of the pristane-
induced lupus mice and cultured with or without resveratrol in vitro for 3-5 days and B cell activation, plasma B cell differentiation and
Prdm1 gene expression were assessed by flow cytometry or real-time PCR.
Results: The expression of Sirt1 in CD19+B cells of SLE patients was significantly decreased when compared to healthy donors (p=0.0071).
The expression of Sirt1 negatively correlated with CD19+ B cell frequencies (p=0.0008). In pristane-induced lupus mice, Sirt1 activator-
resveratrol dramatically decreased the expression of CD69, CD80, CD86 expression of B lymphocytes in a dose-dependent manner.
Resveratrol significantly inhibited CDl38+ plasma cell differentiation of B lymphocytes after stimulation with LPS plus anti-CD40 antibody.
Finally, resveratrol significantly inhibited the expression of PRDM1(gene encoding Blimp-1) mRNA in B-cells.
Conclusion: Sirt1 is downregulated in SLE patients. The use of resveratrol, Sirt1 agonist may present a novel approach for treatment of SLE
by inhibiting B cell activation and plasma cell differentiation.
Disclosure: T. Wang, None; X. Song, None; X. Luo, None; M. Li, None; X. Zeng, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/resveratrol-regulates-sirt1-to-control-b-cells-activation-

and-plasma-b-cells-differentiation
Abstract Number: 43
Regulation of TLR7 Signalling By UBE2L3 Dependent Linear Ubiquitination Explains

Dimethyl Fumarate Suppression of Autoreactive B Cell Development in SLE
Daniele Mauro1, Victoria Tsang2, Isabelle A. Clayton-Lucey3, Sara Pagani2, Farah Alam2, Elena Pontarini2, Alessandra Nerviani2, Angela
Pakozdi4, Andrea Cove-Smith4, Ravindra Rajakariar4, Debasish Pyne4, Timothy J Vyse5, Costantino Pitzalis2 and Myles J. Lewis4,6,
1Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London, School of Medicine and
Dentistry, Queen Mary University of London, London, United Kingdom, 2Experimental Medicine & Rheumatology, William Harvey Research
Institute, Queen Mary University of London, London, United Kingdom, 3Experimental Medicine & Rheumatology, William Harvey Research
Institute, Queen Mary University of London, EC1M 6BQ, United Kingdom, 4Barts Lupus Centre, Barts Health NHS Trust, London, United
Kingdom, 5Division of Genetics and Molecular Medicine, King's College London, Guy's Hospital, London, United Kingdom, 6Rheumatology,
Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London, School of Medicine and
Dentistry, Queen Mary University of London, London, United Kingdom
SESSION INFORMATION
Background/Purpose:
A single risk haplotype spanning UBE2L3 is strongly associated with SLE and multiple autoimmune diseases. The E2 ubiquitin-conjugating
enzyme UBE2L3 regulates TNFα and CD40 induced NF-kB activation via regulation of the Linear Ubiquitination Chain Assembly Complex
(LUBAC). We have shown that the UBE2L3 risk allele correlates with plasmablast and plasma cell expansion in SLE individuals by
regulating NF-κB activation in B cells. Dimethyl Fumarate (DMF), a current oral therapy for multiple sclerosis and psoriasis, has been
recently identified as a UBE2L3 inhibitor. Given the known role of excessive TLR7 signalling in SLE, we aimed to determine the effect of
UBE2L3 and linear ubiquitination on TLR7 signalling and to explore whether UBE2L3-mediated plasmablast differentiation can be inhibited
by DMF.
Methods:
Transient overexpression and shRNA silencing were used in TLR7-HEK293 NF-kB reporter cell line to investigate the effect of
UBE2L3/LUBAC on NF-kB activation, gene expression by qPCR and IL-8 secretion by ELISA. Western blot was used to measure linear
ubiquitin chain polymerisation, confirmed by confocal microscopy. DMF was administered to CD19+ peripheral blood human B cells
cultured in the presence of resiquimod, IFNα, or both for up to 7 days. B cell viability, activation, differentiation and proliferation were
analysed by flow cytometry. Immunoglobulin secretion was quantified by ELISA and ANA detected by Hep2 immunofluorescence assay.
Results:
Overexpression of catalytically active LUBAC components increased TLR7-induced NF-kB activation by reporter assay. NF-kB activation,
NF-κB target gene expression by qPCR and IL-8 secretion were further enhanced by co-overexpression of UBE2L3 with LUBAC, basally
and after TLR7 stimulation, but was abolished by dominant negative mutant UBE2L3(C86S) or HOIP(C885S), and in UBE2L3 silenced cells.
TLR7 engagement triggered accumulation of linear ubiquitin chains comparable to TNFα. DMF exerted a dose-dependent suppression of NF-
kB activation following TLR7 engagement. DMF reduced human primary B cell survival, and suppressed proliferation of switched and
unswitched CD27+ memory B cells. DMF inhibited TLR7 stimulated immunoglobulin secretion by in vitro differentiated B cells. Co-
stimulation of B cells with TLR7 ligand resiquimod and IFNa induced anti-nuclear autoantibody production which was suppressed by DMF.
Conclusion:
Our results establish that linear ubiquitination and UBE2L3 regulate TLR7 activation of NF-κB. Silencing UBE2L3/LUBAC, use of dominant
negative mutant UBE2L3 or HOIP, or use of the UBE2L3 inhibitor DMF suppressed TLR7 driven NF-κB activation. Excessive TLR7
signalling has been linked to SLE development by impaired checkpoint permissiveness in autoreactive B cells, leading to autoantibody
production in the context of type I interferon. DMF demonstrated potent suppression of CD27+ memory B cell differentiation and inhibited
TLR7 and IFNa induced autoantibody production. These results suggest that there may be a role for repositioning DMF in the treatment of
SLE and autoantibody driven autoimmune diseases.
Disclosure: D. Mauro, None; V. Tsang, None; I. A. Clayton-Lucey, None; S. Pagani, None; F. Alam, None; E. Pontarini, None; A.
Nerviani, None; A. Pakozdi, None; A. Cove-Smith, None; R. Rajakariar, None; D. Pyne, None; T. J. Vyse, None; C. Pitzalis, None; M.
J. Lewis, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/regulation-of-tlr7-signalling-by-ube2l3-dependent-linear-

ubiquitination-explains-dimethyl-fumarate-suppression-of-autoreactive-b-cell-development-in-sle
Abstract Number: 44
Characterization of Novel Stromal-Derived Autoantigens Recognized By RA Synovial

Monoclonal Antibodies
Elisa Corsiero1, Lucas Jagemann1, Costantino Pitzalis2 and Michele Bombardieri3, 1Centre for Experimental Medicine & Rheumatology,
William Harvey Research Institute, Queen Mary University of London, London, United Kingdom, 2Centre for Experimental Medicine and
Rheumatology, William Harvey Research Institute, Barts and The London, School of Medicine and Dentistry, Queen Mary University of
London, London, United Kingdom, 3Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Queen Mary
University of London, London, United Kingdom
SESSION INFORMATION
Background/Purpose: We previously showed that up to 40% of RA synovial recombinant monoclonal antibodies (RA-rmAbs) generated
from germinal center-like structure (GC-LS+) RA synovium recognize citrullinated antigens contained in neutrophils extracellular traps
(NETs) (1). The cellular source of other potential autoantigens targeted by the majority of locally differentiated B cells remains undefined.
Recently, RA-fibroblast-like synoviocytes (RA-FLS) have been implicated in the release of citrullinated antigens (2, 3). However, whether
these cells are targeted by RA-rmAbs is still unknown. Here, we aimed to define i) the RA-rmAbs immunoreactivity towards RA-FLS and ii)
identify potential stromal-derived autoantigens.
Methods: 67 RA-rmAbs were generated from single CD19+ B cells FACS-sorted from fresh synovial cell suspensions following IgVH+VL
genes cloning (1). RA-rmAbs were tested by means of i) cell-based immunofluorescence assays with FLS of RA patients and controls
(osteoarthritis (OA)-FLS and RA-dermal fibroblast (RA-DF)), ii) co-localization with stromal specific markers and iii) immunoenzymatic
tests with co-localizing antigens. Control rmAbs were also used (Sjögren’s syndrome/healthy donor-IgG rmAbs).
Results: Immunofluorescence on RA-FLS demonstrated reactivity of 22.4% of RA-rmAbs (15/67 rmAbs) towards FLS. Only 4 rmAbs out of
15 were binding both FLS and NETs components. For some RA-rmAbs this reactivity was not specific to RA-FLS since it was also
observed for OA-FLS (3% rmAbs). Interestingly, strong co-localization was observed with calreticulin (CRT) which has been shown to bind
the RA shared-epitope (SE) ligand and to increase the signalling pathway activated by the SE ligand in its citrullinated form (3). When tested
in ELISA for native vs cit-CRT, 20% (14/67 rmAbs) of the FLS-reactive RA clones showed binding to CRT with 6 out of 14 RA-rmAbs
displaying increased immunoreactivity towards cit-CRT. Controls rmAbs showed no reactivity to either FLS or CRT. RA-rmAbs binding to
CRT was further confirmed in western blot immunoassays.
Conclusion: Here, we provide novel evidence that a subset of locally differentiated B cells within RA synovial GC-LS can react towards
RA-FLS derived antigens. Preliminary data suggest that part of this reactivity is directed towards CRT. Identification of immunodominant
epitopes within CRT is under investigations.
References:
(1) Corsiero et al, ARD 2015
(2) Sorice et al, Rheumatology 2016
(3) Ling et al, AR 2013
Disclosure: E. Corsiero, None; L. Jagemann, None; C. Pitzalis, None; M. Bombardieri, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/characterization-of-novel-stromal-derived-autoantigens-

recognized-by-ra-synovial-monoclonal-antibodies
Abstract Number: 45
BIIB063, a Potent Anti-CD40 Antagonistic Monoclonal Antibody (MAb): Lessons

Learned from an Early Development Program.
Cristina Musselli, Claudia Harper, Linda Burkly, Joan Lane, Chase Chen, Dough Donaldson, Million Arefayene, Karen Smirnakis, Devangi
Mehta, Dale Morris and Nathalie Franchimont, Biogen, Cambridge, MA
SESSION INFORMATION
Background/Purpose:
CD40/CD40L is a cornerstone pathway for both innate and adaptive immune responses and a suitable target for autoimmune diseases
including Sjogren’s. BIIB063 is a high affinity MAb, engineered to reduce Fc effector function and avoid half antibody formation in vivo
(IgG4P). BIIB063 has the potential to inhibit germinal center formation, immunoglobulin class switching, T cell activation and cytokine
release with a potent inhibition of inflammation and autoimmunity. The results of the first in human and the GLP-toxicology findings are
presented.
Methods:
In the single ascending dose (SAD) study, 58 healthy volunteers (HV) subjects were assigned to 8 cohorts. Seven cohorts of 4, 6, or 8
subjects were planned to receive increasing single IV doses of BIIB063 (0.003, 0.03, 0.3, 1, 3, 10, and 20 mg/kg) or placebo. One cohort of
8 subjects was planned to receive a single 150 mg SC dose of BIIB063 or placebo. Staggered dosing was used within each cohort to ensure
subject safety. Blood samples were analyzed by ELISA for PK and ADA, and flow cytometry for the PD measure of CD40 receptor
occupancy (RO). Safety data, including adverse events (AEs) and laboratory tests, were collected. A 26-Week SC and IV Toxicity Study in
Cynomolgus Monkeys with a 16-Week Recovery Period was conducted; animals received 10, 30 or 150 mg/kg BIIB063 twice monthly.
Results:
In the SAD study, a total of 29 subjects had been enrolled when the study was voluntarily put on hold due to findings from the ongoing 26-
week toxicology study where 4 unscheduled terminations occurred. A thorough investigation revealed Immune complex (IgM-IgG4) deposits
in multiple organs of affected animals, consistent with a type 3 hypersensitivity. This reaction occurred in 44% animals irrespective of the
dose level and no NOAEL could be established. .
In the SAD, BIIB063 serum concentrations for the lowest two doses (0.003–0.03 mg/kg), were below the LLOQ. BIIB063 Cmax and AUCinf
ranged from 3.7 to 22 ug/mL and 100 to 1880 hr*ug/mL following doses of 0.3 and 1 mg/kg, respectively. BIIB063 showed nonlinear PKs
and a dose-dependent CD40 RO and RO duration. There was no significant RO of CD40 at dose levels of BIIB063 <0.3 mg/kg, while full
CD40 RO was observed at doses of 0.3 and 1 mg/kg. CD40 RO declined within 96 hr for the 0.3mg/kg dose while CD40 RO lasted 8 days
for the 1 mg/kg dose. BIIB063 was generally well tolerated.
No ADA was observed in the 0.003-0.03 mg/kg cohorts where serum concentrations of drug were undetectable, while 67% - 100% subjects
had positive ADA in the 0.3-1 mg/Kg cohorts. Interestingly, ADA responses were typically detected several weeks after BIIB063 drug
clearance, and in the absence of CD40RO. Hence, the potential impact of ADA on PK and PD was undeterminable.
Conclusion:
BIIB063 administered to HV exhibited a PK profile consistent with an IgG4 molecule. Target engagement as measured by CD40 RO was
clearly demonstrated and its duration was dose dependent. ADA response was present in the higher doses cohorts in the SAD. The
preclinical toxicology findings and the high immunogenicity of BIIB063 led to the voluntary discontinuation of the trial.
Disclosure: C. Musselli, Biogen Idec, 1,Biogen Idec, 3; C. Harper, Biogen Idec, 3,Biogen Idec, 1; L. Burkly, Biogen Idec, 3; J. Lane,
Biogen Idec, 3,Biogen Idec, 1; C. Chen, Biogen Idec, 3,Biogen Idec, 1; D. Donaldson, Biogen Idec, 1,Biogen Idec, 3; M. Arefayene, Biogen
Idec, 1,Biogen Idec, 3; K. Smirnakis, Biogen Idec, 1,Biogen Idec, 3; D. Mehta, Biogen Idec, 1,Biogen Idec, 3; D. Morris, Biogen Idec,
1,Biogen Idec, 3; N. Franchimont, Biogen Idec, 3,Biogen Idec, 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/biib063-a-potent-anti-cd40-antagonistic-monoclonal-

antibody-mab-lessons-learned-from-an-early-development-program
Abstract Number: 46
Secondary Light Chain Editing and Allelic Inclusion in Antibody Secreting Cells from
the Minor Salivary Gland
Kristi A. Koelsch1, Kenneth Smith2, Astrid Rasmussen3, C. Erick Kaufman4, David M. Lewis5, Lida Radfar6, Christopher J Lessard2, Biji
T Kurien2, Judith A. James3, Kathy L. Sivils3, A. Darise Farris7 and R. Hal Scofield8, 1Arthritis and Clinical Immunology Program,
Oklahoma Medical Research Foundation, Okalahoma City, OK, 2Arthritis and Clinical Immunology, Oklahoma Medical Research
Foundation, Oklahoma City, OK, 3Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City,
OK, 4Medicine, University of Oklahoam Health Sciences Center, Oklahoma City, OK, 5Department of Oral Pathology, University of
Oklahoma College of Dentistry, Oklahoma City, OK, 6Department of Oral Diagnosis and Radiology, University of Oklahoma College of
Dentistry, Oklahoma City, OK, 7Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma
City, OK, 8Oklahoma Medical Research Foundation, Oklahoma City, OK
SESSION INFORMATION
Background/Purpose:
Heavy and light chain gene usage and mutational analyses of the Ig variable regions (V-regions) enable the identification of gene usage within
B cell populations. Within the context of antibody secreting cells (ASC) isolated from the minor salivary glands of Sjogren’s syndrome (SS)
patients it may give clues to the loss of tolerance that leads to the genesis of autoreactive cells described in these patients.
Methods:
Fourteen subjects were included in this study. Each had symptomatic dry eyes and mouth; 8 subjects met American/European Consensus
Group (AECG) primary SS criteria and 1 subject also met the American College of Rheumatology criteria for SLE. Six subjects that did not
meet the SS classification criteria (DNMC) served as sicca controls. Labial salivary glands were collected, ASCs were isolated and single-
cell sorted using a new method that allows for probing of both kappa and lambda light chains within in the same single cells in rare
populations. Cells were sequenced and analyzed for V-region gene usage.
Results:
We identified a total of 83 unique heavy/light chain pairs from the SS patient group and 21 from the DNMC control group. No significant
differences in the VH- or JH- gene-family usage were noted between SS or DNMC. The Ig VH family usage in both the SS patient and DNMC
control groups was dominated by the VH3 and VH4 gene families and JH4 was the predominant JH gene family used by both groups. The light
chain analysis revealed that kappa variable region (Vκ) gene families, Vκ1 and Vκ3, were the most frequently used in both groups. The kappa
joining (Jκ) gene analysis revealed that J-genes, Jκ-1 through Jκ-5, were represented in sequences from both groups. The light chain sequence
analyses also revealed the incidence of secondary light chain editing in the sequences from 2 pSS subjects and one DNMC, indicated by
clonally related heavy chains with different light chain usage. These light chain sequences were unique and not found in any of the other pairs
utilized by any of the other subjects. In addition, allelic inclusion, or 1 heavy chain with 2 distinct light chains within the same cell, was
identified in 2 instances from the ASCs isolated from one pSS patient. In each case, both a kappa and a lambda light chain sequence were
amplified from the same cell.
Conclusion:
In summary, we have developed an improved method for the isolation, characterization and mAb production for rare B cells populations,
which has provided data suggesting ASC light chain editing and allelic inclusion not previously reported in SS.
Disclosure: K. A. Koelsch, None; K. Smith, None; A. Rasmussen, None; C. E. Kaufman, None; D. M. Lewis, None; L. Radfar, None; C.
J. Lessard, None; B. T. Kurien, None; J. A. James, None; K. L. Sivils, None; A. D. Farris, None; R. H. Scofield, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/secondary-light-chain-editing-and-allelic-inclusion-in-

antibody-secreting-cells-from-the-minor-salivary-gland
Abstract Number: 47
Claudin-11 Regulates Bone Homeostasis Via Bidirectional EphB4-EphrinB2 Signaling

Jong Min Baek1, Chong Hyuk Chung2, Ju-Young Kim3, Wan-Hee Yoo4, Yunjung Choi5, Changhoon Lee6 and Myeung Su Lee7, 1Department
of Anatomy, School of Medicine, Wonkwang University, Iksan, Korea, Republic of (South), 2Division of Rheumatology, Department of
Internal Medicine, Wonkwnag University Hospital, Wonkwang University Hospital, IKSAN, Korea, Republic of (South), 3Imaging Science-
based Lung and Bone Diseases Research Center, Wonkwang University, IKSAN, Korea, Republic of (South), 4Division of Rheumatology,
Department of Internal Medicine, Chonbuk National University Hospital, Jeonju, Korea, Republic of (South), 5Division of Rheumatology,
Department of Internal Medicine, Chonbuk National University Hospital, jeonju, Korea, Republic of (South), 6Division of Rheumatology,
Department of Internal Medicine, Wonkwang University Hospital, Iksan, Korea, Republic of (South), 7Division of Rheumatology,
Department of Internal Medicine, Wonkwang University Hospital, Iksan, Chonbuk, Korea, Republic of (South)
SESSION INFORMATION
Session Title: Biology and Pathology of Bone and Joint Poster I
Background/Purpose:
Claudins (Cldns) are well-established components of tight junctions (TJs) that play a pivotal role in the modulation of paracellular
permeability. Several studies have explored the physiologic aspects of Cldn family members in bone metabolism. However, the effect of
Cldn11, a major component of central nervous system myelin, on bone homeostasis has not been reported. this study was performed to
identify the effects of Cldn on bone metabolism via regulation of osteoclast and osteoblast differentiation and their function
Methods:
We performed various in vitro and in vivo studies using gain- and loss-of function of Cldn11 that is belong to the Cldn group. Osteoclast
formation from bone marrow cells (BMC) and Osteoblast formation was evaluated in specific condition with over-expression or down-
regulation of Cldn11. The expression of osteoclast associated gene and osteoblast related gene mRNA were assessed by RT-PCR. The levels
of c-fos and NFATc1 protein were assessed by western blot. Also the mitogen-activated protein (MAPK)s and important signal pathways
were measured using Western blot analysis. Osteoclast function was evaluated with resorption pit assay and osteoblastic effects of Cldn11
was evaluated with new bone formation of mouse calvaria. With LPS and co-treated Recombinant protein of Cldn11 on mouse calvaria, we
evaluated the effects of Cldn11 on LPS induced bone loss by using histologic analysis.
Results:
We found that Cldn11 played a negative role in receptor activator of nuclear factor kappa B ligand dependent osteoclast (OC) differentiation
by downregulating the phosphorylated form of extracellular signal-regulated kinase (ERK), Bruton’s tyrosine kinase, and phospholipase C
gamma 2, in turn impeding c-Fos and nuclear factor of activated T cells c1 expression. Osteoblast (OB) differentiation by positive feedback
of Cldn11 was achieved through the phosphorylation of Smad1/5/8, ERK, and c-Jun amino-terminal kinase. Importantly, this Cldn11-
dependent dual event arose from targeting EphrinB2 ligand reverse signaling into OC and EphB4 receptor forward signaling into OB. In
agreement with these in vitro effects, subcutaneous injection of Cldn11 recombinant protein exerted similar effects on local calvarial regions
in mice.
Conclusion:
These findings suggest that Cldn11 is a novel regulator in bone homeostasis.
Disclosure: J. M. Baek, None; C. H. Chung, None; J. Y. Kim, None; W. H. Yoo, None; Y. Choi, None; C. Lee, None; M. S. Lee, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/claudin-11-regulates-bone-homeostasis-via-bidirectional-

ephb4-ephrinb2-signaling
Abstract Number: 48
Modulation of Subchondral Bone Turnover Is Associated with Alteration of Cartilage

Tissue Quality
Cedric Lavet, Isabelle Badoud and Patrick Ammann, Division of Bone Diseases, Geneva, Switzerland
SESSION INFORMATION
Background/Purpose: Osteochondral unit is a bio composite responsible for an optimal distribution of load during movements and axial
compression of a joint. Any alteration of tissue mechanical properties (cartilage or bone) could interfere with an optimal function. One
obvious question is to understand whether alteration of subchondral bone turnover (i.e. quality) could affect cartilage quality and thus
represent a potential risk of OA development.
Methods:
To verify this hypothesis, 15 adult female rats where ovariectomized (OVX, n=10) or SHAM operated (n=5). One group of OVX rats was
treated for 8 weeks with pamidronate (APD) at dose of 0.6 mg/kg, 5 days/mo SC to inhibit the increase of bone turnover, and the other two
groups received the solvent. At the end of the study, distal femurs were harvested. Bio-indentations (CSM, Switzerland) were performed at
the level of the medial condyle at three different area submitted physiologically to different mechanical loading. Elastic modulus (MPa) and
indentation depth (mM) were recorded, using different load from 0.05 to 8 mN. Indentation depths were located in the upper third of the
hyaline cartilage. Cartilage thickness was evaluated by contrast enhanced computed tomography with ionic contrast agent using (Hexabrix®)
at the site of indentation as well as subchondral bone micro architecture. Blood and urine were collected to evaluate bone turnover using
measurement of osteocalcin and deoxypyridinoline excretion. Values are mean±SEM; significance of differences was obtained using an
ANOVA.
Results:
OVX+APD
SHAM (n=5) OVX (n=5)
(n=5)
68.63 ±
Pyridinolines/Creat 23.81 ± 3.03° 26.8 ± 2.83°
11.02*
BV/TV (%) 48.0 ± 3.0° 35.0 ± 1.7* 48.7 ± 3.4°
0.074 ± 0.063 ± 0.079 ±
Tb.Th (mm)
0.003° 0.002* 0.004°
Modulus (MPa) 2.72 ± 0.22° 1.58 ± 0.14* 3.19 ± 0.32°
Indentation Depth
15.87 ± 1.12° 23.7 ± 1.22* 12.5 ± 0.88*°
(mm)
* versus sham, ° versus OVX (ANOVA)
An increment of markers of bone turnover was observed in OVX rats and was fully prevented by APD administration. OVX resulted in
alteration of bone microarchitecture of the subchondral bone as demonstrated by a reduce bone volume (BV/TV) and trabecular thickness
(Tb.Th); all these alterations were fully prevented by APD administration. Hyaline and mineralized cartilage thicknesses were not affected
by OVX nor by APD treatments. OVX was associated with alteration of cartilage tissue quality as indicated by a decreased of modulus and
increased indentation depth. All these alterations were fully prevented by APD treatment preventing the increment in subchondral bone
turnover.
Conclusion:
All together these results demonstrate that in rat, an increment of subchondral bone turnover and/or alteration of the local micro architecture
is associated with degradation of the cartilage tissue quality independently of the estrogen deficiency. These results underline the crucial role
plays by subchondral bone as “regulator” of cartilage quality.
Disclosure: C. Lavet, None; I. Badoud, None; P. Ammann, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/modulation-of-subchondral-bone-turnover-is-associated-

with-alteration-of-cartilage-tissue-quality
Abstract Number: 49
G Protein-Coupled Receptor Kinase 3 Modulates Mesenchymal Stem Cell Proliferation

and Differentiation through Sphingosine-1-Phosphate Receptor Regulation
Jaime M. Brozowski1, Roman G. Timoshchenko2, D. Stephen Serafin2, Jessica Koontz2, Brittney Allyn2, Amanda M. Eudy3, Taylor
Harris4, David Abraham4, Clinton T. Rubin5, Janet Rubin6, Nancy Allbritton4, Matthew J. Billard2 and Teresa K. Tarrant7, 1Microbiology
and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 2Thurston Arthritis Research Center, The University of
North Carolina at Chapel Hill, Chapel Hill, NC, 3Division of Rheumatology, Department of Medicine, Duke University Medical Center,
Durham, NC, 4Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 5Biomedical Engineering, Stony Brook
University, Stony Brook, NY, 6General endocrinology, metabolic bone diseases, The University of North Carolina at Chapel Hill, Chapel
Hill, NC, 7Rheumatology and Immunology, Duke University, Durham, NC
SESSION INFORMATION
Background/Purpose: Mesenchymal stem cells are multipotent stromal cells that can differentiate into tissue-specific lineages, such as
osteocytes and chondrocytes. Their multipotency has made them an intriguing candidate for potential cellular therapy for rheumatic and
musculoskeletal diseases; however, a substantial improvement in the understanding of the intracellular signaling, function, and regulation of
mesenchymal stem cells is warranted before therapeutic use. Our data suggest G protein-coupled receptor kinase 3 (GRK3) functions as a
negative regulator of G protein-coupled receptor (GPCR) signaling of sphingosine-1-phosphate receptor (S1PR) on bone marrow-derived
mesenchymal stem cells (BmMSCs) and lack of such regulation alters BmMSC functionality.
Methods: BmMSCs were isolated from GRK3-deficient (Grk3-/-) and wildtype mice for evaluations of differentiation (chondrogenic,
adipogenic, and osteogenic), CXCL12 secretion (ELISA), and proliferation (CCK8 assay). To better understand the functional differences
noted with Grk3-/- BmMSCs, we investigated GPCR signaling through S1PR stimulation (ERK1/2 western blot). GRK3 β-arrestin
recruitment to S1PR1 was demonstrated by TANGO, and S1PR1 internalization was determined by flow cytometry quantification of surface
receptor expression.
Results: Grk3-/- BmMSCs have enhanced proliferation and osteogenic differentiation ex vivo compared to wildtype BmMSCs in identical
culture conditions and passages. Grk3-/- BmMSCs also secrete more CXCL12, an essential chemokine for hematopoietic stem and progenitor
development, and Grk3-/- mice have increased hematopoietic cell numbers isolated from the bone marrow. However, Grk3-/- mice do not
show enhanced trabecular or cortical bone density, which suggest GRK3 deficiency in BmMSCs may have more pronounced effects on
hematopoiesis as opposed to mature bone development in vivo. Both Grk3-/- BmMSC proliferation and osteogenic differentiation were
reduced to wildtype level upon sphingosine kinase inhibitor treatment, and Grk3-/- BmMSCs have sustained ERK1/2 signaling upon
stimulation of S1PR with S1P ligand. In addition, we report GRK3 recruits β-arrestin to the C-terminus of S1PR1, and we demonstrate
BmMSCs lacking GRK3 regulation have impaired S1PR1 internalization.
Conclusion: Our work suggests GRK3 regulates S1PR on BmMSCs and lack of such regulation induces increased cellular proliferation and
osteogenic differentiation, indicating GRK3 may serve as a potential therapeutic target to alter BmMSC functionality.
Disclosure: J. M. Brozowski, None; R. G. Timoshchenko, None; D. S. Serafin, None; J. Koontz, None; B. Allyn, None; A. M. Eudy,
None; T. Harris, None; D. Abraham, None; C. T. Rubin, None; J. Rubin, None; N. Allbritton, None; M. J. Billard, None; T. K. Tarrant,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/g-protein-coupled-receptor-kinase-3-modulates-

mesenchymal-stem-cell-proliferation-and-differentiation-through-sphingosine-1-phosphate-receptor-regulation
Abstract Number: 50
Quality Controls Monitoring As Indicator of Stability in Bone and Cartilage Turnover

Markers for Clinical Trials
Yannick Lhoste, Vanessa Di Cataldo, Philippe Vergnaud and Tanja Schubert, Bioclinica Lab, LYON, France
SESSION INFORMATION
Background/Purpose:
Protein biomarkers are widely used in clinical studies to assess drug efficacy, such as bone and cartilage turnover markers in osteoarthritis or
rheumatoid arthritis clinical studies. In most of these clinical studies it is highly recommended to analyze as many visits, including all follow-
up visits, at the same time, often requiring sample storage below -70°C for an extended period of time. Thus, determination of long-term
stability of the biomarkers upon storage is critical.
Typically, long-term stability is measured in samples with a baseline assessment before storage in order to determine the nominal value.
Subsequently, samples are assessed in the same condition at frequent intervals, covering different storage periods. However, this method
requires numerous samples with a large volume, which is often challenging to obtain. Thus, we suggest an alternative approach by monitoring
in-house quality control (QCs) as indication of analyte stability.
Methods:
We investigated the long-term stability of the most widely analyzed serum biomarkers in musculoskeletal related clinical trials:
carboxyterminal of type 1 collagen (S-CTX-I), osteocalcin (S-OC), aminoterminal propeptide of type 1 collagen (S-PINP), and
metalloproteinases 3 and 9 (S-Total-MMP-3 and S-MMP-9). At least 12 serum samples were assayed at baseline and re-assayed after a
storage period. Subsequent results were compared to baseline.
Additionally, we monitored the performance of our in-house QC samples for the same biomarkers and compared the data with the stability
data previously determined. Urinary carboxyterminal telopeptide of type 2 collagen (U-CTX-II) long-term stability was assessed in samples
after QC monitoring to validate our approach. QC monitoring was also performed for serum cartilage oligomeric matrix protein (S-COMP),
another cartilage turnover marker.
An analyte is considered stable when the coefficient of variation (CV) and the accuracy (variation from target value) of the QC results are
inferior to ± 15%.
Results:
S-CTX-I S-OC S-PINP S-Total MMP-3 S-MMP-9 U-CTX-II
N-MID Quantikine® Urine CartiLaps®
Serum β- Total PINP, Quantikine®
Method of Osteocalcin, Human total EIA,
CrossLaps, Roche Roche Human MMP-9,
analysis Roche MMP-3, R&D Immunodiagnostic
Diagnostics Diagnostics R&D Systems, Inc
Diagnostics Systems, Inc System, Ltd.
Mean variation
(%; absolute 12.4 5.8 5.1 6.7 9.7 9.8
value)
Off limit
8/30 2/78 0/37 2/12 6/28 6/29
(CV >15%)
Stability at -
70°C
Until 3 years Until 8 years Until 3 years Until 3.5 years Until 18 months Until 55 months
(validation
method)
QC monitoring
30 months 37 months 39 months 22 months 11 months 37 months
period
Number of QCs 6 5 6 4 4 4
QCs mean
0.067 to 3.89 4.35 to 185.0 14.46 to 844.5 6.229 to 56.72 277.5 to 960.9 1.091 to 6.843
(ng/mL)
QCs CV (%) 3.6 to 8.5 3.4 to 5.2 1.8 to 6.1 7.6 to 9.7 10.2 to 14.1 8.4 to 9.4
QCs variation
-7.6 to 6.9 -6.2 to 1.5 -8.4 to 10.7 -4.0 to 3.5 0.5 to 5.2 -6 to 6.8
with target (%)
Stability based
39 months 37 months 39 months 22 months 11 months 37 months
on monitoring
Consistency
with stability YES YES YES YES YES YES
data
S-COMP
QCs S21 S22
Period 19 months 19 months
Method of analysis COMP® ELISA, AnaMar Medical
Number of assay 106 106
Target value (U/L) 11.08 14.44
Mean (U/L) 10.92 14.06
SD (U/L) 0.92 1.27
CV (%) 8.4 9
Accuracy (%) -1.5 -2.6
Stability indication Stable until 19 months
Conclusion:
Assay analysis of protein biomarkers for clinical trials require a very stringent and robust quality process, which is based on the use of
independent, endogenous QC samples throughout the complete duration of the clinical trial. We proved that long-term stability for biomarkers
can be assessed by monitoring in-house QCs as confirmed by the U-CTX-II results.
Thus, based on the data obtained during QC monitoring for S-COMP we suggest that this marker is stable up to 19 months below -70°C.
However, these data should be confirmed by a standard validation stability test.
Disclosure: Y. Lhoste, Bioclinica Lab, 3; V. Di Cataldo, Bioclinica Lab, 3; P. Vergnaud, Bioclinica Lab, 3; T. Schubert, Bioclinica Lab,
3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/quality-controls-monitoring-as-indicator-of-stability-in-

bone-and-cartilage-turnover-markers-for-clinical-trials
Abstract Number: 51
Irisin Ameliorates Infrapatellar Adiposity in Knee Osteoarthritis Pathogenesis By

Orchestrating Adipokine Signaling
Feng-Sheng Wang1, Yi-Chih Sun1 and Jih-Yang Ko2, 1Core Facility for Phenomics & Diagnostics, Department of Medical Research, Core
Facility for Phenomics & Diagnostics, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Taiwan, Kaohsiung,
Taiwan, 2Department of Orthopedic Surgery, Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, Taiwan,
Kaohsiung, Taiwan
SESSION INFORMATION
Background/Purpose: Aberrant infrapatellar fat metabolism is a prominent feature that exacerbates inflammation and fibrosis relative to
joint deterioration during osteoarthritis (OA). Irisin, a secretory subunit of fibronectin type III domain containing 5 (FNDC5), is found to
regulate adipose morphogenesis, energy expenditure, skeletal muscle, and bone metabolism. This study is undertaken to investigate the
association of Irisin expression and end-stage knee OA and verify whether Irisin signaling changed infrapatellar fat remodeling and joint
homeostasis in the progression of OA.
Methods: Injured articular specimens were harvested from 19 patients with end-stage knee OA and 11 patients with femoral neck fracture
(non-OA) who required total hip arthroplasty. Knee joints in mice that overexpressed FNDC5 were subjected to suprapatellar injection of
collagenase to provoke OA. Expressions of Irisin, adipokines, and MMPs were probed with RT-quantitative PCR. Infrapatellar adiposity,
cartilage damage, and synovial integrity were verified with histomorphometry and immunohistochemistry. Irisin recombinant protein was
produced for the treatment of collagenase-affected knees.
Results: Infrapatellar adipose and synovial tissues instead of articular cartilage exhibited distinguishable Irisin immunostaining. Injured
specimens from the end-stage OA group showed 40% decline in Irisin expression compared with those in the non-OA group. In vitro, a gain
of Irisin function enabled synovial fibroblasts but not chondrocytes to display minor responses to the IL-1β provocation of MMP3 and MMP9
expression. Of note, Irisin signaling enhancement resulted in 85% decrease in adipogenic gene expression and 65% reduction in adipocyte
formation of mesenchymal progenitor cells. In collagenase-mediated knee OA pathogenesis, the FNDC5-overexpressing mice showed
moderate responses to infrapatellar adipose hypertrophy concomitant with slight synovial hypercellularity and membrane hyperplasia within
the affected joints. These adipose-regulatory actions warded off the affected knees from cartilage destruction and gait aberrance. Likewise,
administration of Irisin recombinant protein mitigated the development of infrapatellar adiposity and synovitis, a remedial effect that slowed
down the progression of articular cartilage erosion and walking profile irregularity. Affected joints and adipocytes responded to the Irisin
recombinant protein treatment by reducing the expressions of cartilage-deleterious adipokines IL-6, leptin, and adiponectin through regulating
PPARγ function.
Conclusion: Irisin dysfunction is relevant to the occurrence of end-stage knee OA. Irisin signaling protects from excessive adipogenesis of
mesenchymal precursor cells and diminishes inflammation and cartilage catabolism actions aggravated by adipocytes and synovial cells. This
study sheds an emerging new light on the Irisin signaling stabilization of infrapatellar adipose homeostasis and the prospective of the
therapeutic potential of Irisin recombinant protein for deescalating knee OA development.
Disclosure: F. S. Wang, None; Y. C. Sun, None; J. Y. Ko, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/irisin-ameliorates-infrapatellar-adiposity-in-knee-

osteoarthritis-pathogenesis-by-orchestrating-adipokine-signaling
Abstract Number: 52
In Vivo Effect of Opticin Deficiency in a Surgically Induced Mouse Model of

Osteoarthritis
Aina Farran1, Gladys Valverde-Franco2, Laura Tio3, Bertrand Lussier4, Hassan Fahmi2, Jean-Pierre Pelletier2, Paul Bishop5, Jordi
Monfort6 and Johanne Martel-Pelletier2, 1Osteoarthritis Research Unit (CRCHUM), Montreal; Inflammation and Cartilage Cellular
Research Group, IMIM (Hospital del Mar Research Unit) Rheumatology Department, Parc de Salut Mar, Hospital del Mar, Barcelona,
Barcelona, Spain, 2Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, QC, Canada,
3Inflammation and Cartilage Cellular Research Group, IMIM (Hospital del Mar Research Unit) Rheumatology Department, Parc de Salut
Mar, Hospital del Mar, Barcelona, Spain, 4Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM);
Faculty of Veterinary Medicine, Clinical Sciences, University of Montreal, Sainte-Hyacinthe, QC, Canada, 5Manchester Royal Eye Hospital,
Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre; School of Biological
Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom, 6Inflammation and Cartilage
Cellular Research Group, IMIM (Hospital del Mar Research Unit) Rheumatology Department, Parc de Salut Mar; Rheumatology Department,
Hospital del Mar, Barcelona, Spain
SESSION INFORMATION
Background/Purpose: Opticin (OPTC) is a small leucine-rich proteoglycan (SLRP) that has been previously demonstrated to be produced
and degraded in osteoarthritic (OA) human cartilage. Here, we further investigated the in vivo effect of OPTC deficiency in OA cartilage.
Methods: OA was induced in 10-week-old Optc-/- (knock-out) and Optc+/+ (wild type) mice by destabilization of the medial meniscus
(DMM). Ten weeks post-surgery, cartilage was processed for histology, and immunohistochemistry. SLRP expression was determined in
non-operated mouse cartilage at day 3 (P03) and 10 weeks of age. Collagen ultrastructure was analyzed by transmission electron microscopy
in 10-week-old non-operated mouse cartilage.
Results: OA Optc-/- mice demonstrated significant protection against cartilage degradation. Data revealed that in non-operated Optc-/-
mouse cartilage, the SLRPs lumican and epiphycan were significantly up-regulated at P03 (p≤0.010) and 10 weeks old (p≤0.007), and
fibromodulin down-regulated at 10 weeks of age (p≤0.001). Immunohistochemistry of OA mice showed a similar pattern. In OA Optc-/-
mouse cartilage, markers of cartilage degradation and complement factors C5b-9 and CCL2 were all down-regulated (p≤0.050). In Optc-/-
mouse cartilage, collagen fibers were thinner and better organized (p=0.038) than in OA Optc+/+ mouse cartilage.
Conclusion: This work demonstrates a protective effect of OPTC deficiency during OA, resulting from an overexpression of lumican and
epiphycan, known to bind and protect collagen fibers, and a decrease in fibromodulin, contributing to a reduction in the complement
activation/inflammatory process. This work suggests that the evaluation of the composition of the different SLRPs in OA cartilage could be
applied as a new tool for OA prognosis classification.
Disclosure: A. Farran, None; G. Valverde-Franco, None; L. Tio, None; B. Lussier, None; H. Fahmi, None; J. P. Pelletier, None; P.
Bishop, None; J. Monfort, None; J. Martel-Pelletier, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/in-vivo-effect-of-opticin-deficiency-in-a-surgically-

induced-mouse-model-of-osteoarthritis
Abstract Number: 53
Poly-γ-Glutamic Acid Inhibits RANKL- Induced Osteoclast Differentiation and

Prevents Bone Destruction in Rheumatoid Arthritis: Human and CIA Mouse Model
Bitnara Lee 1, Jong-Dae Ji2 and Tae-Hwan Kim1, 1Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea, Republic of (South),
2Rheumatology, Korea University Hospital, Seoul, Korea, Republic of (South)
SESSION INFORMATION
Background/Purpose:
Rheumatoid arthritis (RA) is an inflammatory disease that is characterized by chronic inflammation and bone destruction. Osteoclasts, which
are bone-resorbing cells, are generally known to play a pivotal role in the pathogenesis of bone destruction in RA. Poly–γ-glutamic acid (γ-
PGA), a natural polymer derived from Bacillus subtilis, has anti-inflammatory activity. It is mediated by suppressing differentiation of Th17
cells in asthma model. However, the effects of γ-PGA in RA osteoclast differentiation is unclear. Therefore, we evaluated whether γ-PGA
prevents inflammation and joint damage of RA by regulating osteoclast differentiation in human and mice.
Methods:
We tested the inhibitory effect of γ-PGA on osteoclastogenesis in healthy human peripheral blood monocytes, RA synovial fluid
macrophages, and mouse bone-marrow-derived macrophages (BMMs). The osteoclastogenesis was assessed by generation of TRAP-
positive multinucleated cells and actin ring formation. We analyzed the expressions of essential genes and proteins for osteoclast
differentiation by real-time PCR and western blot analysis. We observed whether treatment of γ-PGA efficiently reduces osteoclast formation
and bone destruction in animal model of rheumatoid arthritis (collagen-induced arthritis [CIA] in DBA/1J mice).
Results:
Firstly, we showed that γ-PGA strongly inhibits osteoclast differentiation in normal PBMC-derived osteoclast precursors and RA synovial
fluid macrophages. γ-PGA suppressed RANK mRNA and protein level by down-regulating of M-CSF receptor protein, which is required for
RANK expression. Furthermore, we found that in vitro, treatment with γ-PGA suppressed osteoclastogenesis in wild-type (WT) mice, but the
inhibition mechanism of γ-PGA was not TLR4-dependent since γ-PGA still inhibited osteoclast formation in TLR4-deficient mouse BMMs.
Reflecting on these in vitro effects, oral administration of γ-PGA markedly reduced bone destruction in CIA mice. Histological analysis
confirmed that γ-PGA prevented bone destruction and osteoclast formation in the bone tissues. In addition, treatment with γ-PGA also
suppressed the expressions of IL-1β and TNF-α.
Conclusion:
Our results show that γ-PGA markedly suppresses osteoclastogenesis in human and mice. γ-PGA also reduces bone destruction, osteoclast
formation, and inflammatory cytokines in animal model of RA. Thus, these data suggest that γ-PGA can be a good candidate for the
therapeutic application of joint destruction in RA.
Disclosure: B. Lee, None; J. D. Ji, None; T. H. Kim, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/poly-%ce%b3-glutamic-acid-inhibits-rankl-induced-

osteoclast-differentiation-and-prevents-bone-destruction-in-rheumatoid-arthritis-human-and-cia-mouse-model
Abstract Number: 54
Maintaining Angiogenesis Prevents Glucocorticoid Induced Osteonecrosis

Alanna Dubrovsky1, Wei Yao1, Geetha Mohan1, Mie Jin Lim1, Yu-An Evan Lay1, Donald Kimmel2 and Nancy E. Lane3,4,5,6,7,8, 1UC
Davis Center for Musculoskeletal Health, Sacramento, CA, 2Creighton University School of Medicine Osteoporosis Research Center,
Omaha, NE, 3Center for Musculoskeletal Health, University of California, Davis School of Medicine, Sacramento, CA, 4Internal Medicine,
Center for Musculoskeletal Health, UC Davis School of Medicine, Sacramento, CA, 5UC Davis Medical Center, Sacramento, CA, 6Center
for Musculoskeletal Health, Univ of California at Davis, Sacramento, CA, 7Medicine, U.C. Davis, Sacramento, CA, 8UCDMC, Sacramento,
CA
SESSION INFORMATION
Background/Purpose: Atraumatic osteonecrosis (ON) results from reduced bone vascularity. Glucocorticoids (GC) are a major risk factor
for ON, as GCs reduce vascular endothelial growth factor, vascular density, and bone mass [Mohan et al CTI 2017]. Mice treated with GCs
and either PTH or LLP2A-Ale, a bone targeted therapy that directs mesenchymal stem cells to bone surfaces, showed significantly less GC-
induced bone mass changes. The aim of this study was to determine if PTH or LLP2A-Ale co-treatment could prevent or reduce the severity
of GC-induced ON.
Methods: Seven-week-old male BALB/c mice were randomized into placebo (PL), PL+GC (4 mg/L dexamethasone in drinking water),
Methods: Seven-week-old male BALB/c mice were randomized into placebo (PL), PL+GC (4 mg/L dexamethasone in drinking water),
GC+250 µg/kg or GC+500 µg/kg LLP2A-Ale (subcutaneous (SC), 1X/2 wks), or GC+40 µg/kg PTH (hPTH(1-34), 5x/wk, SC) (n=8 for PL
and 16 for all GC groups). Mice were sacrificed on Day 30 or Day 45. Both distal femurs (DF) from each mouse were decalcified, and
coronal sections were made and stained with H&E. ON was identified in the DF epiphysis (DFE) using modified criteria [Yang et al., JOR,
2009] (presence of empty osteocyte lacunae, nuclear pyknosis, ghost osteocytes in bone trabeculae, bone marrow/stromal necrosis, > 30% fat
in marrow, and fibrin thrombi in blood vessels). ON was diagnosed when three or more of the above features were seen, by three
independent, blinded observers, with >80% agreement. Immunohistochemical staining for blood vessels was performed on the DFE using
CD31 and endomucin antibodies.
Results: PL+GC mice had 15-20% lower body weight than PL (p<0.05). At Day 30, ON prevalence was 18%, 6%, 0% and 6%,
respectively, in PL+GC, GC+LLP2A-Ale (250), GC+LLP2A-Ale (500) and GC+PTH groups. At Day 45, ON prevalence was 81%, 25%,
18% and 12%, respectively, in PL+GC, GC+LLP2A-Ale (250), GC+LLP2A-Ale (500), and GC+PTH. Blood vessels (anti-
CD31/endomucin) appeared more intact in GC+LLP2A-Ale and GC+PTH groups than in PL+GC at both times (p<0.05). At Day 45, both
GC+LLP2A-Ale and GC+PTH groups had 50% greater sinusoid density, and 50% lower adipocyte density at the DFE compared to PL+GC
alone (p<0.05).
Conclusion: Co-treatment of murine GC-induced ON with PTH or LLP2A-Ale reduced the prevalence of ON after 45 days. Additional
studies to ascertain the mechanism by which these agents prevent GC-induced ON are warranted.
Disclosure: A. Dubrovsky, None; W. Yao, LLP2A-Ale, 4; G. Mohan, None; M. J. Lim, None; Y. A. E. Lay, None; D. Kimmel, None; N. E.
Lane, LLP2A-Ale, 4.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/maintaining-angiogenesis-prevents-glucocorticoid-

induced-osteonecrosis
Abstract Number: 55
Nrf2 Inhibits Apoptosis and Suppresses Oxidative Stress By Activating

NOX4/ERK1/2/ELK1 Signaling Axis in Human Chondrocytes
Mohammad N. Khan1, Imran Ahmad1, Mohammad Y Ansari2 and Tariq M Haqqi1, 1Anatomy & Neurobiology, Northeast Ohio Medical
University, Rootstown, OH, 2Anatomy & Neurobiology, Northeast Ohio Medical University, Roostown, OH
SESSION INFORMATION
Background/Purpose: Nrf2 is a redox sensitive transcription factor that regulates the expression of phase II antioxidant enzymes and
cytoprotective genes and is crucial for maintaining the cartilage integrity. However, mechanisms underlying the cartilage/chondroprotective
effects of Nrf2 remains largely unknown. Here, we examined the critical role of Nrf2 in protecting human OA chondrocytes against oxidative
damage and induction of apoptosis under pathological conditions.
Methods:
Deidentified and discarded OA cartilage was obtained at the time of total joint arthroplasty and chondrocytes were prepared by enzymatic
digestion. qRT-PCR and immunoblotting with validated antibodies were used to assess the gene and protein expression respectively. Nrf2
activation was determined by luciferase reporter assay. Chondrocytes were transfected with Nrf2 overexpression plasmid, ARE reporter
vector or siRNAs using nucleofection. ROS levels were measured by H2DCF-DA staining. Apoptosis was measured by TUNEL assay.
Agarose gel electrophoresis was used to analyze DNA fragmentation.
Results:
Expression of Nrf2 and its downstream targets HO-1, NQO1, and SOD2 was significantly higher in damaged OA cartilage compared with the
smooth cartilage of the same patient. A luciferase reporter assay demonstrated that IL-1β-stimulation was a potent inducer of Nrf2 activity in
OA chondrocytes. Interestingly, pretreatment of OA chondrocytes with antioxidants significantly inhibited the IL-1β-mediated activation of
Nrf2/ARE signaling indicating that the activity was due to oxidative stress. Over-expression of Nrf2 in OA chondrocytes significantly
suppressed the IL-1β-mediated generation of ROS, production of H2O2 and expression of NOX4 whereas Nrf2 knockdown significantly
enhanced the basal as well as induced levels of ROS and expression of NOX4. OA chondrocytes with overexpression of Nrf2 showed
inhibition of both the extrinsic and intrinsic apoptotic pathways as IL-1β-induced DNA fragmentation, activation of Caspase-3, cleavage of
PARP, cleavage of Caspase-8,-9, release of cytochrome-c, suppression of mitochondrial ROS production and mitochondrial dysfunction
were not observed. Further, enhanced expression of Nrf2 stimulated the expression of anti-apoptotic proteins-Bcl2, Bcl-xl and Mcl-1-and
significantly suppressed the expression of pro-apoptotic proteins-Bax, Bad and Bid-in IL-1β stimulated OA chondrocytes. Nrf2
overexpression enhanced the phosphorylation of ERK1/2 and its downstream target proteins-Elk-1, P70S6K and P90RSK in OA
chondrocytes, whereas pharmacological inhibition of ERK1/2 activation enhanced the ROS generation and increased apoptosis in IL-1β-
stimulated OA chondrocytes.
Conclusion: Taken together, these results show that Nrf2 is a stress response protein in OA chondrocytes with an anti-apoptotic function. IL-
1β-induced stress causes activation of Nrf2 which activates the ERK1/2/ELK1-P70S6K-P90RSK signaling pathway to inhibit apoptosis of
OA chondrocytes. These activities of Nrf2 make it a promising candidate for the development of novel therapies for the management of OA.
Disclosure: M. N. Khan, None; I. Ahmad, None; M. Y. Ansari, None; T. M. Haqqi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/nrf2-inhibits-apoptosis-and-suppresses-oxidative-stress-

by-activating-nox4erk12elk1-signaling-axis-in-human-chondrocytes
Abstract Number: 56
Baicalein, a Plant-Derived Small Molecule, Activate Nrf2/Autophagy Signaling Axis Via

MEK1/2-ERK1/2-Elk1 Pathway to Suppress the Expression of IL-6 in Human
Osteoarthritis Chondrocytes
Mohammad N. Khan1, Imran Ahmad1, Mohammad Y. Ansari2 and Tariq M Haqqi1, 1Anatomy & Neurobiology, Northeast Ohio Medical
University, Rootstown, OH, 2Anatomy & Neurobiology, Northeast Ohio Medical University, Roostown, OH
SESSION INFORMATION
Background/Purpose: Inflammation is an important component of osteoarthritis (OA) pathogenesis. IL-6 is implicated in OA pathogenesis
as it suppresses anabolic factors and upregulate the expression of catabolic proteins. Here, we used an in vitro model of inflammation in OA
to investigate the potential of Baicalein, a natural flavonoid found in root extract of Scutellaria baicalensis, to suppress the expression of IL-
6 and determined the molecular mechanism by investigating the role of Nrf2 and autophagy activation in human OA chondrocytes.
Methods: Primary human OA chondrocytes were prepared by enzymatic digestion of deidentified and discarded cartilage from donors with
OA who underwent total knee arthroplasty. Autophagy activation was investigated by immunoblotting for LC3-I and LC3-II, ATG5,
autophagic flux and immunofluorescence staining for LC3 puncta. Expression and activation of Nrf2 was determined by immunoblotting and
by a luciferase reporter assay, respectively. mRNA and protein expression of Nrf2 regulated genes HO-1, NQO1, SOD2 was studied by
qPCR and immunoblotting, respectively. Total protein levels and activation of ERK1/2 and its upstream and downstream signaling molecules
was assayed by immunoblotting. For molecular docking studies using the Glide tool in Schrödinger Maestro suite, the crystal structure of
Keap1 protein in complex with a small chemical compound K67 (PDB CODE: 4ZY3) was extracted from the Protein Data Bank and used as
docking structure template.
Results:
OA chondrocytes showed high levels of IL-6 expression upon stimulation with IL-1β. However, pre-treatment of OA chondrocytes with
Baicalein, in a dose dependent manner, abolished the IL-1β-induced upregulation of IL-6 expression. Baicalein induced macro-autophagy in
OA chondrocytes in vitro as indicated by significantly (p<0.05) increased expression of LC3, ATG5, ATG3, enhanced autophagy flux and
increased number of autophagic puncta in OA chondrocytes. Baicalein treated OA chondrocytes also showed enhanced activity of Nrf2/ARE
as revealed by a Nrf2/ARE reporter assay. Molecular docking studies indicated that Baicalein activates Nrf2 by disrupting the Keap-1/Nrf-2
interaction by blocking the Nrf-2 binding site in the Keap-1 protein. Additionally, OA chondrocytes treated with Baicalein, and in a dose
dependent manner, showed enhanced expression, both at mRNA and protein levels, of Nrf2 target genes HO-1, NQO1, and SOD2. We next
determined the molecular events involved in Baicalein mediated activation of Nrf2 and it was found that treatment of OA chondrocytes with
Baicalein activated MEK1/2-ERK1/2-Elk-1 signaling in a time dependent manner. Inhibition of ERK1/2 activation or inhibition of autophagy
using small molecules or siRNA mediated depletion of target genes expression abolished the protective effects of Baicalein in OA
chondrocytes under pathological conditions.
Conclusion: The present study indicates that Baicalein act, at least in part, by activating Nrf2/autophagy axis and increased expression of
HO-1, NQO1 and SOD2 in OA chondrocytes. This property indicates that Baicalein could be developed as an effective adjunct therapy for
the suppression of OA pathogenesis.
Supported by USPHS/NIH grants
Disclosure: M. N. Khan, None; I. Ahmad, None; M. Y. Ansari, None; T. M. Haqqi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/baicalein-a-plant-derived-small-molecule-activate-

nrf2autophagy-signaling-axis-via-mek12-erk12-elk1-pathway-to-suppress-the-expression-of-il-6-in-human-osteoarthritis-chondrocytes
Abstract Number: 57
Accelerated Development of Aging-Associated and Instability-Induced Osteoarthritis in

12/15-Lipoxygenase Deficient Mice
Lauris Habouri1, Yassine Ouhaddi1, Gadid Guedi1, Jean-Pierre Pelletier2, Johanne Martel-Pelletier2, mohamed benderdour1 and Hassan
Fahmi2, 1Medicine, CRCHUM, Montreal, QC, Canada, 2Osteoarthritis Research Unit, University of Montreal Hospital Research Centre
(CRCHUM), Montreal, QC, Canada
SESSION INFORMATION
Background/Purpose:
12/15-Lipoxygenase (12/15-LOX) catalyzes the generation of various anti-inflammatory lipid mediators, and has been implicated in several
inflammatory and degenerative diseases. However, there is currently no evidence that 12/15-LOX has a role in osteoarthritis (OA). The aim
of this study was to investigate the role of 12/15-LOX in the pathogenesis of OA.
Methods:
The development of aging-associated and destabilization of the medial meniscus (DMM)-induced OA were compared in 12/15-LOX-
deficient (12/15-LOX-/-) and wild-type (WT) mice. The extent of cartilage damage was evaluated by histology. The expression of OA
markers was evaluated by immunohistochemistry and RT-PCR. Cartilage explants were stimulated with IL-1α in the absence or presence of
the 12/15-LOX metabolites, 15-HETE, 13-HODE or LXA4, and the levels of MMP-13, NO and PGE2 were determined. The effect of LXA4
on the progression of OA was evaluated in WT mice.
Results:
The expression of 12/15-LOX in cartilage increased during the progression of DMM-induced OA and with aging in WT mice. Cartilage
degeneration was more severe in 12/15-LOX-/- mice compared to WT mice in both models of OA, and this was associated with increased
expression of MMP-13, ADAMTS5, iNOS, and mPGES-1. Treatment of cartilage explants with 12/15-LOX metabolites, suppressed IL-1α-
induced production of MMP-13, NO and PGE2, with LXA4 being the most potent. Intra-peritoneal injection of LXA4 reduced the severity of
DMM-induced cartilage degradation.
Conclusion:
These data suggest an important role of 12/15-LOX in the pathogenesis of OA. They also suggest that activation of this pathway may provide
a novel strategy for prevention and treatment of OA.
Disclosure: L. Habouri, None; Y. Ouhaddi, None; G. Guedi, None; J. P. Pelletier, None; J. Martel-Pelletier, None; M. benderdour,
None; H. Fahmi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/accelerated-development-of-aging-associated-and-

instability-induced-osteoarthritis-in-1215-lipoxygenase-deficient-mice
Abstract Number: 58
Cartilage-like Tissue Generation By 3D-Bioprinting of Induced Pluripotent Stem Cells

Rocío Castro-Viñuelas1, Alma Forsman2, Erdem Karabulut3, Erik Romberg3, Camilla Brantsing2, Mats Brittberg4, Anders Lindahl2, Paul
Gatenholm3 and Stina Simonsson2, 1Cell Therapy and Regenerative Medicine research group. Rheumatology Division. Institute of
Biomedical Research of A Coruña (INIBIC). Dep. of Biomedical Sciences, Medicine and Physiotherapy, University of A Coruña, A Coruña,
Spain, 2Institute of Biomedicine at Sahlgrenska Academy, Department of Clinical Chemistry and Transfusion Medicine, University of
Gothenburg., Gothenburg, Sweden, 33D Bioprinting Center, Dept. of Chemistry and Chemical Engineering, Chalmers University of
Technology, Gothenburg, Sweden, 4Cartilage Repair Unit, University of Gothenburg, Region Halland Orthopaedics, Kungsbacka Hospital,
Kungsbacka, Sweden
SESSION INFORMATION
Background/Purpose: Cartilage lesions due to traumatic or pathological conditions slowly grow over the time and may lead to osteoarthritis
(OA). As a prospective treatment for such lesions, it has been shown that human-derived induced pluripotent stem cells (iPSCs) can be 3D
bioprinted and directed to form cartilage-like tissue (Nguyen et al. 2017). The advantages of using an established iPSC line are unlimited
cell source with regeneration capacity and chondrogenic differentiation potential. The aim of this study was to improve the generation of
cartilage-like tissue when 3D bioprinting of iPSCs by using molecularly modified nanocelullose/alginate bioink to resemble natural
environment found in the tissue.
Methods: In this study the chondrocyte-derived iPSc line “A2B” was used (Borestrom et al. 2014). These cells were bioprinted in
combination with a modified bioink composed by nanocellulose and alginate. One week after bioprinting, the constructs were cultured in
chondrogenic medium in order to stimulate cell differentiation towards chondrocytes. Cell number and viability was studied. Histological
analyses of the 3D printed constructs were performed. Furthermore, expression of pluripotency and chondrogenic specific genes was
assessed by Taqman qPCR before and after differentiation.
Results: High viability of the iPSCs inside the constructs was found after bioprinting. 3D printed constructs were positively stained for
alcian blue van gieson staining, showing proteoglycans presence inside the prints. Molecular analyses showed high relative expression levels
of the pluripotency-related gene Oct4 before initiating the differentiation protocol. Cells inside the constructs express chondrogenic specific
genes, such as collagen type 2 and Sox9 after 6 weeks of differentiation. Moreover, 3D printed constructs showed cartilage-resembles
(Figure 1).
Conclusion : Modified Nanocellulose/alginate bioink allowed 3D printing of the iPSCs and the in vitro generation of cartilage-like tissue.
This approach could be used in the future to model OA disease or to perform screenings of different therapeutic compounds.
Figure 1. Cartilage mimic by 3D bioprinting iPSCs differentiated
for 6 weeks in modified bio ink.
Disclosure: R. Castro-Viñuelas, None; A. Forsman, None; E. Karabulut, None; E. Romberg, None; C. Brantsing, None; M. Brittberg,
None; A. Lindahl, None; P. Gatenholm, None; S. Simonsson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/cartilage-like-tissue-generation-by-3d-bioprinting-of-

induced-pluripotent-stem-cells
Abstract Number: 59
Abaloparatide, a Novel PTHrP Analog, Increased Bone Mass and Density at Cortical
and Trabecular Sites in an Orchiectomized Rat Model of Male Osteoporosis
Heidi Chandler1 and Gary Hattersley2, 1Research, Radius Health Inc, Waltham, MA, 2Radius Health, Inc., Waltham, MA
SESSION INFORMATION
Background/Purpose: Male osteoporosis, a disease of reduced bone mass leading to an increased risk of fragility fractures, often results
from androgen deficiency caused by hypogonadism or androgen deprivation therapy. Abaloparatide (ABL) is an anabolic PTHrP analog that
reduced the incidence of new vertebral and nonvertebral in postmenopausal women with osteoporosis at a high risk for fractures by
increasing bone formation and bone mineral density (BMD) 1. These attributes suggest ABL may have utility for increasing bone mass and
strength in men with osteoporosis. The effects of ABL on bone mass were studied in orchiectomized (ORX) rats, a commonly used
preclinical model of male osteoporosis.
Methods: 40 Male SD rats underwent sham or ORX surgery at 4 months of age. After an 8-week bone depletion period, ORX rats received
vehicle (VEH) or ABL at 5 (ABL5) or 25 (ABL25) μg/kg/d by daily sc injection for 8 weeks (n = 10/group), while sham controls (n = 10)
received VEH. Animals underwent dual X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) scans after
0, 4, and 8 weeks of treatment, followed by necropsy.
Results: DXA conducted 8 weeks after surgery showed the VEH group had significantly lower areal bone mineral content (aBMC) and
density (aBMD) at the whole body, lumbar spine, total femur, and proximal femur (including the hip) vs Sham controls, indicating ORX-
induced osteopenia at the treatment baseline (BL). Between BL and week 8, whole body aBMD increased by 13.8% and 17.3% in the ABL5
and ABL25 groups, respectively, versus 6.3% in VEH controls (both P < 0.001). Lumbar spine aBMD increased from BL to week 8 by
24.5% and 29.1% in the ABL5 and ABL25 groups, versus 7.6% in VEH controls (both P < 0.001). Total femur aBMD increased by 19.3%
and 26.0% from BL to week 8 in the ABL5 and ABL25 groups, versus 7.2% in VEH controls (both P < 0.001). Proximal femur aBMD
(including the hip) increased from BL to week 8 by 16.9% and 23.2% in the ABL5 and ABL25 groups, vs 5.0% in VEH controls (both P <
0.001). By treatment week 8, aBMD values for all four of these sites in the ABL5 and/or ABL25 groups were fully restored to the levels of
Sham controls. pQCT of the tibial diaphysis showed significantly greater gains from BL to week 8 in cortical thickness for the ABL5 (7.3%)
and ABL25 (7.1%) groups compared with VEH controls (0.9%; both P < 0.05). Tibial diaphysis cortical volumetric BMC (vBMC) was also
significantly increased from BL to week 8 in the ABL5 (11.7%) and ABL25 (13.2%) groups compared with VEH controls (6.3%; both P <
0.05). pQCT of the proximal tibial metaphysis showed greater gains in trabecular vBMD in the ABL5 (96.4%) and ABL25 (163.0%) groups
from BL to week 8 compared with VEH controls (6.9%; both P < 0.05).
Conclusion: Androgen deficiency via ORX led to significant deficits in bone mass for the whole body and for axial and appendicular sites in
mature male rats. Abaloparatide fully reversed the ORX-related deficit in whole body bone mass by promoting the accrual of cortical and
trabecular bone. These data provide preclinical support for investigations into the effects of abaloparatide in men with osteoporosis.
1. Miller, JAMA 2016;316:722-33
Disclosure: H. Chandler, Radius Health Inc, 3; G. Hattersley, Radius Health Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/abaloparatide-a-novel-pthrp-analog-increased-bone-

mass-and-density-at-cortical-and-trabecular-sites-in-an-orchiectomized-rat-model-of-male-osteoporosis
Abstract Number: 60
Low and Moderate Intensity Exercise Suppresses Inflammatory Responses in an Acute

Mouse Model of Gout and Suggests Therapeutic Efficacy
Nicholas A. Young1, Kyle Jablonski2, Juhi Sharma1, Evelyn Thomas1, Brian Snoad1, Jeffrey Hampton3, Wael Jarjour1 and Naomi
Schlesinger4, 1Department of Internal Medicine, Division of Immunology and Rheumatology, The Ohio State University Wexner Medical
Center, Columbus, OH, 2The Ohio State University Wexner Medical Center, Columbus, OH, 3Immunology and Rheumatoloty, The Ohio State
University Wexner Medical Center, Columbus, OH, 4Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ
SESSION INFORMATION
Background/Purpose: Little is known regarding the potential benefits of exercise on managing acute gout. Consequently, recent clinical
practice guidelines released by the American College of Rheumatology (2012) and the American College of Physicians (2016) contain no
recommendations regarding exercise in gout patients. Currently, many rheumatologists recommend resting the involved joints during an acute
attack based on animal studies performed nearly a half century ago. Since the potential for exercise to suppress gouty inflammation is an area
of study that has yet to be researched sufficiently, the aim of this study was to determine the efficacy of exercise in an acute mouse model.
Methods: BALB/C-Tg(NFκB-RE-luc)-Xen mice, which contain a firefly luciferase cDNA reporter gene under the regulation of NFκB, were
exercised by daily treadmill walking (45 min/day for 2 weeks) at low intensity (35% VO2max; 8 m/min), moderate intensity (55% VO2max;
11 m/min), and high intensity (75% VO2max; 15 m/min). At the end of the 2 week conditioning period, monosodium urate (MSU) crystal-
induced arthritis was induced by intra-articular injection of MSU (0.5 mg) into the tibio-tarsal joint (ankle) under anesthesia. Localized
NFκB activity was measured using the Xenogen in vivo imaging system (IVIS 200). Serum was collected to measure cytokine expression and
tissue was collected for histological analysis.
Results: Histopathology of feet/ankle regions demonstrated a decrease in cellular infiltrate into the joint spaces by H&E staining and a
marked decrease in macrophage and neutrophils, as indicated by immunohistochemistry and quantification in mice exercised at low intensity
(8 m/min) when compared to non-exercised controls. Low intensity exercise also significantly suppressed serum expression of IL-12,
KC/GRO, TNF-α, and IL-6 in MSU-induced gout mice relative to non-exercised and wild-type controls. Caliper measurements of foot pads
revealed a significant reduction in swelling with both low and moderate exercise when compared to non-exercised controls, while no
difference was observed with high intensity exercise. Additionally, IVIS measurements of the injected ankles demonstrated that NFκB
activity was significantly reduced with low and moderate exercise, but slightly elevated following the high intensity regimen relative to non-
exercised control mice.
Conclusion: Our results from an acute gout mouse model suggest that low and moderate exercise may be effective in decreasing gouty
inflammation. Thus, these data could support a change in the conventional exercise recommendations provided by Rheumatologists in gout
patients. Further studies are needed to more comprehensively evaluate this potentially important observation and to elucidate the mechanism
responsible for this observation.
Disclosure: N. A. Young, None; K. Jablonski, None; J. Sharma, None; E. Thomas, None; B. Snoad, None; J. Hampton, None; W. Jarjour,
None; N. Schlesinger, AstraZeneca, 2,AstraZeneca, 2,AstraZeneca, Horizon, Pfizer, BMS, Celgene, 5,AstraZeneca, Horizon, Pfizer, BMS,
Celgene, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/low-and-moderate-intensity-exercise-suppresses-

inflammatory-responses-in-an-acute-mouse-model-of-gout-and-suggests-therapeutic-efficacy
Abstract Number: 61
Resolution of Systemic Joint Inflammatory Processes and Regeneration of Existing Bone

Damage upon TNF Blockade As Monitored By In Vivo Multimodal PET-CT Imaging in
Progressed Experimental Arthritis
Silvia Hayer1, Markus Zeilinger2,3, Volker Weiss3,4, Markus Seibt5, Birgit Niederreiter1, Tetyana Shvets6, Monika Dumanic6, Florian
Pichler6, Marcus Hacker6, Josef S. Smolen7, Kurt Redlich8 and Markus Mitterhauser6, 1Department of Internal Medicine III, Division of
Rheumatology, Medical University of Vienna, Vienna, Austria, 2Faulty of Engineering, University of Applied Sciences, Winer Neustadt,
Austria, 3Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, 4Faculty of
Engineering, University of Applied Sciences, Wiener Neustadt, Austria, 5Department Internal Medicine III, Division Rheumatology, Medical
University of Vienna, Vienna, Austria, 6Medical University of Vienna, Vienna, Austria, 7Medical University Vienna, Division of
Rheumatology, Department of Internal Medicine III, Vienna, Austria, 8Division of Rheumatology, Medical University of Vienna, Vienna,
Austria
SESSION INFORMATION
Background/Purpose:
To use in vivo multimodal [18F]FDG (fluoro-D-glucose, tracer for inflammation) and [18F]Sodium Fluoride (bone tracer) positron emission
tomography/computed tomography (PET-CT) imaging for the monitoring of systemic inflammatory and bone remodeling processes as well as
colocalized bone destructions before and after TNF blockade in human tumor necrosis factor transgenic (hTNFtg) mice, an established mouse
model of chronic inflammatory, erosive polyarthritis.
Methods:
8 week-old hTNFtg mice were treated with anti-TNF antibodies (Infliximab, i.p., 3x times per week, 10mg/kg body weight) for 4 weeks.
Before and after the treatment period mice received [18F]FDG or [18F]Sodium Fluoride (~25MBq) static PET scans (45min post injection)
followed by whole-body and high resolution leg CT scans (800kV, 500µA, 800ms, 360 projections) using an Inveon PET/CT/SPECT
multimodality system (Siemens Medical Solutions). PET reconstructions were conducted with OSEM3D/MAP, FBP algorithm. Standard
uptake values (SUV) were calculated using PMOD software. Radiographic damage score was evaluated by in vivo CTs using
InveonResearchWorkplace software. Joints were further analyzed by ex vivo µCT scans (Scanco µCT35) and H&E, TRAP and TB stained
paraffin-sections.
Results: Before therapeutic intervention, we observed an increased accumulation of [18F]FDG in various joints of hTNFtg mice including
knees, ankles and shoulders compared to wt littermates indicating ongoing systemic inflammatory processes. Moreover, existing bone
destructions were detected by in vivoCTs. However, [18F]SodiumFluoride was equally accumulated within bone tissues such as long bones,
in particular at growth plates, and vertebrae between both genotypes. After four weeks, placebo-treated hTNFtg animals showed significantly
increased [18F]FDG SUVs as well as progressive bone destruction in knees, ankles and shoulders as shown by in vivoCTs. In contrast, TNF-
blockade led to a significant decrease in [18F]FDG SUVs supposing complete resolution of inflammatory processes in those individuals.
Comparison of repeated in vivoCT images demonstrated a significant reduction in radiographic bone damage score and reversal of existing
bone destructions upon TNF blockade. Histological analysis demonstrated regeneration processes of former bone erosion sites present as
refillings of cartilaginous or fibro-cartilaginous tissue as well as signs of endochondral ossifications or even intact bone surfaces upon TNF
blockade. Surprisingly, we found no marked changes in [18F]Fluoride SUVs in joints between both hTNFtg groups and wt mice suggesting
that age-related high [18F]Fluoride accumulations in growth plates interfere, thus preventing to monitor inflammatory bone damage.
Conclusion: In vivo small animal multimodal [18F]FDG, but not [18F]Fluoride, PET-CT imaging provides an objective, non-invasive
imaging tool for the longitudinal monitoring of (I) reversibility of ongoing inflammatory processes in various joints and (II) regeneration of
existing bone erosions during therapeutic intervention in TNF-driven experimental arthritis.
Disclosure: S. Hayer, None; M. Zeilinger, None; V. Weiss, None; M. Seibt, None; B. Niederreiter, None; T. Shvets, None; M. Dumanic,
None; F. Pichler, None; M. Hacker, None; J. S. Smolen, AbbVie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead,
Glaxo, ILTOO, Janssen, Eli Lilly and Company, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, UCB,
5,AbbVie, Janssen, Eli Lilly and Company, MSD, Pfizer, Roche, 2,AbbVie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai,
Gilead, Glaxo, ILTOO, Janssen, Eli Lilly and Company, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis,
UCB, 8; K. Redlich, None; M. Mitterhauser, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/resolution-of-systemic-joint-inflammatory-processes-and-

regeneration-of-existing-bone-damage-upon-tnf-blockade-as-monitored-by-in-vivo-multimodal-pet-ct-imaging-in-progressed-experimental-
arthritis
Abstract Number: 62
Convergence of Joint Repair and Pain Pathways Via Nerve Growth Factor and p75
Expressing Mesenchymal Stem Cells in Established Osteoarthritis
Thomas Baboolal1, Sumaiya Al Hinai2, Elena Jones2, Jill Reckless3, Martyn Foster4, Rachel Doyle5, Kerry af Forselles4, Simon
Westbrook4 and Dennis McGonagle2, 1PhD, Leeds, United Kingdom, 2Leeds Institute of Rheumatic and Musculoskeletal Medicine,
University of Leeds, Leeds, United Kingdom, 3Rxcelerate Ltd, Cambridge, United Kingdom, 4Levicept Ltd, Ramsgate, United Kingdom,
5Tetrad Discovery Ltd, Ramsgate, United Kingdom
SESSION INFORMATION
Background/Purpose:
Nerve growth factor (NGF) is a key regulator of pain and anti-NGF therapy reduces osteoarthritis (OA) associated pain. However, anti-NGF
therapy is associated with rapidly progressive OA (RPOA) [1]. In hip OA there is a 5-fold increase in mesenchymal stem cells (MSCs) from
MRI bone marrow (BM) lesions, areas associated with OA progression [2]. MSCs in such lesions are uniformly positive for the NGF
receptor, p75, which is also linked to chemotaxis and proliferation in other stromal cell compartments [3]. We therefore sought to evaluate
anti-NGF treatment in monoiodoacetate (MIA) induced OA and test whether NGF influences human BM- MSC function.
Methods:
Human tibial plateau (TP) bone was isolated from patients undergoing total knee replacement. OA was induced in male Wistar rats (n=6) by
intra-articular injection of 0.3 mg MIA. Each animal was treated with subcutaneous injection of control human IgG or anti-NGF (3 mg/kg) on
Days 30, 35, 39, 45 and 50. Human and animal tissues sections were prepared for histological analysis using H&E staining and
immunohistochemistry (IHC) using anti-p75 and anti-NGF antibodies. BM-MSCs were isolated from iliac crest aspirates and cultured under
normal conditions. Expression of p75 was induced following overnight incubation with 400mM ethanol (EtOH) and confirmed by flow
cytometry. Proliferation and chemotaxis was assessed with and without induction of p75 and in the presence of 0-1 μg/ml NGF.
Results:
Regions adjacent to cartilage loss in human TP showed abundant stromal proliferation, NGF and p75 immunoreactivity. In the MIA model, by
Day 28 there was substantial loss of cartilage, bone remodelling and stromal proliferation mimicking human disease and animals
demonstrated unequal weight-bearing (p<0.05). Anti-NGF provided sufficient analgesia to normalise weight-bearing by Day 42. Features
associated with joint damage and MIA treatment such as fibrogranular reactions and palisading osteoblasts were strongly p75
immunopositive. NGF positive staining was widespread in naïve and MIA-injected knees. To investigate increased p75 positivity in knee
OA, we restored p75 expression loss in expanded cell, to 97% of BM-MSCs (n=3) using EtOH. Increased MSC proliferation was seen at
Days 6 and 9 (26%, p=0.03 and 30%, p=0.01 increase respectively, n=7) for 1 μg/ml NGF in the presence of EtOH compared to control (no
NGF). In cultures without EtOH induction (absent p75) NGF had no effect. NGF was not chemotactic for MSCs with or without the induction
of p75.
Conclusion:
TP bone from OA patients and rat MIA-treated subchondral bone contains p75 positive staining in regions of cartilage destruction and
associated NGF positivity. In vitro, NGF increased BM-MSC proliferation, suggesting NGF may be involved in the stromal proliferation
seen at sites of OA damage. Thus, NGF may regulate MSC function. Complete blockade represents a novel mechanism for accelerated joint
destruction in OA.
Reference:
1. Hochberg MC et al. Arthritis Rheumatol 2016;68:382–91. 2.Campbell TM et al Arthritis Rheumatol 2016 Jul;68(7):1648-59. 3. Jiang Y,
Hu C, Yu S, et al. Cartilag Arthritis Res Ther 2015;:1–13.
Disclosure: T. Baboolal, None; S. Al Hinai, None; E. Jones, None; J. Reckless, None; M. Foster, Levicept Ltd, 5; R. Doyle, None; K. af
Forselles, None; S. Westbrook, Levicept Ltd, 1,Levicept Ltd, 3; D. McGonagle, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/convergence-of-joint-repair-and-pain-pathways-via-

nerve-growth-factor-and-p75-expressing-mesenchymal-stem-cells-in-established-osteoarthritis
Abstract Number: 63
MiR-146a a Key Player in Bone Metabolism

Victoria Saferding1, Melanie Hofmann1, Julia S. Brunner2, Antonia Puchner1, Melanie Timmen3, Richard Stange3, Josef S. Smolen4 and
Stephan Blüml4, 1Medical University of Vienna, Austria, Vienna, Austria, 2Vascular Biology and Thrombosis research, Medical University
of Vienna, Austria, Vienna, Austria, 3Institute for Experimental Muskuloskeletal Medicine, University Hospital Muenster, Muenster,
Germany, 4Medical University Vienna, Division of Rheumatology, Department of Internal Medicine III, Vienna, Austria
SESSION INFORMATION
Background/Purpose:
Micro RNAs (miRNAs) play a crucial role in the regulation of bone metabolism. MiR-146a, an important anti-inflammatory miRNA, was
found to negatively impact osteogenesis and bone regeneration in vitro, by controlling the differentiation of mesenchymal stem cells. But to
date the role of miR-146a in bone remodelling, its influence on bone stability and development of osteoporosis is not known.
Methods:
Systemic bone, tibiae and femur, of wt and miR-146a deficient animals was assessed histologically and via µCT analysis, over a period of 3
to 18 months of age. Serum cytokine levels were analysed by Elisa. MRNA expression levels in bone were analysed by qPCR. To induce
osteoporosis, ovariecotmy (OVX) induced bone loss was performed.
Results:
When we analysed bone volume of long bones histologically as well as with µCT analysis we detected significantly increased trabecular
bone mass in miR-146a deficient compared to wt animals, starting at an age of 6 months. However, cortical thickness of systemic bones from
miR-146a knock out animals was significantly reduced compared to control mice. Analysis of serum in aged miR-146a deficient animals
displayed elevated activity of bone resorbing osteoclasts as amounts of CTX I in miR-146a-/- mice were significantly increased compared to
wt animals. Q-PCR analysis of important osteoclast as well as osteoblast marker genes in bones ex vivo displayed elevated expression of
signature molecules of both cell types in aged miR-146a deficient mice, suggesting a regulatory role of miR-146a in both osteoclasts as well
as osteoblasts. When we induced osteoporosis using the OVX disease model, histological analysis of long bones showed significant
trabecular bone loss in ovariectomized wt mice. In contrast, we detected no trabecular bone loss in ovariectomized miR-146a knock out
animals, suggesting that loss of miR-146a deficiency protects bone loss induced by estrogen deficiency.
Conclusion:
MiR-146a seems to control bone turnover and miR-146a deficient mice accrue bone over time. Moreover this miRNA has a negative
influence on bone loss occurring during oestrogen loss induced osteoporosis. Therefore miR-146a could be possibly used as a therapeutic
target in the treatment of osteoporosis.
Disclosure: V. Saferding, None; M. Hofmann, None; J. S. Brunner, None; A. Puchner, None; M. Timmen, None; R. Stange, None; J. S.
Smolen, None; S. Blüml, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/mir-146a-a-key-player-in-bone-metabolism
Abstract Number: 64
The Effect of Adenosine A2A Receptor Stimulation on Mitochondrial Metabolism in the

Pathogenesis and Treatment of Osteoarthritis
Cristina Castro1, Carmen Corciulo2 and Bruce Cronstein3, 1Medicine, NYU School of Medicine, New York, NY, 2Department of
Medicine, Division of Rheumatology, NYU School of Medicine, New York, NY, 3Rheumatology, New York University School of Medicine,
Division of Rheumatology, New York, NY
SESSION INFORMATION
Background/Purpose: Osteoarthritis (OA) is the most common form of arthritis, affecting nearly 10% of the US population. There is no
therapy to prevent the progression of or reverse OA pathology. Endogenous adenosine 2A receptor (A2AR) stimulation is crucial for
chondrocyte viability and cartilage homeostasis as its downstream signaling mediates inflammation. In recent preliminary studies we have
found that mice lacking the A2AR or ecto-5’nucleotidase (CD73, an ectoenzyme critical for extracellular adenosine production) develop
spontaneous OA. These findings suggest that diminished extracellular adenosine levels promote the development of OA. Since human OA
chondrocytes have been found to have diminished mitochondrial content, we propose to test the hypothesis that OA pathogenesis deregulates
A2AR signaling at least in part by affecting the cell's capacity for ATP production via reduced number or functionality of mitochondria.
Methods: A human chondrocyte cell line, TC28a2, was used to determine the effects of IL1B-induced inflammation and A2AR stimulation in
vitro. Cells were treated with IL1B (5ng/mL) and with the A2AR-specific agonist, CGS21680 (CGS; 1uM). Mitochondrial content was
measured by mtDNA to nDNA ratios and MitoTracker mean cellular intensity. Mitochondrial health and functionality was assessed by mean
pixel intensity (MPI) of a fluorescent probe for monitoring mitochondrial membrane potential, TMRM, and by measuring oxygen consumption
rates (OCR) on Seahorse Mito Stress Kit Assays. The role of A2AR ligation on mitochondrial health was also studied by histology for
8hydroxyguanosine (8OH-G) residues as a marker for reactive oxygen species (ROS) in A2ARKO mice and Sprague Dawly rats that
underwent ACL rupture (post-traumatic OA model) and subsequently received CGS-filled liposomal injections.
Results: A2AR agonism increases mitochondrial content in vitro. IL1B incubation for 3 hours followed by A2AR ligation increases
mitochondrial membrane potential (2867±165.5 MPI) compared to control (1582±183.9 MPI), IL1B alone (1483±120.6 MPI) and CGS
alone (1788±137.8 MPI) as measured by TMRM staining (p≤0.0001). IL1B incubation for 4 hours with a last hour of A2AR stimulation
increases basal oxygen consumption rate and maximal respiratory rate. IL1B+CGS treated cells had significantly increased ATP production
(113.04±13.44 of OCR) than the control (83.86±11.89 of OCR), IL1B (81.00±12.80 of OCR) and CGS (76.04± 23.52 of OCR) treated cells
as measured by one-way ANOVA (p values =**0.0088, *0.0128, and *0.0259 respectively). A2ARKO mice exhibit increased 8OG-G
staining in histology as early as 8 weeks. A2AR stimulation after ACL rupture in rats, results in preserved cartilage volumes, improved
OARSI scores (p<0.001) and reduced ROS as seen by reduced 8OH-G staining in histology.
Conclusion: A2AR ligation improves mitochondrial functionality during inflammation and OA progression. Increased mitochondrial function
is not seen when the chondrocytes are treated with IL1B or CGS alone; perhaps suggesting that A2AR stimulation is necessary to maintain
homeostasis when cells are already under physiological or pathological stress.
Disclosure: C. Castro, None; C. Corciulo, None; B. Cronstein, NIH grant, 2,Athritis foundation grant, 2,AstraZeneca, 2,Celgene, 2,Eli Lilly
& Co., 5,AstraZeneca, 5,Canfite Biopharma, 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-effect-of-adenosine-a2a-receptor-stimulation-on-

mitochondrial-metabolism-in-the-pathogenesis-and-treatment-of-osteoarthritis
Abstract Number: 65
RA-Associated Antibodies Targeting Post Translational Modification Have Different

Osteoclastogenetic Potential
Akilan Krishnamurthy1, Johanna Steen2, Caroline Grönwall3, Gustaf Wigerblad4, Camilla Svensson5,6, Heidi Wähämaa1, Vivianne
Malmström1, Bence Rethi1 and Anca I. Catrina1, 1Rheumatology Unit, Department of Medicine, Karolinska Institute, Karolinska University
Hospital, Stockholm, Sweden, 2Dept. of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm,
Sweden, 3Dep. of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, 4Department of
Medicine, Solna, Karolinska Institutet, Stockholm, Sweden, 5Dept. of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden,
6Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
SESSION INFORMATION
Background/Purpose:
Some but not all antibodies against citrullinated modified proteins (ACPA) promote osteoclastogenesis and bone destruction in vitro and in
vivo. We aimed to investigate the ACPA specificity pattern that is related to this effect and if this effect is limited to ACPA or encompasses
also other RA-associated antibodies.
Methods:
Polyclonal ACPA IgG and IgGs others than ACPA were obtained from the peripheral blood of RA patients by purification on a G column
followed by an anti-CCP2 column. Monoclonal ACPA, anti-MDA and rheumatoid factor (RF) IgGs were generated from either single plasma
cells isolated from the synovial fluid or tetramer-positive sorted single B-cell isolated from the plasma of RA patients. Osteoclasts were
generated from CD14+ monocytes of healthy individuals or bone marrow cells of Fc gamma III or Fc gamma chain knockout mice, in the
presence or absence of polyclonal ACPA, monoclonal antibodies (ACPA, and anti-MDA antibodies and RF) and IgG controls. TRAP
positive multinucleated cells were counted and bone erosion assay was done in parallel.
Results:
Polyclonal ACPA increased osteoclastogenesis, by a fold of 1.6±0.03One out of 4 tested plasma cell derived monoclonals ACPAs and one
out of the five tested tetramer positive B-cell derived monoclonals have similar effects (with a fold increase of 1.63 ±0.15 for the plasma
cell derived antibody and 1.4± 0.16 for the tetramer positive B-cell derived) have similar OC effects. Two additional tetramer positive B-
cell derived monoclonals inhibited osteocalstogenesis while the remaining had no significant effect. All monoclonal ACPA were relatively
highly cross-reactive to several citrullinated epitopes but not to native arginine peptides. Anti-MDA monoclonals antibodies displaying
somatic hypermutations and low reactivity had significant in vitro functional properties and enhanced osteoclastogenesis (fold increase of for
somatic hypermutations and low reactivity had significant in vitro functional properties and enhanced osteoclastogenesis (fold increase of for
one antibody 4.0±0.76 and fold increase of for the second one 2.3±0.2), while the natural antibody related high-reactivity anti-MDA antibody
did not. Anti MDA antibodies had no cross reactivity to other antigen modifications such as citrullination or carbamylation. Monoclonal RF
had no direct effect on ostecoalstogenesis but were able to significantly increase ACPA-mediated osteoclastogenesis (fold increase of 1.68
±0.03 for ACPA alone and for the combination of ACPA and RF 3.15±0.24). Dimeric Fab fragments of polyclonal ACPA increased OC
numbers by a fold of 1.78, suggesting that epitope recognition is involved in the observed osteocalstogenetic effect of ACPA. Interestingly
however while ACPA increased osteoclastogenesis from bone marrow precursors of wild type mice, it had no effect on the bone marrow
precursors of the Fc gamma chain knockout and Fc gamma III mice bone marrow samples, implying a more complex mechanism than epitope
recognition alone that involves Fc receptors.
Conclusion:
We demonstrate that RA-associated antibodies targeting different post translational modifications have the capacity to increase
osteoclastogenesis while others have not. The mechanism is mediated through both Fc dependent and independent mechanisms.
Disclosure: A. Krishnamurthy, None; J. Steen, None; C. Grönwall, None; G. Wigerblad, None; C. Svensson, None; H. Wähämaa, None;
V. Malmström, None; B. Rethi, None; A. I. Catrina, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/ra-associated-antibodies-targeting-post-translational-

modification-have-different-osteoclastogenetic-potential
Abstract Number: 66
Genome-Wide DNA Methylation Profiling of OA PBMCs Reveals Slowed Epigenetic

Aging Among Rapid Radiographic Progressors: Data from the Osteoarthritis Initiative
(OAI)
Alexander Rivas1, Madison Andrews2 and Matlock A. Jeffries3, 1Rheumatology, Immunology, and Allergy, University of Oklahoma Health
Sciences Center, Oklahoma City, OK, 2College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK,
3Department of Medicine, Division of Rheumatology, Immunology, and Allergy, University of Oklahoma Health Sciences Center, Oklahoma
City, OK
SESSION INFORMATION
Background/Purpose: Extensive evidence has correlated epigenetic alterations in articular tissues with both the presence and progression of
human osteoarthritis. A recent study demonstrated that accelerated DNA methylation aging was present in OA cartilage compared to controls
but not in peripheral blood samples from a mixed population of knee, hip, and hand OA patients. To further clarify epigenetic age changes
specifically in knee OA, we examined the DNA methylation aging rate in peripheral blood mononuclear cells (PBMCs) at baseline from knee
OA patients with rapid radiographic progression compared to well-matched nonprogressors enrolled in the Osteoarthritis Initiative (OAI).
Methods: Peripheral blood mononuclear cell (PBMC) DNA was obtained from baseline blood draws of 64 OA patients enrolled in the
Osteoarthritis Initiative (OAI) longitudinal study. 32 rapidly-progressive OA patients, defined as ≥1.0mm radiographic joint space loss or
joint replacement within the first 24 months of follow-up were compared to 32 non-progressive OA patients defined as ≤0.5mm radiographic
joint space loss over 48 months of follow-up. There were no differences in age, sex, race, BMI, baseline K/L grade, or calculated PBMC
subset composition between rapid- and non-progressors. DNA methylation was quantified with Illumina HumanMethylation 450k arrays.
Epigenetic age was estimated with the algorithm described by Horvath et. al., using 353 age-associated CpG sites. This epigenetic age was
compared to chronological age to calculate epigenetic-chronological age discordance (ΔAge) and group differences compared with a Student
t-test. ΔAge was correlated with individual CpG methylation sites of rapid progressors, and Pearson values calculated. Correlation was
considered significant if Pearson’s r values were ≤-0.55 or ≥0.55 (p≤0.001). Pathway analysis of correlated genes was performed with the
Ingenuity Pathway Analysis (IPA) system.
Results: The baseline DNA methylation aging rate in rapidly progressive (RP) knee OA patients was decelerated compared to
nonprogressors (NP) and to chronological age (ΔAge-RP: -4.9±1.4 vs. ΔAge-NP: -0.071±1.3 mean±SEM years less than chronological age,
p=0.015). 1165 CpG sites were correlated with ΔAge in rapid progressors, corresponding to 755 genes. Ontologic analysis of highly
correlated genes showed association of the STAT3 pathway (p=6E-4), Notch signaling (p=1E-3), axonal guidance signaling (p=7E-3),
CREB signaling (p=2E-2), NFAT signaling (p=2E-2), and autophagy (p=4E-2) among others. Associated upstream regulators included FGF2
(p=3E-5), SMAD4 (p=9E-4), SMAD5 (p=1E-3, TNF (p=4E-3), and TGFB1 (p=4E-3), among others.
Conclusion: Our data reveal that a decelerated peripheral blood differential DNA methylation age epigenotype is present at baseline in
rapidly progressive knee OA patients, but not in nonprogressive knee OA patients. The genes correlated with this methylation age
deceleration cluster in pathways previously associated with OA in articular tissues. Our data reinforce the notion that OA is a heterogeneous
disease composed of distinct subgroups, and suggests that future epigenetic investigation of immune cell subsets may be beneficial in
unraveling OA pathogenesis.
Disclosure: A. Rivas, None; M. Andrews, None; M. A. Jeffries, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/genome-wide-dna-methylation-profiling-of-oa-pbmcs-

reveals-slowed-epigenetic-aging-among-rapid-radiographic-progressors-data-from-the-osteoarthritis-initiative-oai
Abstract Number: 67
The Oxygen Sensor PHD1 Is an Indispensable Regulator of Arthritis Development

Katelijne De Wilde1, Peggy Jacques2 and Dirk Elewaut3, 1Inflammation Research Center - VIB UGhent, Molecular Immunology and
Inflammation Unit, Ghent, Belgium, 2Ghent University Hospital, Ghent, Belgium, 3VIB Inflammation Research Center, University of Ghent,
Ghent, Belgium
SESSION INFORMATION
Background/Purpose: Oxygen supply is a fundamental requirement for all living tissues. Some tissues such as articular joints are
characterized by a physiological state of hypoxia. Interestingly, under conditions of inflammation such as in arthritic disease, this level of
hypoxia is even further enhanced. However, the functional significance of these observations and the molecular mechanisms involved remain
poorly characterized to date. We therefore examined the role of 3 known oxygen sensors, prolyl hydroxylase domain (PHD) proteins: PHD1,
PHD2 and PHD3. They are enzymes whose function is essentially controlled by oxygen. Their expression pattern varies between either of
them and all of them have been ascribed specific roles in a myriad of biological processes. Our goal was to examine the role of oxygen
sensors PHD1, PHD2 and PHD3 in preclinical models of rheumatoid arthritis, and to delineate the cellular source involved.
Methods: We subjected the collagen antibody induced arthritis (CAIA) model (resembling rheumatoid arthritis) to hypoxic (10% O2) and
normoxic conditions (21% O2), respectively. Furthermore, the CAIA-model was induced in mice with germline deficiency of the specific
PHD’s and in mice with a myeloid cell-specific PHD1 deficiency versus controls. Arthritis development was assessed by clinical scoring of
paw swelling, histopathology of knee joints and μCT.
Results: Mice kept in hypoxic conditions during CAIA experiments showed markedly less arthritis (both by clinical and histopathological
assessment) compared to mice in normoxic conditions. Furthermore, we demonstrated that PHD1 knock-out (KO) mice had significantly less
joint inflammation compared to wildtype mice. PHD1 KO mice were also protected against inflammation induced bone loss as evidenced by
μCT. By contrast, no differences were found between PHD2 heterozygous (PHD2 KO mice are not viable) or PHD3 KO mice and littermate
controls. Because myeloid cells are considered critical effector cells upon passive transfer of arthritogenic antibodies in the CAIA model we
also generated myeloid cell specific ko mice (PHD1myelKO). Of interest, PHD1myelKO mice developed less arthritis compared to wildtype
mice and were protected against inflammation induced bone loss.
Conclusion: Our data are consistent with a new paradigm that the oxygen sensor PHD1 is a critical regulator of myeloid cell function in
arthritic disease. Overall, the data suggest that PHD1 is a potential target in the treatment of arthritis.
Disclosure: K. De Wilde, None; P. Jacques, None; D. Elewaut, Scientific Research Flanders; Research Council Ghent University;
Interuniversity Attraction Pole., 2,Boehringer Ingelheim; Pfizer; UCB; Merck; Novartis; Janssen; Abbvie, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-oxygen-sensor-phd1-is-an-indispensable-regulator-of-

arthritis-development
Abstract Number: 68
Tankyrase/Wnt Inhibitor Upregulates Osteoclastogenesis and Osteoblastogenesis Via
SH3BP2
Shunichi Fujita1, Tomoyuki Mukai1, Takafumi Mito1, Shoko Kodama1, Akiko Nagasu1, Mizuho Kittaka2, Yasuyoshi Ueki3 and Yoshitaka
Morita1, 1Department of Rheumatology, Kawasaki Medical School, Kurashiki, Okayama, Japan, 2Department of Oral and Craniofacial
Sciences, School of Dentistry, University of Missouri-Kansas City, Missouri-Kansas City, MO, MO, 3Department of Oral and Craniofacial
Sciences, School of Dentistry, University of Missouri-Kansas City, Missouri-Kansas City, MO
SESSION INFORMATION
Background/Purpose: Tankyrase is a poly (ADP-ribose) polymerase that leads to ubiquitination and degradation of target proteins. Since
tankyrase inhibitors increase Axin protein, a negative regulator of Wnt pathway, they are widely used as Wnt inhibitors. Tankyrase inhibitors
have attracted the attention as a promising drug candidate for cancer and fibrotic diseases, in which Wnt pathways are critical in the
pathogenesis. Tankyrase has recently been reported to degrade an adaptor protein SH3BP2 (SH3 domain-binding protein 2). We have
previously shown that SH3BP2 gain-of-function mutation enhances RANKL-induced osteoclastogenesis in murine bone marrow-derived
macrophages (BMMs). Though the interaction between tankyrase and SH3BP2 has been reported, it is not fully elucidated whether tankyrase
is involved in bone metabolism. In this study, we investigated the effect of tankyrase inhibition in bone metabolism in vitro and in vivo.
Methods: Primary murine BMMs from wild-type (WT) mice and SH3BP2 knockout (KO) mice and human peripheral blood mononuclear
cells (PBMCs) were treated with tankyrase inhibitors (IWR-1 or G007-LK) in the presence of RANKL. Osteoclasts formation, function and
intracellular signaling were analyzed by TRAP staining, resorption assay and western blotting, respectively. Primary calvarial osteoblasts
from WT mice and SH3BP2 KO mice were also cultured with tankyrase inhibitors. Osteoblast differentiation and intracellular signaling were
analyzed by qPCR, Alizarin red staining and western blotting. To examine in vivo effect of the tankyrase inhibitor, 7-week-old WT male
mice were treated with G007-LK for 4 weeks, and then tibias and lumber vertebras were analyzed by micro-CT.
Results: In murine BMMs and human PBMCs culture, both tankyrase inhibitors enhanced osteoclast formation and function. Tankyrase
inhibitors increased SH3BP2 protein and augmented phosphorylation of Syk and nuclear localization of NFATc1 in response to RANKL.
Moreover, in SH3BP2 KO BMMs culture, tankyrase inhibitors did not promote osteoclast formation, indicating that the osteoclast-inducing
effect is mediated by SH3BP2. Next, in primary calvarial osteoblasts culture, tankyrase inhibitors significantly increased osteoblast-
associated genes expression and enhanced mineralization even though they have Wnt inhibitory effect. The osteogenic effect of tankyrase
inhibitors were diminished by SH3BP2 deficiency, suggesting increased SH3BP2 expression enhanced osteoblastogenesis by surpassing the
Wnt inhibitory effect. Finally, in vivo experiment, the administration of G007-LK significantly decreased trabecular bone volume of both
tibias and vertebras.
Conclusion: Tankyrase inhibition upregulates both osteoclastogenesis and osteoblastogenesis through the accumulation of SH3BP2. Our
findings highlight the role of tankyrase as the novel regulator of bone metabolism. Also, we demonstrated that in vivo administration of the
tankyrase inhibitor induces bone loss. This indicates that we should carefully evaluate the potential adverse effect on bone when tankyrase
inhibitors are applied to patients with cancer or fibrotic diseases.
Disclosure: S. Fujita, None; T. Mukai, Takeda Pharmaceutical Co., Ltd., 2,Pfizer Japan Inc., 2,Mitsubishi Tanabe Pharma Co., 2,Chugai
Pharmaceutical Co., Ltd., 2,AbbVie GK, 2,TEIJIN Pharma Ltd., 2,Astellas Pharma Inc., 2,Japan Blood Products Organization, 2,Shionogi ＆
Co., Ltd., 2,Actelion Pharmaceuticals Japan Ltd., 2,Eli Lilly Japan K.K., 2,DAIICHI SANKYO Co., Ltd., 2,UCB Japan Co. Ltd., 2; T. Mito,
None; S. Kodama, None; A. Nagasu, None; M. Kittaka, None; Y. Ueki, None; Y. Morita, Takeda Pharmaceutical Co., Ltd., 2,Pfizer Japan
Inc., 2,Mitsubishi Tanabe Pharma Co., 2,Chugai Pharmaceutical Co., Ltd., 2,AbbVie GK, 2,TEIJIN Pharma Ltd., 2,Astellas Pharma Inc.,
2,Japan Blood Products Organization, 2,Shionogi ＆ Co., Ltd., 2,Actelion Pharmaceuticals Japan Ltd., 2,Eli Lilly Japan K.K., 2,DAIICHI
SANKYO Co., Ltd., 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/tankyrasewnt-inhibitor-upregulates-osteoclastogenesis-

and-osteoblastogenesis-via-sh3bp2
Abstract Number: 69
The Effect of Myostatin Inhibition on Bone Loss in Murine Osteoporosis Models

Tomoyuki Mukai1, Takafumi Mito1, Shunichi Fujita1, Shoko Kodama1, Akiko Nagasu1, Teruki Sone2, Shinichiro Nishimatsu3, Yutaka
Ohsawa4, Yoshihide Sunada4 and Yoshitaka Morita1, 1Department of Rheumatology, Kawasaki Medical School, Kurashiki, Okayama,
Japan, 2Department of Nuclear Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan, 3Department of Natural Sciences,
Kawasaki Medical School, Kurashiki, Okayama, Japan, 4Department of Neurology, Kawasaki Medical School, Kurashiki, Okayama, Japan
SESSION INFORMATION
Background/Purpose:
Myostatin, also called as growth differentiation factor-8 (GDF-8), is a secreted member of TGF-β superfamily. Myostatin is a negative
regulator of skeletal muscle mass as shown by increased muscle mass in myostatin-deficient mice. A recent study reported the regulatory role
of myostatin on bone metabolism (Dankbar B, et al. Nat Med 2015). The study showed that myostatin directly regulates osteoclastogenesis
and its inhibition reduces inflammatory joint destruction in murine arthritis models. In contrast to this, another group reported that myostatin
inhibition by the administration of anti-myostatin antibody did not affect bone mass of femur and vertebra in wild-type mice (Bialek P, et al.
Bone 2014). Therefore, it is still controversial whether myostatin inhibition could regulate bone mass. Here, we report the effect of genetic
inhibition of myostatin on bone loss in murine osteoporosis models.
Methods:
We used mutant myostatin transgenic (MstnPro) mice, in which myostatin prodomain, an endogenous myostatin suppressor, is excessively
expressed and subsequently inhibits myostatin activity. For a RANKL-induced osteoporosis model, 1 mg/kg of RANKL was injected
intraperitoneally at day 0 and 1, and the sera and bones were collected at day 2. For a tail-suspension unloading model, the tails of mice were
suspended for 2 weeks. At the end of the period, the sera and bones were collected. Serum TRAP5b and P1NP levels were measured by
ELISA. Bone properties of vertebra and tibia were determined by micro-CT. For cell culture experiments, bone marrow cells were isolated
from long bones of wild-type (WT) and MstnPro mice. Bone marrow-derived macrophages (BMMs) were treated with RANKL, and then
osteoclast differentiation and function were determined by TRAP staining and resorption assay.
Results:
MstnPro mice exhibited increased muscle mass similarly to the previously reported myostatin null mice. RANKL injection induced severe
bone loss in MstnPro mice to the similar extent to that seen in WT mice (WT: 31.0 ± 10.0% reduction, MstnPro: 42.8 ± 9.6% reduction
compared to control mice of each genotype). Serum TRAP5b and P1NP levels were also comparable between RANKL-treated WT and
MstnPro mice. In the tail-suspension model, genetic inhibition of myostatin did not also prevent bone loss. In WT BMMs culture, myostatin
stimulation slightly enhanced RANKL-induced osteoclastogenesis. Osteoclast formation and resorbed area in response to RANKL were
comparable between WT and MstnPro BMMs.
Conclusion:
Genetic inhibition of myostatin did not alleviate bone loss in the osteoporosis models we tested. The role of myostatin inhibition might vary
in different pathological conditions (e.g. inflammatory or non-inflammatory conditions). Further research will be required to clarify the
clinical implications of myostatin inhibition in various disease settings.
Disclosure: T. Mukai, Takeda Pharmaceutical Co., Ltd., 2,Pfizer Japan Inc., 2,Mitsubishi Tanabe Pharma Co., 2,Chugai Pharmaceutical Co.,
Ltd., 2,AbbVie GK, 2,TEIJIN Pharma Ltd., 2,Astellas Pharma Inc., 2,Japan Blood Products Organization, 2,Shionogi ＆ Co., Ltd., 2,Actelion
Pharmaceuticals Japan Ltd., 2,Eli Lilly Japan K.K., 2,DAIICHI SANKYO Co., Ltd., 2,UCB Japan Co. Ltd., 2; T. Mito, None; S. Fujita,
None; S. Kodama, None; A. Nagasu, None; T. Sone, None; S. Nishimatsu, None; Y. Ohsawa, None; Y. Sunada, None; Y. Morita, Takeda
Pharmaceutical Co., Ltd., 2,Pfizer Japan Inc., 2,Mitsubishi Tanabe Pharma Co., 2,Chugai Pharmaceutical Co., Ltd., 2,AbbVie GK, 2,TEIJIN
Pharma Ltd., 2,Astellas Pharma Inc., 2,Japan Blood Products Organization, 2,Shionogi ＆ Co., Ltd., 2,Actelion Pharmaceuticals Japan Ltd.,
2,Eli Lilly Japan K.K., 2,DAIICHI SANKYO Co., Ltd., 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-effect-of-myostatin-inhibition-on-bone-loss-in-

murine-osteoporosis-models
Abstract Number: 70
Excessive Cyclic Compressive Stress Increases Susceptibility to IL-1 in 3D-Cultured

Chondrocytes
Yuki Takeda1, Yasuo Niki2, Yusuke Fukuhara2, Yoshitsugu Fukuda2, Kazuhiko Udagawa2, Toshiyuki Kikuchi2, Takeshi Miyamoto2, Morio
Matsumoto2 and Masaya Nakamura2, 1Department of Orthopaedic Surgery, Keio University, Tokyo, Japan, 2Keio University, Tokyo, Japan
SESSION INFORMATION
Session Title: Cytokines, Mediators, Cell-Cell Adhesion, Cell Trafficking and Angiogenesis Poster I: The Variable World of Intercellular
Signalling
Background/Purpose: The mechanism of chondrocyte mechanotransduction is not fully understood. Recently, transient receptor potential
vanilloid 4 (TRPV4) has been reported to transduce dynamic compressive loading in articular chondrocytes. The expression of the IL-1
receptor 1 (IL-1R1) on the surface of chondrocytes can be stimulated by compressive stress, and such increment of IL-1 susceptibility has
been implicated in the OA pathology. The purpose of this study was to examine mechanical induction of IL-1R1 by chondrocytes in three-
dimensional (3D) culture, and the effects of TRPV4 channel regulation on IL-1R1 expression. Methods: Mouse embryonal carcinoma-
derived clonal cell line (ATDC5) was used and cultured in alginate beads with the growth medium for 6 days. These cells were collected
and seeded in collagen gels and scaffolds, which maintained chondrogenic phenotype in 3D environment (Fig.1). Cyclic compressive loading
of 40 kPa at 0.5Hz was applied to this 3D constructs using a cyclic load bioreactor for 3 hours. Thereafter, the PGE2 concentration and
mRNA expressions of Col-II, ADAMTS4 and IL-1R1 were measured in real-time PCR. The effects of subtle amount of IL-1beta (1pg/ml)
was determined with or without compressive stress, and the effects of TRPV4 agonist/antagonist on IL-1-induced ADAMTS4 was
determined. Results: The PGE2 production in culture media and mRNA levels of ADAMTS4 and IL-1R1 were substantially increased by the
excessive compressive stress. Compressive stress plus IL-1beta (1pg/ml) upregulated ADAMTS4 and IL-1R1 expressions by 3-fold and 8-
fold, respectively, but IL-1beta alone failed to do so (Fig.2). TRPV4 agonist suppressed upregulation of ADAMTS4 and IL-1R1 mRNAs by
cyclic compressive stress, conversely, TRPV4 antagonist rather accelerated these mRNA expressions (Fig.3). Conclusion: In chondrogenic
3D environment, the cells gained IL-1 susceptibility under excessive cyclic compressive stress. In this context, the cells would produce
ADAMTS4 and MMPs in response to subtle level of IL-1 derived from synovia or cartilage itself, whereas TRPV4 downregulated
expression of IL-1R1 and control IL-1 susceptibility to maintain cartilage homeostasis. To control IL-1 susceptibility is a key to prevent the
development of OA, when excessive mechanical stress is applied on the articular cartilage.
Disclosure: Y. Takeda, None; Y. Niki, None; Y. Fukuhara, None; Y. Fukuda, None; K. Udagawa, None; T. Kikuchi, None; T. Miyamoto,
None; M. Matsumoto, None; M. Nakamura, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/excessive-cyclic-compressive-stress-increases-

susceptibility-to-il-1-in-3d-cultured-chondrocytes
Abstract Number: 71
The Critical Role of Interleukin-33 in Promoting Angiogenesis and Regulates

Inflammation through Mast Cells in Takayasu Arteritis
Anne-Claire Desbois1, Patrice Cacoub2, Aurélie LEROYER3, Edwige Tellier4, Marlène Garrido5, Anna Maciejewski-Duval6, Cloé
Comarmond7, Stéphane Barete6, Michel Arock6, Patrick Bruneval8, Jean-Marie Launay9, Pierre Fouret10, Ulrich Blank11, Michelle
Rosenzwajg6, David Klatzman12, Mohamed Jarraya13, Philippe Cluzel14, Fabien Koskas15, Gilles Kaplanski16 and David Saadoun17,
1Hôpital Pitié-Salpêtrière, Internal Medicine and Clinical Immunology, Paris, France, 2Department of Internal Medicine and Clinical
Immunology, Groupe Hospitalier Pitié-Salpêtrière, Paris, France, 3Faculté de Pharmacie, Marseille, France, 4Université Marseille,
Marseille, France, 5I3 laboratory, Pitié-Salpétrière, Paris, France, 6GHPS, Paris, France, 7DHU 2iB Internal Medicine Referal Center for
Autoimmune diseases Pitie Hospital, Paris, France, 8HEGP, Paris, France, 9Hôpital lariboisière, Paris, France, 10Hôpital La Pitié
Salpétrière, Paris, France, 11Hôpital Bichat, Paris, France, 12UPMC Université Paris 06, UMR 7211, Paris, France, 13Hôpital Saint Louis,
Paris, France, 14Department of cardiovascular imagery, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié
Salpétrière, 83 Boulevard de l'Hôpital, 75013, Paris, France., Paris, France, 15Department of vascular surgery, Assistance Publique-
Hôpitaux de Paris (AP-HP), Paris, France, 16Aix-Marseille Université - Internal Medicine hopital conception - F-13000 Marseilles,
Marseille, France, 17Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department
(DHU i2B), F-75005, Paris, France; INSERM, UMR_S 959, F-75013, Paris, France; CNRS, FRE3632, F-75005, Paris, France; AP-HP,
Groupe Hospitalier, Paris, France
SESSION INFORMATION
Signalling
Background/Purpose:
Large vessel vasculitis (LVV) include Takayasu arteritis (TA) and giant cell arteritis (GCA). Arterial lesions in LVV result from chronic
inflammation and neoangiogenesis. IL-33, a cytokine involved in angiogenesis and vascular permeability has been previously found
overexpressed in arteries of large vessel vasculitis. We aimed at assessing its effects on the regulation of immune response and angiogenesis.
Methods:
In vitro studies on angiogenesis were performed by using human endothelial cells to assess migration, proliferation and angiogenesis.
Vascular permeability was assessed in vivo, using Miles assay. The effects of IL-33 on immune response were determined by assessing the
production of cytokines by Multiplex in cultures of peripheral mononuclear cells (PBMC) with or without IL-33 stimulation and the
proportion of regulatory T cells in cultures of mast cells and CD4+ T cells with or without IL-33 stimulation.
Results:
We identified increased IL-33 levels in serum and in inflammatory lesions of TA and GCA patients as compared to controls. Sera from TA
patients have angiogenic properties by promoting HUVECs proliferation, tube and sprout formation and were also able to induce vessel
permeability in vivo. The addition of neutralizing anti-IL-33 antibody inhibits neoangiogenesis, migration of endothelial cells in vitro and
vascular permeability in vivo. As mast cells are one of the main targets of IL-33, we repeated these experiments in mast-cells deficient mice
in which in vivo effects were abolished. Significant increased number of mast cells was observed in aorta lesions of both diseases as
compared to non-inflammatory aorta controls. IL-33 overexpression was accompanied by an increased expression of Th2-related cytokines
by enhancing the secretion of IL-5 and IL-4. IL-33 also promoted the regulatory immune response by increasing the proportion of regulatory T
(Tregs) cells. Consistently, IL-33 and mast cells dramatically increased the proportion of Tregs and the activity of indoleamine 2 3-
dioxygenase (IDO).
Conclusion:
IL-33/ST2 axis, through its interaction with mast cells, has a critical role in the pathogenesis of LVV.
Disclosure: A. C. Desbois, None; P. Cacoub, None; A. LEROYER, None; E. Tellier, None; M. Garrido, None; A. Maciejewski-Duval,
None; C. Comarmond, None; S. Barete, None; M. Arock, None; P. Bruneval, None; J. M. Launay, None; P. Fouret, None; U. Blank,
None; M. Rosenzwajg, None; D. Klatzman, None; M. Jarraya, None; P. Cluzel, None; F. Koskas, None; G. Kaplanski, None; D.
Saadoun, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-critical-role-of-interleukin-33-in-promoting-

angiogenesis-and-regulates-inflammation-through-mast-cells-in-takayasu-arteritis
Abstract Number: 72
The Presence of IgM Rheumatoid Factor Impede Immunodetection of Tnfa on

Circulating Extracellular Vesicles Obtained from Rheumatoid Arthritis Patients
Onno J. Arntz 1, Bartijn C.H. Pieters1, Rogier Thurlings2, Peter M. van der Kraan3, F van den Hoogen2 and Fons A.J. van de Loo3,
1Experimental Rheumatology, Radboudumc, Nijmegen, Netherlands, 2Rheumatology, Radboudumc, Nijmegen, Netherlands, 3Experimental
Rheumatology, Radboud university medical center, Nijmegen, Netherlands
SESSION INFORMATION
Signalling
Background/Purpose: Tumor-necrosis factor (TNF)-α plays a key role in the pathophysiology of rheumatoid arthritis (RA) and membrane
bound TNFα is sufficient to induce arthritis in mice [1]. Zhang [2] demonstrated membrane bound TNFα on extracellular vesicles (EVs)
derived from RA synovial fibroblasts. EVs are stable in body fluids and mediate intercellular communication over short and long distances.
In this study we want to determine whether TNFα is also present on circulating EVs from RA patients and not in healthy individuals.
Methods: pEVs were obtained from 28 RA patients and 24 healthy controls (HC) by size exclusion chromatography. Protein content was
measured by micro-BCA, size and concentration by Nanoparticle Tracking. TNFα was detected by bead-based multiplex immunoassays
(BBI) and flowcytometry (FC). To control for specificity, pEVs were preincubated with anti-TNFα (etanercept and certolizumab pegol).
Immunoglobulin M rheumatoid factor (IgM-RF) was measured in pEVs by ELISA. RF+ and RF- pEVs were preincubated with Protein L
beads to bind RF-IgM before TNFα was measured by FC.
Results: Particle size and protein content per particle were significantly higher in RA-pEVs as compared to HC (154nm, 484fg and 116nm,
216fg, resp) while particle concentration was not statistically different between RA patients and HC (0.89, 2.59 x1010/ml, resp). In 13 out of
28 RA patients TNFα (220 pg/ml) was detectable in pEVs by BBI whereas in HC TNFα was undetectable. Presence of TNFa on RA-pEVs
was confirmed by FC. Preincubation of pEVs with anti-TNFα antibodies (etanercept) fully blocked TNFα detection. Unexpected, after
preincubation with anti-TNFα Fab fragments (certolizumab pegol) TNFα was still detectable which suggested aspecific binding of the TNFa
detection antibody. By ELISA IgM-RF was detectable on pEVs in 9 out of 13 RA patients. By preincubation with Protein-L coupled magnetic
beads, to scavenge RF, TNFα levels on pEVs isolated from RF+ RA patients were reduced to background.
Conclusion: This study shows for the first time that IgM-RF is present on pEVs in a subpopulation of RA patients and this impedes with
immunodetection of TNFα. To obtain conclusive evidence for the presence of TNFα other laboratory techniques are needed. However, the
presence of RF on EVs could be important in the immunopathophysiology of RA by directing putative immunoregulatory and potentially
inflammatory EVs to sites of immune-complex formation.
1: Keffer. EMBO J. (1991)
2: Zhang. J Immunol (2006)
Disclosure: O. J. Arntz, None; B. C. H. Pieters, None; R. Thurlings, None; P. M. van der Kraan, Contract research UCB, 2; F. van den
Hoogen, None; F. A. J. van de Loo, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-presence-of-igm-rheumatoid-factor-impede-

immunodetection-of-tnfa-on-circulating-extracellular-vesicles-obtained-from-rheumatoid-arthritis-patients
Abstract Number: 73
Regulation of Th17 Cell Responses By IL-25

Sophie Archer, Ash Maroof, Meryn Griffiths and Stevan Shaw, UCB Pharma, Slough, United Kingdom
SESSION INFORMATION
Signalling
Background/Purpose:
IL-17A is a Th17 proinflammatory cytokine that contributes to the pathophysiology of several immune-mediated inflammatory diseases
including PsA; while previously underestimated, there is increasing evidence supporting a similar proinflammatory role for IL-17F. IL-17E
(IL‑25), another IL-17 cytokine, is implicated in Th2 responses, and signals via the IL‑17RA/RB receptor complex, sharing the IL-17RA
subunit with IL-17A and IL-17F. Extending upon previous work, we hypothesized that IL-25 indirectly regulates production of Th17 cell
cytokines,1 and a broad range of other inflammatory mediators through effects on polyfunctional T cells. Consequently, selectively targeting
IL-17A and IL-17F may offer a therapeutic alternative, in the treatment of immune-mediated inflammatory diseases, to targeting broader
signaling pathways by interfering with IL-25. The aim of this study was to investigate the effects of IL-25 on Th17 and polyfunctional T cell
responses.
Methods:
Isolated human Th17 cells or peripheral blood mononuclear cells (PBMCs) were either stimulated with Th2 cytokines (IL-4, IL-5 and/or IL-
13, IL-25) or Th2-cytokine neutralizing antibodies (10 µg/mL) for 72 hrs, to assess their modulatory effect on Th17 cells in addition to other
Th cell subsets. Cytokines in cell supernatant and intracellular cytokines were measured using ELISA and flow cytometry, respectively. To
investigate how IL-25 or IL-4 affected polyfunctional T cell responses, PBMCs were stimulated with these cytokines for 72 hrs and
intracellular cytokine production was assessed by mass cytometry.
Results:
While IL-25 did not effectively inhibit IL-17A production in stimulated PBMCs, IL-25 did elevate levels of IL-4 in treated versus untreated
PBMCs. In contrast to IL-25, IL-4 effectively reduced the percentage of PBMCs expressing IL-17A and IL-17F and inhibited the secretion of
IL-17A; the opposite effect was observed using anti-Th2-cytokine antibodies. Both IL-25 and IL-4 inhibited polyfunctional T cell production
of the proinflammatory molecules IL-17A, IL-17F, TNF, and IFNγ (Figure 1).
Conclusion: Taken together these data show that IL-25, via IL-4, indirectly modulates IL‑17A and IL-17F production, as well as production
of a variety of other proinflammatory molecules (including TNF and IFNγ), through effects on Th17 and polyfunctional T cells. Targeted dual
neutralization of IL-17A and IL-17F may therefore produce optimal inhibition of inflammatory signaling responses in immune-mediated
inflammatory diseases, without interfering with the regulatory role of IL-25.
1Liu et al. Sci Rep 2016;6(36002)
Figure 1: IL-4 and IL-25 (10 ng/mL) regulate production of proinflammatory cytokines from polyfunctional T cells.
Disclosure: S. Archer, Crescendo Biologics, Cambridge, 3,UCB Pharma, 3; A. Maroof, UCB Pharma, 3,UCB Pharma, 9; M. Griffiths,
UCB Pharma, 3; S. Shaw, UCB Pharma, 3,UCB Pharma, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/regulation-of-th17-cell-responses-by-il-25
Abstract Number: 74
IL-17 Blockade Attenuates Osteoblastic Activity and Differentiation in Ankylosing

Spondylitis
Sungsin Jo1, Ye-Soo Park2, Il-Hoon Sung3 and Tae-Hwan Kim1, 1Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea,
Republic of (South), 2Orthopaedic, Hanyang University Guri Hospital, Guri, Korea, Republic of (South), 3Orthopaedic, Hanyang University
Seoul Hospital, Seoul, Korea, Republic of (South)
SESSION INFORMATION
Signalling
Background/Purpose:
Ankylosing spondylitis (AS) is a chronic inflammatory bone disease mediated by proinflammatory cytokine secreted by specialized T cells
population. The mechanism by which the development of and function of Th17 cells and emerging IL-23/IL-17 axis may be involved in the
pathogenesis of AS. However, the effect of IL-17 and IL-23 in osteoblast remain to be elucidated.
Methods:
AS patients satisfying the modified New York criteria were recruited for the study. Healthy donor, rheumatoid arthritis patients and
osteoarthritis patients were included as controls. TNFa, IL-17, and IL-23 level were quantized by ELISA in the serum and synovial fluid.
Bone tissues were obtained at surgery from facet joints of 10 patient with AS and 26 patients with noninflammatory spinal disease from
traffic trauma or spinal compression disease, who served as controls. Immunohistochemistry and RNA level of bone tissue and isolated
primary osteoprogenitor cells were performed to identify dominant JAK2 expression. IL-17 cytokine or patient serum with AS stimulated
primary osteoprogenitor cells was analyzed by intercellular alkaline phosphatase (ALP) activity, mineralization, real-time PCR, and
immunoblotting.
Results:
IL-17 and IL-23 basal level were significantly elevated in serum and synovial fluid of AS patients compared to those of the controls.
Expression of JAK2 was enriched in bone tissues and isolated primary osteoprogenitor cells of AS patient. An addition of IL-17 cytokine in
osteogenic differentiation exhibited an increase in ALP activity and calcium deposit in cellular level and sustained phos-JAK2 and phos-
STAT3, and C/EBPβ in molecular level. Furthermore, adding IL-17A blockade in presence of patient serum with AS upon differentiation
exhibited reduced intercellular ALP activity, mineralization, and phos-JAK2 expression in both control and AS osteoprogenitor cells.
Intriguing, AG490, a JAK2 specific inhibitor, suppressed ALP activity despite the presence of patient serum with AS.
Conclusion:
This study supports a role of IL-17A in the pathogenesis of AS and attempts to provide a link between proinflammatory cytokine and
osteoblast activity in an unexplored cellular system. Blocking of IL-17 could attenuate bony ankyloses in AS.
Disclosure: S. Jo, None; Y. S. Park, None; I. H. Sung, None; T. H. Kim, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/il-17-blockade-attenuates-osteoblastic-activity-and-

differentiation-in-ankylosing-spondylitis
Abstract Number: 75
Factors Associated with TNF Receptor 2 Levels Above the Measurable Range in
Rheumatoid Arthritis
Michelle Frits1, Gary Bradwin2, Nancy A. Shadick1, Christine Iannaccone3, Michael Weinblatt1, Nader Rifai2 and Katherine P. Liao4,
1Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 2Laboratory Medicine,
Childrens Hospital Boston, Boston, MA, 3Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, 4Division
of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
SESSION INFORMATION
Signalling
Background/Purpose: Tumor necrosis factor-alpha (TNFa) is involved in the pathogenesis of RA and is increasingly being studied as a
biomarker of cardiovascular disease (CVD). While TNF receptor 2 (TNFR2) and TNFa levels are correlated, TNFR2 is used more
frequently as a biomarker in studies because of its stability in stored blood samples. We investigated whether TNF inhibitor (TNFi) use may
influence measured TNFR2 levels. Since the mechanism of action for TNFi is binding TNFa, a component of these drugs is a TNF receptor.
Thus, we hypothesize that there may be cross-reactivity between specific TNFi’s and the TNFR2 assay.
Methods: All subjects were part of a CVD sub-study performed in a large prospective RA cohort study with blood samples collected
annually, data on treatment and C-reactive protein (CRP). TNFR2 was measured using a commercial ELISA kit (R&D Systems,
Minneapolis, MN). We categorized TNFR2 levels into 3 groups: (1) >46 and £10,000 pg/mL, typical range; (2) >10,000 pg/mL and
≤100,000 pg/mL, samples requiring 200-fold dilution; (3) >100,000 pg/mL, levels exceeding measurable values. We examined the
association individual TNFi’s and having a TNFR2 level in group 3. Additionally, we assessed the correlation between natural log
transformed CRP and TNFR2.
Results: We studied 190 RA subjects, mean age 60 years, 84% female, 73% anti-CCP positive and CRP ranged from 0.31-310 mg/L.
Subjects on TNFi comprised 47% of the study: 14% on adalimumab, 26% on etanercept, and 8% on infliximab (no subjects on certolizumab
or golimumab). All subjects with TNFR2 exceeding measurable levels (group 3) were on etanercept (Table). Samples that required 200-
fold dilution (group 2) not on etanercept therapy had higher levels of CRP compared to those on etanercept (Table). We observed no
significant correlation between CRP and TNFR2 for all subjects, r=0.05, p=0.51. After excluding subjects on etanercept, the correlation was
significant, r=0.46. p<0.0001 (Figure). We observed no significant changes in the correlation between CRP and TNFR2 after excluding
patients on adalimumab or infliximab.
Conclusion: Our data suggest cross-reactivity between etanercept and the TNFR2 assay, as 100% of subjects on etanercept had levels of
TNFR2 above measurable levels. Of the TNFi’s, only etanercept has a TNF binding domain modeled after TNFR2. Thus, it is plausible that
the TNFR2 assay has a high affinity for the TNFR portion of etanercept. These data should be considered when designing studies using
TNFR2 in populations where etanercept is a treatment option.
Disclosure: M. Frits, None; G. Bradwin, None; N. A. Shadick, Mallinckrodt, 2,Amgen, 2,Bristol-Myers Squibb, 2,UCB, 2,DxTerity,
2,Sanofi, 2,Crescendo Biosciences, 2,Bristol-Myers Squibb, 5; C. Iannaccone, None; M. Weinblatt, Amgen, BMS, Crescendo Bioscience,
UCB, Genzyme, 2,Amgen, Abbvie, BMS, Eli Lilly and Company, Gilead, Merck, Pfizer, Novartis, Roche, UCB, Crescendo Bioscience,
Genzyme, Samsung, 5; N. Rifai, None; K. P. Liao, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/factors-associated-with-tnf-receptor-2-levels-above-the-

measurable-range-in-rheumatoid-arthritis
Abstract Number: 76
TNF-α Potentiates Uric Acid-Induced Interleukin-1β Secretion in Human Neutrophils

Shuzo Sato1, Makiko Yashiro1, Tomoyuki Asano1, Tomohiro Koga2, Eiji Suzuki1, Hiroko Kobayashi1, Hiroshi Watanabe1 and Kiyoshi
Migita3, 1Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan, 2Department of Immunology and
Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, 3Fukushima Medical University School of
Medicine, Fukushima, Japan
SESSION INFORMATION
Signalling
Background/Purpose: Gout is an inflammatory arthropathy due to the deposition of uric acid (monosodium urate: MSU) crystals in synovial
tissue. MSU leads to activate nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)
inflammasome and following IL-1beta secretion via caspase-1 activation in human monocytes. Synthesis of mature IL-1beta is a 2-step
processes. In the 1st step, microbial-derived signals (binding of bacterial products such as LPS) up-regulate pro-IL-1beta, resulting in
synthesis of pro-IL-1beta. However, priming signals for NLRP3 infammasome pathway had not been completely elucidated in sterile
inflammatory arthritis including gout. In this study, we investigated the role of TNF-alpha on MSU-mediated IL-1beta induction in human
neutrophils.
Methods: Venous peripheral blood was collected from healthy volunteers. Human neutrophils were stimulated with MSU (200 µg/ml), in the
presence or absence of TNF-alpha priming (2 to 50 ng/ml). The cellular supernatants were analyzed for IL-1beta, IL-18 and caspase-1 by
ELISA. Pro-IL-1beta mRNA expressions in human neutrophils were analyzed by real-time PCR.
Results: TNF-alpha stimulation induced pro-IL-1beta mRNA expression, however, MSU stimulation alone did not induce pro-IL-1beta
mRNA expression in neutrophils. TNF-alpha alone or MSU stimulation did not result in efficient IL-1beta secretion. Whereas MSU
stimulation to TNF-alpha-primed neutrophils resulted in a marked IL-1beta (Figure 1) as well as IL-18 secretion. TNF-alpha-primed
neutrophils secreted cleaved caspase-1 (p20) with MSU stimulation.
Conclusion: These results indicate that priming of human neutrophils with TNF-alpha promotes uric acid-mediated NLRP-3 activation and
IL-1beta secretion in the absence of microbial stimulation, that provide new insights into the neutrophils-mediated inflammatory processes in
gouty arthritis.
Figure 1. MSU induces IL-1beta synthesis from TNF-alpha-pretreated neutrophils.
Disclosure: S. Sato, None; M. Yashiro, None; T. Asano, None; T. Koga, None; E. Suzuki, None; H. Kobayashi, None; H. Watanabe,
None; K. Migita, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/tnf-%ce%b1-potentiates-uric-acid-induced-interleukin-

1%ce%b2-secretion-in-human-neutrophils
Abstract Number: 77
Platelets Induce IL-1b Production in Human Monocytes through NLRP3

Inflammasome Activation
Shota Nakano1, Hiroki Mitoma1, Shotaro Kawano1, Shoichiro Inokuchi2, Masahiro Ayano1, Yasutaka Kimoto3, Mitsuteru Akahoshi1,
Yojiro Arinobu1, Koichi Akashi1, Takahiko Horiuchi4 and Hiroaki Niro5, 1Department of Medicine and Biosystemic Science, Graduate
School of Medical Sciences, Kyushu University, Fukuoka, Japan, 2Department of Medicine and Biosystemic Science, Kyushu University
Graduate School of Medical Sciences, Fukuoka, Japan, 3Department of Internal Medicine, Kyushu University Beppu Hospital, Oita, Japan,
4Department of Internal Medicine, Kyushu University Beppu Hospital, Beppu, Japan, 5Department of Medical Education, Kyushu University
Graduate School of Medical Sciences, Fukuoka, Japan
SESSION INFORMATION
Signalling
Background/Purpose: Recent studies have revealed that platelets play pivotal roles in inflammation in addition to hemostasis. The thrombus
induces subsequent local inflammation and reversely the local inflammation results in the formation of thrombus. Therefore, to suppress
activation of platelets is important for preventing tissue damages. In this study, we aim to reveal effects of activated platelets on IL-1b
production in human PBMCs and to clarify the mechanism.
Methods: We investigated whether IL-1b production is enhanced by co-culture of PBMCs and platelets compared to PBMCs alone. We
analyzed the production of IL-1 b in co-culture of each fraction of PBMCs, T cells, B cells, NK cells and monocytes with platelets. NLRP3,
or caspase-1 was knocked down by shRNA in THP-1 monocytes, and IL-1b production induced by co-culture with platelets were compared
among shRNA-cell lines and scramble controls. We investigated mediators derived from platelets that induced IL-1 b production from
monocytes, using inhibitors and neutralization antibodies. Furthermore, we compared CD16 positive monocytes with CD16 negative
monocytes, regarding IL-1b productivities, expression levels of NLRP3 and caspase-1 mRNA, and platelets-monocytes-aggregates (PMA)
ratios. Activation of platelets in inflammatory diseases, rheumatoid arthritis (RA) and Behcet's disease (BD) were analyzed using CD62P
and PMA ratio.
Results: IL-1b production was enhanced by co-culture of PBMCs with platelets compared to PBMCs alone. Among PBMCs, monocytes
showed the most prominent IL-1b production by co-culture with platelets. NLRP3- and caspase-1-knockdown THP-1 cells showed
significantly lower IL-1b production in co-culture with platelets than scramble controls. CCR5 inhibitor and ATP inhibitor significantly
attenuated IL-1b production of monocytes co-cultured with platelets. CD16-positive monocytes produced more IL-1b in co-culture with
platelets than CD16-negative monocytes. CD16-positive monocytes showed higher NLRP3 mRNA expression and higher PMA ratio than
CD16-negative monocytes. Platelets were activated in patients with active RA and BD compared to health controls.
Conclusion: Platelets stimulate monocytes and have the ability to enhance IL-1b production via CCL 5 and ATP. They activate NF-kB
pathway and NLRP3 inflammasomes in monocytes and enhance IL-1b production. Among monocytes, CD16-positive monocytes are highly
bound to platelets and produce IL-1b. Activated platelet may be involved in disease progression of inflammatory diseases.
Disclosure: S. Nakano, None; H. Mitoma, None; S. Kawano, None; S. Inokuchi, None; M. Ayano, None; Y. Kimoto, None; M. Akahoshi,
None; Y. Arinobu, None; K. Akashi, None; T. Horiuchi, None; H. Niro, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/platelets-induce-il-1b-production-in-human-monocytes-

through-nlrp3-inflammasome-activation
Abstract Number: 78
IL-37 Is Associated with Increased Atherogenesis in Patients with Rheumatoid Arthritis

Barbora Sumova1,2, Tereza Lennerova1,2, Lucie Andres Cerezo1, Hana Hulejova1, Romana Jandova1, Karel Pavelka1,2, Jiri Vencovsky1,2
and Ladislav Senolt1,2, 1Institute of Rheumatology, Prague, Czech Republic, Prague, Czech Republic, 2Department of Rheumatology, 1st
Faculty of Medicine, Charles University, Prague, Czech Republic, Prague, Czech Republic
SESSION INFORMATION
Signalling
Background/Purpose: Interleukin-37 (IL-37) is one of few anti-inflammatory cytokines belonging to the IL-1 cytokine family. It is mainly
produced by immune cells of innate immunity such as monocytes and dendritic cells. Recent data suggest its role in several autoimmune and
cardiovascular diseases. The aim of this study was to analyse the expression of IL-37 in synovial tissue, synovial fluid (SF) and serum of
patient with established rheumatoid arthritis (RA) and osteoarthritis (OA) and to analyse its potential role in the pathogenesis of RA.
Methods: Serum and synovial fluid levels of IL-37 were determined in 52 patients with established RA and 49 control subjects with
osteoarthritis (OA) by ELISA. All RA patients fulfilled the 2010 ACR/EULAR criteria for RA. Disease activity was assessed based on the
Disease Activity Score of 28 joints (DAS28-ESR). For in vitro studies, fibroblast-like synoviocyte (FLS) were obtained from patients with
RA and OA (n=6-9). Serum C-reactive protein (CRP) and lipid profile were determined. Immunofluorescence and immunohistological
staining was used to localize IL-37 protein expression in synovial tissue cells (n=4-6) and FLS.
Results: The expression of IL-37 was upregulated in synovial tissue of patients with RA compared to OA, and co-localized with B-
lymphocyte, T-lymphocyte, fibroblast-like synoviocyte (FLS) and macrophage specific markers. Further, stimulation with lipopolysacharide
(LPS) increased the nuclear expression of IL-37 in synovial fibroblasts cell cultures. The serum levels of IL-37 were significantly higher
compared to synovial fluid levels of RA and OA patients (77.50 ± 56.73 vs. 51.50 ± 43.17, p<0.001; 57.00 ± 73.25 vs. 27.00 ± 38.38,
p<0.001, respectively). Further, the synovial fluid levels, but not the serum levels, of IL-37 were significantly higher in RA patients
compared to OA patients (77.50 ± 56.73 vs. 57.00 ± 73.25, p<0.01) and there was a significant correlation between serum and synovial fluid
IL-37 levels in RA patients (r=0.55, p<0.001). Although, neither serum nor synovial fluid IL-37 levels were associated with disease activity,
synovial fluid IL-37 levels positively correlated with a leukocytes count in SF (r=0.33, p<0.05) and serum levels of CRP (r=0.31, p<0.05).
Interestingly, serum levels of IL-37 negatively correlated with high density lipoprotein (HDL) levels (r=-0.33, p<0.05) and positively with
atherogenic index (r=0.34, p<0.05), but not with low density lipoprotein (LDL)-cholesterol, triacylglycerol (TAG) or total cholesterol
levels.
Conclusion: Our data suggest possible role of IL-37 in accelerated atherosclerosis and increased cardiovascular burden in patients with RA.
Acknowledgement: This study was supported by Research Project No. 00023728.
Disclosure: B. Sumova, None; T. Lennerova, None; L. Andres Cerezo, None; H. Hulejova, None; R. Jandova, None; K. Pavelka, None;
J. Vencovsky, Samsung Bioepis Co., Ltd., Biogen, 5; L. Senolt, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/il-37-is-associated-with-increased-atherogenesis-in-

patients-with-rheumatoid-arthritis
Abstract Number: 79
Functional Analysis of the Novel G58V Mutation in the TNFRSF1A Gene Identified in a
Family with TNF Receptor-Associated Periodic Syndrome (TRAPS)
Shoko Kodama1, Hidenori Matsuzaki2, Tomoyuki Mukai1, Akiko Nagasu1, Masanori Iseki3, Nami Kurosaki1, Takafumi Mito1, Shunichi
Fujita1, Takahiko Horiuchi4, Ryuta Nishikomori5 and Yoshitaka Morita1, 1Department of Rheumatology, Kawasaki Medical School,
Kurashiki, Okayama, Japan, 2Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama, Japan, 3Department of Immunology
and Molecular Genetics, Kawasaki Medical School, Kurashiki, Okayama, Japan, 4Department of Internal Medicine, Kyushu University
Beppu Hospital, Beppu, Japan, 5Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan
SESSION INFORMATION
Signalling
Background/Purpose: Mutations in the TNFRSF1A, which encodes tumor necrosis factor receptor 1 (TNFR1), are associated with the
autosomal dominant disease TNF Receptor- Associated Periodic Syndrome (TRAPS). TRAPS is an autoinflammatory disease characterized
by intermittent self-limited inflammatory episodes of fever. More than 100 heterozygous TNFRSF1A mutations associated with TRAPS or
TRAPS-like clinical phenotype have been reported. T50M mutation and cysteine mutations are reported to cause intracellular accumulation
of TNFR1 and exhibit a severe disease phenotype. Single nucleotide polymorphism in TNFR1, such as T61I and R92Q mutations, occurs in
1-5% of the general population and can be associated with a TRAPS-like phenotype. Therefore, there are multiple responsible mechanisms
to induce inflammation in patients with TRAPS, and the molecular pathogensis is not yet fully understood. Recently we have identified a
novel mutation, G58V (p.G87V) in TNFRSF1A, in two individuals in a family. They also had T61I mutation, and had suffered from recurrent
episodes of intermittent fever and abdominal pain. In this study, we functionally characterized this novel G58V TNFRSF1A mutation.
Methods: The possible pathogenicity of the G58V mutation was analyzed using the four online prediction tools (SIFT, Polyphen2,
PROVEAN and PANTHER). Wild-type (WT) or mutated TNFRSF1A (T50M, G58V, T61I, R92Q) constructs were generated by cloning the
individual cDNAs into the pcDNA3.1 vector. The TNFR1 constructs were transfected into HEK-293 cells. Expression levels of the TNFR1
were examined by western blotting. To evaluate the NF-κB promoter activity, HEK-293 cells were transfected with the TNFR1 constructs
along with NF-κB promoter-driven luciferase plasmid and the secreted alkaline phosphatase control vector pSEAP. NF-κB activation levels
at 24 hours after the transfection were measured by the dual-luciferase reporter assay.
Results: The novel G58V mutation was predicted to be a highly damaging amino acid substitution that could cause a disease. The result is
similar to those of pathogenic T50M and cysteine mutations. Expression levels of the WT and mutated TNFR1 proteins are comparable in the
whole cell lysates of HEK-293 cells. NF-κB promoter activities in the T50M or the G58V TNFR1-expressing cells were significantly
decreased compared to those in WT TNFR1-expressing cells (mean±SD; T50M 29.6±7.5% vs. WT 100±11.5%, p<0.001; G58V 40.1±0.9%
vs. WT, p<0.001). The T61I mutation showed a small but significant reducation in NF-κB promoter activity (67.4±18.8%, p<0.05 vs. WT).
In contrast, the R92Q mutation did not suppress NF-κB promoter activity (93.2±18.4%).
Conclusion: Consistent with a previous report (Blood 2006;108:1320-1327), the T50M mutation suppressed spontaneous NF-κB promoter
activity, in spite of the clinical inflammatory features of TRAPS. The newly identified G58V mutation developed the similar phenotype to the
pathogenic T50M mutation. These findings indicate that G58V could be a responsible mutation causing TRAPS.
Disclosure: S. Kodama, None; H. Matsuzaki, None; T. Mukai, Takeda Pharmaceutical Co., Ltd., 2,Pfizer Japan Inc., 2,Mitsubishi Tanabe
Pharma Co., 2,Chugai Pharmaceutical Co., Ltd., 2,AbbVie GK, 2,TEIJIN Pharma Ltd., 2,Astellas Pharma Inc., 2,Japan Blood Products
Organization, 2,Shionogi ＆ Co., Ltd., 2,Actelion Pharmaceuticals Japan Ltd., 2,Eli Lilly Japan K.K., 2,DAIICHI SANKYO Co., Ltd., 2,UCB
Japan Co. Ltd., 2; A. Nagasu, None; M. Iseki, None; N. Kurosaki, None; T. Mito, None; S. Fujita, None; T. Horiuchi, None; R.
Nishikomori, None; Y. Morita, Takeda Pharmaceutical Co., Ltd., 2,Pfizer Japan Inc., 2,Mitsubishi Tanabe Pharma Co., 2,Chugai
Pharmaceutical Co., Ltd., 2,AbbVie GK, 2,TEIJIN Pharma Ltd., 2,Astellas Pharma Inc., 2,Japan Blood Products Organization, 2,Shionogi ＆
Co., Ltd., 2,Actelion Pharmaceuticals Japan Ltd., 2,Eli Lilly Japan K.K., 2,DAIICHI SANKYO Co., Ltd., 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/functional-analysis-of-the-novel-g58v-mutation-in-the-

tnfrsf1a-gene-identified-in-a-family-with-tnf-receptor-associated-periodic-syndrome-traps
Abstract Number: 80
Production and Characterization of Human Interferon-Epsilon and Interferon-Kappa to

Investigate Their Potential Role in Lupus
Bethany D. Harris1, Jessica Schreiter2, Matteo Cesaroni3, Marc Chevrier3, Jarrat Jordan3, Jacqueline Benson3 and Mark R. Walter1,
1Microbiology, University of Alabama at Birmingham, Birmingham, AL, 2Estrela Lupus Venture, Janssen Research and Development, LLC.,
Spring House, PA, 3Janssen Research and Development, LLC., Spring House, PA
SESSION INFORMATION
Signalling
Background/Purpose: IFNє and IFNκ are members of the type-I IFN family that also consists of 12 IFNα subtypes, IFNβ, and IFNω. IFNє
and IFNκ share approximately 35% sequence identity with each other and the other 14 IFN proteins. In contrast, IFNα subtypes and IFNω
share 60%-95% sequence identity. The role of human IFNє and human IFNk in autoimmune disease in general, and SLE in particular, is
unknown. However, the unique expression of IFNє in vaginal tissues, and IFNκ in the skin, are consistent with the sex bias and extensive
cutaneous manifestations of lupus. Work to understand the role of IFNє/κ in SLE has been hampered by a paucity of quality reagents for
biochemical and biological analysis. To overcome this problem, we have produced and purified human IFNє and IFNκ from E. coli for
biochemical and functional studies.
Methods: The IFNs were expressed, refolded, and purified from E.coli, and characterized using SDS-PAGE gel electrophoresis, mass
spectrometry, surface plasmon resonance, gene expression using reporter cells lines and PCR, and ELISAs performed using serum for Lupus
patients.
Results: Purified IFNє and IFNκ bind to the IFNAR receptors and induce reporter cell gene activation. Gene expression induced by IFNє, or
IFNκ, was neutralized by anti-IFNAR neutralizing antibodies, but not by the anti-IFNα neutralizing antibodies examined. IFNє and IFNκ both
induced a type-I IFN gene signature in human whole blood. ELISA studies suggest serum from some SLE patients contain antibodies that
recognize IFNє or IFNκ.
Conclusion: Taken together, these data suggest IFNε and IFNκ may be contributing to the dysregulated type-I IFN environment observed in
some lupus patients, making them putative targets for anti-IFN therapy.
Disclosure: B. D. Harris, Janssen Research and Development, LLC., 2; J. Schreiter, Janssen Pharmaceutica l, 3; M. Cesaroni, Janssen
Pharmaceutica Product, L.P., 3; M. Chevrier, Johnson & Johnson, 1,Janssen Research Development LLC, 3; J. Jordan, Janssen Research &
Development, LLC, USA., 1,Janssen Research & Development, LLC, USA., 3; J. Benson, Janssen Pharmaceutica Product, L.P., 3; M. R.
Walter, Janssen Research and Development, LLC., 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/production-and-characterization-of-human-interferon-

epsilon-and-interferon-kappa-to-investigate-their-potential-role-in-lupus
Abstract Number: 81
Selective Inhibition of the Immunoproteasome Subunit LMP7 Is Not Sufficient for

Blocking Cytokine Production or Attenuating Progression of Experimental Arthritis
Eric Lowe 1, Janet Anderl1, R Andrea Fan1, Henry W. B. Johnson2, Christopher J Kirk3 and Tony Muchamuel4, 1Biology, Kezar Life
Sciences, South San Francisco, CA, 2Medicinal Chemistry, Kezar Life Sciences, South San Francisco, CA, 3Kezar Life Sciences, South San
Francisco, CA, 4Pharmacology and Toxicology, Kezar Life Sciences, South San Francisco, CA
SESSION INFORMATION
Signalling
Background/Purpose:
The proteasome inhibitor (PI) PR-957/ONX 0914 blocks cytokine production in vitro and attenuates disease progression in experimental
models of rheumatoid arthritis (RA) (Nature Medicine 2009 15;781-788). While these anti-inflammatory effects were demonstrated to be
due to inhibition of the immunoproteasome versus the constitutive proteasome, there remained a question as to which immunoproteasome
subunits, LMP7, LMP2, or MECL-1, were necessary and sufficient for these effects. Here we utilize subunit-selective PIs to address this
question.
Methods:
Proteasome subunit inhibition was measured in mice following administration and/or in MOLT-4 cells (human leukemia) and human PBMCs
following exposure to the immunoproteasome subunit-selective inhibitors, ONX 0914 (LMP7, LMP2, MECL-1), KZR-329 (LMP7), KZR-
504 (LMP2), and KZR-082 (MECL-1), via a subunit active site occupancy assay (ProCISE). Cytokine release (TNF-α, IL-6, IL-12/23p40
[p40], and IFN-γ) was measured in human PBMCs stimulated with either endotoxin (LPS) or antibodies to CD3 and CD28 (anti-CD3/CD28)
via Meso Scale Discovery electrochemiluminescent detection (MSD). Cell viability was measured by CellTiter-Glo. The therapeutic effect
of selective inhibitors alone or in combination was evaluated in the Collagen Antibody-Induced Arthritis (CAIA) mouse model of RA.
Results:
Consistent with previous studies, at a concentration that inhibited multiple immunoproteasome subunits, ONX 0914 blocked secretion of all
cytokines tested in stimulated PBMCs. KZR-329 partially blocked secretion of p40 following LPS stimulation and IFN-γ following anti-
CD3/CD28 stimulation, but had minimal effect on TNF-α and IL-6. KZR-504 and KZR-082 had no effect on cytokine production. A
combination of KZR-329 and either KZR-504 or KZR-082 resulted in a blockade of cytokine release similar to that of ONX 0914. Blockade
of all 3 immunoproteasome subunits resulted in enhanced cytokine inhibition compared to the combination of any 2 selective inhibitors,
although the triple combination also resulted in a slight decrease in cell viability. In the CAIA model, KZR-329 resulted in a slight
attenuation of disease progression, while KZR-504 treatment had no effect. However, in combination, these two inhibitors prevented disease
progression at a level similar to ONX 0914.
Conclusion:
Selective inhibition of individual immunoproteasome subunits resulted in minimal decreases in cytokine production in vitro, and was not
sufficient to prevent disease progression in a mouse model of RA. Combined inhibition of LMP7 and LMP2, comparable to that achieved
with ONX 0914, blocked multiple inflammatory cytokines in vitro and attenuated disease progression in mice. These data suggest that
development of selective inhibitors of the immunoproteasome that target multiple subunits will be necessary in order to achieve a therapeutic
benefit in rheumatic diseases such as RA.
Disclosure: E. Lowe, Kezar Life Sciences, 3; J. Anderl, Kezar Life Sciences, 3; R. A. Fan, Kezar Life Sciences, 3; H. W. B. Johnson,
Kezar Life Sciences, 3; C. J. Kirk, Kezar Life Sciences, 3; T. Muchamuel, Kezar Life Sciences, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/selective-inhibition-of-the-immunoproteasome-subunit-

lmp7-is-not-sufficient-for-blocking-cytokine-production-or-attenuating-progression-of-experimental-arthritis
Abstract Number: 82
CKD-506, a Novel Inhibitor of Histone Deacetylase 6 (HDAC6) Has a Therapeutic

Potential in Rheumatoid Arthritis and Inflammatory Bowel Disease
Jieun Shin1, Nina Ha1, Daekwon Bae1, Dong-Hyeon Suh1, Yu Jin Jang2, Sehui Shon3, Ji-yeon Baek1, Jae Hyun Jun1, Yong Jae Lee1,
Changsik Lee1, Sei-Hwan Kim1, Hosung Yu1, Young Il Choi1, Keun Ho Ryu1, Soung-Min Lee4, Yeong Wook Song2, Su K Seo4 and Seong
Kon Kim1, 1Research Institute of Chong Kun Dang Pharmaceutical Corporation, Yongin, Korea, Republic of (South), 2Department of
Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine,
Seoul National University, Seoul, Korea, Republic of (South), 3Department of Molecular Medicine and Biopharmaceutical Sciences,
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College
of Medicine, Seoul National University, Seoul, Korea, Republic of (South), 4Department of Microbiology and Immunology, Inje University
College of Medicine, Busan, Korea, Republic of (South)
SESSION INFORMATION
Signalling
Background/Purpose: Autoimmune disease such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) is a chronic
inflammatory disorder, significantly limiting quality of life. Even though the dramatic improvement with the new therapeutics had appeared
over the past dedicates, there is still huge unmet medical needs. Recently, it was reported that epigenetic regulation is deeply involved in the
development of autoimmune disease and that the inhibition of histone deacetylase showed significant immunomodulation. Herein, we
introduce highly potent and selective histone deacetylase 6 inhibitor CKD-506 as a novel therapeutic drug for RA and IBD.
Methods: The inhibitory activity and selectivity of CKD-506 for HDAC6 were determined by enzyme assay. The acetylation of tubulin in
PBMCs by CKD-506 was determined by western blot. The in vivo efficacy of CKD-506 in RA or IBD was evaluated in adjuvant (AIA)- and
collagen (CIA)-induced arthritis or DSS- and CD4+CD45RBhi T cell adaptive transfer-induced colitis animal model respectively. To test the
effect of CKD-506 on T cell function, CFSE-labeled effector T cells (Teff) from mouse splenocytes were co-cultured with Treg in the
presence of CKD-506 and Teff proliferation was analyzed by flow cytometry. The ex vivo anti-inflammatory effect of CKD-506 was tested
with peripheral mononuclear cells (PBMCs) or synoviocytes from RA patients. The effect of CKD-506 on inflammatory mediators in T cell
adaptive transfer colitis was screened by real time RT-PCR.
Results: CKD-506 was had a potent and selective inhibitory activity on HDAC6 with an IC50 of 5 nM. CKD-506 highly induced acetylation
of tubulin a substrate for HDAC6 in human PBMCs and lymphoid tissue collected from normal rat. In the arthritis animal models, CKD-506
inhibited severity of arthritis in a dose dependent manner and showed strong synergistic efficacy with methotrexate combination. The
proliferation of Teff was suppressed by CKD-506. Interestingly, the CKD-506 significantly inhibited TNF a but induced IL-10 production in
PBMCs. CKD-506 inhibited IL-1b induced CCL-2, CXCL-8, CXCL-10 production in fibroblast-like synoviocytes from RA patients. In IBD
animal models, CKD-506 significantly repressed disease progression and highly inhibited the expression of inflammatory mediators in colon
tissues of T cell adaptive transferred colitis animal. (Current status: Phase I in EU, EudraCT number: 2016-002816-42)
Conclusion: The novel HDAC6 inhibitor, CKD-506 had a therapeutic potential in autoimmune disease such as RA and IBD through the
inhibition of inflammatory mediators and the regulation of T cell functions.
Disclosure: J. Shin, Chond Kun Dang Research Institute, 2; N. Ha, Chong Kun Dang Research Institute, 2; D. Bae, Chong Kun Dang
Research Institute, 2; D. H. Suh, Chong Kun Dang Research Institute, 2; Y. J. Jang, Chong Kun Dang Research Institute, 2; S. Shon, CKD
Research Institute, 2; J. Y. Baek, Chong Kun Dang Research Institute, 2; J. H. Jun, Chong Kun Dang Research Institute, 2; Y. J. Lee, Chong
Kun Dang Research Institute, 2; C. Lee, Chong Kun Dang Research Institute, 2; S. H. Kim, Chong Kun Dang Research Institute, 2; H. Yu,
Chong Kun Dang Research Institute, 2; Y. I. Choi, CKD Research Institute, 2; K. H. Ryu, Chong Kun Dang Research Institute, 2; S. M. Lee,
Chong Kun Dang Research Institute, 2; Y. W. Song, CKD Research Institute, 2; S. K. Seo, Chong Kun Dang Research Institute, 2; S. K. Kim,
Chong Kun Dang Research Institute, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/ckd-506-a-novel-inhibitor-of-histone-deacetylase-6-

hdac6-has-a-therapeutic-potential-in-rheumatoid-arthritis-and-inflammatory-bowel-disease
Abstract Number: 83
Whole Blood Stimulations Identify Elevated T Cell Cytokines and Altered

Granulocyte/Dendritic Cell Signaling in SLE Patients with Variable Disease Activity
Samantha Slight-Webb1, Krista M. Bean1, Holden T. Maecker2, Paul J. Utz3, Judith A. James4 and Joel M. Guthridge5, 1Arthritis and
Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, 2Division of Immunology and Rheumatology, Stanford
University School of Medicine, Stanford, CA, 3Medicine, Stanford University School of Medicine, Stanford, CA, 4Arthritis & Clinical
Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 5Arthritis and Clinical Immunology Program, Oklahoma
Medical Research Foundation, OKC, OK
SESSION INFORMATION
Signalling
Background/Purpose: Systemic lupus erythematosus (SLE) is characterized by loss of immune tolerance to self-antigens and periods of
waxing and waning disease. The clinical aspects of SLE differ significantly from individual to individual and are altered during periods of
heightened disease activity. Activation of innate and adaptive signaling pathways, such as endosome expressed TLR3, TLR7 and TLR9, are
linked to SLE development, yet differences in innate and adaptive immune signaling and responding cytokine production during variable
disease activity remains unclear.
Methods: Peripheral whole blood samples of 10 African American healthy controls and 12 SLE patients with either high (SLEDAI³4) or low
(SLEDAI<4) disease activity were stimulated with T-cell receptor (TCR), B-cell receptor (BCR), and Toll-like receptor (TLR) ligands for
either 4 minutes (TLR and BCR) or 30 minutes (TCR) for phospho-protein analysis, and 24 hours for cytokine analysis of cell culture
supernatants. Phospho-protein analysis was assessed by mass cytometry and analyzed using Cytobank. Plasma cytokine and soluble mediator
concentrations of stimulated cell culture supernatants were determined by 37-plex assay and by ELISA. Spotfire (version 6.0.1) and
GraphPad Prism 5.04 for Windows (GraphPad Software, San Diego, CA) was used for analysis and Mann-Whitney test was used to compare
non-normally distributed data. All SLE patients met ACR classification criteria.
Results: SLE patients with high disease activity had a significantly increased fold change in T cell associated cytokines following overnight
stimulation, namely sCD40L (p=0.045), IL-2 (p=0.041), and IL-13 (p=0.045) in response to TLR4, TLR7/8 and PMA-Ionomycin compared
to patients with low disease activity. In general, most SLE patient cytokines had a decreased fold change in response to stimulation compared
to healthy controls (p<0.05). CD4+ T cells and CD8+ T cells exhibited no significant differences in immune signaling following CD3/CD28
stimulation between SLE patients with high and low disease activity. TLR3, TLR4 and TLR9 stimulation drive heightened phosphorylation of
STAT5 (p<0.0061) and PLCg2 (p<0.045) in granulocytes of high SLE disease activity patients compared to low disease activity following
Poly I:C, LPS, and CpG, respectively. In contrast, dendritic cells had a reduced signaling response to TLR7/8, TLR9 and BCR stimulation
with lower pSTAT3 (TLR7/8) (p=0.0427), pp38 (TLR9) (p=0.0285), and Syk (p=0.0080), pSTAT1 (p=0.046) and pSTAT5 (p=0.0106)
(BCR) in high disease activity patients compared to low disease activity. B cells also had reduced phosphorylation of p38 (p=0.0427) in
response to TLR4 stimulation of high disease activity patients compared to low disease activity patients.
Conclusion: Our results suggest that altered signaling in response to TLRs in granulocyte and antigen presenting cells may contribute to
elevated SLE disease activity by driving T cell proliferation and cytokine production.
Disclosure: S. Slight-Webb, None; K. M. Bean, None; H. T. Maecker, None; P. J. Utz, None; J. A. James, None; J. M. Guthridge, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/whole-blood-stimulations-identify-elevated-t-cell-

cytokines-and-altered-granulocytedendritic-cell-signaling-in-sle-patients-with-variable-disease-activity
Abstract Number: 84
Physiological Autoantibodies Against the Endthelin Receptor Type-a Are Critically

Involved in the Homeostasis of Immune Cells
Otávio Cabral-Marques1, Harald Heidecke2, Frank Petersen3, Xinhua Yu4 and Gabriela Riemekasten5, 1Department of Rheumatology,
Vasculitis Center UKSH, University of Lübeck, Luebeck, Germany, 2CellTrend GmbH Luckenwalde, Luckenwalde, Germany, 3Research
Centre Borstel, Borstel, Germany, 4Lung Centre Borstel, a Leibniz institute, Borstel, Germany, 5Department of Rheumatology,
Universitatsklinikum Schleswig-Holstein, Lubeck, Germany
SESSION INFORMATION
Signalling
Background/Purpose:
G protein-coupled receptors (GPCRs) are a family of integral membrane proteins mediating cell trafficking and cellular homeostasis. In the
last decades, several functional autoantibodies (ab) against GPCR have been described to be involved in the pathogenesis of various
diseases including systemic sclerosis. As suggested by our studies for the autoantibodies against angiotensin and endothelin receptors, anti-
GPCR ab may also be present in healthy individuals. However; the role of autoantibodies in physiology is under debate.
Methods:
Antibodies against 10 different GPCR were analysed in 198 healthy donors, 249 patients with SLE, 376 patients with SSc, 47 patients with
rheumatoid arthritis, and 128 patients with granulomatosis with polyangiitis (GPA) by ELISA. In patients with SSc, we also have analysed
the ab levels against 31 targets including GPCR, growth factors, and signalling molecules. Possible functional interactions of the 31
autoantibody target molecules were studied by STRING, DAVID, and enriched Gene Ontology. Migration assays were performed as well as
cell culture experiments stimulating PBMC with IgG from healthy donors. C56Bl/6 mice were immunized with ETAR and the cellular
homeostasis was studied by flow cytometry, histology, and compared with the ab levels against anti-ETAR ab.
Results: The detection of antibodies against 10 different GPCR revealed either increased or decreased antibody levels in a disease-specific
manner when compared to healthy donors. Antibodies against ETAR were increased in patients with SSc and SLE and decreased in patients
with GPA. In addition to the disease-specific ab signatures, we identified SSc-specific correlations between the 31 target antibodies.
Possible functional interactions of the 31 autoantibody revealed a network of GPCR, growth factors, and signalling molecules with
endothelin receptor type A (ETAR) in the centre. Migration and locomotion were suggested to be the most significant functions regulated by
an assumed antibody network. Accordingly, IgG from healthy donors induced both IL-8 expression in PBMC as well as, depending on the
anti-ETAR ab levels, migration of neutrophils and lymphocytes, which was specifically diminished by the ETAR blocker sitaxentan. In vivo,
increased anti-ETAR ab levels were associated with an altered homeostasis of innate and adaptive immune cells in different tissues.
Conclusion: As indicated for anti-ETAR antibodies, anti-GPCR antibodies reveal physiological levels in healthy donors and specific
alterations in different autoimmune diseases. The antibodies are involved in the homeostasis of immune cells and could contribute to disease
pathogenesis.
Disclosure: O. Cabral-Marques, None; H. Heidecke, Heideckes, 4,Riemekasten, 4; F. Petersen, None; X. Yu, None; G. Riemekasten,
CellTrend, 4.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/physiological-autoantibodies-against-the-endthelin-

receptor-type-a-are-critically-involved-in-the-homeostasis-of-immune-cells
Abstract Number: 85
Enhanced IFN-γ STAT1 Signaling in CD4 T Cell Populations and Attenuated IL-2
STAT5 Signaling Contribute to the Pathogenesis of Rheumatoid Arthritis (RA)
Brandon Pope 1, Vishal Sharma2, Molly Boland2, Richard Reynolds2, S. Louis Bridges Jr.3 and Chander Raman4, 1Medicine, University of
Alabama at Birmingham, Birmingham, AL, 2University of Alabama at Birmingham, Birmingham, AL, 3Clinical Immunology & Rheum, Univ
of Alabama, Birmingham, AL, 4Medicine/Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham,
Birmingham, AL
SESSION INFORMATION
Signalling
Background/Purpose:
Type I (IFN-α) and type II (IFN-γ) interferons are important mediators of autoimmunity. However, there is conflicting evidence regarding the
contribution of IFN-γ to the pathogenesis of RA. We recently showed a strong association of IFN-γ receptor 1 (Ifngr1) expression and of
IFN-γ receptor 2 (Ifngr2) expression in peripheral blood mononuclear cells (PBMC) with the presence of RA and its radiographic severity,
respectively (Arthritis Rheumatol. 2015 67:1165). IL-2 has essential regulatory function in inflammatory diseases and is considered as a
potential therapy for autoimmune disease. In this study, we tested the hypothesis that RA is associated with alterations in IFN-γ and IL-2
STAT signaling within certain subsets of PBMCs.
Methods:
We used a high-definition phospho-flow approach to evaluate the activation of STAT1 (assessed using antibody to phosphorylated tyrosine at
position 701 [pY701]), STAT3 (pY705) and STAT5 (pY694) after stimulation with IFN-γ or IL-2. We analyzed subsets of PBMCs from 35
RA patients and 12 healthy controls (HC) as shown in Table.
Subset Markers
CD4 T cells
Naïve CD45RA+CCR7+
Central Memory CD45RA-CCR7+
Effector Memory CD45RA-CCR7-
Follicular Helper T CD4+PD1+CX3CR5+
cells (Tfh)
Regulatory T cells CD4+CD25hiCD127lo
(Treg)
CD8 T cells
Naïve CD45RA+CCR7+
Central Memory CD45RA-CCR7+
Effector Memory CD45RA-CCR7-
B cells CD20+
Monocytes CD14+CD11b+
Table. Subsets of PBMCs analyzed in this study.
Results:
We found that IFN-γ induced STAT1 activation was significantly greater in naïve, central memory, Tfh and Treg subsets of CD4+ T cell
populations from RA patients compared to HC (p<0.05). IFN-γ induced STAT1 activation in RA was similar to HC in effector memory CD4
T cells, all CD8 T cell populations, B cells and monocytes. Phosphatases dephosphorylate STATs to regulate the activation of cytokine
induced signals. We found that phenyl-arsine oxide (PAO), a broadly active phosphatase inhibitor, had no effect on IFN-γ induced STAT1
activation in any T cell population from RA or HC. This result indicates that IFN-γ induced acute activation of STAT1 is not regulated by a
phosphatase in RA or HC. IFN-γ did not activate STAT3 any mononuclear cell population among RA or HC. IL-2 very efficiently activated
STAT5 in all T and B cell populations in RA and HC. The activation of STAT5 in RA was significantly greater than HC in only one
population: effector memory CD4 T cells (p<0.01). Remarkably, treatment with PAO greatly enhanced IL-2 induced activation of STAT5 in
RA, but not HC CD4 T cell populations (naïve, central memory effector memory, Treg, Tfh). PAO had no effect on STAT5 activation in CD8
T cell populations from RA and HC. This result suggests that the regulatory activity of IL-2 in RA CD4 T cell populations is attenuated by a
STAT5-specific phosphatase.
Conclusion:
Our results indicate that CD4 T cell subpopulation dependent enhanced IFN-γ STAT1 signals and attenuated IL2-STAT5 signals (possibly
due to a phosphatase inhibitor) contribute to the pathogenesis of RA. Future studies will focus on stratifying patients by disease activity and
other covariates.
Disclosure: B. Pope, None; V. Sharma, None; M. Boland, None; R. Reynolds, None; S. L. Bridges Jr., None; C. Raman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/enhanced-ifn-%ce%b3-stat1-signaling-in-cd4-t-cell-

populations-and-attenuated-il-2-stat5-signaling-contribute-to-the-pathogenesis-of-rheumatoid-arthritis-ra
Abstract Number: 86
Regulation of Interleukin-1β Signaling By Inhibition of O-Glc-Nacase in Rheumatoid

Arthritis Synovial Fibroblasts
Mahamudul Haque 1, Anil Singh2, Kelly Kopczynski1 and Salahuddin Ahmed1, 1Department of Pharmaceutical Sciences, Washington State
University, College of Pharmacy, Spokane, WA, 2Washington State University, College of Pharmacy, Spokane, WA
SESSION INFORMATION
Signalling
Background/Purpose: O-GlcNAcylation is an important post-translational modification of nuclear and cytosolic proteins involved in the
cytokine signaling networks. Studies show both pro- and anti-inflammatory roles of O-linked N-acetyl glucosamine (O-GlcNAc) depending
on different cell types and diseases. However, the role of O-GlcNAcylation in chronic inflammatory diseases such as rheumatoid arthritis
(RA) is yet to be explored.
Methods: Human normal SFs (NLSFs) and RASFs were isolated from healthy synovial tissues and RA synovial tissues, respectively, under
the IRB-approved protocol. Cell lysates and tissue homogenates were used to determine the differences in the expression of the O-
GlcNAcylation in NLSFs and RASFs by Western immunoblotting. Effects of IL-1β (10 ng/ml) on O-GlcNAcylation and two enzymes that
control glycosylation (O-GlcNAc transferase, OGT and O-GlcNAcase, OGA) in human RASFs were studied. The effect of OGT inhibitor
(OSMI-1; 5-50 µM) or OGA inhibitor (Thiamet-G; 1-10 µM) was evaluated on IL-1β-induced IL-6 and IL-8 production and the underlying
mechanisms were studied. In rat adjuvant-induced arthritis (AIA) model, ankle, liver, and spleen homogenates from naïve and AIA rats were
analyzed to determine the temporal expression pattern of O-GlcNAcylation.
Results: The expression of O-GlcNAc is upregulated in RA synovial tissues compared with healthy synovial tissues, and also showed a
similar trend in SFs isolated from these tissues. We also observed IL-1β stimulation resulted in the upregulation of O-GlcNAc levels in
RASFs in vitro. Interestingly, pretreatment of RASFs with OGA inhibitor (Thiamet-G) inhibited IL-1β-induced IL-6 and IL-8 production,
whereas OGT inhibitor (OSMI-1) had no inhibitory effect, suggesting that OGA inhibition may be of potential therapeutic value in RA.
Evaluation of the IL-1β signaling proteins (TAK1, TAB1, or NF-kBp65) that are critical in relaying downstream signaling showed a marked
increase in O-GlcNAc levels upon IL-1β stimulation. Thiamet-G pretreatment showed a protective role of OGA inhibition in regulating
inflammation. Similarly, in rat AIA model, we observed a higher O-GlcNAc expression pattern in rat joint homogenates, whereas no change
in O-GlcNAcylation expression was observed in liver. Surprisingly, O-GlcNAcylation in spleen homogenates elicited differential expression
at the onset of arthritis (day 8) and at the establishedarthritis (day 18) compared to naïve, which correlated with the clinical scores and
splenomegaly in arthritic animals. Interestingly, O-GlcNAc levels of protein such as NF-kBp65 was found to be downregulated in spleen
microenvironment whereas that of NF-kBp50 remained the same.
Conclusion: Our findings point to an important mediatory role of O-GlcNAc in stabilizing IL-1β signaling proteins to activate downstream
inflammatory proteins. OGA inhibition may serve as a potential therapeutic target in regulating synovial inflammation in RA.
Disclosure: M. Haque, None; A. Singh, None; K. Kopczynski, None; S. Ahmed, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/regulation-of-interleukin-1%ce%b2-signaling-by-

inhibition-of-o-glc-nacase-in-rheumatoid-arthritis-synovial-fibroblasts
Abstract Number: 87
A Novel Histone Deacetylase 6 Inhibitor, CKD-M808, Regulates the Adhesion and

Migration of Fibroblast-like Synoviocytes, and Enhances Suppressive Function of
Regulatory T Cells in Rheumatoid Arthritis
Sehui Shon1, Ji Soo Park1, Shin Eui Kang1, Jeong Yeon Kim1, Dong-Hyeon Suh2, Daekwon Bae2, Nina Ha2, Young Il Choi2, Jin Kyun
Park1,3, Eun Young Lee3, Eun Bong Lee3 and Yeong Wook Song3,4, 1Department of Molecular Medicine and Biopharmaceutical Sciences,
Graduate School of Convergence Science and Technology, and College of Medicine, Seoul National University, Seoul, Korea, Republic of
(South), 2Research Institute of Chong Kun Dang Pharmaceutical Corporation, Yongin, Korea, Republic of (South), 3Division of
Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea, Republic of (South), 4Department of
Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University,
Seoul, Koer, Seoul, Korea, Republic of (South)
SESSION INFORMATION
Signalling
Background/Purpose:
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by bone and cartilage destruction with leukocyte
infiltration and activation at synovial tissue. Recently, upregulated histone deacetylase (HDAC) activity has been reported in peripheral
blood mononuclear cells (PBMCs) from RA patients. In addition, it has been reported that HDAC inhibitor (HDACi) improved cancers,
neurological diseases and inflammatory diseases by suppressing pro-inflammatory cytokines such as TNF-α and IL-6. Previously, we
reported that a novel histone deacetylase 6 inhibitor (HDAC6i), CKD-M808 (M808) decreased clinical score in adjuvant induced arthritis
(AIA) rat model. Here, we investigated the effect of M808 on cell adhesion, migration and suppressive function of regulatory T cells (Treg)
derived from RA patients.
Methods:
Fibroblast-like synoviocytes (FLS) were isolated from synovial tissues of RA patients, and treated with HDAC6i such as tubastatin A and
M808 under IL-1β stimulation. The expression of α-tubulin, acetylated tubulin, intracellular adhesion molecule (ICAM)-1 and vascular cell
adhesion molecule (VCAM)-1 were measured in RA FLS by western blotting. The levels of CCL2, CXCL8 and CXCL10 were measured in
culture supernatant. Wound healing assay were performed to confirm cell migration ability. The adhesion of U937 or Jurkat cells onto RA
FLS was measured by cell adhesion assay. CD4+CD25- T cells (effector T cells, Teff) were isolated from RA PBMCs, and differentiated
into induced Treg (iTreg) under differentiating media. After the differentiation, Foxp3 and CTLA-4 were analyzed by flow cytometry. iTreg
were also co-cultured with carboxyfluorescein succinmidyl ester (CFSE)-labeled Teff derived from healthy donor. The proliferation of Teff
was analyzed by flow cytometry.
Results:
M808 increased the acetylation of tubulin in RA FLS. The number of migrated cell was decreased in M808-treated RA FLS without the
change in cell viability. The expression of ICAM-1 and VCAM-1 were decreased in HDAC6i-treated groups in a dose-dependent manner.
M808 reduced the levels of chemokines including CCL2, CXCL8 and CXCL10 in RA FLS. In addition, M808 attenuated the adhesion of
U937 and Jurkat cells on RA FLS. The suppressive function of iTreg were significantly increased in M808-treated groups.
Conclusion:
M808 increased the acetylation of tubulin, and decreased the migration of RA FLS. M808 also decreased the expression of ICAM-1, VCAM-
1 and chemokines such as CCL2, CXCL8 and CXCL10. The adhesion between RA FLS and U937 or Jurkat cells was decreased in the
presence of M808. M808 increased the suppressive function of iTreg derived from RA PBMCs. The novel HDAC6i, M808, may provide a
new therapeutic option in RA patients.
Disclosure: S. Shon, CKD Research Institute, 2; J. S. Park, None; S. E. Kang, None; J. Y. Kim, None; D. H. Suh, CKD Research Institute,
2; D. Bae, CKD Research Institute, 2; N. Ha, CKD Research Institute, 2; Y. I. Choi, CKD Research Institute, 2; J. K. Park, None; E. Y. Lee,
None; E. B. Lee, None; Y. W. Song, CKD Research Institute, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-novel-histone-deacetylase-6-inhibitor-ckd-m808-

regulates-the-adhesion-and-migration-of-fibroblast-like-synoviocytes-and-enhances-suppressive-function-of-regulatory-t-cells-in-
rheumatoid-arth
Abstract Number: 88
Mind Map Use in Rheumatology Education

Alex Papou, Rheumatology, Consultant Rheumatologist, North West Anglia NHS Foundation Trust, Peterborough City Hospital,
Peterborough, United Kingdom
SESSION INFORMATION
Session Title: Education Poster
Background/Purpose: Medical knowledge is a constantly expanding and changing field. One of the challenges for healthcare professionals,
including doctors in training, is to be able to find the most relevant source of reliable information with minimal reasonable efforts. Search for
information is often time-consuming and each educational resource has limitations. Traditional forms of study such as textbooks are often out-
of-date and inaccessible at work; internet-based information is often too abundant, and can be disorganized, not relevant to clinical practice,
and inaccurate; direct learning from seniors is limited in a busy hospital environment; ward experience learning can lead to mistakes. There
is an unmet need for a unified resource that will serve the purpose of being accessible wherever you are, comprehensive, reliable, up-to-date,
and easily searchable.
Methods: A simple way to organize information is to use mind maps. A mind map is a tree-like structure that consists of radial nodes when
the next level can be expanded or collapsed by a mouse click or a tap. Within a few clicks you can reach any information you need, visual
hierarchical approach is intuitive and allows easy search, associated topics can be linked, and a web-based application offers easy
modification and update of the mind map or its adjustment according to the needs of a trainee.
Results: We have developed a free mind mapping educational resource for health care professionals (www.rheumatologymindmap.com,
www.rheumatologymindmap.co.uk, images 1-3). It is based on current rheumatology practice in the United Kingdom and is being updated in
accordance with the new information and feedback received from the UK trainees. The mind map has direct online links to appropriate
British, European, and American guidelines, incorporates downloadable templates, has hyperlinks to online calculators and to websites
providing advice for doctors and patients. The mind map works in desktop and mobile browsers and can be transferred to other platforms
including Android and iOS.
Conclusion: Mind mapping can offer a new structured approach in medical training and clinical practice, with fast access to the relevant
information. The rheumatology mind map can become an important practical tool and its main benefits are accessibility, intuitive interface,
easy search, and modifiability.
Image 1.
Image 2.
Image 3.
Disclosure: A. Papou, None;
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/mind-map-use-in-rheumatology-education
Abstract Number: 89
The CLASS-Rheum (Critical Literature Assessment Skills Support – Rheumatology)

Question-Based Tool Is Associated with Sustained Improvement in Knowledge of
Relevant Epidemiology and Biostatistics in Rheumatology Fellows
Lisa A. Mandl1, Julie Schell2, Karina Torralba3, Pascale Schwab4, Christopher E. Collins5, Lisa Criscione-Schreiber6, Anne R. Bass1,
Jessica R. Berman1, Alexa Adams7, Michael D. Tiongson8, Stephen A. Paget9, Jackie Szymonifka10 and Juliet Aizer1, 1Rheumatology,
Hospital for Special Surgery/Weill Cornell Medicine, New York, NY, 2The University of Texas at Austin, Austin, TX, 3Rheumatology,
Loma Linda University, Loma Linda, CA, 4Rheumatology, Oregon Health and Science University, Portland, OR, 5Medicine, MedStar
Washington Hospital Center/ Georgetown University Medical Center, Washington, DC, 6Internal Medicine, Duke University Medical Center,
Durham, NC, 7Hospital for Special Surgery/Weill Cornell Medicine, New York, NY, 8Hospital for Special Surgery, New York, NY,
9Division of Rheumatology, Hospital for Special Surgery/Weill Cornell Medicine, New York, NY, 10Rheumatology, Hospital for Special
Surgery, New York, NY
SESSION INFORMATION
Background/Purpose:
Understanding epidemiology and biostatistics (epi/biostats) is crucial for rheumatologists to interpret literature and make appropriate data-
driven clinical decisions. Based on retrieval-enhanced learning theory, we developed CLASS-Rheum, a cloud-based modular assessment
tool to support learning of epi/biostats relevant to rheumatology fellows. In this study we test whether sequential administration of
isomorphic Question Sets is associated with sustained learning.
Methods:
CLASS-Rheum Question Sets are organized into 10 modules, each focused on a concept in epi/biostats, framed in rheumatologic context.
Administration via Learning Catalytics® allows access on web-enabled devices. With IRB-exemption, 6 rheumatology programs of varying
size across the US participated in sequential administration of 2 Question Sets. Question Set 2 (QS2) was comprised of 56 unique questions
assessing the same content and learning objectives as Question Set 1 (QS1). We examined face and construct validity, item difficulty,
psychometrics, and change in knowledge with sequential administration of Question Sets. Fellows providing individual responses to > 50%
of questions were included in the quantitative analysis. Mean change in percent correct and change in Likert-scale ratings were compared
with paired-t tests and Wilcoxon Signed-Rank tests, respectively. Mixed effects modeling was used to examine whether year of fellowship
impacted percent correct (SAS v9.4).
Results:
From 2/2016-5/2017, 51 rheumatology fellows enrolled in CLASS-Rheum. 39 provided individual responses to >50% of questions and were
included in the quantitative analysis. 67% of participating fellows were women. At enrollment, 10% had degrees in epi/biostats, 61%
reported being very interested in epi/biostats, and 65% considered their understanding of epi/biostats average compared to other
rheumatology fellows. 28 fellows’ data were analyzed in QS1 (all first time takers), and 25 fellows’ in QS2 (11 first time takers). 14 fellows
completed both Question Sets, with mean interval between pairs of isomorphic modules of 260 days (SD 70.7).
Difficulty was similar between modules. Mean percent correct for first time takers was 64.4% (SD 15.1%) for QS1 vs. 64.8 (SD 11.9%) for
QS2 (p = 0.93). Point biserial correlations were positive for 93% of questions from QS1 and QS2, suggesting strong psychometrics. Based
on data from QS1 and QS2, 3rd year fellows had statistically higher average scores than 1st year fellows (p=0.032).
Among the 14 fellows completing QS1 and QS2, mean percent correct increased from 61.8% to 67.9% (p = 0.036). 14% of fellows’ scores
increased >20%. Upon completing QS1, 14/14 fellows described CLASS-Rheum as “very useful/useful” in learning epi/biostats, as did
13/14 after completing QS2 (p=0.75).
Conclusion:
Two psychometrically sound modular Question Sets (“CLASS-Rheum”) covering important concepts in epi/biostats, framed in a
rheumatologic context, were successfully administered to fellows in diverse rheumatology training programs. Sustained increases in
knowledge were demonstrated with sequential administration of isomorphic Question Sets over 15 months. CLASS-Rheum will be evaluated
in additional programs.
Disclosure: L. A. Mandl, None; J. Schell, None; K. Torralba, None; P. Schwab, None; C. E. Collins, None; L. Criscione-Schreiber, None;
A. R. Bass, None; J. R. Berman, None; A. Adams, None; M. D. Tiongson, None; S. A. Paget, None; J. Szymonifka, None; J. Aizer, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-class-rheum-critical-literature-assessment-skills-

support-rheumatology-question-based-tool-is-associated-with-sustained-improvement-in-knowledge-of-relevant-epidemiology-and-biostatist
Abstract Number: 90
Developing a Pediatric Rheumatology Curriculum for Pediatric Residents

Miriah Gillispie 1,2 and Amanda Brown3, 1Texas Children's Hospital, Houston, TX, 2Pediatrics, Department of IAR, Baylor College of
Medicine, Houston, TX, 3Allergy, Immunology and Rheumatology, Texas Children's Hospital, houston, TX
SESSION INFORMATION
Background/Purpose: The purpose of this project was to develop a curriculum to teach residents these skills. Due to a paucity of pediatric
rheumatologists and the growing patient population, pediatricians must be able to recognize and begin a basic work up for suspected
autoimmune disease. The project includes 30-minute case based lectures on the topics of systemic lupus erythematosis (SLE), juvenile
idiopathic arthritis (JIA), periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA), Kawasaki Disease (KD), juvenile
dermatomyositis (JDMS), and Henoch Schonlein purpura (HSP).
There are 300,000 children in the US with rheumatic conditions and the incidence is increasing with better recognition of this subset of
chronic diseases. This makes rheumatic disease one of the most common chronic illnesses in pediatrics. Most recent estimates from 2015
show that there are 407 pediatric rheumatologists in the country and of those, many have very little clinical time are involved more heavily in
research. Sadly, most recent estimates suggest that up to 10% of pediatric rheumatologists will be retiring within the next several years and
that demand exceeds supply by 25-50%. Many children who do have access to a pediatric rheumatologist travel >4 hours to see a
subspecialist and wait times at many centers are several weeks to months. As a result, the practicing pediatric rheumatologists often must rely
heavily on generalists and those in other subspecialties to help manage these patients. However, 40% of residency programs do not have
access to an onsite pediatric rheumatologist and 11 states are still without a board certified/eligible pediatric rheumatologist. Even within
institutions who have access to a pediatric rheumatologist, exposure is limited with estimates of approximately 5 hours of teaching time for
the residents who do not rotate with rheumatology as an elective at our institution. This is similar to exposure in other institutions who have
pediatric rheumatology.
Methods: All pediatrics and med-peds residents at our institution were anonymously surveyed to get their opinion on which topics in
rheumatology they thought were most important and also on their preference for content delivery. Based on responses, a series of six lectures
were composed in a case based, interactive format. Second year pediatrics and third year med-peds residents rotate through the inpatient
rheumatology service and received this curriculum. Pre and post surveys were used to evaluate improvement in comfort level with
rheumatology topics.
Results: Per self-assessment from the residents’ comfort level with laboratory work up, musculoskeletal exam, and referrals improved after
working through cases in the curriculum while on the inpatient rotation.
Conclusion: Although exposure to pediatric rheumatology is limited in our institution, we were able to effectively increase comfort level
with regards to work up and diagnosis of autoimmune diseases. Ideally, exposure to patients in both the inpatient and outpatient setting would
also help increase comfort level with this subset of patients, but ACGME guidelines for residency training do not require exposure to
pediatric rheumatology during residency training.
Disclosure: M. Gillispie, None; A. Brown, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/developing-a-pediatric-rheumatology-curriculum-for-

pediatric-residents
Abstract Number: 91
Development of Musculoskeletal Physical Examination Checklists: A Formal Consensus

Project Involving National Educators
Andrea Barker1, Arben Brahaj2, Paula Carvalho3, Analia Castiglioni4, Dan Doan5, Krista Gager6, Karen E. Hansen7, Michelene Hearth-
Holmes8,9, Laura Kim10, Antonio A. Lazzari11, Tiffany F. Lin12, Christopher Olson13, Vanessa C. Osting14, Mary M. Pearson15, Noelle A.
Rolle4, Bernadette C. Siaton16,17, Joan Marie Von Feldt18, Yasuharu Okuda19 and Michael J. Battistone1, 1Veterans Affairs Salt Lake City
Health Care System and University of Utah School of Medicine, Salt Lake City, UT, 2VA New England Healthcare System, Bedford, MA,
3Boise VAMC, Boise, ID, 4Orlando VAMC and University of Central Florida, Orlando, FL, 5VA Puget Sound Healthcare System and
University of Washington, Seattle, WA, 6San Francisco VAMC, San Francisco, CA, 7Department of Medicine, Division of Rheumatology,
University of Wisconsin School of Medicine and Public Health, Madison, WI, 8Internal Medicine/Rheumatology Division, Univ. of Nebraska
Medical Center, Omaha, NE, 9Internal Medicine, Omaha VA Medical Center and University of Nebraska Medical Center, Omaha, NE,
10Orlando VAMC and VHA SimLEARN National Center, Orlando, FL, 11VA Boston Healthcare System & Boston University School of
Medicine, Boston, MA, 12VHA Madison & University of Wisconsin, Madison, WI, 13JA Haley Veterans Hospital, Tampa, FL, 14JA Haley
Veterans Hospital & University of South Florida, Tampa, FL, 15San Francisco VAMC & University of California, San Francisco, San
Francisco, CA, 16Baltimore VAMC, Baltimore, MD, 17Rheumatology, University of Maryland School of Medicine, Baltimore, MD,
18Rheumatology, University of Pennsylvania/Philadelphia VAMC, Philadelphia, PA, 19VHA SimLEARN National Center, Orlando, FL
SESSION INFORMATION
Background/Purpose:
Musculoskeletal (MSK) physical exam checklists for a Veterans Affairs (VA) continuing professional development (CPD) course were
developed and validated in a broad educational effort for primary care providers (PCPs). These tools were introduced to national leaders in
MSK education in the VA National Simulation, Learning, Education and Research Network (SimLEARN) MSK Master Educator course. The
aim of this project is to further enhance these through a statistically guided consensus effort.
Methods:
Twenty MSK educators attending the 2017 MSK Master Educator course were invited to participate in a 3-step Delphi process. Step 1
involved review of current versions of the 21-item shoulder and 26-item knee checklists with invitation to suggest additional items. In step 2,
each educator rated every item’s importance to be included in a curriculum for PCPs, using a 5-point Likert scale (1 = not at all important; 5
= extremely important). In the 3rd step, educators were given the groups’ average rating for each item, reminded of their own initial rating,
and asked to make a final 5-point rating. Individual responses to each step remained anonymous. After the final step, items meeting the
predetermined criteria of mean ³4 and standard deviation ≤1 were retained; these items defined the consensus checklists.
Results:
Eighteen educators (90%; 16 physicians, 1 physician assistant, 1 nurse practitioner) completed the project. Nine educators’ practice area was
primary care; 9 were in specialty care, of which 7 were rheumatologists.
In step 1, 11 items were added to the shoulder and 14 to the knee checklists. There were no significant differences in ratings from step 2 to
step 3, though standard deviations were significantly smaller for both shoulder and knee (p < 0.005) in step 3, after respondents were
provided with the groups’ mean ratings from step 2.
Final ratings for the shoulder and knee are listed in the figures below:
When stratifying ratings by practice area, significant differences were seen between ratings by those in primary care and those in specialty
care, for both shoulder (p = 0.03) and knee (p = 0.004).
Conclusion:
This is a feasible method for a national group of experts to create statistically guided educational tools. The differences between specialist
and primary care educators’ ratings of item importance suggest these groups may have different expectations for CPD programs. These
findings should inform future educational initiatives, ensuring that both subject matter experts and those familiar with the clinical duties of
target learners are included in consensus projects.
Disclosure: A. Barker, None; A. Brahaj, None; P. Carvalho, None; A. Castiglioni, None; D. Doan, None; K. Gager, None; K. E. Hansen,
None; M. Hearth-Holmes, None; L. Kim, None; A. A. Lazzari, None; T. F. Lin, None; C. Olson, None; V. C. Osting, None; M. M.
Pearson, None; N. A. Rolle, None; B. C. Siaton, None; J. M. Von Feldt, None; Y. Okuda, None; M. J. Battistone, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/development-of-musculoskeletal-physical-examination-

checklists-a-formal-consensus-project-involving-national-educators
Abstract Number: 92
Hospital for Special Surgery Academy of Rheumatology Medical Educators: 5 Year

Outcomes Demonstrate the Value of Supporting Education Research in the Academic
Environment
Jessica R. Berman1, Juliet Aizer1, Anne R. Bass2, Edward Parrish1, Laura Robbins3, Michael D. Tiongson4 and Stephen A. Paget1,
1Rheumatology, Hospital for Special Surgery Weill Cornell Medical College, New York, NY, 2Rheumatology, Hospital for Special
Surgery/Weill Cornell Medicine, New York, NY, 3Education & Academic Affairs, Hospital for Special Surgery, New York, NY, 4Hospital
for Special Surgery, New York, NY
SESSION INFORMATION
Background/Purpose: It has been previously demonstrated that educators do not receive the same recognition as their colleagues in clinical
and basic science, and financial support for education research is often inadequate. With this in mind, in 2011 the Academy of Rheumatology
Medical Educators was founded at Hospital for Special Surgery (HSS) in order to: 1) create a stimulating academic environment for
educators that enhances the quality of teaching and 2) award pilot grants to educators interested in research.
Methods: Directed fund-raising was earmarked specifically for annually awarded education grants to serve as a hospital wide impetus for
the development of new teaching programs and curricular change through new or improved opportunities for teaching and learning. A request
for proposals (RFP) was sent out yearly from 2011-2016 to the HSS rheumatology faculty. One year the RFP was extended to the entire
hospital offering matching funds with departments such as nursing and anesthesia. Grants of up to $50,000 a year were awarded to
applications with merit that met the requisite funding priorities. All grants were reviewed and scored according to Glassick’s criteria for
scholarship by individuals nationally recognized for their education expertise and reviewed by the HSS Education Council, which provides
ongoing oversight of the Academy’s activities.
Results: To date, 23 grants have been awarded for a total of $ 690,695 in funding. The awardees have produced 19 national meeting
abstracts, given 24 presentations (11 posters, 13 oral) at national meetings and written 7 manuscripts (5 published, 2 submitted) and 2
editorials. Funding has resulted in the creation of 8 unique curricula and two iBooks. Diverse topics have been represented such as the
assessment of professionalism, new pedagogical techniques for teaching epidemiology to fellows, use of technology in education, an inter-
professional gout education program for patients and a hospital based mentorship program.
Conclusion: The HSS Rheumatology Academy aims to create a stimulating academic educational environment that enhances the quality of
teaching and promotes teaching careers and education research. The formation of the education research funding pilot highlights the talents of
heretofore unsupported and unrecognized teaching faculty by allowing them to distinguish themselves academically. This emphasizes the
clear advantages of such a formalized structure to achieve the hospital’s heightened educational goals and demonstrates the importance of
recognizing the quality of education research as equivalent with clinical and basic science research.
Disclosure: J. R. Berman, None; J. Aizer, None; A. R. Bass, None; E. Parrish, None; L. Robbins, None; M. D. Tiongson, None; S. A.
Paget, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/hospital-for-special-surgery-academy-of-rheumatology-

medical-educators-5-year-outcomes-demonstrate-the-value-of-supporting-education-research-in-the-academic-environment
Abstract Number: 93
Peer-Developed E-Learning Resource Can Address Rheumatology Knowledge Gaps in

Junior Learners
Larissa Petriw1, Tabitha Kung2 and Mala Joneja2, 1Internal Medicine, Queen's University, Kingston, ON, Canada, 2Rheumatology, Queen's
University, Kingston, ON, Canada
SESSION INFORMATION
Background/Purpose: The symptoms related to Rheumatologic diseases are responsible for one third of visits to general practitioners, yet
medical students and residents remain inadequately prepared to approach and manage Rheumatologic problems (Freedman and Bernstein,
2002). There are few resources available to junior learners in Rheumatology. Several handbooks written by Canadian Rheumatologists exist,
though none combine clinical images, interactivity and case-based learning in an electronic format. Electronic learning (e-learning) provides
a highly flexible medium for information presentation, multimedia and self-assessment in a mobile, searchable, user-friendly platform.
Evidence suggests that peer-generated e-learning adds value, though most residents do not have extensive software expertise in developing e-
resources. Here we present an interactive, peer-developed case-based Rheumatology iBook produced by residents for learners in
Rheumatology aimed to address these gaps.
Methods: Our iBook was written in the free, easy-to-use program “iBooks Author”. The target audience was medical students and residents
completing a rotation in Rheumatology. Key learning objectives for a Rheumatology rotation were identified and addressed as the main
sections of the iBook. Sections include approaches to common rheumatologic presentations, case presentations of rheumatologic conditions
commonly encountered over a rotation or general practice, and appendices, including approaches to serology, medications and joint
aspiration. Clinical images and self-assessments add interactivity. The iBook was evaluated in a survey of learners rotating through
Rheumatology at Queen’s University, with pre- and post-rotation surveys.
Results: The survey is ongoing, however preliminary data shows high satisfaction with our resource and improvement in learners'
knowledge. All learners surveyed agree or strongly agree the iBook is user-friendly (75% strongly agree), well organized (75% agree, 25%
strongly agree), and has an appropriate level of material and cases (75% strongly agree). All participants found the iBook useful for rotation
preparation (50% agree, 50% strongly agree) and would recommend it to a colleague (57% agree, 43% strongly agree). All participants
improved their comfort with Rheumatology topics on a Likert scale pre- and post-assessment. Pre-intervention global comfort level was
2.3/4 and post-intervention was 3/4, with similar trends of improvement in the specific topics surveyed. The iBook itself was free and easy
to create without additional training in computer programming.
Conclusion: We present the first peer-developed e-learning resource of its kind in Rheumatology that can be used as a rotation resource for
junior learners across the country. Although content writing remains labour-intensive, the iBook modality allows easy updating and minimal
knowledge of programming by the writers. Conversion to non-iBook format is possible for further distribution across platforms. The iBook
structure can easily be adapted to other medical education topics and is a user-friendly method of e-publication for busy residents interested
in medical education.
Disclosure: L. Petriw, None; T. Kung, None; M. Joneja, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/peer-developed-e-learning-resource-can-address-

rheumatology-knowledge-gaps-in-junior-learners
Abstract Number: 94
Validity Evidence for an Objective Structured Clinical Examination Station to

Assess Knee Arthrocentesis Skill
Tawnie Braaten1, Andrea Barker2, J. Peter Beck3 and Michael J. Battistone2, 1University of Utah, Salt Lake City, UT, 2Veterans Affairs
Salt Lake City Health Care System and University of Utah School of Medicine, Salt Lake City, UT, 3Orthopaedics, Salt Lake City VA
Medical Center and University of Utah, Salt Lake City, UT
SESSION INFORMATION
Background/Purpose:
We developed an objective structured clinical examination (OSCE) station to guide preceptors’ observations of trainees’ performance of
simulated knee arthrocentesis and to organize feedback in preparation for performing these procedures in patient care. The aim of this project
was to examine the evidence for validity of this OSCE.
Methods:
Content:
An orthopedic surgeon, a rheumatologist, and a primary care provider with expertise in musculoskeletal (MSK) medicine developed a
checklist to guide rater observations in evaluating arthrocentesis technique. Content was proposed by faculty, supplemented by literature
review, and finalized through consensus.
Response Process
A multi-disciplinary cohort of 71 learners (53 postgraduate trainees, 12 physician assistant students, 5 advanced practice nursing students,
and one university undergraduate student) participated in the OSCEs in 2016-2017. To promote accuracy of the simulated patient (SP)
responses to assessment prompts, one faculty member served as the SP and another as rater; ratings were recorded in real time.
Internal Structure
Two faculty members independently rated a portion of the cases. Percent agreement was calculated and Cohen’s kappa corrected for chance
agreement on binary outcomes.
Relations to other variables
Relationship to self-assessment of confidence and competence to perform knee arthrocentesis was explored by written surveys utilizing a 5-
point Likert scale. Response scores were compared with OSCE scores through Pearson’s correlation coefficient.
Results:
Checklists were developed for knee arthrocentesis (19 items). The checklist was scored by assigning one point for each error observed, in
order to capture multiple errors; thus a score of 0 indicated no errors were noted. Mean score was 3.7 (range = 0-8; s.d. = 1.9). Frequency
distribution of scores is reported in the Figure:
Inter-rater agreement was near perfect at 93% (k = 0.8), as shown in the Table:
Rater 1
No Error Error Total
Noted Noted
Rater 2 No Error 116 5 121
Noted
Error 6 31 37
Noted
Total 122 26 158
Observed Agreement = (116 + 31)/158 = 0.93
Chance Agreement = 0.64
Cohen’s kappa = 0.8
Pearson’s coefficient indicated no correlation between self-assessment and OSCE performance (-0.002).
Conclusion:
Validity evidence supports use of this OSCE in educational programs preparing learners for clinical settings where MSK procedures may be
performed. Evidence for validity includes systematic development of content, response process control, and demonstration of acceptable
interrater agreement. Lack of correlation with self-assessments suggests that the OSCE measures a construct different than self-perceived
ability.
Disclosure: T. Braaten, None; A. Barker, None; J. P. Beck, None; M. J. Battistone, None.

View Abstract and Citation Information Online - http://acrabstracts.org/abstract/validity-evidence-for-an-objective-structured-clinical-
examination-station-to-assess-knee-arthrocentesis-skill
Abstract Number: 95
Globalisation of Paediatric Musculoskeletal Matters’ (PMM)

Nicola Smith1, Sharmila Jandial2, Ruth Wyllie2, Christine English3, Barbara Davies3, Raju Khubchandani4, Mercedes Chan5, Jane Munro6,
Virgínia Ferriani7, Claudia Saad Magalhães8, Ricardo Russo9, Jacqueline Yan10, Chris Scott11, Sirirat Charuvanij12, Khulood Khawaja13,
Jelena Vojinovic14, Tim Rapley15 and Helen Foster16, 1Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United
Kingdom, 2Paediatric Rheumatology, Great North Children’s Hospital, Newcastle Upon Tyne, United Kingdom, 3Department of Nursing,
Midwifery and Health, Northumbria University, Newcastle Upon Tyne, United Kingdom, 4Department of Paediatrics, Jaslok Hospital and
Research Center, Mumbai, India, 5Paediatric Rheumatology, University of Alberta, Edmonton, AB, Canada, 6Paediatric Rheumatology,
Royal Children's Hospital, Victoria, Australia, 7Department of Paediatrics, Ribeirão Preto Medical School, University of São Paulo (USP-
RP), Sao Paulo, Brazil, 8Department of Pediatrics, São Paulo State University (UNESP), Botucatu, Brazil, 9Service of
Immunology/Rheumatology, Hospital de Pediatría Garrahan, Buenos Aires, Argentina, 10Paediatric Rheumatology, Starship Children’s
Health, Auckland, New Zealand, 11Department of Paediatrics, University of Cape Town, Cape Town, South Africa, 12Department of
Pediatrics, Siriraj Hospital, Mahidol University, Bangkok, Thailand, 13Department of Immunology/Rheumatology, Al-Mafraq Hospital, Abu
Dhabi, United Arab Emirates, 14Paediatric Rheumatology, Faculty of Medicine, University of Nis, Nis, Serbia, 15Institute of Health and
Society, Newcastle University, Newcastle Upon Tyne, United Kingdom, 16Institute of Cellular Medicine and Paediatric Rheumatology,
Newcastle University and Great North Children's Hospital, Newcastle Upon Tyne, United Kingdom
SESSION INFORMATION
Background/Purpose: paediatric musculoskeletal matters’ (PMM–www.pmmonline.org) is a free, evidence-based and peer reviewed open
e-resource for paediatric musculoskeletal (MSK) medicine targeting non-MSK specialists. Since launch (Nov-2014) PMM has reached 183
countries with >57,000 users, >194,000 hits. Users who have declared their training background on the website are mainly non-MSK
specialists. Feedback from users has requested further content to reflect international healthcare systems. PMM India was developed in
collaboration with the Indian Academy of Paediatrics (IAP; Sept-2015, >2,200 users, 14,000 hits to date) and showcases successful
partnership with local clinicians in developing PMM with local context. Further ‘internationalisation’ is now ongoing with additional global
partners to develop ‘PMM International’. Here, we describe the process for international development.
Methods: Paediatric rheumatologists in countries around the world were approached to identify additional PMM content to reflect MSK
medicine in their health care systems (e.g. case mix, clinical presentations, care pathways), with the focus on maintaining the level of
knowledge relevant for non-MSK specialists. New content was developed by local teams identified by the paediatric rheumatologist(s) who
then collated and provided expert overview before submission for editorial review. All contributions were provided in English. Additional
cases and images were included with appropriate consent.
Results: PMM International additions to the original website brings new content predominately focused on infections / infection-related
disease with MSK features or as differential diagnoses for rheumatic disease. Most content is in English with requests for translation of some
content (e.g. pGALS which will be available in >7 languages). PMM International will be further peer reviewed with open access to all. A
PMM app is planned to facilitate access where internet capacity is limited.
Conclusion: Rapid globalisation necessitates appropriate e-resources with content that reflect international health care contexts. PMM
International targets non-MSK specialist audiences to raise awareness and early recognition of MSK pathology. Our work reflects strong
collaborative global partnerships within the paediatric rheumatology community. PMM has been endorsed by PReS as an educational
resource to aid teaching and learning. Implementation of PMM International has yet to be formally evaluated, but PMM data so far, supports
wide reach and positive uptake from the target audience user groups.
Disclosure: N. Smith, None; S. Jandial, None; R. Wyllie, None; C. English, None; B. Davies, None; R. Khubchandani, None; M. Chan,
None; J. Munro, None; V. Ferriani, None; C. S. Magalhães, None; R. Russo, None; J. Yan, None; C. Scott, None; S. Charuvanij, None;
K. Khawaja, None; J. Vojinovic, None; T. Rapley, None; H. Foster, Pfizer, BioMarin, Sobi, Genzyme, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/globalisation-of-paediatric-musculoskeletal-matters-pmm

Abstract Number: 96
Impact of a Student Led Rheumatology Interest Group on Medical Student Interest in

Rheumatology
Sonia Silinsky Krupnikova1, Adey Berhanu2, Sean McNish3, Derek Jones1 and Victoria K. Shanmugam2, 1The George Washington
University, Washington, DC, 2Rheumatology, The George Washington University, Washington, DC, 3Division of Rheumatology, The George
Washington University, Washington, DC
SESSION INFORMATION
Background/Purpose: Based on data from the Rheumatology Workforce Study, there are currently insufficient rheumatologists to serve the
needs of the population. The purpose of this longitudinal observational study is to investigate the impact of developing a student-led
Rheumatology Interest Group on medical student interest in rheumatology at a single institution. We report updated longitudinal follow-up
data on the impact of this intervention at the two year follow-up stage.
Methods: A student-led Rheumatology Interest Group was established at our institution in April 2015. The Interest Group runs several
meetings per year, including a session on careers in rheumatology, finding research projects and mentors, and joint injection workshops. To
assess the impact of the Interest Group on medical student interest in rheumatology we collected data prior to and subsequent to development
of the Interest Group based on three parameters: the number of medical student abstract submissions to the University Research Day, the
number of medical students enrolling in the rheumatology elective, and the number of manuscripts published by faculty with medical students.
The mean number of student-rheumatology interactions per 6 months in the pre and post intervention periods was assessed for each
parameter. Data lock for the current analysis was in April 2017 and analysis was performed using GraphPad Prism version 5.00 for
Windows (GraphPad Software, San Diego, CA).
Results: Analysis of the two years of follow up data indicates that there continues to be a significant increase in medical student enrollment
in the rheumatology elective following the Interest Group development, with a mean number of students per 6 months of 2.0 ± 0.89 in the pre-
intervention period and 5.25 ± 2.06 in the post-intervention period (p=0.0083). The number of abstract submissions also significantly
increased from 0.5 ± 0.84 to 6.5 ±4.65 (p=0.0131). Finally, the number of manuscripts submitted by student-faculty dyads increased from
0.17 ± 0.41 to 1.5 ± 0.58 (p=0.0026).
Conclusion: Based on data at two years of follow-up, a simple and low cost intervention of developing a student-led interest group has
dramatically increased ongoing student engagement with rheumatology at a single institution.
Disclosure: S. S. Krupnikova, None; A. Berhanu, None; S. McNish, None; D. Jones, None; V. K. Shanmugam, Multiple, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/impact-of-a-student-led-rheumatology-interest-group-on-

medical-student-interest-in-rheumatology-2
Abstract Number: 97
Medical Student Interest in Rheumatology As a Career

Peter Berger1, Adey Berhanu2, Derek Jones1, Sean McNish3 and Victoria K. Shanmugam2, 1The George Washington University,
Washington, DC, 2Rheumatology, The George Washington University, Washington, DC, 3Division of Rheumatology, The George Washington
University, Washington, DC
SESSION INFORMATION
Background/Purpose:
Based on data from the Rheumatology Workforce Study, there are insufficient rheumatologists to serve the needs of the population. Little is
currently known about factors that contribute to career choices of graduating medical students. The purpose of this study was to investigate
medical student interest in rheumatology at the time of graduation, and to assess factors which drive career choices.
Methods:
This prospective survey study was IRB approved and conducted at a single center. A web-based REDCap survey was sent to graduating
medical students via listserv approximately 1 month prior to graduation. Students self-reported demographics, information on whether and
when they decided on their career specialty, how likely they were to consider a career in rheumatology, and what factors appealed to them
about rheumatology as a specialty.
Results:
From the graduating class of 208 students, 52 matched into internal medicine or pediatrics. The survey was completed by 28 students
(response rate 13.5%). Respondents were 64% female and 36% male; 57% Caucasian and 28% of African American descent. All
respondents reported that they had decided on a specialty at the time of survey completion, with 78.5% reporting that they decided during
their third or fourth year of medical school. While only one respondent reported planning a career in rheumatology, factors which appealed to
the students about rheumatology as a specialty included: favorable work hours (78.5%), work-life balance (78.5%) and interest in complex
medical care (54%). Of the experiences that stimulated their interest in rheumatology as a specialty, the most frequent response was the
exposure to rheumatology teaching during their second year musculoskeletal block (36%). Interest in a specialty was the primary driver of
career choice (85.7%) while earning potential, student debt, and length of training did not play a role.
Conclusion:
In this survey of medical students at a single US medical school, the majority of respondents decided their specialty during their clinical
years. Interest in the specialty was the most important factor that drove career choice for this graduating class. Rheumatology teaching during
the second year module was the most frequently reported exposure during which interest in rheumatology as a specialty was stimulated.
Disclosure: P. Berger, None; A. Berhanu, None; D. Jones, None; S. McNish, None; V. K. Shanmugam, Multiple, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/medical-student-interest-in-rheumatology-as-a-career
Abstract Number: 98
Impact of a Lung Ultrasound Course for Rheumatology Specialist (IMPACT-2)

Christopher Gasho1, Karina Torralba2, David Chooljian3, Cong-Bin Wang4 and Vi Dinh4, 1Pulmonary and Critical Care Medicine, Loma
Linda Medical Center, 12354 Anderson St, CA, 2Division of Rheumatology, Department of Internal Medicine, Loma Linda University, Loma
Linda, CA, 3Loma Linda Veteran Affairs Hospital, Loma Linda, CA, 4Loma Linda University Medical Center, Loma Linda, CA
SESSION INFORMATION
Background/Purpose: Although much emphasis is focused on lung ultrasonography(US) within the critical care field, there is a
growing interest in the use of lung US and its role in diagnosis and monitoring of Interstitial Lung Disease(ILD). A large burden of ILD is
attributed to connective tissue disorders(CTD) and often presents symptomatically after irreversible fibrosis has ensued. With increasing use
of point-of-care musculoskeletal US among rheumatologists, translation of this expertise towards lung US places the rheumatologist in a
unique position to screen for asymptomatic lung involvement among patients with CTD. Despite recent evidence of the feasibility and utility
of using lung US in screening of patients with CTD-ILD, the field is relatively immature and standardized training curriculum for the
rheumatology community is lacking. The aim of this study is to determine the effectiveness of a formalized lung US training course for
Rheumatology fellows and attending physicians in incorporating and improving skills and attitudes in lung US.
Methods: Four rheumatology fellows and four board-certified rheumatologists were enrolled in a 4-hour training session including didactics,
live models and simulation experience. Pre-course, post-course and 6-month follow-up surveys evaluated participant perceptions towards
previous US experience, training, clinical utility and attitudes toward dedicated lung US. Written exams (21 multiple-choice questions) were
completed before, after training, and at 6 months to evaluate basic knowledge in ultrasound physiology, lung US anatomy, artifact and
pathology recognition. In addition, a 30-point practical exam using live models and simulation, evaluated competency in machine setup,
anatomical, artifact and pathology recognition
Results: The results of this study show overall improvement in written test scores ( 43% v 66% p<0.001) Considerable improvement was
also noted in overall practical skill score following training course. ( 16.8% v. 93.4% p<0.001). Sub category improvements were seen in
ultrasound setup and anatomical landmark identification (18.8% v 94.4% p<0.001 ) identification of pulmonary artifact (15.6% v 91%
p<0.001) and pulmonary pathology identification (29% v. 91% p<0.001). 6 month retention rate was excellent for: Written Scores ( 92.3%)
, Practical Skills (93%) , Setup/Landmark Identification (88%) Artifact Identification (100%).
Conclusion: Dedicated lung ultrasonography training can be integrated into a rheumatology fellowship program for potential screening of
CTD-ILD.
Disclosure: C. Gasho, None; K. Torralba, None; D. Chooljian, None; C. B. Wang, None; V. Dinh, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/impact-of-a-lung-ultrasound-course-for-rheumatology-

specialist-impact-2
Abstract Number: 99
A Pilot Study of the Use of a Validated Gout Script Concordance Test Assessment in an
Interdisciplinary Musculoskeletal Education Program
Bernadette C. Siaton1, Andrea Barker2 and Michael J. Battistone2, 1Rheumatology, University of Maryland School of Medicine, Baltimore,
MD, 2Veterans Affairs Salt Lake City Health Care System and University of Utah School of Medicine, Salt Lake City, UT
SESSION INFORMATION
Background/Purpose: A validated script concordance assessment (SCT) for gout was created for use in the internal medicine residency
program at the University of Maryland Medical Center (UMMC). The assessment demonstrated high reliability and large effect size in a
population of 143 learners.1 The aim of this pilot study was to explore the feasibility of using this tool with interprofessional, multilevel
groups of learners at the Center of Excellence in MSK Care and Education (MSK COE) at the Salt Lake City Veterans Affairs Medical
Center (SLC VAMC), to inform full implementation of the SCT in July, 2017.
Methods: A convenience sample of 19 learners (14 students or trainees; 5 practicing primary care providers (PCPs)) participating in
programs at the SLC VAMC MSK COE, were asked to complete the SCT before and after a didactic session on gout. They were then sent
emails containing the URL to access the SCT before and after the didactic. Time to complete the survey was not provided during the course.
SCT was scored using an aggregate scoring method based on the results of an expert panel. Average pre- and post-test scores were
calculated. A one-way ANOVA was used to compare pre- and post-test scores.
Results: Nine learners (47%) completed both the pre- and post-didactic SCT. The maximum possible SCT score was 50.16 points. For
reference, the average score of the expert panel was 40.65 (SD=1.72) points. The average pre- and post-test scores for the UMMC
population were 31.32 (SD=3.12) points and 33.98 (SD=2.72) points, respectively. The average pre-test score for the SLC VAMC
population was 29.71 (SD=5.08) points. The average post-test score was 32.04 (SD=2.73) points. SLC VAMC learners did not show a
statistically significant increase in scores after didactics, p=0.243. Individual learner demographics, pre-test scores, and post-test scores are
below.
Learner Type Pre-test Post-test
Score Score
Nurse Practitioner
Student 31.74 35.72
Physician Assistant
Student 31.86 30.99
Medicine Resident 30.84 34.95
Physician 32.95 33.76
Nurse Practitioner 26.87 31.60
Physician 32.65 33.05
Nurse Practitioner 33.16 27.48
Conclusion: This pilot study demonstrates feasibility of implementing a validated SCT to assess knowledge of gout in a different institution,
across an interprofessional and multilevel group of learners. The response rate was low, indicating that different methods of interfacing with
this instrument, including confirmation of participation, are needed with our learner groups. The larger pre-course variance, relative to the
reference population, may reflect the comparative diversity of our learners, but the small sample size and response rate limit the validity of
statistical inferences. We will continue to use the SCT assessment in the MSK Education Week curriculum and accrue additional learners in
order to better understand its use as an assessment.
Reference: 1. Siaton BC, Clayton E, Kueider AM, Rietschel M. Use of Script Concordance Testing to Evaluate the Efficacy of a Web-Based
Module on Gout: Three Years of Experience [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10).
Disclosure: B. C. Siaton, None; A. Barker, None; M. J. Battistone, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-pilot-study-of-the-use-of-a-validated-gout-script-

concordance-test-assessment-in-an-interdisciplinary-musculoskeletal-education-program
Abstract Number: 100
Improving Internal Medicine Resident’s Knowledge through a Web-Based

Musculoskeletal Educational Module
Uzma Haque 1,2, Clifton O. Bingham III3 and Allan C. Gelber4, 1Rheumatology, Johns Hopkins School of Medicine, Lutherville, MD,
2Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, 3Rheumatology, Johns Hopkins University, Baltimore, MD,
4Johns Hopkins University School of Medicine, Baltimore, MD
SESSION INFORMATION
Background/Purpose: Musculoskeletal (MSK) complaints account for 15-30% of the ambulatory care visits in the United States. MSK
training during Internal Medicine (IM) residency remains suboptimal, and residents report low self-confidence in managing MSK conditions.
To address this gap, we developed an internet-based MSK module to improve IM residents’ knowledge and skills in evaluation and
management of ambulatory MSK complaints. We examined the effectiveness of this educational intervention using data from the first 150
residents who completed this module.
Methods: The MSK module was disseminated on Physician Education and Assessment Center (PEAC), a web-based extramural ambulatory
curriculum, currently used by 50% (194 out of 389) of the accredited IM Programs in the US and available to 11,000 IM residents as a key
component to their ambulatory curricula. The module “Approach to a Patient with a Joint Complaint” was based on pretest-case based
didactics-posttest format. The goal of this module was to give IM residents foundational knowledge and a systematic initial approach to a
patient with a joint complaint, which leads to an appropriate initial diagnostic differential and work-up. Didactics and content was written to
address the specific cognitive/knowledge objectives of the module, such as “to distinguish arthralgia from arthritis”. MSK knowledge was
assessed using pre-tests and post-tests. We compared scores between first (PGY-1), second (PGY-2) and third year (PGY-3) residents to
assess baseline knowledge, pretest and posttest scores among different years of training. Analyses were performed using SPSS v24.
Results: Of 151 residents completing the module, 32% were program year (PGY)-1, 32% were PGY-2, and 36% were PGY-3. The
programs were 23.2% university training programs, 59.6% were community training programs, 7.3% were “other” training programs, and
9.9% were unknown training programs. Baseline mean (SD) pre-test scores were 59.4% (23.4). Pre-test scores were significantly higher
when comparing PGY3 to PGY1 (p=0.02) only, but not between other years. The mean post-test score was 91.2% (11.2). Completion of the
MSK module led to significant improvement from pre- to post-test scores (mean improvement =31.84% (SD=24.53). There was no
difference in the post-test scores among the three years of trainees.
Conclusion: Web-based modules can be effective in augmenting and disseminating MSK knowledge to IM trainees. Additional modules and
topics are being implemented. Further studies are required to evaluate whether knowledge gained from this intervention translates into
improved care for patients with MSK complaints.
Disclosure: U. Haque, None; C. O. Bingham III, None; A. C. Gelber, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/improving-internal-medicine-residents-knowledge-

through-a-web-based-musculoskeletal-educational-module
Rime (Reporter-Interpreter-Moderator-Educator) Evaluation Tool to Assess Fellows in

Rheumatology
Michelene Hearth-Holmes1,2, Amy C. Cannella3 and Alan R. Erickson4, 1Internal Medicine/Rheumatology Division, Univ. of Nebraska
Medical Center, Omaha, NE, 2Internal Medicine/Rheumatology Division, University of Nebraska Medical Center, Omaha, NE, 3Section of
Rheumatology, University of Nebraska Medical Center, Omaha, NE, 4Omaha VA Medical Center and University of Nebraska Medical
Center, Omaha, NE
SESSION INFORMATION
Background/Purpose:
Rheumatologists in academic settings strive to be excellent teachers and educators. The ACR reinforces this perspective by bestowing yearly
education awards for outstanding clinician educators who assist in maintaining and increasing the workforce. The RIME method of evaluation
is a teaching tool used to gauge medical students and residents in multiple clinical settings, focusing on whether a student has mastered the
subjects of reporting and interpreting data followed by the ability to teach medical information. The ability to teach medical information
enhances a student’s ability to recall information during standardized testing. The purpose of this study is to assess if rheumatology fellow
performance on RIME evaluations can predict improvement in in-service examination scores from year 1 to year 2 of their fellowship.
Methods:
An evaluation tool using RIME format was adapted to assess four domains (presentation quality, presentation skills, analysis, critical
thinking). Fellows were given a number score for each domain as well as a total score (1-does not meet expectations; 2-meets expectations;
3-exceeds expectations). Seven teaching faculty were trained on the use of the tool to determine a RIME designation of reporter, interpreter,
moderator, or educator. Every presentation given during the two-year fellowship was evaluated. The in-service scores were from first and
second year rheumatology fellow examinations. All fellows’ ITE scores improved in absolute numbers and percentile rank from year 1 to
year 2. RIME scores for each domain were tabulated and compared to the in-service scores. The RIME score was calculated as the mean of
the 4 separate domains using a 1-3 scale. The overall RIME score was calculated as the mean of the four sections scored. These scores were
compared against the year 1, year 2, and the mean ITE scores for years 1 and 2. All presentations were completed and evaluated prior to the
year 2 ITE. Statistical models used were generalized estimating equation models with an exchangeable variance structure to account for
repeated measurements within fellows.
Results:
Data was collected on eight fellows over four years. There were a total of 34 encounters with an average of four encounters per fellow. This
data was compared to in-service examinations from years 1 and 2. Year 1 ITE scores and mean year 1 and 2 ITE scores were not
significantly associated with RIME scores (p=0.194; p=0.083). Year 2 ITE scores were significantly associated with RIME scores
(p=0.036). RIME designations noted that of the 29 completed encounters, 21 presentations were marked as educator, 4 each as interpreter or
moderator and none were marked as reporters. Five encounters were not completely scored and were excluded from the analysis.
Conclusion:
(1) Only the 2nd year ITE scores were significantly associated with RIME scores.
(2) RIME scores for year 1 and the combined years 1 and 2 ITE scores did not correlate.
(3) This data would suggest that RIME feedback to the fellows during their training program prior to year 2 ITE (approximately 19 months),
reinforces the skills needed to master, retain, and communicate medical knowledge.
(4) RIME, as well as ITE, is an important tool in the training and evaluation of rheumatology fellows.
Disclosure: M. Hearth-Holmes, None; A. C. Cannella, None; A. R. Erickson, Amgen, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rime-reporter-interpreter-moderator-educator-evaluation-

tool-to-assess-fellows-in-rheumatology
Incorporating Temporal Artery Ultrasound in a UK District General Hospital with No

Prior Colour Doppler Sonography Service: An Encouraging Preliminary Analysis
Othman Kirresh1, Chintu Gademsetty2 and Charles Li1, 1Rheumatology, NHS Royal Surrey County Hospital, Surrey, United Kingdom,
2Radiology, NHS Royal Surrey County Hospital, Surrey, United Kingdom
SESSION INFORMATION
Background/Purpose:
Temporal Arteritis (TA) is the most common large vessel vasculitis, affecting adults over the age of 50. It is associated with significant
morbidity due to ischemic manifestations such as blindness and stroke.1 The gold standard for diagnosis has always been temporal artery
biopsy (TAB) and although highly specific (98%) it lacks sensitivity, and can yield false-negative results in up to 60% of cases. The
emergence of CDS in the diagnosis of GCA has now been widely acknowledged, further supported by meta-analyses confirming its validity.2
Prospective postulate a better sensitivity compared to TAB.3 For hospitals with no prior experience in TA-CDS a common validity concern
lies in the procedures intra-operator reliability.
Methods:
A temporal arteritis (TA) pathway incorporating CDS was introduced into a small UK district general hospital serving a population of
200,000. It was presented at a local hospital medical meeting attended by all doctors to raise awareness. Subsequently the pro forma was
distributed throughout the trust including medical wards, Accident and Emergency (A&E) and the Medical assessment unit (MAU).
As part of the pathway every patient who was referred for a TAB (performed by the Maxillofacial surgeons), also underwent a CDS. The
latter was performed by one musculoskeletal (MSK) Consultant Radiologist who was blinded in terms of patient symptoms i.e. side of
headache. Crucially the radiologist although experienced (n= 20,000 MSK Ultrasound studies) has not been trained specifically in temporal
artery ultrasound. Patients would then be followed up in Rheumatology Outpatients with the results of the investigations within 4 weeks.
Results:
Table 1:
Referrals N= 20
Treated for TA 13/20
Gender Male: 10/20
Female: 10/20
Age Range 56- 85
Mean Age 71
Mean time prior to Range: 48 hours
TAB on GC 10.2 Days - 17 days
Mean time prior to Range: 24 hours
CDS on GC 5.1 Days - 11 days
Mean duration of
GC Neg for TA 5.7 weeks
Average initial GC Range: 40 - 60
dosage 42.3mg mg
TAB positive TAB Negative

CDS Positive 3/12 (3/13) 7/20 (7/13)
CDS Negative 0/20 (0/13) 2/20 (2/13)
Positive TAB 3/20 (3/13)

Positive CDS 11/20 (11/13)
McNemar Test
(CDS vs TAB) P = 0.023
TAB had a specificity of 100% in contrast the sensitivity was 23% (Sensitivity 84% for CDS).
Conclusion:
TA can be a challenging diagnosis for clinicians to make; hence diagnostic investigations are important. Our results demonstrate the critical
role and value of CDS in the diagnosis and management of TA. When clinical suspicion is high for TA our data shows CDS as specific as
TAB, but more importantly even when a radiologist is new to the procedure significantly higher sensitivity when compared to TAB (84%,
P<0.023). Despite non familiarity of the operator the procedure adds to the diagnostic process. Our study data is line with existing data, 2,3
and highlights the necessity to incorporate CDS in the diagnosis of TA.
References
1.Jennette JC, Falk RJ, Bacon PA et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides.
Arthritis Rheum 2013;65:1-11
2. Karassa FB, Matsagas MI, Schmidt WA et al. Meta-analysis: test performance of ultrasonography for giant-cell arteritis. Ann Intern Med
2005;142:359-69.
3. Luqmani R, Lee E, Singh S, Gillett M et al (2016). The role of Ultrasound Compared to biopsy of Temporal Arteries in the Diagnosis and
Treatment of Giant Cell Arteritis
Disclosure: O. Kirresh, None; C. Gademsetty, None; C. Li, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/incorporating-temporal-artery-ultrasound-in-a-uk-district-

general-hospital-with-no-prior-colour-doppler-sonography-service-an-encouraging-preliminary-analysis
Teaching Musculoskeletal Examination to Internal Medicine Residents in Digital Age

Sonam Kiwalkar and Odunayo Olorunfemi, Internal Medicine, Rochester General Hospital, Rochester, NY
SESSION INFORMATION
Background/Purpose: The resident-run internal medicine clinic at our community hospital caters to an inner city population. Lower back
pain and knee pain are among the top 5 presenting complains. We have a heterogeneous group of residents who graduated from medical
school from different parts of the world, who vary in experience of practicing medicine before residency, many of whom were exposed to a
minimal or unstructured musculoskeletal (MSK) curriculum in medical school affecting their confidence in performing MSK exam. Our
objectives were to improve resident knowledge, skills and engage a heterogeneous group of residents in an active learning classroom activity
designed to improve MSK exam skills.
Methods: We designed a MSK workshop incorporated into our mandatory ambulatory curriculum. There were 2 sessions (upper & lower
extremity), 2 hours each, that all 58 residents completed. Based on a flipped classroom design, pre-classwork was assigned including review
articles and short videos. Classwork comprised of case discussions and peer led MSK skill demonstration and practice sessions. A pretest
multiple choice questions was conducted 5 weeks prior to the first session, a post test immediately after and another after 6 months. Pre and
post surveys measured levels of confidence and engagement in this active learning experience compared to passive learning. T-test and Chi
was used to analyze data.
Results: Residents did better on posttest compared to pretest (p<0.0001). PGY3 sustained their scores even after 6 months. Mean increase in
scores were higher for PGY 1 compared to seniors (p<0.0081). Self-reported confidence in MSK exam increased across the board
(p<0.004). Those who practiced medicine before joining residency and those who demonstrated MSK skills to their peers sustained this
confidence even after 6 months. Use of smart phone during this active workshop compared to traditional classroom passive teaching is shown
in Figure 1 & 2, which was used as a marker of resident engagement.
Conclusion: The data suggests that a flipped classroom based MSK curriculum improves medical knowledge and skills of performing a MSK
exam in a heterogeneous group of Internal Medicine residents. Moreover, it was successful in capturing attention of residents in a digital age.
The reason that PGY 3 did better on knowledge component after 6 months may be attributed to their preparation for boards. Compared to
similar endeavors in the past, we had a 100% retention rate because our sessions were mandatory. We hope to enhance our curriculum by
embedding standardized patients and observed structured clinical assessments.
Disclosure: S. Kiwalkar, None; O. Olorunfemi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/teaching-musculoskeletal-examination-to-internal-

medicine-residents-in-digital-age
Utility of a Virtual Rheumatology Clinic for Community Based Internal Medicine

Residency Program
Sonam Kiwalkar1 and Bethany A. Marston2, 1Internal Medicine, Rochester General Hospital, Rochester, NY, 2Rheumatology, University of
Rochester, Rochester, NY
SESSION INFORMATION
Background/Purpose: At our mid-sized community hospital, internal medicine residents have little routine access to subspecialty
rheumatology faculty clinical and didactic teaching, which has been reflected in below-average in-training exam scores in recent years. We
needed an active learning resource to disseminate practical aspects of rheumatologic diagnoses and management. Hence, we partnered with
the University of Rochester, and collaborated to further develop the ‘Virtual Rheumatology Clinic’ Tool. University residents had found the
online tool as an engaging, interactive and user friendly series of virtual patients, which we felt would benefit residents and students at
Rochester General. Our primary outcome was to improve confidence in diagnosis and treatment of rheumatologic conditions. Our secondary
outcomes were to improve knowledge base in rheumatology and obtain user feedback for these modules.
Methods: We had a total of 58 participants (19 PGY 1, 20 PGY 2, 19 students) using the tool. Login instructions were sent via email. 6
modules (lupus, lower back pain, gout, myositis, giant cell arteritis and osteoporosis) were completed over 3 months. Knowledge was
assessed by a pretest and posttest covering a broad range of rheumatology topics. Confidence and usefulness of the tool was determined by
pre and post surveys. Data was analyzed by T test and Chi square test.
Results: Self-reported confidence in diagnosis and treatment of rheumatologic diseases was below average to average among students and
residents before using the modules (P=0.560). Students gained more confidence compared to residents after completing the modules
(P=0.04). There was no difference in pretest and posttest scores across the board (P=0.08). Improvement was greater in those concepts
covered by the modules compared to those which were not (P=0.001), Residents had a greater mean increase in scores compared to students
(P=0.001). Perceived usefulness of modules is shown in Figure 1.
Conclusion: The modules seem to be more appropriate for residents than students, based on overall improvement in objective test scores.
Students and residents both acknowledged the usefulness of the modules. Improvement in global post-tests were not detected, likely in part
because these were not limited to topics covered; sub scores on covered diagnoses did improve. Our future goals would be to expand the
range of topics covered to include rheumatoid arthritis and psoriatic arthritis, expand access to other trainee groups such as family medicine
residents and compare utility among groups, and compare the in-training exam scores for cohorts who used this tool to historic cohorts.
Disclosure: S. Kiwalkar, None; B. A. Marston, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/utility-of-a-virtual-rheumatology-clinic-for-community-

based-internal-medicine-residency-program
Tweeting the Meeting: Analysis of Twitter Use during the American College of
Rheumatology 2016 Annual Meeting
Mosaab Mohameden1, Victoria Malkhasyan2, Baker Alkhairi3, Najla Aljaberi4 and Candice Yuvienco5, 1Internal Medicine, University of
California San Francisco - Fresno Medical Education Program, Fresno, CA, 2University of California San Francisco - Fresno Medical
Education Program, Fresno, CA, 3Internal Medicine, Blake Medical Center, Bradenton, FL, 4Cincinnati Children’s Hospital Medical Center,
Cincinnati, OH, 5Internal Medicine, Division of Rheumatology Director, University of California San Francisco, Fresno Medical Education
Program, Fresno, CA
SESSION INFORMATION
Background/Purpose: The American College of Rheumatology (ACR) annual meeting is the premier rheumatology research and education
event of the year. The ACR adopted the use of social networks to spread medical knowledge. Twitter is a popular social network site with
hundreds of millions of users and over 500 million Tweets being sent each day, there is a great opportunity for ideas to reach a global
audience of new and existing professionals and patients. The ACR has specifically used and encouraged the use of twitter for such purpose
and to promote its events and disseminate news and educational tweets from the annual meeting. In this study, we aim to analyze the use of
twitter at the 2016 ACR annual meeting.
Methods: The Sympular Signals, a specialized healthcare social media analytics platform was used to analyse the hashtag #ACR16, the
official hashtag of the ACR 2016 meeting. The analysis was conducted on tweets during the meeting days November 11th-16th of 2016. The
number of tweets, participants, impressions, average tweets per hour and average tweets per participant was determined. Advanced search
on Twitter was also conducted using the hashtag #ACR16 with timeframe between November 11th-16th. The resulted tweets were sorted by
category “top tweets” which are the most popular tweets according to Twitter. The top 50 tweets were categorized by content to scientific,
social, administrative, industry promotion, or irrelevant.
Results: The 2016 ACR annual meeting had over 16,000 attendees from around the world. The number of people who participated in the
hashtag #ACR16 was 3,298 (about 20% of the attendees) sending 16,796 tweets during the meeting days, with an average of 5 tweets per
participant and 117 tweets per hour, leaving 50,302 million impressions. The hashtag activity reached a peak of 4146 tweets on the 4th day of
the meeting, November 14th. Seventy percent of the top tweets were by physicians, 10% by medical journals, 10% by patient advocate
groups, and 10% by non-medical patient advocate individuals.
Forty two percent of the top 50 tweets had scientific content ranging from disease progression to treatment options. Whereas 28% had social
content such as selfies and group photos to commemorate the event. Irrelevant tweets were mostly appreciation tweets addressed to some of
the presenters at the meeting and represented 26%. Surprisingly, only 2% of content was industrial promotions and 2% were administrative
tweets.
Conclusion: Twitter has facilitated communication between attendees and helped in delivering valuable information to them and to the public
efficiently and free of cost. Most of the tweets were posted by physicians and the posts were mostly scientific. A more targeted approach can
be implemented to increase tweets generally and scientific posts specifically by attendees, and to encourage industrial companies to tweet
about their products. This is a useful and cost-effective way to deliver valuable information and knowledge to a much further audience than
just attendees.
Disclosure: M. Mohameden, None; V. Malkhasyan, None; B. Alkhairi, None; N. Aljaberi, None; C. Yuvienco, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/tweeting-the-meeting-analysis-of-twitter-use-during-the-

american-college-of-rheumatology-2016-annual-meeting
Rheumatology Fellows Teaching in a Consult Setting: Pilot Project at Two Training

Hospitals
Holly Smith1, Sarah Kazzaz 1, Anju Mohan2 and Jammie Barnes1, 1Rheumatology, UT Health, McGovern Medical School Houston,
Houston, TX, 2Internal Medicine, UT Health, McGovern Medical School Houston, Houston, TX
SESSION INFORMATION
Background/Purpose:
Subspecialty consults in a hospital setting often contribute to disjointed patient care and frustrated providers. Miloslavsky et al (1) previously
demonstrated improvement in rheumatology fellows’ ability to teach in a consult setting in a standardized learner environment. We sought to
perform a similar intervention in a pilot real-world setting at our two teaching hospitals. Our goals were to improve fellows’ ability to teach,
create interest in the field, and facilitate more collaborative patient care.
Methods:
A 10-question pre-intervention survey was administered to residents on internal medicine teams at each of the 2 training hospitals. The
survey utilized a 5-point Likert scale to address 7 aspects of rheumatology fellows’ ability to teach, overall effectiveness and
approachability, as well as quantifying percentage of time recommendations were shared in person. Our intervention included: a workshop
for fellows on adult learning theory and self-directed learning; provision of pocket card containing medicine team locations, contact numbers,
and prompt questions; monthly email reminders of the project goals to attendings and fellows. Rheumatology attendings standardized consult
rounds by visiting teams following patient evaluations to relay our recommendations; fellows were instructed to lead the discussion. We
employed this strategy for four months, after which the same survey was administered to residents on medicine teams. There was no
randomization or blinding due to the nature of the study.
Results:
There were 33 pre-intervention and 15 post-intervention completed surveys. Mean scores on each of the 10 questions improved from pre- to
post-intervention. Overall teaching effectiveness improved from mean of 3.55 to 4.4 (on 5-point scale). Prior to the intervention, 9% of
respondents reported receiving in-person recommendations at least 50% of the time compared to 60% of respondents after the intervention.
Conclusion:
The findings of our pilot project are similar to the “Rheumatology Fellows as Teachers” project by Miloslavsky et al (1). With a simple
teaching intervention and standardization of the workflow, we improved perceived teaching skills in all areas measured. Our limitations
included few survey respondents and inability to control for improvements in fellow teaching due to increased experience. Despite these
limitations, our findings suggest that having a standardized process for consultation that fosters a positive teaching interaction and
collaboration can have far reaching effects on resident fellow interactions as well as patient care. Future studies could include other consult
services, and a paired pre- and post-intervention analysis.
1. Miloslavsky, E. M., et al (2016), Fellow As Teacher Curriculum: Improving Rheumatology Fellows’ Teaching Skills During Inpatient
Consultation. Arthritis Care & Research, 68: 877–881.
Disclosure: H. Smith, None; S. Kazzaz, None; A. Mohan, None; J. Barnes, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rheumatology-fellows-teaching-in-a-consult-setting-pilot-

project-at-two-training-hospitals
A Blended Learning Approach to Clinical Skills Teaching: E-Learning for Paediatric

Gait, Arms, Legs and Spine Examination (pGALS)
Sarah Cope 1, Sharmila Jandial2 and Helen E. Foster3, 1Paediatric Rheumatology, Great North Children's Hospital, Royal Victoria
Infirmary, Newcastle upon Tyne, Paediatric Rheumatology, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom,
2Department of paediatric rheumatology, Great North Children's hospital, Royal Victoria Infirmary, Newcastle upon Tyne, Department of
paediatric rheumatology, Great North Children's hospital, Royal Victoria Infirmary, Newcastle upon Tyne, Newcastle upon Tyne, United
Kingdom, 3Institute of Cellular Medicine and Paediatric Rheumatology, Newcastle University and Great North Children's Hospital,
Newcastle Upon Tyne, United Kingdom
SESSION INFORMATION
Background/Purpose:
Musculoskeletal (MSK) presentations in childhood are common and often present initially to clinicians who are not specialists in paediatric
MSK medicine.
Many doctors report lack of confidence and competence in paediatric MSK clinical skills relating to lack of teaching both at undergraduate
(1) and postgraduate levels (2). The paediatric Gait, Arms, Legs and Spine (pGALS) examination is a clinical skill targeting non-specialists
and is widely taught (3).
One of the ongoing challenges in paediatric MSK education is the reliance on MSK specialists to deliver teaching yet often this resource is
limited. Blended learning combines face-to-face with digital resources, and allows greater reach to learners. Using an evidence-based
approach, we have developed an e-learning module focused on paediatric MSK clinical skills to complement pGALS teaching, and describe
the development and evaluation process.
Methods:
Identification of the learning needs for this module came from previous research with medical students and family medicine clinicians,
alongside curriculum review and qualitative work with medical students. In conjunction with web-developers we developed an interactive,
case-based module using key e-learning strategies such as question & answer, click and reveal, and reiteration of key learning points. The
module focused on key elements; MSK history, pGALS manoeuvres and common abnormalities found, red flags, next steps (investigations
and management) and links to Paediatric Musculoskeletal Matters website (www.pmmonline.org) for more information.
The evaluative strategy focused on qualitative methods including pre-testing and focus groups to allow a greater understanding of the user
experience of both the module and perceptions of e-learning in general. Focus groups were audio-recorded, transcribed and underwent
thematic analysis.
Results:
The final e-module had 22 pages, taking 30 minutes to complete. Emergent themes from the focus groups were positive and related to
navigation and usability, content and language, application and reach, learning styles and use of technology. An iterative approach to the
module development gave greater clarity to the case and presentation of key learning points. The students valued cased based learning and the
use of questioning to re-inforce learning. They deemed the variety of modalities useful for their learning.
Conclusion:
Iterative development of this e-learning module, in conjunction with learners, has led to a well-received resource as part of blended learning
to complement face-to-face teaching. The module will be openly available to support teaching and learning of paediatric MSK clinical skills.
Further e-module development is planned.
References:
1. Jandial S, Rapley T, Foster H: Current teaching of paediatric musculoskeletal medicine within UK medical schools – a need for change.
Rheumatology (Oxford) 2009, 48(5):587-590.
2. Foster HE, Everett S, Myers A: Rheumatology training in the UK: the trainees’ perspective. Rheumatology (Oxford) 2005, 44(2):263-
264
3. Foster, H.E. and S Jandial (2013) ‘pGALS – paediatric Gait Arms Legs and Spine: a simple examination of the musculoskeletal system.
Pediatric Rheumatology 11 (1):44
Disclosure: S. Cope, None; S. Jandial, None; H. E. Foster, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-blended-learning-approach-to-clinical-skills-teaching-

e-learning-for-paediatric-gait-arms-legs-and-spine-examination-pgals
Impact of Antiphospholipid Syndrome Ibook on Medical Students’ Improvement of

Knowledge: An International Randomized Controlled Experimental Study
Stephane Zuily1, Laurent Phialy2, Eloïse Germain2, Ozan Unlu3, Virginie Dufrost4, Isabelle Clerc-Urmès4, Jessica R. Berman5, Michael
Lockshin6, Denis Wahl7 and Doruk Erkan8, 1Regional Competence Center For Rare Vascular And Systemic Autoimmune Diseases, CHRU
de Nancy, Vascular Medicine Division and Regional Competence Center for Rare Vascular and Auto-Immune Diseases; Inserm U1116;
Lorraine University, Nancy, France, 2Lorraine University, Nancy School of Medicine, Nancy, France, 3Barbara Volcker Center for Women
and Rheumatic Diseases, Hospital for Special Surgery, Weill Cornell Medicine, New York, NY, 4Nancy Academic Hospital, Nancy, France,
5Rheumatology, Hospital for Special Surgery, New York, NY, 6Hospital for Special Surgery, NYC, NY, 7CHU de Nancy, Vascular
Medicine Division and Regional Competence Centre For Rare Vascular And Systemic Autoimmune Diseases; and UMR_S U1116 Research
Unit, Nancy, France, 8Rheumatology, Hospital for Special Surgery- Weill Cornell Medicine, New York, NY
SESSION INFORMATION
Background/Purpose: iBooks, a free electronic book application by Apple, is well-suited for publishing interactive medical texts. To date,
no iBook on Antiphospholipid Syndrome (APS) exists, and the utility of an Apple iBook for medical students as a teaching method in APS
has never been assessed. Our objective was to assess medical students' improvement of knowledge and satisfaction with an interactive APS
iBook, in comparison with conventional teaching methods.
Methods: The APS iBook was developed both in French and English by a professional iBook developer (LP) with the guidance of a medical
team. Second year medical students, who were naïve of lectures regarding APS, were enrolled from two institutions (Nancy University,
France; Weill Cornell Medicine, New York, NY). For the “teaching intervention”, following IRB approvals, participants were randomly
distributed to three groups: a) APS iBook with interactive capability (Group A); b) printed copy of the material contained in the interactive
APS iBook (Group B); and c) classroom presentation of the material contained in the APS iBook (Group C) by a physician (SZ or DE). A
standardized medical questionnaire about APS (total score: 10 points) was filled by the participants before and after teaching interventions.
Furthermore, participants were asked to fill out a standardized satisfaction survey (max: 10). Recall capability of students was tested four
months after the intervention (score: 10 pts).
Results: 233 second-year medical students were enrolled (iBook group: 73; print group: 79, and lecture group: 81). Mean improvement of
knowledge was significantly higher in the lecture group in comparison to the iBook group. Satisfaction was significantly higher in both the
lecture and the iBook groups, compared to the print group on several dimensions including overall quantitative satisfaction, subjective
enhanced knowledge, interactivity, quality of content, comprehensibility, and pleasure of learning. Recall capability of students (n=109) was
not significantly different among groups (Table).
Conclusion: Based on our international two-center randomized control study of medical students, a classroom APS lecture is the most
effective method in improving medical students’ knowledge, when compared to self-learning methods, i.e., APS iBook or APS printed
material. Among these two self-learning methods, medical students were more satisfied with the APS iBook, although both resulted in the
same degree of improvement of knowledge. Given the complexity of the spectrum and the management of aPL-related clinical manifestations,
we hope that our APS iBook will help medical students in their curriculum and increase the awareness of APS among the community.
APS iBook: https://itunes.apple.com/fr/book/antiphospholipid-syndrome/id1185542915?mt=11
Group A Group B Group C p

(iBook) (Print) (Lecture)
Improvement of 3.65±2.474.19±3.215.06±3.21*A vs B: 0.54
Knowledge*
A vs C: 0.003
Satisfaction Score 5.7±3.0 4.0±2.6 6.4±4.0 A vs B:
<0.0001
Recall Capability** 7.9±2.0 7.8±2.1 7.6±2.0 A vs B vs C:
0.86
*Increased # of correct answers pre- and post-intervention medical questionnaires
**# of correct answers
Disclosure: S. Zuily, None; L. Phialy, None; E. Germain, None; O. Unlu, None; V. Dufrost, None; I. Clerc-Urmès, None; J. R. Berman,
None; M. Lockshin, None; D. Wahl, None; D. Erkan, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/impact-of-antiphospholipid-syndrome-ibook-on-medical-

students-improvement-of-knowledge-an-international-randomized-controlled-experimental-study
The Creation of a Structured Curriculum Outline for the Expansion of a Rheumatology

Practice to Include Nurse Practitioners and Physician Assistants
Benjamin J Smith1, Marcy B. Bolster2, Barbara Slusher3, Christine A. Stamatos4, Jeanne Scott5, Heather Benham6, Salahuddin Kazi7,
Elizabeth A. Schlenk8, Daniel Schaffer9, Vikas Majithia10, Calvin Brown Jr11, Joan Marie Von Feldt12, Joseph Flood13, David Haag14 and
Karen Smarr15, 1School of Physician Assistant Practice, Florida State University College of Medicine School of Physician Assistant
Practice, Tallahassee, FL, 2Rheumatology, Allergy and Immunology, Endocrine Associates, Massachusetts General Hospital, Boston, MA,
3Physician Assistant Studies, University of Texas Medical Branch, League City, TX, 4Rheumatology, Northwell Health, Great Neck, NY,
5Rheumatology, Cheshire Medical Clinic, Keene, NH, 6Pediatric Rheumatology, Texas Scottish Rite Hospital for Children, Dallas, TX,
7University of Texas Southwestern, Dallas, TX, 8School of Nursing Room 415, University of Pittsburgh, Pittsburgh, PA, 9Rheumatology,
Mayo Clinic, Rochester, MN, 10Division of Rheumatology, University of Mississippi, Jackson, MS, 11Rheumatology Division, Northwestern
University Feinberg School of Medicine, Chicago, IL, 12Rheumatology, UPenn, Wilmington, DE, 13Columbus Arthritis Center and The Ohio
State University College of Medicine, Columbus, OH, 14Association of Rheumatology Health Professionals, Atlanta, GA, 15Harry S. Truman
Memorial Veterans Hospital and University of Missouri-Columbia, Columbia, MO
SESSION INFORMATION
Background/Purpose: Rheumatology practices are expanding to include non-physician healthcare providers, such as nurse practitioners and
physician assistants (NP/PAs). To date, there has not existed a structured curriculum for NP/PAs for the acquisition of rheumatology
knowledge. The Association of Rheumatology Health Professionals (ARHP), a division of the American College of Rheumatology (ACR),
charged a task force (TF) to recommend ways to facilitate the preparation of NP/PAs to work in a rheumatology practice setting.
Methods: The TF, consisting of private practice and academic rheumatologists, NPs and PAs, including those in adult and pediatric settings,
assimilated information from many sources and resources to develop mechanisms for NP/PAs to acquire rheumatology knowledge. Through
face-to-face and webinar meetings, the TF designed a Rheumatology Curriculum Outline (RCO), incorporating stakeholder’s feedback, to
provide a framework for the training of NP/PAs new to rheumatology practice.
Results: The core competencies, from the Accreditation Council for Graduate Medical Education (ACGME) Core Competencies, Nurse
Practitioner Core Competencies, and Competencies for the Physician Assistant Profession, of patient care, medical knowledge, systems-
based learning, practice-based learning and improvement, professionalism, and interpersonal and communication skills, served as a
framework for the RCO creation. (Table 1) Informed by stakeholder’s feedback, a NP/PA RCO was developed, endorsed by the ACR
Board of Directors and is ready for use by community-based and academic rheumatology practices, whether pediatric or adult, who desire to
add a NP/PA to their practice. The RCO includes a Rheumatology Toolbox for Suggested Learning Activities and Assessments to facilitate
the development of a robust learning environment for the NP/PA new to rheumatology practice. The Toolbox is an amalgam of resources that
were identified by the task force as important and useful for the development and experience of the early NP/PA rheumatology provider.
Foundational knowledge, skills and attitudes embodied in the RCO are generally believed to be attainable within one year for NP/PAs.
Realizing the needs of individual practices vary, foundational and aspirational expectations are included in the RCO, allowing for flexibility
in the application of the RCO to specific practice settings.
Conclusion: The ACR/ARHP NP/PA Rheumatology Curriculum Outline is a valuable tool to facilitate efficient and effective training of a
NP/PA new to rheumatology and incorporate him/her proficiently as a patient care provider. Increasing the number of NP/PAs trained in
rheumatology assists in closing the workforce gap, thus providing access to care for more persons with rheumatic disease.
Table 1
Disclosure: B. J. Smith, None; M. B. Bolster, None; B. Slusher, None; C. A. Stamatos, None; J. Scott, None; H. Benham, None; S. Kazi,
None; E. A. Schlenk, None; D. Schaffer, None; V. Majithia, None; C. Brown Jr, None; J. M. Von Feldt, None; J. Flood, None; D. Haag,
None; K. Smarr, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-creation-of-a-structured-curriculum-outline-for-the-
expansion-of-a-rheumatology-practice-to-include-nurse-practitioners-and-physician-assistants
Consensus-Building on a Rheumatology Musculoskeletal Ultrasound Scanning Protocol

for Rheumatology Fellowship Programs
Karina Torralba1,2, Midori Jane Nishio3, Ralf G. Thiele4, Robert Fairchild5, Kristal Choi6, Lorena Salto6, Amy C. Cannella7 and Eugene
Y. Kissin8, 1Internal Medicine/Rheumatology, Loma Linda University, Loma Linda, CA, 2Division of Rheumatology, Department of Internal
Medicine, Loma Linda University, Loma Linda, CA, 3John Muir Hospital, Walnut Creek, CA, 4Medicine, University of Rochester Medical
Center, Rochester, NY, 5Stanford University, Palo Alto, CA, 6Loma Linda University, Loma Linda, CA, 7Section of Rheumatology,
University of Nebraska Medical Center, Omaha, NE, 8Boston University, Boston, MA
SESSION INFORMATION
Background/Purpose: Musculoskeletal ultrasound (MSUS) is currently taught at 95% of adult United States Rheumatology fellowship
programs. Only 30 (41%) programs have a formal curriculum. MSUS curriculum development for rheumatology fellowship programs is
ongoing with ACR support. In 2011, at Rochester NY, a group of rheumatology MSUS experts developed a document on documentation,
scanning conventions, and tier designations (1, Rheumatology sonographers need to know and need to perform routinely; 2, Rheumatology
sonographers need to know but do not need to perform routinely; 3, Rheumatology sonographers may know about & may perform based on
individual practice focus) for each view of the major joints. The objective of this study is to update consensus of the 2011 Rochester
document to serve as the foundation for the development and implementation of a rheumatology MSUS curriculum for fellowship training
programs.
Methods: A 96-item IRB-approved survey was developed for use in a Delphi study. Apart from demographics (8), there were 86 questions
testing for agreement/disagreement on documentation (5), scanning conventions (5), and tier designations for 8 peripheral joint-specific areas
(76). 108 lead faculty at 113 rheumatology fellowship programs were identified based on prior surveys. 101 respondents (including the 38
who developed the 2011 document) were selected based on selected criteria including lead MSUS faculty experience, course instruction,
ACR-RhMSUS certification, or publication in MSUS. The survey was disseminated via Qualtrics¨. Survey initiation and completion
indicated consent for study participation.
Results: 55 (55%) rheumatologists responded: 39 (71%) were full time academic faculty, 40 (73%) had certification, with a third of the
respondents certified via ACR-RhMSUS pathway. 51 (59%) questions achieved high (³85%) agreement. Questions with less than 85%
agreement all concerned tier designations. 13 questions with 30-60% disagreement favored tier 1 designation over 2011 tier 2. Table 1 lists
areas of disagreement.
Conclusion: Initial phase of consensus-building reveals 41% disagreement on areas related to anatomic-region tier designation. Many
respondents favored Tier 1 over Tier 2 for many of those items, indicating a shift in overall expert opinion towards including more views in
the MSUS mastery requirements. Further clarification through subsequent rounds of this Delphi study is needed to resolve areas of
disagreement, and facilitate development of a standardized MSUS fellowship curriculum.
Table 1. Delphi Study Round 1: 2011 vs
2017 Consensus, Joint Views
MSUS Joint Views 2011 2017 Results
Agree, Disagree,
Tier n (%) n (%) Tier
Shoulder
Acromio-clavicular joint, 34
longitudinal 2 (61%) 20 (36%) 1
46
Posterior transverse 2 (83%) 8 (14%) 1
41
Dynamic impingement 2 (74%) 12 (21%) 1
36
Suprascapular transverse 2 (65%) 17 (30%) 3
37
Axillary longitudinal 2 (67%) 18 (31%) 3
Elbow
46
Olecranon bursa 2 (83%) 8 (14%) 1
44
Posterior transverse medial 2 (80%) 6 (10%) 3
Posterior longitudinal 45
medial 2 (81%) 8 (14%) 3
Wrist
Scapholunate ligament, 39
dorsal transverse 2 (70%) 15 (27%) 1
Radial orthogonal 39
compartment 1 tendons 2 (70%) 15 (27%) 1
33
Ulnar transverse 2 (60%) 20 (36%) 1
Volar longitudinal median 34
nerve 2 (61%) 21 (38%) 1
Dorsal orthogonal extensor 39
compartments 2-5 2 (70%) 14 (25%) 1
Hand
Dorsal orthogonal MCP 45
joint/PIP joint in flexion 2 (81%) 7 (12%) 3
MCP radial/ulnar 35
orthogonal 2 (63%) 20 (36%) 1
PIP joint transverse (dorsal 43
and volar) 2 (78%) 12 (21%) 1
Hand inflammatory arthritis 33
scan set 2 (60%) 20 (36%) 1
Hip
Anterior transverse femoral 37
neck 2 (67%) 18 (32%) 1
45
Lateral hip transverse 2 (81%) 10 (18%) 1
46
Snapping hip dynamic scan 3 (83%) 8 (14%) 2
25
Transverse sacral iliac joint 2 (45%) 28 (50%) 3
Knee Views
Anterior transverse 22
suprapatellar 2 (40%) 33 (60%) 1
Anterior transverse in 45
maximum flexion 1 (81%) 10 (18%) 2
Anterior transverse 37
infrapatellar 2 (67%) 18 (32%) 1
29
Medial longitudinal 2 (52%) 26 (47%) 1
32
Lateral longitudinal 2 (58%) 23 (41%) 1
41
Posterior transverse medial 2 (74%) 13 (23%) 1
Ankle
27
Anterior transverse 2 (49%) 27 (49%) 1
Dorsal longitudinal midfoot 43
joints 2 (78%) 6 (10%) 1
2 6 (10%) 3
Medial longitudinal 38
perimalleolar 2 (69%) 16 (29%) 1
38
Lateral longitudinal 2 (69%) 16 (29%) 1
Lateral oblique subtalar 46
joint 2 (83%) 6 (10%) 1
30
Posterior transverse 2 (54%) 25 (45%) 1
42
Plantar orthogonal 2 (76%) 12 (21%) 1
Foot
Dorsal transverse 38
symptomatic MTP joint 2 (69%) 17 (30%) 1
Tier Designations: Tier 1, Rheumatology sonographers
need to know and need to perform routinely;
Tier 2, Rheumatology sonographers need to know but do
not need to perform routinely; Tier 3,
Rheumatology sonographers may know about & may
perform based on individual practice focus
Disclosure: K. Torralba, None; M. J. Nishio, None; R. G. Thiele, Amgen, 8,AbbVie, 8,BioClinica, 5,Fujifilm SonoSite, 9; R. Fairchild,
None; K. Choi, None; L. Salto, None; A. C. Cannella, None; E. Y. Kissin, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/consensus-building-on-a-rheumatology-musculoskeletal-

ultrasound-scanning-protocol-for-rheumatology-fellowship-programs
Focused Musculoskeletal Ultrasound Teaching: Effect on Medical Students’ Physical

Examination Skills
Bhavna Seth1, Lorraine Stanfield2 and Eugene Y. Kissin3, 1Internal Medicine, Boston Univeristy Medical Center, Boston, MA, 2Internal
Medicine, Boston Univeristy, Boston, MA, 3Boston University, Boston, MA
SESSION INFORMATION
Background/Purpose:
Musculoskeletal ultrasound provides instant feedback for spatial understanding and the evaluation of abnormalities with great precision and
accuracy, and may aid in developing physical examination skills.
Methods:
We framed a teaching exercise to develop examination skills in medical students using ultrasound imaging as an aid in order to assess
ultrasound utility in improving these skills. Of 158 second year medical students, 63 volunteered to participate in a 2-day musculoskeletal
exercise. Students who were not able to commit to both days were excluded. On day one, all students were taught examination of the knee and
shoulder in 1 hour. We randomized 24 students for inclusion of ultrasound demonstration of key joint landmarks (Ultrasound aided group-
USG) within the same 1hr period.
Student performance was evaluated in a 20-minute OSCE on day 2 with standardized patients. Students were graded by an observer blinded
to instruction group using a standardized checklist, that included key inspection, palpation, and maneuvers for joint exams. The study was
exempted from review by the local IRB. Participant confidentiality was maintained with anonymized codes. The Mann-Whitney-Wilcoxon
test was used to analyze the results given the small sample and non-normal distribution of the scores.
Results:
The maximum score for knee and shoulder examinations were 14 and 15 respectively. For the knee examination, the mean score of the USG
(10.38±2.35) was significantly higher than the non-USG group (8.95±2.14) p=0.013. There was a non-significant trend towards improved
performance of shoulder examination in the USG (12.58±1.82) compared to non-USG (11.59±2.49) group (p=0.11).
Since ultrasound visualization is more likely to improved inspection and palpation components, we analyzed them separately. For knee
examination, the USG group fared significantly better (7.5±1.72 vs. 6.10±1.67, p=0.003); a similar trend towards improved performance in
the shoulder examination, did not reach significance in the USG group (4.96±0.99 vs. 4.49±1.12, p=0.075).
In sub-components of the knee exam, significant improvement was seen in the USG-aided group in palpation of the lateral collateral ligament
(p=0.016), popliteal space for Baker’s cysts (p=0.017), and the patellofemoral shrug test (p=0.004). For sub-components of the shoulder
exam, improvement was significant in the USG-aided group for shoulder inspection (p=0.043), palpation of the sternoclavicular joint
(p=0.008), acromioclavicular joint (p=0.043), and shoulder range of motion (p=0.045).
Conclusion:
Incorporation of ultrasound into musculoskeletal exam curriculum demonstrated short-term improvement in knee examination performance,
with a trend toward improvement in shoulder exam in second-year medical students.
Table: Knee and Shoulder Exam- ultrasound vs. non-ultrasound group scores
Disclosure: B. Seth, None; L. Stanfield, None; E. Y. Kissin, None.

View Abstract and Citation Information Online - http://acrabstracts.org/abstract/focused-musculoskeletal-ultrasound-teaching-effect-on-
medical-students-physical-examination-skills
A Qualitative Assessment of a CME “City Rounds” Workshop Educational Program to

Meet the Educational Needs of Rheumatologists
John J. Cush1, Leonard H. Calabrese2, Greg Salinas3 and Sergio Schwartzman4, 1Baylor Scott & White Research Institute, Dallas, TX,
2Rheumatic & Immunologic Disease and Infectious Disease, Cleveland Clinic Foundation, Cleveland, OH, 3CE Outcimes, Birmingham, AL,
4Hospital for Special Surgery, New York, NY
SESSION INFORMATION
Background/Purpose: : An Annual Rheumatology & Therapeutics Review for Organizations & Societies (ARTHROS) initiative called
“City Rounds” was created to meet the educational needs of rheumatologists with regard to advances in therapeutic s in Rheumatoid arthritis.
The program was designed to introduce and assess advances in diagnosis, therapeutic s and safety through an interactive roundtable, small-
group format wherein rheumatologists would interact and discuss case based issues with local and national RA experts .
Methods: These, roundtable programs were delivered in 16 US cities and attended by 5-15 rheumatologists using a case-based workbook
covering three topics: Targeted Therapies in RA, Immunopathogenesis of RA, and Safety Issues in RA Management. ARTHROS partnered
with CE Outcomes to qualitatively evaluate the impact of the City Rounds on rheumatologists using structured interviews with 12 randomly
chosen participants. Transcripts of the interviews were analyzed to identify common themes and compare practices reported by interviewees
to evidence-based guideline recommendations and learning objectives of the City Rounds program.
Results: The findings of the qualitative analysis demonstrate the City Rounds program enabled rheumatologists to provide more thorough
patient education. Participant interviews showed the following: 94% of participants believed that these educational objectives impacted their
knowledge; 98% of the participants indicated that this activity enhanced their effectiveness in treating; 91% of participants indicated that this
activity will change in their practice behavior; 24% of participants indicated they will create or revise policies for patient care; 55% of
participants indicated they will change their management and treatment of RA; 38% of participants indicated that they have no barriers in
implementing changes learned in this education. Several interviewees reported greater confidence in managing hard-to-treat patients after
participating in the education. The City Rounds program also reinforced rheumatologist use of evidence-based care in several key areas,
including: selection of tests and exams for diagnosis and monitoring; active use of evidence-based guidelines; and selection of treatments for
patients with high RA disease activity who have failed methotrexate. The findings of the assessment also suggest that, despite the positive
impact of the program, educational gaps in these same areas persist among some rheumatologists.
Conclusion: Small group, workshop or roundtable style educational programs are highly impactful as they: a) well attended by a wide
variety of practitioners (from trainees to professors; urban and suburban); b) allow for intense, impactful interactions between colleagues and
experts on important teaching points and practice issues; and c) are a conduit for the introduction and integration of guidelines and standards
of care into daily practice.
Disclosure: J. J. Cush, Pfizer, Janssen, Abbvie, Celgene, Novartis, AstraZeneca, Genentech, 2,Janssen, Abbvie, Novartis, Amgen,
Genentech, Lilly, Horizon, 5; L. H. Calabrese, Celgene, Crescendo, 2,Celgene, Crescendo, 5,Celgene, Crescendo, 8; G. Salinas, CE
Outcomes, 5; S. Schwartzman, Abbvie, Genentech, Janssen, Novartis, Pfizer, UCB, Sanofi, Regeneron, 2,Abbvie, Janssen, Genentech,
Pfizer, UCB, Crescendo, Novartis, 8,Crescendo Biosciences, Discus Analytics, National Psoriasis Foundation, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-qualitative-assessment-of-a-cme-city-rounds-

workshop-educational-program-to-meet-the-educational-needs-of-rheumatologists
A Primer on Exercise: An Interactive, Online Educational Module Incorporating Spaced

Education to Supplement the ACR Core Curriculum Outline for Rheumatology
Fellowship Programs
Amit Patel and Kenneth O'Rourke, Department of Internal Medicine, Section on Rheumatology and Immunology, Wake Forest School of
Medicine, Winston-Salem, NC
SESSION INFORMATION
Background/Purpose:
The 5 topics in rehabilitative rheumatology (RR) included in the ACR Core Curriculum Outline include exercise, adaptive equipment,
orthotics, thermal modalities and splinting. A 2004 survey of Program Directors (PD) led to a subsequent increase in RR clinical symposia at
ACR Annual Meetings. Fellowship program instruction in RR is still felt to be under-represented.
Methods:
An online needs assessment survey of PD (107), therapy providers (34), and physicians with an interest in RR (31) yielded response rates of
37%, 27% and 16%, respectively. For PD respondents, 56% did not offer a RR rotation, 71% had no one interested in leading a group
teaching session, but 93% said self-study could be part of teaching resources. There was consensus among all respondents that exercise
should be the first RR content to be addressed. Using certain software, we created a two-part, interactive, online educational module on
exercise. The first part addresses exercise modalities, CDC exercise recommendations and creating an exercise prescription, and the second
part presents current literature for self-directed study on exercise applications in selected rheumatic diseases.
An educational trial of the content in the first part of the exercise module was completed with fellows in the Carolina Fellows Collaborative
as our study participants. Fellow level of confidence in, and frequency of, prescribing exercise, as well as providing an exercise prescription
for a simulated patient, was assessed during a rheumatology OSCE (ROSCE) station. Fellows were then asked to provide an exercise
prescription immediately after, and 6 weeks after completion of the exercise module. In a randomized subset of fellows, spaced education by
email was used as a means to improve retention during the 6 weeks between the second and third prescription assignments. All prescriptions
were scored using the same metrics applied during the ROSCE station.
Results:
18 fellows (85.7%) participated in the ROSCE. 4 of 21 fellows (19.0%) completed the exercise prescriptions immediately following
completion of the module and 5 fellows (23.8%) completed the prescriptions 6 weeks after completion of the module, 1 of which had
participated in the spaced education program. Only 2 fellows (9.5%) completed all 3 sets of prescriptions, none of which had completed the
spaced education program. The average correct responses paralleled level of training, overall increasing from 70.94% to 85.42% with the
introduction of the module content. At 6-week follow-up, the average score had fallen to 67.91%. Fellow confidence in prescribing exercise,
assessed on a 6-point Likert-type scale, increased over the study from an average rating of somewhat unconfident to somewhat confident.
Conclusion:
We have created an online primer on exercise for use as part of a mini-curriculum on RR. In a pilot trial, completion of the module led to an
immediate improvement in the completeness of an exercise prescription, but this improvement was not durable in the short-term, most likely
due to the low participation rate and small sample sizes. A larger study including the effect of faculty supervision of learner participation is
warranted.
Disclosure: A. Patel, None; K. O'Rourke, ACR Curriculum Subcommittee, 6.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-primer-on-exercise-an-interactive-online-educational-

module-incorporating-spaced-education-to-supplement-the-acr-core-curriculum-outline-for-rheumatology-fellowship-programs
Early Diagnosis and Treatment of RA: Clinical Performance and Economic Outcomes
from a Continuing Education Initiative
David Gazeley1, Michael Weinblatt2 and Stephen Bender3, 1Medicine, Medical College of Wisconsin, Milwaukee, WI, 2Rheumatology,
Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 3FACTORx, Cherry Hill, NJ
SESSION INFORMATION
Background/Purpose:
The CME initiative RAPID® (Rheumatoid Arthritis: Primary Care Initiative for Improved Diagnosis and Outcomes) is a 7-year series of
activities that used national-scope aggregated healthcare claims data to identify primary care clinicians who diagnose and refer patients for
RA at a low frequency. Medical claims data have been used since 2008 to measure the implementation of the diagnostic and referral clinical
strategies resulting from the RAPID activities by analyzing performance changes of participants. Since its inception, over 65,516 physicians
have completed the RAPID educational activity. We have reported statistically significant improvements in the participants’ diagnostic and
referral performance (Bender S, et al. CE Measure, 2016;10:10-15).
Methods:
Rates of increased RA diagnoses and referral among providers were determined for a sample of the RAPID initiative (RAPID III) using a
national-scope administrative healthcare claims database representing over 870,000 US clinicians. New RA diagnoses were defined as the
number of unique patients with a diagnosis of RA (ICD-9 codes 714.X) who had a claim from both a primary care provider and a
rheumatologist (shared patients) in the time period prior to, or after the CME activity date [2011] and who had been prescribed (and filled) a
prescription for an appropriate RA therapy. Comparisons were made among highly matched controls of non-participants, with approximately
40 non-participant controls for every participating clinician. The follow period was approximately 2.5 years. An exploratory predictive
model was used to estimate the economic impact of earlier diagnosis and treatment of RA. The model estimated how many patients with
moderate/high disease activity were likely to transition to remission and the associated costs averted by decreased healthcare utilization and
productivity losses. Prevention of joint arthroplasty was also predicted. Deterministic and probabilistic sensitivity analyses were performed
to evaluate the influence of model parameters on the estimated outcomes of the model.
Results:
A sample of 3,919 RAPID III participants (n=1,691) was evaluated. These participants managed 265,834 patients and had 1,837 newly
diagnosed patients with RA. There was a statistically significant 11% increase in the proportion of RA diagnoses by learners following
participation in the CME initiative. All referred patients received appropriate therapy for RA. There was no change in the proportion of RA
diagnoses among the control group. The estimated costs averted when newly diagnosed patients underwent treatment leading to remission
were $11,618,483 (95% CI; $3,954,798 to $24,547,314).
Conclusion:
A CME initiative improved the post-activity performance of targeted learners significantly more than non-targeted providers. Analysis of
medical claims data is a useful tool for assessing performance change in CME initiative participants. Earlier diagnosis and treatment of RA
may be associated with decreased costs.
Disclosure: D. Gazeley, None; M. Weinblatt, FACTORx and the RAPID CME initiative, 5; S. Bender, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/early-diagnosis-and-treatment-of-ra-clinical-

performance-and-economic-outcomes-from-a-continuing-education-initiative
Training the Next Generation of Investigative Rheumatologists: Results of the Usbji’s

Young Investigator Initiative for Academic Rheumatologists
Nancy E. Lane 1, Ann Rosenthal2, Howard Hillstrom3 and Edward Puzas4, 1Center for Musculoskeletal Health, University of California,
Davis School of Medicine, Sacramento, CA, 2Division of Rheumatology, Medical College of Wisconsin, Milwaukee, WI, 3orthopedics,
Hospital for special surgery, New York City, NY, 4Orthopedic Surgery, University of Rochester School of Medicine, Rochester, NY
SESSION INFORMATION
Background/Purpose: The success of a physician scientist in academic rheumatology requires effective skills to obtain peer-reviewed
funding. The number of NIH-funded junior investigators is low in proportion to the prevalence of musculoskeletal (MSK) diseases. As well-
conceived and structured research is more likely to be funded, in 2005 the U.S. Bone and Joint Decade/Initiative (USBJI) and Bone and Joint
Canada initiated a grant mentoring and career development program for junior faculty in all fields of MSK research in the US/Canada who
had not obtained an Independent Peer Reviewed Research Grant (RO1/equivalent) in order to foster the next generation of investigators. The
purpose of this study was to determine the outcomes of Rheumatologists who attended the program 2005-2016.
Methods: The Young Investigator Initiative (YII) program included two 2-day workshops held 12-18 months apart with training in specific
aspects of the development of well-founded research studies and grantsmanship (specific aims, experimental design, budget, collaborations),
benefitting from multi-disciplinary perspectives on their proposed studies. Each mentee was assigned 2-4 experienced external mentors from
the YII faculty to complement their institutional mentors until the Young Investigator obtained funding. Mentors made themselves available to
assigned mentees for review of specific aims, evaluating grant drafts, and discussing research strategies. External mentors’ research expertise
across the MSK disciplines included rheumatology, epidemiology, orthopaedics, bioengineering, biology, PTs, OTs.
Results: The YII is a competitive, peer-reviewed program. Of 736 applicants 2005-2016, 364 (49.5%) were accepted, including 59
Rheumatologists developing studies in common and less common forms of Rheumatic disease. Program metrics are tabulated in Table 1.
Total external funding obtained by YII Rheumatology participants 2005-2016 is $48.5 million, from a combination of NIH/Canadian Institutes
of Health Research/Foundations/Granting Agencies/Institutions, including the ACR-RRF; 34/59 (58%) received peer-reviewed funding.
Conclusion: The YII program has been successful in assisting junior investigators in academic rheumatology obtain peer-reviewed funding
by providing education and external mentoring on grant structure and writing until funding is obtained.
Disclosure: N. E. Lane, LLP2A-Ale, 4; A. Rosenthal, None; H. Hillstrom, None; E. Puzas, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/training-the-next-generation-of-investigative-

rheumatologists-results-of-the-usbjis-young-investigator-initiative-for-academic-rheumatologists
Immunotherapy-Induced Rheumatic Disease: How Prepared Are Rheumatologists to

Address This Emerging Condition?
Laura Cappelli1,2, Cassandra Calabrese3, Leonard H. Calabrese3 and Clifton O. Bingham III4, 1Division of Rheumatology, Johns Hopkins
University School of Medicine, Baltimore, MD, 2Medicine/Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD,
3Rheumatic & Immunologic Disease, Cleveland Clinic Foundation, Cleveland, OH, 4Rheumatology, Johns Hopkins University, Baltimore,
MD
SESSION INFORMATION
Background/Purpose: Cancer immunotherapy targeting immune checkpoints represents a major advance in oncology, yet has been associated
with immune-related adverse events (IRAEs) affecting many organ systems, including an expanding range of rheumatic manifestations.
Rheumatologists are new to this field, and we sought to examine their awareness, experience, clinical confidence, and educational needs
regarding IRAEs by surveying rheumatology practitioners.
Methods: In the 2nd quarter of 2016, questionnaires were sent via email to health care provider cohorts at Johns Hopkins University (JHU)
and Cleveland Clinic (CC). The survey population came from their Continuing Medical Education (both) and Rheumatology Website (JH)
databases. Both cohorts had physicians and advanced practitioners. Survey questions addressed domains of awareness, clinical experience,
and interest in IRAE-specific medical education.
Results: Response rates were 114/2198 (5.2%) at CC and 39/789 (5.0%) at JHU. Male physicians from private practices and academic
institutions predominated (table 1). Only 24.1% reported familiarity with IRAEs, with most unaware of IRAEs or lacking sufficient
knowledge on the topic (table 2). Only 14.8% had seen a patient with an IRAE, with inflammatory arthritis the most common. Most (60.7%)
did not feel confident managing IRAEs. All but one participant indicated interest in educational activities on IRAEs, with
description/recognition of IRAEs perceived as the biggest educational need.
Conclusion: We conclude that most respondents 1) had limited experience with rheumatic IRAEs, 2) lacked confidence in clinically
addressing IRAEs, and 3) had a strong expressed desire for targeted education. Although limited by response rate, responder bias, and the
timing of the survey shortly after the approval of these drugs, the results suggest a considerable need for rheumatology-specific education
around this topic.
Table 1. Demographic Variables (N = 153)
Sex: N (%) Male: 93 (61%)
Female: 60 (39%)
Age: mean (SD) 55.0 (12.4)
Degree: N (%) MD/DO: 127 (83%)
NP: 8 (5.2%)
PA: 4 (2.6%)
RN: 9 (5.9%)
Other: 5 (3.3%)
Years in medical practice: 22.1 (12.9)
mean (SD)
Practice Setting: N (%) Academic: 43 (28.1%)
Private Practice: 68
(44.4%)
Hospital-based Practice: 25
(16.3%)
Industry: 5 (3.3%)
Other: 9 (5.9%)
Table 2. ICI/IRAE provider experience
Familiarity with ICIs I am unaware: 29 (21.8%)
(N= 133) I have heard of them, but am not knowledgeable:

68 (51.1%)
Familiar: 32 (24.1%)
Very familiar: 2 (1.5%)
Unsure: 2 (1.5%)
Awareness of IRAEs I am unaware: 54 (41.5%)
(N= 130) I have heard of them, but am not knowledgeable:

33 (25.4%)
Familiar: 32 (24.6%)
Very familiar: 8 (6.2%)
Unsure: 3 (2.3%)
Have seen a patient with an Yes: 18 (14.8%)
IRAE
No: 104 (85.2%)
(N = 122)
Types of IRAEs seen Inflammatory arthritis: 17
Sicca syndrome: 6
Myositis: 4
Vasculitis: 3
Colitis: 7
Confidence in management Not confident: 74 (60.7%)
of IRAEs (N = 122)
Somewhat confident: 30 (24.6%)
Moderately confident: 14 (11.5%)
Very confident: 4 (3.3%)
Disclosure: L. Cappelli, Bristol-Myers Squibb, 2; C. Calabrese, None; L. H. Calabrese, Bristol-Myers Squibb, 5; C. O. Bingham III,
Bristol-Myers Squibb, 2,Bristol-Myers Squibb, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/immunotherapy-induced-rheumatic-disease-how-

prepared-are-rheumatologists-to-address-this-emerging-condition
Using Goutpro to Make Medical Trainees Gout Pros- a Single Blinded Randomized
Control Study
Linh Ngo1, Eric Miller2, Peter A. Valen3 and Alisa Duran4, 1Division of Rheumatology, University of Minnesota, Minneapolis, MN,
2Medicine, Hennepin County Medical Center, Minneapolis, MN, 3Rheumatology/ Dept of Medicine, University of Minnesota/Minneapolis
VAMC, Minneapolis, MN, 4Department of Medicine, University of Minnesota, Minneapolis, MN

SESSION INFORMATION
Session Title: ARHP Education Poster
Background/Purpose: Gout is the most common type of inflammatory arthritis in the U.S., affecting 4% of the population. Despite modern
advancements and the availability of reference tools, the current care from primary care providers is felt to be suboptimal in the U.S. One
barrier to improving care in gout includes limited education during medical training.
To address limited education during training, we developed a digital adjunctive teaching tool, GoutPro, on the topic of gout. Utilizing a
clinically integrative model proposed by Khan et al, it takes into consideration different learning styles, current guidelines on gout,
interactive activities and clinical problem solving. In our pilot study, we obtained positive subject feedback through survey. To assess
objective trainee improvement of gout knowledge, a single-blinded randomized controlled study assessing knowledge prior to and after
GoutPro intervention was conducted.
Methods: We recruited a total of 19 medical trainees from Hennepin County Medical Center to participate in our study. Trainees included
medical students of MS 3-4 training levels and residents of PGY 1-4 training levels. All trainees registered via an online registration form
and consent forms were signed digitally. Registered participants were randomized proportionally according to level of training into the
control and the study group via a novel automated cloud based system to keep the investigators blinded. Correspondence with participants
was also managed by the automated system. All participants were sent an e-mail with a link to a pre-test of 14 questions on crystalline
arthropathy based on recommendations from the 2012 ACR Gout Guidelines and MKSAP 17. The study group was instructed to attend a live
session led by the investigators that utilized GoutPro. The control group was provided both the ACR Guidelines and UpToDate reference
articles on crystalline arthropathy for review. All participants received an identical post-test 27 days later to avoid coinciding with trainee
change of rotations. 15 out of 19 subjects completed the post-test. Our primary outcome was difference in pre- and post-quiz scores between
the control and study group. The StudentÕs t-test was used for analysis.
Results:
Average Control Study

Scores Group Group
(n=10) (n=5)
Pre-Quiz 38% 52%
Post-Quiz 41% 59%
% 3% 7%
Improvement
Conclusion:
1) The study group had a slightly higher percent improved test scores (7%) compared to those in control group (3%). The results did not
reach statistical significance due to the small study size (P=0.99).
2) At baseline, medical trainees in the study demonstrated low knowledge on gout demonstrating the need for improved gout curriculum.
3) Future GoutPro studies with larger sample size from multiple centers will be needed.
4) Utilization of a novel cloud-based automated system to randomize and communicate with study subjects was an effective cost-efficient
way to recruit, organize and manage study subjects while maintaining investigator blindness.
Disclosure: L. Ngo, None; E. Miller, None; P. A. Valen, None; A. Duran, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/using-goutpro-to-make-medical-trainees-gout-pros-a-

single-blinded-randomized-control-study
Experiences and Perceptions of Patients with Rheumatoid Arthritis Participating in an

Online Support Group: The Use of Social Media
Jude K. A. des Bordes1, Jessica Foreman1, Susan K. Peterson2, Maria A. Lopez-Olivo3, Tiffany Westrich-Robertson4, Catherine
Hofstetter5, Anne Lyddiatt6, Amye L. Leong7 and Maria Suarez-Almazor3, 1Section of Rheumatology and Clinical Immunology, Department
of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA, Houston, TX, 2Department of
Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston Texas, USA, Houston, TX, 3Section of Rheumatology
and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX,
USA, Houston, TX, 4International Foundation for Autoimmune and Autoinflammatory Arthritis, Saint Louis, Missouri, USA, St Louis, MO,
5Canadian Arthritis Patients Alliance (CAPA), Toronto Ontario, Canada, Toronto, ON, Canada, 6Musculoskeletal Group, Cochrane
Collaboration, Hamilton, ON, Canada, 7Spokesperson; Strategic Relations, Bone and Joint Decade, Santa Barbara, CA
SESSION INFORMATION
Session Title: ARHP Education Poster
Background/Purpose: Providing social support is an important component in the management of chronic diseases. In rheumatoid arthritis
(RA), peer support is particularly important for coping with the psychosocial aspects of the disease. The aim of this study was to assess the
participation, experiences, and perceptions of patients in an online support group for patients with RA using social media.
Methods: A private online support group was created on Facebook including 105 participants who were 18 years or older, residing in the
United States or Canada and had been diagnosed with RA for less than 10 years. Each week, a moderator posted a topic for discussion,
however, participants could also share other disease-relevant information not directly related to the discussion of the week. We analyzed
participants’ posts in the first 5 weeks, their reaction to responses of other participants, and how often and what information was being
shared outside the main discussion topics.
Results: Most participants were female and non-Hispanic white (94% and 87.6%, respectively). Nearly two-thirds (65%) were married or
lived with a significant other or partner and 62 (59%) had a Bachelor’s or higher degree. The mean age was 52.7 years. Although nearly all
participants visited the forum, only an average of about 50 (48%, range 42-62) actively participated in the discussions each week, with the
most and least participation recorded respectively in the first and fifth weeks. About 10 percent of participants never contributed to the
discussions. Topics discussed included physical challenges, emotional health, self-care, exercise, and socializing. Discussion on physical
challenges attracted the highest number of posts (n=311) while self-care had the least (n=120). Other information shared by participants
outside the discussion topics included their disease experiences, medications, social lives, other websites on RA, frustrations and messages
of encouragement. They also shared pictures of themselves, their families, pets and satirical depictions of their disease experience. Many
participants expressed excitement and thankfulness for the social support provided by the group.
Conclusion: Participants were generally enthusiastic about the online support group. Social media based groups may provide an alternative
means of facilitating education and peer support that is so often lacking in traditional models of care. However, more research is needed to
find better ways to encourage more participation and to sustain participant interest.
Disclosure: J. K. A. des Bordes, None; J. Foreman, None; S. K. Peterson, None; M. A. Lopez-Olivo, None; T. Westrich-Robertson,
None; C. Hofstetter, None; A. Lyddiatt, None; A. L. Leong, None; M. Suarez-Almazor, Rheumatology Research Foundation, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/experiences-and-perceptions-of-patients-with-

rheumatoid-arthritis-participating-in-an-online-support-group-the-use-of-social-media
Occupational Exposure to Asbestos and Risk of Rheumatoid Arthritis

Anna Ilar1, Per Gustavsson1, Pernilla Wiebert1, Camilla Bengtsson1, Lars Klareskog2 and Lars Alfredsson1, 1The Institute of
Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, 2Rheumatology unit, Department of Medicine, Karolinska Institutet,
Stockholm, Sweden
SESSION INFORMATION
Session Title: Epidemiology and Public Health Poster I: Rheumatoid Arthritis
Background/Purpose:
Due to the known association between silica dust and rheumatoid arthritis (RA), we wanted to study the association between RA and another
silicate mineral; asbestos. The aim was to estimate the risk of seropositive or seronegative RA from ever occupational asbestos exposure as
well as years with exposure.
Methods:
The study base consisted of men and women living in Sweden between 2006 and 2013. RA patients were identified from the Swedish
Rheumatology Quality Register (SRQ). We matched ten controls from the national population register per case on age, county and sex. Data
on occupational histories were collected from the national population and housing censuses carried out in 1960, 1970, 1975, 1980 and 1990.
A job-exposure matrix (JEM) containing historical exposure estimates from 1955-1995 to asbestos was applied to the study participants’
occupational histories. We used conditional logistic regression to assess the odds ratios (ORs) and 95 % confidence intervals (CIs) of RA
associated with ever exposure and years of exposure to asbestos. ORs were adjusted for ever exposure to respirable crystalline silica dust
and household disposable income divided into quartiles.
Results:
9 704 cases and 90 271 controls were included in the analysis. Ever vs. never asbestos exposure resulted in an OR of 1.35 (95 % CI: 1.22-
1.48) among men and 1.10 (95 % CI: 0.94-1.29) among women for seropositive RA. The ORs decreased to 1.12 (95 % CI: 1.01-1.25) and
1.02 (95 % CI: 0.86-1.22) for men and women respectively after adjusting for silica exposure and household disposable income. Asbestos
exposed men were more likely than women to have worked with asbestos for a longer period of time and their risk of seropositive RA
increased with years with the exposure. Male participants with more than 20 years of asbestos exposure at work had an adjusted OR of 1.27
(1.06-1.53, p for trend: 0.008).
Conclusion:
Asbestos exposure is associated with seropositive RA among men. The increased risk remained after adjustments for potential confounding
from silica exposure and household disposable income.
Disclosure: A. Ilar, None; P. Gustavsson, None; P. Wiebert, None; C. Bengtsson, None; L. Klareskog, None; L. Alfredsson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/occupational-exposure-to-asbestos-and-risk-of-

Patients with Rheumatoid Arthritis Have Higher Lifetime Professional and Non-
Professional Exposure to Silica Dust Particles Compared to General Population
Luca Semerano1,2,3, Catherine Cavalin4,5,6, Odile Macchi4,7, Sara El Rharras3, Mylene Petit3, Patrice Decker8,9, Emma Andre10, Paul
André Rosental4,11 and Marie-Christophe Boissier12, 1UMR 1125, Inserm, Bobigny, France, 2EA4222, University of Paris 13, Sorbonne
Paris Cité, Bobigny, France, 3Service de Rhumatologie, Assistance Publique – Hôpitaux de Paris (AP-HP) Groupe hospitalier Avicenne -
Jean Verdier – René Muret, Bobigny, France, 4SILICOSIS project, ERC Advanced Grant, Centre for European Studies, Sciences Po, Paris,
France, 5Centre for Employment and Labour Studies (CNAM), Noisy-le-Grand, France, 6Laboratory for Interdisciplinary Evaluation of
Public Policies (LIEPP, Sciences Po, Paris), Paris, France, 7Centre for Historical Research, CNRS-EHESS, Paris, France, 8Li2P, University
of Paris 13, Sorbonne Paris Cité, Bobigny, France, 9UMR 1125, INSERM, Bobigny, France, 10UMR1125, Inserm, Bobigny, France,
11National Institute for Demographic Studies (INED), Paris, France, 1274 rue Marcel Cachin, INSERM, Bobigny, France
SESSION INFORMATION
Background/Purpose:
Occupational exposure to silica dust has been associated with increased risk of developing ACPA positive Rheumatoid arthritis (RA)1,2,3.
Little is known about non-occupational exposure, as there are no available tools to assess it in clinical practice.
The Dust Exposure Life-Course Questionnaire (DELCQ) longitudinally quantifies lifetime occupational and non-occupational (e.g. body
care; hobbies such as DIY, woodworking, stone cutting etc.. ).
The DELCQ, developed within a European Research Council Advanced Grant, provides clinical research with a tool derived from social
sciences .In the DELCQ, the identification of situations likely to put people at risk of exposure is grounded on an extensive list of products
and activities summed up by the International Agency on Research on Cancer IARC4 and on a wide overview of the literature that in
medicine, epidemiology and industrial hygiene has been addressing silica exposure and silica-related (or suspected-to-be-related) diseases.
The aim of this study was to use this novel tool to explore occupational and non-occupational silica exposure in a series of consecutive RA
patients and to explore the association of quantified silica dust exposure with major disease features (ACPA positivity) or outcomes (erosive
disease).
Methods:
The DELCQ was administered to 97 consecutive RA patients (77F, 20M, mean age 59.1+/- 13.3 yrs.,75 ACPA positives, 66 with erosive
disease) attending the department of rheumatology of the Avicenne teaching Hospital (Bobigny, FRANCE).The DELQQC scores of patients
were compared to those of 261 controls, matched for sex, age and smoking status, from a 825-subject national cohort, representative of the
general French population (ELIPSSilice). Within RA subjects, the association of the scores with ACPA positivity and with erosive disease
was assessed after adjustment for tobacco exposure.
Results:
RA patients had higher scores of total (median [Q1, Q3]: 25 [13, 36] vs. 9 [4, 19]), occupational (10 [0, 17] vs. 0 [0, 4]) and non-
occupational (15 [8, 20] vs. 7 [0, 15]) exposure vs. controls (p<0.0001 for all comparisons). Amongst RA patients, male vs. female patients
had higher occupational scores of exposure (12 [2, 18] vs. 0 [0, 3] p<0.005), while non-occupational exposure was not significantly different
(12 [3, 25] vs. 8[4, 15]). After adjusting for smoking (ever smokers vs. nonsmokers), neither professional of non-professional scores were
associated with erosive disease, despite a strong negative interaction with tobacco exposure.
Conclusion:
By using a tool developed in collaboration of social sciences, this work shows for the first time that RA patients have higher nonprofessional
lifetime exposure to silica dust compared to age and sex-matched subjects from the general population. Moreover, higher occupation
exposure in RA is confirmed, in accordance with previous literature. Neither occupational nor non-occupational exposure was associated
with ACPA positivity or erosive disease, likely due to the high prevalence of ACPA positivity and severe disease in the patient series.
Disclosure: L. Semerano, None; C. Cavalin, None; O. Macchi, None; S. El Rharras, None; M. Petit, None; P. Decker, None; E. Andre,
None; P. A. Rosental, None; M. C. Boissier, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/patients-with-rheumatoid-arthritis-have-higher-lifetime-

professional-and-non-professional-exposure-to-silica-dust-particles-compared-to-general-population
Depression As a Risk Factor for the Development of Rheumatoid Arthritis: A

Population-Based Cohort Study
Isabelle Vallerand1, Ryan Lewinson2, Mark Lowerison1, Alexandra Frolkis3, Gilaad Kaplan3, Andrew Bulloch4, Scott Patten1 and Cheryl
Barnabe5, 1Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada,
2Biomedical Engineering Program, Schulich School of Engineering, University of Calgary, Calgary, AB, Canada, 3Department of Medicine,
Cumming School of Medicine, University of Calgary, Calgary, AB, Canada, 4Department of Physiology & Pharmacology, Cumming School
of Medicine, University of Calgary, Calgary, AB, Canada, 5Division of Rheumatology, University of Calgary, Calgary, AB, Canada
SESSION INFORMATION
Background/Purpose: The underlying risk factors for the development of Rheumatoid Arthritis (RA) remain poorly understood; however,
prospective studies have demonstrated that individuals with elevated Tumor Necrosis Factor alpha (TNFα), a pro-inflammatory cytokine, are
at increased risk of subsequently developing RA. It remains unknown whether elevated TNFα by means of a different disease process can
subsequently increase the risk of developing RA. Recently, major depressive disorder (MDD) has been identified to have a direct effect on
cytokines, including increased serum concentrations of TNFα relative to healthy controls independent of underlying inflammatory disease.
Based on this, our hypothesis is that exposure to MDD may increase the risk of subsequently developing RA. In this study using a large
population-based cohort, we assessed if patients with MDD were at increased risk of subsequently developing RA compared to the general
population without MDD.
Methods: A retrospective cohort study was conducted using The Health Improvement Network (THIN) Database between the years 1986-
2012 for up to 26 years of follow-up. The MDD cohort comprised patients with a diagnostic (Read) code for MDD and the remainder of
patients formed the referent cohort. Both cohorts were followed until patients developed RA or were censored. Cox proportional hazards
models were used to determine the risk of developing RA among patients with MDD, as reported using Hazard Ratios (HRs) and 95%
confidence intervals (CIs) (α=0.05). A backward elimination procedure was used to determine the presence of effect modification (using a
Wald test) or confounding by age or sex.
Results: A cohort of 403,932 patients with MDD and a referent cohort of 5,339,399 patients without MDD were identified in THIN. A total
of 2,192 (0.54%) patients with MDD developed RA, and 24,021 (0.45%) patients without MDD developed RA over this period. Cox
proportional hazards models identified a confounding effect by sex and a significant interaction by age (p<0.0001), whereby younger patients
with MDD (age<40) had a 42% increased risk of developing RA (sex-adjusted HR=1.42, 95%CI: 1.31 – 1.53). In older patients (age>40),
the risk of developing RA among those with MDD was lower but demonstrated a 14% increased risk (sex-adjusted HR=1.14, 95%CI: 1.08-
1.21).
Conclusion: MDD was found to be a risk factor for the development of RA. This risk was highest among younger patients with MDD, and the
risk was only somewhat increased among older patients with MDD. These results provide support the hypothesis that MDD may be
associated with the development of RA.
Disclosure: I. Vallerand, Canadian Rheumatology Association and Novartis, 3; R. Lewinson, None; M. Lowerison, None; A. Frolkis,
None; G. Kaplan, None; A. Bulloch, None; S. Patten, None; C. Barnabe, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/depression-as-a-risk-factor-for-the-development-of-

rheumatoid-arthritis-a-population-based-cohort-study
Poor Prognostic Factors at the Start of Methotrexate Therapy Are Not Associated with
Worse Treatment Response: Results from the Rheumatoid Arthritis Medication Study
JM Gwinnutt1, Kimme L. Hyrich1, M Lunt1, Darren Plant1, M Brazil2, R Postema2, Anne Barton1 and Suzanne M Verstappen1,
1Manchester Academic Health Science Centre, Manchester, United Kingdom, 2Bristol-Myers Squibb, Uxbridge, United Kingdom
SESSION INFORMATION
Background/Purpose: As anti-citrullinated protein antibody positivity (+), RF+ and erosions are independently associated with poor
outcomes in patients (pts) with RA, clinicians may use these prognostic factors in treatment decisions. However, it is not known whether pts
with these poor prognostic factors respond equally well to conventional synthetic DMARD therapy. The aim of this analysis was to compare
clinical and pt-reported outcomes (DAS28 [CRP], HAQ) of pts with RA with poor prognostic factors (RF+ and/or anti-cyclic citrullinated
peptide antibody 2+ [anti-CCP2+] and erosions) vs those without over 1 year. Methods: Pts with RA in the UK starting MTX therapy were
recruited to the Rheumatoid Arthritis Medication Study (RAMS), a 1-year, prospective cohort study. RF was determined from baseline blood
samples, and data about anti-CCP status and erosions were obtained from medical notes. Pts who were anti-CCP2+ and/or RF+ and had
erosions were classified as having poor prognosis (PP), while those not were classified as not having poor prognosis (NPP). For this
analysis, pts were excluded if they were recruited >2 years following symptom onset or had missing data for any of the three prognostic
factors. At baseline, 6-month and 12-month demographic and clinical data were recorded by a research nurse and pts completed the HAQ.
The association between prognosis group and DAS28 (CRP) and HAQ at 6 and 12 months was assessed using linear and negative binomial
regression, respectively. The association between prognosis group and longitudinal DAS28 (CRP) and HAQ was assessed using linear and
negative binomial random effects models, respectively. Baseline age, sex and symptom duration were included in the models as covariates.
Results: In total, 545 pts with RA were included (PP, n=79 [14.5%]; NPP, n=466 [85.5%]). At baseline, PP pts were older, but other
characteristics were similar (Table). DAS28 (CRP) and HAQ scores were similar between groups at 6 months (median [interquartile range
(IQR)] DAS28 [CRP]: PP, 3.03 [2.4, 4.1] vs NPP, 3.2 [2.3, 4.3], coefficient –0.11, 95% CI –0.52, 0.29; HAQ: PP, 0.88 [0.25, 1.50] vs NPP,
0.63 [0.13, 1.25], incidence rate ratio [IRR] 1.12, 95% CI 0.76, 1.64) and 1 year (median [IQR] DAS28 [CRP]: PP, 2.98 [2.25, 3.75] vs
NPP, 3.00 [2.05, 4.05], coefficient 0.02, 95% CI –0.39, 0.43; HAQ: PP, 0.75 [0.13, 1.38] vs NPP, 0.63 [0.00, 1.25], IRR 1.12, 95% CI 0.76,
1.64). Similar results were seen when using longitudinal models to combine all the repeated measures (DAS28 [CRP]: coefficient –0.02,
95% CI –0.30, 0.26; HAQ: IRR 1.17, 95% CI 0.92, 1.48).
Conclusion: Treatment response is similar in pts with and without poor prognostic factors. These results suggest that, at this early stage of
disease, baseline poor prognostic factors do not predict treatment response to conventional synthetic DMARDs, nor do they indicate that RA
disease is reported as worse at 6 or 12 months in pts with vs without these poor prognostic factors.
Table. Patient Demographic and Clinical Data at Baseline

Total cohort PP NPP
p-value*
(N=545) (n=79) (n=466)
Age at onset, years 57 (47, 66) 60 (48, 71) 56 (47, 66) 0.03†
Female, n (%) 354 (65.0) 49 (62.0) 305 (65.5) 0.54‡
Symptom duration 6 (4, 12) 7 (4, 11) 6 (4, 12) 0.93†
(months)
Smoking status, n (%) 201 (37.2) 31 (39.7) 170 (36.8) 0.83‡
Never Ex- 208 (38.5) 30 (38.5) 17 178 (38.5)
smoker Current 131 (24.3) (21.8) 114 (24.7)
SJC (28) 4 (2, 9) 4 (2, 9) 4 (2, 9) 0.72†
TJC (28) 6 (2, 12) 5.5 (2, 9) 6 (2, 12) 0.56†
CRP (mg/L) 5 (2, 16) 6 (3, 16) 5 (2, 16) 0.23†
DAS28 4.25 (3.25, 4.30 (3.55, 4.20 (3.25, 0.96†
5.20) 4.80) 5.25)
HAQ 0.88 (0.38, 1.00 (0.38, 0.88 (0.38, 0.25†
1.50) 1.75) 1.50)
RF status, n (%) 372 (68.3) 74 (93.7) 5 298 (64.0) <0.001‡
Positive Negative 173 (31.7) (6.3) 168 (36.1)
Anti-CCP2 status, n 344 (63.1) 66 (83.5) 278 (59.7) <0.001‡
(%) Positive 201 (36.9) 13 (16.5) 188 (40.3)
Negative
Erosions, n (%) 98 (18.0) 79 (100.0) 19 (4.1) <0.001‡
Positive Negative 447 (82.0) 0 (0.0) 447 (95.9)
Other csDMARD at 66 (12.3) 13 (16.5) 53 (11.6) 0.22‡
baseline, n (%) 22 (3.9) 4 (5.1) 18 (3.9)
0.61‡
Hydroxychloroquine
Sulfasalazine
Steroids at baseline, n 104 (19.2) 14 (18.0) 90 (19.4) 0.76‡
(%)
Data are median (IQR) unless otherwise stated *p-values resulting from
comparison of baseline score across the two prognosis groups †Mann–
Whitney U test ‡Chi-square test CCP=cyclic citrullinated peptide;
IQR=interquartile range; NPP=patient group not having poor prognosis;
PP=patient group with poor prognosis; csDMARD=conventional synthetic
DMARD
Disclosure: J. Gwinnutt, None; K. L. Hyrich, None; M. Lunt, None; D. Plant, None; M. Brazil, Bristol-Myers Squibb, 1,Bristol-Myers
Squibb, 3; R. Postema, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; A. Barton, Roche-Chugai, Celgene and Boehringer Engelheim,
5,Bristol-Myers Squibb, 2; S. M. Verstappen, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/poor-prognostic-factors-at-the-start-of-methotrexate-

therapy-are-not-associated-with-worse-treatment-response-results-from-the-rheumatoid-arthritis-medication-study
Relationship between Shift Work and the Onset of Rheumatoid Arthritis; Results from a
Swedish Case-Control Study
Lars Alfredsson1, Anna Karin Hedström2, Torbjörn Åkerstedt3 and Lars Klareskog4, 1The Institute of Environmental Medicine, Karolinska
Institutet, Stockholm, Sweden, 2Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, 3Stockholm University;
Karolinska Intitutet, Stockholm, Sweden, 4Dept. of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital,
Stockholm, Sweden
SESSION INFORMATION
Background/Purpose: Shift work has previously been associated with increased RA risk in females. The aim of this study was to investigate
the potential association between permanent night shift work, rotating shift work, and day oriented shift work, and risk of developing
anti-citrullinated peptide antibodies (ACPA) positive and ACPA negative RA.
Methods: The present report is based on a Swedish population-based, case-control study with incident cases of RA (1951 cases, 2225
matched controls). Using logistic regression, occurrence of RA among subjects who have been exposed to different kinds of shift work was
compared with that among those who have never been exposed, by calculating the odds ratio (OR) with a 95% confidence interval (CI).
Results: Rotating shift work and day oriented shift work were associated with a 30% increased risk of developing ACPA positive RA, but
not ACPA negative RA (table 1). There was an inverse association between permanent night shift work and risk of both ACPA positive RA
(OR 0.7, 95% CI 0.6-0.9) and APCA negative RA (OR 0.8, 95% CI 0.6-1.0) (table 1). For both subsets of RA, significant trends showed a
lower risk of developing RA with increasing duration of permanent night shift work (table 2).
Conclusion: Sleep restriction as a consequence of shift work is associated with several biological effects among which changes in melatonin
production may be involved. The present epidemiological findings of a complex relationship between sleep patterns and different forms of
RA may be of importance for increasing the understanding of the pathophysiology of RA.
Disclosure: L. Alfredsson, None; A. K. Hedström, None; T. Åkerstedt, None; L. Klareskog, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/relationship-between-shift-work-and-the-onset-of-

rheumatoid-arthritis-results-from-a-swedish-case-control-study
Smoking and Rheumatoid Arthritis Susceptibility; Quantification of the Impact of

Cumulative Dose, Frequency and Duration of Smoking, and Smoking Cessation
Lars Alfredsson1, Anna Karin Hedström2, Camilla Bengtsson3 and Lars Klareskog4, 1The Institute of Environmental Medicine, Karolinska
Institutet, Stockholm, Sweden, 2Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, 3Inst of Environmental
Medicine, Karolinska Institutet, Stockholm, Sweden, 4Dept. of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University
Hospital, Stockholm, Sweden
SESSION INFORMATION
Background/Purpose: Smoking is one of the most established risk factors for rheumatoid arthritis (RA). The aim of this study was to
estimate how age at smoking debut, smoking cessation, duration, intensity, and cumulative dose of smoking influence the risk of developing
ACPA positive and ACPA negative RA.
Methods: The present report is based on a Swedish population-based, case-control study with incident cases of RA (3655 cases, 5883
matched controls). Using logistic regression models, subjects with different smoking habits were compared regarding risk of developing the
two subsets of RA, by calculating odds ratios (OR) with 95% confidence intervals (CI).
Results: Smoking increased the risk of developing both ACPA positive (OR 1.9, 95% CI 1.7-2.1) and ACPA negative RA (OR 1.3, 95% CI
1.2-1.5). For both subsets of RA, a cumulative dose of smoking less than five pack years was not significantly associated with increased
disease risk. A dose-response association was observed between cumulative dose of smoking (exceeding five pack years) and risk of
developing both ACPA positive and ACPA negative RA (p values for trend <0.0001) (table 1). Duration of smoking had a higher influence
on the association between smoking and RA than did intensity of smoking (table 2). Among both subsets of RA, the detrimental effect of
smoking decreased after smoking cessation. Twenty years after smoking cessation, there was no longer an association between smoking and
risk of ACPA negative RA, whereas the association between smoking and ACPA positive RA risk persisted and was dependent on the
cumulative dose of smoking (table 3).
Conclusion: Smoking increases the risk of both subsets of RA with a more pronounced influence on the risk of ACPA positive RA.
Preventive measures in order to reduce smoking are essential and may result in a decline in RA incidence.
Disclosure: L. Alfredsson, None; A. K. Hedström, None; C. Bengtsson, None; L. Klareskog, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/smoking-and-rheumatoid-arthritis-susceptibility-

quantification-of-the-impact-of-cumulative-dose-frequency-and-duration-of-smoking-and-smoking-cessation
Exposure to Passive Smoking and RA Risk; Results from a Swedish Case-Control Study
Lars Alfredsson1, Anna Karin Hedström2 and Lars Klareskog3, 1The Institute of Environmental Medicine, Karolinska Institutet, Stockholm,
Sweden, 2Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, 3Dept. of Medicine, Rheumatology Unit,
Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
SESSION INFORMATION
Background/Purpose: Smoking has consistently been associated with increased risk of developing rheumatoid arthritis (RA). We
investigated the influence of passive smoking on the risk of developing ACPA positive and ACPA negative RA.
Methods: A population-based case-control study using incident cases of RA was performed in Sweden, and the study population in this
report was restricted to include never smokers (589 cases, 1764 controls). Cases and controls answered an extensive questionnaire. The
incidence of RA among never smokers who had been exposed to passive smoking was compared with that of never smokers who had never
been exposed, by calculating the odds ratio (OR) with a 95% confidence interval (CI) employing logistic regression.
Results: No association was observed between exposure to passive smoking and risk of ACPA positive or ACPA negative RA, regardless if
the exposure took place within 10 years prior to index, or earlier in life.
Compared with those who had never been exposed to passive smoking, the OR was 1.0 (95% CI 0.7-1.2) for ACPA positive RA, and 0.9
(95% CI 0.7-1.2) for ACPA negative RA among those ever exposed to passive smoking. There were no significant age or gender related
differences.
There was no suggestion of a trend between duration of passive smoking and RA risk. Long term exposure to passive smoking for 20 years or
longer was not significantly associated with increased disease susceptibility (table 1).
Conclusion: No association was observed between exposure to passive smoking and risk of ACPA positive or ACPA negative RA among
never smokers. Our finding may be explained by a threshold below which no association between smoke exposure and RA occurs.
Disclosure: L. Alfredsson, None; A. K. Hedström, None; L. Klareskog, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/exposure-to-passive-smoking-and-ra-risk-results-from-a-

swedish-case-control-study
Smoking Is Causally Associated with Disease Activity in Rheumatoid Arthritis

Milena Gianfrancesco1, Laura Trupin2, Stephen Shiboski3, Mark van der Laan4, Jonathan Graf5, John B. Imboden Jr.6, Jinoos Yazdany2
and Gabriela Schmajuk7, 1Medicine/Rheumatology, University of California, San Francisco, San Francisco, CA, 2Medicine/Rheumatology,
University of California San Francisco, San Francisco, CA, 3Department of Epidemiology and Biostatistics, University of California, San
Francisco, San Francisco, CA, 4University of California, Berkeley, Berkeley, CA, 5Department of Medicine, Division of Rheumatology
Zuckerberg San Francisco General Hospital, University of California, San Francisco, San Francisco, CA, 6Medicine, University of
California, San Francisco, San Francisco, CA, 7San Francisco VA Medical Center, University of California San Francisco, San Francisco,
CA
SESSION INFORMATION
Background/Purpose: The association between smoking and risk of rheumatoid arthritis (RA) has been well documented; however, the
relationship between smoking and RA disease activity is less clear. Previous studies have indicated a null association between smoking and
pain, swollen joint count, physical function, and radiographic joint damage, while others have demonstrated an inverse association.
Inconsistent findings may be ascribed to heterogeneous study designs or biases in statistical analyses. We examined the causal association
between smoking and RA outcomes using methods that account for time-varying confounding and loss to follow-up.
Methods: We used electronic health record data from a safety-net health system between 2013-2017. We included individuals with a
diagnosis of RA and at least 2 clinic visits within 12 months (n=291). Timepoints during the study period were defined in 3-month intervals.
We assessed smoking status (yes/no) at each timepoint; additional covariates included sex, race/ethnicity, age, obesity (BMI > 30 kg/m2), and
medications. We also controlled for depression among a subset of patients (n=165) who had completed the Patient Health Questionnaire
(PHQ-9). We used longitudinal targeted maximum likelihood estimation to estimate the causal effect of smoking on disease activity as
measured by the clinical disease activity index (CDAI) and patient global assessment (PGA) at 30 months (or 2.5 years). We also accounted
for time-varying covariates and informative missingness of data.
Results: Patients were 82% female, with a mean age 59.2 + 12.2 and 91% racial/ethnic minorities. Eleven percent of patients were smokers
and the mean BMI was 29.0 + 6.9 (Table 1). Smoking was associated with a CDAI score of 16.67 at 30 months compared to a score of 12.05
for non-smoking after adjusting for covariates. Conversely, smoking was associated with a lower PGA score compared to non-smoking over
the same period (40.53 vs. 45.42, respectively; p<0.001). However, additional control for depression based on the PHQ-9 did not change the
association between smoking and disease activity based on CDAI (p<0.001), but eliminated the significant inverse relationship between
smoking and PGA (p=0.24).
Conclusion: Smoking may be causally associated with higher levels of disease activity over time as measured by the CDAI. Differences in
CDAI between smokers and non-smokers are likely clinically meaningful for individuals with low to moderate disease activity. Patient
reported outcomes such as PGA may be influenced by other factors such as depression. These methods may be useful for investigations of
additional exposures on longitudinal outcome measures in rheumatologic disease.
Table 1. Baseline characteristics of rheumatoid arthritis patients included in the study (n=291)
N (%) or
Mean (SD)
Female 238 (82)
Age 59.16
(12.2)
White, non- 26 (9)
Hispanic
84 (29)
Asian
23 (8)
Black, non-
Hispanic 158 (54)
Hispanic
Current 31 (11)
Smoker
BMI 29.04 (6.9)
CDAI Score 14.17
(12.6)
PGA Score 48.65
(27.9)
Prescribed 52 (18)
Biologic
Prescribed 230 (79)
Synthetic
Disclosure: M. Gianfrancesco, None; L. Trupin, None; S. Shiboski, None; M. van der Laan, None; J. Graf, None; J. B. Imboden Jr.,
None; J. Yazdany, None; G. Schmajuk, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/smoking-is-causally-associated-with-disease-activity-in-

Diet Change and Omega-3 Supplementation in the First Three Years Following a
Diagnosis with Rheumatoid Arthritis in Sweden
Maxine Lancelot1,2, Olivier Grimaud3, Saedis Saevarsdottir4, Johan Askling5, Lars Klareskog6, Lars Alfredsson7 and Camilla Bengtsson8,
1IMM, Karolinska Institutet, Stockholm, Sweden, 2EHESP, Paris, France, 3EHESP, Rennes, France, 4Rheumatology Unit, Department of
Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden, 5Unit of Clinical Epidemiology, Department of
Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden, 6Dept. of Medicine, Rheumatology Unit, Karolinska
Institutet, Karolinska University Hospital, Stockholm, Sweden, 7The Institute of Environmental Medicine, Karolinska Institutet, Stockholm,
Sweden, 8Inst of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
SESSION INFORMATION
Background/Purpose:
Major dietary modification and omega-3 supplements are often promoted on patient counseling websites for those with RA. Given uncertainty
regarding such approaches, we aim to study the frequency and characteristics of patients who undertake these complementary measures.
Methods:
Included were 810 participants in the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) in Sweden who answered
questionnaires including diet (normal/Mediterranean/vegetarian/vegan/low glycemic index/other) and omega-3 supplement use at diagnosis,
1 year, and 3 years post-diagnosis. Prevalence of diet changes and supplement use were assessed. Logistic regression was used to analyze
associations between changing diet post-diagnosis, omega-3 supplement use, and the lifestyle/demographic characteristics of education, sex,
age, BMI, smoking, and pre-diagnosis diet.
Results:
Between 1999 and 2016, 810 EIRA participants (women: 74%, median age at inclusion: 58 (min 17-max 85), median BMI at inclusion 25.1
(min 15.5-max 50.1), university degree holders: 30%). The proportion of participants with a non-normal diet increased from 23% in 2008 to
30% in 2013. 26% reported a major change in diet within 3 years post-diagnosis (Table). Those who made a change were more likely to be
younger (OR 0.98 per year of age, 95% CI 0.96-0.99), have a university education (OR 1.89, 95% CI1.28-2.80), be women (OR 1.77, 95%
CI 1.28-2.80), be obese (OR 2.28, 95% CI 1.38-3.78), and have an non-normal diet at baseline (OR 2.81, 95% CI 1.36-5.79 for vegetarian;
OR 10.12, 95% CI 5.79-17.71 for Mediterranean; OR 24.82, 95% CI 8.09-76.1 for others). Omega-3 supplement use increased from 20.4%
at baseline to 30.9% at one year and decreased to 11.9% three years post-diagnosis. Participants were more likely to both change diets and
use omega-3 supplements if they were younger (OR 0.98 per year increase, 95% CI 0.96-0.99), following an alternative diet at baseline
(12.0, 95% CI 6.61-21.6), or obese (OR 2.05, 95% CI 1.09-3.88).
Conclusion:
Many RA patients change their diets or use supplements after diagnosis. To better target messaging about these complementary therapies, it
may be beneficial to consider them by the sociodemographic and lifestyle characteristics that distinguish them.
Disclosure: M. Lancelot, None; O. Grimaud, None; S. Saevarsdottir, None; J. Askling, MSD, BMS, Pfizer, AbbVie, SOBI, UCB, Roche,
Lilly, AstraZeneca, 2; L. Klareskog, None; L. Alfredsson, None; C. Bengtsson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/diet-change-and-omega-3-supplementation-in-the-first-

three-years-following-a-diagnosis-with-rheumatoid-arthritis-in-sweden
Use of Machine Learning and Traditional Statistical Methods to Classify RA-Related

Disability Using Administrative Claims Data
Jeffrey R. Curtis1, Huifeng Yun2, Carol J. Etzel3, Shuo Yang4 and Lang Chen4, 1Rheumatology & Immunology, University of Alabama at
Birmingham, Birmingham, AL, 2University of Alabama at Birmingham, Birmingham, AL, 3Departments of Epidemiology and Biostatistics,
University of Texas School of Public Health, Houston, TX, 4Division of Clinical Immunology & Rheumatology, University of Alabama at
Birmingham, Birmingham, AL
SESSION INFORMATION
Background/Purpose: Administrative claims and electronic health record (EHR) data are commonly used to assess outcomes in rheumatoid
arthritis (RA). However, direct measures of functional status are typically not available in these data sources to control for confounding in
comparative effectiveness research.
Methods: Corrona registry data linked to Medicare claims (2006-2014) were used to build a claims-based disability classifier, measured by
HAQ. Eligible patients had RA per Corrona rheumatologist, and >=1yr prior coverage. Demographics, socioeconomic factors,
comorbidities, healthcare utilization, and medications from claims data were included as predictors.
In separate analyses, HAQ was classified dichotomously (<1, ≥1), as 3 categories (0–<0.5, ≥0.5–<1.5, and ≥1.5–3), and as a continuous
variable, converted to corresponding HAQ category. Generalized logistic regression (GenLogit) with LASSO for variable selection and
results were compared with machine learning methods including RandomForests, using a forest of 2000 trees. Separate models were run
classifying each of the 8 HAQ subdomains separately, and then summing to form the composite HAQ score. Misclassification rates were
compared and the area under the receiver operator curves (AUROC) was described.
Results: A total of 2,788 RA patients were eligible, classifying 52% of patients with low (n=1448) and 48% with high (n=1340) HAQ; and
as 3 categories, low (n=887), moderate (n=1109), and high (n=792). Univariable analysis showed higher HAQ was associated with older
age, being disabled (per Medicare), rural residence, and greater comorbidity burden, and higher healthcare utilization.
Variables selected by various methods were similar (Table). In the 2 category HAQ models, overall misclassification was 29%
(RandomForests), 28% , and 38% (LASSO), with an AUROC of 0.84. In the 3 category HAQ models, RandomForests yielded
misclassification of ~48% that did not meaningfully differ across the 3 HAQ categories. Misclassification of the GenLogit model varied
widely by HAQ category. When misclassification did occur in the 3 category analysis, patients were usually 1 category off; more extreme
misclassification (categorizing low HAQ patients as high, or vice-versa) was uncommon (<8%). The median (IQR) difference in the
(observed – predicted) HAQ was 0.00 (-0.45, 0.41) units. Ongoing work is refining these models, reducing the misclassification rate, and
validating the approach.
Conclusion: Results from this preliminary analysis suggest that administrative claims and EHR data might be useful to classify RA-related
disability as measured by the HAQ with reasonable accuracy. Larger datasets and richer information in EHR data likely will improve the
accuracy of these methods.
Table: Key variables from administrative claims data selected by
machine learning methods to classify HAQ category*
RandomForests Generalized logistic regression
with LASSO
Age X X
Number of rheumatology visits X X
Number of AHRQ CCS comorbidities X X
Number of unique medications (any type) X X
Number of outpatient physician visits X X
Baseline steroid use X X
Median household income X X
Elixhauser comorbidity index X
Wheelchair X
Disable X
Sex X
*results shown for 3 category HAQ models
Disclosure: J. R. Curtis, AbbVie, Roche/Genentech, BMS, UCB, Myraid, Lilly, Amgen, Janssen, Pfizer, Corrona, 5,Amgen, Pfizer,
Crescendo Bio, Corrona, 9; H. Yun, Bristol-Myers Squibb, 2; C. J. Etzel, Corrona, LLC, 3,Merck Human Health, 9; S. Yang, None; L.
Chen, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/use-of-machine-learning-and-traditional-statistical-

methods-to-classify-ra-related-disability-using-administrative-claims-data
Impact of the Multi-Biomarker Disease Activity Score Results on Whether

Rheumatologists Changed Biologic Therapy for RA Patients
Jeffrey R. Curtis1, Kerri Ford2, Lang Chen3, Huifeng Yun3 and Fenglong Xie4, 1Rheumatology & Immunology, University of Alabama at
Birmingham, Birmingham, AL, 2Crescendo Bioscience Inc., South San Francisco, CA, 3University of Alabama at Birmingham, Birmingham,
AL, 4Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, AL
SESSION INFORMATION
Background/Purpose: The multi-biomarker disease activity (MBDA) score is a validated test used to assess disease activity for patients
with rheumatoid arthritis (RA). How it is used in clinical practice in the U.S. is unclear. We evaluated the likelihood that rheumatologists
would add or switch biologic therapies based on the MBDA test result.
Methods: Using previously published methods, we linked results of MBDA tests obtained as part of routine clinical care to 2012-2014
Medicare fee for service claims data for RA patients. We characterized patients as being on a biologic or targeted synthetic DMARD in the
90 days prior to the MBDA test and evaluated biologic/tofacitinib treatment changes in the 90 days following the MBDA test. MBDA test
scores were classified as low (<30), moderate (30-44), and high (>44). The unit of analysis was the 90-day interval before and after each
MBDA test score. Alternating logistic regression was used to compute odds ratios (OR) to quantify the likelihood that patients made any
change (add or switch), accounting for the clustered nature of the data (intervals nested within patients, and patients nested within doctor
change (add or switch), accounting for the clustered nature of the data (intervals nested within patients, and patients nested within doctor
practices) and physician-level variability, controlling for patient age and sex. Sensitivity analyses used a 6-month interval for outcome
ascertainment after the MBDA test.
Results: Using previously validated methods, a total of 27,621 unique RA patients were linked to 44,438 MBDA test scores. For the 27,256
intervals where RA patients were not on biologic therapy when the MBDA score was obtained, a total of 13.2% of patients added a biologic.
Patients with high MBDA scores were significantly more likely to add a biologic (Table). For the 17,182 intervals where RA patients were
already on a biologic, a total of 19.1% of patients switched or stopped the biologic that they were taking. Patients with lower MBDA scores
were significantly more likely to stay on their therapy, whereas those with higher scores were more likely to stop and/or switch biologics.
After adjustment, results from the regression analyses showed that patients with moderate MBDA scores were 1.47 (95% 1.29-1.67)-fold
more likely to add or switch biologics, and those with high MBDA scores were 2.54 (95% CI 2.19-2.94)-fold more likely to add or switch
biologics. Men (OR=0.90, 95% 0.82-0.98) and older patients (OR=0.92 per 5 year increment, 95% CI 0.91-0.93) were less likely to add or
switch therapy, even after controlling for variability between physicians (OR = 1.10, 95% CI 1.02-1.19). These results were robust and ORs
were numerically larger when extending the interval to 6 months.
Conclusion: Results from the MBDA score were significantly associated with the likelihood that a physician added or switched biologic
therapies, with either type of change being more frequent when the MBDA score was high. Further evaluation of outcomes after switching,
conditional on the MBDA score, is warranted.
Table: Proportion of patients who added or switching biologics after the
MBDA test
MBDA Score Non-biologic users Biologic Users Who
who added a biologic Switched or Stopped
after the MBDA test their Current Biologic
after the MBDA test
N=27,256
N=17,182
Low (<30) 8.4% 14.0%
Moderate (30-44) 10.8% 16.2%
High (>44) 16.3% 23.1%
Chi-square p value <0.0001 <0.0001
Crescendo Bio, Corrona, 9; K. Ford, Myriad Genetics, Inc., 1,Crescendo Bioscience Inc., 3; L. Chen, None; H. Yun, BMS, 2; F. Xie, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/impact-of-the-multi-biomarker-disease-activity-score-

results-on-whether-rheumatologists-changed-biologic-therapy-for-ra-patients
Availability of Clinical Measures for Patients with Rheumatoid Arthritis in Integrated

Delivery Networks Who Receive a Biologic or Targeted Synthetic Disease-Modifying
Antirheumatic Drug: A Real-World Analysis of an Electronic Health Records Database
Benjamin Chastek1, Chieh-I Chen2, Toshio Kimura2, Jonathan Fay2, Stephanie Korrer3 and Stefano Fiore4, 1Optum, Eden Prairie, MN,
2Regeneron Pharmaceuticals, Inc., Tarrytown, NY, 3Health Economics and Outcomes Research, Optum, Eden Prairie, MN, 4Clinical
Science, Sanofi Genzyme, Bridgewater, NJ
SESSION INFORMATION
Background/Purpose: In patients with rheumatoid arthritis (RA), ACR treatment guidelines recommend treating to targets based on
quantitative endpoints, with modification of therapy as needed to achieve those targets. Integrated Healthcare Delivery Networks (IDNs)
collect data in electronic health records (EHR), which can be used to assess quality of care, manage costs, and support treatment decisions.
This study examined the availability of clinical measures across IDNs among patients with RA who received a biologic or a targeted
synthetic disease-modifying antirheumatic drug (tsDMARD).
Methods: In this retrospective analysis of the Optum One EHR database, patients were 18 years or older, had RA diagnoses ≥7 days apart
between June 30, 2008 and July 31, 2015. For patients who switched from a tumor necrosis factor inhibitor (TNFi) to a different medication,
the index date was the switch date. Among other patients with a prescription for a biologic or tsDMARD, the index date was the first
prescription written. Analysis periods were “baseline” (1 year pre-index), or “follow-up” (1 year post-index). EHR reporting rates were
determined for quantitative measures to guide treatment decisions: clinical measurements (height, weight, blood pressure, cholesterol,
erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], or tuberculosis [TB] test) and validated disease severity instruments
(Routine Assessment of Patient Index Data [RAPID3], Disease Activity Score [DAS28], or Clinical Disease Activity Index [CDAI]). Mean
ESR and CRP in follow-up were summarized.
Results : The 29,829 patients were 76.8% female, 80.1% age ≥45 years, and 83.8% Caucasian. Baseline TB reporting rate in EHRs was
18.8%. EHR reporting rates in follow-up (median, 6 office visits) were: 49.0% ESR or CRP; and 6.5% ≥1 disease severity measure (5.8%
RAPID3, 0.2% DAS28, 0.6% CDAI). Data reporting in EHRs varied significantly across the 10 largest IDNs, including a range of 0.0% to
25.2% for disease severity measure reporting in follow-up. Mean±SD values for ESR and CRP in follow-up were 13.9±8.0 mm/hr and
5.7±4.2 pcg/mL, respectively; variations in ESR and CRP values were less pronounced than variations in EHR reporting rates.
Table. EHR reporting rates and reported ESR/CRP values, by IDN
Baseline Follow-up
ESR, mm/hr CRP, pcg/mL ≥1 RAPID3,
≥1 TB ≥1 ESR or n Mean±SD n Mean±SD DAS28, or
Test in EHR, % CRP Test in EHR, % CDAI Test in EHR, %
Total (N=29,829) 18.8% 49.0% 7,750 13.9±8.0 9,303 5.7±4.2 6.5%
IDN Rank 1 (N=4,116) 22.0% 52.9% 1,068 13.2±8.1 1,470 5.1±4.2 25.2%
IDN Rank 2 (N=3,307) 19.3% 55.4% 1,059 14.5±7.5 946 5.1±4.5 1.8%
IDN Rank 3 (N=2,963) 13.6% 41.0% 693 15.1±7.6 839 5.8±4.1 0.0%
IDN Rank 4 (N=2,787) 22.7% 38.5% 632 13.1±8.3 501 6.0±3.7 3.5%
IDN Rank 5 (N=2,143) 9.1% 43.9% 550 14.6±8.0 634 5.4±4.1 0.3%
IDN Rank 6 (N=1,916) 27.9% 60.7% 735 13.1±8.2 855 5.7±4.1 2.8%
IDN Rank 7 (N=1,566) 14.7% 23.4% 231 14.2±8.1 186 5.8±4.5 0.0%
IDN Rank 8 (N=1,484) 13.3% 65.1% 499 13.5±8.3 627 5.8±4.4 9.4%
IDN Rank 9 (N=1,065) 44.6% 70.4% 92 11.2±7.8 624 5.2±4.3 0.1%
IDN Rank 10 (N=1,027) 20.5% 65.1% 465 13.8±7.5 463 5.7±3.8 6.7%
Other IDN 15.8% 46.3% 1,726 14.3±8.1 2,158 6.3±4.3 6.7%
(N=7,455)
p-value* <0.001 <0.001 <0.001 <0.001 <0.001
*p-value for the comparison across individual IDNs by Chi-square test (for proportions) or ANOVA (for means).
Conclusion: In this analysis of EHR reporting of clinical data among RA patients in IDNs who switched from a TNFi or received a biologic
or tsDMARD, approximately 1 in 5 had a TB test reported pre-index and half had ESR and/or CRP reported post-index. Validated measures
of disease severity (RAPID3, DAS28, or CDAI) were reported infrequently, and EHR reporting was highly variable across IDNs. With
greater emphasis on a treat-to-target approach, more consistent and more complete EHR reporting is recommended to assist rheumatologists
in tracking whether treatment targets for RA are being met with biologic or tsDMARD therapy appropriately.
Disclosure: B. Chastek, Optum, 3; C. I. Chen, Regeneron Pharmaceuticals, 3,Regeneron Pharmaceuticals, 1; T. Kimura, Regeneron
Pharmaceuticals, 3,Regeneron Pharmaceuticals, 1; J. Fay, Regeneron Pharmaceuticals, 3,Regeneron Pharmaceuticals, 1; S. Korrer, Optum,
3; S. Fiore, Sanofi, 3,Sanofi, 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/availability-of-clinical-measures-for-patients-with-

rheumatoid-arthritis-in-integrated-delivery-networks-who-receive-a-biologic-or-targeted-synthetic-disease-modifying-antirheumatic-drug-a-
real-world
What Does It Mean to Have Rheumatoid Arthritis Now? a Current Burden of Disease
Assessment in the United States
Rebecca Schumacher1, A Dominique2, Sofia Pedro1, TA Simon2 and Kaleb Michaud1,3, 1National Data Bank for Rheumatic Diseases,
Wichita, KS, 2Bristol-Myers Squibb, Princeton, NJ, 3University of Nebraska Medical Center, Omaha, NE
SESSION INFORMATION
Background/Purpose:
Known since 1859, RA is the most common inflammatory joint disease with 0.5-1% worldwide prevalence. Currently, there is a larger
number of medications and strategies for treating RA earlier and more aggressively, which also necessitates a greater understanding of the
current burden of RA. Our objective is to measure the impact of RA on the individual and society through patient reported outcomes using a
large US registry.
Methods:
We performed descriptive statistics of a random observation from RA patients enrolled in the National Data Bank for Rheumatic Diseases
(NDB), a longitudinal US-wide study with comprehensive 6-month questionnaires from 1998-2017. We limited analysis to observations in
the last decade (2007-2017) with a comparison to the previous 8 years (1998-2006). Health-related Quality of Life measures examined
included HAQ, EQ5D, SF-36, activities of daily living, economic factors, and illness-related employment. With each of these individual
testing measures, a total of 65 variables were considered for comparable analysis. Results:
Our study included 18,168 participants in the last decade with 82.2% female, mean (SD) age of 60.6 (13.5) and RA duration of 15.7 (12.1)
years. The 1998-2006 cohort included 20,412 patients, with 77.1% female, age of 60.4 (13.5) and RA duration of 14.2 (11.0) years.
Descriptive item responses are detailed in Table. Patient reported consequences of the burden within the 2007-2017 cohort show a slight
improvement in HAQ, pain, fatigue, and SF-36 physical component score (PCS), but a worsening in global severity, sleep, SF-36 mental
component score (MCS), quality of life (QOL) scale, health satisfaction, and functional limitations. When stratified by RA duration (Figure),
patients with a duration of ²2 years had the lowest HAQ, pain, PCS, comorbidities, functional limitations and a higher QOL while duration of
>20 years had the lowest fatigue, sleep and MCS score. Patients that took a DMARD or Biologic showed a definite improvement over
patients that did not take any or prednisone. Conclusion:
Even in this era of effective new treatments, we found the burden of RA to still be severe and important. Current analyses show that HrQOL
measures appear to be less related to type of treatment than decade of RA onset. Further analysis will be performed evaluating biologic vs.
non-biologic treatments.
Table. Characterization of RA patients by decade.
2007-2017 1998-2006
N=18.168 N=20.412
P-
Variable Mean SD Mean SD value
Age (years) 60.6 13.5 60.4 13.4 0.2
Sex (% male) 17.8 22.9 <0.01
Disease duration
(years) 15.7 12.1 14.1 11.0 <0.01
Married (%) 65.8 67.9 <0.01
Total Income (US
dollars)54771.735033.944973.729141.5<0.01
HAQ (0-3) 1.0 0.7 1.1 0.7 <0.01
Pain (0-10) 3.9 2.8 4.0 2.8 0.3
Global severity (0-
10) 3.8 2.5 3.7 2.5 <0.01
Fatigue (0-10) 4.4 3.0 4.5 3.0 <0.01
Sleep disturbance (0-
10) 4.1 3.2 3.8 3.1 <0.01
Physical component score
(SF-36) 36.9 11.2 35.9 11.1 <0.01
Mental component score
(SF-36) 48.0 11.8 49.1 11.5 <0.01
Comorbidity Index
(0-9) 2.0 1.7 1.7 1.5 <0.01
VAS QOL scale (0-
100) 64.6 20.8 66.0 20.8 <0.01
Health satisfaction (0-4) 1.9 1.3 1.8 1.2 <0.01
Functional Limitations 7.4 5.4 7.1 5.3 <0.01
Function Now compared to
6 Months 2.9 1.0 2.9 0.9 <0.01
Pain Now compared to 6
Months 3.0 1.0 2.9 1.0 0.1
P-
Health Aides Mean SD Mean SD value
Cane 0.3 0.4 0.2 0.4 <0.01
Crutches 0.0 0.1 0.0 0.1 <0.01
Walker 0.1 0.3 0.1 0.3 <0.01
Wheelchair 0.1 0.3 0.0 0.2 <0.01
Person Help-Dressing &
Grooming 0.1 0.3 0.1 0.3 <0.01
Person Help-Arising 0.1 0.3 0.1 0.3 0.3
Person Help-Eating 0.0 0.1 0.0 0.1 0.9
Person Help-Walking 0.1 0.3 0.1 0.3 <0.01
P-
Economic Mean SD Mean SD value
Employed at Onset of
Disease 0.8 0.4 0.8 0.4 <0.01
Retired Early due to
Arthritis or Pain 0.3 0.5 0.3 0.5 <0.01
Retired Early due to Other
Medical 0.1 0.3 0.1 0.3 <0.01
Days Limited Activity in 6
Months 40.2 56.9 44.8 0.4 <0.01
Days Health kept from
Usual Activities (30
days) 8.0 10.1 7.5 10.0 <0.01
Able to Perform Activities
Completely 2.6 1.1 2.6 1.1 <0.01
Financial Problem After
Insurance (No/Limited.
Moderate. Great) 1.6 0.7 1.6 0.7 <0.01
Patient or Family Member
Pay for All or Part
Insurance 0.7 0.4 0.7 0.4 0.4
Problem of Paying for
Medical Insurance
(No/Slight/Moderate/Great) 0.9 1.0 0.9 1.0 0.5
P-
Medications Mean SD Mean SD value
DMARD or
biologic (%) 84.2 83.8 <0.01
DMARD
(%) 71.4 77.0 <0.01
Biologic
(%) 49.2 34.8 <0.01
Current DMARDs
(count) 0.9 0.7 1.1 0.8 <0.01
No DMARD/biologic or
prednisone (%) 12.0 12.2 0.7
Figure. Means of health-related Quality of Life measures by decade and RA duration.
Disclosure: R. Schumacher, National Data Bank for Rheumatic Diseases, 3; A. Dominique, Bristol Myers Squibb, 3; S. Pedro, National
Data Bank for Rheumatic Diseases, 3; T. Simon, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1, 9; K. Michaud, National Data Bank for
Rheumatic Diseases, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/what-does-it-mean-to-have-rheumatoid-arthritis-now-a-

current-burden-of-disease-assessment-in-the-united-states
Occupational Physical Workload and Development of Anti-Collagen Type II Antibodies

in Rheumatoid Arthritis Patients
Pingling Zeng1, Lars Alfredsson2, Lars Klareskog3, Mohammed Mullazehi4, Saedis Saevarsdottir5, Camilla Bengtsson6 and Johan
Rönnelid7, 1Institute of Environmental Medicine, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden, Stockholm,
Sweden, 2The Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, 3Dept. of Medicine, Rheumatology Unit,
Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, 4Department of Immunology, Genetics and Pathology,Uppsala
University, Uppsala, Sweden, Uppsala, Sweden, 5Karolinska Institute and Karonlinska University Hospital, Stockholm, Sweden, 6Inst of
Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, 7Department of Immunology Genetics and Pathology, Uppsala
University, Uppsala, Sweden
SESSION INFORMATION
Background/Purpose: We have previously observed an association between exposure to occupational physical workload (PW) and risk of
developing rheumatoid arthritis (RA)[1].We posit that PW could impose mechanical stress on the joints leading to neo-epitope formation and
immune activation. The major solid component of the articular cartilage is collagen type II (CII). Elevated level of anti-CII antibodies do not
predate RA development, but are transiently found in 6-9% early RA patients. These antibodies are associated with acute RA onset and
HLA-DRB1*01 and *03, yet predict good long-term prognosis[2]. We hypothesized that exposure to PW especially in the period closely
predating RA diagnosis would associate with anti-CII positive RA but not anti-CII negative RA.
Methods: Data involving 1396 incident RA cases and 5935 controls from the Swedish population-based case-control study,
Epidemiological Investigation of Rheumatoid Arthritis (EIRA), were analyzed. Information on self-reported exposure to occupational PW
was collected through questionnaire. Anti-CII was measured using ELISA. The odds ratio (OR) with 95% confidence interval (CI) of
developing anti-CII positive RA or anti-CII negative RA associated with PW exposure was calculated using logistic regression. Adjustment
for sex, age, residential area, educational level, alcohol consumption, body mass index, cigarette smoking, silica exposure and occupational
class did not substantially change the estimates.
Results: The ORs observed for the association between anti-CII positive RA and different types of PW ranged from 1.0 (95% CI, 0.4-2.4) to
2.3 (95% CI, 1.3-4.0). There was no difference in the ORs for PW exposure at diagnosis or five years earlier (table1). The ORs for the
association between anti-CII negative RA and PW ranged from 1.0(95% CI, 0.8-1.3) to 1.8(95% CI, 1.5-2.1). No statistically significant
difference was observed between the ORs for anti-CII positive RA and the ORs for anti-CII negative RA (all p-values > 0.2).Stratification
for HLA-DRB1*01/*03 or symptom duration did not change the results.
Conclusion: Since physical workload is associated with rheumatoid arthritis irrespective of anti-CII status or the presence of anti-CII
associated HLA alleles, and regardless of whether the timing of PW exposure was close to the appearance of anti-CII. We found no evidence
suggesting an association between PW and development of anti-CII in RA.
References
1. Zeng P, Klareskog L, Alfredsson L, Bengtsson C. Physical workload is associated with increased risk of rheumatoid arthritis: results from
a Swedish population-based case-control study. RMD open 2017;3(1):e000324.
2. Manivel VA, Mullazehi M, Padyukov L, et al. Anticollagen type II antibodies are associated with an acute onset rheumatoid arthritis
phenotype and prognosticate lower degree of inflammation during 5 years follow-up. Annals of the rheumatic diseases 2017.
Disclosure: P. Zeng, None; L. Alfredsson, None; L. Klareskog, None; M. Mullazehi, None; S. Saevarsdottir, None; C. Bengtsson, None;
J. Rönnelid, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/occupational-physical-workload-and-development-of-

anti-collagen-type-ii-antibodies-in-rheumatoid-arthritis-patients
Impact of the Five Components of the Euroqol 5-Dimensions Instrument on Healthcare

and Work-Loss Costs in Rheumatoid Arthritis: Observational Data from Southern
Sweden
Anders Gülfe1, Tor Olofsson1, Jonas K Söderling2, Martin Neovius2 and Johan K Wallman1, 1Department of Clinical Sciences Lund,
Rheumatology, Lund University, Lund, Sweden, 2Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm,
Sweden
SESSION INFORMATION
Background/Purpose: Healthcare and work-loss costs are markedly higher in RA patients than in the general population. The EuroQol 5-
Dimensions (EQ-5D) instrument, commonly applied to measure utility and quality-adjusted life-years (QALYs) in health-economic
evaluations, is based on a questionnaire, asking respondents to value 5 health dimensions (mobility; self-care; usual activities;
pain/discomfort; anxiety/depression) on a 3-leveled scale. In this study, we aimed to compare how these 5 EQ-5D components relate to
healthcare, work-loss, and total societal costs in RA.
Methods: Clinical visits of anti-TNF treated RA patients, monitored in the observational South Swedish Arthritis Treatment Group register
2005-2011, were included (11674 visits in 2246 patients; >95% fulfillment of 1987 ACR criteria in a prior validation). EQ-5D
questionnaire responses at visits were linked to register-derived costs of anti-rheumatic drugs, out- and inpatient care, and work-loss due to
sick leave or disability pension from 30 days before to 30 days after each visit. Associations of the 5 EQ-5D components to healthcare
(patient care and drugs), work-loss (in patients <65 years), and total societal costs (healthcare + work-loss costs; <65 years) were studied in
separate, adjusted, generalized estimating equations regression models, comparing standardized β coefficients by nonparametric
bootstrapping to assess which component best reflects costs.
Results: The strongest associations with both healthcare and work-loss (and thus also societal) costs were observed for the usual activites
component (p<0.05 vs. all other components; Figure). Apart from that, the mobility and self-care components were more closely associated
with healthcare costs than anxiety/depression, while stronger associations with work-loss costs were revealed for mobility and
anxiety/depression than for pain/discomfort. For comparison, cost associations with the composite EQ-5D utility score (United Kingdom
peference set) were (standardized β (95%CI)): -0.11 (-0.14 to -0.09) for healthcare, -0.07 (-0.08 to -0.05) for work-loss, and -0.12 (-0.15 to
-0.09) for societal costs.
Conclusion: Of the 5 EQ-5D components, problems to perform one’s usual daily activities was most strongly related to both healthcare and
work-loss (as expected) costs. Moreover, the associations of the usual activities component to costs were on par with those observed for the
composite EQ-5D utility score, making it an interesting simple marker of total societal costs in RA. Somewhat unexpectedly, relatively weak
cost associations were observed regarding the pain/discomfort component.
Disclosure: A. Gülfe, None; T. Olofsson, None; J. K. Söderling, AbbVie, Merck, Novartis, Shire, 5; M. Neovius, Schering-Plough,
AstraZeneca, Novo Nordisk, Pfizer, Roche, 2,Pfizer, Abbott, 5; J. K. Wallman, AbbVie, Celgene, Novartis, UCB, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/impact-of-the-five-components-of-the-euroqol-5-

dimensions-instrument-on-healthcare-and-work-loss-costs-in-rheumatoid-arthritis-observational-data-from-southern-sweden
Baseline Characteristics and Rates of Hospitalized Infections in Patients with

Rheumatoid Arthritis Treated with Non-TNF Inhibitors in Denmark and Sweden
Kathrine Lederballe Grøn1, Elizabeth V. Arkema2, Bente Glintborg1, Johan Askling3 and Merete Lund Hetland4, 1The DANBIO registry
and the Danish Departments of Rheumatology, Copenhagen, Denmark, 2Clinical Epidemiology Unit, Department of Medicine, Karolinska
University Hospital and Karolinska Institutet, Stockholm, Sweden, 3Unit of Clinical Epidemiology, Department of Medicine, Karolinska
University Hospital and Karolinska Institutet, Stockholm, Sweden, 4The DANBIO registry and the Danish Departments of Rheumatology,
Glostrup, Denmark
SESSION INFORMATION
Background/Purpose: Hospitalized infections during treatment with biologic disease modifying drugs (bDMARDs) in rheumatoid arthritis
(RA) are a concern. This have mainly been studied in patients (pts) treated with tumor necrosis factor inhibitors (TNFi), and only to a limited
degree in pts treated with non-TNFi (abatacept (ABA), rituximab (RTX), tocilizumab (TCZ)). The aims of this interim report, which is part
of an ongoing collaborative project between Denmark (DK) and Sweden (S), were to explore a) baseline characteristics and b) 12-month
risks of hospitalized infections in RA pts treated with ABA, RTX and TCZ in routine care.
Methods: Observational, prospective cohort study conducted in parallel in DK and S. RA pts who started treatment with a non-TNFi
between Jan 2010 and 2015 (DK: July 2015 and S: Dec 2015) were identified in the Danish DANBIO(1) and the Swedish ARTIS/SRQ
registries(2). By use of unique identification codes, information on pts’ baseline clinical characteristics from the registers was enriched with
information on previous malignancies, hospitalizations and hospitalized infections from the National Patient Registries (NPR). Information on
hospitalized infections during follow-up was obtained from the NPRs. Follow-up was 12 months after treatment start or 90 days after
withdrawal, whichever came first. Crude incidence rates (IR) of hospitalized infections were calculated for each drug in each country. For
the current interim analysis, no formal comparisons of rates were conducted.
Results: 8931 treatment series were identified. The numbers of ABA/RTX/ TCZ treatment series were 830/718/1098 in DK and
1872/2630/1783 in S, respectively (Table). Age, gender, functional status and disease activity were typical for RA pts, but a pattern of higher
age, more frequent previous cancer, hospitalizations or hospitalized infections in RTX treated patients was observed in both countries
(Table). The crude 12-month hospitalized infection rates were 5.84-8.76 in DK and 4.28-6.81 in S (Table).
Conclusion: This collaborative project between DK and S included >8000 treatment series of RA pts treated with ABA, RTX and TCZ in
routine care, and it demonstrated some channeling of patients to certain treatments, as reflected in differences in baseline characteristics.
Variation in crude rates of hospitalized infections was observed across drugs and countries. Further analyses will explore underlying reasons
that might explain differences in rates between the countries, as well as the impact of channeling, on the risk of hospitalized infections
associated with each drug under study.
References 1)Ibfelt et al. Clin Epi 2016;8:737-42
2)Eriksson et al. Clin Exp Rheu 2014;32:S-147-9
ADDIN EN.REFLIST
Disclosure: K. Lederballe Grøn, None; E. V. Arkema, None; B. Glintborg, Abbvie, Biogen, 2; J. Askling, MSD, BMS, Pfizer, AbbVie,
SOBI, UCB, Roche, Lilly, AstraZeneca, 2; M. Lund Hetland, Abbvie, BMS, Biogen, Celltrion, MSD, Novartis, Pfizer, Roche, UCB, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/baseline-characteristics-and-rates-of-hospitalized-

infections-in-patients-with-rheumatoid-arthritis-treated-with-non-tnf-inhibitors-in-denmark-and-sweden
Comorbidity Measures Differentially Predict Longitudinal Disease Activity, Remission,

and Disability in Rheumatoid Arthritis
Bryant R. England1, Harlan Sayles2, Kaleb Michaud2, Grant Cannon3, Andreas Reimold4, Liron Caplan5, Gail S. Kerr6, Namrata Singh7,
Gleb Haynatzki8, Michael D. George9, Joshua Baker10 and Ted R. Mikuls11, 1Division of Rheumatology & Immunology, Department of
Internal Medicine, Nebraska-Western IA VA Health Care System & University of Nebraska Medical Center, Omaha, NE, 2University of
Nebraska Medical Center, Omaha, NE, 3Salt Lake City VA Medical Center and University of Utah, Salt Lake City, UT, 4Hospital of Southern
Norway, Kristiansand, Norway, 5Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, 6VAMC, Georgetown
University, Washington, DC, 7Internal Medicine, University of Iowa Hospitals and Clinics and Iowa City VA, Iowa City, IA, 8Biostatistics,
University of Nebraska Medical Center, Omaha, NE, 9Division of Rheumatology, University of Pennsylvania, Philadelphia, PA,
10Rheumatology, University of Pennsylvania, Philadelphia, PA, 11Internal Medicine, Division of Rheumatology, University of Nebraska
Medical Center, Omaha, NE
SESSION INFORMATION
Background/Purpose: Comorbidity frequently complicates rheumatoid arthritis (RA) leading to poor long-term outcomes. However,
whether comorbidity influences measures of RA activity over time is less well established. The purpose of this study was to examine the
association of different comorbidity assessments with longitudinal disease activity and functional status.
Methods: Participants were enrollees in a multicenter, longitudinal observational cohort of US veterans with RA. Comorbid conditions were
collected at enrollment by treating rheumatologists and modeled using the Rheumatic Disease Comorbidity Index (RDCI) score, comorbidity
count (range 0-53), or by the individual comorbid conditions. Disease activity (DAS28) and functional status (MD-HAQ) were assessed at
routine clinic visits. Associations of comorbidity measures with disease activity and functional status over the initial 3 years of follow-up
were examined using multivariable linear mixed effects models. Comorbidity measures were examined as main effects as well as by using
interaction terms with time, the latter to examine whether a given measure was associated with diverging disease activity and functional
status trajectories over follow-up. The odds of ever achieving DAS28 remission (<2.6) were examined using multivariable logistic
regression.
Results: Among 2,516 participants with mean age of 64 (SD 11) years, RA duration 11 (11) years, 90% male, 79% RF positive, 78% anti-
CCP positive, and 80% with smoking history, 75% had a RDCI ³1. Hypertension (53%), hyperlipidemia (41%), lung (20%), and
cardiovascular (CV) disease (19%) were the most prevalent comorbidities. Comorbidity, measured by RDCI ³1, count, or RDCI score, was
not associated with longitudinal disease activity or remission (Table 1, Figure 1) although comorbidity count and RDCI score were
associated with reduced physical function (Table 1). Select individual comorbidities, including CV, lung, and psychiatric disease, were
more closely associated with unfavorable longitudinal disease activity, remission achievement, and physical function (Table 1, Figure 1).
CV and interstitial lung disease (ILD) were the only comorbidities with a significant time-interaction term (DAS28 models), suggesting a
widening gap in disease activity over time for these conditions.
Conclusion: CV, lung, and psychiatric comorbidities, but not composite comorbidity scores, are associated with higher measures of disease
activity and lower odds of achieving remission in RA. Specific comorbidities and composite measures are associated with longitudinal
functional status.
Table 1. Associations of comorbidities with longitudinal
disease activity and functional status.
log DAS28 MD-HAQ
_ (Std Error) _ (Std Error)

Composite
measures
RDCI ³1 -0.017 (0.025) 0.034 (0.039)
RDCI score 0.002 (0.006) 0.048 (0.010)**
Comorbidity count 0.000 (0.002) 0.016 (0.003)**
Individual
conditions
Lung disease -0.002 (0.023) 0.109 (0.035)**
Interstitial lung -0.093 (0.042) ± 0.032 (0.064)
disease (ILD)
ILD x time (years) 0.079 (0.012)** -
COPD 0.021 (0.025) 0.132 (0.037)*
Cardiovascular -0.012 (0.024) ± 0.081 (0.036)*
(CVD)
CVD x time 0.044 (0.016)** -
(years)
Diabetes mellitus 0.001 (0.024) 0.079 (0.036)*
Hypertension -0.013 (0.020) 0.021 (0.030)
Hyperlipidemia -0.039 (0.019) 0.047 (0.029)
Chronic kidney 0.006 (0.044) 0.094 (0.066)
disease
Cancer -0.030 (0.030) 0.006 (0.044)
PTSD 0.177 (0.038)** 0.206 (0.058)**
Depression 0.093 (0.031)** 0.157 (0.046)**
Covariates: RF, current smoking, DMARD, biologic
DMARD, prednisone + (DAS28) smoking*time (MD-
HAQ) education, race, disease duration.
* p < 0.05, ** p < 0.01
± Result from model with a significant comorbidity x time

interaction term
Abbreviations: RDCI Ð rheumatic disease comorbidity

index; COPD Ð chronic obstructive pulmonary disease;
PTSD Ð post-traumatic stress disorder
Disclosure: B. R. England, None; H. Sayles, None; K. Michaud, None; G. Cannon, Amgen, 2; A. Reimold, Bristol-Myers Squibb,
2,Janssen Pharmaceutica Product, L.P., 2,Pfizer, 2,Human Genome Sciences, 2,Novartis, 2; L. Caplan, None; G. S. Kerr, Janssen, BMS,
Genetech, Pfizer, 2; N. Singh, None; G. Haynatzki, None; M. D. George, None; J. Baker, None; T. R. Mikuls, BMS, 2,Ironwood Pharm,
2,Pfizer Inc, 5,NIH, VA, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/comorbidity-measures-differentially-predict-longitudinal-

disease-activity-remission-and-disability-in-rheumatoid-arthritis
Prevalence of Rheumatoid Arthritis and Associated Comorbidities in the 2011-2015

Medicare Population
Suying Li, Julia T. Molony, Yi Peng, Kimberly M. Nieman and David T. Gilbertson, Minneapolis Medical Research Foundation, Chronic
Disease Research Group, Minneapolis, MN
SESSION INFORMATION
Background/Purpose: Rheumatoid arthritis (RA) is a systemic inflammatory disease affecting about 1.5 million adults in the US (Helmick et
al., 2008). Patients with RA have an increased burden of comorbidity such as cardiovascular disease (CVD), diabetes, cancer, and other
inflammatory diseases. This study aimed to update prevalence estimates of RA and associated comorbidity in the US.
Methods: This was a retrospective descriptive study using the 2010-2015 20% Medicare sample data. Yearly prevalent RA cohorts (2011-
2015) were defined based on ICD-9 diagnosis code 714.0 with the addition of ICD-10 codes for the 2015 cohort. For each cohort year,
included patients were required to have Medicare Part A and Part B coverage with no Medicare Advantage, and to be alive for the entire
year preceding a cohort year and through the first month of the cohort year. RA was defined if a diagnosis code was present in at least 1
inpatient claim or 2 or more outpatient claims, separated by at least 30 days. The baseline period was 1 year preceding the cohort year and
was used to define comorbidity, including CVD, diabetes, hypertension, hyperlipidemia, cancer, anemia, and other inflammatory conditions
such as psoriasis, psoriatic arthritis, non-alcoholic fatty liver disease (NAFLD), and cirrhosis. Prevalence of comorbidity was presented as a
percentage of RA patients.
Results: This study included approximately 6 million Medicare beneficiaries in each year, 2011-2015; average RA prevalence was about
2.0% (Table 1). RA patient demographics were similar across years, with mean age 72.4 years; 77.0% were female, 83.4% white, and
10.7% black in the 2015 cohort. Common comorbid conditions in the 2015 RA cohort included hypertension (prevalence 67.3%),
hyperlipidemia (48.5%), diabetes (26.6%), anemia (26.4%), arteriosclerotic heart disease (21.5%), peripheral artery disease (17.2%),
congestive heart failure (13.2%), and cancer (8.8%) (Table 1). Prevalence of inflammatory conditions increased across years; for example,
NAFLD was 0.96% in 2011 and 1.36% in 2015; corresponding values were 0.04% and 0.07% for cirrhosis, 1.14% and 1.45% for psoriasis,
and 1.58% and 1.81% for psoriatic arthritis.
Table 1. Prevalence of RA and Associated Comorbid Conditions in 2011-2015 Medicare Patients

Cohort Year 2011 2012 2013 2014 2015
N Medicare patients in the
5,845,175 5,859,826 5,906,084 5,975,397 6,324,354
20% sample
N with RA in the 20% sample 117,014 117,494 118,660 120,448 123,137
% with RA 2.0 2.0 2.0 2.0 2.0
Baseline characteristics in RA
patients
71.8 71.8 71.7 71.8 72.4
Mean age in years (SD) (11.6) (11.5) (11.5) (11.4) (11.4)
% of Female 75.8 75.9 75.7 75.5 77.0
Race, %
White 82.2 82.3 82.3 82.5 83.4
Black 11.7 11.6 11.5 11.2 10.7
Other 6.1 6.1 6.2 6.3 6.0
Comorbidity (%) in RA
patients
Diabetes 26.7 27.2 27.1 27.2 26.6
Hypertension 65.9 66.5 66.6 66.8 67.3
Hyperlipidemia 45.5 47.3 47.8 48.1 48.5
CVD
ASHD 21.9 22.1 21.9 21.6 21.5
CHF 13.2 13.4 13.0 12.8 13.2
CVA/TIA 8.5 8.7 8.6 8.6 8.8
PVD 16.2 16.7 16.4 16.7 17.2
Other cardiac 13.6 14.5 14.0 14.1 14.7
Cancer 8.5 8.8 8.7 8.8 8.8
Anemia 26.8 27.7 27.0 26.7 26.4
GI bleeding 3.2 3.4 3.2 3.2 3.2
Liver 1.76 1.87 1.89 2.03 2.08
NAFLD 0.96 1.05 1.19 1.27 1.36
Cirrhosis 0.04 0.04 0.05 0.05 0.07
Psoriasis 1.14 1.30 1.36 1.43 1.45
Psoriatic arthritis 1.58 1.69 1.77 1.84 1.81
RA 69.7 71.2 71.6 72.0 73.7
RA=Rheumatoid arthritis; CVD=Cardiovascular disease; ASHD=Arteriosclerotic
Heart Disease;
CHF=Congestive heart failure; CVA/TIA=Cerebrovascular Accidents/Transient
Ischemic Attack;
PVD=peripheral artery disease; NAFLD=Non-alcoholic fatty
liver disease
Conclusion: Hypertension, CVD, hyperlipidemia, diabetes, anemia, and cancer are common in RA patients. Other inflammatory conditions
increased over the years studied. Further analysis should evaluate the effect of RA treatment and of secondary prevention in patients with
other inflammatory conditions.
Disclosure: S. Li, None; J. T. Molony, None; Y. Peng, None; K. M. Nieman, None; D. T. Gilbertson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prevalence-of-rheumatoid-arthritis-and-associated-

comorbidities-in-the-2011-2015-medicare-population
Rheumatoid Arthritis and the Risk for Interstitial Lung Disease: A Comparison of Risk
Associated with Biologic and Conventional Dmards
Fenglong Xie 1, Narender Annapureddy2, Lang Chen1, Jason Leonard Lobo3, Jim C. Oates4, Ankoor Shah5, Huifeng Yun6, Shuo Yang1 and
Jeffrey R. Curtis7, 1Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, AL, 2Vanderbilt
University Medical Center, Nashville, TN, 3Med-Pulmonary, University of North Carolina, Chapel Hill, NC, 4Medicine/Rheumatology &
Immunology, Medical University of South Carolina, Charleston, SC, 5Medicine, Duke University Medical Center, Durham, NC, 6University
of Alabama at Birmingham, Birmingham, AL, 7Rheumatology & Immunology, University of Alabama at Birmingham, Birmingham, AL
SESSION INFORMATION
Background/Purpose: Interstitial Lung Disease (ILD) is a rare but often severe consequence of several rheumatologic conditions including
rheumatoid arthritis (RA). The comparative risk of incident ILD between RA therapies remains undetermined.
Methods: A retrospective cohort study using 2006-2014 Medicare and 2010-2015 Market Scan data was conducted to assess the risk of ILD
among biologic and conventional DMARDs (cDMARDs) users. Adults with at least one ICD-9-CM RA diagnosis code from rheumatologist,
initiated at least one biologic or cDMARDs were included. Patients had to have at least 1 year of full coverage (medical and pharmacy) prior
to their RA treatment. Those with a diagnosis code for prevalent ILD, malignancy, HIV or organ transplantation (MHO), or prior oxygen use
(suggesting treatment for pre-existing ILD) were excluded. Patients initiating cDMARDs with prior exposure to biologic or synthetic
DMARDS (all available data) were also excluded. Follow up started at the initiation date of each therapy and ended at the earliest of: event,
loss of full coverage, end of exposure (with 90 days extension), switch to other biologic or synthetic DMARDS, diagnosis of MHO (except
for lung transplant), or end of study. ILD was defined as: one or more hospital discharge diagnosis code (any position) or 2 outpatient
diagnosis codes from a physician visit with diagnostic tests for chest CT or lung biopsy. Incidence rates (IR) of ILD were calculated using
Poisson regression; hazard ratios (HR) were calculated using COX regression, accounting for the clustering of RA treatments within patients.
Among patients who developed ILD, initiation of home oxygen and death (Medicare only) were reported.
Results: A total of 150,225 RA patients with 208,641 initiations of biologics or DMARDs were eligible for analysis. A total of 958 patients
developed ILD among 199,739 person years, resulting in an overall IR of 4.78 per 1,000 person years. The crude IRs for ILD ranged from a
low of 3.05 (95%CI: 1.15-8.14) for tofacitinib to a high of 8.37 (7.29-9.61) for infliximab (INF) in Medicare (Table 1); and a low of 0.58
(0.08-4.13) for certolizumab (CER) to 3.87(2.08-7.19) for INF in Market Scan. Compared to abatacept (ABA), the adjusted HR ranged from
0.82 (0.30-2.22) for tofacitinib to 2.07 (1.62-2.64) for INF in Medicare; from 0.41 (0.05, 3.41) for CER to 2.85 (1.03-7.89) for INF in
Market Scan.
Among 880 Medicare patients with ILD, 359 (41%) died after a mean (SD) 529 (640) days since diagnosis; 328 (37%) initiated home
oxygen, at a mean (SD) of 177 (418) days. Among 78 Market Scan patients with ILD, 22 (28%) initiated oxygen at a mean (SD) of 114(262)
days.
Conclusion: Compared to ABA, INF, rituximab, adalimumab, tocilizumab and etanercept were associated with increased risk of ILD,
although the absolute IR differences between therapies were small. Initiation of home oxygen and mortality was high among RA patients with
incident ILD.
Table: Incidence Rates of Interstitial Lung Disease and Adjusted Hazard Ratio in RA
Patients
DMARDS Medicare Market Scan
Number of patients=104,870 Number of patients=45,355
Number of initiations=143,540 Number of initiations=65,101

Event Person IRs aHR* EventPerson IRs aHR
Years Years
(95% CI) (95% CI) (95% CI) (95% CI)
ABATACEPT 99 23,939 4.14 Reference 6 4,154 1.44 Reference
( 3.40- ( 0.65-
5.04) 3.21)
ADALIMUMAB 82 13,382 6.13 1.77 14 7,268 1.93 1.42
( 4.94- (1.32- ( 1.14- (0.54-

7.61) 2.38) 3.25) 3.72)
CERTOLIZUMAB 14 4,306 3.25 0.83 1 17,198 0.58 0.41
( 1.93- (0.48- ( 0.08- (0.05-

5.49) 1.46) 4.13) 3.41)
ETANERCEPT 75 14,038 5.34 1.47 10 76,838 1.30 0.98
( 4.26- (1.09- ( 0.70- (0.35-

6.70) 1.99) 2.42) 2.7)
GOLIMUMAB 15 2,683 5.59 1.55 2 16,118 1.24 0.93
( 3.37- (0.90- ( 0.31- (0.19-

9.27) 2.67) 4.96) 4.64)
HCQ, LEF, or SSZ 115 25,221 4.56 1.03 10 6,877 1.45 1.00
( 3.80- (0.78- ( 0.78- (0.34-

5.47) 1.38) 2.70) 2.89)
INFLIXIMAB 202 24,136 8.37 2.07 10 2,584 3.87 2.85
( 7.29- (1.62- ( 2.08- (1.03-

9.61) 2.64) 7.19) 7.89)
METHOTREXATE 174 30,747 5.66 1.28 14 8,751 1.60 1.04
( 4.88- (0.97- ( 0.95- (0.37-

6.57) 1.68) 2.70) 2.93)
RITUXIMAB 63 7,968 7.91 1.93 3 1,519 1.98 1.16
( 6.18- (1.41- ( 0.64- (0.28-

10.12) 2.65) 6.13) 4.71)
TOCILIZUMAB 37 5,666 6.53 1.69 4 2,637 1.52 1.03
( 4.73- (1.16- ( 0.57- (0.29-

9.01) 2.47) 4.04) 3.67)
TOFACITINIB 4 1,310 3.05 0.82 4 1,540 2.60 1.68
( 1.15- (0.30- ( 0.97- (0.47-

8.14) 2.22) 6.92) 5.99)
All exposure 880 153,395 5.74 78 46,344 1.68
(5.37- (1.35-
6.13) 2.10)
CI: Confidence interval; aHR: Adjusted hazard ratio; IR: Incidence rate, per 1000 years.
* Adjusted for age, sex, systemic sclerosis, systemic lupus erythematosus, Sicca
syndrome, Hemiplegia or paraplegia, Diabetes, hypertension, Pneumonia, Chronic
pulmonary disease, Myocardial infarction, Coronary heart disease, Peripheral vascular
disorder, Cerebrovascular disease, Dementia, Liver disease.
Disclosure: F. Xie, None; N. Annapureddy, None; L. Chen, None; J. L. Lobo, None; J. C. Oates, None; A. Shah, None; H. Yun, Bristol-
Myers Squibb, 2; S. Yang, None; J. R. Curtis, AbbVie, Roche/Genentech, BMS, UCB, Myraid, Lilly, Amgen, Janssen, Pfizer, Corrona,
5,Amgen, Pfizer, Crescendo Bio, Corrona, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rheumatoid-arthritis-and-the-risk-for-interstitial-lung-

disease-a-comparison-of-risk-associated-with-biologic-and-conventional-dmards
Prediction of Cardiovascular Events in Rheumatoid Arthritis Patients Using a Multi-

Biomarker of Disease Activity
Fenglong Xie 1, Lang Chen2, Huifeng Yun2 and Jeffrey R. Curtis3, 1Division of Clinical Immunology & Rheumatology, University of
Alabama at Birmingham, Birmingham, AL, 2University of Alabama at Birmingham, Birmingham, AL, 3Division of Clinical Immunology and
Rheumatology, University of Alabama at Birmingham, Birmingham, AL
SESSION INFORMATION
Background/Purpose: The ACC/AHA recommends preventive strategies for patients with a high predicted risk of atherosclerotic
cardiovascular disease (CVD). RA patients are at higher risk for CVD events, yet the role of systemic inflammation and the influence of
traditional CVD risk factors is unclear with respect to risk prediction in RA. A simple and accurate algorithm for predicting CVD event risk
that includes systemic inflammation might help risk assessment for RA patients and optimize preventive care.
Methods: We derived a U.S. cohort of RA patients with multi-biomarker disease activity (MBDA) test results linked to Medicare claims
data. Patients had to have ≥1 year baseline with Medicare coverage prior to the first MBDA test. Exclusions were past MI, PCI/CABG,
stroke, or cancer. Follow-up ended at the earliest of 1) CVD event; 2) other than CVD cause of death; 3) loss of coverage; or 4) 12/31/2014.
The composite CVD event comprised of incident MI, stroke or fatal CVD event, using validated algorithms. MBDA scores were grouped as
low (<30), moderate (30-44), and high (>44). Other predictors included demographics, healthcare utilization, and comorbidities. Three
separate models were developed using Cox regression. Model 1 included age, sex and race. Model 2 included age, sex race, 9 comorbidities
and CVD medication classes, plus interaction terms. Model 3 included age, sex, and race plus categorized MBDA score. We calculated the
net reclassification index (NRI) for model 2 and 3 compared to model 1. We also plotted the observed vs. predicted probability of CVD
event for each model, with risk categorized as low (<7.5), moderate (7.5-<15) and high (≥15) per 1000 person-years based upon annualized
ACC/AHA cutpoints.
Results: A total of 15,757 RA patients were included; mean (SD) age 68.6(10.8) years, 80% female, 80% white. A total 209 CVD events
occurred in 14,843 person years (1.41/100 py). The median (IQR) follow up time was 0.84 (0.41, 1.27) year. The maximum event time was
at 2.7 year. All models had reasonable discrimination and calibration; model 3 was better than models 1 and 2 and observed vs predicted
risk is shown (Figure). The sum of the absolute difference between observed and predicted probability was 0.56, 0.57 and 0.33 for models 1,
2 and 3 respectively. Compared to model 1, model 2 resulted in a positive overall NRI of 0.214 (non-event NRI=0.173, event NRI=0.041);
model 3 resulted in positive overall NRI of 0.279 (non-event NRI=0.092, event NRI=0.187), consistent with more accurate CVD event
classification.
Conclusion: Preliminary results from this analysis suggest that a simple algorithm consisting only of age, sex and race plus a multi-biomarker
score can provide an accurate method to predict short term CVD risk in RA. Further validation with more extended time frames should
improve the utility of this approach.
Figure: Observed vs. Predicted One-Year CVD Risk per 1000 person-years in RA Patients, using only Age, Sex, Race, and MBDA score
(Model 3)
Disclosure: F. Xie, None; L. Chen, None; H. Yun, BMS, 2; J. R. Curtis, UCB Pharma, Janssen-Cilag, Amgen, Roche, Myriad Genetics,
Lilly, Novartis, BMS, Pfizer, 2,UCB Pharma, Janssen-Cilag, Amgen, Roche, Myriad Genetics, Lilly, Novartis, BMS, Pfizer, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prediction-of-cardiovascular-events-in-rheumatoid-

arthritis-patients-using-a-multi-biomarker-of-disease-activity
No Effect of Tumor Necrosis Factor-a Inhibitors on Renal Function in Patients with

Rheumatoid Arthritis from Kobio Registry from 2012 to 2016
Seong-Kyu Kim1, Jung-Yoon Choe2, Sung-Hoon Park3 and Hwajeong Lee2, 1Rheumatology, Catholic University of Daegu School of
Medicine, Daegu, Korea, Republic of (South), 2Catholic University of Daegu School of Medicine, Daegu, Korea, Republic of (South),
3Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea, Republic of (South)
SESSION INFORMATION
Background/Purpose: Renal disease is prevalent in patients with rheumatoid arthritis (RA), although the precise prevalence of RA has not
been determined. Increased mortality in patients with RA is associated with concurrent renal diseases. Impaired renal function in patients
with RA is likely due to a chronic inflammatory response, antirheumatic drug toxicity, and renal involvement of RA itself. The effect of
biological disease-modifying antirheumatic drugs (bDMARDs) on renal function in patients with RA has not been well establisehd. We
assessed whether tumor necrosis factor (TNF) inhibitors could affect renal function in RA.
Methods: A total of 2110 patients with RA enrolled in the Korean College of Rheumatology Biologics (KOBIO) registry were analyzed. All
patients were taking bDMARDs or conventional synthetic DMARDs (csDMARDs). Renal function was evaluated by calculating the
estimated glomerular filter rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation. Renal insufficiency was defined
as eGFR < 60 mL/min/1.73 m2. Differences in eGFR changes between different types of DMARDs were assessed at each follow-up time
using the generalized linear model (GLM) method. Risk factors for renal insufficiency were identified using binary logistic regression
analysis.
Results: The changes of eGFR values in patients treated with TNF inhibitors were not significantly different from those with csDMARDs
alone or non-TNF inhibitors in all RA patients regardless of renal function. Among patients with renal insufficiency, GLM analysis revealed
that the changes of eGFR values by TNF inhibitors were also compatible to those treated with csDMARDs alone or non-TNF inhibitors.
Older age (> 55 years), longer disease duration (> 5 years), and use of methotrexate were identified as clinical determinants for renal
insufficiency.
Conclusion: TNF inhibitors did not influence the change of renal function during RA treatment. TNF inhibitors may be a safe treatment option
irrespective of renal function.
Disclosure: S. K. Kim, None; J. Y. Choe, None; S. H. Park, None; H. Lee, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/no-effect-of-tumor-necrosis-factor-a-inhibitors-on-renal-

function-in-patients-with-rheumatoid-arthritis-from-kobio-registry-from-2012-to-2016
Estimating Prevalence and Cost of Depression Among Japanese RA Patients: A

Retrospective Claims Data Base Analysis
Rosarin Sruamsiri1, Jörg Mahlich2 and Yuko Kaneko3, 1Health Economics, Janssen Pharmaceutical KK,, Tokyo, Japan, 2Health Economics,
Janssen Pharmaceutical KK, Tokyo, Japan, 3Division of Rheumatology, Department of Internal Medicine, Keio University School of
Medicine, Tokyo, Japan
SESSION INFORMATION
Background/Purpose:
Significant evidence in the scholarly literature suggests that depression is a common comorbidity among patients with rheumatoid arthritis
(RA) causing significant burden for the healthcare system. However, no studies are available for Japan and, hence, this is the first attempt to
systematically assess the cost of depression in an RA patient cohort.
Methods:
We used a large administrative claims data base (JMDC) to calculate prevalence and associated costs of depression within RA patients
between March 2009 and September 2015. Descriptive statistics is used to describe baseline characteristics of included patients, healthcare
utilization and total health care cost. Propensity score matching is applied to eliminate confounding effects (potential imbalances in baseline
covariates) using 1:4 matching type.
Results:
We identified 101,512 patients in the database with neither RA or depression diagnosis. 6,838 were diagnosed with RA but not with
depression and 473 had a co-diagnosis of depression and RA indicating a prevalence of depression within RA patients of 6.5%. After
matching, RA patients with depression had 55% more outpatient visits (p=0.010) and caused 46% higher health care costs than those without
depression (p=0.000). Mean healthcare costs per patient per month was 102,101 JPY for the former and 70,079 JPY for the latter population.
Conclusion:
A co-morbidity of RA patients with depression adds significant costs to the healthcare system and rheumatologists should be aware of this
co-morbidity to ensure timely treatment initiation when necessary.
Disclosure: R. Sruamsiri, Janssen Pharmaceutical KK, 3; J. Mahlich, JNJ, 3; Y. Kaneko, AbbVie, Eisai, Daiichi Sankyo, Sanofi, 2,Bristol-
Myeres Squibb, Eli Lily, Janssen, 5,AbbVie, Eisai, Astellas, Chugai Pharmaceutical, UCB, Pfizer, Bristol-Myeres Squibb, Janssen, Tanabe-
Mitsubishi, Ayumi Pharmaceutical, and Takeda Pharmaceutical, Taisho-Ttoyama, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/estimating-prevalence-and-cost-of-depression-among-

japanese-ra-patients-a-retrospective-claims-data-base-analysis
Refractory Disease in Rheumatoid Arthritis: Results from the British Society of

Rheumatology Biologics Register for Rheumatoid Arthritis
Lianne Kearsley-Fleet1, Diederik De Cock1, Kath Watson1, Maya H. Buch2, John D Isaacs3 and Kimme L. Hyrich1,4, 1Arthritis Research
UK Centre for Epidemiology, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom, 2Leeds
Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Leeds Musculoskeletal Biomedical Research Unit,
Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom, 3National Institute for Health Research Newcastle Biomedical Research
Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle, United Kingdom, 4National Institute of
Health Research Manchester Musculoskeletal Biomedical Research Centre, Central Manchester NHS Foundation Trust, Manchester
Academic Health Science Centre, Manchester, United Kingdom
SESSION INFORMATION
Background/Purpose: Biologic therapy has revolutionised treatment pathways and improved outcomes for patients with Rheumatoid
Arthritis (RA) who do not tolerate or respond to conventional synthetic therapies. However, for some patients on biologics, disease control
remains elusive with so-called refractory disease. The aim was to quantify the frequency of biologic resistant disease and identify factors,
measured at the start of first biologic, associated with resistant disease.
Methods: Patients with RA starting first-line TNFi (previously failed ≥2 DMARDs) in the BSRBR-RA were included if they had a full 10
years of study follow-up (N=5755). Patients were classified as “refractory” if they had used ≥3 classes of biologic, and were compared with
“persistent” patients who remained on first TNFi for 10 years. Stop reasons were investigated. HAQ was assessed at 3 years (end of patient
follow-up) and DAS28 at 10 years. Associations with age, gender, disease duration, baseline DAS28 and components, comorbidities, HAQ
and refractory disease were analysed in a multivariable logistic analysis. Multiple imputation was used to account for missing data.
Results: Of the whole cohort, 2147 (37%) were classed as persistent TNFi patients, and 272 (5%) as refractory (Table 1). Refractory
patients remained on their first TNFi for a mean of 2.9 years, and 51% stopped for inefficacy. Refractory patients had also used rituximab
(94%), tocilizumab (77%), and other classes (48%), whilst 74% had also used >1 TNFi. In the refractory cohort, 34% reported recurrent
drug inefficacy only, 8% recurrent adverse events only and 50% a combination of reasons for repeated drug failures (with reasons missing in
8%). Disease activity was higher among patients with refractory disease (DAS28 5.0 vs 3.7; HAQ 2.0 vs 1.6). In multivariable analysis,
older patients (>50 years, OR 0.5 (95% CI 0.4, 0.7)) and those with longer disease duration (>10 years, OR 0.7 (95% CI 0.6, 0.95)) had
reduced odds of refractory disease. In addition, greater baseline HAQ (OR 1.8 (95% CI 1.4, 2.4)), and patient global assessment (OR 1.1
(95% CI 1.0, 1.2)) had increased odds of refractory disease (Table 2).
Conclusion: In this real-world cohort of patients with RA, followed for 10 years, approximately 5% had biologic resistant disease, with 2/3
reporting lack of response to any biologic. This may be an under-estimate as many patients in this study may have died before alternative non-
TNFi biologics became available. Higher disability at the start of first TNFi predicted resistant disease but in general persistent and resistant
patients were similar at the outset of therapy.
Multiple Failures Persistent First Users
Table 1: Baseline Characteristics. p-value
[N=272] [N=2147]
Etanercept: 115 (42%) Etanercept: 1045 (49%)
First TNFi, n (%) Infliximab: 74 (27%) Infliximab: 511 (24%) P=0.1
Adalimumab: 83 (31%) Adalimumab: 591 (28%)

Females, n (%) 222 (82%) 1612 (75%) P=0.02
Age (years), median (IQR) 51 (43, 58) 55 (47, 62) P<0.001
11 (6, 18)
Disease Duration (years), median
9 (4, 17) P=0.01
(IQR)
N=2125
1331 (62%)
Rheumatoid Factor Positive, n (%) 175 (64%) P=0.5
N=2143
Fulfilled RA ACR criteria at
272 (100%) 2147 (100%) -
baseline, n (%)
On concurrent methotrexate, n (%) 165 (61%) 1377 (64%) P=0.3
On steroids at baseline, n (%) 116 (43%) 848 (40%) P=0.3
Total Comorbidities* P=0.2
None 128 (47%) 1137 (53%)
1 comorbidity 95 (35%) 711 (33%)
2 comorbidities 38 (14%) 241 (11%)
3+ comorbidities 11 (4%) 58 (3%)
SF-36 scores [range 0 (worse) to
N=221 N=1707
100], median (IQR)
Physical Component Score 14 (9, 19) 16 (11, 23) P<0.001
Mental Component Score 40 (33, 49) 43 (35, 53) P=0.007
Disease Activity, median (IQR)
17 (12, 24) 15 (10, 21)
Tender Joint Count (range 0 - 28) P=0.002
N=265 N=2095
12 (7, 17) 11 (7, 15)
Swollen Joint Count (range 0 – 28) P=0.05
N=265 N=2096
8.0 (6.9, 9.0) 7.5 (6.0, 8.5)
Patient Global Assessment, cms (range
P<0.001
0 – 10) N=264 N=2091
38 (23, 69) 38 (22, 59)
ESR (mm/hr) P=0.8
N=253 N=2011
6.5 (5.8, 7.2)
DAS28 (range 0 – 10) 6.8 (6.0, 7.5) P<0.001
N=2124
2.1 (1.9, 2.5) 2.0 (1.5, 2.4)
HAQ (range 0 – 3) P<0.001
N=266 N=2034
*Total comorbidities = hypertension, ischemic heart disease, stroke, lung disease, renal disease, diabetes,
depression, liver disease.
Tumour Necrosis Factor inhibitor (TNFi), interquartile range (IQR), Rheumatoid Arthritis (RA), American
College of Rheumatology (ACR), 36-item Short Form Survey for quality of life (SF-36), erythrocyte
sedimentation rate (ESR), 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ)
Table 2: Multivariable analysis (imputed data, 71
datasets), odds ratios for having refractory Odds Ratio P-value [mean]
disease compared with persistent first users.
Females 1.3 (0.95, 1.8) P=0.1
Age Groups (>50 years vs ≤ 50 years) 0.5 (0.4, 0.7) P<0.001
Disease Duration Groups (>10 years vs ≤ 10
0.7 (0.6, 0.95) P=0.02
years)
Tender Joint Count 1.0 (1.0, 1.1) P=0.07
Swollen Joint Count 1.0 (1.0, 1.0) P=0.6
Patient Global Assessment (cms) 1.1 (1.0, 1.2) P<0.05
ESR (mm/hr) 1.0 (1.0, 1.0) P=0.4
DAS28 (whole unit) 0.9 (0.5, 1.5) P=0.6
HAQ (whole unit) 1.8 (1.4, 2.4) P<0.001
Total Comorbidities* (vs none)
1 comorbidity 1.2 (0.9, 1.6) P=0.3
2 comorbidities 1.3 (0.9, 2.0) P=0.2
3+ comorbidities 1.6 (0.8, 3.1) P=0.2
*Total comorbidities = hypertension, ischemic heart disease, stroke, lung disease, renal
disease, diabetes, depression, liver disease.
Erythrocyte sedimentation rate (ESR), 28-joint Disease Activity Score (DAS28), Health
Assessment Questionnaire (HAQ)
Disclosure: L. Kearsley-Fleet, None; D. De Cock, None; K. Watson, None; M. H. Buch, Pfizer Ltd, 2,Roche Pharmaceuticals, 2,Abbott
Immunology Pharmaceuticals, 5,Sandoz, 5; J. D. Isaacs, None; K. L. Hyrich, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/refractory-disease-in-rheumatoid-arthritis-results-from-

the-british-society-of-rheumatology-biologics-register-for-rheumatoid-arthritis
Incidence of Hip Fracture in Rheumatoid Arthritis: British Columbia, Canada

C. Allyson Jones1, Pierre Guy2, Hui Xie3, Eric C. Sayre4 and Diane Lacaille5,6, 1Physical Therapy, University of Alberta, Edmonton, AB,
Canada, 2Department of Orthopaedics, University of British Columbia / Centre for Hip Health and Mobility, Vancouver, BC, Canada,
3Biostatistics, Faculty of Health Sciences, Simon Fraser University / Arthritis Research Canada, Burnaby, BC, Canada, 4Arthritis Research
Canada, Richmond, BC, Canada, 5Arthritis Research Canada/ University of British Columbia, Vancouver, BC, Canada, 6University of
British Columbia, Arthritis Research Canada, Richmond, BC, Canada
SESSION INFORMATION
Background/Purpose: Hip fractures have serious long-term effects, including a high 1-year mortality rate (usually 20-30%) and poor
functional recovery, with approximately 50% not attaining pre-fracture functional status. Although risk of hip fractures is known to be
increased in rheumatoid arthritis (RA), few studies specifically look at the incidence of hip fractures in patients with RA compared to general
population controls. We estimated the incidence of hip fractures in a population-based cohort including all incident RA cases in a Canadian
province, using administrative health data.
Methods: Using physician billing data and a previously published RA definition, we assembled an incident cohort of all cases with RA onset
between 1997 and 2009. Controls (with no diagnosis of RA or other inflammatory arthritis) selected randomly from the general population
were matched 2:1 to RA patients on birth year, gender and index year. RA and controls with prior hip fractures, pathological fractures or
Paget’s disease were excluded. Hip fractures (ICD9-CM codes 820.0, 820.2; ICD10-CA codes S72.0, S72.1, S72.2) were identified using
hospitalization data (includes ≤25 codes defining reason for admission or complications during hospitalization). Crude incident rates were
calculated as number of new hip fractures per person-year (PY). Cox-regression models were used to compare age and sex adjusted risk of
hip fracture in RA relative to controls.
Results: A total of 60,101 RA patients and 120,462 controls (mean age 57.2 yrs; 68% females for each cohort) were followed to December
2014, yielding 0.596 million PY and 1.23 million PY, resp. Incident hip fractures were observed in 2463 RA and 3566 controls. Mean (SD)
age at time of fracture was 78.9 (10.9) yrs in RA and 82.1 (9.0) yrs in controls. Crude incidence rate was 4.1 and 2.9 per 1000 PY for RA
and controls, resp., yielding an incidence rate ratio (IRR) of 1.42 [95% CI 1.35, 1.50]. Crude IRRs decreased with age and did not differ by
sex (Figure 1). Adjusting for age and sex, persons with RA had 48% greater risk of hip fracture than persons without (HR 1.48, 95%CI 1.41,
1.56).
Conclusion: Risk of hip fractures in persons with RA is higher than age/sex matched controls particularly at younger ages. Given the impact
of hip fractures, this has important implications for functional status and quality of life of people with RA. Further work on course of
recovery, mortality and health services use post-fracture is needed.
Disclosure: C. A. Jones, None; P. Guy, None; H. Xie, None; E. C. Sayre, None; D. Lacaille, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/incidence-of-hip-fracture-in-rheumatoid-arthritis-british-

columbia-canada
Patient Rheumatoid Arthritis Data from the Real World (PARADE) Study: Preliminary
Results from an Apple Researchkit™ Mobile App-Based Real World Study in the
United States
Rachel Williams1, Emilia Quattrocchi2, Sarah Watts3, Sherry Wang4, Pam Berry4 and Michelle Crouthamel4, 1Real World Evidence and
Epidemiology, GSK, Collegeville, PA, 2R&D Immunoinflammation, GSK, Middlesex, United Kingdom, 3GSK, Stevenage, United Kingdom,
4GSK, Collegeville, PA
SESSION INFORMATION
Background/Purpose: Smartphone apps and sensors enable researchers to design novel endpoints and collect real world data directly from
patients in a cost-effective, fast, and patient-focused approach. ResearchKit™, created by Apple in 2015, is an iOS-based, open-source
platform for researchers to conduct App-based studies. We were the first pharmaceutical company to utilize the ResearchKit™ by conducting
the Patient Rheumatoid Arthritis Data from the Real World (PARADE) Study. The objectives were to investigate the feasibility of utilizing a
mobile app to recruit and enroll patients into a study and to gain insights about Rheumatoid Arthritis (RA) in a real world setting.
Methods: The PARADE study was conducted in the United States (US) using a customized Apple ResearchKit™ App. The PARADE App
included study video, eligibility screen, electronic informed consent, and data collection. The enrolment period was July 12 through August
12, 2016. Recruitment was enhanced with advertisement on various targeted social media platforms. Participants could enroll if they were 21
years or older, spoke English, lived in the US, and had been diagnosed with RA by a doctor. Participants were asked to provide
demographics, comorbidities, medications, and RA symptoms including pain, fatigue, mood and morning stiffness. Additionally, over the
course of 12 weeks, participants were asked to complete validated questionnaires routinely used in RA clinical trials, namely HAQ, FACIT,
and EQ-5D. All data were self-reported and collected via their iPhone.
Results: There were 1170 downloads of the PARADE App with 428 consents to participate in the study. Of these, 399 participants provided
analyzable data, defined as those completing all demographic questions. The study population was 80% female, 81% Caucasian, mean age
47.9 years, and 77% college graduates. The duration of diagnosed RA included 122 (30.6%) participants with RA for <2 years, 91 (22.8%)
for 2-5 years, 91 (22.8%) for 5-10 years and 95 (23.8%) for >10 years. Most bothersome RA symptoms included joint pain (87.5%), fatigue
(73.5%), morning stiffness (57.5%), poor sleep (52.4%), walk and balance (32.8%), and mood variations (23.7%). Mean pain score was
4.4 (SD 0.14) on a numerical rating scale of 0 (no pain) to 10 (worst pain imaginable). Mean scores for validated questionnaires were HAQ-
DI, 1.1 (SD 0.04); Patient Global Assessment of Disease Activity, 5.4 (SD 0.14) (0=I don’t feel arthritis to 10=Arthritis affects me severely);
EQ-5D, 0.6983 (SD 0.00822), and FACIT, 25.5 (SD 0.66). RA medications are listed in the Table.
Conclusion: The PARADE study was the first Pharma-sponsored study in which real world patients could self-recruit, consent, enroll, and
report data entirely via their iPhone using a ResearchKit™ App. This study successfully demonstrated the feasibility of this novel technology
to gather insights into RA from a real world perspective.
Current RA medications among Proportion of population that

PARADE study participants answered this question (n=388)
Painkillers 170 (43.8%)
NSAIDs 194 (50.0%)
Corticosteroids 117 (30.2%)
Methotrexate 155 (39.9%)
Azathioprine 5 (1.3%)
Auranofin 1 (0.3%)
Chloroquine 1 (0.3%)
Hydroxychloroquine 107 (27.6%)
Leflunomide 30 (7.7%)
Mycophenolate 3 (0.8%)
Sulfasalazine 29 (7.5%)
Abatacept 29 (7.5%)
Adalimumab 42 (10.8%)
Certolizumab 10 (2.6%)
Etanercept 34 (8.8%)
Golimumab 11 (2.8%)
Infliximab 16 (4.1%)
Rituximab 11 (2.8%)
Tocilizumab 13 (3.4%)
Tofacitinib 18 (4.6%)
Others 40 (10.3%)
Disclosure: R. Williams, GSK, 3; E. Quattrocchi, GSK, 3; S. Watts, gsk, 3; S. Wang, gsk, 3; P. Berry, gsk, 3; M. Crouthamel, gsk, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/patient-rheumatoid-arthritis-data-from-the-real-world-

parade-study-preliminary-results-from-an-apple-researchkit-mobile-app-based-real-world-study-in-the-united-states
Are RA Patients at a Higher Risk for Car Accidents?

Kaleb Michaud1,2, Sofia Pedro1 and Ted R. Mikuls3, 1National Data Bank for Rheumatic Diseases, Wichita, KS, 2University of Nebraska
Medical Center, Omaha, NE, 3Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE
SESSION INFORMATION
Background/Purpose:
Automobile driving is an important instrumental activity of daily living with heightened importance among arthritis sufferers who are
disproportionately reliant on driving for the preservation of health, well-being, and quality of life. Despite its importance to patients, scant
data exists regarding the impact of arthritis on driving performance. We investigated occurrences of motor vehicle accidents (MVA) in
patients with RA and how clinical function measures may be associated with MVA.
Methods:
Using a large US observational cohort, the National Data Bank for Rheumatic Diseases (NDB), we compare RA and adult non-RA rheumatic
disease patients who had a validated MVA. Within each group, we also compare patients with and without a MVA measured at a random
observation before the accident or at any time for those without an accident. Patients with <2 questionnaires were excluded. MVAs were
identified by validated hospitalizations (code 162) and by death codes (ICD9, E81*). We conducted a principal component analysis (PCA)
using the 20 items from the HAQ. Scree plot and the Kaiser criterion were used to select the number of components.
Results:
From a total of 37,743 patients, we found 142 MVA, 103 recorded as hospitalizations and 39 as deaths. From the 26,905 RA adults, 90
(0.33%) had a MVA while the 10,838 non-RA patients had somewhat higher number of 52 (0.48%) (P=0.037). There was no statistical
difference in demographic or clinical outcomes between those with or without a MVA in patients with RA, though there was an association
with the number of individuals living the patient s household with those in MVA having fewer (p=0.02). Non-RA patients with MVA were
older than patients with no accidents or compared to RA patients (Table). Scree plot analysis and Kaiser criterion identified the first two
components as being the most associated with MVA (Figure). Component 1 (overall disability score) accounted for 56% of the variance in
MVA risk while Component 2 (individual HAQ items) accounted for an additional 8% of variance. Of note, Component 2 included HAQ
response items focused on upper extremity function / mobility (i.e. opening a car door, eating, opening a jar) and did not include items
focused on lower extremity function (Figure).
Conclusion:
These findings provide evidence that reduced functional independence and hand mobility, outcomes associated with RA disease activity, may
be linked to poor driving and/or future vehicle accidents.
Table –Comparison between RA and non-RA patients with and without car accidents
P-value
Variables RA patients (N=26,905) Non-RA patients (N=10,838) for
No car Car No car Car car
accidents accidents accidents accidents accidents
mean (sd) RA vs
or % (N=26,815)(N=90) P (N=10,786) (N=52) P non-RA
60.81 60.17 60.88 66.98
Age (yrs) (13.31) (13.25) 0.65 (13.69) (15.21) 0.00 0.01
Sex (% 0.22 0.22
Male) 0.21 (0.41)(0.42) 0.72 0.15 (0.36) (0.42) 0.22 0.93
Employed 0.26 0.22
(%) 0.34 (0.47)(0.44) 0.12 0.34 (0.47) (0.42) 0.08 0.59
Educational 13.67 13.36 14.10 14.04
level (yrs) (2.38) (2.47) 0.21 (2.32) (2.50) 0.86 0.12
1.36 1.17
Dependency1.23 (0.96) (0.94) 0.42 1.17 (0.97) (1.07) 0.22 0.22
None of the
time (%) 29.27 19.70 29.78 25.61
A little of
the time
(%) 41.46 36.36 33.14 35.51
Some of the
time (%) 14.63 31.82 28.70 30.26
Most of the
time (%) 12.20 12.12 7.33 7.33
All of the
time (%) 2.44 0.00 1.05 1.29
Number of
person in 1.97 1.97
household 2.21 (1.05) (0.82) 0.02 2.19 (1.07) (1.26) 0.20 0.98
Figure 1- Component loadings of the first two PCAs.
Disclosure: K. Michaud, National Data Bank for Rheumatic Diseases, 3; S. Pedro, National Data Bank for Rheumatic Diseases, 3; T. R.
Mikuls, BMS, 2,Ironwood Pharm, 2,Pfizer Inc, 5,NIH, VA, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/are-ra-patients-at-a-higher-risk-for-car-accidents
Cause-Specific Mortality in a Large Population-Based Cohort of Rheumatoid Arthritis

Patients in Italy
Francesca Ometto1, UGO FEDELI2, ELENA SCHIEVANO2, Costantino Botsios3, MARIA CHIARA CORTI2 and Leonardo Punzi4,
1Rheumatology Unit, Department of Medicine - DIMED, University of Padova, PADOVA, Italy, 2Epidemiological Department, Veneto
Region, VENETO, Italy, 3Rheumatology Unit, Department of Medicine - DIMED, University of Padova, Padova, Italy, 4Rheumatology Unit,
Department of Medicine DIMED, University of Padova, Padova, Italy
SESSION INFORMATION
Background/Purpose: Studies on mortality in RA from Italy are completely lacking. The aim of our study was to investigate cause-specific
mortality in RA subjects living in the Veneto Region (Italy).
Methods: We identified in the electronic archive of the Veneto Region patients aged 20Ð89 years who were exempt from copayment for RA
in January 2010, and linked them with the archive of causes of deaths of the period 2010-2015. Causes of death were coded according to the
International Classification of Diseases, 10th Edition. The selection of the underlying cause of death (UCOD) was performed by means of the
Automated Classification of Medical Entities (US National Center for Health Statistics). Each subject was followed from 1st January 2010
either until death, or 90 years of age, or 31st December 2015, whichever came first. Standardized Mortality Ratios (SMRs) with 95%
confidence intervals were computed as the ratios between deaths observed in the cohort, and those expected according to age- and gender-
specific regional mortality rates.
Results: Overall 16,098 residents diagnosed with RA and aged 20-89 years were enrolled in the cohort (Figure 1). The overall follow-up
amounted to 88,599 person-years, with 2,142 registered decedents. The most common causes of death were circulatory diseases (36.6%),
neoplasms (24.2%), and respiratory diseases (8.3%). Overall SMR in RA subjects was 1.42 (1.36-1.48). Mortality was significantly
increased from circulatory (SMR=1.56, 1.45-1.67), respiratory (SMR=1.83, 1.57-2.12), digestive (SMR=1.93, 1.60-2.32), infectious
(SMR=2.34, 1.88-2.89), and hematological diseases (SMR=3.22, 2.04-4.83), and falls (SMR=1.95, 1.19-3.01) (Table I). Particularly SMR
for circulatory diseases was higher in patients aged <65 years: SMR 1.86 (1.06-3.02) in males, and 2.07 (1.23-3.28) in females. RA was
selected as the UOCD in 6.1% of all deaths in the cohort and was mentioned in 25.4% of death certificates. Diseases often reported in the
certificate without being selected as the UCOD where sepsis, pneumonia, diabetes mellitus, and hypertensive diseases (Table II).
Conclusion : In the Veneto Region, a 42% excess risk of death was observed among subjects with RA compared to the general population.
Adverse effects of therapy and comorbidities should be identified and adequately monitored in RA subjects.
Table 1. Number of deaths and standardized mortality ratio
(SMR) with 95% Confidence Interval (CI).
n.
SMR (CI)
deaths
Certain infectious and parasitic diseases 2.34 (1.88-
88
(A00-B99) 2.89)
3.07 (2.37-
Septicemia (A40ÐA41) 66
3.90)
0.98 (0.90-
Neoplasms (C00-D48) 519
1.07)
1.04 (0.67-
Malignant neoplasm of stomach (C16) 25
1.54)
Malignant neoplasms of colon, rectum and 0.96 (0.71-
51
anus (C18-C21) 1.26)
1.04 (0.76-
Malignant neoplasm of pancreas (C25) 45
1.39)
Malignant neoplasms of trachea, bronchus 1.10 (0.89-
102
and lung (C33-C34) 1.33)
0.87 (0.63-
Malignant neoplasm of breast (C50) 44
1.16)
1.36 (0.84-
Non-HodgkinÕs lymphoma (C82-C85) 21
2.08)
1.31 (0.82-
Leukemia (C91-C95) 22
1.99)
Diseases of the blood and blood-forming 3.22 (2.04-
23
organs (D50-D89) 4.83)
Endocrine, nutritional and metabolic 0.96 (0.73-
57
diseases (E00-E90) 1.25)
0.93 (0.67-
Diabetes mellitus (E10-E14) 43
1.26)
Mental and behavioural disorders (F00- 0.90 (0.67-
50
F99) 1.18)
0.86 (0.62-
Dementia (F00-F03) 44
1.15)
Diseases of the nervous system (G00- 0.89 (0.68-
61
G99) 1.14)
0.90 (0.59-
AlzheimerÕs disease (G30) 27
1.31)
Diseases of the circulatory system (I00- 1.56 (1.45-
783
I99) 1.67)
1.51 (1.23-
Hypertensive diseases (I10-I15) 101
1.83)
1.51 (1.33-
Ischemic heart diseases (I20-I25) 247
1.71)
1.64 (1.42-
Other heart diseases (I00-I09, I26-I51) 201
1.88)
1.43 (1.23-
Cerebrovascular diseases (I60-I69) 182
1.65)
Diseases of the respiratory system (J00- 1.83 (1.57-
177
J99) 2.12)
2.22 (1.70-
Pneumonia (J12-J18) 61
2.86)
Chronic lower respiratory diseases 1.47 (1.10-
54
(J40ÐJ47) 1.92)
3.47 (2.12-
Interstitial pulmonary diseases (J84) 20
5.36)
Diseases of the digestive system (K00- 1.93 (1.60-
117
K93) 2.32)
2.40 (1.48-
Vascular disorders of intestine (K55) 21
3.66)
0.95 (0.58-
Diseases of liver (K70-K76) 20
1.47)
Diseases of the musculoskeletal system 17.3 (14.7-
149
(M00-M99) 20.4)
63.3 (52.9-
Rheumatoid arthritis (M05-M06) 130
Rheumatoid arthritis (M05-M06) 130
75.2)
Diseases of the genitourinary system 1.29 (0.85-
27
(N00-N95) 1.88)
1.65 (1.28-
External causes of mortality (V01-Y84) 70
2.08)
1.95 (1.19-
Falls (W00-W19) 20
3.01)
1.42 (1.36-
All causes 2142
1.48)
Table 2. Number of deaths and standardized mortality ratio

(SMR) with 95% Confidence Interval (CI), by gender and
age class.
Males Females
n SMR (CI) n SMR (CI)
All causes
20-64 yrs 62 1.50 (1.15- 106 1.54 (1.26-
1.93) 1.86)
65-74 yrs 141 1.30 (1.10- 235 1.41 (1.23-
1.54) 1.60)
75-89 yrs 452 1.32 (1.20- 1146 1.47 (1.39-
1.45) 1.56)
Neoplasms (C00-D48)
20-64 yrs 21 1.03 (0.64- 52 1.17 (0.87-
1.58) 1.53)
65-74 yrs 50 0.91 (0.67- 79 0.87 (0.69-
1.20) 1.09)
75-89 yrs 117 1.03 (0.85- 200 0.98 (0.85-
1.23) 1.12)
Circulatory system
(I00-I99)
20-64 yrs 16 1.86 (1.06- 18 2.07 (1.23-
3.02) 3.28)
65-74 yrs 43 1.62 (1.17- 62 1.80 (1.38-
2.18) 2.30)
75-89 yrs 179 1.48 (1.27- 465 1.53 (1.40-
1.71) 1.68)
Respiratory system
(J00-J99)
20-64 yrs 3 2.94 (0.59- 4 2.62 (0.71-
8.59) 6.71)
65-74 yrs 6 1.31 (0.48- 14 2.23 (1.22-
2.85) 3.74)
75-89 yrs 54 1.76 (1.33- 96 1.82 (1.47-
2.30) 2.30)
Disclosure: F. Ometto, None; U. FEDELI, None; E. SCHIEVANO, None; C. Botsios, None; M. C. CORTI, None; L. Punzi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/cause-specific-mortality-in-a-large-population-based-

cohort-of-rheumatoid-arthritis-patients-in-italy
Major Cardiovascular Events Among an Inception Cohort of Seniors with Rheumatoid

Arthritis
Jessica Widdifield1,2, Michael Paterson2, Anjie Huang2, Bindee Kuriya3, Carter Thorne4, Janet E. Pope5 and Sasha Bernatsky6, 1Clinical
Epidemiology, Research Institute of the McGill University Health Centre, Montreal, ON, Canada, 2Institute for Clinical Evaluative Sciences,
Toronto, ON, Canada, 3Sinai Health System, University of Toronto, Toronto, ON, Canada, 4Southlake Regional Health Centre, Newmarket,
ON, Canada, 5Department of Medicine, Division of Rheumatology, University of Western Ontario, St Joseph's Health Care, London, ON,
Canada, 6Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
SESSION INFORMATION
Background/Purpose:
We previously observed that incident RA patients have an increased risk of cardiovascular (CV) mortality relative to the general population
in Ontario. Our aim was to evaluate the incidence and factors associated with major CV events subsequent to RA diagnosis.
Methods:
We studied incident RA patients within the population-based Ontario Rheumatoid Arthritis Database (ORAD). We analyzed all individuals
who were diagnosed with RA after their 65th birthdate (ensuring comprehensive drug coverage) between 2000 and 2013. Our primary
outcome was a composite measure which included acute myocardial infarction (AMI), stroke, congestive heart failure (CHF),
revascularization with either percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. All patients were
followed from cohort entry until major CV event, censored on death, out-migration, or end of study period (Dec 2013), whichever occurred
first. Factors associated with experiencing a major CV event during follow-up were analyzed using multivariable Cox regression to estimate
hazard ratios (HRs), exploring the effects of baseline and time-varying medication exposures (including methotrexate, other DMARDs, anti-
TNFs, COXIBS, NSAIDs, glucocorticosteroids, statins, antihypertensives), baseline comorbidities, time-varying development of extra-
articular manifestations (as proxy for disease severity), healthcare use, and demographics (age, sex, rurality, socioeconomic status).
Results:
Among 23,994 incident RA patients, 67% were female. Patients had a high CV risk burden at the time of diagnosis (70% had pre-existing
hypertension, 23% diabetes, 16% coronary artery disease, 3% previous AMI and 1% cerebrovascular disease). During 115,453 person-
years of follow-up, 3,294 (14%) patients experienced a CV event for a crude rate of 28.5 events (95% CI 27.6,29.5) per 1,000 person-years
[24.6 events (95% CI 23.5,25.7) among females and 37.4 events (95% CI 35.5,39.5) among males]. In our multivariable analysis, we did not
observe clear associations with use of anti-rheumatic treatment during follow-up. Greater use of statins was associated with a lower CV
event risk [HR 0.96 (95% CI 0.94,0.98)], whereas greater cumulative exposure to glucocorticosteroids was associated with an increased risk
[HR 1.08 (95% CI 1.05,1.11)]. The strongest independent risk factors for a major CV event were pre-existing comorbidities at time of RA
diagnosis, including coronary artery disease [HR 1.72 (95% CI 1.57,1.87)], prior AMI [HR 1.53 (95% CI 1.32,1.76)], renal disease [HR
1.43 (95% CI 1.20,1.70)], diabetes [HR 1.41 (95% CI 1.30,1.52)], cerebrovascular disease [HR 1.36 (95% CI 1.03,1.80)], and hypertension
[HR 1.16 (95% CI 1.05,1.28)].
Conclusion:
Senior RA patients have a high CV risk burden at the time of RA diagnosis. Risk of experiencing a subsequent major CV event during follow-
up was high. Pre-existing co-morbidities and glucocorticosteroids were positively associated with CV events, while statins were protective.
This clearly highlights strategies to decrease CV events in RA.
Disclosure: J. Widdifield, None; M. Paterson, None; A. Huang, None; B. Kuriya, None; C. Thorne, AbbVie, Amgen, Celgene, Lilly,
Novartis, Pfizer, Sanofi, and UCB; has served as a consultant for AbbVie, Amgen, Celgene, Centocor, Genzyme, Hospira, Janssen, Lilly,
Medexus/Medac, Merck, Novartis, Pfizer, Sanofi, and UCB, 2,Medexus/Medac, 8; J. E. Pope, AbbVie, Amgen, Bayer, BMS, Celtrion, Eli
Lilly and Company, Merck, Novartis, Pfizer, Roche, UCB, 5,Amgen, Bayer, BMS, GSK, Merck, Novartis, Pfizer, Roche, UCB, 2; S.
Bernatsky, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/major-cardiovascular-events-among-an-inception-cohort-

of-seniors-with-rheumatoid-arthritis
Performance of Cardiovascular Risk Age and Vascular Age Estimations in Predicting

Cardiovascular Events in Rheumatoid Arthritis
Grunde Wibetoe 1, Cynthia S. Crowson2, Joseph Sexton3, Silvia Rollefstad1, Eirik Ikdahl1, George D. Kitas4, Piet van Riel5, Sherine E.
Gabriel6, Tore K. Kvien7, Karen Douglas8, Aamer Sandoo8,9, Elke Arts5, Solveig Wållberg-Jonsson10, Solbritt Rantapää Dahlqvist10,
George Karpouzas11, Patrick H. Dessein12,13, Linda Tsang14, Hani El-Gabalawy15, Carol A Hitchon15, Virginia Pascual-Ramos16, Irazu
Contreras-Yañez17, Petros P Sfikakis18, Evangelia Zampeli19, Miguel Angel González-Gay20, Alfonso Corrales21, Iris J. Colunga-
Pedraza22, Dionicio A. Galarza-Delgado23, Jose Ramon Azpiri-Lopez24 and Anne Grete Semb1, 1Preventive Cardio-Rheuma clinic, Dept.
of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, 2Department of Medicine, Division of Rheumatology,Mayo Clinic, Rochester,
MN, 3Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, 4School of Sport, Exercise and Rehabilitation, University of
Birmingham, Birmingham, United Kingdom, 5Department of Rheumatic Diseases, Radboud University Nijmegen Medical Centre, Nijmegen,
Netherlands, 6Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, 7NORDMARD, Oslo, Norway, Oslo, Norway, 8Dudley
Group NHS Foundation Trust, West Midlands, United Kingdom, 9School of Sport, Health and Exercise Sciences, Bangor University, Bangor,
United Kingdom, 10University of Umeå, Umeå, Sweden, 11Division of Rheumatology, Harbor-UCLA Medical Center, Torrance, CA, 12Vrije
Universiteit Brussel, Brussel, Belgium, 13Universitair Ziekenhuis Brussel, Brussel, Belgium, 14Rheumatology, Universitair Ziekenhuis
Brussel, Brussels, Belgium, 15University of Manitoba, Winnipeg, MB, Canada, 16Instituto Nacional de Ciencias Médicas y Nutrició, Mexico
City, Mexico, 17Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico, 18First Department of
Propedeutic Internal Medicine, Laikon Hospital, Athens University Medical School, Athens, Greece, 19Institute of Autoimmune Systemic and
Neurological Diseases, National and Kapodistrian University of Athens, Athens, Greece, 20Rheumatology, Hospital Universitario Marqués
de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Johannesburg, South Africa, 21Rheumatology, Hospital Universitario
Marqués de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain, 22Rheumatology, Hospital Universitario,
UANL., Monterrey, Mexico, 23Chief of Rheumatology, Hospital Universitario, UANL., Monterrey, Mexico, 24Cardiology, Hospital
Universitario, UANL., Monterrey, Mexico
SESSION INFORMATION
Background/Purpose: Rheumatoid arthritis (RA) patients are at high risk of cardiovascular disease (CVD). Risk algorithms for the general
population lack precision when applied to RA patients and validated RA-specific CVD prediction models are missing. Risk age estimations
are recommended as adjuncts to assessment of absolute 10-year risk of fatal CVD events. Two risk age models based on the Systematic
Coronary Risk Evaluation (SCORE) algorithm have been developed; the cardiovascular risk age and the vascular age. However, the
performance of these models has not been compared. Using longitudinal data on CVD events in RA patients, we aimed to compare the
discriminative ability of cardiovascular risk age and vascular age among RA patients and in subgroups of RA patients based on disease
characteristics.
Methods: Patients with RA were included from an international consortium, aged 30-70 years at baseline. Those with prior CVD, diabetes
and/or users of lipid-lowering and/or antihypertensive therapy at baseline were excluded. Cardiovascular risk age was estimated based on
chronologic age, smoking status, total cholesterol and systolic blood pressure at baseline. Vascular age was derived from the 10-year risk of
CVD according to the SCORE algorithm, with or without high density lipoprotein cholesterol, using the equations for low and high risk
countries. Performance of each risk age model in predicting CVD events was assessed using the concordance index.
Results: Among the1867 RA patients included, 74% were female, median (inter-quartile range) age and disease duration were 52.0 (44.0,
59.9) and 0.6 (0.1, 6.4) years, 72.5% were rheumatoid factor positive, 24.7% were using glucocorticoids and 10.3% were using biologics at
baseline. Overall, 144 CVD events occurred and median follow-up time was 5.0 (2.6, 9.3) years. Median difference between estimated risk
age and chronologic age was 4.0 to 6.7 years, depending on the specific risk age model applied. Overall, the C-index across risk models
ranged from 0.71 to 0.73 with standard errors of 0.03. Across prediction models, the lowest observed concordance was found among women
and in glucocorticoid users and in those with new-onset disease (≤1 year). Additional analyses including RA patients on cardio preventive
therapy yielded slightly lower c-indexes. Since SCORE was developed for use in Europe, we performed analyses on European RA patients,
which yielded similar results. The trend of reduced concordance among women, glucocorticoid users and RA patients with short disease
duration was preserved in these additional analyses.
Conclusion: The cardiovascular risk age and vascular age models have comparable performance in predicting CVD in RA patients. Sex,
disease duration and/or glucocorticoid treatment may influence the performance of risk age estimations.
Disclosure: G. Wibetoe, None; C. S. Crowson, None; J. Sexton, None; S. Rollefstad, None; E. Ikdahl, None; G. D. Kitas, None; P. van
Riel, None; S. E. Gabriel, None; T. K. Kvien, AbbVie, Biogen, BMS, Celltrion, Eli Lilly and Company, Janssen, Merck-Serono, MSD,
Novartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Samsung, Sandoz, UCB, 5,AbbVie, Biogen, BMS, Celltrion, Eli Lilly and Company,
Janssen, Merck-Serono, MSD, Novartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Samsung, Sandoz, UCB, 8; K. Douglas, None; A.
Sandoo, None; E. Arts, None; S. Wållberg-Jonsson, None; S. Rantapää Dahlqvist, None; G. Karpouzas, None; P. H. Dessein, None; L.
Tsang, None; H. El-Gabalawy, None; C. A. Hitchon, None; V. Pascual-Ramos, None; I. Contreras-Yañez, None; P. P. Sfikakis, None; E.
Zampeli, None; M. A. González-Gay, None; A. Corrales, None; I. J. Colunga-Pedraza, None; D. A. Galarza-Delgado, None; J. R.
Azpiri-Lopez, None; A. G. Semb, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/performance-of-cardiovascular-risk-age-and-vascular-

age-estimations-in-predicting-cardiovascular-events-in-rheumatoid-arthritis
Lack of Screening By Rheumatologists and Primary Care Physicians for Childhood

Sexual Abuse in Patients with Fibromyalgia-Depression Overlap: An Unrecognized
Crisis?
M. Anthony Albornoz 1, Christian Albornoz2 and Daniel J. Clauw3, 1Rheumatology, Riddle Memorial Hospital/Mainline Health System,
Media, PA, 2Temple University School of Medicine, Philadelphia, PA, 3Chronic Pain & Fatigue Research Center, University of Michigan,
Ann Arbor, MI
SESSION INFORMATION
Session Title: Fibromyalgia, Soft Tissue Disorders, Regional and Specific Clinical Pain Syndromes Poster I
Background/Purpose: Depression is reported in as many as 71% of patients with Fibromyalgia (FM). An association between Childhood
Sexual Abuse (CSA) and FM has been well documented and is responsible for inducing disturbing levels of chronic physical and psycho-
affective morbidity. Based on the 28-year experience of the lead author, the frequency of CSA in patients with Fibromyalgia-Depression
Overlap (FDO) is thought to be highly underestimated, principally due to the underutilization of validated screening questions by
Rheumatologists (RH), Internists and Family Medicine Physicians (PCP). We primarily sought to determine the frequency of CSA screening
by RH and PCP in patients with FDO and the incidence of CSA in new patients with FDO. Additional clinical and psychosocial variables
were secondarily assessed.
Methods: A retrospective analysis conducted over a 12 month period in an outpatient, community-based, solo private practice setting of 131
consecutive new adult patients diagnosed with FM by one RH. All patients were screened for depression, anxiety and CSA using validated
tools(PHQ-9, GAD-7,Gen Hosp Psychiatry. 2007 Jan-Feb;29(1):8-13) . CSA patients were asked whether past and/or present PCP and past
RH inquired about CSA. All patients met the 2010 ACR criteria for FM.
Results: All data is summarized in Table. Noteworthy clinical findings included: Of the 131 FM patients, 100% were female, 82 (63%)
were diagnosed with FDO and 18 (22%) of FDO patients revealed they were victims of CSA; CSA was not encountered in the non-FDO
population; CSA mean age was 42 with an age range of 18-74; mean age at time of abuse 13; oldest age when CSA first divulged was 74; 16
(89%) of CSA patients were under age 65 and of these 13 (81%) were either on disability or unemployed; 6 (33%) family member('s) did
not believe claim of CSA; 14 (78%) of CSA patients requested that abuse history not be included in the medical record; 11 (61%) of
assailants were 1st degree relatives; CSA patients never queried by physicians about sexual abuse: active and/or past PCP 15 (83%) and
past RH 9 (100 %); Psychiatric/Psychological care given in 18 (100%) of CSA patients; 18 (100%) of CSA patients experienced past
suicidal ideations and 11 (61%) active suicidal ideations; 8 (44 %) attempted suicide; 18 (100%) had active depression and 16 (89%) had
active anxiety; 15 (83%) active severe depression; 14 (78%) active severe anxiety; 16 (89%) active panic attacks.
Conclusion: The structure and small sample size of this investigation limits our ability to draw definitive conclusions. However, these data
reveal that in an alarmingly high number of FDO patients previously evaluated by RH and PCP, CSA escaped detection. The results of this
analysis highlights that patients with FDO-CSA likely represent a particularly at-risk population who are in need of greater physician
awareness and a more focused assessment. A multi-state study addressing this topic is in progress.
Disclosure: M. A. Albornoz, None; C. Albornoz, None; D. J. Clauw, Abbott Pharmaceutical, 5,Aptinyx, 5,Astellas Phamaceutical,
5,Cerephex, 5,Daiichi Sankyo, 5,Pfizer Inc, 5,Pierre Fabre, 8,Samumed, 5,Theravance, 5,Tonix, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/lack-of-screening-by-rheumatologists-and-primary-care-

physicians-for-childhood-sexual-abuse-in-patients-with-fibromyalgia-depression-overlap-an-unrecognized-crisis
Effect of Vitamin D Supplementation in Chronic Widespread Pain: A Systematic Review

and Meta-Analysis
Wai Chung Yong, Anawin Sanguankeo and Sikarin Upala, Bassett Medical Center, Cooperstown, NY
SESSION INFORMATION
Abstract
Background/Purpose: Chronic non-specific widespread pain (CWP) including fibromyalgia (FM) is characterized by widespread pain,
reduced pain threshold and multiple tender points on examination, causing disability and decreased quality of life. Vitamin D has been
proposed as an associated factor in CWP. This meta-analysis aimed to explore the benefit of vitamin D supplementation in the management of
CWP.
Methods: A comprehensive search of the CENTRAL, MEDLINE and EMBASE databases was performed from inception through January
2017. The inclusion criterion was the randomized clinical trials’ evaluating the effects of vitamin D treatment in adult subjects with CWP or
fibromyalgia. CWP was defined as chronic recurrent musculoskeletal pain without secondary causes; fibromyalgia patients met the American
College of Rheumatology criteria for fibromyalgia. Study outcome was assessed using visual analog scale (VAS) of pain intensity. Pooled
mean difference (MD) of VAS and 95% confidence interval (CI) were calculated using a random-effect meta-analysis. Meta-regression
analysis using random-effects model was performed to explore the effects of change in vitamin D in the treatment group on difference in mean
of VAS. Sensitivity analysis was performed to evaluate the robustness of results. The between-study heterogeneity of effect-size was
quantified using the Q statistic and I2.
Results: Data were extracted from 4 randomized control trials involving 287 subjects. Pooled result demonstrated a significant lower VAS
in CWP patients who received vitamin D treatment compared with those who received placebo (MD=0.46; 95% CI: 0.09 – 0.89, I2 = 48%).
Meta-regression analysis revealed no significant relationship between the changes of vitamin D and VAS with a coefficient = 0.04 (95% CI:
-0.01 to 0.08), p=0.10.
Conclusion: In this meta-analysis, we conclude that vitamin D supplementation is able to decrease pain scores and improve pain despite no
significant change in VAS after increasing serum vitamin D level. Further study needs to be conducted in order to explore the improvement of
functional status, quality of life, and the pathophysiological change that improves chronic widespread pain.
Disclosure: W. C. Yong, None; A. Sanguankeo, None; S. Upala, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effect-of-vitamin-d-supplementation-in-chronic-

widespread-pain-a-systematic-review-and-meta-analysis
Effects of Taping Therapy in the Management of Fibromyalgia: A Randomized

Controlled Study
Hae Joo Suh1 and Sang Tae Choi2, 1Seoul National University Hospital, Seoul, Korea, Republic of (South), 2Internal Medicine, Chung-Ang
University College of Medicine, Seoul, Korea, Republic of (South)
SESSION INFORMATION
Background/Purpose: Fibromyalgia is a medical condition characterized by chronic widespread musculoskeletal pain, accompanied by
fatigue, insomnia, cognitive problems, psychiatric symptoms and various somatic symptoms. While a number of pharmacological and
nonpharmacological therapies are attempting to treat the patients with fibromyalgia, fibromyalgia is still difficult to manage. Taping therapy
has been reported to be effect in relieving pain in a variety of musculoskeletal diseases. However, there were no reports of the patients with
fibromyalgia. Therefore, in this study, we aimed to evaluate the effectiveness of taping therapy in fibromyalgia management.
Methods: This is a randomized controlled trial, and total 60 patients with fibromyalgia were enrolled in this study. All patients were met the
2010 American College of Rheumatology (ACR) diagnostic criteria for fibromyalgia. Participants were randomized into the Kinesio taping
group (n = 30) and the inelastic paper taping group (n = 30) as control. Kinesio taping therapy or inelastic paper taping was performed twice
a week for three weeks in both groups. Three weeks later, Kinesio taping was applied to the control group for additional three week. To
assess the effect, the widespread pain index (WPI), severity score (SS) and fibromyalgia impact questionnaire (FIQ) by ACR were used to
measure pain, disease severity and dysfunctions in daily life. The Beck depression inventory (BDI) was used to assess depression, and
quality of life was assessed by the EQ-5D INDEX and EQ-5D VAS by EurQol group.
Results:
There were no significant differences between the two groups in mean ages, sex ratio and type of medications including anti-depressants and
muscle relaxants. The Kinesio taping group showed significant improvement in pain (WPI, 10.50 ± 3.98 vs. 5.70 ± 2.73, p < 0.001), symptom
severity (SS, 7.93 ± 2.24 vs. 5.27 ± 1.98, p < 0.001), dysfunction in daily life (FIQ, 65.03 ± 18.75 vs. 43.25 ± 18.87, p < 0.001), depression
(BDI, 18.17 ± 8.55 vs. 13.00 ± 6.75, p < 0.001) and QoL (EQ-5D INDEX, 9.10 ± 1.54 vs. 7.67 ± 1.40, p < 0.001; EQ-5D VAS, 38.33 ±
24.65 vs. 56.67 ± 27.93, p < 0.001), respectively. In the control group, however, the significant difference was noted only in pain (WPI,
10.53 ± 3.87 vs. 9.27 ± 3.57, p = 0.014). The changes in the Kinesio taping group before and after treatment showed significant differences
compared to the control group; WPI (p < 0.001), SS (p < 0.001), FIQ (p < 0.001), BDI (p = 0.001) , EQ-5D INDEX (p < 0.001), and EQ-5D
VAS (p < 0.001), respectively. After changing from inelastic paper taping to Kinesio taping, all parameters have been significant improved
(WPI, p <0.001; SS, p <0.001; FIQ, p <0.001; BDI, p <0.001; EQ-5D INDEX, p <0.001; EQ-5D VAS, p <0.001, respectively). There was no
serious adverse event to all participants.
Conclusion: This randomized controlled study showed that Kinesio taping therapy is effective in pain, symptom severity, dysfunctions in
daily life, depression, and quality of life in patient with fibromyalgia. Taping therapy could be a useful treatment modality in the management
of fibromyalgia.
Disclosure: H. J. Suh, None; S. T. Choi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effects-of-taping-therapy-in-the-management-of-

fibromyalgia-a-randomized-controlled-study
Prevalence of Fibromyalgia in Nurses; A Cross Sectional Study

Sarah Alajmi1, Faisal Shahwan1, Yazeed Bajuaifer1, Rand Al Ohaly2, Maha Edrees2, Alanood Asiri2 and Mohammed Omair3, 1Internal
Medicine, King Saud University Medical City, Riyadh, Saudi Arabia, 2King Saud University Medical City, Riyadh, Saudi Arabia, 3Division
of Rheumatology, Department of Medicine, King Saud University, Riyadh, Saudi Arabia
SESSION INFORMATION
Background/Purpose:
Nurses are at increased of developing pain sensitization syndromes due to stress and interrupted sleep. The prevalence of fibromyalgia (FM)
in nurses is unknown. The aim of this study is to evaluate the prevalence of FM in nurses using different screening tools.
Methods:
This was a cross-sectional study conducted in King Saud University Medical City (KSUMC). Nurses were invited to fill a questionnaire. The
fibromyalgia Rapid Screening tool (FIRST), Fibromyalgia Survey Questionnaire (FSQ) and London Fibromyalgia Epidemiology Study
Screening Questionnaire (LFESSQ) were used to identify patients with FM. Descriptive analysis was used for demographics. Non-
parametric tests were to compare PIT with and without FM.
Results:
A total of 335 nurses completed the questionnaire. They were mostly females (93.7%), married (64.5%) with a median (interquartile range)
age and body mass index of 32 (10) years and 24.8 (4.7) respectively. Of those, 121 (36.1%) nurse admitted having body pain. The
prevalence of FM using the FIRST, FSQ and LFESSQ were (1.8%), (0.6%) and (19.4%) respectively. None of them fulfilled the 3 criteria
concurrently. Using the LFESSQ criteria, nurses with FM were more likely to complain from irritable bowel syndrome (p=0.018), dry mouth
(p=0.026), chest pain (p=0.002) and headache (p<0.001). the underlying specialty had an impact on the prevalence of FM based on specialty
was; emergency department (23.1%), clinics (17.2%), intensive care (10.6%), ward (5.3) and operation room (4.3%).
Conclusion: The prevalence of FM is variable among nurses based on the used screening tool. Educational programs and screening clinics
are justified.
Disclosure: S. Alajmi, None; F. Shahwan, None; Y. Bajuaifer, None; R. Al Ohaly, None; M. Edrees, None; A. Asiri, None; M. Omair,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prevalence-of-fibromyalgia-in-nurses-a-cross-sectional-

study
Patients Failing to Fulfill 2016 Criteria for Fibromyalgia Represent a Truly Different
Population Subset
Marco Antivalle 1,2, Maria Chiara Ditto3, Alberto Batticciotto3, Rossella Talotta3, Maria Chiara Gerardi3, Alessandra Mutti3, Fabiola
Atzeni3 and Piercarlo Sarzi-Puttini3, 1Rheumatology, Rheumatology Unit, ASST Fatebenefratelli - Sacco, L. Sacco University Hospital,
Milano, Italy, 2Rheumatology Unit, ASST Fatebenefratelli - Sacco, L. Sacco University Hospital, Milan, Italy, 3Rheumatology Unit, ASST
Fatebenefratelli - Sacco, L. Sacco University Hospital, Milano, Italy
SESSION INFORMATION
Background/Purpose: The 2010/2011 fibromyalgia (FMS) diagnostic criteria (1) were recently revised, with the addition of a generalized
pain criterion in order to avoid misclassification of regional pain syndromes; furthermore, the diagnosis of fibromyalgia is now valid
irrespective of other diagnoses. Aim of the present study was to evaluate whether patients classified as having (2016+) or not having (2016-)
FMS by 2016 revised criteria truly represent different populations.
Methods: 334 patients (306 F and 28 M) with a diagnosis of FMS according to 2011 criteria were included in the study; mean age was
46.82 yrs (range 16 – 75), and mean disease duration 6.25 yrs (range 3 months -34 yrs). Widespread Pain Index (WPI) and Symptom
Severity Scale (SSS) were assessed by a localized version of the Fibromyalgia Survey Questionnaire; furthermore, patients were asked to
report the presence or absence -in the last 7 days- of each of the 41 somatic symptoms suggested by the original 2010 classification paper (2).
An evaluation of overall pain level in the last 7 days (0-10 numeric rating scale, NRS), and of fatigue by the FACIT-Fatigue questionnaire
were available in 101 and 137 patients respectively. Statistical analysis was performed by IBM SPSS v 22. Differences of mean values and
of proportions were evaluated by parametric or non-parametric methods as appropriate.
Results: the diagnosis of FMS was confirmed by 2016 criteria in 290 (86.8%) patients, and not confirmed in 44 (13.2%) patients. Mean
age (47.62 ± 10.6 yrs vs 46.69 ± 11.7 yrs, p=0.625), mean disease duration (6.27 ± 6.37 vs 6.25 ± 6.10 yrs, p=0.982), the percentage of
females (93.2% vs 91.4%, p=0.688), and the association with other clinically relevant diseases (27.3% vs 18.6%, p=0.179) were not
different in the 2016- group as compared to 2016+ group. 2016- patients had significantly lower values of polysymptomatic distress scale
(PSD: 16.59 ± 2.4 vs 21.86 ± 4.5 p < 0.001), and of pain-related variables (WPI: 7.57 ± 2.1 vs 12.66 ± 3.4, p< 0.001; TP: 10.54±5.4 vs
13.28 ± 4.3, p=0.001; NRS: 5.64 ± 2.9 vs 7.46 ± 1.9 p=0.022). SSS was similar in the 2 groups (9.03 ± 1.9 vs 9.20 ± 1.9 p=0.599), but the
number of somatic symptoms reported was significantly lower in 2016- patients (14.44 ± 5.0 vs 17.49 ± 6.6 p=0.005, Fig. 1), which reported
higher levels of fatigue (FACIT-Fatigue 28.3 ± 10.8 vs 21.17 ± 10.0, p=0.010).
Conclusion: The rate of disagreement between 2011 and 2016 criteria (13.2%) in our study is very close to the results (13.8%) reported in
the only comparison study published to date (3). Patients failing to meet 2016 criteria seem to represent a truly different population,
characterized by lower polysymptomatic distress, lower overall pain, and fewer somatic symptoms.
References:
1. Wolfe F, et al. Semin Arthritis Rheum. 2016 Dec;46(3):319-329
2. Wolfe F, et al. Arthritis Care Res (Hoboken). 2010 May;62(5):600-10
3. Ablin JN, Wolfe F. J Rheumatol. 2017 Jun 1. [Epub ahead of print]
Disclosure: M. Antivalle, None; M. C. Ditto, None; A. Batticciotto, None; R. Talotta, None; M. C. Gerardi, None; A. Mutti, None; F.
Atzeni, None; P. Sarzi-Puttini, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/patients-failing-to-fulfill-2016-criteria-for-fibromyalgia-

represent-a-truly-different-population-subset
Prevalence of Fibromyalgia in Physician in Training; A Cross Sectional Study

Sarah Alobud1, Nour Alsultan1, Abeer Alhazzani1, Yasmin Altymani1, Muneera Albugami1, Maha Omair2 and Mohammed Omair3, 1King
Saud University, Riyadh, Saudi Arabia, 2Department of Statistics, College of Science, King Saud University, Riyadh, Saudi Arabia,
3Division of Rheumatology, Department of Medicine, King Saud University, Riyadh, Saudi Arabia
SESSION INFORMATION
Background/Purpose: Physicians in training (PIT) are at increased of developing pain sensitization syndromes due to stress and interrupted
sleep. The prevalence of fibromyalgia (FM) in PIT is unknown. The aim of this study is to evaluate the prevalence of FM in PIT using
different screening tools.
Methods: This was a cross-sectional study conducted in King Saud University Medical City. PIT were invited to fill a questionnaire which
included the fibromyalgia Rapid Screening tool (FIRST), Fibromyalgia Survey Questionnaire (FSQ) and London Fibromyalgia Epidemiology
Study Screening Questionnaire (LFESSQ) to identify patients with FM. Non-parametric tests were used for the analysis.
Results: A total of 183 PIT completed the questionnaire. They were predominantly males (56.8%), single (56.3%) and at resident level
(86.3%). The median (interquartile range) age and body mass index were 28 (4) years and 26.3 (7.86) respectively. Seventy-two (39.3%)
PIT admitted having generalized body pain. The prevalence of FM using the FIRST, FSQ and LFESSQ were (8.2%), (11.5%) and (8.2%)
respectively. Seven (3.8%) of them fulfilled the 3 criteria concurrently. Using the LFESSQ criteria, PIT with FM were more likely to have a
family history of FM (37.5% vs 3.5%; p<0.001), complain from irritable bowel syndrome (p<0.001), non-specific headaches (p=0.001),
migraines (p<0.001), interrupted sleep (p=0.003), snoring (p=0.046), and impaired concentration (0.045). Surgical residents had the highest
prevalence (14.8%) followed by anesthesia (14.3%) and medical residents (13.4%).
Conclusion: The prevalence of FM is increased among PIT regardless of the used screening tool. Educational programs and screening clinics
are justified.
Disclosure: S. Alobud, None; N. Alsultan, None; A. Alhazzani, None; Y. Altymani, None; M. Albugami, None; M. Omair, None; M.
Omair, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prevalence-of-fibromyalgia-in-physician-in-training-a-

cross-sectional-study
Frequency of Fibromyalgia in Patients with Antiphospholipid Syndrome. a Cross-

Sectional Study
Nicole Mouneu Ornelas1, Laura-Aline Martinez-Martinez2, Vijaya Rivera3, Ricardo Alberto Venegas Yañez4, Victor Alejandro Escamilla
Gomez5, Gumaro Acosta Peña6, Luis H. Silveira7, Angelica Vargas Guerrero3, Luis M. Amezcua-Guerra3 and Manuel Martínez-Lavín3,
1Internal Medicine, Instituto Nacional de Cardiología - Ignacio Chávez, IGNACIO CHÁVEZ, Mexico, 2Rheumatology, Instituto Nacional de
Cardiologia Ignacio Chavez, Mexico City, TX, Mexico, 3Rheumatology, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City,
Mexico, 4Reumatologia, Instituto Nacional de Cardiología "Ignacio Chavez", Ciudad de México, Mexico, 5Rheumatology, Instituto Nacional
de Cardiología - Ignacio Chávez, Mexico City, Mexico, 6Instituto Nacional de Cardiología, Ciudad de mexico, Mexico, 7Rheumatology,
Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City DF, Mexico
SESSION INFORMATION
Background/Purpose:
The observation of several cases with coexistent antiphospholipid syndrome (APS) and fibromyalgia led us to this investigation. The
objective was to define the frequency of fibromyalgia in a group of patients with antiphospholipid syndrome.
Methods:
From March 24th to June 8th 2017 we studied all APS patients attending our outpatient rheumatology clinic. All of them fulfilled the Sapporo
and/or Sydney APS classification criteria. The Institutional Ethics Committee approved the protocol. All patients underwent a history +
physical examination with emphasis on musculoskeletal features. All filled-out the following questionnaires: the Revised Fibromyalgia
Impact Questionnaire (FIQ-R), the 2016 revision of Wolfe’s Fibromyalgia Diagnostic Criteria, and the quality of life EuroQol 5D-5L. The
Damage Index in Thrombotic Antiphospholipid Syndrome (DIAPS) was also obtained. Spearman method was used to correlate APS clinical
features with fibromyalgia questionnaire scales. Chi square to compare categorical variables.
Results:
Sixty one patients with APS were included. Their mean age: 44 ± 15 years, 70% are female and 54% have primary APS. The prevalence of
fibromyalgia was different when using the 1990 ACR diagnostic criteria (4.9%) compared to Wolfe’s criteria (16.4%) p<0.0001. The
frequency of fibromyalgia was not different in patient with primary vs. secondary APS. In those patient who had concurrent APS and
fibromyalgia according to Wolfe’s criteria (n = 10), there was a correlation between total number of thrombotic events with headache,
depression, and abdominal pain (r=0.636, p=0.048), as well as with FIQ-R balance problems (r=0.754, p=0.012). Oddly, cumulative organ
damage measured by DIAPS inversely correlated with FIQ-R quality of sleep (r=-0.820, p=0.004). Quality of life measured by Euro Qol is
poorer in APS + fibromyalgia patients (85±16 vs 64±12, p<0.001).
Conclusion:
In this cohort of patients with APS, more individuals can be classified as having concurrent fibromyalgia when the 2016 revised Wolfe’s
criteria is used. Recurrent thrombosis is associated to several fibromyalgia symptoms such as headache, depression and abdominal pain.
Patients with APS and concurrent fibromyalgia have poorer quality life.
Disclosure: N. M. Ornelas, None; L. A. Martinez-Martinez, None; V. Rivera, None; R. A. Venegas Yañez, None; V. A. Escamilla
Gomez, None; G. Acosta Peña, None; L. H. Silveira, None; A. Vargas Guerrero, None; L. M. Amezcua-Guerra, None; M. Martínez-
Lavín, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/frequency-of-fibromyalgia-in-patients-with-

antiphospholipid-syndrome-a-cross-sectional-study
Xerostomia in Patients with Fibromyalgia

Nicolas Lloves1, Anastasia Secco2, Virginia Durigan3, Santiago Scarafia2, Felix Romanini Sr.4 and Marta Mamani4, 1Rheumatology
Department, Hospital Rivadavia, Buenos Aires, Argentina, 2Hospital Bernardino Rivadavia, CABA, Argentina, 3Reumatology, Hospital
Bernardino Rivadavia, CABA, Argentina, 4Hospital Rivadavia, Buenos Aires, Argentina
SESSION INFORMATION
Background/Purpose:
Fibromyalgia (FM) is a rheumatic disease characterized by diffuse, chronic musculoskeletal pain, of non-articular origin, which is evidenced
by the palpation of painful points in specific anatomical areas and is usually accompanied by non-repairing sleep, Tiredness, morning
stiffness, cognitive alterations, among others.
FM affects approximately 0.5 -5% of the population, having a maximum prevalence between 40 and 50 years. No racial or socioeconomic
predisposition has been determined to date.
Sicca syndrome whose term encompasses xerophthalmia, xerostomia, xeroderma and xerovagina, has been described in patients with FM.
Xerostomia is the sensation of dry mouth due to lack or decrease of saliva. There are no clinical studies that determine the prevalence of
xerostomia in patients with FM and on the other hand the reduction of salivary flow in these patients has not been studied with objective tests.
The aim of this study was to determinate the frecuency of xerostomia in patients with diagnosis of Fibromyalgia and describe their clinical
and epidemiologic characteristics.
Methods: Patients were included according 1990 and 2010 ACR Classification criteria. Patients taking drugs that cause xerostomia were
excluded as well as the ones presenting other rheumatologic diseases. Xerostomia was assessed by interrogation and physical examination,
and a sialometry was performed in order to determinate the decrease of salival flow. A sialometry was positive if the saliva flow was under
1.5 ml in 15 minutes. In case of presenting positive sialometry patients were studied to rule out Sjogren Syndrome with laboratory and minor
salivary gland biopsy.
Results: 50 patients were recruited during the study. The 100 % of them were women. The mean age was 47 years old (DS+-8.5), while the
mean time of evolution of FM was 6 years. 29 patients reported xerostomia of which 4 presented positive sialometry. No positive sialometry
was found in the group that did not referred xerostomia. Smoking was more prevalent in patients with FM who did not report xerostomia with
respect of those who reported xerostomia (31.8% vs 6.9%, p 0.02). There were not associations between xerostomia and hypothyroidism,
diabetes or menopause. The presence of Sjogren Syndrome was rule out in those 4 patients whose sialometry was positive.
Conclusion: The prevalente of xerostomía was 51%. No statistically significant associations were found in patients who reported
xerostomia. A decrease in objective salivary flow was not demonstrated in patients with FM.
Disclosure: N. Lloves, None; A. Secco, None; V. Durigan, None; S. Scarafia, None; F. Romanini Sr., None; M. Mamani, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/xerostomia-in-patients-with-fibromyalgia
Unexpectedly High Prevalence of Immunoglobulin Deficiency in Fibromyalgia – II

Xavier J. Caro1,2 and Earl F. Winter2, 1Northridge Hospital Medical Center, Northridge, CA, 2Southern California Fibromyalgia Research
and Treatment Center, Northridge, CA
SESSION INFORMATION
Background/Purpose: We have recently reported that 70% of an unselected FM cohort (n = 107) had subtle laboratory findings of Primary
Immune Deficiency (PID), usually consisting of one or more immunoglobulin subclass deficiencies (Arthritis Rheum 2014;55(11): S905). To
better understand this finding we surveyed a second cohort of FM subjects for laboratory evidence of PID, and – additionally - any clinical
evidence of recurrent infections. Our results are reported here.
Methods: We retrospectively reviewed serum Ig concentration values on all FM subjects seen between December 2013 and May 2017 in an
outpatient, rheumatology office setting. No other diagnosis precluded inclusion in the study unless it was likely that it might predispose to Ig
deficiency. A total of 81 consecutive FM subjects, meeting 2010 ACR criteria, were screened; 4 were excluded (i.e., alcohol abuse; prior
cancer chemotherapy; age < 18 yrs.). Data on 77 remaining FM subjects were reviewed; 43 of these had coincident RA (26 % seropositive).
Ig deficiency was defined as an Ig value below the lower limits of normal (LLN) suggested by PaulÕs Fundamental Immunology ( ); all
deficient specimens were tested in duplicate. Ig abnormalities were confirmed by repeat analysis 6 - 9 weeks later. We also reviewed the
prevalence of deficient or low mannose binding lectin in these subjects (deficient < 50 ng/ml; low < 500 ng/ml). In an attempt to further
ascertain the role of Ig deficiency in FM we also studied the prevalence of any Ig level > LLN but within the lower most quartile of normal
values (range / 4). We also collected data regarding a ÒLifetime History of InfectionsÓ on all FM subjects and 26 ÒApparently HealthyÓ
aged-matched, community volunteers (± 5 years).
Results: Our findings are listed below:
Serum Ig Deficiency in 77 FM Subjects Compared to Literature Based Controls

Fibromyalgia Subjects
Immunoglobulin No. with Estimated P-value
No. without Ig Prevalence of FM Ig
deficiency Deficiency
Ig deficiency Normal Prevalence (2-tailed)
IgG Subclass 1 27 50 35% 1/1200 <0.0001
IgG Subclass 2 12 65 16% 1/1200 <0.0001
IgG Subclass 3 37 40 48% 1/1200 <0.0001
IgG Subclass 4 34 43 44% 1/1200 <0.0001
IgA Subclass 1 20 57 26% 1/500 <0.0001
IgA Subclass 2 11 66 14% 3/100 0.002
IgM 1 76 1% 3/100 NS
IgE 11 66 14% 2.5/100 0.002
Any Ig 64 13 83% 1/1200 <0.0001
Schroeder HW, et al: Immunoglobulin Structure and Function. In Fundamental Immunology. 7th Ed.
Ed: Paul, WE. Lippincott, New York 2013. Analysis was by Chi-square test.
Of 71 FM subjects in whom Mannose Binding Lectin (MBL) was measured 18 (23 %) had levels <500 ng/ml, and 12 (16%) had levels <50
ng/ml. The prevalence any Ig in FM subjects being within our estimate of PaulÕs ( ) lowest quartile for normal Ig levels ranged from 40% to
74%. There was no significant difference in the prevalence of Ig deficiency in FM subjects with concomitant RA compared to those without
RA. A history of recurrent sinus infections was not significantly more common in our FM subjects compared to controls, but a history of
recurrent serious, non-sinus infections was more prevalent for FM (P(1) = 0.009), and FM + RA (P(1) = < 0.0001).
Conclusion: Our study shows that clinically significant Ig deficiency, particularly IgG subclass deficiency, is a common accompaniment to
FM. It also strengthens the argument that FM may be a disorder associated with immune dysregulation. The precise mechanism of this
interaction remains unclear, but deserves further investigation.
Disclosure: X. J. Caro, None; E. F. Winter, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/unexpectedly-high-prevalence-of-immunoglobulin-

deficiency-in-fibromyalgia-ii
A Systematic Review of the Upper Limb Soft Tissue Comorbidities in Patients with
Type 2 Diabetes Mellitus
Michelle C Papandony1, Anita E Wluka2, Ar Kar Aung3, Yuanyuan Wang1, Sultana Monira Hussain4 and Flavia M Cicuttini1, 1Monash
University, Department of Epidemiology and Preventive Medicine, Melbourne, Australia, 2Australia, Armadale, Australia, 3Department of
General Medicine, Alfred Health, Melbourne, Australia, 4Monash University, Department of Epidemiology and Preventative Medicine,
Melbourne, Australia
SESSION INFORMATION
Background/Purpose:
Soft tissue disorders affecting the upper limb are not commonly thought of as “classic” complications of type 2 diabetes mellitus. However,
the majority of upper limb disorders including adhesive capsulitis, carpal tunnel syndrome, Dupuytren’s disease, flexor tenosynovitis, limited
hand mobility and rotator cuff tendinitis are more frequent in patients with type 2 diabetes mellitus compared to the general population. With
population aging and increasing obesity, the epidemic of type 2 diabetes mellitus is expected to grow. As such, targeting upper limb soft
tissue diseases, which contribute to difficulty performing activities of daily living, increased morbidity, poorer health outcomes and higher
health service related costs will be important.
The aim of this systematic review is to determine the type and magnitude of upper limb soft tissue comorbidities in patients with type 2
diabetes mellitus compared to the general population.
Methods:
A systematic literature review of the MEDLINE and EMBASE databases was performed. Any study describing upper limb soft tissue disease
in patients with type 2 diabetes mellitus was included. A risk of bias assessment was performed. Where the prevalence of a condition was
available, the median and range was presented.
Results:
8035 manuscripts were identified by the search strategy. 31 articles were eligible for inclusion. Most studies were cross sectional in design.
The risk of bias assessment was high. We found that upper limb soft tissue disease is common in type 2 diabetes mellitus (median 32.1%,
range 19-57.7%).
Based on data from two studies, the prevalence of any hand abnormality was higher in T2DM compared to controls (median prevalence 45%
(range 20.5-69.5%) and 4.9% respectively). Limited hand mobility in type 2 diabetes mellitus was common, with a median prevalence of
26.7% (range 0-80%) (data from19 studies). Dupuytren’s disease was more common in type 2 diabetes mellitus, with a median prevalence
18.8%, (range 0-43.4%), compared to 8% (range 0-39%) in controls (data from 18 studies). Carpal tunnel syndrome was also more common
in type 2 diabetes mellitus compared to controls, with a median prevalence of 14% (range 0.32-83.3%) and 3.1% (range 0-17.5%)
respectively. The median prevalence of flexor tenosynovitis in type 2 diabetes mellitus was 7.2% (range 2-16.7%) compared to 2% (range0-
3.6%) in controls (data from 13 studies).
The prevalence of any shoulder abnormality in type 2 diabetes mellitus was 19.5% compared to 4.4% in controls (data from one study).
Adhesive capsulitis in type 2 diabetes mellitus was more common (median prevalence was 14.6%, range 7-29%) compared to 2.5% (range
0.5-17%) in controls (data from 8 studies). The median prevalence of rotator cuff tendinitis in type 2 diabetes mellitus was also higher
(23.3% (range 9.5-43.3%)) compared to 8.7% (range 0.8-50%) in controls (data from 3 studies).
Conclusion:
This systematic review has demonstrated that upper limb soft tissue disease is more prevalent in patients with type 2 diabetes mellitus
compared to the general population. These associations need to be further investigated and targeted in patients with type 2 diabetes mellitus
in order to optimize health outcomes.
Disclosure: M. C. Papandony, None; A. E. Wluka, None; A. K. Aung, None; Y. Wang, None; S. M. Hussain, None; F. M. Cicuttini, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-systematic-review-of-the-upper-limb-soft-tissue-

comorbidities-in-patients-with-type-2-diabetes-mellitus
Is Lu Eight-Brocades Exercise Beneficial for Patients with Fibromyalgia?

Juan Jiao1, Irwin Jon Russell2, Wen Wang3, Ya-yun Zhao4, Rou-man Zhang4, Jing Wang4 and Quan Jiang5, 1Rheumatism Department,
Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China, 2Affiliated with Arthritis & Osteoporosis Center of
South Texas, Medical Director, Fibromyalgia Research and Consulting, San Antonio, Texas, San Antonio, TX, 3JCW Education Consulting,
Conway, AR, 4Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China, 5Rheumatology Department,
Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
SESSION INFORMATION
Background/Purpose: Fibromyalgia is a chronic debilitating musculoskeletal pain syndrome that causes substantial physical and
psychological impairments. With the release of the 2016 revised EULAR recommendations for the management of fibromyalgia, there is a
growing interest in developing new exercise program aiming to improve patients’ physical function and wellbeing. The Eight Brocades (EB)
is an eight-section Qigong physical exercise, originated more than eight-hundred years ago in China, and it has been used by people to
improving their general health or existing health issues. Lu Eight Brocades (LEB) is a modified EB, adapted by Chinese Medicine Master
Zhi-zheng Lu, which is specifically tailored for patients with rheumatic diseases and is simple and easy to learn. The clinical study reported
here was aimed to evaluate the effectiveness of LEB in the management of fibromyalgia in Chinese patients in China.
Methods: In this randomized blank-control study, 62 patients with fibromyalgia were assigned to LEB or control group by computer using the
SAS system with a ratio of 1:1. Trained and guided by LEB certified physicians, patients practiced LEB one hour, twice a week for 12 weeks
in GUAN AN MEN hospital. The primary outcome measure is Visual Analogue Scales for pain (pain VAS), and the secondary outcomes
include the followings: Revised Fibromyalgia Impact Questionnaire (FIQR), Multidimensional Assessment of Fatigue (MAF), Pittsburgh
Sleep Quality Index (PSQI), Beck Depression Inventory (BDI), Perceived Stress Scale (PSS), and Tender Points Count (TP). The outcome
measures were assessed at baseline and at the end of week 4, 8, 12. As compensation, patients in blank-control group received LEB training
for additional 12 weeks after the end of the study. Statistical analyses were conducted by a statistician using intention to treat analysis set.
Results: Sixty-two subjects were mostly women (55, 87.7%), mean age was 51.2 years (SD 10.6 years, range: 29-69 years), and mean
duration was 32.1 months (SD 26.3 months, range: 4-128 months). At the baseline, there were no significant differences on demographics and
disease characteristics between LEB and control groups. At the week 4, except for BDI and PSS, improvement of pain VAS, FIQR, MAF,
PSQI, and TP were greater in LEB group compared to those in the control group (Ps ≤0.046). At week 8, all above the measures further
improved in LEB group than those in control group (Ps ≤0.033). At the week 12, all the outcome measures were improved in LEB group
compared with control (Ps ≤0.004). There were no complaints about side effects of LEB exercise during the study period using the side-
effect report form.
Conclusion: This pilot study demonstrated the effectiveness of physician-guided LEB practice for 12 weeks in improving all spectrum of
debilitation symptoms and the feeling of wellbeing in fibromyalgia participants. The study suggests LEB exercise could be a potential
valuable nonpharmacological treatment for patients with fibromyalgia, thus warrants for further larger scale investigations.
Disclosure: J. Jiao, None; I. J. Russell, None; W. Wang, None; Y. Y. Zhao, None; R. M. Zhang, None; J. Wang, None; Q. Jiang, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/is-lu-eight-brocades-exercise-beneficial-for-patients-

with-fibromyalgia
The Use of “Fibromyalgia Rapid Screening Tool” for Detection of Fibromyalgia in

Patients with Chronic Arthritis Treated with Full and Tapered Biological Disease-
Modifying Antirheumatic Drugs
Larissa Valor1, Diana Hernández-Flórez2, Tamara del Río2, Juan Gabriel Ovalles-Bonilla3, Julia Martínez-Barrio4, Iustina Janta5, Belen
Serrano6, Claudia Saez5, Roberto Gonzalez5, Juan Carlos Nieto5, Carlos M Gonzalez5, Indalecio Monteagudo5 and Francisco Javier López
Longo7, 1Rheumatology, Hospital general Universitario Gregorio Marañón, Madrid, Spain, 2Rheumatology, Gregorio Marañón University
General Hospital, Madrid, Spain, 3Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain, 4Servicio de Reumatologia,
Hospital General Universitario Gregorio Marañón, Madrid, Spain, 5Rheumatology, Hospital General Universitario Gregorio Marañón,
Madrid, Spain, 6Rheumatology, Hospital General Universitario Gregorio Marañón, Genoa, Italy, 7Facultad de Medicina, Universidad
Complutense de Madrid, Madrid, Spain
SESSION INFORMATION
Background/Purpose: The coexistence of fibromyalgia (FM) and chronic arthritis is a challenge for an accurate identification of signs and
symptoms associated with rheumatoid arthritis (RA), psoriatic arthritis (PsA), peripheral (PerSpA) and axial spondyloarthropathies
(AxSpA). The Fibromyalgia Rapid Screening Tool (FiRST) is a validated questionnaire with high sensitivity and moderate specificity to
identify 89% of FM cases, even when it is accompanied by anxiety, depression or functional disability. The use of full or tapered biological
disease-modifying antirheumatic drugs (bDMARD) depends in many cases on the reliability of clinical indices which can be altered by the
subjectivity of the patient and/or concomitant pathologies. Objective: To evaluate the prevalence of FM using the FiRST questionnaire in
patients diagnosed with chronic arthritis and treated with bDMARD.
Methods: This cross-sectional study included 325 patients [178 (54,8%) females and 147 (45,2%) males] diagnosed of chronic arthritis and
treated with bDMARDs. They were consecutively recruited in the Biological Therapy Unit from January to March 2015, all patients were in
full or tapered bDMARD for at least 1 year. The dosage tapering had been made in patients with a maintained remission according to their
rheumatologist attendant and the patient approval. All patients self-completed the FiRST questionnaire and a score> 5/6 was considered
positive. The clinical assessment was always performed by the same investigator. Demographic, clinical and laboratory variables were
collected and clinical indices related to each pathology were calculated (DAS28-ESR, DAS28-CRP, SDAI, CDAI, BASDAI, BASFI,
ASDAS-CRP). Patients were classified as peripheral arthritis (PerAR: RA, PsA, PerSpA) and axial spondyloarthropathies (AxSpA).
Results:
A total of 68/325 (21%) patients had a FiRST>5/6. The time since diagnosis and the number of previous used bDMARD were not significant
respect to FiRST<5/6. In the PerRA vs. AxSpA group we observed that 19% (n=43) and 35% (n=25) had FiRST>5/6, respectively (p=NS).
Fifteen % of patients with tapered bDMARD had FiRST>5/6 vs. 85% of patients in full bDMARD dosage (p=0.001). Patients in clinical
remission were higher in the PerAR group with tapered bDMARD dosage according to DAS28-ESR, SDAI and CDAI [(96%, 94% and
94%) (p=0.01, p=0.04, p=0.032), respectively]. In the PerAR subgroups, we found an association between tapered bDMARD and remission
only in patients with RA according to DAS28-VSG, SDAI and CDAI (p=0.026, p=0.04, p=0.043, respectively). In the AxSpA group with
tapered bDMARD dosage 86% of patients were in clinical remission according to BASDAI (p=0.019).
Conclusion: There was no difference between PerAR and AxSpA groups regarding FiRST>5/6. Patients with tapered bDMARD dosage had
a lower proportion of FiRST>5/6, therefore early detection of patients with FiRST>5/6 might help us to better understand clinical activity in
chronic arthritis and to improve diagnostic and therapeutic approaches of FM in these patients treated with bDMARD in terms of its efficacy
and cost-effectiveness.
Disclosure: L. Valor, Roche, Novartis, Celgene, Janssen; Sanofi, 8; D. Hernández-Flórez, None; T. del Río, None; J. G. Ovalles-Bonilla,
Pfizer, Roche, BMS, Asacpharma, Nordic Pharma, 8,Sanofi-Aventis Pharmaceutical, 5; J. Martínez-Barrio, None; I. Janta, None; B.
Serrano, None; C. Saez, None; R. Gonzalez, None; J. C. Nieto, None; C. M. Gonzalez, MSD, Celgene, Novartis, Abbvie, Janssen,
5,MSD, Celgene, Novartis, Janssen, UCB Pharma, 8; I. Monteagudo, None; F. J. López Longo, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-use-of-fibromyalgia-rapid-screening-tool-for-

detection-of-fibromyalgia-in-patients-with-chronic-arthritis-treated-with-full-and-tapered-biological-disease-modifying-antirheumatic-drugs
Fibromyalgia Screening Form in the Diagnosis of Concomitant Fibromyalgia

Robert S. Katz 1 and Jessica L. Polyak2, 1Rush University Medical Center, Chicago, IL, 2Rheumatology Associates S.C., Chicago, IL
SESSION INFORMATION
Background/Purpose: We have found that patients with a variety of rheumatic diseases who have concomitant fibromyalgia more frequently
fail therapies for the underlying inflammatory rheumatic disease and osteoarthritis. Based on the 2010 ACR criteria for the diagnosis of
fibromyalgia, a screening form was developed at the time of the study for accurate diagnosis. The screening assessment form is filled in by
patients. It includes 19 pain areas as well as questions concerning sleep, energy, cognition, headache, abdominal pain, and depression.
Adding this fibromyalgia screening questionnaire to the patient’s initial visit can also help validate the diagnosis in the minds of patients and
also clinicians. We had patients in a rheumatology office practice complete this diagnostic form.
Methods: There are 19 pain areas listed. Patients checked a box next to the areas of pain during the last 7 days and replied to questions for
the other symptoms- sleep (0-3), energy (0-3), cognition (0-3), and abdominal pain (0-1), headaches (0-1) and depression (0-1). A score of
12 and above is consistent with fibromyalgia.
Results: 60 patients with various rheumatic diseases, but excluding primary fibromyalgia, filled out the assessment form developed for the
2010 ACR diagnostic criteria. In those patients with an underlying inflammatory rheumatic disease diagnosis, without known fibromyalgia,
14 (23.3%) had a finding of 12 or more points using the fibromyalgia diagnostic screening form.
Conclusion: The fibromyalgia screening form developed in conjunction with the ACR 2010 criteria for fibromyalgia diagnosis can be quite
helpful in determining the presence of concomitant fibromyalgia. 23.3% of a group of patients with inflammatory arthritis, lupus, and
osteoarthritis also had fibromyalgia, according to the screening form results.
This form can be used to suggest the possibility of concomitant fibromyalgia in patients with other rheumatic diseases. Concomitant
fibromyalgia and an inflammatory rheumatic disease may be a reason for the failure of biologic modifier and other therapy aimed at reducing
pain and improving global well-being.
Disclosure: R. S. Katz, None; J. L. Polyak, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/fibromyalgia-screening-form-in-the-diagnosis-of-

concomitant-fibromyalgia-2
The Effectiveness of Medications for Fibromyalgia Based on Patient Experiences

Robert S. Katz and Frank Leavitt, Rush University Medical Center, Chicago, IL
SESSION INFORMATION
Background/Purpose: To assess patients’ global assessment of frequently used treatments for the fibromyalgia syndrome (FMS), we asked
patients with fibromyalgia to rank medications they have tried in the order of their effectiveness.
Methods: 95 patients (mean age of 50.5) diagnosed with fibromyalgia based on the 2011 ACR criteria, 88 females and 7 males, completed
an in-office questionnaire regarding the effectiveness of various medications often used to treat fibromyalgia. The study ranked 9
medications, which include pregabalin, gabapentin, duloxetine, Muscle Relaxants, Sleep Aids, Stimulants, ADD Medications, Pain
Medications, and NSAIDS. Patients rated the medications using this scale: 1=minimally helpful, 2=somewhat helpful, 3=moderately helpful,
4=very helpful.
Results: The three medications that were most positively rated by patients were opiate pain meds (mean=2.8), meds to improve sleep
(mean= 2.8), and ADD stimulants for fibro fog symptoms (mean=2.6).
Effectiveness ratings by fibromyalgia patients for other medications included: gabapentin (mean=0.73); duloxetine (mean=1.02); pregabalin
(mean=1.26). 59.1% of FMS patients reported little or no help from pregabalin, and 83.3 % found gabapentin to be little help.
Conclusion: Fibromyalgia patients rated the effectiveness of various medications that had tried. Pain medication, sleep aids and stimulants
given for the attention deficit component of fibro fog were judged by patients to be the most helpful.
Disclosure: R. S. Katz, None; F. Leavitt, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-effectiveness-of-medications-for-fibromyalgia-based-

on-patient-experiences-2
Depression Versus Frustration

Robert S. Katz 1 and Jessica L. Polyak2, 1Rush University Medical Center, Chicago, IL, 2Rheumatology Associates S.C., Chicago, IL
SESSION INFORMATION
Background/Purpose: Patients with fibromyalgia may feel depressed. But is it a clinical depression, suggesting the need for SSRI, SNRI, or
other medication, or is it frustration related to the presence of the symptoms of the disease?
Methods: 115 fibromyalgia syndrome (FMS) patients, meeting the 2010 ACR criteria for the diagnosis, completed a questionnaire in a
rheumatology office practice asking whether they were depressed and also whether they felt frustrated. The 62 FMS patients who responded
yes to having depression also filled out a Patient Health Questionnaire-9 (PHQ-9) for depression. The PHQ-9 asked the following questions:
little interest in doing things; feeling down/depressed; trouble with sleep; feeling tired/low energy; poor appetite; feeling bad about oneself;
poor concentration; moving and speaking slowly or excessively fidgety; and thoughts of hurting oneself. Patients were asked to rate these
questions based on how they felt over the last two weeks, as follows: 0 for not at all, 1 for several days, 2 for "more than half the days and 3
for nearly every day. A score of 5-9 minimal symptoms, 10-14 minor depression, 15-19 major depression, moderate; and >20 major
depression, severe.
Results: 96 FMS patients responded yes to the question “are you frustrated?” When asked, “Are you depressed?”, 62 FMS patients
answered yes. Scores of the PHQ-9 in the 62 FMS patients feeling depressed were as follows: 12 (19.3%) that scored in the 5-9 range
(“minimal symptoms”), 18 (29.2%) that scored in the 10-14 range (“minor depression”), 22 (35.4%) that scored in the 15-19 range (Major
depression, moderate), and 10 (16.1%) that scored in the >20 range (Major depression, severe).
Conclusion: Of 115 patients with fibromyalgia, 62 reported depression. Using the PHQ-9 depression questionnaire 22 of these patients had a
moderate major depression and 10 severe major depression. The great majority of patients with fibromyalgia express frustration but don’t
meet the criteria for depression, based on the PHQ-9 questionnaire. Psychotherapy, including ventilation of the patient’s symptoms in the
rheumatologist’s office, and continued in a psychologist’s or psychiatrist’s office, can be important. Separating depression, with the
possibility of prescribing antidepressant medications, and frustration can be clinically and therapeutically important.
Disclosure: R. S. Katz, None; J. L. Polyak, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/depression-versus-frustration
Fibromyalgia Patients Identify More Causes of Disease Flare Ups Than RA Patients
Robert S. Katz 1, Lauren Kwan2 and Jessica L. Polyak2, 1Rush University Medical Center, Chicago, IL, 2Rheumatology Associates S.C.,
Chicago, IL
SESSION INFORMATION
Background/Purpose: We compared patients with the Fibromyalgia Syndrome (FMS) and Rheumatoid Arthritis (RA) patients with respect
to stresses that the patients believe may have caused their diseases to flare.
Methods: 201 office patients with FMS or RA (150 FMS:130 women and 20 men; mean age 51±12, 61 RA:45 women and 16 men; mean
age 55±15) completed a questionnaire as to whether the following conditions caused their disease to flare: lack of sleep, fatigue, emotional
stress, physical stress, depression, anxiety, traumatic events, overdoing it, being overworked, feeling overwhelmed, illness, personal
changes, and confrontations with friends or family members. The chi-square test of association was done to compare FMS and RA patients
with respect to their responses, using a 0.05 significance level.
Results: FMS patients were significantly more likely than RA patients to report that stress caused their disease to flare including, with
regard to frequency, emotional stress (58% vs. 43%, p= 0.042), physical stress (54% vs. 34%, p= 0.010), and also lack of sleep (53% vs.
33%, p= 0.007), concomitant illness (39% vs. 12%, p < 0.001), anxiety (31% vs. 16%, p= 0.027),depression (25% vs. 10%, p = 0.012), and
traumatic events (25% vs. 12%, p = 0.026).
Conclusion: FMS patients were significantly more likely to be sensitive to a variety of factors compared with RA patients. Fibromyalgia
patients recognize many things that tend to aggravate their symptoms. Stress reduction strategies might help fibromyalgia patients.
Disclosure: R. S. Katz, None; L. Kwan, None; J. L. Polyak, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/fibromyalgia-patients-identify-more-causes-of-disease-

flare-ups-than-ra-patients-3
Association of Natural Killer Cell Ligand Polymorphism, HLA-C Asn80Lys, with the
Development of Anti-SSA/Ro Associated Congenital Heart Block
Hannah C. Ainsworth1, Miranda C Marion1, Antonio Brucato2, Nathalie Costedoat-Chalumeau3, Tiziana Bertero4, Rolando Cimaz5,
Micaela Fredi6, Patrick M. Gaffney7, Jennifer A. Kelly7, Kateri Levesque8, Alice Maltret8, Nathalie Morel8, Véronique Ramoni9, Amelia
Ruffatti10, Carl D Langefeld1, Jill P. Buyon11 and Robert M Clancy11, 1Wake Forest University, Winston Salem, NC, 2Ospedale Papa
Giovanni XXIII, Bergamo, Italy, 3Service de médecine interne Pôle médecine, Hôpital Cochin, Centre de référence maladies auto-immunes
et systémiques rares de l’île de France, Paris, France, 4Ospedale Mauriziano, Torino, Italy, 5Department of Paediatrics, University of
Florence and Anna Meyer Children's Hospital, Florence, Italy, Florence, Italy, 6Department of Rheumatology and Clinical Immunology,
Rheumatology and Clinical Immunology, Rheumatology and Clinical Immunology, Spedali Civili of Brescia, Brescia, Italy, 7Oklahoma
Medical Research Foundation, Oklahoma City, OK, 8Université Paris Descartes-Sorbonne Paris Cité, Paris, France, 9Ospedale Papa
Giovanni XXIII of Bergamo, Policlinico San Matteo of Pavia, Bergamo, Pavia, Italy, 10Unità di Reumatologia, Dipartimento di Medicina-
DIMED, Università di Padova., Padova, Italy, 11NYU Langone Medical Center, New York, NY
SESSION INFORMATION
Session Title: Genetics, Genomics and Proteomics Poster I
Background/Purpose:
Fetal exposure to maternal anti-SSA/Ro antibodies is necessary but insufficient for the development of congenital heart block (CHB),
suggesting the potential of a fetal genetic predisposition. Prior studies identified an association of HLA and CHB risk providing a possible
avenue into pathogenesis involving an interactive genetic effect between 6p21 and 19q13 wherein HLA-C acts as a ligand for the checkpoint
receptor killer cell immunoglobulin-like receptors (KIR). A dimorphism at position 80 in HLA-C creates two epitope subgroups, defined by
their KIR interactions: C1 (Asn80) and C2 (Lys80). We tested whether C2, which binds with high affinity to an inhibitory KIR rendering an
NK cell incapable of restricting inflammation, contributes to CHB.
Methods:
192 pedigrees from the US, Italy, and France (194 CHB, 91 unaffected siblings, 152 fathers, 167 mothers) and 1073 out-of-study controls
were genotyped on the Immunochip single nucleotide polymorphism (SNP) microarray. There were 79 discordant CHB sibling pairs. HLA-C
Asn80Lys and KIR imputation was completed. Tests for association used logistic regression, and matched analyses between affected and
unaffected children employed McNemar’s test.
Results:
The C1 allele was enriched (and C2 allele reduced) in mothers compared to female controls (P=0.0014; OR=0.63). In contrast, C2 was
increased in fathers compared to male controls (P=0.0123; OR=1.40). This gender-by-C2 interaction was statistically significant (P=0.0002).
CHB offspring had comparable C2 frequencies to the fathers (affected offspring frequency=0.42; fathers frequency=0.45) while unaffected
C2 offspring frequencies were comparable to the mothers (unaffected frequency=0.31; mothers frequency=0.29). Formal assessment of C2
differences within a pedigree showed a significant increase in the C2 allele in affected vs. unaffecteds (P=0.0027; OR=4.00). Results were
comparable in the CHB discordant sibling pairs in which mothers were homozygous for C1 (n=46 pairs, P=0.07; OR=2.75). When the
paired-sibling analysis was stratified by geographic region the results remained significant in each stratum (U.S. P=0.0325; OR=3.67; Europe
P=0.0348; OR=4.50). There was no difference in the inhibitory KIR genotype (AA KIRs) between affected and unaffected children (P=0.55).
Conclusion:
The HLA-C–encoded supertypic epitope C2 was significantly enriched in CHB vs. unaffected offspring, establishing C2 as a novel genetic
risk factor associated with disease. This observation supports a model in which anti-SSA/Ro exposed fetuses expressing C2 ligands may
have impaired NK surveillance resulting in unchecked cardiac inflammation and scarring.
Disclosure: H. C. Ainsworth, None; M. C. Marion, None; A. Brucato, None; N. Costedoat-Chalumeau, None; T. Bertero, None; R.
Cimaz, None; M. Fredi, None; P. M. Gaffney, None; J. A. Kelly, None; K. Levesque, None; A. Maltret, None; N. Morel, None; V.
Ramoni, None; A. Ruffatti, None; C. D. Langefeld, None; J. P. Buyon, None; R. M. Clancy, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/association-of-natural-killer-cell-ligand-polymorphism-

hla-c-asn80lys-with-the-development-of-anti-ssaro-associated-congenital-heart-block
Rheumatoid Arthritis Risk Polymorphisms in CCR6, SNP and Estrogen-Dependent

Response to Immune Mediator Gene Expression, and NF-κb Transcriptional Activity:
Crosstalk between the Immune and Endocrine Systems
Ming-Fen Ho1, Tim Bongartz2, James N. Ingle3, Liewei Wang1 and Richard M. Weinshilboum1, 1Department of Molecular Pharmacology
and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 2Emergency Medicine, Vanderbilt University, Nashville, TN, 3Department of
Medical Oncology, Mayo Clinic, Rochester, MN
SESSION INFORMATION
Background/Purpose:
The rheumatoid arthritis (RA) risk locus CCR6 rs3093024 SNP is associated with increased risk of RA in a sex-specific pattern in Asian
populations. Specifically, the variant allele was associated with increased RA disease risk in ACPA-positive women. This SNP is in tight
linkage disequilibrium with rs3093023, which has been associated with both RA risk and increased serum IL17 levels. We previously
reported that these two SNPs altered estrogen receptor binding to estrogen response elements and resulted in the induction of CCR6 by
estradiol (E2) in a SNP-dependent fashion. Specifically, CCR6 expression could be induced by E2 only in cells carrying the variant
genotype. Strikingly, IL17A and IL17RA responded in a parallel fashion. The present study was designed to study mechanisms underlying the
CCR6 SNP effect on the estrogen-dependent regulation of immune mediators in relation to the pathogenesis of RA—a disease for which 2/3
of patients are women.
Methods:
“Human Variation Panel” lymphoblastoid cell lines (LCLs) consisting of LCLs from 300 subjects were used to obtain genome-wide mRNA
expression and genome-wide SNP data, and to perform functional genomic studies including site-directed mutagenesis, luciferase reporter
assays, qPCR, NF-κB reporter assays and co-immunoprecipitation.
Results:
A reporter construct with variant genotypes for the CCR6 SNPs increased luciferase activity in response to E2 treatment as compared to
wild-type (p<0.001), providing direct evidence for the functional role of these SNPs in the regulation of CCR6 transcription. Use of the LCL
model system allowed us to determine global mRNA expression profiling for functional study. We then performed pathway analysis using
genes correlated with CCR6 expression with p≤1E-08 and found that those genes were enriched in immunological regulation pathways. Next,
we validated genes significantly correlated with CCR6 expression, with a focus on immunological genes, including cytokines, chemokines
and toll-like receptors, all of which have been implicated in the pathogenesis of RA. CCR6 knock down using LCLs with known CCR6 SNP
genotypes resulted in significant changes (p<0.05) in the expression of CCL20, IL7R, IL7, IL17RA, IL17A, IL6R, IL6, TLR2, TLR4 and NF-
κB p65. Additionally, significant induction for IL17RA, TLR2, TLR4 and NF-κB p65 in response to E2 treatment was observed only in
variant genotype cells (p<0.05). In parallel, NF-κB transcriptional activity responded in a CCR6 SNP and E2-dependent fashion. Finally,
CCR6 could physically interact with NF-kB p65 as determined by co-immunoprecipitation. These results suggest that NF-κB signaling might
be associated with CCR6 SNP and estrogen-dependent effects.
Conclusion:
CCR6 SNPs are functionally relevant to the pathogenesis of RA. CCR6 is estrogen inducible in a SNP-dependent fashion, resulting in
downstream effects modulating the expression of proinflammatory cytokines and NF-κB transcriptional activity. Our results provide a
mechanistic explanation for the results of previous genome-wide association studies that have linked these SNPs in the CCR6 gene to RA risk
and the differential effects of these SNPs on E2 treatment.
Disclosure: M. F. Ho, None; T. Bongartz, None; J. N. Ingle, None; L. Wang, None; R. M. Weinshilboum, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rheumatoid-arthritis-risk-polymorphisms-in-ccr6-snp-

and-estrogen-dependent-response-to-immune-mediator-gene-expression-and-nf-%ce%bab-transcriptional-activity-crosstalk-between-the-
immune-and-endoc
Integrative Systems Biology Approach Identifies Key Transcription Factors and Novel
Rheumatoid Arthritis (RA) and Individualized Therapeutic Targets
RIchard Ainsworth1, Kai Zhang2, Gary S. Firestein3 and Wei Wang4, 1UC San Diego, La Jolla, CA, 2UCSD School of Engineering, San
Diego, CA, 3Medicine, University of California San Diego, La Jolla, CA, 4Chemistry and Biochemistry, UC San Diego, La Jolla, CA
SESSION INFORMATION
Background/Purpose: The search for novel targets in RA requires novel computational methods and in silicosystems to identify non-obvious
pathways that account for the diversity of responses to targeted agents. We developed and applied a novel integrative systems biology method
that identifies transcription factors (TFs) central to regulatory patterns in RA fibroblast-like synoviocytes (FLS) and significant variations in
gene networks between RA patients.
Methods: Our whole genome ATAC-seq and RNA-seq data (from 11 RA and 11 osteoarthritis [OA] FLS lines) were evaluated for overlaps
between ATAC-seq peaks and known gene promoter regions (4kb upstream and 1kb downstream from the TSS). ATAC-seq peaks not
assigned to promoters were considered as enhancer regions and linked with the nearest gene. TF binding motifs were curated from the CIS-
BP database. 745 TFs had binding sites within 150-bp regions in ATAC-seq peak summits. 22 unique network topologies were constructed
by forming directed edges between any parent node TF and child node gene or child node TF. Via the integration of RNA-seq expression data
for each sample, the Personalized PageRank (PPR) algorithm was developed and run measure the global influence of each node and variance
between RA patients.
Results: Initial analysis focused on differences between RA and OA. The mean PPR was calculated for TFs from RA and OA samples and
were ranked based on the largest absolute difference between RA and OA (DPPR). Of these, 33 TFs were significantly different for RA vs.
OA (p < 0.05). For example, the glucocorticoid receptor NR3C1 was the highest rank DPPR (p value = 0.03). BACH1, which regulates
osteoclastogenesis, was the second highest rank DPPR (p = 0.0005). Other high DPPR genes included STAT1, YY1 (JAK-STAT signaling)
and SP1. We then looked within RA for inter-RA patient differences to understand individual network profiles. The intersection of the 33
significant RA vs OA TFs with TFs that have the highest variance of normalized PPR within the RA networks, yielded 15 hits. MGA (MAX
gene-associated protein), which regulates the expression of MYC-MAX and T-box family target genes, had the highest intra-RA variance
with a high rank DPPR (p = 0.024) suggesting that this TF defines differences in RA pathogenesis between patients. Another high intra-RA
variance gene within the intersection includes TBX2, which participates in mesenchymal cell differentiation. A smaller subset of RA patients
(~30%) have high PPR values for ID1. ID family genes play a role in cell proliferation and angiogenesis in RA.
Conclusion: This systems biology approach not only defines disease specific TFs that contribute to the RA phenotype but also distinguishes
patient-to-patient differences. The unique computational approach identifies novel targets and helps elucidate the mechanism of differential
responses to highly targeted agents in RA. Key transcription factors, including well known genes such as NR3C1 and STAT1, along with
novel patient-specific TFs targets like MGA emerge from this in silico method to individualize treatment.
Disclosure: R. Ainsworth, None; K. Zhang, None; G. S. Firestein, None; W. Wang, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/integrative-systems-biology-approach-identifies-key-

transcription-factors-and-novel-rheumatoid-arthritis-ra-and-individualized-therapeutic-targets
Differentially Co-Expressed Gene Networks in Previously DMARD-Naïve Patients with

Early RA Achieving Sustained Drug-Free Remission after Step-up Methotrexate
Therapy
Xavier M Teitsma1, Johannes WG Jacobs1, Michal Mokry2, Attila Pethö-Schramm3, Michelle EA Borm4, Jacob M. van Laar5, Johannes
W.J. Bijlsma6 and Floris PJ Lafeber5, 1Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht,
Netherlands, 2Division of Pediatrics, University Medical Center Utrecht, Utrecht, Netherlands, 3F. Hoffmann-La Roche, Basel, Switzerland,
4Beneluxlaan 2a, Roche Nederland BV, Woerden, Netherlands, 5Rheumatology & Clinical Immunology, University Medical Center Utrecht,
Utrecht, Netherlands, 6Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, Netherlands
SESSION INFORMATION
Background/Purpose: According to current standards, methotrexate (MTX) is an anchor drug in the treatment of rheumatoid arthritis (RA)
and should be used in the initial line of treatment in newly diagnosed patients. Some of these patients do not need additional therapy to reduce
disease activity and even achieve sustained drug-free remission (sDFR) after tapering and stopping MTX. To identify these patients, we
performed network analyses within differentially expressed genes (DEGs) and identified clusters (i.e. modules) of co-expressed genes
associated with achieving sDFR.
Methods: Data was used from DMARD-naïve patients with early RA who in the U-Act-Early trial were randomized to initiate treat-to-target
MTX therapy. MTX was given at a starting dose of 10 mg/week orally and was increased with 5 mg every 4 weeks until 30 mg or the
maximum tolerable dose. When the treatment target, sustained remission (defined as disease activity score assessing 28 joints (DAS28) <2.6
with ≤4 swollen joints for ≥24 weeks), was achieved, therapy was tapered and hereafter stopped if remission was maintained. Patients
achieved sDFR if they remained ≥3 months in remission while being-drug free. Blood samples were collected of those achieving sDFR
(n=13) and those not able to discontinue medication (n=11) as controls. Hereafter ‘cluster of differentiation 4’-positive (CD4+) T Helper
cells and CD14+ monocytes were isolated and analyzed using RNA sequencing. DEGs were identified and weighted gene co-expression
network analysis was used to identify clusters (i.e. modules) of co-expressed genes.
Results: Nine modules were identified in CD4+ cells and the module best correlated with achieving sDFR (Pearson correlation coefficient
0.60, p=0.012) included 49 co-expressed genes. Within this module, when performing pathway analyses in the Gene Ontology (GO)
database, 304 terms were significantly overrepresented. Of these, response to bacterium (p=1.92E-07), response to external biotic stimulus
(p=6.11E-07), and response to other organism (p=6.11E-07) were the most significant. In addition, two significant enriched pathways were
found in the Kyoto Encyclopedia of Genes and Genomics database: “p53 signaling pathway” (p=8.44E-06) and “Jak-STAT signaling
pathway” (p=2.22E-04). The down-regulated SESN3 and ZNF585B and the upregulated CPXM1 genes showed the highest intramodular
connectivity and are therefore considered as signature genes (Fig. 1). Network analyses in CD14+ cells yielded no significant modules.
Conclusion: By network analyses of differentially expressed genes, several pathways were identified important for achieving sDFR in
DMARD-naïve with early RA after initiation of an MTX-based strategy. SESN3, ZNF585B and CPXM1 were identified as signature genes
that might be used as biomarkers for RA outcome.
Disclosure: X. M. Teitsma, None; J. W. Jacobs, None; M. Mokry, None; A. Pethö-Schramm, F Hoffmann-La Roche, 3; M. E. Borm,
Roche Nederland BV, 3; J. M. van Laar, MSD, Pfizer, Eli Lilly, and BMS, 5; J. W. J. Bijlsma, Roche, AbbVie, Bristol-Myers Squibb,
Merck Sharp & Dohme, Pfizer, and UCB, 2; F. P. Lafeber, Roche Nederland BV, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/differentially-co-expressed-gene-networks-in-previously-

dmard-naive-patients-with-early-ra-achieving-sustained-drug-free-remission-after-step-up-methotrexate-therapy
Identification of Novel Susceptibility Loci in a Large UK Cohort of Juvenile Idiopathic

Arthritis (JIA) Cases
Samantha Smith1, John Bowes1, Joanna Cobb2, Anne Hinks1, Sunil Sampath1, Annie Yarwood1, Lucy R Wedderburn3, Kimme L. Hyrich4
and Wendy Thomson1, 1Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Manchester
Academic Health Sciences Centre, The University of Manchester, Manchester, United Kingdom, 2NIHR Manchester Musculoskeletal
Biomedical Research Unit, Manchester Academic Health Science Centre, Central Manchester Foundation Trust, Manchester, United
Kingdom, 33Arthritis Research UK Centre for Adolescent Rheumatology, UCL GOS Institute of Child Health, University College London,
London, United Kingdom, 4Arthritis Research UK, Centre for Epidemiology, Centre for Musculoskeletal Research, Manchester Academic
Health Sciences Centre, The University of Manchester, Manchester, United Kingdom
SESSION INFORMATION
Background/Purpose:
Juvenile idiopathic arthritis (JIA) is a group of chronic arthropathies of unknown cause affecting children under 16yrs, and is the most
common childhood inflammatory rheumatic diagnosis, affecting 1 in 1,000 UK children. In recent years great advances in dissecting the
genetic basis of JIA have been made. In one landmark study, conducted on the two most common subtypes (oligoarthritis and RF-negative
polyarthritis), 17 susceptibility loci were identified at genome-wide significance (p-value<5x10-08) with a further 11 reaching suggestive
significance (p-value<1x10-06). These findings were the results of a large international collaboration using the ImmunoChip array, which
targets 186 known loci in 12 autoimmune diseases. However, one limitation to the afore-mentioned study was that the analysis was limited to
the selected loci; large genome-wide studies are now needed.The aim of this work is to identify novel genetic loci associated with disease
susceptibility using a large cohort of UK JIA cases.
Methods:
Whole-genome genotyping data was generated using four platforms (Illumina). Following stringent quality control common variants to all
four platforms were extracted from the individual datasets before merging together. Imputation was performed using the Haplotype Reference
Consortium panel on the Michigan Imputation Server using Minimac3 software. SNPs with imputation accuracy (r2>0.5), minor allele
frequency>1% and Hardy-Weinberg p-value>1x10-03 were retained for analysis. Association was conducted using logistic regression; using
the top three principal components as covariates. Bioinformatics analysis was performed using in-house Capture Hi-C data, to study long-
range interactions, to elucidate the potential function of the associated SNPs.
Results:
Post-QC, 2,585 cases and 5,181 controls were available for analysis with ~7.4 million SNPs. Analysis conducted within oligoarthritis and
RF-negative polyarthritis cases, (n=1,617) confirmed 13 previously identified JIA risk loci and identified more than 20 potentially novel
regions above suggestive significance (2.25 x 10-05). Of these, rs7874896, an intergenic SNP located between TNFSF15 and TNFSF8 on
chromosome 9 was one of the most strongly associated (p-value 3.67x10-07). TNFSF15 in particular is interesting, as it has been found that
TNFSF15 drives expression of pro-inflammatory cytokines (IFNγ) and TNFα from CD4+CD161+ T-cells, yet these cells were found to be
resistant treatment with an anti-TNF; suggesting that blockade of TNFSF15 may possess therapeutic benefit in JIA. Further investigation of
associated SNPs using Capture Hi-C data has yielded potentially interesting interactions within T- and B-cell lines.
Conclusion:
This study represents the largest GWAS conducted in JIA to date and our preliminary results have identified novel associations with the most
common subtypes of the disease and may have highlighted a potentially novel therapeutic target.
Disclosure: S. Smith, None; J. Bowes, None; J. Cobb, None; A. Hinks, None; S. Sampath, None; A. Yarwood, None; L. R. Wedderburn,
None; K. L. Hyrich, None; W. Thomson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/identification-of-novel-susceptibility-loci-in-a-large-uk-

cohort-of-juvenile-idiopathic-arthritis-jia-cases
New Autoinflammatory Phenotype Associated with Homozygous AGBL3 Variant

Ahmet Gül1, Neslihan Abaci2 and Sema Sirma Ekmekci2, 1Department of Internal Medicine, Division of Rheumatology, Istanbul University,
Istanbul Faculty of Medicine, Istanbul, Turkey, 2Department of Genetics, Istanbul University Institute for Experimental Medical Research,
Istanbul, Turkey
SESSION INFORMATION
Background/Purpose: To identify new genes/pathways associated with autoinflammatory phenotype.
Methods: We screened genomic variations by whole exome sequencing in 3 families presented with autoinflammatory findings despite
negative results for known autoinflammatory gene mutations. A systematic search was carried out specifically for identification of deleterious
genetic variants in genes involved in novel inflammatory pathways.
Results: We identified a deleterious mutation in the AGBL3 (ATP/GTP binding protein-like 3) gene, in a consanguineous family of Assyrian
origin. Index case, now 22-year-old male, presented to our outpatient clinic with recurrent attacks of fever, urticarial rash on the extremities
and trunk, conjunctival injections and arthralgia. His attacks started when he was 13, and two to three day lasting attacks recurred more
frequently during warm weather conditions or following hot baths. He had highly elevated CRP and ESR during attacks, but his acute phase
response did not return to normal values in between the flares. Low C3 and C4 values were also observed during asymptomatic periods. He
responded partially to corticosteroids as well as canakinumab and anakinra treatments, and he is currently on low dose steroids and 200
mg/day anakinra. Whole exome sequencing revealed homozygous c.769C>T mutation in AGBL3 gene, which results in early termination of
the protein (p.Gln257Ter) and deletion of carboxypeptidase domain. This protein belongs to metallocarboxypeptidases that mediate both
deglutamylation and deaspartylation of target proteins. AGBL3 is suggested to catalyze the deglutamylation of polyglutamate side chains,
especially in proteins such as tubulins. Also, STRING search revealed interaction of AGBL3 with complement regulatory proteins, such as
CD46, CD55, and CD59, which are potent inhibitors of the complement membrane attack complex.
We searched databases from Turkey and other sources, and we could not identify this variant in other individuals.
Conclusion: This study identifies the AGBL3 metallocarboxypeptidase gene as a potential autoinflammatory gene involved in a novel
pathway, and its loss of function mutations may result in a potent innate inflammatory response associated with lower complement levels and
a partial response to IL-1 blockade.
Disclosure: A. Gül, None; N. Abaci, None; S. Sirma Ekmekci, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/new-autoinflammatory-phenotype-associated-with-

homozygous-agbl3-variant
Genome-Wide Association Study of Clinically-Ascertained Gout and Subtypes Identifies

Multiple Susceptibility Loci Including Transporter Genes
Hirotaka Matsuo1, Akiyoshi Nakayama2, Hirofumi Nakaoka3, Ken Yamamoto4, Masayuki Sakiyama5, Amara Shaukat6, Yu Toyoda7,
Yukinori Okada8, Yoichiro Kamatani9, Masahiro Nakatochi10, Takahiro Nakamura5, Tappei Takada7, Hiroshi Nakashima5, Seiko Shimizu5,
Makoto Kawaguchi5, Asahi Hishida11, Kenji Wakai11, Blanka Stiburkova12, Karel Pavelka13, Lisa K. Stamp14, Nicola Dalbeth15, Tatsuo
Hosoya16, Michiaki Kubo9, Hiroshi Ooyama17, Toru Shimizu18, Kimiyoshi Ichida19, Tony R. Merriman20 and Nariyoshi Shinomiya21,
1Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Japan, 2Dept Integrative
Physiol, National Defense Med College, Tokorozawa, Japan, 3National Inst Genet, Mishima, Japan, 4Department of Medical Chemistry,
Kurume University School of Medicine, Kurume, Japan, 5National Defense Med College, Tokorozawa, Japan, 6Univ Otago, Dunedin, New
Zealand, 7Univ Tokyo Hosp, Tokyo, Japan, 8Osaka University, Osaka, Japan, 9Center for Integrative Medical Sciences, RIKEN, Yokohama,
Japan, 10Nagoya Univ Hosp, Nagoya, Japan, 11Nagoya Univ Grad Sch Med, Nagoya, Japan, 12Institute of Inherited Metabolic Disorders,
First Faculty of Medicine, Charles University, Prague, Czech Republic, 13Institute of Rheumatology, Prague, Czech Republic, 14University of
Otago, Christchurch, New Zealand, 15University of Auckland, Auckland, New Zealand, 16Jikei Univ Sch Med, Tokyo, Japan, 17Ryougoku
East Gate Clin, Tokyo, Japan, 18Kyoto Industr Health Assoc, Kyoto, Japan, 19Tokyo Univ Pharmacy Life Sci, Tokyo, Japan, 20Biochemistry
Dept, PO Box 56, University of Otago, Dunedin, New Zealand, 21National Defense Med College, Saitama, Japan
SESSION INFORMATION
Background/Purpose: We performed a genome-wide association study (GWAS) of gout and its subtypes to identify novel gout loci
including those that are subtype-specific.
Methods: Putative causal association signals from a GWAS of 945 cases and 1,213 controls were replicated with 1396 clinically-
ascertained gout cases and 1,268 controls of Japanese males by using a custom chip of 1,961 single nucleotide polymorphisms (SNPs). We
also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zealand Polynesian samples was done to further validate
the loci identified in this study.
Results: In addition to the five loci we reported previously, further susceptibility loci were identified at a genome-wide significance level
(p<5.0×10−8): urate transporter genes (SLC22A12 and SLC17A1) and HIST1H2BF-HIST1H4E for all gout cases, and NIPAL1 and FAM35A
for the renal underexcretion gout subtype. Although NIPAL1 encodes a magnesium transporter, functional analysis did not detect urate
transport via NIPAL1, suggesting its indirect association with urate handling. Localization analysis in the human kidney revealed expression
of NIPAL1 and FAM35A mainly in the distal tubules, which suggests the involvement of the distal nephron, as well as the proximal nephron,
in urate handling in humans. Clinically-defined male gout cases and controls of Caucasian and Polynesian ancestries were also genotyped,
and FAM35A was associated with gout in all cases. A meta-analysis of the three populations revealed FAM35A to be associated with gout at
a genome-wide level of significance (Pmeta=3.58×10-8). Further findings after this GWAS will be presented at the meeting. We also
revealed by a fine mapping that rs671, a common functional SNP of ALDH2, is a genuine gout-associated SNP in the CUX2 locus, which was
detected by the previous gout GWAS. Further results of a replication study with Japanese for loci detected by a previous gout GWAS with
Chinese population will be also discussed at the meeting.
Conclusion: Our findings including novel gout risk loci provide further understanding of the molecular pathogenesis of gout and lead to a
novel concept for the therapeutic target of gout and hyperuricemia.
Disclosure: H. Matsuo, None; A. Nakayama, None; H. Nakaoka, None; K. Yamamoto, None; M. Sakiyama, None; A. Shaukat, None; Y.
Toyoda, None; Y. Okada, None; Y. Kamatani, None; M. Nakatochi, None; T. Nakamura, None; T. Takada, None; H. Nakashima, None;
S. Shimizu, None; M. Kawaguchi, None; A. Hishida, None; K. Wakai, None; B. Stiburkova, None; K. Pavelka, None; L. K. Stamp,
Amgen, 8; N. Dalbeth, Takeda, AstraZeneca, Abbvie, 9; T. Hosoya, None; M. Kubo, None; H. Ooyama, None; T. Shimizu, None; K.
Ichida, None; T. R. Merriman, Ardea Biosciences, 2; N. Shinomiya, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/genome-wide-association-study-of-clinically-

ascertained-gout-and-subtypes-identifies-multiple-susceptibility-loci-including-transporter-genes
Finding Transcriptional Regulators Central to RA with Transcriptomics of IL17 Dose

Response, Time Series, and siRNA Silencing in Stromal Cells
Kamil Slowikowski1, Hung Nguyen2, Gerald Watts2, Fumitaka Mizoguchi3, Erika H. Noss4, Michael Brenner5 and Soumya Raychaudhuri6,
1Harvard University, Boston, MA, 2Brigham and Women's Hospital, Boston, MA, 3Department of Rheumatology, Graduate School of
Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan, 4Division of Rheumatology, University of
Washington, Seattle, WA, 5Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 6Division of Medicine and
Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
SESSION INFORMATION
Background/Purpose: Rheumatoid arthritis (RA) is characterized by immune cell infiltration into the synovial membrane of the joint, where
they engage stromal cells such as synovial fibroblasts in a persistent proinflammatory feedback loop. Tumor necrosis factor alpha (TNF) and
interleukin 17 (IL17) are elevated in RA and activate synovial fibroblasts. Chronically activated fibroblasts proliferate, degrade joint
cartilage, and recruit additional immune cells. We found that stimulation of fibroblasts with IL17 alone produced little response compared to
TNF, but the combination of IL17 and TNF synergistically increased chemokine and cytokine gene expression. The purpose of this study is to
define the transcriptional network controlling the synergistic response to IL17 and TNF.
Methods: We assessed transcriptional changes over time and IL17 doses. We did 175 Smart-seq2TM RNA-seq experiments on synovial
fibroblast cell lines from knee joint tissues obtained from 4 RA and 3 osteoarthritis (OA) donors. For each donor, we did a time series with 8
time points over 24 hours and 3 IL17 doses (0, 1, and 10 ng/mL) in combination with TNF (1 ng/mL). We repeated a subset of these RNA-
seq experiments after siRNA silencing of specific transcription factors, this time with fewer time points and independent cell lines.
Results: We identified 813 genes at 5% false discovery rate (FDR) and >1.5 fold change between RA and OA, including two homeobox
genes HOXC10 and HOXD11. Statistical analysis with linear models revealed 34 genes at 5% FDR and >1.5 fold change that respond to
IL17 in a dose dependent manner, 10 of which are also differently expressed between RA and OA. We identified motifs enriched in these 34
genes' promoters representing binding sites for known transcription factors (TFs) such as NFKB p65 (Rel A) and CEBP. We also found a
novel transcription factor, CUX1. Two CUX1 target genes, CXCL2 and CXCL3, are highly dose-responsive to IL17 and these targets have
CUX1 peaks in their promoters in ENCODE ChIP-seq data. Finally, exon level differential expression analysis revealed IL17 dose-
dependent exon inclusion of 38 exons in 21 genes at 5% FDR, including an exon in NFkappaB inhibitor zeta (NFKBIZ) for an ankyrin repeat
that likely binds to NFKB. Analysis of siRNA silencing experiments is ongoing.
Conclusion: IL17 and TNF costimulation activates a different transcriptional network than TNF or IL17 alone. A specific set of genes
responds to dose of IL17, and putative transcription factors controlling these genes include NFKB p65 (Rel A), CEBP, and CUX1.
Disclosure: K. Slowikowski, None; H. Nguyen, None; G. Watts, None; F. Mizoguchi, None; E. H. Noss, None; M. Brenner, None; S.
Raychaudhuri, Pfizer Inc, 2,Roche Pharmaceuticals, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/finding-transcriptional-regulators-central-to-ra-with-

transcriptomics-of-il17-dose-response-time-series-and-sirna-silencing-in-stromal-cells
Optimizing Precision Medicine By Using Genetics to Assign Diagnostic Prior

Probabilities to Patients with Synovitis
Rachel Knevel1,2,3,4, Chikashi Terao5,6,7, Jing Cui1,8, Kamil Slowikowski2,9,10, TWJ Huizinga3, Elizabeth Karlson11 and Soumya
Raychaudhuri1,2,12,13, 1Division of Medicine and Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA,
2Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA, 3Department of Rheumatology, Leiden
University Medical Center, Leiden, Netherlands, 4Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Bosten,
MA, 5Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan, 6Clinical Research Center,
Shizuoka General Hospital, Shizuoka, Japan, 7Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of
Medicine, Kyoto, Japan, 8Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 9Division of
Medicine and Rheumatology, Brigham and Women's Hospital, Harvard Medical Schoo, Boston, MA, 10Division of Genetics, Brigham and
Women's Hospital, Harvard Medical Schoo, Boston, MA, 11Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and
Harvard Medical School, Boston, MA, 12Department of Institute of Inflammation and Repair, University of Manchester, Manchester, United
Kingdom, 13Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
SESSION INFORMATION
Background/Purpose:
As the cost of genome-wide genotyping plummets, and biobanking efforts integrating medical records and genetics are rapidly expanding,
many patients will have genotyping available in medical records prior to patient visits. The question emerges: how informative this data is in
a rheumatology clinic.
This study tests the potential for genetics to assign prior probabilities for six synovitis phenotypes; ACPA positive rheumatoid arthritis,
ACPA negative rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis and gout.
Methods:
Risk allele information was obtained from Immunobase and GWAS publications. The genetic probability (GP) for each phenotype was
calculated using Bayesian theorem with the summation of the risk alleles times the risk effects of each genetic variant as the likelihood and
the sex adjusted disease prevalence as the prior. The GPs were normalized so that the total of the six probabilities for each individual was
one. If GPs are accurate we expect that the percent of individuals that have a disease tracks with GP.
I Benchmarking performance by simulation
We simulated a population of one million people with random genotypes using minor allele frequencies from the 1000 genome project. We
randomly assigned phenotypic status based on the known genetic risk alleles, sex, and disease prevalence. We then scored all individuals
with disease for posterior probabilities.
II Validation
We selected clinical cases on their ultimate diagnosis from BostonÕs Partners BIOBANK, using a rule-based algorithm based on clinical
notes, lab tests and medication prescriptions.
Results:
I In the simulation data set we observed that GPs were concordant with the phenotypic status, demonstrating that our model works in a
theoretical dataset.
II We identified 297 out of the 15,000 patients in the BIOBANK that had one of the six diseases of interest. We used these individuals and
assessed the performance of the GP.
We observed that there was a high positive correlation between the GP and the clinical case risk for the phenotypes (r2 = 0.95). A high GP
correctly corresponded with the clinical phenotypes: in all cases where the probability > 0.9, the patient indeed had that phenotype. More
importantly, the GP could discard phenotypes: GPs < 0.1 correctly corresponded with a clinical disease risk of < 10%, whereby for all
individuals 1-4 phenotypes could be effectively ruled out. We note however that the GP (mean 0.24) somewhat overestimated the clinical
risk (mean 0.16).
Conclusion:
In a cohort of synovitis patients, genetic information can facilitate decision making in early disease by ruling out and pointing towards the
most likely phenotype. Seeing the importance of an early diagnosis in patients presenting with synovitis, genetics can be considered as part of
a patientÕs medical history and as such it can inform us about the most likely diagnosis, without having to wait for more symptoms to arise.
Disclosure: R. Knevel, None; C. Terao, None; J. Cui, None; K. Slowikowski, None; T. Huizinga, Abbott Laboratories, Biotest AG,
Bristol-Myers Squibb, Crescendo Bioscience, Novartis Pharmaceuticals Corporation, Pfizer Inc, Roche, sanofi-aventis, Schering-Plough,
UCB, Eli Lilly, 5,METEOR Board, 6,EU & Dutch Arthritis Foundation, 2,Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Novartis
Pharmaceuticals Corporation, Pfizer Inc, Roche, sanofi-aventis, Schering-Plough, 8,Abbott Laboratories, Roche, 9; E. Karlson, None; S.
Raychaudhuri, Pfizer Inc, 2,Roche Pharmaceuticals, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/optimizing-precision-medicine-by-using-genetics-to-

assign-diagnostic-prior-probabilities-to-patients-with-synovitis
Applying Urine Proteomics for Discovery of Lupus Nephritis Damage Biomarkers in a

Pediatric Cohort
Jessica Turnier1, Bruce Aronow2, Kenneth Greis3, Michael Bennett4, Wendy Haffey3, Sherry Thornton5, Gaurav Gulati6, Michael
Wagner7, David Witte8, Prasad Devarajan9 and Hermine I. Brunner10, 1Pediatric Rheumatology, Cincinnati Children's Hospital Medical
Center, Cincinnati, OH, 2Computational Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 3University of Cincinnati
College of Medicine, Cincinnati, OH, 4Nephrology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 5Division of
Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 6Division of Immunology, Allergy and Rheumatology,
University of Cincinnati College of Medicine, Cincinnati, OH, 7Biomedical Informatics, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH, 8Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 9Nephrology, Cincinnati Children’s Hospital
Medical Center, Cincinnati, OH, 10Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
SESSION INFORMATION
Background/Purpose: Non-invasive biomarkers of lupus nephritis (LN) damage are needed to guide treatment decisions and determine risk
for kidney failure. Urinary proteomics has advanced as a tool for novel biomarker discovery in recent years. Specifically, Isobaric Tags for
Relative and Absolute Quantification (iTRAQ) is an advanced proteomics technique that quantifies and compares protein expression among
samples by mass spectrometry in a single experiment. We aimed to use iTRAQ for discovery of candidate urine biomarkers (CUBMs) for LN
chronicity in a pediatric lupus cohort and then further pursued validation of CUBMs.
Methods: For the initial discovery cohort, urine was collected from children with LN (n=21) at the time of kidney biopsy. LN damage was
characterized as per the NIH chronicity index (NIH CI, score range: 0-12) and categorized as none (0), low (1), moderate (2), or high (≥3).
iTRAQ experiments compared protein composition in four urine samples from different LN damage categories, respectively. The relative
expression of differentially excreted proteins was tested for significant differences using a log-rank test. We then generated heat maps and
performed network analysis to identify proteins associated with LN damage, also considering concurrent histological LN activity (NIH
activity index scores). Upon identification of CUBMs from the discovery cohort, specific commercial ELISAs were performed on urine
samples from children with varying levels of LN chronicity in a separate validation cohort (n=41). Analysis of Variance was performed to
detect statistical differences between each of the CUBMs and LN chronicity, with adjustment for clinical LN activity.
Results: Overall, iTRAQ detected 112 proteins from the urine sample sets of the discovery cohort, and 51 proteins were quantifiable in all
replicate sample runs. Initial log-rank test revealed 4 differentially expressed proteins with p-values <0.05. Further evaluation by heat map
and network analysis led to identification of 7 CUBMs for LN chronicity: Afamin (AFM), Immunoglobulin Heavy Constant Alpha 1
(IGHA1), Alpha-1-Antichymotrypsin (SerpinA3), Transthyretin (TTR), Retinol Binding Protein 4 (RBP4), Alpha-1-Acid Glycoprotein, Type
2 (ORM2) and Transferrin (TF). In the validation cohort, only SerpinA3 was found to be different based on degree of LN chronicity after
adjustment for concurrent LN activity. SerpinA3 levels were found to increase with higher degrees of LN chronicity.
Conclusion: Using advanced proteomic techniques followed by confirmation using specific ELISAs, we identified SerpinA3 as a potential
urine biomarker to help quantify the degree of tissue damage from LN. Elevated levels of SerpinA3, a known inhibitor of neutrophil cathepsin
G and angiotensin II production, could serve as both a danger signal and protective mechanism from further kidney damage. Further
validation of SerpinA3 as an LN damage biomarker in an independent cohort is needed to determine its ability to guide treatment and predict
prognosis.
Disclosure: J. Turnier, None; B. Aronow, None; K. Greis, None; M. Bennett, None; W. Haffey, None; S. Thornton, None; G. Gulati,
None; M. Wagner, None; D. Witte, None; P. Devarajan, NIDDK, 2; H. I. Brunner, NIDDK, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/applying-urine-proteomics-for-discovery-of-lupus-

nephritis-damage-biomarkers-in-a-pediatric-cohort
Transcriptional Profiling of Synovial Macrophages from RA Patients to Capture Disease

Heterogeneity
Philip J. Homan1, Arthur M. Mandelin II2, Salina Dominguez1, Emily Bacalao3, S. Louis Bridges Jr.4, Joan M. Bathon5, John Atkinson6,
David Fox7, Eric L. Matteson8, Chris Buckley9, Costantino Pitzalis10, Deborah Parks11, Laura Hughes12, Laura Geraldino-Pardilla13,
Robert Ike14, Kristine Phillips15, Kerry Wright16, Andrew Filer17, Stephen Kelly18, Eric M. Ruderman19, Carla Cuda1, Hiam Abdala-
Valencia3, Alexander Misharin3, G. R. Scott Budinger3, Richard M. Pope19, Harris Perlman20 and Deborah R. WInter1, 1Department of
Medicine Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, 2Rheumatology, Northwestern
University, Chicago, IL, 3Northwestern University, Chicago, IL, 4Clinical Immunology & Rheum, Univ of Alabama, Birmingham, AL,
5Division of Rheumatology, Columbia University Medical Center, New York, NY, 6Washington University in St. Louis, St. Louis, MO,
7Department of Medicine [Division of Rheumatology], University of Michigan Medical System, Ann Arbor, MI, 8Rheumatology, Mayo
Clinic College of Medicine and Science, Rochester, MN, 9University of Birmingham, Birmingham, United Kingdom, 10Centre for
Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London, School of Medicine and Dentistry,
Queen Mary University of London, London, United Kingdom, 11Washington University School of Medicine in St. Louis, St. Louis, MO,
12University Alabama Birmingham, Birmingham, AL, 13Columbia University, New york, NY, 14Division of Rheumatology, University of
Michigan, Ann Arbor, MI, 15University of Michigan, Ann Arbor, MI, 16Rheumatology, Mayo Clinic, Rochester, MN, 17Institute of
Inflammation and Ageing (IIA), University of Birmingham, Birmingham, United Kingdom, 18William Harvey Research Institute, London,
United Kingdom, 19Medicine/Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, 20Department of Medicine,
Division of Rheumatology, Northwestern University Feinberg School of Medicine, Northwestern University Feinberg School of Medicine,,
Chicago, IL
SESSION INFORMATION
Background/Purpose: In a given patient with rheumatoid arthritis (RA), it is difficult to predict disease progression or identify to which
treatments they will respond. Macrophages have been strongly implicated in the pathogenesis of RA and reduction in the number of
macrophages in the synovial sublining of the joint is a key biomarker for better outcomes. However, without a deeper knowledge of the genes
regulated in vivo, such as provided by unbiased high-throughput sequencing, it is difficult to discern the function of these macrophages in RA.
Here, we describe our work to profile the genome-wide transcriptome of synovial macrophages in RA patients.
Methods: We used tissue obtained from synovial biopsies of the wrist joints in RA patients for histology and cell sorting via FACS. We
gated for CD45+Lin-CD64+CD11b+CD14+HLA-DR+ macrophages and distinguished 2 populations based on the expression of CD206. As a
comparison, we also collected and sorted macrophages from OA patients via surgical discards. We processed all macrophage populations
for RNA-seq and sequenced the libraries on an Illumina NextSeq 500 to an average depth of 5 million reads. The reads were aligned and
mapped to genes using bowtie and HTseq, respectively, followed by bioinformatic analysis as described below.
Results: The quality of the RNA-seq data from RA macrophages was comparable to OA, confirming the feasibility of our approach. Next,
we assessed the ability of our macrophage-specific RNA-seq to identify differentially expressed genes between RA and OA by fold-change,
as compared with RNA-seq of the unprocessed whole synovial tissue. While the approaches generally agreed, we found many genes that
were differentially expressed only in macrophages, supporting the value of cell-specific RNA-seq to uncover gene pathways that would be
obscured in whole tissue RNA-seq. Next, we considered the heterogeneity of macrophages across RA patients by calculating the pairwise
correlation between samples. We found that there were significant differences between RA transcriptional profiles that were best explained
by classification of patients into lymphoid, myeloid, or pauci-immune phenotypes based on the dominant cell type. In order to overcome this
difficulty in identifying genes associated with RA pathology, we focused on clustering genes into co-regulated modules based on their
expression across samples. This allowed us to identify pathways with significant expression patterns, even if the relevant genes were up-
regulated in only a portion of RA samples. For example, we found that a subset of RA patients demonstrated over-expression of certain
cytokine-mediated pathways (including IL3, IL5, and IL13), while another subset was enriched for type 1 interferon signaling. Similarly, we
found that Dock2, a gene involved in actin remodeling that was not significant at the whole-tissue level, was preferentially expressed in RA
macrophages that also expressed Ccr1.
Conclusion: Together, these results help us to understand the role of different macrophage populations in RA heterogeneity. Our goal is to use
these studies as the basis for predicting clinical outcomes and choosing between therapeutic options for treatment.
Disclosure: P. J. Homan, None; A. M. Mandelin II, None; S. Dominguez, None; E. Bacalao, None; S. L. Bridges Jr., None; J. M. Bathon,
Regeneron, 5; J. Atkinson, None; D. Fox, None; E. L. Matteson, None; C. Buckley, None; C. Pitzalis, None; D. Parks, None; L. Hughes,
None; L. Geraldino-Pardilla, None; R. Ike, None; K. Phillips, None; K. Wright, None; A. Filer, None; S. Kelly, None; E. M. Ruderman,
AbbVie, Amgen, BMS, GSK, Janssen, Eli Lilly and Company, Novartis, Pfizer, Roche/Genentech, 5; C. Cuda, None; H. Abdala-Valencia,
None; A. Misharin, None; G. R. S. Budinger, None; R. M. Pope, None; H. Perlman, None; D. R. WInter, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/transcriptional-profiling-of-synovial-macrophages-from-

ra-patients-to-capture-disease-heterogeneity
Precisely Controlled Differential Gene Expression System to Investigate the Effect of

eQTL
Xiaoming Lu, PhD1,2, Xiaoting Chen1, Carmy Forney1, Connor Schroeder1, John B. Harley1, Matthew Weirauch3 and Leah C. Kottyan4,
1Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2Immunobiology
Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH, 3Center for Autoimmune Genomics and Etiology (CAGE)
and Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH,
4Center for Autoimmune Genomics and Etiology (CAGE), Division of Allergy and Immunology, Cincinnati Children's Hospital, Cincinnati
Children's Hospital Medical Center, Cincinnati, OH
SESSION INFORMATION
Background/Purpose: Genome-wide association studies and large-scale sequencing studies identify many non-coding genetic variants that
increase disease risk. At least 60% of these loci have been associated with genotype-dependent expression of nearby genes. It remains to be
determined that 50-100% expression differences are biologically relevant in specific immune cell types. We focus on the expression
quantitative trait loci (eQTL) at the ETS1 lupus-risk locus.Patients with lupus have 50% less peripheral blood mononuclear cell mRNA
expression of ETS1 than people without SLE, and people with the risk haplotype at the ETS1 locus have 50% less mRNA expression than
people with the non-risk haplotype. Since ETS1 is a transcription factor, differential ETS1 expression could have easily measurable
consequences on transcription factor binding and downstream gene expression. There are nearly 800 genes that are known to be dysregulated
in subjects with SLE.
Methods: We developed a system combining the Clustered regularly interspaced short palindromic repeats (CRISPR) Homology-directed
Repair technique with Tet-inducible Controlled Gene Expression technique to precisely control gene expression. This system allows us to
mimic the differential gene expressions caused by genetic variants.
Results: Our analyses of these genes using publically available ChIP-seq data sets from B cell line GM12878 and epithelial cell line K562
indicates that 191 and 151 of these genes, respectively, have ETS1 binding sites proximal to the transcription start site (enrichment of 3-4
fold compared to randomly chosen gene sets, p<10-46). We hypothesize that these changes in ETS1 levels are important in 1) ETS1 binding
throughout the genome, 2) expression of ETS1 downstream target genes (such as BLIMP1), and 3) immunological dysfunction and
hyperactivity of B cells. We test these hypotheses by analyzing the binding of ETS1 (ChIP-seq) and the changes to the transcriptome of cells
with 2-fold differences in ETS1expression (RNA-seq). Our CRISPR system successfully mimics the differential gene expressions.
Conclusion: The investigation of the ETS1 eQTL will allows us to make important progress in the field of human genetics and especially
complex genetic disease etiology.
Disclosure: X. Lu, PhD, None; X. Chen, None; C. Forney, None; C. Schroeder, None; J. B. Harley, NowDiagnostics, 1; M. Weirauch,
None; L. C. Kottyan, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/precisely-controlled-differential-gene-expression-system-

to-investigate-the-effect-of-eqtl
SEC16A and Antigen Presentation Abnormalities in the Pathogenesis of

Axial Spondyloarthritis
Fanxing Zeng1, Vidya Ranganathan2, Proton Rahman3, Darren O’Rielly4 and Nigil Haroon5, 1University Health Network, Toronto, ON,
Canada, 2University of Toronto, Toronto, ON, Canada, 3Rheumatology, St Claires Mercy Hospital, St Johns, NF, Canada, 4Memorial
University, St John's, NF, Canada, 5Rheumatology, Toronto Western Hospital, University of Toronto, Spondylitis Clinic, Toronto, ON,
Canada
SESSION INFORMATION
Background/Purpose:
Axial Spondyloarthritis (AxSpA) is a chronic inflammatory rheumatic disease of axial skeleton. Our group recently identified a novel rare
mutation of the SEC16A gene that strongly tracked with AxSpA in a multiplex family. Remarkably, all individuals with HLA-B27 and the
SEC16A mutation had or went on to develop AxSpA. Sec16a is an important player in the ER-Golgi transport pathway with potential effects
on antigen presentation and the pathogenesis of AxSpA. We have previously shown that the SEC16A mutation hinders the assembly of COPII
vesicles budding from the ER that leads to abnormal MHC I trafficking and ER stress. In this study we explore the functional impact of
Sec16A abnormalities on CD8+ T cell immune response. In addition, protein-protein interaction assays followed by pathway analysis help us
understand the impact of SEC16A mutation on different cellular processes.
Methods:
AxSpA patients from the multiplex family (N=9) had both SEC16A mutation and HLA-B27. Controls (N=5) were family members with no
disease and had HLA-B27 and wild-type (WT) SEC16A. B cell lines were generated from patients and controls by EBV transformation. For
validation, SEC16A was silenced in B-lymphoblastoid cells with stable HLA-B27 expression (C1R-B27) and assays repeated. Total protein
was extracted from B cells and the formation of HLA free heavy chain homodimer (FHC) was studied using HC-10 western blot under non-
reducing and reducing conditions. HLA-B27 mediated immune response was assessed by cytotoxic T-lymphocyte assay. NP383-391 specific
CTL clones were generated from HLA-B27 positive donor. The GFP-ubiquitin-NP383-391 construct was introduced by DNA transfection in
B cells. Two days after transfection, B cells were incubated with NP383-391 specific CTL at a ratio of 1:10 for 4 hours. CTL activity was
evaluated using caspase 3 cleavage in target cells. Pathway analysis assessed by protein-protein interaction was carried out to investigate the
interactome of SEC16A variants.
Results:
Both SEC16A mutation in patients’ B cells and Sec16a deficiency (90% suppression) in C1R-B27 significantly (P<0.01 and P<0.001
respectively) increased the level of HLA-B27 FHC homodimers. This is likely due to a general disruption of MHC I trafficking by Sec16A
abnormalities as we previously reported. GFP-ubiquitin-NP383-391 constructs were stably expressed in EBV-B cells at a similar level
without having an effect on HLA-B27 surface expression. However, the cytotoxicity of NP 383-391 specific T cells were significantly lower
against EBV-B cells with mutant SEC16A compared to EBV-B cells with WT SEC16A (p<0.01). T cell cytotoxicity was almost completely
abolished in SEC16A-suppressed C1R-B27 cells. Using protein-protein interaction and pathway analysis, we found that mutant Sec16a had
lower affinity to interactors involved in ER-to-Golgi vesicle mediated transport, membrane budding, vesicle organization, and antigen
processing/presentation.
Conclusion:
Sec16a abnormalities can affect HLA-B27 intracellular transport, dimerization, antigen presentation and cytotoxic T cell responses. These
changes can potentially play a role in AS pathogenesis.
Disclosure: F. Zeng, None; V. Ranganathan, None; P. Rahman, Janssen Pharmaceutica Product, L.P., 8,Amgen, AbbVie, BMS, Celgene,
Pfizer, Janssen, Wyeth, EliLiiy, Novartis, 8,Amgen, AbbVie, BMS, Celgene, Pfizer, Janssen, Wyeth, EliLiiy, Novartis, 5; D. O’Rielly, None;
N. Haroon, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/sec16a-and-antigen-presentation-abnormalities-in-the-

pathogenesis-of-axial-spondyloarthritis
Intronic Variants of the B-Cell Proliferator RASGRP3 Affect Its Expression, and Might
Contribute to Lupus Risk
Bhupinder Singh1, Philip Borden2, Julio Molineros3, Celi Sun3, Loren Looger2 and Swapan Nath1, 1Arthritis and Clinical Immunology
Research Program, Oklahoma Medical Research Foundation, OKlahoma City, OK, 2Howard Hughes Medical Institute, Ashburn, VA,
3Oklahoma Medical Research Foundation, OKlahoma City, OK
SESSION INFORMATION
Background/Purpose: Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease with complex genetic underpinnings.
Variants from RASGRP3 (RAS Guanyl Releasing Protein 3) is one of the most consistently replicated SLE susceptibility genes. We recently
reported that two intronic variants (rs13385731 and rs12612030) explained RASGRP3-SLE association in Asians [Sun et al. 2016, Nat
Genet]. However, the “causal” functional variants and the genetic mechanism(s) by which associated variants contribute to disease are
largely unknown. We hypothesized that these intronic variants affect epigenetic regulation and modulate RASGRP3 expression.
Methods: First, we used in-silico bioinformatics and epigenetic analyses to define the potential regulatory effects of the candidate variants
on gene expression using data on several histone marks, DNAse-1 hypersensitivity, and eQTLs across multiple tissues from ENCODE,
ROADMAP and GTEx data bases. Luciferase reporter assays in HEK293 cells were used to measure the effects of risk and non-risk
variants/haplotypes on gene expression. Next, we used a combination of DNA pulldown, Electrophoretic Mobility Shift Assay (EMSA),
Super-shift, Western blot and Mass Spectrometry to identify DNA-bound proteins followed by quantitative chromatin immunoprecipitation-
PCR (ChIP-qPCR) to assess the allele-specific binding of interacting proteins. To assess the effect of risk alleles/haplotypes on cis-
regulatory elements we also performed ChIP-qPCR with H3K27Ac and P300. Finally, using EBV-transformed cell lines, RASGRP3 mRNA
and protein expressions were compared between risk and non-risk alleles/haplotypes.
Results: Bioinformatics predicted that these variants are located in active chromatin and have the potential to be dual enhancers/promoters.
We also predicted allele-specific binding to PARP1 and IRF1 at rs13385731. We observed significant (p<0.005) difference in RASGRP3
transcript and protein levels with increased expression in rs13385731 risk genotype (TT). Luciferase assays demonstrated significant
(p<0.005) allele-specific enhancer and promoter activities. DNA pulldown and EMSA suggested allele-specific bound protein ~100 kD,
which was identified as PARP1 protein by Mass Spectrometry and later confirmed by super shift and Western blot. We also verified
differential allele-specific binding of PARP1 and IRF1 against rs13385731 using ChIP-qPCR. Interestingly, while PARP1 binding affinity is
higher with risk (TT) genotype, IRF1 binding shows strong binding affinity with non-risk (CC) genotype of rs13385731.
Conclusion: Our results showed that rs13385731 is an eQTL, and the risk (TT) genotype is associated with increased RASGRP3 expression.
Furthermore, this variant showed significant allele-specific binding to H3K27Ac, P300, PARP1 and IRF1 proteins, which might alter
expression of RASGRP3, contributing to SLE risk. The activity of this variant provides insight into the molecular mechanisms underlying its
association with SLE.
Disclosure: B. Singh, None; P. Borden, None; J. Molineros, None; C. Sun, None; L. Looger, None; S. Nath, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/intronic-variants-of-the-b-cell-proliferator-rasgrp3-

affect-its-expression-and-might-contribute-to-lupus-risk
Genome-Wide DNA Methylation Study in Lupus in an Admixed Mexican Population

Maria Teruel1, Patrick Coit2, Mikhail Dozmorov3, Mario Cardiel4, Ignacio Garcia-De La Torre5, Marco A Maradiaga-Ceceña Sr.6, José
Francisco Moctezuma7, Maria Teresa Tusié-Luna8, Marta Alarcón-Riquelme9,10 and Amr H Sawalha2, 1GENYO, Center for Genomics and
Oncological Research Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain, 2Division of Rheumatology,
University of Michigan, Ann Arbor, MI, 3Department of Biostatistics, Virginia Commonwealth University, Richmond, VA, 4Centro de
Investigación Clínica de Morelia SC, Morelia, Mexico, 5Immunology & Rheumatology, Centro de Est. de Invest. Bas. y Clin., S.C.,
Guadalajara, JAL, Mexico, 6Hospital General de Culiacán, Culiacán, Mexico, 7Servicio de Reumatología, Hospital General de Mexico,
Ciudad de Mexico, Mexico, 8Medicina Genómica y Toxicología Ambiental, Universidad Nacional Autonoma de Mexico, Ciudad de Mexico,
Mexico, 9Uppsala University, Uppsala, Sweden, 10Centro de Genomica e Investigación Oncológica, Pfizer-University of Granada-Junta de
Andalucía, Granada, Spain
SESSION INFORMATION
Background/Purpose: Our knowledge about the pivotal role DNA methylation plays in the pathogenesis of SLE has significantly increased
in the last few years. However, we still have a relatively poor idea about the role of this epigenetic mark in the development of SLE in
admixed populations. In addition, we do not yet understand the role of DNA methylation in explaining the higher prevalence and severity of
SLE in these populations. To achieve these goals, we have conducted a genome-wide DNA methylation case-control study on individuals
with different degrees of Amerindian ancestry.
Methods: Whole blood DNA from 60 females SLE patients and 59 female healthy individuals from Mexico were included in the study. The
Native American ancestry was estimated using STRUCTURE and a set of ancestry informative markers (AIMs), and data from 1000
Genomes populations and a set of individuals of Nahua population were used as reference panel. In order to minimize the effect of other
minor ancestries, all individuals were selected to have less than 10 % of Asian and African ancestries. DNA methylation data were
generated using the Infinium MethylationEPIC BeadChip (Illumina). Differential methylation between groups was estimated by beta
regression after adjusting for age, technical variables and estimated cell type composition. SLE patients were stratified according to clinical
manifestations. Functional annotations were performed using DAVID/Panther.
Results: Differential DNA methylation pattern was observed among individuals with different degrees of native Amerindian ancestry. The
probe cg03693186 located in DAPK1 gene had the most significant signal detected (p-value =3.0 E-19). In a case-control association
analysis, an overall hypomethylation in lupus was observed, especially in genes involved in the type I interferon response and regulation such
as IFIH1, IF44, IF44L, MX1 and NLRC5, consistent with findings in other populations. When comparing DNA methylation changes
associated with lupus nephritis, a significant enrichment in the canonical WNT/β-catenin signaling pathway (p-value adjusted= 1.1 E-7) was
found among hypomethylated genes. Hypermethylated genes in lupus nephritis show a significant enrichment in Angiotensin II-stimulated
signaling through G proteins and beta-arrestin (p-value adjusted= 0.0034).
Conclusion: Differential methylation of interferon-regulated genes is associated with SLE in an admixed Amerindian population from
Mexico, consistent with the epigenetic interferon signature observed in other ethnicities. The Amerindian association found for DAPK1 gene,
a positive mediator of gamma-interferon induced programmed cell death, might provide clues to explain the higher SLE prevalence and
severity observed in these populations. In addition, our results also identify other biological pathways associated with lupus nephritis that
might help to clarify the high prevalence and severity of lupus nephritis in admixed populations.
Disclosure: M. Teruel, None; P. Coit, None; M. Dozmorov, None; M. Cardiel, None; I. Garcia-De La Torre, None; M. A. Maradiaga-
Ceceña Sr., None; J. F. Moctezuma, None; M. T. Tusié-Luna, None; M. Alarcón-Riquelme, Genzyme/Sanofi Corporation, 2; A. H.
Sawalha, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/genome-wide-dna-methylation-study-in-lupus-in-an-

admixed-mexican-population
Mass Spectrometry Imaging of Synovium: A Novel Approach to Classify the

Rheumatoid and Psoriatic Arthritis Patients
Beatriz Rocha1,2, Berta Cillero-Pastor3, Gert Eijkel3, Lennart R. Huizing3, Cristina Ruiz-Romero1,4, Andrea Cuervo5,6, Ron M A Heeren3,
Juan D. Cañete5,6 and Francisco J Blanco1,6, 1Rheumatology Division, ProteoRed/ISCIII Proteomics Group, INIBIC - Hospital Universitario
de A Coruña, A Coruña, Spain, A Coruña, Spain, 2The Maastricht Multimodal Molecular Imaging Institute (M4I), Division of Imaging Mass
Spectrometry, Maastricht University, The Netherlands, Masstricht, Netherlands, 3The Maastricht Multimodal Molecular Imaging Institute
(M4I), Division of Imaging Mass Spectrometry, Maastricht University, The Netherlands, Maastricht, Netherlands, 4CIBER-BBN Instituto de
Salud Carlos III, INIBIC-CHUAC, A Coruña, Spain., A Coruña, Spain, 5Arthritis Unit, Rheumatology Department, Hospital Clinic,
IDIBAPS, Barcelona, Spain, Barcelona, Spain, 6RIER-RED de Inflamación y Enfermedades Reumáticas, INIBIC-CHUAC, A Coruña, Spain,
A Coruña, Spain
SESSION INFORMATION
Background/Purpose:
Psoriatic arthritis (PsA) and Rheumatoid arthritis (RA) are immune-mediated chronic inflammatory diseases. Synovial membrane is the
initial site of inflammation in PsA and RA joints. This tissue can be used for diagnostic purposes since pathophysiological events occurring
in the synovial are more likely than dispersed serum factors to reflect the clinical status and outcome in patients. Even though both tissues are
morphologically similar, we hypothesize that there are differences in the molecular signature of the PsA and RA synovial membranes that can
be employed for an accurate diagnosis of both pathologies. The purpose of this study is to create a new method for arthritic patient
classification based on the spatially resolved molecular profiles detected by mass spectrometry imaging (MSI).
Methods:
Synovial membrane slices obtained from 10 PsA and 10 RA patients were analyzed by matrix-assisted laser desorption/ionization fourier-
transform ion cyclotron resonance mass spectrometry imaging (MALDI-FT-ICR-MSI) to characterize the specific profile and distribution of
metabolites. Images of differentially expressed metabolites were generated with FlexImaging 4.1 software. Principal component analysis
(PCA) and discriminant analysis (DA) were used to look for the metabolites with the highest differences between PsA and RA synovial
membranes. Annotation of the detected metabolites was performed by matching accurate mass with METLIN and Human Metabolome
Databases.
Results:
PsA and RA synovial membranes were discriminated based on their metabolic signature using discriminant analysis. Sugars including N-
acetylgalactosamine 6-sulfate (m/z 282,0276), glucuronic acid 1-phosphate (m/z 273,0026), N-acetylneuraminic acid (m/z 290,0876) and
different small lipids were identified and localized. Fatty acids and lysophosphatidic acids (LPAs) showed a higher expression in PsA
compared to RA (Figure 1). On the contrary, all sugars displayed a stronger intensity in RA synovial tissues when compared to PsA. N-
acetylneuraminic acid showed a higher abundance in the synovial sublining layer whereas glucuronic acid 1-phosphate was specifically
localized in the lining layer (Figure 2).
Conclusion:
We have localized and identified for the first time metabolites from human PSA and RA synovial membranes using MALDI-FT-ICR-MSI.
Our results provide a fast and reliable classification of patients affected by PsA and RA.
Disclosure: B. Rocha, None; B. Cillero-Pastor, None; G. Eijkel, None; L. R. Huizing, None; C. Ruiz-Romero, None; A. Cuervo, None;
R. M. A. Heeren, None; J. D. Cañete, None; F. J. Blanco, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/mass-spectrometry-imaging-of-synovium-a-novel-

approach-to-classify-the-rheumatoid-and-psoriatic-arthritis-patients
Identification of a Functional Susceptible Variant in Distal Enhancer of Mir-146a By

CRISPR-Cas9
Guojun Hou1, Jing Zeng2, Yuanjia Tang3 and Nan Shen4,5, 1Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS),
Chinese Academy of Sciences (CAS) &Shanghai Jiao Tong University School of Medicine (SJTUSM), ShangHai, China, 2Shanghai Institute
of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 3Shanghai Institute of
Rheumatology,Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 4Shanghai Institute of Rheumatology,
Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, Shanghai, China, 5The Center for Autoimmune
Genomics and Etiology (CAGE), Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America, Cincinnati, OH
SESSION INFORMATION
Background/Purpose: The majority of trait-associated SNPs occur in noncoding regions and are enriched in enhancers. GWAS have
identified numerous genetic variants associated with Systemic Lupus Erythematosus (SLE), but mechanistic insights remain limited, particular
for noncoding polymorphisms. miR-146a is a negative regulator of the interferon pathway. In SLE patients, the expression of miR-146a is
low and contributes to the abnormal activation of interferon pathway. rs2431697 is associated with the miR-146a expression level and
located approximately 15.3 kb upstream of miR-146a exon 1, but how this risk variant regulates miR-146a expression and functionally
contributes to the underlying pathogenesis is still unclear. Now, the application of CRISPR-Cas9 for genome engineering provides a new
approach to study the function of disease susceptibility variants. This study was undertaken to investigate the role of rs2431697-containing
region in the regulation of miR-146a expression by CRISPR-Cas9 technology.
Methods: To confirm whether rs2431697-containing region is a distal enhancer, we carried out ATAC-seq and formaldehyde-assisted
isolation of regulatory elements (FAIRE) to test chromatin accessibility of this region. Chromatin immunoprecipitation (ChIP) followed by
qRT–PCR (ChIP-qRT–PCR) was adopted to probe the enrichment of active enhancer makers-H3K4me1 and H3K27ac. SAM system is a
dCas9-based transcription activation system comprising of dCas9-VP64 and MS2–p65–HSF1 complex, which can transactivate target genes
from distal enhancers. We also take this system to test the function of this region. To detect whether rs2431697-containing region is actually
involved in the regulation of miR-146a expression, CRISPR-Cas9 technology was used to generate a 30 bp-deletion of the genomic region
containing rs2431697 in U937 cells and miR-146a expression was analyzed by TaqMan microRNA assay. We also generated rs2431697 T
allele and rs2431697 C allele containing cell clone in U937 cells by CRISPR-Cas9 induced homology-directed repair, and using
bioinformatics to predict the SNP-specific binding transcription factor.
Results: ChIP-qRT–PCR analysis showed that rs2431697-containing region was enriched with H3K27ac and H3K4me1 modification.
ATAC-Seq and FAIRE-qRT-PCR indicated that the region was open. Additionally, dCas9-vp64-SAM system could activate miR-146a
expression based on the guide RNAs around this region. Importantly, the generation of 30 bp-deletions comprising rs2431697 dramatically
reduced the miR-146a expression at transcriptional level of up to 10-fold, but had no effect on the expression of the neighbor gene PTTG1.
rs2431697 T allele and C allele comprising cell clone had different miR-146a expression level at both native and TNFα stimulation.
Bioinformatics analysis suggested that rs2431697 T and C allele may have differential RelA binding.
Conclusion: Using CRISPR-Cas9 technology, we first indicate that rs2431697-containing region participates in the regulation of miR-146a
expression. We also demonstrate that rs2431697 is located in a distal enhancer and has differential transcription factor binding that
modulates miR-146a expression involving in the pathogenesis of SLE.
Disclosure: G. Hou, None; J. Zeng, None; Y. Tang, None; N. Shen, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/identification-of-a-functional-susceptible-variant-in-

distal-enhancer-of-mir-146a-by-crispr-cas9
Identification of Disease-Susceptible Lncrna Contributed to Abnormal Activation of

Type I Interferon Pathway in Systemic Lupus Erythematosus
Nan Shen1,2, Yuanjia Tang3, Zhixin Xue3 and Chaojie Cui4, 1Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong
University School of Medicine, Shanghai, China, Shanghai, China, 2The Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati
Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America, Cincinnati, OH, 3Shanghai Institute of Rheumatology,Renji
Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 4Shanghai Institute of Rheumatology, Renji Hospital,
Shanghai Jiao Tong University School of Medicine, Shanghai, China
SESSION INFORMATION
Background/Purpose:
Dysregulation or dysfunction of some key moleculars in signaling pathway is involved in disease pathogenesis. Long non-coding RNA
(lncRNA), as a regulator of gene expression, plays great role in signaling pathway. The majority of susceptible single nucleotide
polymorphisms (SNPs) of systemic lupus erythematosus (SLE) identified in GWAS studies are located in noncoding regions of the human
genome. We hypothesized that disease-related functional SNP linked to lncRNA may affect expression or function of lncRNA and involve in
key signaling pathway of SLE.
Methods:
Deep sequencing of human renal samples to screen differential expression of lncRNAs between LN patients and healthy donors and mining
GWAS data were applied to get candidate lncRNAs. RNA-FISH was used to identify subcellular location of lncRNA. Reporter gene assay
was applied to ascertain effect of disease-related SNP on lncMKLN1 transcription. Stimulation in human renal mesangial cells (HRMC) by
all kinds of TLR ligands, IFNs, and TNFα, and transfection in HRMC cells by antisense oligonucleotides (ASOs), and quantitative real-time
polymerase chain reaction (RT-qPCR) were used to analyze the relative genes expression. LncMKLN1 transcription was activated or
inhibited through CRISPR-dCas9 system in Hela cell line. RNA-seq was executed to examine the gene expression profile after changing
lncMKLN1 expression, and western blot was applied to determine the key signaling molecules of IFN pathway.
Results:
LncMKLN1, dominantly located in nucleus, was up-regulated in lupus patients compared to healthy donors, and could be induced by IFNα
and TLR ligands in HRMC. GWAS data showed that there were two lupus-related SNPs located within proximal region of lncMKLN1
promoter. Promoter constructs containing susceptible allele have higher activity of transcription compared to another allele. Silencing
lncMKLN1 significantly reduced the expression of a group of interferon-inducible genes, including IFIT3, OAS1, CXCL10, etc. We used
lose-of-function and gain-of-function strategy through CRSIPR system to confirm that lncMKLN1 positively regulated type I interferon
pathway. Furthermore, it was identified the involvement of lncMKLN1 in interferon signaling pathway was through regulating the expression
of STAT1, IRF9 and phosphorylation of IRF9 and STAT1 although its mechanism is also needed to investigate.
Conclusion:
Functional susceptible SNP enhances lncMKLN1 expression, resulting in abnormal activation of interferon pathway of SLE.
Disclosure: N. Shen, None; Y. Tang, None; Z. Xue, None; C. Cui, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/identification-of-disease-susceptible-lncrna-contributed-

to-abnormal-activation-of-type-i-interferon-pathway-in-systemic-lupus-erythematosus
Genetic Determinants of Fatigue in Primary Sjögren`s Syndrome – a Genome Wide

Association Study
Katrine Norheim1, Andrei Alexsson2, Juliana Imgenberg-Kreuz3, Johan Gorgas Brun4,5, Roland Jonsson6, Wan-Fai Ng7,8, Elke Theander9,
Thomas Mandl10, Kathy L. Sivils11, Lars Rönnblom12, Gunnel Nordmark13 and Roald Omdal5,14, 1Clinical Immunology Department,
Stavanger University Hospital, Stavanger, Norway, 2Rheumatology and Science for Life Laboratory, Department of Medical Sciences,
Uppsala University, Sweden, Uppsala, Sweden, 3Department of Medical Sciences, Uppsala University, Uppsala, Sweden, 4Section for
Rheumatology, Haukeland University Hospital, Bergen, Bergen, Norway, 5Department of Clinical Science, University of Bergen, Bergen,
Norway, 6Department of Clinical Science, Broegelmann Research Laboratory, University of Bergen, Bergen, Norway, 7Newcastle-upon-
Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK, Newcastle-Upon-Tyne, United Kingdom, 8Musculoskeletal Research
Group, Institute of Cellular Medicine, Newcastle University, Newcastle-Upon-Tyne, UK, Newcastle-Upon-Tyne, United Kingdom, 9Dept of
Rheumatology, Skane University Hospital Malmo, Lund University, Malmö, Sweden, 10Department of Rheumatology, Skåne University
Hospital, Malmö, Sweden, Lund, Sweden, 11Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation,
Oklahoma City, OK, 12Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden, 13Rheumatology,
Department of Medical Sciences, Uppsala University, Sweden, Uppsala, Sweden, 14Clinical Immunology Unit, Department of Internal
Medicine, Stavanger University Hospital, Stavanger, Norway
SESSION INFORMATION
Background/Purpose:
Fatigue is common in primary Sjögren`s syndrome (pSS), but the mechanisms that lead to fatigue are not fully understood. We hypothesized
that there is a genetic basis for fatigue, and that specific gene-variants (single nucleotide polymorphisms – SNPs) influence the severity of
fatigue. To investigate this further we performed a genome wide association study (GWAS) of 367 Scandinavian pSS patients.
Methods:
PSS patients from 4 sites in Norway and Sweden were collected through the Scandinavian Sjögren’s syndrome network. Genotyping was
performed at the SNP&SEQ platform, Uppsala University, Sweden using the Illumina Human OmniExpressExome array. All included cases
fulfilled the American-European Classification Criteria for pSS. Fatigue was assessed using the fatigue Visual Analogue Scale or the
European Sjøgren`s Syndrome Patient Reported Index. Imputation was performed using SHAPEIT2 and IMPUTE2. After genotype and
sample quality control and imputation a total of 365 samples and 4 966 159 SNPs remained for analysis. A linear regression analysis of
fatigue scores versus minor alleles was performed.
Results:
The pSS patients were 92% females, mean age 57 years with a median fatigue score of 66 (range 0-100). Our analysis revealed five SNPs
exceeding the genome wide significance (GWS) threshold of p=5E-8 with a beta coefficient of 12.8. All five SNPs were in linkage
disequilibrium and two of the SNPs, rs7626469 and rs73182503, were in the gene Receptor Transporter Protein 4 (RTP4), in which the
minor allele was associated with less fatigue. RTP4 encodes a Golgi chaperone, involved in the cell surface expression of opioid receptors.
In addition, 58 SNPs in 4 genes (Endoplasmatic Reticulum to Nucleus Signaling 1 (ERN1), Long intergenic non-protein coding RNA 1553
(LINC01553), Long intergenic non-protein coding RNA 1184 (LINC01184) and (RP11-15I11.2) reached a suggestive significance level
(p<1E-5).
Conclusion:
We identified genetic variants in RTP4 exceeding the GWS level for association with fatigue. Notably, this gene encodes a protein involved
in pain processing. Pain is known to influence fatigue, and this finding could point to a possible molecular explanation. The present study is
the largest GWAS of fatigue in autoimmune disease, and adds further evidence to a genetic regulation of fatigue.
Disclosure: K. Norheim, None; A. Alexsson, None; J. Imgenberg-Kreuz, None; J. G. Brun, None; R. Jonsson, None; W. F. Ng, None; E.
Theander, None; T. Mandl, None; K. L. Sivils, None; L. Rönnblom, None; G. Nordmark, None; R. Omdal, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/genetic-determinants-of-fatigue-in-primary-sjogrens-

syndrome-a-genome-wide-association-study
Allele-Dependent Binding of a Viral Protein to Autoimmune Disease-Associated Genetic

Variants
Matthew Weirauch1, Daniel Miller2, Leah C. Kottyan3, Ignacio Ibarra4, Arthur Lynch2, Sayeed Syed5, Xiaoting Chen2, Erin Zoller2,
Connor Schroeder2, Josh Lee2, Albert Magnusen6, Ally Yang7, Timothy R. Hughes7, Joo-Seop Park8, Charles Vinson5 and John B.
Harley2,9, 1Center for Autoimmune Genomics and Etiology (CAGE) and Divisions of Biomedical Informatics and Developmental Biology,
Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati
Children's Hospital Medical Center, Cincinnati, OH, 3Center for Autoimmune Genomics and Etiology (CAGE), Division of Allergy and
Immunology, Cincinnati Children's Hospital, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 4Structural and Computational
Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany, 5NCI, Bethesda, MD, 6Center of Autoimmune Genomics and
Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 7University of Toronto, Toronto, ON, Canada, 8Divisions
of Urology and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 9US Department of Veterans Affairs
Medical Center, Cincinnati, OH
SESSION INFORMATION
Background/Purpose: Risk factors are known for many diseases, but the etiologies of most autoimmune diseases remain unknown and are
idiopathic. Pathogenesis of disease likely involves complex interplay between genetic and environmental risk factors. Specifically, Epstein
Barr virus (EBV) has suggestive associations with many autoimmune diseases, and EBV infection is nearly ubiquitous in adults. The
molecular mechanisms underlying these associations, however, remain unclear.
Methods: We tested the hypothesis that some autoimmune variants might act by altering the binding of the EBV-encoded transcription factor
Zta, consequently resulting in downstream changes in gene expression. To this end, we comprehensively characterized the DNA binding of
Zta to both methylated and unmethylated DNA sequences using protein binding microarrays (PBMs). Based on these data, we identified
plausible causal variants for multiple sclerosis (MS), systemic lupus erythematosus (SLE), and juvenile idiopathic arthritic (JIA) predicted
to alter Zta binding. From among these, we identified variants located within likely regulatory regions in EBV-infected B cells using
publically available functional genomic datasets. We screened these candidate variants using electrophoretic mobility shift assays (EMSAs)
to identify general differential binding of nuclear factors, and validated differential Zta binding using EMSA-supershift and DNA Affinity
Precipitation Assays coupled with Western blots (DAPA-Westerns).
Results: These experiments revealed three genetic variants, associated with MS, SLE, and JIA, respectively, exhibiting stronger Zta binding
to the risk allele. We provide data showing that each of these variants is associated with genotype-dependent expression in EBV-transformed
B cell lines. Using luciferase reporter assays, we further demonstrate that the MS risk allele in the RGS14 promoter results in greater
promoter activity, and that this activity is significantly diminished in cell lines lacking EBV.
Conclusion: Collectively, these data demonstrate for the first time that differential binding of a viral protein to a disease-associated genetic
variant can result in altered levels of host gene expression in ways that are predicted to influence autoimmune disease. Since Zta is a viral
protein, and is expressed throughout human life subsequent to EBV infection, but only in virally infected cells, these results offer a potential
therapeutic target for multiple autoimmune diseases.
Disclosure: M. Weirauch, None; D. Miller, None; L. C. Kottyan, None; I. Ibarra, None; A. Lynch, None; S. Syed, None; X. Chen, None;
E. Zoller, None; C. Schroeder, None; J. Lee, None; A. Magnusen, None; A. Yang, None; T. R. Hughes, None; J. S. Park, None; C.
Vinson, None; J. B. Harley, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/allele-dependent-binding-of-a-viral-protein-to-

autoimmune-disease-associated-genetic-variants-2
An Epigenome-Guided Approach to Causal Variant Discovery in Autoimmune Disease

Richard C. Pelikan1, Jennifer A. Kelly2, Yao Fu2, Caleb Lareau3, Graham B. Wiley1, Stuart Glenn1, Martin Aryee3,4, Courtney
Montgomery5 and Patrick Gaffney2, 1Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation,
Oklahoma City, OK, 2Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, 3Department of
Biostatistics, Harvard T.H. Chan School of Public Health, Charlestown, MA, 4Department of Pathology, Harvard Medical School, Boston,
MA, 5Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK
SESSION INFORMATION
Background/Purpose: Genome-wide association studies have identified thousands of genetic associations with complex human diseases and
traits. However, establishing the truly causal regions of risk haplotypes is complicated by the correlation of many non-causal variants to
genetic associations through linkage disequilibrium (LD). This has made translating genetic findings into functional mechanisms an
inefficient, resource-intensive task.
Methods: Here, we expedite causal variant discovery for autoimmune diseases by identifying genetic variants (epiQTLs) that leave an
epigenomic footprint of allelic imbalance in sequencing reads recovered by chromatin immunoprecipitation of enhancer marks (H3K4me1
and H3K27ac ChIP-seq). We aligned sequencing reads using the WASP pipeline to control for reference genome bias. We used the combined
haplotype test (CHT) to statistically test for robust footprints of allelic imbalance. We also characterized the three-dimensional chromatin
interaction topography among H3K27ac-marked active enhancers of our cell lines by HiChIP.
Results: We discovered a total of 6261 epiQTLs across 25 patient-derived EBV-transformed B-cell lines. We overlaid these epiQTLs onto
risk haplotypes from 21 autoimmune (AI) diseases and found that 145 reported AI risk haplotypes contained one or more of our epiQTLs. A
total of 14 epiQTL SNPs matched AI risk SNPs reported in the NHGRI GWAS catalog, while 180 epiQTLs were proxies of these reported
SNPs. We found that epiQTLs located on disease risk haplotypes disproportionately influence gene expression variance, beyond what can be
expected by random chance, over non-epiQTL variants in tight linkage disequilibrium. A majority (78%) of epiQTLs were located in
chromatin loop anchors. Using a generalized linear model, we identified 571 epiQTLs – not associated with autoimmune disease - that
modify gene expression from 68 previously established AI disease risk haplotypes through chromatin looping at FDR ≤5%. Expanding this
analysis to include both risk haplotypes and independent eQTLs increased the number of epiQTLs with significant (FDR ≤ 5%) modifier
effects on gene expression to 1062. Of these gene expression modifying interactions, 717 (68%) increased eQTL-driven gene expression by
the epiQTL, while 345 (32%) suppressed eQTL-driven gene expression.
Conclusion: Our data suggest that the epiQTL approach can facilitate the decomposition of risk haplotypes into specific regions that are
highly likely to contain functional causal variants. Moreover, epiQTLs not associated with disease haplotypes function to modify gene
expression from risk haplotypes and eQTLs through long-range allele-dependent epigenetic mechanisms.
Disclosure: R. C. Pelikan, None; J. A. Kelly, None; Y. Fu, None; C. Lareau, None; G. B. Wiley, None; S. Glenn, None; M. Aryee, None;
C. Montgomery, None; P. Gaffney, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/an-epigenome-guided-approach-to-causal-variant-

discovery-in-autoimmune-disease
Effect of Pre-Appointment Consult Triage on Patient Selection and Revenue Generation

in a University Rheumatology Practice
Sterling West1, Duane Pearson1, Christopher C. Striebich2, Ryan Goecker1 and Jason Kolfenbach1, 1Division of Rheumatology, University
of Colorado School of Medicine, Aurora, CO, 2Division of Rhuematology, University of Colorado School of Medicine, Aurora, CO
SESSION INFORMATION
Session Title: Health Services Research Poster I
Background/Purpose: Academic hospital leadership puts a priority on all patients (pts) having access to subspecialists. Often the demand
for rheumatology consultation exceeds the ability to see pts promptly. This necessitates a consult triage system to ensure timely appointments
for pts with inflammatory rheumatic diseases (IRD). The aim of this study was to evaluate the effectiveness of pre-appointment consult
screening to identify pts with potential IRD who need timely access and the revenue implications of caring for these IRD pts compared to
non-IRD pts.
Methods: During a 9 month period, all pts referred by a healthcare provider to our University rheumatology practice were screened and
classified as either possible IRD or non-IRD based on a pre-appointment records request and review by a rheumatologist. Pts with possible
IRD were scheduled for an appointment and diagnosis after clinical evaluation was recorded. Using the 2015 Medicare fee schedule, revenue
generated through the care of pts accepted for evaluation was recorded for the subsequent 12 months after initial consultation (Table 1).
Outpatient services necessary for initial diagnosis and subsequent patient monitoring were analyzed. Costs of medications, surgical
procedures, and hospitalizations were not included. Revenues between IRD and non-IRD pts were compared using a Student’s t-test. Pts
categorized as non-IRD based on pre-appointment screening and denied evaluation received subsequent care through their referring provider
and clinical outcome at one year was recorded if available.
Results: Of the 961 referrals, 673 pts (70%) were classified after consult review as possible IRD pts and scheduled for evaluation. Of the
597 pts who presented for initial evaluation (average time to first appointment 13 days, range 1-31), 357 pts (60%) were found to have an
IRD (139 RA, 83 SLE/SSc/UCTD/ Sjogren’s, 44 crystal dz, 38 spondylo, 34 vasculitis/myositis, 19 other) and 240 pts (40%) had a non-
IRD. Of the 288 pts who were denied evaluation, 128 had follow-up data for at least one year with only six (0.5%) developing an IRD. The
sensitivity of consult screening to identify IRD was 98% with a positive predictive value of 60%. Complete revenue data was available for
510 pts (318 pts with IRD, 192 pts with non-IRD); analysis demonstrated that care of pts with IRD generated 5.6 times more revenue
compared to non-IRD pts (p<0.05).
Conclusion: Pre-appointment consult screening is an effective method to identify pts with IRD. This allows for timely access to care for pts
in highest need of evaluation and for significantly more revenue generation.
Table 1: Total revenue (dollars) generated by patients with IRD versus non-IRD over 12 months
Care modality/Service IRD (318 pts) Non-IRD (192 pts)
Followup visits/Provider 68,580 1,620
fees
Labs/radiology/rheumatology 108,980 15,495
procedures
Specialty consults/PT/OT 38,500 6,300
Total 216,060; 679/pt 23,415; 122/pt
Disclosure: S.West, None; D.Pearson, None; C.Striebich, None; R.Goecker, None; J.Kolfenbach, None
Disclosure: S. West, None; D. Pearson, None; C. C. Striebich, None; R. Goecker, None; J. Kolfenbach, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effect-of-pre-appointment-consult-triage-on-patient-

selection-and-revenue-generation-in-a-university-rheumatology-practice
Paediatric Musculoskeletal (MSK) Triage in the Community – Rightpath – a Pilot Study

Nicola Smith1, Sharmila Jandial2, Jill Firth3, Helen Light3, Katharine Kinsey3, Neil Snowden3, Judith McNaught4, Tim Rapley5, Alan Nye3
and Helen E. Foster6, 1Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom, 2Paediatric
Rheumatology, Great North Children’s Hospital, Newcastle Upon Tyne, United Kingdom, 3Pennine MSK Partnership Ltd, Oldham, United
Kingdom, 4Physiotherapy, South Tyneside NHS Foundation Trust, South Shields, United Kingdom, 5Institute of Health and Society,
Newcastle University, Newcastle Upon Tyne, United Kingdom, 6Institute of Cellular Medicine and Paediatric Rheumatology, Newcastle
University and Great North Children's Hospital, Newcastle Upon Tyne, United Kingdom
SESSION INFORMATION
Background/Purpose:
We are piloting a children and young people (CYP) community-based triage (called Rightpath) based on a validated adult MSK triage model
developed by Pennine MSK Partnership Ltd (PMSKP), Greater Manchester. Rightpath aims to promptly identify CYP with MSK pathology
and triage them to the appropriate service (rheumatology, orthopaedics, neurodisability or urgent care), and to manage those who do not need
specialist referral appropriately within the community. Triage and referral guidance has been developed in partnership with MSK specialists
and this study aims to test its safety, feasibility and acceptability in the community, and through application across two geographical areas in
the UK to assess transferability.
Methods:
Piloted first at PMSKP, with iteration of the triage guidance and process followed by roll out at a second site (South Tyneside NHS Trust).
Using mixed methods, evaluation focused on key areas:
Implementation – workshops with service providers (triagers and clinicians) held at two time points to refine triage guidance and process.
Training – for triagers based on their weekly log of triage experiences and regular case based discussions and feedback.
Evaluation – (i) Parent/ patient questionnaire, incorporating the ‘Friends and Family’ test and ‘Collaborate’ (a patient reported measure of
shared decision-making), completed immediately after consultation to explore expectations and satisfaction; (ii) Service providers weekly
log documenting experiences and training needs; (iii) Routine patient data including demographic details, referral information, triage
outcome, ultimate diagnosis/outcome and communication between triage teams and health care providers; (iv) Service providers signposted
to key areas for self-directed learning (paediatric musculoskeletal matters [PMM] – www.pmmonline.org) and usage monitored.
This study had ethical approval.

Results:
Total triaged 05/09/16 - 30/04/17 (101 to Rightpath, 264 to specialist paediatric services). The most common CYP MSK referrals from the
community were knee pain, foot pain, flat feet and back pain; the most common conditions triaged to Rightpath were foot pain, knee pain, flat
feet, and in-toeing. No significant pathology has been triaged inappropriately so far to Rightpath. Feedback from 66 Rightpath family
participants was positive (no complaints or requests for onward specialist referral); 100% would recommend the service, with satisfaction
(1-10) scores about community providers being high (1=’no’ and 9=’every’ effort made); ‘helped understand your/your child's health
issues’ (8.9), ‘listened to things that matter most to you about your/your child's health’ (8.9), ‘included what matters most to you in
choosing what to do next’ (8.9). Community therapists and podiatry described the clinical workload to be appropriate for their existing
skills. Triage staff deemed the triage process manageable (57% of decisions ‘easy/very easy’) and triage guidance to be useful commenting
that paediatric experience was important to support decision-making.
Conclusion:
Initial data shows Rightpath to be feasible, safe and acceptable. Phase 2 of the pilot is in progress at the second site.
Disclosure: N. Smith, None; S. Jandial, None; J. Firth, None; H. Light, None; K. Kinsey, None; N. Snowden, None; J. McNaught, None;
T. Rapley, None; A. Nye, None; H. E. Foster, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/paediatric-musculoskeletal-msk-triage-in-the-community-

rightpath-a-pilot-study
Improved Identification of Pseudogout in Electronic Medical Records By Adding Text

String Searching to a Billing Code Algorithm
Sara K. Tedeschi, Kazuki Yoshida and Daniel H. Solomon, Division of Rheumatology, Immunology and Allergy, Brigham and Women's
Hospital, Boston, MA
SESSION INFORMATION
Background/Purpose: Calcium pyrophosphate deposition disease (CPPD) has a spectrum of manifestations, of which pseudogout is the most
acute inflammatory phenotype. To facilitate clinical research on CPPD, an ICD-9 algorithm for “definite or probable CPPD” (per Ryan and
McCarty’s diagnostic criteria) was developed at a Veterans’ Administration (VA) Medical Center.1 The algorithm includes ≥1 ICD-9 code
275.49 (“other disorders of calcium metabolism”) or 712.1-712.39 (“chondrocalcinosis” due to dicalcium phosphate crystals, pyrophosphate
crystals, or cause unspecified). We hypothesized that the algorithm would be suboptimal for identifying pseudogout, and aimed to enhance its
ability to identify pseudogout in electronic medical records (EMR).
Methods: Following the published methods, we applied the ICD-9 algorithm to patients with ≥1 encounter at our non-VA academic medical
center over 2 years (1/1/15-12/31/16). 100 patients were randomly selected for EMR review from date of 1st qualifying ICD-9 code through
5/1/17. We evaluated whether patients fulfilled each of 3 clinical definitions: “definite or probable CPPD”—which the algorithm was
designed to identify—and 2 pseudogout definitions (Table). We calculated the positive predictive value (PPV) and 95% confidence intervals
(CI) of the ICD-9 algorithm for identifying each phenotype. We then modified the ICD-9 algorithm to include text string searching for
“pseudogout” or “calcium pyrophosphate crystals” in narrative notes and re-assessed test performance characteristics.
Results: 55% of 100 patients were female; mean age was 68.6 (±13.9) years. Joint pain was present in 86% and synovitis in 34%. The
published algorithm had 68% (59-77%) PPV for “definite or probable CPPD” in our sample (Table), compared to 91% (88-94%) PPV in
the VA derivation study. The published algorithm identified only 18% (10-26%) of patients with crystal-proven pseudogout. In our sample of
100 patients, 50 had a positive text string search. Of these, 17 had crystal-proven pseudogout per EMR review, producing a PPV of 34% (25-
43%) and NPV of 98% (95-100%). Text string searching was 94% sensitive (89-99%) and 60% specific (50-70%) for crystal-proven
pseudogout in the sample.
Conclusion: Adding text string searching to a published ICD-9 CPPD algorithm improved PPV for identifying crystal-proven pseudogout
from 18% to 34%, with excellent sensitivity and moderate specificity. The accuracy of identifying pseudogout in EMR data might be further
improved using more advanced text searching methodology, such as natural language processsing.
1. Bartels C, Singh J, Parperis K, et al. Validation of administrative codes for calcium pyrophosphate deposition. J Clin Rheum 2015;21:189-
92
2. Zhang W, Doherty M, Bardin T, et al. EULAR recommendations for calcium pyrophosphate deposition. Ann Rheum Dis 2011;70:563-70
Positive predictive value (PPV) of a published ICD-9 algorithm* for identifying CPPD or
pseudogout in an electronic medical record dataset
Phenotype PPV% (95% CI) for phenotype
Published CPPD definition
Ryan and McCarty “definite or probable
CPPD”** 68 (59-77)#
Pseudogout definitions
Crystal-proven pseudogout+ 18 (10-26)
Modified EULAR acute CPP crystal arthritis++ 25 (17-34)
*Algorithm for Ryan and McCarty “definite or probable CPPD”: ≥1 ICD-9 code 275.49 or 712.1-
712.39
#PPV 91% reported by Bartels et al.1 at Milwaukee VA Medical Center
**Joint pain, and either synovial fluid with calcium pyrophosphate crystals or chondrocalcinosis in
any joint, or both
+Synovitis (pain, swelling and tenderness) in the affected joint and synovial fluid with calcium
pyrophosphate crystals
++Synovitis in the knee, wrist or shoulder reaching maximum intensity in 6-24 hours and either (1)
age >65 or (2) chondrocalcinosis in any joint. Modified from Zhang et al.2
Disclosure: S. K. Tedeschi, None; K. Yoshida, None; D. H. Solomon, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/improved-identification-of-pseudogout-in-electronic-

medical-records-by-adding-text-string-searching-to-a-billing-code-algorithm
Lupus Low Disease Activity State Is Associated with Reduced Direct Medical Costs in
Patients with Systemic Lupus Erythematosus
Ai Li Yeo1, Rachel Koelmeyer2, Rangi Kandane-Rathnayake1, Vera Golder2, Alberta Y. Hoi2, Edward R. Hammond3, Henk Nab4, Molla
Huq5, Mandana Nikpour6 and Eric F Morand7, 1Rheumatology, Monash University, Melbourne, Australia, 2Centre for Inflammatory
Diseases, Monash University, Melbourne, Australia, 3AstraZeneca, Gaithersburg, MD, 4AstraZeneca, Cambridge, United Kingdom,
5Department of Medicine (Rheumatology), Melbourne University, Melbourne, Australia, 6Melbourne University, Melbourne, Australia,
7Monash University, Melbourne, Australia
SESSION INFORMATION
Background/Purpose: High health care utilization and direct costs have been documented in multiple studies of SLE. The recently described
lupus low disease activity state (LLDAS) has been associated with reduced flares and damage accrual. We hypothesized that LLDAS
attainment would be associated with reduced healthcare cost.
Methods: This study utilized data from a single tertiary centre cohort of SLE patients (ACR criteria) between October 2013 and June 2016.
Baseline demographics, and per visit disease activity (SLEDAI-2K, physician global and flare index) and medication use were matched to
healthcare utilization and cost data obtained from hospital information systems. LLDAS was defined as described (Franklyn K, et al. Ann
Rheum Dis 2016;75:1615). Statistical analyses were performed using Stata version 14.
Results: 200 SLE patients (88% female, median age 42 years) were followed for 357.8 person-years. A history of lupus nephritis was
present in 42%, anti-dsDNA antibodies in 70%, and SLICC damage index (SDI)>0 at study commencement in 57.3%. During the observation
period, median (range) time adjusted mean SLEDAI was 4.0 (0–16.9), there were 571 hospitalizations (24.2% multi-day), and 31% of
patients had at least one emergency room attendance. The mean (standard deviation) annual direct medical cost per patient was US$7,413
(US$13,133)/year. Patients in the highest quartile of annual cost were more likely to accrue new damage during the observation (34 vs 11%,
p<0.001) and had significantly more physician visits, hospitalizations, and emergency room visits (all p<0.001). Mean annual costs were
significantly greater in patients with baseline SLEDAI >6 or SDI>0, or who during observation had time-adjusted mean SLEDAI >6, renal
disease activity, or used corticosteroids (all p<0.01). In multivariable analysis, baseline organ damage, and moderate–high corticosteroid use
(>7.5 mg/day) were significantly associated with increased cost (see table). In contrast, meeting LLDAS criteria for >50% of the observed
time was associated with a 25% reduction in annual direct medical cost (p=0.041).
Association of LLDAS with Annual Direct Medical Cost

Multivariable Association with Annual Direct
Medical Cost#
Estimated
Increment/ Estimated
Parameter Ratio of Decrement Incremental/
P Value for in Annual Decremental
Geometric
Association Direct in Annual
Means
Cost Direct Cost
(US$)
(%)
>50% time spent in 0.74 0.041 -25.6 -895
LLDAS
Treatment
Annual
prednisolone
dosage
Low dosage (≤7.5 1.0
mg/day)
Moderate dosage 1.56 0.018 56.5 1975
(>7.5–15 mg/day)
High dosage (>15 3.0 <0.001 203.7 7123
mg/day)
Damage
Organ damage 1.43 0.008 42.7 1493
present at baseline
#Adjusted for variables in table and geographic distance from the treating centre.
Conclusion: As in previous studies, baseline organ damage, high disease activity, and corticosteroid use were associated with increased
cost. Our findings demonstrate that LLDAS attainment is associated with significantly reduced health care cost among patients with
SLE.#Adjusted for variables in table and geographic distance from the treating centre.
Disclosure: A. L. Yeo, None; R. Koelmeyer, None; R. Kandane-Rathnayake, None; V. Golder, None; A. Y. Hoi, None; E. R. Hammond,
AstraZeneca, 3; H. Nab, AstraZeneca, 3; M. Huq, None; M. Nikpour, None; E. F. Morand, AstraZeneca, 2,AstraZeneca, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/lupus-low-disease-activity-state-is-associated-with-

reduced-direct-medical-costs-in-patients-with-systemic-lupus-erythematosus
Challenges and Opportunities of Implementing a Patient-Reported Measure of Physical

Function through an Online Electronic Health Record Patient Portal in Routine
Rheumatology Practice
Jing Li1, Jinoos Yazdany2, Laura Trupin2, Zara Izadi3, Milena Gianfrancesco1, Sarah Goglin1 and Gabriela Schmajuk4,
1Medicine/Rheumatology, University of California, San Francisco, San Francisco, CA, 2Medicine/Rheumatology, University of California
San Francisco, San Francisco, CA, 3Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, 4San
Francisco VA Medical Center, University of California San Francisco, San Francisco, CA
SESSION INFORMATION
Background/Purpose:
Despite significant interest in the collection of patient-reported outcomes (PROs) to make care more patient-centered, few studies have
evaluated implementation efforts to collect PROs in real-world practice settings that serve diverse patient populations. In this study, we
assessed the collection of PROs from rheumatoid arthritis (RA) patients in an academic rheumatology clinic, using a paper form and
subsequently, an online form through the electronic health record (EHR) patient portal.
Methods:
We identified patients seen at the clinic from June 2012-July 2016 with at least 2 face-to-face encounters with a rheumatology provider and
ICD codes for RA, ≥30 days apart. In February 2013, the clinic implemented a paper version of the Patient Reported Outcome Measurement
Information System (PROMIS) physical function (PF) form that was administered to patients upon their check-in at the clinic; in January
2015, an online version of the form became available via the EHR patient portal to patients with active portal accounts. We queried our
EHR’s SQL server to obtain demographic information, paper and online PROMIS scores, and their dates of completion. We compared the
proportion of visits with documented PROMIS scores across age, race/ethnicity, and language, using chi-square and ANOVA tests and p-
chart.
Results:
We included 1,078 patients with RA with 7,049 in-person encounters at the rheumatology clinic over 4 years, with an average of 168
visits/month. 80% of patients were female; mean age was 55 (SD 16). Overall PROMIS PF score documentation increased from 60% of
visits in 2013 to 74% in 2016. Online score documentation increased from 10% in 2015 to 19% in 2016 (Figure 1). Most users of the online
form used it only once, reverting to the paper form in subsequent visits. African Americans were less likely to have any PROMIS PF
recorded (63% vs. 81% for other racial groups, p<0.001). Compared with Whites, both African American and Hispanics were less likely to
have active online EHR portal accounts (50% and 57% respectively, vs. 84% of Whites; p<0.001) and, once activated, less likely to use the
online survey (14% and 18% respectively, vs. 31% of Whites; p=0.02). There was no significant difference in the proportion of any PROMIS
PF recorded between Non-English vs. English speakers. However, Non-English speakers were less likely to use the online survey, likely
because the online survey existed only in English (7% vs. 23% of English speakers; p<0.001). No significant differences were found across
age or gender.
Conclusion:
PROMIS PF form completion improved overall over 4 years, but lagged among racial/ethnic minorities and non-English speaking patients.
Future studies should address issues of portal access, enrollment, satisfaction and persistence, and focus on developing PRO implementation
strategies that accommodate the needs and preferences of diverse populations.
Disclosure: J. Li, None; J. Yazdany, None; L. Trupin, None; Z. Izadi, None; M. Gianfrancesco, None; S. Goglin, None; G. Schmajuk,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/challenges-and-opportunities-of-implementing-a-patient-

reported-measure-of-physical-function-through-an-online-electronic-health-record-patient-portal-in-routine-rheumatology-practice
Opioid Dispensation Among Systemic Lupus Erythematosus (SLE) Patients Who

Persistently Frequent the Emergency Department (ED)
Jiha Lee 1, Lisa Gale Suter2,3 and Liana Fraenkel3,4, 1Rheumatology, Yale University School of Medicine, New Haven, CT, New Haven,
CT, 2Medicine, Rheumatol., TAC S541, Rheumatology, VA Connecticut Healthcare System, West Haven, CT, New Haven, CT,
3Rheumatology, Rheumatology, Yale University School of Medicine, New Haven, CT, New Haven, CT, 4Medicine, Section of
Rheumatology, Rheumatology, VA Connecticut Healthcare System, West Haven, CT, New Haven, CT
SESSION INFORMATION
Background/Purpose: Patients who persistently frequent the ED are more likely to be prescribed opioids for pain, and opioid initiation in
the ED has been found to increase the risk of long-term opioid therapy (LOT). Pain is frequently experienced by SLE patients, and a major
cause of ED use. We sought to understand the prevalence of, and factors associated with opioid dispensation among SLE patients who
persistently frequent the ED to identify opportunities to improve quality of care.
Methods: We identified SLE patients who persistently frequented the ED from 2013-2016 at a large urban academic medical center.
Persistent use was defined as having three or more ED visits during the 12 months in a calendar year, for at least two out of the four years,
consecutive or non-consecutive, during the study period. We collected patient-level variables including demographics and LOT use. Each
encounter was categorized as either SLE-, infection-, pain-related or other. Additional encounter-level variables such as healthcare resource
utilization and disposition were recorded. We used mixed effects logistic regression to analyze patient- and encounter-level factors
associated with opioid administration in the ED and opioid prescription upon discharge from the ED. Variables with p-value <0.1 in
univariate analysis were included in a multivariate model.
Results: Seventy-seven SLE patients had 1143 ED encounters. Opioids were administered in the ED for 38.4% of all encounters. In
multivariate analysis, Medicaid, LOT use, MD as the ED provider (proxy measure for higher acuity), more imaging tests, and rheumatology
evaluation were associate with increased odds of opioid administration in the ED (Table 1). Opioids were prescribed on discharge for
16.8% of encounters discharged from the ED. In multivariate analysis, African American patients, those on Medicaid, and patients utilizing
the ED for SLE-related activity/complications were more likely to receive an opioid prescription upon discharge from the ED, than their
respective counterparts (Table 2).
Conclusion: Opioids are commonly dispensed from the ED for SLE patients, even for those utilizing the ED for lupus-related
activity/complications. Further study is warranted to inform how best to decrease opioid use in SLE patients both in the ED and upon
discharge.
Disclosure: J. Lee, None; L. G. Suter, CMS, 3; L. Fraenkel, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/opioid-dispensation-among-systemic-lupus-

erythematosus-sle-patients-who-persistently-frequent-the-emergency-department-ed
Is the Nature of Rheumatology Practice Changing? Damage and Distress Contribute a

Greater Proportion to Decision-Making Than Inflammation in Contemporary Care
Theodore Pincus1, Isabel Castrejón2 and Joel A Block2, 1Rheumatology, Rush University Medical Center, Chicago, IL, 2Division of
Rheumatology, Rush University Medical Center, Chicago, IL
SESSION INFORMATION
Background/Purpose: Inflammation generally is regarded as the primary concern of rheumatologists, and measures of inflammation, such as
laboratory tests and pooled indices, usually are the only quantitative data recorded in routine care. Structural damage to joints and other
organs, as well as patient distress seen as fibromyalgia, depression, etc., are recognized, but not quantitated routinely in clinical care. In
recent years, advances in control of inflammation, along with increases of degenerative diseases in an aging population, and recognition of a
high prevalence of fibromyalgia, may have shifted rheumatology patient mix and decision-making more toward damage and distress vs
inflammation. We sought to analyze the importance of inflammation, damage, and distress in care of individual rheumatology patients, by
quantifying levels on 0-10 visual analog scales (VAS) and estimating their relative contributions to management decisions.
Methods: As part of routine care, rheumatologists at one academic site complete a 0-10 physician global assessment (DOCGL) VAS, as
well as 3 further 0-10 VAS to assess inflammation (reversible disease) (DOCINF), joint and other organ damage (irreversible disease)
(DOCDAM), and patient distress (fibromyalgia, depression), etc. (DOCSTR). The proportion of clinical management decisions attributed to
inflammation, damage, and distress (total=100%) also is estimated. Mean values were analyzed in a cross-sectional study of 570 patients,
and compared in subgroups of 98 with rheumatoid arthritis (RA), 131 with osteoarthritis (OA) and 89 with fibromyalgia (FM), using t tests
and analysis of variance (ANOVA).
Results: Mean 0-10 DOCGL scores were 4.4 in all patients, 4.4 in OA, 4.6 in RA, and 5.2 in FM (Table) (p=0.04). Highest mean scores
were seen for DOCINF in RA, DOCDAM in OA, and DOCSTR in FM, and differing significantly in each diagnosis (Table), confirming face
validity. Importantly, damage VAS scores (DOCDAM) were higher than inflammation (DOCINF) scores in all groups, including in RA, and
mean estimates of the proportion of clinical management decisions attributed primarily to damage were greater than to inflammation in all
conditions (Table). Scores for DOCSTR were higher than for DOCINF in all patients and subgroups, other than in RA.
Mean VAS Scores and % of clinical management decision attributed to inflammation, damage, and distress in patients with rheumatic
diseases
ALL RA OA FM P*
N 570 98 131 89
Mean VAS
Scores
VAS DOCGL 4.4 (1.6) 4.6 (1.8) 4.4 (1.5) 5.2 (1.6) 0.04
VAS DOCINF 1.8 (2.0) 2.8 (2.4) 0.7 (1.1) 0.8 (1.3) <0.001
VAS DOCDAM 3.1 (2.2) 3.8 (2.3) 4.4 (1.8) 1.7 (1.9) <0.001
VAS DOCSTR 2.1 (2.9) 1.2 (2.2) 1.5 (2.5) 6.0 (2.5) <0.001
P (DOCINF vs 0.001 0.01 <0.001 <0.001
DOCDAM)
P (DOCINF vs 0.11 <0.001† <0.001 <0.001
DOCSTR)
Mean % of clinical management decision attributed to...
%inflammation 29 (31) 39 (29) 12 (19) 6 (11) <0.001
%damage 48 (35) 52 (30) 73 (31) 18 (23) <0.001
%distress 22 (34) 9 (20) 15 (27) 76 (27) <0.001
*ANOVA - RA vs OA vs FM
† -only comparison in which DOCINF higher than DOCSTR
Conclusion: Physician VAS scores and attributions to clinical decisions in individual patients were higher for damage than for inflammation
in all groups seen in a rheumatology setting, even in RA patients as a group. Control of inflammation remains the primary concern for
rheumatologists, but has improved considerably in recent years, as damage and distress may have become more prominent in routine patient
care, and systematic quantitation appears of value.
Disclosure: T. Pincus, Theodore Pincus, 7; I. Castrejón, None; J. A. Block, None.

View Abstract and Citation Information Online - http://acrabstracts.org/abstract/is-the-nature-of-rheumatology-practice-changing-damage-
and-distress-contribute-a-greater-proportion-to-decision-making-than-inflammation-in-contemporary-care
Patient Education Materials in Rheumatology: Only Adequate at Best

Aleksander Lenert1 and Sujin Kim2, 1Internal Medicine, Div. of Rheumatology, University of Kentucky, Lexington, KY, 2Division of
Biomedical Informatics, College of Medicine, University of Kentucky, Lexington, KY
SESSION INFORMATION
Background/Purpose: Low health literacy and reading ability of rheumatologic patients is associated with poor outcomes [1]. In practice,
patient education is commonly delivered via patient education materials (PEMs). However, readability of PEMs has been reported to be high
and PEMs remain poorly understood [2]. We sought to determine the suitability of PEMs used in rheumatology practice.
Methods: Sixteen PEMs from 2 resources (ACR 2015 & UpToDate Basics 5-2017) were analyzed. PEMs on 4 diseases (OA, RA, SLE,
vasculitis) and 4 treatments (abatacept, hydroxychloroquine, NSAIDs, rituximab) were scored for clinical complexity by 16 clinical
rheumatologists. Suitability assessment of materials (SAM), a validated method to assess health-related educational resources, was used to
score PEMs by 3 reviewers [3]. SAM scores were categorized and mean scores reported. Readability was measured by validated methods.
PEMs were additionally assessed with 2 novel tools: information entropy and medical subject heading (MeSH) complexity. These methods
provide further insight into information quantity and content complexity of PEMs. We compared means for ACR and UpToDate PEMs by
Student t-test (1-sided alpha=0.05).
Results: Sixteen PEMs were rated by SAM: 3 were superior (with 2/3 on OA) and 13 were adequate (Figure 1). The mean SAM score for
disease-PEM was highest for OA and lowest for vasculitis, and for therapy-PEM was highest for NSAIDs and lowest for abatacept. Mean
SAM, information entropy and MeSH complexity scores did not significantly differ between ACR and UpToDate (p>0.05) (Table 1).
Readability was at 6th grade for only 4 PEMs (all UpToDate) while it was >8th grade level for 12 PEMs; 4 ACR PEMs had readability
>12th grade. Mean readability grade was significantly higher for ACR compared to UpToDate (p=0.002).
Conclusion: The suitability of PEMs in rheumatology is adequate at best for less complex topics but remains low for clinically complex
topics. The majority of PEMs exceed the recommended 6th-grade reading level, especially PEMs by ACR. Development of personalized
PEMs in rheumatology is needed to improve patient health literacy and impact outcomes.
References:
1. Hirsh JM, et al. Limited health literacy is a common finding in a public health hospital's rheumatology clinic and is predictive of disease
severity. J Clin Rheumatol. 2011 Aug;17(5):236-41.
2. Rhee RL, et al. Readability and suitability assessment of patient education materials in rheumatic diseases. Arthritis Care Res (Hoboken).
2013 Oct;65(10):1702-6.
3. Doak CC, et al. Teaching patients with low literacy skills. 1985. Lippincott.
Disclosure: A. Lenert, None; S. Kim, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/patient-education-materials-in-rheumatology-only-

adequate-at-best
Evaluation of a Diversionary Back Pain Service

Lynden Roberts, Rheumatology, Monash Medical Centre, Clayton, Australia
SESSION INFORMATION
Background/Purpose: Surgical treatment of spinal pain is rarely indicated. Nevertheless, primary care clinician referrals to spinal surgeons
for evaluation of spinal pain conditions are common. In the publicly funded hospital system in Australia, more than 90% of those referred to
spinal surgeons with back pain do not receive surgery. It may be more appropriate for many people with spinal pain to be diagnosed and
managed under a different model of health care.
Methods: A weekly spinal pain clinic was established at a publicly funded hospital. The clinic was staffed by a rheumatologist and 4
physiotherapists. All spinal pain referrals to the hospital’s spinal surgeons were diverted to the new clinic, with the exception of referrals
assessed as likely spinal cord compression or cauda equina syndrome. Patients with previously diagnosed chronic spinal pain were not seen
in the new clinic. Clinical and administrative data was prospectively and routinely collected including clinical diagnosis, Short Form of the
Örebro Musculoskeletal Pain Screening Questionnaire, and clinical outcomes including whether spinal surgery was done. An 11-point Likert
scale (0-10) was used to collect the patient satisfaction with the clinic following the encounter.
Results: A total of 575 face-to-face patient encounters occurred in the first 12 months of the service including 363 new patients. Low back
pain with radiculopathy was the commonest diagnosis. Average Örebro score was 67%. The failure-to-attend rate was 7%. Nearly half of the
patients were discharged to community physiotherapy management, 2% to a chronic pain service, and 9%to a spinal surgeon. For patients
referred to a spinal surgeon, 80% underwent spinal surgery. Average patient satisfaction was 9.2.
Conclusion: A novel model of care involving the substitution of spinal surgeons with a rheumatologist and physiotherapists for the
assessment of patients with spinal pain was established. The patients assessed had a high estimated risk for future work disability. Efficient
clinical care and a high patient satisfaction was demonstrated.
Disclosure: L. Roberts, None;
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/evaluation-of-a-diversionary-back-pain-service
Kinesiophobia Moderates the Association between Anxiety and Disability in Chronic

Low Back Pain
Jenna Goesling1, Stephanie Moser2, Jennifer Pierce1 and Christian Bolton3, 1Department of Anesthesiology, University of Michigan, Ann
Arbor, MI, 2Anesthesiology, University of Michigan, Ann Arbor, MI, 3University of Michigan, Ann Arbor, MI
SESSION INFORMATION
Background/Purpose:
· Low back pain is a debilitating and costly condition with complex biological, psychological, and social factors contributing to the
development of chronic low back pain (CLBP).
· Kinesiophobia is defined as an “excessive, irrational, and debilitating fear of physical movement and activity resulting from a feeling
of vulnerability to painful injury or re-injury” (1).
· According to cognitive behavioral models of fear and avoidance, maladaptive thoughts may lead to avoiding activity, which in turn
may lead to illness behavior and increased disability.
· Previous research suggests that depression, anxiety and kinesiophobia contribute to pain perception and physical function.
· Yet, little is known about how kinesiophobia and anxiety and depression may interact to predict disability.
· The objective of the present study was to explore the moderating effect of kinesiophobia on the relationship between depression and
anxiety and disability in a sample of adults with chronic low back pain (CLBP).
Methods:
· The study included 283 new patients seeking treatment for chronic pain.
· New patients completed the Oswestry Disability Index, the Hospital Anxiety and Depression Scale, and the Tampa Scale of
Kinesiophobia (TSK). High kinesiophobia was defined as a score greater than 37 on the TSK.
Results:
· High kinesiophobia was reported in 64% (N=181) of participants.
· Kinesiophobia, depression and anxiety were associated with greater disability.
· The moderated effect of depression was nonsignificant.
· Kinesiophobia modified the association between anxiety and disability (Table 1). Namely, anxiety contributed to greater disability at
high levels, but not low levels, of kinesiophobia (Figure 1).
Conclusion:
· Kinesiophobia, anxiety, and depression were associated with greater disability. However, kinesiophobia moderated the relationship
between anxiety and disability, such that having anxiety and high kinesiophobia was associated with a worse outcome.
· Kinesiophobia and anxiety are both modifiable psychological factors that can be addressed using cognitive restructuring and exposure
based behavioral interventions.
References:
· Kori, S. H., et al. (1990). Kinisophobia: A new view of chronic pain behavior. Pain Management, 3, 35-43.
Disclosure: J. Goesling, NIH Project #1K23DA038718-01A1, 2; S. Moser, None; J. Pierce, None; C. Bolton, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/kinesiophobia-moderates-the-association-between-

anxiety-and-disability-in-chronic-low-back-pain
Health Care Costs of Patients with Systemic Lupus Erythematosus (SLE) Versus
Control Patients As a Function of Disease Severity: Analysis of the
Betriebskrankenkassen German Sickness Fund
Edward R. Hammond1, Heiko Friedel2, Elena Garal-Pantaler2, Marc Pignot3, Erica Velthuis4, Xia Wang1, Henk Nab5, Barnabas Desta1
and Andreas Schwarting6, 1AstraZeneca, Gaithersburg, MD, 2Team Gesundheit GmbH, Essen, Germany, 3Kantar Health GmbH, Munich,
Germany, 4Evidera PPD, Utrecht Area, Netherlands, 5AstraZeneca, Cambridge, United Kingdom, 6Universitätsmedizin der Johannes
Gutenberg-Universität Mainz, Mainz, Germany
SESSION INFORMATION
Background/Purpose: SLE is a chronic, debilitating, multisystem autoimmune disorder of connective tissue. In developing new treatment
options, the economic burden of SLE should be quantified as a function of disease severity.
Methods: Anonymized data from the Betriebskrankenkassen (BKK) German Sickness Fund Database were used to perform analyses of real-
world claims of patients (pts) with SLE. Health care utilization and resource use and costs were assessed annually for 2009–2014 for
confirmed pts with SLE identified in 2009 (using repeated claims with SLE diagnosis, co-diagnosis codes, laboratory tests, or prescription
treatment and specialty of diagnosing physician) and compared with those of matched controls. Pts were ≥18 years of age and had data
available for 2009 and ≥3 years prior to index quarter in 2009. SLE cases were matched to controls by age, sex, and baseline Charlson
Comorbidity Index (CCI). Continuous outcomes were compared with a nonparametric test (e.g., Wilcoxon–Mann-Whitney), because most
outcome distributions were positively skewed.
Results: Of the 3,290,701 persons with evidence of 3 years of insurance prior to 2009, 1,228 were identified as SLE cases in 2009,
representing a prevalence of 37.32 per 100,000 and an incidence of 5.96/100,000 per year. The prevalence increased during the next 5 years
to 47.36 per 100,000 in 2014. The final sample included 1,160 confirmed pts with SLE who were ≥18 years of age and had data for 2009.
Pts with SLE were 84% female, and had a mean age of 52 years and a baseline CCI range of 1–13. 85% who qualified for the cohort in 2009
had already been diagnosed with SLE before 2009. A combined approach of International Classification of Diseases-10 GM and
medication/procedures codes classified SLE disease severity as mild for 148, moderate for 484, and severe for 528 pts. Pts with SLE had
significantly greater mean annual total medical costs in 2009 than did matched controls (€6,895 vs. €3,692, p<0.0001), and in all subsequent
years evaluated. Moreover, pts with moderate and severe SLE had significantly greater mean annual total medical costs in 2009 than did
matched controls (moderate SLE: €4,867 vs. €3,380, p<0.0001; severe SLE: €10,001 vs. €4,239, p<0.0001), and in all subsequent years.
Mean costs and numbers of outpatient visits, hospital stays, outpatient prescriptions and other benefits, and total number of hospital days,
were significantly greater for the full SLE population and the moderate and severe SLE subpopulations than for matched controls. For
example, mean costs for hospital stays, outpatient prescriptions, and other benefits in 2009 were €4335 vs. €1414, €2582 vs. €1087, and
€1068 vs. €691, respectively, for pts with mild, moderate and severe SLE vs. controls.
Conclusion: In this analysis, the economic burden of moderate and severe SLE was greater than that of socio-demographically and
morbidity–adjusted controls. Pts with SLE were greater users of the health care system and incurred greater total annual medical costs than
did matched controls. Health care utilization by pts with SLE increased with disease severity, with the greatest burden for those with severe
SLE. New treatments could reduce health care resource use and help alleviate economic burden.
Disclosure: E. R. Hammond, AstraZeneca, 3; H. Friedel, None; E. Garal-Pantaler, None; M. Pignot, None; E. Velthuis, None; X. Wang,
AstraZeneca, 3; H. Nab, AstraZeneca, 3; B. Desta, AstraZeneca, 3; A. Schwarting, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/health-care-costs-of-patients-with-systemic-lupus-

erythematosus-sle-versus-control-patients-as-a-function-of-disease-severity-analysis-of-the-betriebskrankenkassen-german-sickness-fund
Patient Assistance Program Outcomes in a Community Clinic Setting

Stephanie Cerritos1, Yanira Ruiz-Perdomo1, Natalie Tobar1, Ann Biehl2 and James D. Katz3, 1National Institute of Arthritis and
Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 2Department of Pharmacy, National Institutes of Health
Clinical Center, Bethesda, MD, 3National Institute of Arthritis, Musculoskeletal and Skin Disease (NIAMS), Bethesda, MD
SESSION INFORMATION
Background/Purpose:
Uninsured rheumatic disease patients are at risk for inadequate treatment due to issues with access to care, such as medication costs that
average at least $1659/patient/10 weeks (Costs for medications obtained using government prime vendor pricing). Pharmaceutical companies
created patient assistance programs (PAPs) as one way to address these barriers. However, the process of getting assistance is resource-
intensive because eligibility requirements are not standardized across these foundations. This study aims to understand one aspect of direct
care costs in a community health clinic population.
Methods:
A clinical team was created to aid patients needing assistance for high-cost biologics. Patients were followed for about a year. We
determined the rates of successful PAP approvals and stratified our analysis based on a diagnosis of Rheumatoid Arthritis (RA) or Other
Autoimmune diseases (OTHER). We also catalogued reasons why some patients were unable to renew enrollment.
Results:
Data collected from 6/2016-5/2017 revealed a 94% PAP success rate for our patients with identified need (Table 1). RA patients had a 93%
success rate. Success rates were higher in OTHER patients. PAP denial was often due to inadequate income documentation. Delay was
often due to eligibility for Medicaid/Medicare.
Table 1. Biological Therapy Access Rates

Category Patients in need (#) Successful Procurement Rate
(#)
All Patients 75 71 94.6%
RA 59 55 93.2%
Other Autoimmune 16 16 100%
Furthermore, analysis of patients enrolled in PAP from 6/2016-5/2017 revealed a 68% renewal success rate. Reasons for lack of renewal
were: newly acquired health insurance, personal choice, insufficient income documentation, and enrollment in Medicare. Overall savings for
our patient population, was estimated to be $1.2 million per year. Our teams invest in counseling time with the patient, phone time with
sponsoring foundations, computer resources for implementing a program renewal database, and pharmacy handling of infusion medications.
Conclusion:
This study addresses the impact of a dedicated effort, within a community clinic setting, to expedite access to medications through a
streamlined PAP. Outpatient drug costs for rheumatic diseases are important to target when containing overall direct health care costs. Our
observations take this further to show a dedicated health care team can assist limited resource patients with accessing high cost biologics.
Benefits from our program extend beyond immediate financial relief – there is educational value for rheumatology trainees and protected free
time for clinical pharmacists which can used for teaching, clinical oversight, and academic scholarship.
In conclusion, investing resources to support individuals with limited resources in securing of assistance is a successful endeavor. Further
research is necessary to capture the downstream benefits of this effort.
Disclosure: S. Cerritos, None; Y. Ruiz-Perdomo, None; N. Tobar, None; A. Biehl, None; J. D. Katz, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/patient-assistance-program-outcomes-in-a-community-

clinic-setting
Process Evaluation of the Making It Work Program, an Online Program to Help People
with Inflammatory Arthritis Remain Employed
Kathy Tran1, Xi yuan Li2, Xiang Chuin Seah3, Catherine Backman4, Brendan vanAs3, Pam Rogers2, Monique Gignac5, John M. Esdaile3,
Carter Thorne6, Linda Li2 and Diane Lacaille 7, 1Simon Fraser University, Arthritis Research Canada, Richmond, BC, Canada,
2Rheumatology, Arthritis Research Canada, Richmond, BC, Canada, 3Arthritis Research Canada, Richmond, BC, Canada, 4Rehab Medicine,
University of British Columbia, Richmond, BC, Canada, 5Instititue for Work and Health, Toronto, ON, Canada, 6University of Toronto,
Newmarket, ON, Canada, 7University of British Columbia, Arthritis Research Canada, Richmond, BC, Canada
SESSION INFORMATION
Background/Purpose:
Inflammatory arthritis (IA) commonly affects ability to work, yet few arthritis services exist addressing employment. We report on the
process evaluation of the Making it Work program, an online self-management program to help people with IA deal with employment issues,
performed in the context of a RCT testing its effectiveness at preventing work disability and improving at-work productivity.
Methods: Participants, recruited from rheumatology practices, a consumer organization (Arthritis Consumer Experts) and advertisements,
were eligible if they had IA, were currently employed, aged 18-59, concerned about their ability to work. The program consists of five e-
learning modules; five on-line group meetings using video conferencing led by a vocational rehabilitation counsellor (VRC); individual
consults with an occupational therapist (OT) for an ergonomic work assessment and with a VRC.
Results:
All program participants by 06/17 were included (N=236) [80% female, mean(SD) age: 45(10) years, RA:52%, AS:19%, PsA:15%,
SLE:14%]. All participants Jan-Dec 2016 completed a feedback survey post program (n=69). Group meetings were successfully conducted
online. Overall, participation was good. Median(25;75Q) no. group meetings attended: 4(3;5), with highest attendance in the first (86%) and
lowest in the fourth (63%) meetings. Reasons for not attending included work obligations, health issues, family commitments, or other time
constraints. 91% and 88% met with the OT and VRC. Completion of e-learning modules [Median(25;75Q) % of total slides viewed] ranged
from 73(0-100)% for module 4, to 100(30;100)% for modules 1 & 2. Not all content is relevant to all, depending on disease and job
characteristics.
Overall, participants were highly satisfied with the program. 94% would recommend it to others. Median [25Q;75Q] usefulness ratings (0-
10, 0=not at all, 10=very useful) were: 8 [7;10] for online modules; 9[7.5;10] for group meetings; 8 [7;10] each for ergonomic & VRC
assessments. Median time to complete each module was 60 min. Satisfaction with online group meetings was high: 93% were satisfied with
facilitation; 87% with group dynamic; 84% were comfortable with the online format. Median [25Q;75Q] ratings (1-10) for ability to follow
group discussion: 10 [9;10]; getting to know other participants: 7 [7;10]; feeling listened to and understood: 9 [8;10]; feeling that group was
supportive: 9 [7;10].
Conclusion:
Overall, online delivery of the Making it Work program was feasible and participants were highly satisfied. Our study demonstrates that self-
management programs can be successfully delivered using an online format, which facilitates wider dissemination, greater convenience to
patients, and lower costs.
Disclosure: K. Tran, None; X. Y. Li, None; X. C. Seah, None; C. Backman, None; B. vanAs, None; P. Rogers, None; M. Gignac, None; J.
M. Esdaile, None; C. Thorne, None; L. Li, None; D. Lacaille, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/process-evaluation-of-the-making-it-work-program-an-

online-program-to-help-people-with-inflammatory-arthritis-remain-employed
The Impact of Electronic Consults (E-Consults) on Positive ANA Referrals in a Veteran

Population
Veena Patel1,2, Diana Stewart2,3 and Molly Horstman1,2,4, 1Internal Medicine, Baylor College of Medicine, Houston, TX, 2Internal
Medicine, Michael E. DeBakey VA Medical Center, Houston, TX, 3Internal Medicine and Pediatrics, Baylor College of Medicine, Houston,
TX, 4Center for Innovations in Quality, Effectiveness and Safety (iQUEST), Houston, TX
SESSION INFORMATION
Background/Purpose: Referrals to rheumatology for positive ANA in the absence of clinical signs and symptoms is a common practice,
which may lead to unnecessary resource use and contribute to delays in patients seeing a rheumatologist. The electronic consult (E-consult)
was developed for specialists to review a patient’s medical record and make recommendations without an in-person visit in an effort to
improve access to timely care. The aims of this project are to assess how E-consults for positive ANA are being used in clinical practice,
examine their impact on resource use, and evaluate if the introduction of E-consults improved wait times for in-person rheumatology visits.
Methods: Charts were reviewed for Veterans referred to the Houston VA outpatient rheumatology clinic from 1/2015-3/2017 with “positive
ANA” as the reason for consult. Demographic data, referral information, relevant rheumatologic labs and imaging were recorded. Veterans’
final diagnoses were organized into the following categories: AARD (ANA-associated rheumatic disease), ORD (other rheumatic disease),
no AARD or ORD, lost to follow-up or no definitive diagnosis at time of review. Lab costs for Veterans with no AARD or ORD were
calculated using the cost to the Houston VA. The costs of consults were estimated using the 2017 Medicare National Fee Schedule. Imaging
costs were estimated from the Healthcare Bluebook. An XmR control chart was created using average wait times for in-person clinic visits
per month.
Results: A total of 139 Veterans had positive ANA outpatient consults. Figure 1 shows the number of patients with positive ANA consults
and their final diagnosis category. 55/139 (40%) of Veterans received E-consults. 73% of patients with consults (86/139) did not have an
AARD or ORD (n=43 E-consults, n=43 in-person visits). Of these, E-consults spent $1,992 more on lab tests, while clinic visits spent
$5,074 more on imaging studies. Clinic visits were more likely to schedule follow-up visits and on average billed $99 more per visit. Figure
2 is a control chart showing special cause variation with >7 points below the line of central tendency (circled graph points), indicating that
E-consults have made an impact on decreasing in-person visit wait times.
Conclusion: E-consults are an effective way to address positive ANA consults, which has helped decrease wait times for in-person
rheumatology visits. E-consults did spend more on lab tests, but had less follow-up appointments and imaging use. Future studies should
address patient satisfaction and PCP satisfaction with the E-consult process.
Disclosure: V. Patel, None; D. Stewart, None; M. Horstman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-impact-of-electronic-consults-e-consults-on-positive-

ana-referrals-in-a-veteran-population
Incremental Direct Medical Costs of Systemic Lupus Erythematosus Patients in the

Years Preceding Diagnosis and the Impact of Sex: A General Population-Based Study
Natalie McCormick1,2, Carlo Marra3 and J. Antonio Avina-Zubieta4, 1Arthritis Research Canada, Richmond, BC, Canada, 2Pharmaceutical
Sciences, The University of British Columbia, Vancouver, BC, Canada, 3School of Pharmacy, University of Otago, Dunedin, New Zealand,
4Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
SESSION INFORMATION
Background/Purpose:
Little is known about the healthcare costs of systemic lupus erythematosus (SLE) patients in the years leading up to SLE diagnosis. We
estimated the incremental (extra) direct medical costs of a general population-based cohort of incident SLE for five years before diagnosis,
and examined the impact of sex on these costs.
Methods:
Data Source: Our administrative data captured all provincially-funded outpatient encounters and hospitalisations (1990-2013), and all
dispensed medications, for ALL residents of the province of British Columbia, Canada.
Sample: We assembled a population-based cohort of incident SLE: those with a new diagnosis of SLE from at least one hospitalisation or
rheumatologist visit, or two non-rheumatologist visits, between Jan 2001 and Dec 2010, and no prior SLE diagnosis between Jan 1990 and
Dec 2000. For each SLE case, we matched up to 5 non-SLE from the general population on age (±2 years), sex and calendar year of
diagnosis. All persons had ≥ 5 years’ follow-up in the databases before index date (first SLE-coded encounter; random date for non-SLE).
Cost Calculation: Outpatient and prescription costs were summed directly from billing data. Case-mix methodology was used for
hospitalisations.
Analysis:
We estimated the unadjusted incremental costs of SLE (difference in per-person costs between SLE and non-SLE) for the five pre-
diagnosis/pre-index years (Y-5 to Y-1) and index year (Y0).
Generalised linear models were used to further adjust for socioeconomic status (SES), urban/rural and comorbidities between SLE and non-
SLE, and evaluate the impact of sex on costs.
Results:
We included 3,632 incident SLE (86% female, mean age 49.6 years) and 18,152 non-SLE. Index-year (Y0) costs for SLE averaged $12,019
per-person (2013 CDN): 59% from hospitalisations, 24% outpatient, and 18% medications. Costs increased by 35% per year, on average,
with the biggest increases in the two years before diagnosis (see Table). Adjusted cost ratios between SLE and non-SLE rose from 1.7 in
Year -3 (Y-3) to 1.9 (Y-2), 2.4 (Y-1), and 4.0 in Y0.
Among non-SLE, adjusted costs were higher for females than males, but among SLE, males had higher costs, controlling for age, SES and
previous year’s comorbidity score. SLE males had higher odds of hospitalisation than SLE females in Y-1 (OR=1.44, 95% CI=1.18-1.76),
while non-SLE males had 15% lower odds. In Years -2 & -1, encounters with primary diagnosis of diabetes, or renal or cardiovascular
disease accounted for 11% of costs for SLE males, vs. 5% for SLE females.
Adjusted M/F cost ratios in SLE were 1.15 (95% CI 1.03-1.29) in Y-2, 1.22 (1.11-1.35) in Y-1, and 1.44 (1.29-1.61) in Y0. When
comparing costs of SLE and non-SLE, the Male*SLE interaction term was significant in all years.
Conclusion:
The incremental costs of SLE are considerable, even in the years prior to diagnosis. Unlike the general population, SLE males had higher
costs than females, potentially from early comorbidities.
Table: Unadjusted Annual Mean Per-Person Costs for SLE and matched non-SLE, before and after SLE Diagnosis/Index Date
(95% Confidence Interval)
Mean (SD) Year Before SLE Diagnosis
Baseline
Mean
Charlson- Year 0
N (SD)
Romano Year -5 Year -4 Year -3 Year -2 Year -1
Age
Comorbidity (index year)
Score
$3,073 $3,416 $3,682 $4,409 $6,111 $12,019
49.6
All SLE 3,632 0.42 (0.49)
(15.9) ($2,872 - ($3,190- ($3,414- ($4,100- ($5,741- ($11,150-
$3,273) $3,641) $3,951) $4,719) $6,481) $12,888)
$1,709 $1,872 $1,932 $2,113 $2,274 $2,447
All Non- 49.8
18,152 0.14 (0.35)
SLE (15.4) ($1,645- ($1,812- ($1,868- ($2,033- ($2,167- ($2,345-
$1,772) $1,932) $1,995) $2,193) $2,381) $2,549)
Cost
- - - $1,364 $1,544 $1,750 $2,296 $3,837 $9,572
difference
$3,042 $3,310 $3,555 $4,257 $5,869 $10,945
SLE 49.1
3,111 0.40 (0.49) ($2,826- ($3,098- ($3,283- ($3,949- ($5,484- ($10,153-
Females (15.6)
$3,257) $3,521) $3,828) $4,565) $6,254) $11,736)
$2,436
$1,746 $1,875 $1,944 $2,110 $2,268
Non-SLE 49.2
15,547 0.13 (0.34) ($1,677- ($1,812- ($1,880- ($2,024- ($2,148-
Females (15.1)
$1,815) $1,939) $2,009) $2,196) $2,388) ($2,326-
$2,546)
Cost
- - - $1,296 $1,434 $1,611 $2,147 $3,601 $8,508
difference
$3,258 $4,047 $4,440 $5,321 $7,557 $18,433
52.9
SLE Males 521 0.50 (0.50)
(17.1) ($2,710- ($3,109- ($3,513- ($4,193- ($6,393- ($14,682-
$3,806) $4,986) $5,367) $6,449) $8,720) $22,185)
$1,485 $1,852 $1,857 $2,312
$2,133 $2,512
Non-SLE 53.0
2,605 0.17 (0.37)
Males (17.0) ($1,925- ($2,239-
($1,328- ($1,666- ($1,643- $2,341) ($2,101- $2,785)
$1,641) $2,039) $2,071) $2,523)
Cost
- - - $1,773 $2,195 $2,583 $3,188 $5,245 $15,921
difference
Disclosure: N. McCormick, None; C. Marra, None; J. A. Avina-Zubieta, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/incremental-direct-medical-costs-of-systemic-lupus-

erythematosus-patients-in-the-years-preceding-diagnosis-and-the-impact-of-sex-a-general-population-based-study
Implementation and Evaluation of a Novel Nurse-Led Telemedicine Intervention for

Dose Escalation of Urate-Lowering Therapy in Gout: A Clinical Practice Improvement
Project
Sen Hee Tay1,2, Bernadette Poh Lee Low3, Pamela Shi Hui Tan2, Zhi Wei Khong2, Siew Hwa Chong4, Amelia Santosa1,2, Anita Yee Nah
Lim1,2 and Gim Gee Teng2,5, 1Division of Rheumatology, Department of Medicine, National University Hospital, National University Health
System, Singapore, Singapore, Singapore, 2Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore,
Singapore, Singapore, Singapore, 3Division of Primary Care, Department of Care Integration and Alliance, National University Hospital,
National University Health System, Singapore, Singapore, Singapore, 4Clinical Nursing Unit, National University Hospital, National
University Health System, Singapore, Singapore, Singapore, 5Division of Rheumatology, University Medicine Cluster, National University
Health System, Singapore, Singapore, Singapore
SESSION INFORMATION
Background/Purpose:
Urate-lowering therapy (ULT) is the mainstay of gout treatment. In our clinics, time to achieve target serum urate (SU) level during ULT
titration was 37 weeks, during which 15% of patients developed gout attacks requiring hospitalization and the time from last outpatient visit
to incident hospitalization was 16 weeks. The suboptimal management may be due to infrequent follow-up during ULT. We implemented
and evaluated the efficacy and safety of a novel nurse-led telemedicine intervention for dose escalation (DE) of ULT for gout patients in a
real-life clinical practice.
Methods:
Consecutive gout patients fulfilling indications for ULT whose SU ≥ 360 µmol/L were approached. Patients with estimated GFR < 30
mL/min, cognitive impairment and immobility were excluded. A bundle of care was designed to support telemedicine as the main
intervention led by a nurse. The bundle components included: nurse education; a safety program (SP) with 6 fortnightly phone calls for
adverse drug reactions (ADRs); hotline service and virtual monitoring clinic (VMC) appointments. The VMC consisted of 6-weekly
laboratory investigations at government clinics or hospital, protocolized DE of ULT and courier services for ULT. Patient satisfaction and
adherence were assessed using a questionnaire survey of patient experience and Medication Adherence Report Scale (MARS-5),
respectively. The primary outcome was the time to achieve target SU < 360 µmol/L, variables that trended towards a significant association
(p < 0.1) were examined in a multivariable Cox regression model.
Results:
We recruited 100 gout patients from July 2016 to March 2017 with a median age of 52.5 years and 90% men; 53.0% were on pre-existing
ULT. The median time to target SU was 19.0 weeks (IQR 17.5-20.5), with no hospitalizations for gout attacks. One patient had an ADR, 3
SP phone calls were made to the patient and allopurinol was stopped immediately after the rash developed. The average Likert summed
scores were high and similar to the overall patient satisfaction. Cox regression model revealed that high levels of education (university
versus primary), absence of gout attacks, lower baseline SU and number of VMC appointments in 6 months were associated with attainment
of target SU.
Conclusion:
Our study is the first to describe the utility of telemedicine in gout care. A nurse-led telemedicine intervention is effective, safe and well-
accepted for the management of patients with gout. Telemedicine has the potential to improve access to care for gout patients, thereby
decreasing burden of disability and overall healthcare utilization.
Disclosure: S. H. Tay, None; B. P. L. Low, None; P. S. H. Tan, None; Z. W. Khong, None; S. H. Chong, None; A. Santosa, None; A. Y. N.
Lim, None; G. G. Teng, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/implementation-and-evaluation-of-a-novel-nurse-led-

telemedicine-intervention-for-dose-escalation-of-urate-lowering-therapy-in-gout-a-clinical-practice-improvement-project

Computer Learning (artificial intelligence) to Create a Computer-Based Triage Tool
Classifying Referrals As Inflammatory or Non-Inflammatory Requiring Only Patient
Reported Information
Cindy Kim1, Tanner Bohn2, Charles X. Ling3, Nikhil Chopra4 and Janet E. Pope5, 1Faculty of Medicine, University of Western Ontaro,
London, ON, Canada, 2University of Western Ontario, London, ON, Canada, 3Computer Sciences, University of Western Ontario, London,
ON, Canada, 4Rheumatology, Private Practice, London, ON, Canada, 5Department of Medicine, Division of Rheumatology, University of
Western Ontario, St Joseph's Health Care, London, ON, Canada
SESSION INFORMATION
Background/Purpose: To determine if a computer-based triage tool can accurately classify referrals as inflammatory or non-inflammatory
using information obtained from the patient; not requiring assessment by healthcare workers.
Methods: Patient referrals to a single rheumatologist were studied. Patient lists for 11 commonly encountered diagnoses [rheumatoid arthritis
(RA), psoriatic arthritis, lupus, osteoarthritis, gout, soft tissue rheumatism (i.e. arthralgia NYD, tendonitis, mechanical low back pain),
ankylosing spondylitis (AS), polymyalgia rheumatica (PMR), and fibromyalgia] were created. The diagnoses of RA, lupus, AS, PMR, and
other seronegative spondyloarthropathies were classified as inflammatory arthritis (non-crystalline) (IA). At least five patient charts for each
diagnosis were reviewed and eligible for study if a self-reported patient pain diagram was also completed. The following patient-reported
information was collected from each referral: age, sex, symptom duration, and pain diagram. Lab results for ESR, CRP, ANA, ENA, anti-
DNA, anti-CCP antibodies, urate, and rheumatoid factor were also collected where available. Machine learning techniques were used to
create a logistic regression model to classify referrals as inflammatory or non-inflammatory. Backward feature selection was used to enhance
model performance by identifying features most predictive of referral state. Leave-one-out cross-validation was used to predict model
performance. The models were subsequently evaluated on prospectively collected patient data from 20 new referrals seen after the creation
of the triage tool, where data was coded blindly to patients’ diagnosis.
Results: In creation of the triage tool, 168 patient charts were used; 73 were classified as IA after being seen by a rheumatologist. The triage
tool correctly classified 65 of 73 referrals as inflammatory using patient-reported information (model 1) (sensitivity 89%, specificity 52%).
When the referral tool was reevaluated using laboratory markers in addition to the information obtained from the patient (model 2), 67
referrals were correctly classified as inflammatory (sensitivity 92%, specificity 63%). When model 1 was tested on 20 prospective patients,
all 6 patients with IA were correctly classified (sensitivity 100%, specificity 52%). Model 2 correctly classified 14 patients (who had lab
values present) including 5 patients with IA (sensitivity 83%, specificity 64%). The results are shown in table. Further prospective multi-site
testing is ongoing.
Conclusion: A referral tool that can be entered into a database for computer assessment has good sensitivity to detect high priority referrals
from data that can be obtained directly from patients and ascertained by non-healthcare workers. This may be of benefit in areas of limited
resources and long waiting lists to see a rheumatologist.
Model 1 Model 2
Predicted Actual Predicted Actual
(N=168) (N=20) (N=168) (N=20)
Sensitivity 89.0% 100% 91.8% 83.3%
Specificity 51.6% 35.7% 63.2% 64.3%
NPV 86.0% 100% 90.9% 90.0%
PPV 58.6% 40.0% 65.7% 50.0%
IA Referrals
Correctly Classified 65/73 6/6 67/73 5/6
Disclosure: C. Kim, None; T. Bohn, None; C. X. Ling, Director of Data Mining and Business Intelligence Lab, 6; N. Chopra, Amgen,
Novartis, UCB, AbbVie, Janssen, 5; J. E. Pope, AbbVie, Amgen, Bayer, BMS, Celtrion, Eli Lilly and Company, Merck, Novartis, Pfizer,
Roche, UCB, 5,Amgen, Bayer, BMS, GSK, Merck, Novartis, Pfizer, Roche, UCB, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/computer-learning-artificial-intelligence-to-create-a-

computer-based-triage-tool-classifying-referrals-as-inflammatory-or-non-inflammatory-requiring-only-patient-reported-information
Analysis of Provider-to-Provider Variability in the Use of Biologics: Data from the

Rheumatology Informatics System for Effectiveness Registry
Douglas White 1, Michael Evans2, Gabriela Schmajuk3, Rachel Myslinski4, Salahuddin Kazi5 and Jinoos Yazdany6, 1Gundersen Health
System, Onalaska, WI, 2University of California San Francisco, San Francisco, CA, 3San Francisco VA Medical Center, University of
California San Francisco, San Francisco, CA, 4Practice, Advocacy, & Quality, American College of Rheumatology, Atlanta, GA, 5University
of Texas Southwestern, Dallas, TX, 6Medicine/Rheumatology, University of California San Francisco, San Francisco, CA
SESSION INFORMATION
Background/Purpose: Variations in biologic prescribing habits by rheumatology providers may account in part for variability in direct cost
of care for patients with rheumatoid arthritis (RA). We used data from the Rheumatology Informatics System for Effectiveness (RISE)
registry to estimate variability in biologic use among US rheumatologists.
Methods: RISE is a national, EHR-enabled registry that passively collects and houses data on all patients seen by participating practices and
thereby avoids sampling bias. As of December 2016, RISE was connected to 632 providers (99.5% of which were physicians) representing
an estimated 16% of the US workforce. We calculated, on a per-provider basis, the proportion of RA patients prescribed a biologic or
tofacitinib at least once between January and December 2016 (inclusive). The population of patients in the denominator, numbering 58,055
across all participating practices, was defined as those assigned an ICD code for RA in at least two separate encounters in 2016. Consistent
with other national performance analyses, providers who saw fewer than 30 RA patients (315 of the 632 RISE-connected providers) were
excluded. Few patients saw >1 provider, but in those instances prescriptions were attributed only to the provider with the plurality of RA-
coded visits; therefore, each patient was attributed to only one provider.
Results: Provider-to-provider variability in the proportion of RA patients who received a biologic prescription is shown in Figure 1.
Across the US in 2016, an average of 38% of each provider's RA patients were prescribed a biologic but the fraction of patients prescribed a
biologic ranged from 0 to 79%. A regional breakdown is shown in Table 1 and demonstrates statistically significant geographic variability
as well.
Conclusion: These data estimate the degree to which biologic prescription patterns vary across the US. In light of existing data indicating
that biologics account for the majority of the direct cost in providing care for US patients with RA, and ongoing initiatives such as the Merit
Incentive Payment System to incorporate measures of resource utilization in payment reform, this study provides initial benchmarking
information for rheumatology providers in the US. Our study does not address quality of care. Future studies adjusted for case mix and
disease activity will be required to estimate variability in the value (quality divided by cost) of care.
Figure 1. Fraction of RA patients prescribed biologics, by provider. Red line indicates the mean.
Table 1. Fraction of RA patients prescribed biologics, on a per-provider basis, by region.

Region Mean 95% CI
(%) (%)
New England (CT, ME, MA, 36.5 31.3 -
NH, RI, VT) 41.6
Mid Atlantic (DE, NJ, NY, PA) 32.4 27.1 -
37.7
East North Central (IL, IN, MI, 29.6 24.0 -
OH, WI) 35.3
West North Central (IA, KS, 40.3 36.6 -
MN, MO, NE, ND, SD) 44.0
South Atlantic (FL, GA, MD, 41.2 38.4 -
NC, SC, VA, DC, WV) 44.0
East South Central (AL, KY, 37.6 33.0 -
MS, TN) 42.2
West South Central (AR, LA, 45.8 42.5 -
OK, TX) 49.1
Mountain (AZ, CO, ID, MT, 37.6 34.2 -
NV, NM, UT, WY) 41.1
Pacific (AK, CA, HI, OR, WA) 41.9 31.4 -
52.3
Disclosure: D. White, None; M. Evans, None; G. Schmajuk, None; R. Myslinski, None; S. Kazi, None; J. Yazdany, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/analysis-of-provider-to-provider-variability-in-the-use-

of-biologics-data-from-the-rheumatology-informatics-system-for-effectiveness-registry
Intensive Care Unit Admissions Among Patients with Rheumatic Diseases at a Tertiary
Care Center
Ali Al-Marzooq1, Mohammed Al-Charakh1, Sumediah Nzuonkwelle2, Bikash Bhattarai3, Mark McPherson2 and Konstantinos Parperis4,
1Internal Medicine, Maricopa Integrated Health System, Phoenix, AZ, 2Maricopa Integrated Health System, Phoenix, AZ, 3Research,
Maricopa Integrated Health System, phoenix, AZ, 4Rheumatology, Maricopa Integrated Health System and University of Arizona College of
Medicine, Phoenix Campus, phoenix, AZ
SESSION INFORMATION
Background/Purpose:
Patients with autoimmune rheumatic diseases have higher risk of developing organ failure and may require admission to intensive care unit
(ICU), however there are only few studies in the US addressing this topic. The aim of our study is to determine reasons of admission to the
ICU, identify potential risk factors associated with mortality and assess outcomes of patients with rheumatic disease admitted to the ICU.
Methods:
We conducted a retrospective chart review of patients admitted to the ICU from 2011 to 2016 using ICD-9/ICD-10 codes for morbidities. We
identified patients with new or established diagnosis of a rheumatic disease. Patient's data included demographics, ICU admission diagnoses,
co-morbidities, organ involvement, laboratory studies, length of stay in ICU/hospital, complications and immunosuppresive regimen. Short-
term (ICU/30-day post-ICU) stay and long-term (1-year post) outcomes were assessed.
Results:
A total of 80 rheumatic disease patients were identified with mean age of 48.8 (range 19-84), 67% were female, 56% were Hispanic. Most
common disease associated with ICU admission was SLE in 34 patients (42%), followed by RA 21(26%). 10(12%) had Systemic Vasculitis
(5 with Granulomatosis with polyangitis, 2 with PAN, 1 Eosinophilic granulomatosis with polyangiitis, 1 with Takayasu’s, 1 with
Microscopic polyangiitis). 5(6%) had SSc, 5(6%) had DM and 2(3%) had Sarcoidosis. Sjogren’s, APS and AS were present in 1 patient
each case.
Sepsis was the leading cause of ICU admission with 25 patients(31%), followed by acute hypoxemic respiratory failure due to pneumonia
8(10%) and congestive heart failure/CHF 8(10%). Others were respiratory failure due to underlying disease 6(8%) and cardiac tamponade 6
(8%). Less common included cerebrovascular events(4), metabolic disturbances(3), Steven’s Johnson (3), meningoencephalitis (3),
encephalopathy(3), pulmonary hypertensions(2), diffuse alveolar hemorrhage (2), pancreatitis(2), cardiac arrest(2), anemia(1), hypertensive
emergency(1) and pulmonary embolism(1).
45% of patients required mechanical ventilation and 31% vasopressor support. Mean ICU stay was 7 days and hospital stay 13.7 days. 16 of
80 patients (20%) died in ICU, 4(5%) died 30-days post-ICU and 6(7.5%) within 1-year of ICU stay, resulting into an overall mortality of
33% by the end of 1-year. Higher mortality found in patients with DM (40%) and SLE (24%). Predictors of increased mortality during ICU
stay were cardiovascular involvement (p=0.01), renal involvement (p=0.032) and requirement for mechanical ventilation (p<0.01). Worse
outcome 30-days post ICU stay was influenced by development of venous thromboembolic disease (VTE) during hospitalization (p=0.03). At
1-year post ICU-stay, survival for patients with CHF was 76.5% compared to 95.7% without CHF (p=0.041).
Conclusion:
Our findings indicated that SLE is the most common rheumatic disease associated with ICU admission, followed by RA. Sepsis, respiratory
failure due to pneumonia/ CHF were the most common causes leading to ICU admission. Factors associated with higher mortality were
requirement for mechanical ventilation, renal and cardiovascular involvement on admission, development of VTE and history of CHF.
Disclosure: A. Al-Marzooq, None; M. Al-Charakh, None; S. Nzuonkwelle, None; B. Bhattarai, None; M. McPherson, None; K.
Parperis, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/intensive-care-unit-admissions-among-patients-with-

rheumatic-diseases-at-a-tertiary-care-center
Healthcare Utilization Among Young Adults Transitioning from Pediatric to Adult Care
in a Safety Net Population
Nicole Bitencourt1, Una E. Makris1,2, Tracey Wright3,4 and E. Blair Solow1, 1UT Southwestern Medical Center, Dallas, TX, 2Department
of Medicine, VA North Texas Health Care System, Dallas, TX, 3Pediatrics/Rheumatology, UT Southwestern Medical Center, Dallas, TX,
4Texas Scottish Rite Hospital for Children, Dallas, TX
SESSION INFORMATION
Background/Purpose:
The transition from pediatric to adult care for young adults with chronic illness is a vulnerable period especially among socioeconomically
disadvantaged populations. As part of a quality improvement project, we sought to characterize patterns of healthcare utilization, namely
hospitalizations and emergency department (ED) visits during the transfer period between pediatric and adult rheumatologic care in a large
public safety net healthcare system.
Methods:
Using an electronic medical record, 95 patients were identified as being between 17 and 21 years of age at the time of referral to adult
rheumatology between 3/2014 and 4/2017. Following chart review, 65 of these patients were confirmed as transitioning between pediatric
and adult care. Data on disease categories, demographics, medical coverage, and referring provider were extracted and comparisons made
regarding hospitalizations and ED visits (excluding visits which were clearly unrelated to an underlying rheumatic disease) by using unpaired
t-test and one-way analysis of variance.
Results:
Among the 65 patients transitioning to adult care, 72% were female, 74% were Hispanic, 49% had a connective tissue disease (CTD), 49%
had juvenile idiopathic arthritis (JIA), 75% had Medicaid, and 74% were referred by a pediatric rheumatologist (Table 1). Hospitalizations
and ED visits were common (20% and 28% of patients, respectively) during the transfer period, and were more common among those with a
CTD (compared to JIA), and in blacks (compared with Hispanics and whites) (Figure 1). Those with a lapse in medical coverage during the
transfer period and lack of coverage at the time of initial referral had significantly higher healthcare utilization than those with consistent
medical coverage. Those referred to adult care by a pediatric rheumatologist had significantly fewer hospitalizations and ED visits than
those referred by other clinicians (Figure 2).
Conclusion:
Hospitalizations and ED visits are especially prevalent among patients transitioning from pediatric to adult rheumatologic care. Factors
associated with high utilization included having a CTD, black race, lapse in medical coverage during the transfer period, lack of coverage at
initial referral to adult care, and being referred by someone other than a pediatric rheumatologist.
Disclosure: N. Bitencourt, None; U. E. Makris, None; T. Wright, None; E. B. Solow, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/healthcare-utilization-among-young-adults-transitioning-

from-pediatric-to-adult-care-in-a-safety-net-population
What Is the Value of the Prior Authorization Process in Specialty Drug Therapy?
Shally Alendry1, Melad Qodsi1, Travis Hunerdossse1 and Eric M. Ruderman2,3, 1Northwestern Medicine, Chicago, IL, 2Northwestern
University Feinberg School of Medicine, Chicago, IL, 3Medicine/Rheumatology, Northwestern University Feinberg School of Medicine,
Chicago, IL
SESSION INFORMATION
Background/Purpose: As the use of specialty pharmacy drugs has grown, many insurers have instituted strict prior authorization
requirements, ostensibly to ensure that the right patients get the right medications at the right point in their disease process. Rheumatologists,
dermatologists, and patients, however, often question whether this process creates logistical barriers that delay treatment. Northwestern
Medicine established a specialty pharmacy in 2014 to provide medication directly to patients at the institution. Rheumatology and
dermatology clinics began working with this specialty pharmacy in 2015 and now utilize it for all new specialty drug prescriptions. When
possible, medications are filled directly through the health system pharmacy. When insurers require use of an alternative specialty pharmacy,
the prescription is transferred, but the NM specialty pharmacist continues to help guide the prior authorization steps. We analyzed the number
of prescriptions approved or denied through this process, hypothesizing that few medications requiring prior authorization were ultimately
denied.
Methods: We reviewed prior authorization requests from 6/1/2015 through 6/12/2017. We included primarily prescriptions for approved
indications, at labeled doses. Indications included ankylosing spondylitis, juvenile idiopathic arthritis, psoriatic arthritis, rheumatoid
arthritis, and psoriasis.
Results: Of the 3192 prescriptions handled by the specialty pharmacy, 840 did not require prior authorization. A total of 2,352 prior
authorizations were submitted; 2113 of these were approved with the initial request, and 239 (10.1%) were denied. Appeals were submitted
for 126 of these denials in rheumatology; the denial was overturned in 83 cases, upheld in 40, and 3 are pending. Dermatologists appealed
fewer denials. As of the data cut, 2196 (93.4%) of the prescriptions submitted for prior authorization had been approved and filled. Results
for individual diseases are shown in Table 1.
Conclusion: In our academic medical practice, rheumatology and dermatology specialty medications prescribed for approved indications are
seldom denied, and most of the denials are reversed when appealed. These findings suggest that the time spent on prior authorizations, at
substantial cost to the practices involved, may be unnecessary, as appropriate treatments are rarely denied. Insurers may have other interests
in the prior authorization process besides the stated reason of restricting inappropriate or unnecessary prescriptions. There appears to be
little value in the prior authorization process for rheumatology- or dermatology-specific specialty drugs prescribed in an academic practice.
A more streamlined approach could limit wasted time and effort, suggesting a need for exploration of alternative methods in partnership with
payers.
Table 1. Prior Authorization Status for Specialty Drugs in Rheumatology and Dermatology
Not Appeal Appeal Appeal
Disease Approved Denied
Needed Granted Denied
Pending
Ankylosing
133 11 45 2 2 -
Spondylitis
Juvenile
Idiopathic 17 2 4 2 - -
Arthritis
Psoriasis 648 103 288 8 7 1
Psoriatic
253 31 78 20 7 1
Arthritis
Rheumatoid
1062 92 425 51 24 1
Arthritis
Total 2113 239 840 83 40 3
Disclosure: S. Alendry, None; M. Qodsi, None; T. Hunerdossse, None; E. M. Ruderman, Pfizer Inc, 5,Roche Pharmaceuticals, 5,Seattle
Genetics, 5,Abbott Immunology Pharmaceuticals, 5,Amgen, 5,Pfizer Inc, 2,Bristol-Myers Squibb, 5,Janssen Pharmaceutica Product, L.P.,
5,Eli Lilly and Company, 5,Novartis Pharmaceutical Corporation, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/what-is-the-value-of-the-prior-authorization-process-in-

specialty-drug-therapy
Real World IGRA Testing in Rheumatology Practice

Paul DeMarco1,2, Megan Bishop3, Ashling Smith4, Herbert S. B. Baraf1,5, Andrew Gregory DeMarco6, Temitope Ademola7, Deborah
Contreras8, Adalisa Enriquez RMA1, Lisa Klein1, Kayra Perez1, Sandra Ventura1, Janice Whyte-Whitworth1, Vince Calhoun1, Theresa Bass
Goldman1 and Alan K Matsumoto1,9, 1The Center for Rheumatology and Bone Research, Wheaton, MD, 2Division of Rheumatology,
Department of Medicine, Georgetown University School of Medicine, Washington, DC, 3Clinical Trials, The Center for Rheumatology and
Bone Research, Wheaton, MD, 42730 University Blvd West, Suite 306, The Center for Rheumatology and Bone Research, Wheaton, MD,
5Department of Medicine, George Washington University School of Medicine, Washington, DC, 6Department of Biochemistry and Molecular
Cellular Biology, Georgetown University Department of Biochemistry and Molecular Cellular Biology, Washington, DC, 7The Center for
Rheumatology and Bone Research, Washington, DC, 82730 University Boulevard West, Suite 306, The Center for Rheumatology and Bone
Research, Wheaton, MD, 9Department of Medicine, Division of Rheumatology, Johns Hopkins School of Medicine, Baltimore, MD
SESSION INFORMATION
Background/Purpose:
Mycobacterium tuberculosis (MTb) screening is routine for clinical trial protocols, & authorization for immunomodulators use by health
insurances. Real world data is needed to guide clinicians and researchers in appropriate test choice. The two interferon gamma release
assays (IGRAs) available to screen for MTb, QuantiFERON TB Fold In-Tube test (QFT-G) & SPOT TB (T-Spot), rely on an
uncompromised immune system. Both, however, have a “+,” “-,” & “indeterminate (IND)” or in TSpot, “borderline” result. IND or
borderline values have been theorized to result from an immunocompromised state, but the literature varies with regard to the effect of
immunomodulation, particularly with corticosteroids, disease-modifying anti-rheumatic medications (DMARDs) and biologic response
modifiers (BRMs)
Methods: The Center for Rheumatology and Bone Research (CRBR) obtained IRB review / waiver to conduct a retrospective chart review
from 2014 to 2016. CRBR focused on care provided by Arthritis and Rheumatism Associates P.C. regarding medication use at the time of an
IGRA. Data included IGRA type, test result ("+", "-" & IND/borderline), & medication use. Medications were divided by corticosteroid
(prednisone or methylprednisolone), DMARD use (including but not limited to hydroxychloroquine, sulfasalazine, MTX, azathioprine,
leflunomide, cyclosporine) and exposure to a BRM (aka anti-TNFa therapy [such as etanercept, adalimumab, infliximab, certolizumab,
golimumab], tocilizimab, abatacept rituximab and tofacitinib). A medication was considered active at the time of the laboratory if there were
evidence of use within 1 month of testing. Statistical Analysis was performed using a student’s z-test as well as Chi-square analysis.
Results:
A total of 796 IGRAs were reported. There were 722 QTF-G tests and 74 Tspot drawn. Negative QTF-G values occurred in 643/722 (89%),
equally distributed between those on & off immunomodulators. Positive QTF-G values occurred in 41/722 (5.6%), equally distributed
between those on & off immunomodulators. IND QFT-G occurred in 38/722 (5.9%); the distribution was imbalanced. IND QTF-G occurred
in 24/38 (63 %) on immunomodulators while IND QTF-G occurred in 14/38 (37%) with p=0.0087. IND QTF-G were more likely to occur
during corticosteroid + DMARD / BRM treatment, occurring in 19/38 (50%) vs.DMARD ± BRM without corticosteroid, which occurred in
5/38 (13%) with p<0.025. This effect was not seen in non-steroid DMARD or non-steroid BRM treated cohort. This effect was not observed
in the Tspot cohort, as IND / border line values occurred in 1/74 on immunomodulators while 2/72 subjects were not exposed to
immunomodulators.
Conclusion:
Our cohort demonstrated positive, negative and IND rate similar to other published studies. However, our large QTF-G cohort demonstrated
a statistically significant difference in IND values while taking immunomodulators, largely related to steroid exposure. Our smaller Tspot
cohort did not demonstrate this effect, but this may have related to the cohort size. Further study to guide IGRA choice is warranted, but
clinicians should consider Tspot over QTF-G when the subject is exposed to corticosteroid within a month of testing.
Disclosure: P. DeMarco, None; M. Bishop, None; A. Smith, None; H. S. B. Baraf, None; A. G. DeMarco, None; T. Ademola, None; D.
Contreras, None; A. Enriquez RMA, None; L. Klein, None; K. Perez, None; S. Ventura, None; J. Whyte-Whitworth, None; V. Calhoun,
None; T. Bass Goldman, None; A. K. Matsumoto, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/real-world-igra-testing-in-rheumatology-practice
Direct Medical Costs of Systemic Lupus Erythematosus in South Korea

So-Yeon Park1 and Sang-Cheol Bae2, 1Department of Rhematology, Myongji Hospital, Seonam university, Goyang, Korea, Republic of
(South), 2Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea, Republic of (South)
SESSION INFORMATION
Background/Purpose: Systemic lupus erythematosus (SLE) has very high economic burdens on society and healthcare system. The aim of
this study was to estimate the annual direct costs and predictors of cost in Korean patients with SLE
Methods: This study used a national insurance claims database during the period from 2006 to 2010. Information was taken from the Korea
National Health Insurance (KNHI) Claims Database of the Health Insurance Review and Assessment Service (HIRA). Factors associated
with the direct medical costs were analyzed by using multiple regression and multivariate logistic regression.
Results: A total of 13,047 SLE patients were mainly analyzed. The estimated total annual direct medical costs amounted to $2,240 (2010 US
dollars), of which 47.1% was accounted for by inpatient costs and 52.9% by outpatient costs. Among the cost domains for total direct
medical costs, the biggest component was the costs of medication. The mean medication costs were $983, which accounted for 43.9% of the
total healthcare costs, followed by costs for diagnostic procedures and tests, accounting for 32.8% of the total. For the type of insurance,
national health insurance were 92%, and medical aid were 8%. Total reimbursement rates of patients with SLE were 86.4%, and copayment
comprised 13.6%, respectively. Reimbursement rates have shown a tendency to increase, whereas, out-of pocket was decreasing gradually
each year between 2006 and 2010. In the multivariate regression analyses, the predictors of increased direct costs were male sex, medical
aid -insurance type, more comorbidity disease, and the use of immunosuppressant including steroids
Conclusion: We have reported on the first population-based cost study of SLE patients in South Korea. The results of this study will
contribute to a better understanding of the economic burden of SLE, and should provide information that is useful when allocating healthcare
resources.
Table1. Annual direct medical costs* in patients with SLE, 2006~2010 (US $)
Annual direct medical cost per person, mean*
2006 2007 2008 2009 2010
(n=9,878) (n=10,555) (n=11,375) (n=12,103) (n=13,047)

Outpatient 940 1,017 1,046 1,118 1,184
Inpatient 993 1,065 1,138 1,039 1,056

Total direct
1,993 2,082 2,184 2,157 2,240
costs
* Medical costs except non-reimbursement
Table2. Multiple linear regression model of annual direct medical costs in 13,047 patients with SLE in 2010* Medical costs except non-
reimbursement
Univariate Multivariate
Variables
coefficient p coefficient p R2
age -147 0.9428 2,465 0.0939
sex (male=1) 203,811 0.0168 266,052 <0.0001
insurance type
(National health -1,308,571 <0.0001 -471,980 <0.0001

insurane=1)
CCI* 329,655 <0.0001 103,740 <0.0001 56.99
Surgical procedure 5,148,455 <0.0001 3,109,270 <0.0001
Number of visits 117,016 <0.0001 89,275 <0.0001
Length of stay, days 124,607 <0.0001 98,597 <0.0001
Use of immunosupressant 1,704,733 <0.0001 1,001,006 <0.0001
Dosage of glucocorticoid 1,665 <0.0001 648 <0.0001
*Charlson comorbidity index
Disclosure: S. Y. Park, None; S. C. Bae, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/direct-medical-costs-of-systemic-lupus-erythematosus-in-

south-korea
Influence of Depression on Healthcare Expenditures Among Adults with Spondylosis,

Intervertebral Disc Disorders and Other Back Problems in the United States
Jawad Bilal1, Adam Berlinberg1, Jaren Trost1, Sandipan Bhattacharjee2 and Irbaz Bin Riaz1, 1Banner University Medical Center, Tucson,
AZ, 2Department of Pharmacy, University of Arizona, Tucson, AZ
SESSION INFORMATION
Background/Purpose: Back pain is a very prevalent complaint affecting two-thirds of population, and accounts for 90.7 billion dollars
annually in healthcare expenditure. The occurrence of depression is reported in existing literature among patients with back pain, but there is
limited information regarding healthcare expenditures among patients with back pain and concurrent depression. To assess excess total and
subtypes of healthcare expenditures among adults with spondylosis, intervertebral disc disorders and other back problems who reported
having depression compared to those without depression in the United States (US).
Methods: We utilized a cross-sectional design pooling MEPS data from 2010-2012. The eligible study sample comprised of adults (age ≥
18 years), who were alive during the calendar year and reported positive healthcare expenditure. Total and subtypes of healthcare
expenditures constituted the dependent variable. Ordinary least square (OLS) regressions on logged expenditures were performed. Three
models were developed to assess the influence of demographics, functional ability, and concurrent diagnoses on healthcare expenditures. All
expenditure data are presented in terms of 2012 US dollars.
Results: A total of 6,559 adults with spondylosis, intervertebral disc disorders, and other back problems were assessed, 20.2% of which
had concurrent depression. Adults with concurrent depression had significantly higher healthcare expenditures ($13,153) compared to the
non-depression group ($7,477), p<0.001. Inpatient, outpatient, prescription, and home health agency expenditures showed similar findings.
There was no difference in emergency room and other expenditures between the two groups. The excess total expenditure was higher (119%)
among depression group when adjusted for demographic characteristics. After adjusting for healthcare and functional disabilities, and
comorbidities excess cost remained higher in depression group (53%).
Conclusion: This study demonstrates that presence of depression in the adults with spondylosis, intervertebral disc disorders, and other back
problems significantly influence the economic burden. These findings remained consistent despite adjusting for all independent level
variables (demographic characteristics, functional status, comorbidities). The study findings suggest that interventions resulting in better
control of depression have the potential to significantly reduce the economic burden in this population.
Disclosure: J. Bilal, None; A. Berlinberg, None; J. Trost, None; S. Bhattacharjee, None; I. B. Riaz, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/influence-of-depression-on-healthcare-expenditures-

among-adults-with-spondylosis-intervertebral-disc-disorders-and-other-back-problems-in-the-united-states
Epidemiologic Subsets Drive a Differentiated Thoracic and Extrathoracic Presentation

of Sarcoidosis: Analysis of 1082 Patients from the Sarcogeas-SEMI Registry
Soledad Retamozo1,2,3, Roberto Pérez-Alvarez4, Guadalupe Fraile5, Ricardo Gómez De La Torre6, Miguel López Dupla7, Begoña De
Escalante Yangüela8, Ana Alguacil9, Joel Chara-Cervantes10, Jose Velilla Marco10, Francisco Javier Rascón11, Jose Salvador Garcia
Morillo12, Carles Tolosa13, Eva Fonseca Aizpuru14, Mariona Bonet15, José Luis Callejas16, Gloria De la Red17, Eva Calvo Begueria18,
Cristina Soler i Ferrer19, Enrique Peral Gutiérrez De Ceballos20, Jorge Francisco Gómez Cerezo21, Gracia Cruz Caparrós22, Patricia Perez
Guerrero23, Sergio Rodríguez Fernández24, Blanca Pinilla25, Alberto Gato Diez26, Miriam Akasbi27, Angel Robles28, Inmaculada Ojeda29,
Maria José Vives30, César Morcillo31, María Penadés Vidal32, Moisés De Vicente33, Belchin Kostov34, Manuel Ramos-Casals35, Lucio
Pallarés11 and Pilar Brito-Zerón2, 1Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Córdoba, Consejo
Nacional de Investigaciones Científicas y Técnicas (INICSA-UNC-CONICET), Cordoba, Argentina, 2Laboratory of Systemic Autoimmune
Diseases “Josep Font”, CELLEX, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Systemic Autoimmune
Diseases, ICMID, Hospital Clinic, Barcelona, Barcelona, Spain, 3Rheumatology Unit, Hospital Privado Universitario de Córdoba, Institute
University of Biomedical Sciences University of Córdoba (IUCBC), Cordoba, Argentina, 4Department of Internal Medicine, Hospital Alvaro
Cunqueiro, Vigo, Vigo, Spain, 5Autoimmune Diseases Department, Hospital Ramón y Cajal, Madrid, Spain, 6Department of Internal
Medicine, Hospital Universitario Central de Asturias, Oviedo, Oviedo, Spain, 7Department of Internal Medicine, Hospital Universitari Joan
XXIII, Tarragona, Tarragona, Spain, 8Department of Internal Medicine, Hospital Clínico, Zaragoza, Zaragoza, Spain, 9Department of Internal
Medicine, Hospital Virgen de la Salud, Toledo, Toledo, Spain, 10Hospital Universitario Miguel Servet, Zaragoza, Zaragoza, Spain,
11Department of Internal Medicine, Hospital Son Espases. Palma de Mallorca, Palma de Mallorca, Spain, 12Department of Internal
Medicine, Hospital Virgen del Rocio, Sevilla, Sevilla, Spain, 13Department of Internal Medicine, Corporación Sanitaria Universitaria Parc
Taulí, Barcelona, Spain, 14Department of Internal Medicine, Hospital de Cabueñes, Gijón, Gijón, Spain, 15Department of Internal Medicine,
Althaia, Xarxa Assistencial de Manresa, Manresa, Spain, 16Department of Internal Medicine, Hospital Clínico San Cecilio, Granada,
Granada, Spain, 17Department of Internal Medicine, Hospital Esperit Sant, Badalona, Badalona, Spain, 18Hospital General San Jorge,
Huesca, Huesca, Spain, 19Department of Internal Medicine, Hospital de Santa Caterina, Girona, Girona, Spain, 20Department of Internal
Medicine, Hospital Virgen Macarena, Sevilla, Sevilla, Spain, 21Department of Internal Medicine, Hospital Infanta Sofía, San Sebastián, San
Sebastian, Spain, 22Department of Internal Medicine, Hospital de Poniente El Ejido, Almería, Almería, Spain, 23Department of Internal
Medicine, Hospital Universitario Puerta del Mar, Cádiz, Cadiz, Spain, 24Department of Internal Medicine, Hospital da Barbanza, A Coruña,
A Coruña, Spain, 25Department of Internal Medicine, Hospital Gregorio Marañón, Madrid, Madrid, Spain, 26Department of Internal
Medicine, Complejo Hospitalario Albacete, Albacete, Albacete, Spain, 27Department of Internal Medicine, Hospital Infanta Leonor, Madrid,
Madrid, Spain, 28Internal Medicine, Hospital La Paz, Madrid, Spain, 29Department of Internal Medicine, Hospital Valle del Guadiato,
Córdoba, Cordoba, Spain, 30Department of Internal Medicine, Parc Sanitari San Joan de Déu, San Boi de Llobregat, Barcelona, Spain,
31Department of Medicine, Hospital CIMA-Sanitas, Barcelona, Barcelona, Spain, 32Department of Internal Medicine, Hospital De Manises,
Valencia, Valencia, Spain, 33Department of Internal Medicine, Hospital Nuestra Señora del Prado, Talavera, Talavera, Spain, 34Primary
Care Research Group, IDIBAPS, Centre d’Assistència Primària ABS Les Corts, CAPSE, Barcelona, Barcelona, Spain, 35Laboratory of
Systemic Autoimmune Diseases “Josep Font”, CELLEX, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of
Systemic Autoimmune Diseases, ICMID, Hospital Clinic, Barcelona, Spain, Barcelona, Spain
SESSION INFORMATION
Background/Purpose: To analyse whether epidemiologic factors (such as gender or age at diagnosis of the disease) are associated with
particular disease expressions and define specific epidemiological subsets in patients with sarcoidosis.
Methods: In January 2016, the Autoimmune Diseases Study Group (GEAS-SEMI) created a national registry (SARCOGEAS) of patients
with sarcoidosis. Sarcoidosis was diagnosed in agreement with the criteria proposed by the American Thoracic Society/European
Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) 1999 statement on sarcoidosis. Organ
involvement was retrospectively determined in each patient at the time of diagnosis using the 2014 WASOG organ assessment instrument.
Ethnicity was defined according to the FDA classification.
Results: The cohort consisted of 1082 patients (82% biopsy-proven), including 618 (57%) women and 464 (43%) men, with a mean age at
diagnosis of 47.2 ± 15.5 years. One hundred forty (13%) patients were born outside Spain. With respect to the FDA ethnic classification, 965
(89%) patients were classified as White, 69 (6%) as Hispanic, 30 (3%) as Black/African American and 18 (2%) as Asian. Thoracic
involvement was present at diagnosis in 979 (90%) patients, including 437 (40%) patients presenting with stage I, 374 (35%) with stage II,
123 (11%) with stage III and 26 (2%) presenting with stage IV. According to the WASOG classification, the most frequently reported
extrathoracic involvements at diagnosis were cutaneous in 385 (36%) patients, extrathoracic lymph nodes in 218 (20%), liver involvement in
151 (14%) and ocular involvement in 118 (11%).
In the multivariate analysis models, women showed a lower frequency of thoracic involvement (87% vs 93% in men, p=0.019) and a higher
frequency of cutaneous (42% vs 26%, p<0.001) and ocular (13% vs 9%, p=0.012) WASOG involvements, patients with a younger disease
onset (<35 years) were more frequently born out of Spain (17% vs 11%, p=0.027), had a higher frequency of thoracic disease (94% vs 88%,
p=0.008) and a lower frequency of kidney involvement (3% vs 6%, p=0.041), and patients with an elderly onset (age>70 years) were more
frequently born in Spain (99% vs 86%, p=0.007) and had a lower frequency of thoracic (81% vs 90%, p=0.006) and cutaneous (23% vs
37%, p=0.001) involvements and a higher frequency of bone marrow involvement (12% vs 4%, p=0.004).
Conclusion:
This is one of the largest series of sarcoidosis reported out of the US, predominantly composed by White patients in nearly 90% of cases.
Thoracic and extrathoracic involvements at disease presentation were strongly influenced by specific epidemiologic features such as gender,
age and ethnicity.
Disclosure: S. Retamozo, None; R. Pérez-Alvarez, None; G. Fraile, None; R. Gómez De La Torre, None; M. López Dupla, None; B. De
Escalante Yangüela, None; A. Alguacil, None; J. Chara-Cervantes, None; J. Velilla Marco, None; F. J. Rascón, None; J. S. Garcia
Morillo, None; C. Tolosa, None; E. Fonseca Aizpuru, None; M. Bonet, None; J. Luis Callejas, None; G. De la Red, None; E. Calvo
Begueria, None; C. Soler i Ferrer, None; E. Peral Gutiérrez De Ceballos, None; J. F. Gómez Cerezo, None; G. Cruz Caparrós, None;
P. Perez Guerrero, None; S. Rodríguez Fernández, None; B. Pinilla, None; A. Gato Diez, None; M. Akasbi, None; A. Robles, None; I.
Ojeda, None; M. J. Vives, None; C. Morcillo, None; M. Penadés Vidal, None; M. De Vicente, None; B. Kostov, None; M. Ramos-Casals,
None; L. Pallarés, None; P. Brito-Zerón, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/epidemiologic-subsets-drive-a-differentiated-thoracic-

and-extrathoracic-presentation-of-sarcoidosis-analysis-of-1082-patients-from-the-sarcogeas-semi-registry
Pharmacovigilance Surveillance of Autoimmune Diseases Induced By Biological Agents:

A Review of 12013 Cases (aeBIOGEAS-SEMI Registry)
Soledad Retamozo1,2,3, Manuel Ramos-Casals4,5, Marta Pérez de Lis6, Alejandra Flores-Chavez7,8,9, Sofia Arteaga10,11, Celeste
Galcerán-Chaves12, Belchin Kostov13, Roberto Pérez-Alvarez6 and Pilar Brito-Zerón2,14, 1Instituto de Investigaciones en Ciencias de la
Salud, Universidad Nacional de Córdoba, Consejo Nacional de Investigaciones Científicas y Técnicas (INICSA-UNC-CONICET), Cordoba,
Argentina, 2Laboratory of Systemic Autoimmune Diseases “Josep Font”, CELLEX, Institut d’Investigacions Biomèdiques August Pi i Sunyer
(IDIBAPS), Department of Systemic Autoimmune Diseases, ICMID, Hospital Clinic, Barcelona, Barcelona, Spain, 3Rheumatology Unit,
Hospital Privado Universitario de Córdoba, Institute University of Biomedical Sciences University of Córdoba (IUCBC), Cordoba,
Argentina, 4Laboratory of Systemic Autoimmune Diseases “Josep Font”, CELLEX, Institut d’Investigacions Biomèdiques August Pi i Sunyer
(IDIBAPS), Department of Systemic Autoimmune Diseases, ICMID, Hospital Clinic, Barcelona, Spain, Barcelona, Spain, 5Department of
Medicine, University of Barcelona, Barcelona, Spain., Barcelona, Spain, 6Department of Internal Medicine, Hospital Alvaro Cunqueiro,
Vigo, Vigo, Spain, 7Department of Autoimmune Diseases, ICMiD, Hospital Clínic Barcelona, Spain., Barcelona, Spain, 8Unidad de
Investigación Biomédica 02 (Unidad de Investigación en Epidemiología Clínica), UMAE, Hospital de Especialidades, Centro Médico
Nacional de Occidente, Instituto Mexicano del Seguro Social, Jalisco, Mexico, 9Programa de Doctorado en Ciencias Médicas, Centro
Universitario de Investigaciones Biomédicas (CUIB), Universidad de Colima, Colima, Mexico, Mexico, Mexico, 10Residente de
Reumatologia II año, Universidad de Antioquia, Medellin, Colombia, Medellin, Colombia, 11d) Department of Autoimmune Diseases,
ICMiD, Hospital Clínic Barcelona, Spain., Barcelona, Spain, 12Neuroscience Clinical Institute, Hospital Clínic, Barcelona, Spain,
Barcelona, Spain, 13Primary Care Research Group, IDIBAPS, Centre d’Assistència Primària ABS Les Corts, CAPSE, Barcelona,
Barcelona, Spain, 14Autoimmune Diseases Unit, Department of Medicine, Hospital CIMA- Sanitas, Barcelona., Bacelona, Spain
SESSION INFORMATION
Background/Purpose: The increasing use of biological agents has been linked with the paradoxical development of autoimmune processes.
The scenario has dramatically change in recent years due to the increased number and the emerging use of biologics in solid cancers.
Methods: In 2006, the Study Group on Autoimmune Diseases (GEAS) of the Spanish Society of Internal Medicine created the aeBIOGEAS
Registry (autoimmune events) designed to collect data on autoimmune diseases secondary to the use of biologic agents though a systemic and
yearly MEDLINE search. The baseline analysis identified in 2017 nearly 200 cases of autoimmune diseases triggered overwhelmingly anti-
TNF. We present the updated results of the aeBIOGEAS Registry (cases included until May 31, 2017).
Results: The aeBIOGEAS Registry currently includes 12013 cases of autoimmune diseases related to the administration of biological agents,
including more than 50 different systemic and organ-specific autoimmune processes; the most frequently reported were psoriasis (n=6377),
inflammatory bowel disease -IBD- (n=783), demyelinating CNS diseases (n=453), lupus (n=369), interstitial lung diseases -ILD- (n=378),
peripheral neuropathies (n=328), vasculitis (n=291) and hypophysitis (n=207). The main biological agents identified consisted of anti-TNF
agents in 9220 cases (mainly adalimumab in 4051, infliximab in 3109 and etanercept in 1496), B-cell targeted therapies in 729 (mainly
rituximab in 664), immune checkpoint inhibitors in 552 (mainly ipilimumab in 426 and nivolumab in 77) and vascular endothelial growth
factor inhibitors in 504 cases (bevacizumab). With respect to the biologic, the main associations were reported for the development of lupus
and hepatitis in patients treated with infliximab (44% and 45% of the reported cases of induced lupus and hepatitis, respectively),
demyelinating CNS diseases, sarcoidosis, uveitis and IBD in patients treated with etanercept (47%, 41%, 67% and 83%, respectively),
psoriasis in patients treated with adalimumab (56%), ILD in patients treated with rituximab (49%) and hypophysitis in patients treated with
ipilimumab (96%). With respect to the underlying disease for which the patient received the biological agent, the main associations were
reported for the development of lupus, vasculitis and sarcoidosis in patients with RA (68%, 84% and 47% of the reported cases of induced
lupus, vasculitis and sarcoidosis, respectively), uveitis and IBD in patients with JIA (60% and 41%, respectively), psoriasis in patients with
IBD (33%), hypophysitis in patients with melanoma (90%) and ILD in patients with hematological neoplasia (50%).
Conclusion: As the use of biological therapies expands, the number and diversity of induced autoimmune disorders is increasing
exponentially (Figure). Management of these biologic-induced autoimmune diseases will be an increasing clinical challenge in the daily
practice in the next years.
\s
Disclosure: S. Retamozo, None; M. Ramos-Casals, None; M. Pérez de Lis, None; A. Flores-Chavez, None; S. Arteaga, None; C.
Galcerán-Chaves, None; B. Kostov, None; R. Pérez-Alvarez, None; P. Brito-Zerón, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/pharmacovigilance-surveillance-of-autoimmune-diseases-

induced-by-biological-agents-a-review-of-12013-cases-aebiogeas-semi-registry
Hopes and Fears of Patients with Axial Spondyloarthritis in Spain. the Value of Patient
Opinion: Results from the Spanish Atlas
Marco Garrido-Cumbrera1, Pedro Plazuelo-Ramos2, Olta Brace1, David Galvez-Ruiz1 and Jorge Chacon-Garcia1, 1Universidad de
Sevilla, Seville, Spain, 2CEADE, Madrid, Spain
SESSION INFORMATION
Background/Purpose: Not much attention has been paid to listening to the opinions of patients in most scientific studies on
Spondyloarthritis, despite their opinions playing an increasingly important role in decision-making alongside clinical and public health
criteria. To assess the opinions of patients with Axial Spondyloarthritis (ax-SpA) using qualitative information.
Methods: A sample of 680 patients diagnosed with ax-SpA was interviewed during 2016 as part of the Spanish Atlas, which aims to
promote early referral and improve healthcare and the use of effective treatments in patients with ax-SpA. The Atlas is a CEADE initiative
(Spanish Coordinator of Patients with ax-SpA in Spain) developed by the University of Seville and Max Weber Institute in collaboration
with GRESSER (Spanish Rheumatology Society spondyloarthritis study group). Responses to qualitative items about patients’ hopes and
fears for their disease and their personal aims regarding their treatment were analysed.
Results: 53% were females, mean age 46 years and 77.1% were HLA-B27+. The five main hopes of patients are: stopping the disease,
dream of a cure, elimination of pain, improve their quality of life and live without limitations. Additionally, patients has expectations on the
medical research outcomes. Thus, 81% of patients hope that the research will make possible to find the cause and a cure for ax-SpA,
developing more efficient biologic therapies (11%), and finding new techniques or medication (8%). The following stand out among drug
treatment-related concerns: having more effective treatments (32%), sustaining the results of biologic therapies (29%), being able to start on
biologics (8%), the public health system funding non-drug treatments for AS (8%), eliminating secondary effects (15%), reducing prices
(4%), and correct use (4%). With respect to their fears, patients stated that their main concern was mobility loss (31%), followed by loss of
independence (23%), disability (22%), stiffness (12%), structural damage (3%), organ damage (3%), other illnesses and diseases
related(3%), physical decline (3%), and sight loss (1%). Patients who expressed fear regarding their disease listed their greatest concern
was that they would not overcome or tolerate pain (56%), followed by the fear that the disease would develop (32%), along with
was that they would not overcome or tolerate pain (56%), followed by the fear that the disease would develop (32%), along with
apprehension about flare-ups (7%), and tiredness (5%). With respect to patients’ personal objectives in terms of their treatments, they
highlighted the wish that their treatment would, first, help them to reduce and eliminate pain, increasing their in mobility, improved quality of
life, the avoidance of structural damage and the disease eventually being cured.
Conclusion: Analysis of patient opinion using qualitative information has enabled the identification of important concerns for patients such as
discovering the cause of the disease, reducing pain and structural damage, loss of self-sufficiency and disability.
Disclosure: M. Garrido-Cumbrera, None; P. Plazuelo-Ramos, None; O. Brace, None; D. Galvez-Ruiz, None; J. Chacon-Garcia, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/hopes-and-fears-of-patients-with-axial-spondyloarthritis-

in-spain-the-value-of-patient-opinion-results-from-the-spanish-atlas
Treatment Patterns in Large Vessel Arteritis (Giant Cell Arteritis and Temporal
Arteritis): Findings from a Large Contemporaneous Real-World Cohort in the US
Zhaohui Su1, Vandana Menon1, Richard Gliklich2 and Tom Brecht1, 1Research, OM1, Inc, Cambridge, MA, 2OM1, Inc, Cambridge, MA
SESSION INFORMATION
Background/Purpose:
Giant cell arteritis (GCA) is the most common form of primary systemic vasculitis with annual incidence as high as 27 per 100,000 in
persons over the age of 50 years. Key issues in management after a diagnosis of GCA include prompt initiation of therapy, prevention and
treatment of adverse effects related to treatment, and close monitoring for disease flares. Glucocorticoids are the mainstay of therapy and are
used for induction and maintenance of remission. However, there is little consensus on the optimal treatment strategies for GCA. We present
treatment patterns in a large real-world population of patients with GCA managed by rheumatologists across the US.
Methods:
The OM1 platform collects, links, and leverages, structured and unstructured data from electronic medical records (EMR) and other sources
in an ongoing and continuously updating manner to create a next generation registry-a novel approach to real world evidence. The OM1 GCA
Cohort includes data who met our definition of at least two GCA related diagnosis codes [ICD-10: M31.6, M31.5, M31.4; ICD-9:446.7,
446.5] within a 1 year period, treated by rheumatologists, between 2013 and 2016.
Results:
The cohort included 1,567 patients with a mean age of 72 + 10 years, three quarters were Caucasian (78%) and female (76%). Median
follow up time was 24 months with a mean of 12 rheumatology ambulatory encounters. Nearly a third of the cohort had a concomitant
diagnosis of polymyalgia rheumatica (33%) and 17% had rheumatoid arthritis. A majority of the patients had at least one erythrocyte
sedimentation rate (ESR) and C-reactive protein (CRP) measurement. Median ESR at baseline was 21mm/hr (IQR: 8, 48) and median CRP
was 1mg/L (0.3, 4.0). Only 6% of patients had a documented temporal artery biopsy. Patient reported pain scores were available in 26% of
the patients with a median duration of 6 months between first and last assessment. The majority of patients received glucocorticoids (85%),
22% were treated with methotrexate, 8% with hydroxychloroquine, 5% with aspirin, 5% with tocilizumab and 3.5% with azathioprine; 14%
were treated with more than one drug concurrently.
Conclusion:
We present findings from a large, representative, cohort of real-world patients seen in routine clinical practice. There are wide variations in
patient profile and treatment practices which may reflect the lack of clarity around value of additional steroid-sparing agents to avoid the
common glucocorticoid adverse effects and to reduce time to remission.
Disclosure: Z. Su, None; V. Menon, None; R. Gliklich, None; T. Brecht, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/treatment-patterns-in-large-vessel-arteritis-giant-cell-

arteritis-and-temporal-arteritis-findings-from-a-large-contemporaneous-real-world-cohort-in-the-us
Perception of Access to Mental Health Services in Publicly Insured Vs Privately Insured

Patients with Rheumatic Diseases
Elizabeth Soto-Cardona, Jackie Szymonifka and Robert F. Spiera, Rheumatology, Hospital for Special Surgery, New York, NY
SESSION INFORMATION
Session Title: ARHP Health Services Research Poster
Background/Purpose: To assess perception of access to mental health services (MHS) and utilization of those services based on
participant’s insurance type. We compared responses of participants with public insurance (Medicare and Medicaid) and private insurance
receiving rheumatologic care at an urban academic medical center.
Methods: Patients with rheumatic diseases seen in clinic and in private practices at a tertiary care academic medical center underwent a
standardized interview by a single interviewer. Patient reported utilization of medical care and mental health services, as well as perceptions
of access to those services was assessed using a standardized questionnaire. Socio-demographic variables were collected. Health
characteristics included rheumatological diagnosis, physical functional status and mental health, measured by the SF36. High scores, reported
on a scale from 0 to 100, define a more favorable health state. Responses from patients with public health insurance were compared to those
with private commercial insurance.
Results: Participants with private insurance were more likely to be white (p=.037), married (p=.001) and home owners (p <.001), whereas
participants with public insurance where more likely to be disabled (p=.074) and diagnosed with RA (p=.022) or SLE (p=.022). Those with
private insurance scored higher on the SF-36 and were less likely to recognize role limitations due to emotional problems (p=.028), score
lower for pain (p=.019) and to report worse physical function (p=.006). [Table 1]
Conclusion:
Of the 52 participants only 34 had received MHS in the past, 13/34 (38%) of public insurance patients, and 21/34 (61%) of private patients.
Patients with public insurance were less likely to perceive barriers to access to mental health services than were those with private
insurance, although that difference did not reach statistical significance (59% vs 24%, p= 0.227). In terms of relative ease of access to MHS
vs physical health specifically, 38% of participants with public insurance felt they had less access to MHS than to medical services in
general where as 61% of private practice patients reported perceiving less access to MHS (p=.041) than to medical services in general. The
majority of participants in both private (76%) and clinic settings (76%) felt access to MHS was important to their well-being. Conclusion:
Patients with rheumatic diseases commonly value the importance of mental health services, but frequently perceive barriers to access those
services. Perhaps surprisingly, patients with public insurance were less likely to perceive such barriers than those privately insured. Future
investigations should focus on identifying those specific barriers to mental health access for private and publicly insured patients in order to
facilitate provision of such services.
Table 1. SF-36 component scores by insurance type

All patients Medicare or Private
Medicaid insurance
(n=52) p-
SF-36 component (n=25) (n=27) value
Emotional well-being 74 [54, 88] 72 [56, 88] 76 [48, 88] 0.912
Energy/fatigue 48 [30, 73] 50 [30, 70] 45 [30, 75] 0.854
General health 43 [25, 60] 50 [25, 60] 40 [25, 60] 0.497
Pain 51 [23, 73] 33 [20, 68] 58 [45, 78] 0.019
Physical functioning 43 [25, 70] 35 [25, 50] 60 [40, 80] 0.006
Role limitations due to emotional 100 [0, 100] 33 [0, 100] 100 [33, 100] 0.028
problems
Role limitations due to physical health 0 [0, 50] 0 [0, 25] 25 [0, 100] 0.070
Social functioning 63 [50, 88] 63 [38, 75] 75 [50, 88] 0.570
Disclosure: E. Soto-Cardona, None; J. Szymonifka, None; R. F. Spiera, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/perception-of-access-to-mental-health-services-in-

publicly-insured-vs-privately-insured-patients-with-rheumatic-diseases
Ambulatory and Hospital Care for Arthritis and Related Conditions in Ontario, Canada
Y. Raja Rampersaud1, J. Denise Power2, Anthony V. Perruccio2, Michael Paterson3, Christian Veillette2, Elizabeth M. Badley4 and Nizar
Mahomed2, 1Arthritis Program, Krembil Research Institute, University Health Network, Torotno, ON, Canada, 2Arthritis Program, Krembil
Research Institute, University Health Network, Toronto, ON, Canada, 3Institute for Clinical Evaluative Sciences, Toronto, ON, Canada,
4Health Care & Outcomes Research, Krembil Research Institute, University Health Network, Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose: Ontario, Canada’s most populous province, has publicly funded, universal health insurance covering medically
necessary hospital and physician services with no copayments. The purpose of this study was to quantify the burden of arthritis and related
conditions (A&R) on the Ontario health care system, according to service type ( ambulatory vs. inpatient care) physician specialty (primary
care, rheumatology, orthopedics), and hospital setting (emergency department (ED), day surgery, inpatient care).
Methods: Administrative health data were analyzed for fiscal 2013/14 for Ontarians aged 18+ years (N=10,841,302). Data sources
included: the Ontario Health Insurance Plan (OHIP) Claims History Database, which captures data on in- and out-patient physician services;
the Canadian Institute for Health Information (CIHI) Discharge Abstract Database, which records diagnoses and procedures associated with
all inpatient hospitalizations; and the CIHI National Ambulatory Care Reporting System, which captures data on all ED and day surgery
encounters. Services associated with A&R were identified using the International Classification of Diseases (ICD) diagnosis code identified
on each physician service claim as the “main reason” for each outpatient physician visit and the “most responsible” ICD diagnosis code
recorded on each hospitalization, ED visit and day surgery record. Patient visit rates and numbers of patients and visits were tabulated
according to care setting, patient age and sex, and physician specialty for the grouping of all A&R, as well as for specific diagnoses, such as
osteoarthritis (OA) and rheumatoid arthritis (RA).
Results: Overall, 1.3 million adult Ontarians (11.9%) made 2.7 million outpatient physician visits for A&R in 2013/14, with 62% of these
visits occurring in primary care. Patient visit rates for A&R increased with age and were higher in women than men; women accounted for
60% of all A&R visits. Approximately 5% of adult Ontarians made an outpatient physician visit specifically for OA, with about 1% making
at least 1 visit for RA. 63% of outpatient visits for OA, and 35% for RA, were in primary care. Just over 25% of adult Ontarians who saw a
physician for OA consulted an orthopaedic surgeon at least once and 58% who made a visit for RA consulted a rheumatologist at least once.
Just over 1% of adult Ontarians made an ED visit for which the most responsible diagnosis was A&R, for a total of 142,000 visits. Rates of
hospitalization and day surgery for A&R were 410 and 190 per 100,000 population, respectively. The highest rate of inpatient hospitalization
was associated with OA, at 340 per 100,000, which accounted for 82% of all A&R-related hospital admissions.
Conclusion: A&R place a significant burden on the health care system, particularly in primary care. As the population ages, it will be
essential that health system planning takes into account the large demand for arthritis care, both in terms of health human resources planning
and implementation of clinically and cost-effective models of care.
Disclosure: Y. R. Rampersaud, None; J. D. Power, None; A. V. Perruccio, None; M. Paterson, None; C. Veillette, None; E. M. Badley,
None; N. Mahomed, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/ambulatory-and-hospital-care-for-arthritis-and-related-

conditions-in-ontario-canada
Clinical Pharmacist As Part of the Interprofessional Team Improves Quality of Care in

Patients with Rheumatic Disease
Jessica Farrell1, Lee S. Shapiro1 and Mitchell Miller2, 1The Center for Rheumatology, Albany, NY, 2Albany College of Pharmacy and
Health Sciences, Albany, NY
SESSION INFORMATION
Background/Purpose:
Successful multidisciplinary models exist for the management of chronic diseases such as diabetes, cardiovascular disease, infectious
diseases, kidney disease and psychiatric illnesses. A multidisciplinary team including a pharmacist in the ambulatory care setting has shown
to improve patient and population outcomes for various chronic disease states. Rheumatology healthcare providers recognize the burden of
rheumatic disease requires an integrated, multidisciplinary team including a pharmacist. Recent data suggests pharmacists can improve
adherence and health outcomes in the management of gout. This type of pharmacist-led intervention can easily be extrapolated to other
rheumatic diseases. The addition of a pharmacist to the healthcare team can have many benefits, including improving patient compliance and
education, serving as a drug information resource, and obtaining insurance coverage. This includes establishing patient relationships,
gathering medication histories, preventing, identifying and resolving medication related problems, educating patients and other healthcare
providers, monitoring patients and medication effects, and contributing to continuity of care for all patients. Clinical pharmacy services at
The Center for Rheumatology (TCFR) have expanded over the past 8 years.
Methods:
The aim of our project is to 1) provide billable pharmacy consult services which systematize practice-wide medication initiation and safety
monitoring, 2) provide additional support to practice-wide procedures/protocols related to medication therapy and insurance authorizations,
3) provide evidence of improved patient and population outcomes when a pharmacist is part of the interdisciplinary team in a rheumatology
practice, 4) serve as a business model of an innovative practice in pharmacy. Outcome measures include number of reimbursable visits,
assessments of medication prior authorizations, denials and peer-to-peer calls, and provider, support staff and patient surveys.
Results:
The pharmacist provides face-to-face problem/medication focused visits which are reimbursed through incident-to billing. Visits are focused
on initiation and safety monitoring for high-risk DMARD and osteoporosis therapies. The drug information consult services and insurance
authorization assistance have been shown to save providers and support staff time, ranging from 1-3+ hours per week per provider. Providers
report the addition of a pharmacist allows them to provide a higher level of care focused on medication therapy and safety, and helps
improves patient compliance and anxiety related to medications.
Conclusion:
The addition of a pharmacist to the multidisciplinary team in a rheumatology practice can improve the quality of care delivered to patients,
specifically related to medication safety and access by assisting in the prior authorization process and serving as patient advocates. The
addition of clinical pharmacy services sets the practice apart from others by improving patient care and serving as an innovative business
model for rheumatology practices to include a clinical pharmacist as part of their healthcare team.
Disclosure: J. Farrell, None; L. S. Shapiro, None; M. Miller, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/clinical-pharmacist-as-part-of-the-interprofessional-

team-improves-quality-of-care-in-patients-with-rheumatic-disease
Creation of the First Massive Open Online Course for Patients with Rheumatoid
Arthritis
Sonia Tropé 1, Jean-David Cohen2, Catherine Beauvais3, Didier Poivret4, Alain Saraux5, Danielle VACHER6, Hervé Barkatz7, Pascal
Lacoste7, Valérie Weill8 and Gérard Thibaud9, 1149 avenue du Maine, ANDAR, Paris, France, 2IMMUNO-RHEUMATOLOGY, CHU
LAPEYRONIE, MONTPELLIER, France, 3Service de Rhumatologie, Hopital Saint Antoine, Paris, France, 4Rheumatology, Metz, France,
5Rheumatology, Brest University Medical School Hospital, Brest, France, 6expert-patient, ANDAR patient organisation, Paris, France,
7Hbmotion, Paris, France, 8hbmotion, Paris, France, 9ANDAR patient organisation, Paris, France
SESSION INFORMATION
Background/Purpose: People with chronic conditions face the disease more effectively when they develop psychosocial skills and self-
care. Health authorities thus recommend the organization of therapeutic patient education (TPE). Suffering from different limitations, a patient
organisation had the idea to develop a digital training solution, accessible everywhere, complementary to TPE, for patients with rheumatoid
arthritis.
Methods: The choice was made for an online training program such as Massive Open Online Courses (MOOC). A preliminary survey was
carried out among the patients via an electronic questionnaire via social networks and an emailing to the organisation members.
A steering committee (COPIL) made up of representatives of the patients' association, expert patients and rheumatologists with the support of
a specialized agency, determined the timetable, the educational objectives, the contents, the speakers and the evaluations.
Results: The initial investigation was stopped at 100 responses, obtained in 3 days.
The majority of respondents planned to follow the MOOC on their computer (85.9%), but to meet the needs of all, the device is responsive.
More than half of respondents (61%) had never participated in a TPE program and 94% were interested in joining MOOC to learn new
information about the disease (78.8%), treatments (71.7% ), have expert views (67.7%), share experience with other patients (56.6%), and
better live with the disease (50.5%).
Respondents would like to have a weekly webconference lasting from 1 hour to 1h30.
About the MOOC :
• Using the Learning Management System platform drspoc.com
• Intervention of the experts via videos and live courses, evaluation of the achievements and, during two annual sessions, tutoring by patients
trained specifically.
At the beginning and end of the session, learners are invited to answer different questionnaires (knowledge, skills, satisfaction).
The MOOC includes the following modules:
• Introduction and background on MOOC
• Understanding Rheumatoid Arthritis
• Explore the care pathway, current events and treatment prospects
• Everyday life with rheumatoid arthritis

• Manage pain and fatigue.
COPIL identified 15 experts (patient-experts, rheumatologists, occupational therapist, physiotherapist, nutritionist, social worker,
psychologist, sexologist, nurse) who wrote the content of their speech. All texts have been validated by a pedagogical engineer and the
director of the association.
215 people pre-registered during the month preceding the launch, 148 persons active during the first session.
41 responses reccorded to the voluntary assessment questionnaire.
Conclusion: This is the first digital training strategy for people with rheumatoid arthritis.
This project proved to be useful to patients, offering an alternative or complement to TPE.
It will be necessary to evaluate the impact of this MOOC on the quality of life of the patients and their perception on its usefulness after
several sessions. An update is planned according to patient feedback and possible changes in content.
Disclosure: S. Tropé, None; J. D. Cohen, None; C. Beauvais, None; D. Poivret, None; A. Saraux, None; D. VACHER, None; H. Barkatz,
None; P. Lacoste, None; V. Weill, None; G. Thibaud, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/creation-of-the-first-massive-open-online-course-for-

Keeping a Balance: Social Engagement and Care Giving

Elizabeth M. Badley1,2, Dov Millstone2 and Anthony V. Perruccio2,3,4, 1Dalla Lana School of Public Health, University of Toronto,
Toronto, ON, Canada, 2Health Care & Outcomes Research, Krembil Research Institute, University Health Network, Toronto, ON, Canada,
3Arthritis Program, Krembil Research Institute, University Health Network, Toronto, ON, Canada, 4Institute of Health Policy, Management &
Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose:
Arthritis is associated with pain and disability. As a result there has been some interest in examining the receipt of care among those with
arthritis. What has garnered less attention is care giving in this population. The purpose of this study was to describe both care giving and
care receipt, and social engagement, in a nationally representative sample of later working age (age 45-64 years) people with arthritis.
Methods:
Analysis was based on the first wave data from the Canadian Longitudinal Study on Aging (CLSA), a nationally representative sample of
people aged 45-85. The questionnaire covers socio-demographic, health, functioning, social, and work variables. Analyses were limited to
participants aged 45-64 (n=12,319).
Results:
Overall, 30% reported arthritis: 4% reported RA, 17% OA, and 9% other arthritis. Arthritis was reported more frequently by women than
men. Most people with arthritis were married (75%), and 70% had more than a high school education. A significant proportion (70%) of
people with arthritis were overweight or obese. The majority of individuals with arthritis (68%) reported difficulty with at least one daily
activity - most frequently were crouching, kneeling or stooping; standing up after sitting; and standing for a long period. More than 85% were
currently in the labour force, and most were socially connected (e.g. 80% took part in community-based activities at least once a week).
Taking both informal and formal care together, around 20% of people arthritis in this age group received some form of care, with the majority
of care being informal only. A small proportion received professional care - most often assistance around the house (3%) and medical care
(2.5%). Overall, 18% received some kind of non-professional assistance: 14% around the house, 11% with transportation, and 10% with
meal preparation. Nearly 60% of the informal care received came from someone living in the same household, and a similar proportion was
provided by men and women. Almost half of care had been received for 6 months or less, although 22% reported receiving care for 5 years
or more. Over half of individuals with arthritis (53%) reported providing some kind of care to others: 39% gave assistance with
transportation, 31% assistance around the house, 25% assistance with meal preparation. Care was most frequently provided to individuals
living in another household. Care was provided for a median of 12 weeks in the past year and 5 hours per week. People reporting RA were
slightly more likely to report receiving care than those with OA. There was no difference in the proportion with RA and OA giving care.
Conclusion:
Against a backdrop of substantial limitations in activities, the majority of people with arthritis in the later decades of working life were in the
work force and engaged in the community. At the same time, more than half provided care to others, far more than the proportion that received
care. The need to provide care and at the same time balance work and a social and family life for individuals with arthritis may impact their
ability to care for themselves.
Disclosure: E. M. Badley, None; D. Millstone, None; A. V. Perruccio, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/keeping-a-balance-social-engagement-and-care-giving
Social Factors and Racial Disparities in Total Hip Arthroplasty Outcomes

Susan M. Goodman1, Bella Y. Mehta2, Meng Zhang3, Jackie Szymonifka4, Joseph T. Nguyen3, Yuo-Yu Lee3, Mark P. Figgie5, Michael L.
Parks5, Shirin A. Dey4, Daisy B. Crego4, Linda A. Russell6, Lisa A. Mandl7 and Anne R. Bass6, 1Medicine, Hospital for Special
Surgery/Weill Cornell Medicine, New York, NY, 2Rheumatology, Hospital for Special Surgery/Weill Cornell Medicine/Mailman School of
Public Health, New York, NY, 3Epidemiology and Biostatistics, Hospital for Special Surgery, New York, NY, 4Rheumatology, Hospital for
Special Surgery, New York, NY, 5Orthopaedic Surgery, Hospital for Special Surgery/Weill Cornell Medicine, New York, NY,
6Rheumatology, Hospital for Special Surgery/Weill Cornell Medicine, New York, NY, 7Rheumatology, Hospital for Special Surgery Weill
Cornell Medical College, New York, NY
SESSION INFORMATION
Session Title: Healthcare Disparities in Rheumatology Poster
Background/Purpose: Socioeconomic factors such as poverty may mediate racial disparities in health outcomes including those of total hip
arthroplasty (THA), and confound analyses of differences between blacks and whites.
Methods: Using data from a large institutional THA registry, we compared pain and function 2 years after surgery between blacks and
whites. The census tract variable “percent of the population with Medicaid insurance coverage” was used to measure community deprivation.
We used geocoding to link patients to census tracts, built models that incorporated both individual patient and census tract data, and analyzed
the interaction between race and percent of population with Medicaid coverage and its association with patient-reported outcomes 2 years
after THA.
Results: Black patients, comprising 145/4170 (3%) of THA cases, had worse pain and function scores both at baseline and at 2 years after
THA compared to whites (Table 1). There was a strong positive correlation between census tract Medicaid coverage and percent living
below the poverty line (rho = 0.69; p<0.001). Racial disparities in 2-year WOMAC pain and function were magnified in communities with a
high percentage of the population covered by Medicaid (Table 2). For blacks in these communities, 2-year WOMAC function scores were
predicted to be 5.54 points lower (80.42 vs. 85.96) than in blacks from communities with a low prevalence of Medicaid coverage, while
scores for whites did not differ between communities. Pain scores were also lower for blacks living in deprived areas, but the difference
was not significant.
Conclusion: WOMAC pain and function 2 years after THA are similar among blacks and whites in communities with little deprivation
(measured as percent of the population with Medicaid insurance coverage). WOMAC function at 2 years is worse among blacks in areas of
higher deprivation, whereas this poverty gradient does not impact outcomes among whites.
Table 1: Characteristics of the cohort
Characteristic Total White Black P-Value
Number of patients 4170 (100%) 4025 (97%) 145 (3%)
Age at surgery (years), mean 61.69
65.29 (11.01) 65.42 (10.98) 0.0002
(SD) (11.23)
Female, n (%) 2311 (55.42%) 2219 (55.13%) 92 (63.45%) 0.048
BMI (kg/m2), mean (SD) 27.75 (5.48) 27.68 (5.44) 29.74 (6.33) 0.0002
Hispanic, n (%) 75 (1.80%) 73 (1.81%) 2 (1.38%) 1.00
One or more comorbidities, n
1013 (24.29%) 956 (23.75%) 57 (39.31%) <0.0001
(%)
College or above, n (%) 2805 (68.35%) 2721 (68.69%) 84 (58.74%) 0.012
Insurance payer, n (%) 30 (0.75%) 23 (15.86%)
53 (1.27%)
Medicaid 2257 (56.07%) 60 (41.38%)
2317 (55.56%) <0.0001
Medicare 1738 (43.18%) 62 (42.76%)
1800 (43.17%)
Other insurance
ASA Class, n (%) 2 2 0
Missing 3387 (81.26%) 3279 (81.51%) 108

(74.48%) 0.033
I-II 781 (18.74%) 744 (18.49%)
37 (25.52%)
III-IV
Hospital for Special Surgery 83.30 (16.46) 83.17 (16.52) 86.64 0.043
Expectations Score, mean (14.42)
(SD)
WOMAC pain at baseline, 53.58 (17.85) 53.84 (17.72) 46.48 <0.0001
mean (SD) (20.04)
WOMAC pain at 2 Years, 93.63 (11.39) 93.81 (11.13) 88.60 <0.0001
mean (SD) (16.39)
Delta WOMAC pain, mean 40.04 (19.14) 39.97 (18.95) 42.15 0.144
(SD) (23.75)
WOMAC function at baseline, 49.93 (18.04) 50.19 (18.00) 42.78 <0.0001

mean (SD) (17.80)
WOMAC function at 2 Years, 90.86 (13.21) 85.43 (16.09) 77.80 <0.0001
mean (SD) (22.42)
Delta WOMAC function, 40.93 (19.31) 40.89 (19.12) 41.93 0.351
mean (SD) (24.22)
Percent Below Poverty Level, 3363 (80.69%) 3303 (82.10%) 60 (41.38%)
n (%)
626 (15.02%) 585 (14.54%) 41 (28.28%)
<10%
102 (2.45%) 82 (2.04%) 20 (13.79%)
10%-20%
51 (1.22%) 33 (0.82%) 18 (12.41%) <0.0001
20%-30%
26 (0.62%) 20 (0.50%) 6 (4.14%)
30%-40%
>40%
Percent with Medicaid 3128 (75.85%) 3086 (76.71%) 42 (32.31%)
Coverage, n (%)
679 (16.46%) 644 (16.12%) 35 (26.92%)
<=10%
194 (4.70%) 167 (4.18%) 27 (20.77%)
10%-20%
<0.0001
97 (2.35%) 77 (1.93%) 20 (15.38%)
20%-30%
26 (0.63%) 20 (0.50%) 6 (4.62%)
30%-40%
>40%
Table 2: WOMAC pain and function 2 years after total hip arthroplasty: interaction between race and percent of
Medicaid coverage at census-tract level
Percent of WOMAC Pain at 2 Years* WOMAC Function at 2 Years**
Medicaid
Coverage
Race Estimate Est. Difference P- Estimate Est. Difference P-
at Census-
(Standard Error) (Standard Error) Value (Standard Error) (Standard Error) Value
Tract
Level
Black 88.44 (1.59) 85.96 (1.78)
10% -1.99 (1.29) 0.12 -1.99 (1.44) 0.17
White 90.43 (1.05) 87.95 (1.19)
Black 87.54 (1.28) 84.11 (1.43)
20% -2.59 (1.12) 0.02 -3.48 (1.26) 0.01
White 90.13 (1.08) 87.59 (1.22)
Black 86.63 (1.38) 82.27 (1.49)
30% -3.20 (1.45) 0.03 -4.96 (1.60) 0.002
White 89.82 (1.16) 87.23 (1.31)
Black 85.72 (1.81) 80.42 (1.93)
40% -3.80 (2.04) 0.06 -6.45 (2.24) 0.004
White 89.52 (1.28) 86.87 (1.45)
Black 84.81 (2.41) 78.57 (2.56)
50% -4.40 (2.74) 0.11 -7.94 (2.99) 0.01
White 89.21 (1.44) 86.51 (1.63)
Black 83.91 (3.07) 76.73 (3.28)
60% -5.01 (3.47) 0.15 -9.42 (3.78) 0.01
White 88.91 (1.61) 86.15 (1.83)
*Estimation based on linear mixed-effect model assessing the effect of interaction between race and percent of Medicaid
coverage at census-tract level on WOMAC pain at 2 years after THA, using the following assumptions: WOMAC pain at
baseline=53; age at surgery=65; BMI=28/kg/m2; HSS expectation score=83; sex=female; comorbidities=0;
insurance=Medicaid; education=college and above.
** Estimation based on linear mixed-effect model assessing the effect of interaction between race and percent of Medicaid
coverage at census-tract level on WOMAC function at 2 years after THA, using the following assumptions: WOMAC
function at baseline=49; age at surgery=65; BMI=28/kg/m2; HSS expectation score=83; sex=female; comorbidities=0;
insurance=Medicaid; education=college and above.
Disclosure: S. M. Goodman, None; B. Y. Mehta, None; M. Zhang, None; J. Szymonifka, None; J. T. Nguyen, None; Y. Y. Lee, None; M.
P. Figgie, Lima, 7,Mekanika, 1; M. L. Parks, Zimmer Biomet, Inc., 5; S. A. Dey, None; D. B. Crego, None; L. A. Russell, None; L. A.
Mandl, Boehringer Ingelheim, 2,American College of Physicians, 3,Up To Date, 7; A. R. Bass, Pfizer, 9,Abbot, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/social-factors-and-racial-disparities-in-total-hip-

arthroplasty-outcomes
Disparities in Patients’ Expectations of Foot and Ankle Surgery

Mackenzie T. Jones1, Elizabeth A. Cody1, Shirin A. Dey2, Jackie Szymonifka2, Michael L. Parks3, Lisa A. Mandl4, Susan M. Goodman5
and Scott J. Ellis6, 1Hospital for Special Surgery, New York, NY, 2Rheumatology, Hospital for Special Surgery, New York, NY,
3Orthopaedic Surgery, Hospital for Special Surgery/Weill Cornell Medicine, New York, NY, 4Rheumatology, Hospital for Special Surgery
Weill Cornell Medical College, New York, NY, 5Medicine, Hospital for Special Surgery/Weill Cornell Medicine, New York, NY,
6Hospital for Special Surgery/Weill Cornell Medicine, New York, NY
SESSION INFORMATION
Background/Purpose:
A previous study examining patients’ expectations of elective foot and ankle surgery found that race is significantly associated with
expectations. In this study, using a patient-derived institutional Foot & Ankle Surgery Expectations Survey, we aimed to examine the
relationship between patients’ preoperative expectations and census tract (CT) socioeconomic factors in addition to race.
Methods:
All adult patients scheduled for elective foot or ankle surgery by one of six orthopedic surgeons were screened for inclusion between August
2015 and March 2016. Preoperatively, patients completed the Foot & Ankle Surgery Expectations Survey, which contains 23 expectations
categories, each rated on a 5-point Likert scale ranging from “I do not have this expectation” to “complete improvement expected”, with
higher scores (range 1-23) indicating greater expectations. Using geocoding, individual-level registry data was linked to US census tracts
data through patient addresses. Simple and multiple linear regression were used to model expectations scores as a function of individual
race, and CT median income, Gini coefficient, and percentages of blacks, Hispanics, residents living below poverty, residents living alone,
residents with insurance coverage, and residents with Medicaid coverage. The multiple linear regression model used backward selection
methodology, requiring 0.05 significance to remain in the final model. An interaction between race and CT poverty was assessed.
Results:
352 patients (mean age 55±14 years, 66% female) were included in this study. Factors that were significantly associated with higher
expectations in univariate modeling were non-Caucasian race, female sex, and census tract percentage of blacks, census tract percentage of
Hispanics, census tract percentage of residents with Medicaid insurance, census tract poverty level, and census tract Gini coefficient (all
p<0.05, Table 1). In multivariable modeling, females scored 5 points higher (5.00±1.93, p=0.01) on the Expectations Survey than males.
Caucasians scored nearly 11 points lower (-10.98±3.13, p<0.001) than non-whites. There were no community CT variables that remained
significant, and there was no interaction between race and CT poverty (p=0.7).
Conclusion:
Among patients undergoing diverse procedures in foot and ankle surgery, we found that female sex and non-Caucasian race were
independently associated with higher expectations, but community social factors were not significant. These findings may help inform
surgeons’ preoperative discussions as they address patients’ expectations. Future studies are needed to explore whether preoperative
expectations scores correlate with postoperative satisfaction, and whether the factors that affect expectations also affect satisfaction.
Table 1
Univariate Factor Beta coefficient ± SE p-value
Age, per 10 years -0.63 ± 0.69 0.358
Sex: female 4.73 ± 2.09 0.024
(reference=male)
BMI, per 1 kg/m2 0.21 ± 0.17 0.220
Race: white -12.48 ± 3.35 <0.001
(reference=non-white)
Marital status: married -3.46 ± 2.09 0.100
(reference=not married)
FAOS* Pain, per 10 points-2.40 ± 0.43 <0.001
FAOS Symptoms, per 10 -1.47 ± 0.44 <0.001
points
FAOS ADL, per 10 points -2.57 ± 0.41 <0.001
FAOS Sports, per 10 -1.70 ± 0.33 <0.001
points
FAOS QoL, per 10 points -2.76 ± 0.42 <0.001
SF-12 overall, per 10 -2.53 ± 0.85 0.004
points
PCS, per 5 points -2.69 ± 0.41 <0.001
MCS, per 5 points -1.14 ± 0.44 0.010
Census tract data
Percent black, per 1 0.19 ± 0.09 0.036
percent
Percent Hispanic, per 1 0.22 ± 0.09 0.017
percent
Percent single mothers, 0.55 ± 0.46 0.237
per 1 percent
Percent live alone, per 1 -0.07 ± 0.92 0.942
percent
Percent insured, per 1 -0.32 ± 0.18 0.066
percent
Percent Medicaid, per 1 0.42 ± 0.13 0.001
percent
Percent below poverty, 0.53 ± 0.18 0.003
per 1 percent
Median income, per -0.36 ± 0.23 0.114
$10,000
Gini coefficient, per 10 -3.39 ± 1.38 0.015
percent
Multivariable Factor Beta coefficient ± SE p-value

Sex: female 5.00 ± 1.93 0.010
(reference=male)
Race: white -10.98 ± 3.13 <0.001
(reference=non-white)
FAOS ADL, per 10 points -1.50 ± 0.52 0.004
PCS, per 5 points -1.71 ± 0.52 0.001
*FAOS = Foot and Ankle Outcome Score
Disclosure: M. T. Jones, None; E. A. Cody, None; S. A. Dey, None; J. Szymonifka, None; M. L. Parks, Zimmer Biomet, Inc., 5; L. A.
Mandl, Boehringer Ingelheim, 2,American College of Physicians, 3,Up To Date, 7; S. M. Goodman, None; S. J. Ellis, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/disparities-in-patients-expectations-of-foot-and-ankle-

surgery
English Language Proficiency and Total Joint Replacement Outcomes: Is There a

Relationship?
Bella Y. Mehta1, Jackie Szymonifka2, Shirin A. Dey2, Stephen Grassia3, Lisa A. Mandl4, Anne R. Bass4, Linda A. Russell4, Michael L.
Parks5, Mark P. Figgie5, Yuo-Yu Lee6, Joseph T. Nguyen6 and Susan M. Goodman4, 1Hospital for Special Surgery/Columbia University
Mailman School of Public Health, New York, NY, 2Rheumatology, Hospital for Special Surgery, New York, NY, 3Medicine, Hospital for
Special Surgery, New York, NY, 4Rheumatology, Hospital for Special Surgery/Weill Cornell Medicine, New York, NY, 5Orthopaedic
Surgery, Hospital for Special Surgery/Weill Cornell Medicine, New York, NY, 6Epidemiology and Biostatistics, Hospital for Special
SESSION INFORMATION
Background/Purpose:
Healthcare disparities are recognized for surgical outcomes in patients with Limited English Proficiency (LEP) (1). The purpose of this study
is to assess the association of LEP on Total Knee (TKR) and Total Hip Replacement (THR) outcomes.
Methods:
Individual patient-level variables – namely, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function
scores at baseline and 2 years after elective TKR and THR – were collected from a single institution registry between 5/07 and 2/11 and
analyzed. We used census tract LEP -“Less than very well” as recommended for screening individuals. We obtained census level data using
patients’ geocodable addresses (2). Only patients from closest states (NY, NJ and CT) were included (Figure 1). Data was analyzed using
univariate and multivariable linear mixed effects models, with census tracts variables treated as random effects.
Results:
Table 1 describes the characteristics of the patients with THR and TKR. In univariable analyses, for every percent increase in LEP, the
WOMAC scores at baseline and 2 year decreased significantly (p-value<0.001). However when adjusted for neighborhood poverty age,
BMI, sex, comorbidities, and the Gini coefficient these changes were not statistically significant, suggesting potential confounders (Table 2).
While women had worse baseline and 2-year WOMAC pain and function scores (all p≤0.04), this difference was not significantly
influenced by neighborhood LEP (all p_interaction=NS).
Conclusion:
Patients from LEP neighborhoods have worse pain and function scores in unadjusted models. However when adjusted for potential
confounders, the difference is not significant. Community factors contributing to healthcare disparities are multidimensional; thus, further
studies examining individual LEP data would be warranted.
1. John-Baptiste et al., J Gen Int Med. Mar 2004; 19(3):221-228.
2. Karliner et al., J Gen Int Med. Oct 2008; 23(10):1555-1560.

Table 1. Total Joint Replacement Patient characteristics
Characteristic Total Hip Total Knee
Replacement Replacement
(N=4009) (N=3898)
Patient demographics
Age at surgery (years), mean ± SD 65.6 ± 10.6 67.8 ± 9.5
Sex: female, n (%) 2160 (53.9%) 2346 (60.2%)
BMI (kg/m2) 27.9 ± 5.4 30.0 ± 5.9
Race, n (%)
White 3794 (94.6%) 3568 (91.5%)
Black 131 (3.3%) 174 (4.5%)
Asian 25 (0.6%) 74 (1.9%)
Other 43 (1.1%) 56 (1.4%)
Unknown 16 (0.4%) 26 (0.7%)
Hispanic ethnicity, n (%) 102 (2.5%) 129 (3.3%)
Patient status
ASA class
I–II 3307 (82.5%) 3124 (80.1%)
III–IV 700 (17.5%) 773 (19.8%)
One or more comorbidities 895 (22.3%) 1057 (27.1%)
Census tract characteristics
Poverty, n (%)
< 10% 3325 (82.9%) 2787 (71.5%)
10% – < 20% 507 (12.7%) 511 (13.1%)
20% – < 30% 115 (2.9%) 129 (3.3%)
30% – < 40% 49 (1.2%) 56 (1.4%)
≥ 40% 13 (0.3%) 27 (0.7%)
Percent poverty, mean ± SD 6.2 ± 6.5 6.6 ± 7.2
Limited English Proficiency
(LEP), n (%)
< 10% 2981 (74.4%) 2787 (71.5%)
10% – < 20% 614 (15.3%) 650 (16.7%)
20% – < 30% 209 (5.2%) 251 (6.4%)
30% – < 40% 120 (3.0%) 113 (2.9%)
≥ 40% 85 (2.1%) 97 (2.5%)
Percent LEP, mean ± SD 8.6 ± 9.6 9.2 ± 10.0
Gini coefficient, mean ± SD 0.45 ± 0.07 0.45 ± 0.07
Patient-reported outcomes
Baseline survey results, mean ± SD
WOMAC pain 53.3 ± 17.8 54.4 ± 17.5
WOMAC function 49.5 ± 18.0 53.7 ± 17.6
2-year survey results
WOMAC pain, mean ± SD 93.7 ± 11.3 87.9 ± 15.6
WOMAC function, mean ± SD 91.1 ± 13.1 85.6 ± 16.1
Methodology: Categorical variables are summarized as frequency (percent).
Continuous variables are summarized as mean ± standard deviation
Table 2. Impact of every 10% change in neighborhood limited
English proficiency on WOMAC pain and function
Time-point WOMAC p-value WOMAC p-value
pain function
Estimate ± SE Estimate ± SE
Total Hip Replacement
Baseline -1.4 ± 0.3 <0.001 -1.7 ± 0.3 <0.001
(Univariate)
2-year (Univariate) -0.9 ± 0.2 <0.001 -1.2 ± 0.2 <0.001
Baseline -0.6 ± 0.3 0.10 -0.6 ± 0.3 0.07
(Multivariable)
2-year -0.4 ± 0.2 0.054 -0.6 ± 0.3 0.01
(Multivariable)
Total Knee Replacement
Baseline -1.7 ± 0.3 <0.001 -1.8 ± 0.3 <0.001
(Univariate)
2-year (Univariate) -1.0 ± 0.3 <0.001 -1.1 ± 0.3 <0.001
Baseline -0.8 ± 0.3 0.02 -0.5 ± 0.3 0.13
(Multivariable)
2-year -0.2 ± 0.3 0.43 -0.2 ± 0.3 0.54
(Multivariable)
Methodology: Univariate and multivariable linear mixed-effects
models were analyzed, with census tracts treated as random effects. In
addition to neighborhood Limited English Proficiency, variables
included in the model were: age, BMI, sex, ≥ 1 comorbidity,
neighborhood percent poverty (<10%, 10% - < 20%, 20% - < 30%,
30% - < 40%, ≥ 40% [reference group]), neighborhood Gini
coefficient was also included.
Disclosure: B. Y. Mehta, None; J. Szymonifka, None; S. A. Dey, None; S. Grassia, None; L. A. Mandl, Boehringer Ingelheim, 2,American
College of Physicians, 3,Up To Date, 7; A. R. Bass, Pfizer, 9,Abbot, 9; L. A. Russell, None; M. L. Parks, Zimmer Biomet, Inc., 5; M. P.
Figgie, Lima, 7,Mekanika, 1; Y. Y. Lee, None; J. T. Nguyen, None; S. M. Goodman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/english-language-proficiency-and-total-joint-replacement-

outcomes-is-there-a-relationship
Do Immigrant Communities Play a Role in Total Knee Arthroplasty (TKA) Outcomes?

Bella Y. Mehta1, Jackie Szymonifka2, Shirin A. Dey2, Stephen Grassia3, Lisa A. Mandl4, Anne R. Bass4, Linda A. Russell4, Michael L.
Parks5, Mark P. Figgie5, Yuo-Yu Lee6, Joseph T. Nguyen6 and Susan M. Goodman4, 1Hospital for Special Surgery/Columbia University
Mailman School of Public Health, New York, NY, 2Rheumatology, Hospital for Special Surgery, New York, NY, 3Medicine, Hospital for
Special Surgery, New York, NY, 4Rheumatology, Hospital for Special Surgery/Weill Cornell Medicine, New York, NY, 5Orthopaedic
Surgery, Hospital for Special Surgery/Weill Cornell Medicine, New York, NY, 6Epidemiology and Biostatistics, Hospital for Special
SESSION INFORMATION
Background/Purpose: Social factors affect TKA (total knee arthroplasty) outcomes in osteoarthritis, both at the individual and neighborhood
levels. However, prior studies have not evaluated the influence of the proportion of foreign-born individuals within a neighborhood, as
reported for other high-cost procedures (1). Our objective was to determine the association of neighborhood foreign-born resident
proportion (FBRP) on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores at baseline and
2 years after elective TKA. We examined if this is different between sexes.
Methods: Individual patient-level variables were obtained from a single institution TKA registry from 5/07-1/11, including demographics,
baseline and 2 year WOMAC pain and function, and geocodable US addresses. We only included patients living in the hospital’s catchment
area - i.e. New York, Connecticut and New Jersey (Figure 1). Individual patient-level variables were then linked to US Census Bureau data
at the census tract level. Data was analyzed using univariate and multivariable linear mixed effects models, with census tracts variables
treated as random effects. A separate linear mixed-effects model was used to assess the interaction between neighborhood FBRP and gender.
Results: Table 1 describes the 3,898 TKA cases analyzed. In multivariable analyses, patients from neighborhoods with low FBRP (< 10%)
had slightly higher baseline and 2-year WOMAC pain and function scores than those with high FBRP (≥ 40%), but these differences were not
statistically significant (Table 2). While women had worse baseline and 2-year WOMAC pain and function scores (all p ≤ 0.04), this
difference was not significantly influenced by neighborhood FBRP (all pinteraction NS).
Conclusion: Patients coming from high (>40%) FBRP neighborhoods present with worse baseline pain and function. Two years later, worse
pain and function persist; however, the difference is not significant. Although sex differences favoring males are notable, these differences
are not associated with FBRP. Social factor contributions to healthcare disparities are multidimensional, and future studies examining
immigration-related neighborhood characteristics may be warranted.
1) Mojica, C. M., et al., Biomed Res Int 2015:460181.

Table 1. Baseline characteristics
Characteristic FBRP* <10% FBRP* ≥10 - FBRP* > p-value
≤ 40% 40%
(n=1032) (≤ 10% v. >
(n=2527) (n=339) 40%)
Patient demographics
Age at surgery (years), mean 67.0±9.2 68.1±9.6 67.8±9.6 0.16
±SD
Sex: female, n (%) 568 (55.0%) 1538 (60.9%) 240 (70.8%) <0.001
2
BMI (kg/m ), mean±SD 30.1±5.7 29.9±6.0 31.0±6.6 0.03
Race, n (%) <0.001
White 1012 (98.1%) 2297 (90.9%) 259 (76.4%)
Black 5 (0.5%) 128 (5.1%) 41 (12.1%)
Asian 9 (0.9%) 47 (1.9%) 18 (5.3%)
Other 5 (0.5%) 35 (1.4%) 16 (4.7%)
Unknown 1 (0.1%) 20 (0.8%) 5 (1.5%)
Ethnicity, n (%) <0.001
Hispanic 5 (0.5%) 35 (1.4%) 16 (4.7%)
Patient status
ASA class 0.81
I–II 828 (80.2%) 2026 (80.2%) 270 (79.7%)
III–IV 203 (19.7%) 501 (19.8%) 69 (20.4%)
One or more comorbidities 267 (25.9%) 674 (26.7%) 116 (34.2%) 0.003
Sociodemographic
characteristics
Education level (highest), n <0.001
(%)
Some high school, high 359 (36.0%) 849 (35.1%) 158 (49.4%)
school graduate or some
college
College graduate or Masters, 639 (64.0%) 1569 (64.9%) 162 (50.6%)
professional or doctorate
degree
Lives alone, n (%) <0.001
No 863 (84.4%) 1881 (75.9%) 229 (69.0%)
Yes 159 (15.6%) 598 (24.1%) 103 (31.0%)
Census tract characteristics
Poverty, n (%) <0.001
< 10% 975 (94.5%) 2078 (82.2%) 122 (36.0%)
10% – < 20% 48 (4.7%) 300 (11.9%) 163 (48.1%)
≥ 20% 9 (0.9%) 149 (5.9%) 54 (15.9%)
Patient-reported outcomes
Baseline survey results, mean
±SD
WOMAC** pain 54.9±17.6 54.7±17.3 51.0±18.9 <0.001
WOMAC** function 54.2±16.9 54.1±17.7 49.1±17.3 <0.001
2-year survey results
WOMAC** pain, mean±SD 89.3±14.7 87.5±15.7 86.5±17.5 0.01
WOMAC** function, mean 86.7±14.9 85.4±16.2 83.6±17.9 0.005
±SD
*FBRP – Foreign Born Resident Proportion, **WOMAC-Western Ontario and
McMaster Universities Osteoarthritis Index
Methodology: Categorical variables are summarized as frequency (percent).

Continuous variables are summarized as mean ± standard deviation. Comparisons of
categorical variables were made using chi-squared test. Continuous variables were
compared using t-tests (for ≤ 10% v. > 40%) or ANVOA tests (for 3-group
comparisons)
Table 2. Impact of neighborhood foreign born resident
proportion (FBRP) on WOMAC pain and function.
Timepoint WOMAC** p-value WOMAC** p-value
pain function
estimate ± SD estimate ± SD
Baseline 0.36 0.24
FBRP* < 52.30 ± 3.26 51.71 ± 3.28
10%
FBRP* ≥ 51.19 ± 3.33 50.31 ± 3.36
40%
2-year 0.80 0.97
FBRP* < 85.08 ± 3.02 85.95 ± 3.11
10%
FBRP* ≥ 84.81 ± 3.09 85.90 ± 3.18
40%
*FBRP – Foreign Born Resident Proportion, **WOMAC-
Western Ontario and McMaster Universities Osteoarthritis
Index
Methodology: Multivariable models adjusting for age, sex, ≥ 1

comorbidity, neighborhood poverty percentage (<10%, 10% -
< 20%, 20% - < 30%, 30% - < 40%, ≥ 40% [reference group])
Disclosure: B. Y. Mehta, None; J. Szymonifka, None; S. A. Dey, None; S. Grassia, None; L. A. Mandl, Boehringer Ingelheim, 2,American
College of Physicians, 3,Up To Date, 7; A. R. Bass, Pfizer, 9,Abbot, 9; L. A. Russell, None; M. L. Parks, Zimmer Biomet, Inc., 5; M. P.
Figgie, Lima, 7,Mekanika, 1; Y. Y. Lee, None; J. T. Nguyen, None; S. M. Goodman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/do-immigrant-communities-play-a-role-in-total-knee-

arthroplasty-tka-outcomes
Characterization of Unexpected Autoantibody Specificities in American Indian SLE

Patients
Joseph M. Kheir1, Tim Gross1, Carla J. Guthridge1, Krista Bean1, Virginia C. Roberts1, Joel M. Guthridge2, M. Sohail Khan3, Fabio
Mota4, Michael Peercy5, Bobby Saunkeah6 and Judith A. James7, 1Arthritis and Clinical Immunology, Oklahoma Medical Research
Foundation, Oklahoma City, OK, 2Arthritis & Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK,
3Cherokee Nation Health Services, Tahlequah, OK, 4Chickasaw Nation Medical Center, Ada, OK, 5Epidemiology, Chickasaw Nation
Department of Health, Ada, OK, 6Chickasaw Nation Department of Health, Ada, OK, 7Arthritis & Clinical Immunology Program, Oklahoma
Medical Research Foundation, Oklahoma City, OK
SESSION INFORMATION
Background/Purpose:
System Lupus Erythematosus (SLE) is an autoimmune disease that is over-represented in the American Indian (AI) population and often
manifests as a more severe disease. Although the clinical manifestations can be diverse, nearly all patients share the presence of
autoantibodies, including anti-dsDNA and anti-Sm which have high specificity for the disease. American Indian SLE patients often lack
reactivity to autoantigens commonly found in SLE patients of other ethnicities. We have observed that sera from 41% of AI SLE patients
contain unidentified autoantigenic reactivity by precipitin testing compared to 24% for AA, 17% for EA, and 23% for HA. Therefore the goal
of this study is to identify non-traditional autoantibody specificities associated with disease in AI SLE patients.
Methods:
The sera from 100 AI SLE patients, 37 AI unaffected controls, 16 AI unaffected family members, and 17 AI patients with other systemic
autoimmune diseases were screened using a 128 autoantigen protein array. Antigen reactivity based on a mean fluorescence intensity three
standard deviations above the average of the unaffected negative controls for that antigen were considered positive. Hierarchical clustering
of these data was used to identify shared autoantibody reactivities.
Results:
Twenty-two percent (n=22) of all of the positive SLE patients, 19% (n=3) of all positive unaffected family members, and 24% (n=4) of all
positive other autoimmune disease samples had reactivity to the M2 mitochondrial antigen typically associated with primary biliary cirrhosis
(PBC), an autoimmune liver disease. Furthermore, 91% (n=20) of the M2 positive SLE samples also contained 1 or more autoantibodies
specific for or associated with myositis, whereas only 33% (n=1) of M2 positive unaffected family member samples, and 50% (n=2) of the
M2 positive samples from individuals with other autoimmune disease contained myositis specific or associated autoantibodies.
Conclusion:
This study suggests that M2 and myositis autoantibodies are associated with disease in American Indian SLE patients. Although SLE patients
are often diagnosed with more than one autoimmune disease, the coexistence of SLE and PBC or myositis is rare. The study was funded in
part by Native American Research Centers for Health.
Disclosure: J. M. Kheir, None; T. Gross, None; C. J. Guthridge, None; K. Bean, None; V. C. Roberts, None; J. M. Guthridge, None; M.
S. Khan, None; F. Mota, None; M. Peercy, None; B. Saunkeah, None; J. A. James, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/characterization-of-unexpected-autoantibody-

specificities-in-american-indian-sle-patients
Decreased Medication Adherence Is a Major Cause for Increased Risk of

Hospitalizations Among High Risk Lupus Patients
Caroline Thirukumaran1, Katherine McCarthy2, Jessica Patel3 and Allen P. Anandarajah4, 1orthopedics, University of Rochester Medical
Center, Rochester, NY, 2Pharmacy, University of Rochester Medical Center, Rochester, NY, 3Allergy, Immunology and Rheumatology,
University of Rochester Medical Center, Rochester, NY, 4Dept of Rheumatology, Univ of Rochester Medical Ctr, Rochester, NY
SESSION INFORMATION
Background/Purpose: Low medication adherence in lupus has been associated with increased hospitalizations, more severe disease
activity, and irreversible multi-organ damage. While lower socioeconomic levels, education, depression and polypharmacy have been
identified as common determinants of non-adherence among patients with chronic diseases, few studies have investigated the rates of
medication adherence with lupus.
Purpose: To compare medication adherence among patients with lupus at high risk for multiple admissions with all admissions for lupus.
Methods: We previously identified 171 lupus patients with a confirmed diagnosis that were admitted to Strong Memorial Hospital between
July 1st of 2013 and June 30th of 2015. We then classified a high risk group of 28 lupus patients who had required ≥ 3 admissions/ year over
the 2 years. For this study we linked the database of all lupus patients with pharmacy claims database for the same period to calculate the
medication possession ratio (MPR), an indicator of whether a patient had adequate medication supply in a given time frame. For the bivariate
analysis, we used t-tests and chi-square tests to check for the differences in distribution of patient demographics and MPR across the high-
risk and non-high risk group. For the multivariate analyses, we estimated hierarchical linear regression models and controlled for the
clustering of refills by patient and medication. We also controlled for patient demographics and medication details. We used two-tailed
hypothesis tests and p-value<0.05 to indicate statistical significance.
Results: The high-risk group was significantly younger (mean age 39.64 years [SD: 19.09] as compared to mean age of 47.57 years in non-
high risk group, (p=0.03), 82% were females compared to 92% in the non-high risk group and the group had significantly higher proportion of
African Americans 61% as compared to 41% in the non-high risk group (p=0.05) see Table 1. Complete pharmacy data was available for
102 patients. The mean MPR was lower among the high-risk group (73.40% as compared to 79.93% in the non-high risk group). Our
multivariate analysis showed that after controlling for relevant confounders, on average high-risk patients had 10 percent point lower MPR as
compared to non-high risk patients (Estimate: -10.41, 95% CI: [-21.36 to 0.54], p=0.06).
Conclusion: Medication non-adherence is a major cause of increased risk for admissions among patients with lupus. Targeting measures to
improve medication adherence is an important component of the management of patients with lupus.
All lupus High risk Total p-value
patients lupus (n=28) (Fischer/
(n=171) chi-
(n-143) square)
Age: mean (SD) 47.57 (17.32) 39.64 46.27 0.03
(19.09) (17.81)
Females: n (col%) 132 (92.31) 23 (82.14) 155 (90.64) 0.09
Race: n (col%)
Asian 2 (1.40) 2 (7.14) 4 (2.34) 0.13
African-American 58 (40.56) 17 (60.71) 75 (43.86) 0.05
Caucasian 76 (53.15) 8 (28.57) 84 (49.12) 0.02
Hispanic 7 (4.90) 1 (3.57) 8 (4.68) 1.00
Average number of 2.12 (1.02) 2.74 (1.15) 2.24 (1.06) 0.02
medications: mean (SD)
Average number of fills per 6.64 (5.78) 5.29 (4.82) 6.39 (5.62) 0.35
medication: mean (SD)
Average MPR: mean (SD) 79.93 (25.02) 73.40 78.71 0.30
(22.80) (24.64)
Average MPR for top 4
medications: mean (SD)
Prednisone 78.51 (36.42) 69.31 76.67 0.38
(29.02) (35.06)
Hydroxychloroquine 78.78 (22.58) 76.19 78.29 0.71
(25.39) (22.98)
Mycophenolate 83.83 (32.15) 62.22 77.87 0.14
(38.18) (34.63)
Table: 1 Descriptive data of lupus cohorts

Risk factor Confidence p-value
interval
Non high risk Reference [-21.36,0.54] 0.06
High risk -10.41

Age 0.15 [-0.11,0.41] 0.25
Female Reference [-23.50,6.66] 0.27
Male -8.42
Caucasian Reference [-13.29,5.26] 0.40
African American -4.01 [-0.84,56.06] 0.06
Asian 27.61 [-39.08,7.06] 0.17
Hispanic -16.01
Hydroxychloroquine Reference [-14.33,21.32] 0.70
Azathioprine 3.50 [-73.77,37.32] 0.52
Cyclophosphamide -18.23 [-21.82,87.26] 0.24
Cyclosporine 32.72 [-21.54,88.78] 0.23
Dexamethasone 33.62 [-12.84,44.74] 0.28
Leflunomide 15.95 [-16.81,16.35] 0.98
Methotrexate -0.23 [-10.94,16.02] 0.71
Methylprednisolone 2.54 [-11.77,11.88] 0.99
Mycophenolate 0.06 [-8.97,8.62] 0.97
Prednisone -0.18 [1.11,65.94] 0.04
Tacrolimus 33.52*
Table 2: Multivariate analysis of medication possession ratio
Disclosure: C. Thirukumaran, None; K. McCarthy, None; J. Patel, None; A. P. Anandarajah, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/decreased-medication-adherence-is-a-major-cause-for-

increased-risk-of-hospitalizations-among-high-risk-lupus-patients
Patterns of Methotrexate Use in African Countries with Low Versus Medium/High

Human Development Index: Preliminary Results of Semi-Structured Interviews
Carol A Hitchon1, Yan Liu2, Steven Shi3, Girish M Mody4, Candace H. Feldman5, Michael Weinblatt6 and Ines Colmegna7, 1Internal
Medicine, University of Manitoba, Winnipeg, MB, Canada, 2McGill University, Montreal, QC, Canada, 3University de Montreal, Montreal,
QC, Canada, 4Dept of Rheumatology, University of Kwa Zulu-Natal, Durban, South Africa, 5Brigham and Women’s Hospital, Division of
Rheumatology, Immunology and Allergy, Boston, MA, 6Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and
Harvard Medical School, Boston, MA, 7Division of Rheumatology, Department of Medicine, Division of Experimental Medicine, McGill
University, Montreal, Quebec, Canada, Montreal, QC, Canada
SESSION INFORMATION
Background/Purpose: Methotrexate (MTX) is standard therapy for rheumatoid arthritis (RA) and also used to treat other rheumatic diseases.
Existing guidelines for RA treatment/ MTX use did not contemplate the realities of resource limited countries. We aimed to understand MTX
use patterns and barriers in African countries to inform the development of culturally appropriate guidelines.
Methods: We identified African physicians (MDs) from countries classified as low Human Development Index (LHDI) and medium/high
HDI (MHDI) by the United Nations Development Programme and who self-identified as MTX prescribers. Each MD participated in a 45
minute semi-structured interview by phone in either English or French regarding their MTX practices.
Results: 29 MDs (23 rheumatologists; 6 internists) from 29 African countries were interviewed (17 LHDI; 12 MHDI) representing a
population of 1,000.4 million; (LHDI 673.8 million; MHDI 326.6 million). The median (range) of rheumatologists/ million population in
these countries was only 0.17 (0-9.4). LHDI countries had significantly fewer rheumatologists/ million population than MHDI (0.1 (0-0.66)
vs 1.1(0-9.43) p=0.004). MTX was prescribed by non-rheumatologists in 93% LHDI and 67% MHDI countries. Most MDs practised in
capital cities and served adult patients. 88% LHDI and 67% MHDI MDs also provided pediatric care. The main indication for MTX use was
RA with connective tissue diseases and psoriatic arthritis as secondary indications. Prior to prescribing MTX, most MDs (97%) evaluated
patients for pulmonary, hepatic and renal dysfunction and excluded cytopenias. Screening was performed for TB (with CXR) by 62%, HIV by
55% and Hepatitis B/C by 52%. Pregnancy screening was usually by patient self-report (86%). Discussing alcohol consumption was
considered pertinent to the local consumption by 42% of MDs. MTX dosing was similar between LDHI and MDHI countries, and usually
given with folate (83%). Only 55% of countries had parenteral MTX. 55% of MDs reported barriers to MTX use due to drug availability or
costs. Compared to MHDI countries, LHDI countries were more likely to have an inconsistent MTX supply throughout the year (82% LHDI
vs 42% MHDI (p=0.05) and less likely to have MTX available in the hospital pharmacy (35% LHDI vs 83% MHDI; p=0.02). Major
contributors to MTX non-adherence included drug cost or availability (85%), lack of prescribers (15%) and patients’
beliefs/education/tolerance (37%).
Conclusion: The challenges of treating RA patients in African countries with low HDIs are unique. Costs of medical care and drugs, limited
subspecialist availability, patient specific beliefs, and lack of MTX are significant challenges faced by MDs treating patients with rheumatic
disease. Understanding the African LHDIs reality is critical for the development of guidelines to improve care quality and outcomes. Table:
Patterns of MTX prescription in Africa. All values are % or median (range)
Total n=29 LHDI n=17 MHDI n=12 P value
Population (2015) 1,000,446,000673,839,000 326,607,000 P=0.47
Rheumatologists/million 0.17 (0-9.4) 0.8 (0-0.66) 1.1 (0-9.4) P=0.004

Rheumatologic indications for methotrexate
Main reason RA (% reporting) 100 100 100 P=1
Second reasons CTD/ PsA/ JIA 43/43/14 44/38/19 42/50/8 P=0.7

Pre-methotrexate evaluation
Lung, liver, kidney, hematology 97% 94% 100% P=1
Xray done 58% 65% 50% P=0.4
TB screen CXR done 62% 71% 50% P=0.3
HIV done 55% 59% 50% P=0.6
Hepatitis B/C done 52% 41% 67% P=0.3
Pregnancy screen by self-report 86% 88% 83% P=1

only
Methotrexate prescription
Starting dose (mg/wk) 10( 2.5-15) 10(7.5-15) 10(2.5-15) P=0.5
Maximum dose (mg/wk) 25(12.5-30) 25(15-25) 22.5(12.5- P=0.5

30)
Folate prescribed 83% 82% P=1
83%
Prescribing challenges
Cost for 1 month (10-15 17( 0.5-27) 17.25 (1- 10(0.5-27) P=0.7
mg/wk) USD 27)
55% 58% P=0.8
Injectable formulation available 52%
66% 42% P=0.05
Inconsistent MTX supply 82%
55% 83% P=0.02
MTX in hospital pharmacy 35%
Adherence challenges
Cost/drug availability 85% 94% 73% P=0.3
Lack of prescribers 15% 13% 18% P=1
Patient 37% 44% 27% P=0.4

belief/education/intolerance
Disclosure: C. A. Hitchon, None; Y. Liu, None; S. Shi, None; G. M. Mody, None; C. H. Feldman, None; M. Weinblatt, None; I.
Colmegna, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/patterns-of-methotrexate-use-in-african-countries-with-

low-versus-mediumhigh-human-development-index-preliminary-results-of-semi-structured-interviews
Barriers to the Use of Methotrexate in Ethiopia: Survey of Pharmacy Providers

Carol A Hitchon1, Yvon de Jong2, Michele Meltzer3, Rosie Scuccimarri4, Birhanu D Desyibelew5, Addisu Melkie5, Yewondwossen
Mengistu5 and Ines Colmegna6,7, 1University of Manitoba, Winnipeg, MB, Canada, 2Ecumenical Pharmaceutical Network, Nairobi, Kenya,
3Thomas Jefferson University, Philadelphia, PA, 4Department of Pediatrics, McGill University Health Centre, Montreal, QC, Canada,
5Addis Ababa University, Addis Ababa, Ethiopia, 6Division of Rheumatology, Department of Medicine, Division of Experimental Medicine,
McGill University, Montreal, Quebec, Canada, Montreal, QC, Canada, 7Rheumatology, McGill University Health Centre, Montreal, QC,
Canada
SESSION INFORMATION
Background/Purpose:
African countries with a low Human Development Index (LHDI) based on life expectancy, education and income per capita, face competing
social, economic, health and poverty related issues that distract from the treatment of chronic conditions such as Rheumatoid Arthritis (RA).
Methotrexate (MTX) is standard of care for RA and used for other rheumatic diseases. We sought to determine MTX availability and MTX
dispensing practices of pharmacy providers (PP) in Ethiopia, an LHDI country, in order to inform the development of culturally appropriate
guidelines for using MTX to treat rheumatic diseases.
Methods:
The Ecumenical Pharmaceutical Network and the Ethiopian Catholic – Social and Development commission (ECC-SDCO) is the second
largest health institution in Ethiopia (next to the public health system) and oversees 83 health institutions of which 52 have a pharmacy
department (includes 4 hospitals, 16 health centers and 32 clinics). In September 2016, PP attending the Essentials of Pharmacy Practice
course provided by ECC-SDCO were invited to participate in an anonymous survey regarding their experience with dispensing MTX for the
treatment of rheumatic conditions. We also conducted a 45 minute semi-structured interview for pharmacists serving the country’s sole public
rheumatology clinic in Ethiopia. Descriptive statistics are reported from the survey and interview notes.
Results:
Twenty-three PP (18 pharmacy technicians; 5 pharmacists) from hospitals and health centers of 9 regional states and 2 chartered cities of
Ethiopia completed the survey (18/23 were located outside Addis). Seven (32%) worked in a hospital based pharmacy, 12 (55%) in a health
centre pharmacy and 3 (14%) in other areas (i.e. clinic pharmacy). The number of years of practice (median (range)) was less for pharmacy
technicians compared to pharmacists (4 (1-8) vs 10(6-15) p<0.0001). Methotrexate was available in only 3/23 pharmacies (2 were hospital
pharmacies) and was only available as oral tablets. Five PP reported that MTX was available in the hospital pharmacy of their region. Only
2/23 PP had dispensed MTX and in both cases it was not for rheumatic conditions. Only 3(13%) PP reported feeling comfortable educating
patients on how to take methotrexate, (2 had counseled on MTX, 1 had not, 1 counselled but without confidence). Counselling included need
for blood work (n=3), folic acid (n=3) and alcohol intake (n=1). No PP counselled on contraception. While interviewed pharmacists were
confident regarding counselling patients on MTX, contraception was not consistently discussed. Additional barriers to prescribing MTX
identified by interviewed PP included inconsistent supply and prioritizing use of MTX for non-rheumatologic conditions.
Conclusion:
Bridging the gap of RA treatment between developed and emerging countries is both a need and a responsibility. The survey and interview
identified two key aspects limiting the use of MTX in Ethiopia: a) availability of the drug in pharmacies, and b) confidence of designated
pharmacists in supplying and counseling patients for methotrexate. Improved MTX access and recommendations for counselling are needed to
increase the confidence of pharmacists in dispensing MTX.
Disclosure: C. A. Hitchon, ILAR, 2; Y. de Jong, Ecumenical Pharmaceutical Network, 3; M. Meltzer, None; R. Scuccimarri, None; B. D.
Desyibelew, None; A. Melkie, None; Y. Mengistu, None; I. Colmegna, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/barriers-to-the-use-of-methotrexate-in-ethiopia-survey-

of-pharmacy-providers
Biopsy Proven Giant Cell Arteritis in African Descent Populations: Incidence and
Characteristics in Martinique, French West Indies
Florence Moinet1, Vincent Molinie2, Katlyne Polomat1, Harold Merle3, Marie Blettery4, Lauren Brunier-Agot4, Michel DeBandt4 and
Christophe Deligny1, 1Internal medicine, National referral Center for Lupus, Antiphospholipid syndrome and other rare auto-immune
diseases, Hopital Pierre Zobda Quitman, CHU de Martinique, Fort de France, Martinique, 2Pathology unit, Hopital Pierre Zobda Quitman,
CHU de Martinique, Fort de France, Martinique, 3Ophthalmology, Hopital Pierre Zobda Quitman, CHU de Martinique, Fort de France,
Martinique, 4Rheumatology, Hopital Pierre Zobda Quitman, CHU de Martinique, Fort de France, Martinique
SESSION INFORMATION
Background/Purpose: Multiple epidemiological studies ascertained that GCA is one of the most common systemic vasculitis in western
countries. But, there is only one study based on 2 patients in Tennessee to assess the low incidence of GCA in African descent (AD)
populations. Moreover, very few series are devoted to these patients in the literature. Our objective was to describe the characteristics of
GCA and study the incidence in the Afro-Caribbean (AC) population of Martinique, a French region of the West Indies where inhabitants are
more than 90% of AD and have free access to health care including a regional competence center for systemic vasculitis.
Methods: Population based retrospective study in Martinique. Computed files of the 2 pathology units of the island (public and private) were
analyzed to find all patients with a positive temporal arteritis biopsy. All medical files were reviewed to assess the incidence, but only AC
patients (self-declared) were included to describe the disease in an African descent cohort.
Results: 40 patients had a biopsy proven GCA between 1991 and 2016. Mean age at GCA diagnosis was 75.7 years (SD±7.4; range: 63-91).
Main manifestations at diagnosis of the 38 patients of AC origin (30 women, 8 men) were: fever 9.1% (3/33), asthenia 64.5% (20/31),
weight loss 75.7% (25/33), headache 69.4% (25/36), jaw claudication 36.3% (12/33), scalp tenderness 35.2% (12/34), anterior ischemic
optic neuropathy 31.4% (11/35), stroke 2.9% (1/34), and polymyalgia rheumatica 35.2% (12/34). C-reactive protein was over normal value
for 96.8% (n=31; mean value 106.5, range: 7-283). ESR was positive in 86.3% (19/22). Available for 15 patients, CT scan of the aorta and
its branches revealed one aortitis and one arteriopathy of lower limbs. All patients were treated by steroids. Twenty three patients (60.5%)
were followed >18 months and mean follow up duration was 43.7 months. Eleven patients relapsed. Six patients died (15.8%). Kaplan
Meier analysis found 93.9%, 84.6%, 75% survival rates at respectively 6, 12 and 24 months. Crude mean annual incidence of GCA in
Martinique was 3.12 cases for 106 inhabitants from 1991 to 2016. Mean number of GCA gradually increased from 0.5 patient/year between
1991 and 2000, 1.6 between 2001 and 2010 to 3.8 between 2011 and 2016, parallel to the increasing proportion of elderly in the martinican
population (13% was over 60 years old in 1990, 23% in 2016 and official estimation is 39.6% in 2032).
Conclusion: This is the first population based description of GCA in an AD population. The features in Martinique are similar to the
literature, except for the ischemic complications that seem less frequent in our population. Our data confirm the low frequency of GCA in AD
populations compared to Caucasians. The retrospective nature of the study and the absence of negative biopsy GCA could weaken
conclusion. We note a progressive increase of annual number of cases during the 25 years of survey, parallel to the accelerated ageing of the
martinican population. We could hypothesize that low incidence of GCA in AD populations is at least partially related to the low rate of
elderly in most of these populations around the world, and could also increase in the future.
Disclosure: F. Moinet, None; V. Molinie, None; K. Polomat, None; H. Merle, None; M. Blettery, None; L. Brunier-Agot, None; M.
DeBandt, None; C. Deligny, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/biopsy-proven-giant-cell-arteritis-in-african-descent-

populations-incidence-and-characteristics-in-martinique-french-west-indies
Chinese-American Rheumatology Patients Who Use Traditional Chinese-Medicine Have

Worse Patient Reported Outcomes
Kai Sun1, Jackie Szymonifka2, Henghe Tian3, Ya Ju Chang4, Jennifer Leng5 and Lisa A. Mandl6, 1Hospital for Special Surgery/Weill
Cornell medicine, New York, NY, 2Rheumatology, Hospital for Special Surgery, New York, NY, 3Internal Medicine, New York University
School of Medicine, New York, NY, 4Mount Sinai Beth Israel, New York, NY, 5Immigrant Health and Cancer Disparities laboratory,
Memorial Sloan Kettering Cancer Center, New York, NY, 6Rheumatology, Hospital for Special Surgery/Weill Cornell Medicine, New York,
NY
SESSION INFORMATION
Background/Purpose: Chinese-Americans are a fast growing US immigrant group, and many use Traditional Chinese Medicine (TCM).
Ethnic Chinese patients also have worse outcomes in SLE and RA compared to Caucasians. In order to optimally care for this growing
population with rheumatic diseases, rheumatologists must have some understanding of patients’ traditional cultural beliefs and practices,
which may influence medication taking behaviors, and thus ultimately outcomes. TCM use by Chinese-American rheumatology patients has
not previously been studied, and whether patient-reported outcomes differ between TCM users and nonusers is unknown.
Methods: Subjects were recruited from two rheumatology clinics that serve a predominantly Chinese-American immigrant population.
Inclusion criteria were English or Mandarin Chinese fluency and being actively treated for a systemic rheumatic disease. Questionnaires
were used to assess TCM use, acculturation, and demographics. Self-reported health status was assessed using Patient-Reported Outcome
Measurement Information System (PROMIS®) short forms. Chart review was performed to gather clinical data. Parametric and
nonparametric statistics were performed as appropriate. Multivariable logistic regression using step-wise selection was used to examine
factors independently associated with TCM use.
Results: 230 enrolled, median age 55 years (range 20-97), 65% female, 71% ≤ high school education, 70% Medicaid, and 22% reported
English fluency. 50% reported TCM use in the past year, most frequently tuina massage (47%), acupuncture (45%), and herbs (37%). 60% of
TCM users used TCM to treat rheumatic disease, but only 34% discussed TCM use with the rheumatologist. TCM users had worse scores in
PROMIS® anxiety, depression, pain interference, fatigue, physical function, and social health. There was no difference in PROMIS® scores
between herb users and nonusers; however more frequent TCM users and those using TCM to treat rheumatic disease had worse pain and
function. In multivariable analysis, older age (Odds Ratio [OR]1.03, p=0.04), female sex (OR 2.3, p=0.02), ≥ some college education (OR
2.1, p=0.04), US residence for ≥20 years (OR 2.2, p=0.03), more anxiety (OR 1.05, p=0.004), fewer years since rheumatic disease diagnosis
(OR 1.1, p=0.01), reporting western medicine to be ineffective (OR 5.3, p=0.003), and belief in TCM (OR 2.8, p=0.01) were independently
associated with TCM use.
Conclusion: In this group of Chinese-American rheumatology patients with low education, low socioeconomic status, and poor acculturation,
TCM use is common (50%) and is independently associated with older age, female sex, better education, longer US residence, higher levels
of anxiety, more recent rheumatic disease diagnosis, perceived ineffectiveness of western medicine, and stronger belief in TCM. Providers
should ask Chinese-American patients about TCM use because it may be a proxy for unmet therapeutic needs in this population, as TCM
users have worse patient-reported outcomes across many important domains.
Disclosure: K. Sun, None; J. Szymonifka, None; H. Tian, None; Y. J. Chang, None; J. Leng, None; L. A. Mandl, Boehringer Ingelheim,
2,American College of Physicians, 3,Up To Date, 7.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/chinese-american-rheumatology-patients-who-use-

traditional-chinese-medicine-have-worse-patient-reported-outcomes
Characterizing Indigenous Community Engagement Patterns in Published Arthritis

Studies: A Systematic Review of the Literature
Chu-Yang Lin1, Kelle Hurd1, Cheryl Barnabe2 and Adalberto Loyola-Sánchez3, 1University of Calgary, Calgary, AB, Canada, 2Division of
Rheumatology, University of Calgary, Calgary, AB, Canada, 3Rheumatology, University of Calgary, Calgary, AB, Canada
SESSION INFORMATION
Background/Purpose: Indigenous populations in Canada, Australia, New Zealand and the United States of America have a higher
prevalence of arthritis conditions and experience worse outcomes. Research can play a pivotal role in identifying and addressing care gaps,
and community engagement (CE) approaches are the most promising ways for achieving positive and sustainable impacts. This systematic
review characterizes CE patterns in arthritis studies involving Indigenous populations from four countries.
Methods: We performed a secondary systematic review (MEDLINE, EMBASE, CINAHL and Indigenous-specific online indexes up to May
2016) that characterized the epidemiology, clinical outcomes, mortality and health services utilization for arthritis in Indigenous populations
of the four countries (n=5,269 titles and abstracts). 159 studies met inclusion criteria for the relevant outcomes. Included studies were
evaluated for their descriptions of CE at inception of research, data collection, and data usage (i.e. results interpretation and dissemination).
Extraction was performed in duplicate using standardized criteria. Descriptions were subsequently mapped onto a CE spectrum adapted from
the Beacon for Public Engagement, ranging from the lowest to highest level of engagement: inform, consult, involve, collaborate or empower.
Any studies that reported CE above consultation were assigned with meaningful community engagement (MCE) at the respective stage of
research.
Results: Of the 159 included studies, 127 were CAN/USA publications and 32 were AUS/NZ publications. Only 32% (n=51) of the 159
included studies reported any description of CE (n=43 CAN/USA, n=8 AUS/NZ). Few studies report CE activities at the inception of
research (n=6, 12%), with consultation described in 3 studies and collaboration discussed in 3 studies. In comparison, 98% (n=50) of studies
described CE at the data collection stage, which also had the highest frequency of MCE compared to other research stages (n=11 studies).
Here, the majority of studies (n=30) reported community consultation, while 11 studies reported involvement or collaboration. Nine studies
recruited community members to aid data collection. During data usage, ten studies (20%) described CE, including 4 studies where
Indigenous communities were informed or consulted with, and 6 where Indigenous communities were involved or collaborated with.
Regionally, the reporting of MCE was concentrated in CAN/USA, with MCE described in all stages of research, whereas publications from
AUS/NZ only reported MCE at data collection.
Conclusion: The reporting of CE in Indigenous arthritis studies in the specified countries is limited in frequency, with few studies reaching
the higher end of the CE spectrum (i.e. collaboration and empowerment). CE was most frequently reported during the data collection stage
and is mostly described at the consultation level, which can be reached merely by obtaining informed consent. This reflects researchers’
adherence to ethical guidelines rather than a CE effort. Regional differences in CE reporting are likely explained by differences in research
policies for Indigenous research. We call for CE guidelines specific to Indigenous rheumatology research.
Disclosure: C. Y. Lin, None; K. Hurd, None; C. Barnabe, None; A. Loyola-Sánchez, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/characterizing-indigenous-community-engagement-

patterns-in-published-arthritis-studies-a-systematic-review-of-the-literature
Divergent Measures of Lupus Disease Damage and Severity Among Asians in an

Ethnically Diverse Cohort
Laura Trupin1, Patricia P. Katz2, Cristina Lanata2, Lindsey A. Criswell2, Charles G. Helmick3, Maria Dall'Era2 and Jinoos Yazdany1,
1Medicine/Rheumatology, University of California San Francisco, San Francisco, CA, 2Medicine/Rheumatology, University of California,
San Francisco, San Francisco, CA, 3Centers for Disease Control and Prevention, Atlanta, GA
SESSION INFORMATION
Background/Purpose: Systemic lupus erythematosus (SLE) is not well characterized among Asian Americans, particularly among subgroups
of Asians. We aim to compare measures of disease status, including severity, damage, activity, and physical functioning, by race/ethnicity in a
diverse SLE cohort.
Methods: Data were derived from the California Lupus Epidemiology Study (CLUES), a population based, multi-ethnic cohort of SLE
patients in the San Francisco area begun in 2015. SLE was defined according to the 1997 ACR criteria. At baseline, participants had a
physician exam that included the SELENA- SLE Disease Activity Index (SLEDAI) and SLICC/ACR Damage Index (SDI). The Lupus
Severity Index (LSI) was computed based on the ACR criteria confirmed at the study visit. The LSI assigns a weighted value to each criterion
and is scaled 0-10; it has been shown to correlate with disease activity and mortality. Patients completed the SF-36 Physical Functioning
(PF) subscale; this scale has a potential range of 0-100, with higher values indicating better function. They also provided self-identified
race/ethnicity and details of Asian origin. We compared SLE status measures by race/ethnicity and within subgroups of Asian origin, in
regression models controlling for age, disease duration, income < 125% of the federal poverty limit, and gender. Tukey post hoc tests were
used to compare the outcomes among Asian subgroups.
Results: Among 283 patients, 30% were white, 20% Latino, 11% African American, and 39% Asians. The 102 Asian Americans included
62 Chinese, 23 Filipino and 17 from all other subgroups. Nearly 90% of the cohort were women, with mean age 45±14 and mean disease
duration of 16±10 years. Just over half the cohort had some damage (SDI> 0) at baseline. Overall means and distributions of the status
measures are shown in the table, along with results from the regression models. Asian Americans in all subgroups had significantly higher
LSI scores than whites, as did Latinos and African Americans. However, Asians did not differ from whites in SLICC, SLEDAI or SF-36 PF.
Comparing outcomes among the Asian subgroups, the only significant differences were in the SF-36 PF scores, for which Chinese patients
had less impairment (mean 48.0) compared to Filipinos (mean 42.1, p=0.02) or other Asians (mean 42.3, p=0.04).
Conclusion: In this multi-ethnic cohort, Asians had high disease severity, similar to African Americans and Latinos, but accumulated
significantly less damage than these other racial/ethnic groups over time. The social, environmental, biological or health factors leading to
this paradox among Asians requires further investigation. With the exception of physical functioning, there were few differences between the
Asian subgroups, but this analysis was limited by small sample size and should be further explored as the cohort expands.
Table. SLE Disease Status Measures by Race/Ethnicity

Lupus Severity SLICC Damage SF36 Physical
Index Index SELENA-SLEDAI Functioning
unadjusted mean±sd (range)
Total (n=238) 6.8 ± 1.6 (3.4-9.5) 1.2 ± 1.6 (0-7) 2.8 ± 2.9 (0-16) 44.1± 11.9 (15-57)
Race/ethnicity adjusted mean (95% confidence interval)*
Asian 7.1 (6.8-7.4)** 1.2 (0.9-1.5) 2.8 (2.2-3.3) 46.3 (44.1-48.4)
African American 7.1 (6.6-7.6)** 1.8 (1.2-2.3)** 2.5 (1.5-3.5) 38.2 (34.3-42.1)**
Hispanic 7.2 (6.9-7.6)** 1.3 (1.0-1.7) 3.2 (2.5-3.9) 42.0 (39.4-44.7)
White 6.2 (5.9-6.5) 0.8 (0.5-1.2) 2.7 (2.1-3.3) 45.4 (43.0-47.8)
p-value
(diff by race/ethnicity) <0.001 0.02 0.67 0.001

* Adjusted for age, gender, disease duration, poverty level income (<125% federal poverty limit).
** Results significantly different from Whites for indicated measure.
Disclosure: L. Trupin, None; P. P. Katz, Bristol-Myers Squibb, 2; C. Lanata, None; L. A. Criswell, None; C. G. Helmick, None; M.
Dall'Era, None; J. Yazdany, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/divergent-measures-of-lupus-disease-damage-and-

severity-among-asians-in-an-ethnically-diverse-cohort
The Impact of Limited Health Literacy on Patient-Reported Outcomes (PROs) in

Systemic Lupus Erythematosus (SLE)
Patricia P. Katz 1, Maria Dall'Era2, Laura Trupin3, Cristina Lanata2, Stephanie Rush4, Charles G. Helmick5, Lindsey A. Criswell4 and
Jinoos Yazdany3, 1Medicine, University of California, San Francisco, San Francisco, CA, 2Medicine/Rheumatology, University of
California, San Francisco, San Francisco, CA, 3Medicine/Rheumatology, University of California San Francisco, San Francisco, CA,
4University of California, San Francisco, San Francisco, CA, 5Centers for Disease Control and Prevention, Atlanta, GA
SESSION INFORMATION
Session Title: ARHP Healthcare Disparities in Rheumatology Poster
Background/Purpose: PROs play a prominent role in evaluating patient status in rheumatic diseases. PROs often reveal disparities in
individuals with low education or income or among racial/ethnic minorities. Limited health literacy (LHL) may also be more prevalent in
these groups. While some have acknowledged that LHL may create challenges in disease management, the impact of LHL on PROs has
received little attention. We examined the impact of LHL on PROs in a diverse SLE cohort.
Methods: Data were from the California Lupus Epidemiology Study (CLUES), a population-based, multi-ethnic SLE cohort (n=281).
Subjects participated in an in-person research clinic, in which study physicians completed the SLEDAI and SLICC Damage Index (SDI), and
completed a structured interview administered by a trained interviewer, in which the following PROs were administered: SF-36, short forms
of ten PROMIS domains, and self-reported measures of disease damage and activity (Table). Health literacy was assessed using a 3-item
validated scale1. Individual education and household income were self-reported. Bivariate analyses examined differences in all PROs by
education level (≤12 yrs vs. >12 yrs), income (≤125% of federal poverty level for household size vs. >125%), and LHL using t-tests.
Multivariate linear regression analyses examined differences in PROs by LHL controlling for age, sex, race/ethnicity, disease duration,
SLEDAI, SDI, education, and income.
Results: The sample was 29% white (W), 23% Hispanic (H), 11% African American (AA), and 37% Asian (AS); 89% female; mean age 45
(±14) years; 22% with education ≤high school; 12% with poverty-level income; mean disease duration 16 (±10) years. 85% of interviews
were completed in English. 35% had LHL, with significant differences by race/ethnicity (W 21%, AS 36%, AA 42%, H 46%, p<.01).
Physician assessments of SLE activity and damage were not significantly different by health literacy (p>0.50). Bivariate analyses showed
significant differences in all PROs by LHL and income, but few differences by education. In multivariate analyses, significant differences by
LHL remained in all PROs except self-reported disease damage, even after controlling for all covariates including income and education
(Table).
Conclusion: Individuals with SLE and LHL had worse status as measured by a wide range of PROs, even after accounting for physician-
assessed disease, income, education, and race/ethnicity. Whether differences are due to unmeasured effects of LHL or to differential
interpretation of PRO measures by individuals with LHL is unknown. However, findings suggest that attention to health literacy is crucial in
the development and validation of PROs to ensure that variations in scores reflect actual differences in the underlying construct and not
differential understanding or interpretation of the questions.
1Chew et al. Fam Med 2004; 36:588.
Table. Adjusted means* of PROs for individuals with

and without limited health literacy
Limited health literacy
No Yes p
(n=184, (n=97,
65%) 35%)
PROMIS
Physical Function 49.9 46.2 .01
Pain Interference† 54.7 58.8 .007
Fatigue† 50.3 55.6 .02
Sleep Disturbance† 50.7 53.9 .03
Sleep Impairment† 50.7 55.5 .007
Cognitive Ability 50.3 44.8 <.0001
Satisfaction with Social 53.2 48.0 .002
Roles
Participation in Social 51.9 48.5 .02
Roles
Social Isolation† 44.4 48.3 .006
SF-36
Physical Function 46.5 40.7 .001
Role Physical 46.3 40.5 .0006
Pain 48.2 44.4 .03
General Health 42.6 36.9 .003
Vitality 49.5 45.5 .04
Social Functioning 46.9 42.8 .02
Role Emotional 51.2 43.3 <.0001
Mental Health 51.7 45.3 <.0001
Disease-specific
measures
BILD† 1.7 1.7 .98
SLAQ† 7.6 10.9 .007
SLE activity† 2.8 4.3 .0005
* Adjusted means calculated from multivariate linear
regression analyses controlling for age, sex,
race/ethnicity, disease duration SLEDAI, SLICC Damage
Index, education, and income
† Lower scores reflect “better” status. For all other

measures, higher scores are “better.”
Disclosure: P. P. Katz, Bristol-Myers Squibb, 2; M. Dall'Era, None; L. Trupin, None; C. Lanata, None; S. Rush, None; C. G. Helmick,
None; L. A. Criswell, None; J. Yazdany, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-impact-of-limited-health-literacy-on-patient-reported-

outcomes-pros-in-systemic-lupus-erythematosus-sle
Long Term Survival of Biological Agents in Patients with Axial Spondyloarthritis. the
Impact of Sociodemographic Factors in Latin-America
Magdalena Cavalieri1, Emilce E Schneeberger2, Fernando Dal Pra1, Rodrigo Garcia Salinas3, Hernán Maldonado Ficco4 and Gustavo
Citera1, 1Section of Rheumatology, Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina, Buenos Aires, Argentina, 2Instituto de
Rehabilitación Psicofísica, Buenos Aires, Argentina, Buenos Aires, Argentina, 3Section of Rheumatology, Hospital Italiano de La Plata,
Buenos Aires, Argentina, La Plata, Argentina, 4Section of Rheumatology, Hospital San Antonio de Padua, Córdoba, Argentina, Córdoba,
Argentina
SESSION INFORMATION
Background/Purpose: The introduction of biological agents improved the prognosis of axial Spon-
dyloarthritis (axSpA). The Lund Efficacy Index (LUNDEX) allows evaluation of both survival and
efficacy of drugs. Our aims were to evaluate the long-term efficacy of biological disease modifying
drugs (b-DMARD) in axSpA using the LUNDEX, compare them and to determine the variables as-
sociated to the discontinuation of these treatments. Methods: Patients ≥ 18 years old who met
ASAS 2009 criteria for axSpA and who started b-DMARD for the first time between 01/2002 and
12/2016 were included. Sociodemographic variables, comorbidities, type of axSpA, disease dura-
tion and previous treatments were registered. Duration of therapy, causes of its suspension, effi-
cacy and safety were evaluated. BASDAI was assessed at baseline and during the treatment and
LUNDEX was calculated at 6 months and at 1 year of treatment using BASDAI cut-off <4 as effi-
cacy endpoint. Cumulative drug survival was assessed by Kaplan Meier curves and comparisons
using log Rank. Results: We included 101 patients. 80.2% were male, with a median age of 42
years (IQR 35-54.5), and median disease duration of 19.3 years (IQR 9.4-28.8). 26.7% of patients
didn´t have health insurance. 63.4% had pure axSpA, 13.8% Psoriatic Arthritis, 3% Reactive Ar-
thritis, 3% Inflammatory Bowel Disease and 16.8% Juvenile axSpA. The frequency of first b-
DMARD was: 44.6% Etanercept (ETA), 41.6% Adalimumab (ADA), 7.9% Infliximab and 5.9%
Certolizumab. 67.3% received b-DMARD monotherapy. BASDAI significantly improved over
time. The mean (X) cumulative survival time was 66.2 months (95%CI: 51.8-80.5). ADA survival
was longer than ETA one [ADA X 74.8 months (95%CI: 57.2-92.4) versus ETA X 53.2 (95%CI:
35.8-70.6) p = 0.02]. The causes of suspension were: lack of provision of the medication 41.1%, in-
efficacy 26.8%, adverse events 12.5% and other reasons 19.6%. Mean cumulative survival time
was lower for ETA vs ADA (53,18±8,8 vs 74,8 ±8,9, Log Rank=0.02), being the main cause the
lack of provision of the medication. In multivariate Cox regression analysis, after adjusting for
other factors, having private health insurance was the only factor that influenced on the survival of
the b-DMARD (HR 2.54, 95%CI 1.18-5.75). The global LUNDEX was 52.7% at 6 months and
46.9% at 12 months. The ADA LUNDEX was 50% at 6 months and 39.3% at 12 months, while
ETA LUNDEX was 60,2% at 6 months and 52% at 12 months. Conclusion: In our cohort of pa-
tients with axSpA, survival time of b-DMARD was clearly affected by socio-economic factors. Pa-
tients who can afford a private health insurance are more likely to persist with medication.
Disclosure: M. Cavalieri, None; E. E. Schneeberger, None; F. Dal Pra, None; R. Garcia Salinas, None; H. Maldonado Ficco, None; G.
Citera, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/long-term-survival-of-biological-agents-in-patients-with-

axial-spondyloarthritis-the-impact-of-sociodemographic-factors-in-latin-america
The Charla De Lupus (Lupus Chat)® Program: Assessing the Needs of Teens and
Young Adults with Lupus and Their Caregivers to Develop a Family Model Nutrition
and Fitness Intervention
Melissa T. Flores1, Jillian Rose2, Priscilla Toral1, Lillian Mendez1, Dariana M. Pichardo1, Roberta Horton1 and Lisa F. Imundo3, 1Social
Work Programs, Hospital for Special Surgery, New York, NY, 2Hospital for Special Surgery, New York, NY, 3Pediatrics, Columbia
University Medical Center, New York, NY
SESSION INFORMATION
Background/Purpose:
Studies show Hispanics/Latinos are significantly impacted by health disparities, with higher rates of obesity & diabetes than Whites.
Combined with SLE & higher risk for related health conditions, culturally tailored nutrition & fitness education efforts are warranted. A
nutrition & fitness needs assessment was conducted for teens & young adults with SLE & their loved ones who participate in a bilingual
hospital-based SLE support & education group. The program reported on a SLE specific nutrition intervention at ACR/ARHP in the past, &
for the last 3 years, program evaluation data showed that nutrition was rated one of the top 5 topics.
Methods:
Two 72-item surveys with Likert scale, multiple choice & open-ended questions were conducted for teens/young adults (T/YAs) &
parents/caregivers (Ps). Questions covered demographics, food intake, MyPlate food guide & food labels, exercise, & interest in a
nutrition/fitness program. Separate analyses were conducted for T/YAs & Ps.
Results:
There were 147 surveys distributed electronically, 31% completed (55% T/YAs & 45% Ps). Over half (59%) were Hispanic, 30% White,
28% some other race, 25% Black/African American, 10% American Indian & 6% Asian. T/YAs mean age was 24 & 85% female. Most
T/YAs (65%) were diagnosed < 10 years ago. Top reported lupus symptoms were joint pain (72%), fatigue (64%) & muscle weakness
(56%). Top reported lupus medications were plaquenil (84%) & steroids (48%). Most T/YAs (54%) & Ps (90%) reported that their diet
was “good,” but shared they would like to eat healthier (88% & 100%). T/YAs (30%) reported drinking ≤ 3 glasses of water a day & 22%
reported consuming a sugary beverage daily.
While most T/YAs & Ps heard about MyPlate (87% & 72%), only 25% T/YAs & 46% Ps knew that it had 5 food groups. Ps (94%) reported
↑ desire to learn how to use food labels, while T/YAs (87%) had ↑ confidence in their ability to use food labels.
When asked about exercise, 74% T/YAs & 67% Ps reported that they exercised & 63% indicated that a MD suggested they do physical
activity. However, 83% Ps & 61% T/YAs did not feel they were at ideal weight. Most respondents (94% Ps & 80% T/YAs) were interested
in learning more about nutrition/exercise, & 88% Ps & 70% T/YAs expressed specific interest in a team nutrition/exercise program.
When asked about nutrition goals, Ps responses included “eating less fast foods” & “learn new ways to cook healthy.” T/YAs focused on
“build bone mass due to osteoporosis” & “maintain a good weight.” When asked about fitness goals, Ps desired to exercise regularly &
T/YAs indicated a desire to lose weight. When asked about motivation, the top 2 answers for both T/YAs & Ps were group activities (93%
& 80%) & a coach/trainer (87% & 86%). Similarly, both groups reported that they would prefer to track their progress by cell phones (100%
& 71%) & 52% preferred texting.
Conclusion:
Despite a small sample size, results show that nutrition & fitness are areas of concern for both T/YAs with SLE & Ps, with opportunities to
increase nutrition/fitness knowledge & activity. Results reveal that participants were interested in a group-based nutrition/fitness program
that is culturally tailored. Next steps are to organize focus groups with participants to discuss specific interventions.
Disclosure: M. T. Flores, None; J. Rose, None; P. Toral, None; L. Mendez, None; D. M. Pichardo, None; R. Horton, None; L. F. Imundo,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-charla-de-lupus-lupus-chat-program-assessing-the-

needs-of-teens-and-young-adults-with-lupus-and-their-caregivers-to-develop-a-family-model-nutrition-and-fitness-intervention
Engaging Community Stakeholders through a National Lupus Education Workshop

Karen Mancera Cuevas1, Rosalind Ramsey-Goldman2, Sheryl McCalla3, Patricia Canessa4 and Zineb Aouhab1, 1Rheumatology,
Northwestern University, Chicago, IL, 2FSM, Northwestern University, Chicago, IL, 3American College of Rheumatology, Atlanta, GA,
4Illinois Public Health Association, Springfield, IL
SESSION INFORMATION
Background/Purpose:
The Popular Opinion Leader (POL) model based on health education theoretical foundations associated with Social Network Theory and
Diffusion of Innovation was successfully piloted in several local Hispanic communities. The initial aim of the pilot problem was to develop
and teach a core curriculum to address lupus health disparities and a second aim in conjunction, with the American College of Rheumatology
and an Office of Minority Health funded grant, 1-CPIMP-151087-01-00 was to disseminate the program as a workshop in May 2016 to
engage stakeholders in other targeted communities in the United States that served African American and Native American constituents. The
target audience for the curriculum were POLs or Community Health Worker (CHW) equivalents.
Methods:
The multidisciplinary project team who provided training in the POL model included the Project Director who is a rheumatologist, a
community Field Director who is a psychologist with cultural competency expertise, a rheumatology trainee, and the POL project manager.
The 14 stakeholders who are involved in ongoing lupus health disparities projects participated in the workshop training and they represented
a wide range of institutions including community based organizations, academic centers and the ACR. The day long workshop included
training of fundamental concepts, curriculum design, application exercises incorporating theory, community practice, and project
dissemination adapting culturally-competent practices. Training was done in lecture format and interactive roundtable discussions.
Participants completed a qualitative assessment of the workshop at the end of the training sessions.
Results:
Thirteen of fourteen participants responded questions covering workshop purpose and objectives, clarity and appropriateness of the
workshop presentation, roundtable interactiveness, participant involvement, use of workshop time, and overall satisfaction. Additionally,
open-ended questions were provided on expanding on the workshop strengths and weaknesses, and suggestions/additional comments on this
workshop.
All respondents agreed that objectives were clearly stated and that all meeting participants were actively involved and satisfied with the
workshop. The majority of respondents reported that the workshop was clear and relevant, that the round table discussions were interactive,
and that there was shared decision-making in the workshop. The main shortcoming reported was that there were concerns about effective use
of meeting time as some presentations during the workshop were longer than originally programmed.
Conclusion:
The major finding from the workshop is that participants were overall satisfied with their participation, programming of the event,
particularly the roundtable discussion activities. Future directions include building on the initial workshop and based on future funding
expand the learning experience to lupus-specific stakeholders. In future iterations of the workshop, it will be important to follow-up with
program participants to assess program impact.
Disclosure: K. Mancera Cuevas, None; R. Ramsey-Goldman, None; S. McCalla, None; P. Canessa, None; Z. Aouhab, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/engaging-community-stakeholders-through-a-national-

lupus-education-workshop
Impact of Arthritis Among Populations with Chronic Health Conditions in Rural

Counties of the United States – 2015
Michael Boring1, Louise Murphy2, Jennifer M. Hootman3 and Yong Liu2, 1Arthritis Program, Centers for Disease Control and Prevention,
Atlanta, GA, 2Division of Population Health, Centers for Disease Control and Prevention, Atlanta, GA, 3Centers for Disease Control and
Prevention, Kennesaw, GA
SESSION INFORMATION
Background/Purpose: US rural populations have well documented health disparities, including higher prevalence of chronic health
conditions; however, arthritis prevalence among those with other chronic conditions is unknown. We estimated prevalence of arthritis and
arthritis-attributable activity limitations (AAAL), among those with chronic health conditions in rural areas using 2015 Behavioral Risk
Factor Surveillance System (BRFSS) data.
Methods: BRFSS is an ongoing, state-based, random-digit–dialed landline and cellphone survey of the noninstitutionalized adult population
aged ≥18 years of the 50 states, the District of Columbia (DC), and the U.S. territories. Respondents had arthritis if they answered “yes” to
“Have you ever been told by a doctor or other health professional that you have some form of arthritis, rheumatoid arthritis, gout, lupus, or
fibromyalgia?” Among adults with arthritis, AAAL was identified by a “yes” to “Are you now limited in any way in any of your usual
activities because of arthritis or joint symptoms?” Rural categories were created using the National Center for Health Statistics 2013 Urban-
Rural Classification Scheme for Counties; we used 2 rural county classification categories: micropolitan (large rural [LR]) and noncore
(small rural [SR]). Age-standardized prevalence of arthritis and AAAL were estimated by rural categories among those with each of 9
common chronic health conditions (hypertension, coronary artery disease [CAD], obesity, diabetes, chronic obstructive pulmonary disease
[COPD], depression, asthma, cancer, and chronic kidney disease [CKD]). All analyses accounted for BRFSS’ complex sampling design.
Results: Overall, arthritis prevalence was high in rural populations with chronic health conditions (range = 36.0-56.0%). In SR areas,
Results: Overall, arthritis prevalence was high in rural populations with chronic health conditions (range = 36.0-56.0%). In SR areas,
arthritis prevalence was particularly high among those with CKD (53.6%), COPD (51.6%), stroke (49.5%), and CAD (49.5%). In LR areas,
arthritis prevalence was highest among those with CAD (56.0%), COPD (54.8%), and CKD (50.7%). Overall, AAAL prevalence among
those with arthritis and ≥ 1 chronic condition ranged from 58.4 to 76.5%. In SR areas, age-standardized AAAL prevalence was highest
among those with arthritis and depression (71.2%), COPD (68.8%), CAD (65.8%), and stroke (65.5%). In LR areas, AAAL prevalence was
highest among those with depression (66.1%), COPD (71.9%), CAD (69.9%), and stroke (76.3%).
Conclusion: In rural areas, arthritis commonly occurs with other chronic conditions; for some more than half had arthritis. Individuals with
arthritis and chronic conditions in rural areas are significantly impacted by arthritis with roughly 2 in 3 reporting AAAL. Strategies that
reduce arthritis impact include weight loss, routine physical activity and participation in self-management education courses (e.g., Chronic
Disease Self-Management Program); these approaches also reduce adverse effects of co-occurring chronic conditions. By recommending
these strategies to their patients, health care providers can simultaneously manage the impact of arthritis and other chronic conditions. Our
results indicates the high need for these self-management strategies among rural adults.
Disclosure: M. Boring, None; L. Murphy, None; J. M. Hootman, None; Y. Liu, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/impact-of-arthritis-among-populations-with-chronic-

health-conditions-in-rural-counties-of-the-united-states-2015
MRI in Rheumatoid Arthritis: Does Quantifying the Number of Erosive Lesions

Improve Detection of Subtle Erosive Progression Compared to the Omeract RA MRI
Scoring System?
Ulf Sundin1, Anna-Birgitte Aga2, Tore K Kvien3, Siri Lillegraven4 and Espen A. Haavardsholm4, 1*Dept. of Rheumatology, Diakonhjemmet
Hospital, Oslo, Norway, 2Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, 3Diakonhjemmet Hospital, Oslo, Norway,
4Dept. of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
SESSION INFORMATION
Session Title: Imaging of Rheumatic Diseases Poster I
Background/Purpose: Early detection of erosive progression is an important application of MRI in RA. For research purposes the
OMERACT Rheumatoid Arthritis MRI Scoring system (RAMRIS) is commonly applied, with semi-quantitative assessment of erosive
volume. However, over time new erosive lesions can occur without sufficient increase in volume to result in a higher score. This could allow
for subtle erosive progression to go undetected. We aimed to examine if quantifying the number of erosions in addition to erosive volume
could provide improved sensitivity to change.
Methods: In a cohort consisting of 84 patients, all fulfilling the 1987 ACR criteria for RA, with disease duration of < 1 year, MRI of the
dominant wrist was acquired at 0, 3, 6, and 12 months. A trained reader, blinded for patient data, scored the MRI images in known
chronological order according to the RAMRIS method. In addition, we registered the number of erosive lesions at each site. The 78 patients
who had completed at least the baseline and 6- or 12-month exams were by each method identified as either progressors or non-progressors,
using an increase of 1 unit as cut-off value. The results were compared using cross tables and Spearman correlation.
Results: The median baseline age (25th, 75th percentile) was 58.1 (47.3, 66.4) years, disease duration was 107 (70, 186) days, 77% were
female, and 55% were anti-CCP positive. Median baseline RAMRIS erosion score was 8 (5, 11) and the median number of MRI erosions
was 10 (6, 14). Median 1 year change in RAMRIS erosion score was 1 (0, 2), and median change in number of erosions was 1 (0, 2). Both
methods identified an equal number of patients as progressors, and agreement was observed in 82% of cases. Seven patients were
progressors by the RAMRIS method only and 7 by the counting erosive lesions method only (table). The Spearman correlation coefficient of
the two scores was 0.75, p<0.001 (figure).
Conclusion: The RAMRIS erosion score was generally low, both with respect to baseline level as well as progression rate. By
supplementing the assessment with quantification of the number of erosive lesions, we could in this material identify a limited number of
additional patients as progressors. Further longitudinal studies could show to what extent patients with this type of early minimal erosive
lesions on MRI progress on conventional radiographs, and if this is clinically important.
Disclosure: U. Sundin, None; A. B. Aga, None; T. K. Kvien, AbbVie, 2,Pfizer Inc, 2,Roche Pharmaceuticals, 2,UCB, 2,BMS, 2,MSD,
2,AbbVie, 5,Pfizer Inc, 5,BMS, 8,MSD, 8,Roche Pharmaceuticals, 8,UCB, 8,AbbVie, 8; S. Lillegraven, None; E. A. Haavardsholm, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/mri-in-rheumatoid-arthritis-does-quantifying-the-number-

of-erosive-lesions-improve-detection-of-subtle-erosive-progression-compared-to-the-omeract-ra-mri-scoring-system
Are Magnetic Resonance Imaging Features of the Hand Associated with Patient
Reported Physical Function, Global Assessment of Disease Activity, Pain and Health
Related Quality of Life in Rheumatoid Arthritis in Clinical Remission? – Longitudinal
Results from an Observational Cohort
Daniel Glinatsi1, Cecilie Heegaard Brahe2, Merete Lund Hetland1,3,4, Lykke Ørnbjerg1, Simon Krabbe5, Joshua Baker6, Mikael Boesen7,
Zoreh Rastiemadabadi8, Lone Morsel-Carlsen8,9, Henrik Rogind1,3, Hanne Slott Jensen10, Annette Hansen11, Jesper Nørregaard12, Søren
Jacobsen3,13, Lene Terslev1, Tuan Huynh12, Natalia Manilo14, Dorte Vendelbo Jensen1,15, Jakob M. Møller16, Niels Steen Krogh15 and
Mikkel Østergaard1,3,17, 1Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Denmark,
Copenhagen, Denmark, 2Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Denmark,
Glostrup, Denmark, 3University of Copenhagen, Copenhagen, Denmark, 4The DANBIO Registry, Copenhagen Center for Arthritis Research,
Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark, 5Center for Rheumatology and Spine Diseases,
Copenhagen Center for Arthritis Research, Rigshospitalet, Copenhagen, Denmark, 6Corporal Michael J. Crescenz VA Medical Center,
Philadelphia, PA, 7Department of Radiology and the Parker institute, Copenhagen University Hospital Frederiksberg, Copenhagen, Denmark,
8Department of Radiology, Copenhagen University Hospital Frederiksberg, Copenhagen, Denmark, 9Department of Radiology,
Rigshospitalet, Copenhagen, Denmark, 10Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Frederiksberg,
Denmark, Copenhagen, Denmark, 11Department of Rheumatology, Copenhagen University Hospital Gentofte, Copenhagen, Denmark,
12Center for Rheumatology and Spine Diseases, Nordsjællands Hospital, Hillerød, Denmark, 13Center for Rheumatology and Spine
Diseases, Rigshospitalet, Copenhagen, Denmark, 14Center for Rheumatology and Spine Diseases, Copenhagen University Hospital
Frederiksberg, Copenhagen, Denmark, 15The DANBIO Registry, Copenhagen Center for Arthritis Research, Center for Rheumatology and
Spine Diseases, Rigshospitalet, Copenhagen, Denmark, 16Department of Radiology, Copenhagen University Hospital Herlev and Gentofte,
Copenhagen, Denmark, 17Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
SESSION INFORMATION
Background/Purpose: To assess whether magnetic resonance imaging (MRI) inflammation and damage in the wrist and hand of rheumatoid
arthritis (RA) patients are associated with patient-reported outcomes (PROs) at clinical remission and relapse.
Methods: MRIs of the right wrist and hand were obtained in 114 patients with established RA in sustained clinical remission (>1 year),
before tapering their biologic disease-modifying antirheumatic drug. MRIs were assessed according to the Outcome Measures in
Rheumatology (OMERACT) RA MRI score (RAMRIS) for inflammation (synovitis/tenosynovitis/osteitis) and damage (bone erosions/joint
space narrowing (JSN)) at baseline (i.e. remission, n=114) and in case of a relapse (n=70). Status and change MRI-scores were assessed for
associations with patient-reported physical function (health assessment questionnaires (HAQ)), visual analogue scales for global disease
activity and pain, EuroQol 5 dimensions and Short Form 36 physical and mental component summary (SF-36 PCS/MCS) using Spearman
correlations, and in univariate/multivariable linear regression analyses including generalized estimating equations. C-reactive protein and
swollen joint counts were forced into the models. MRI features were also assessed for trends against specific hand-related HAQ-items using
Jonckheere trend tests.
Results: MRI-assessed bone erosion, JSN and combined damage score were associated with impaired PROs, mainly HAQ and SF-36 PCS
at clinical remission and relapse (p<0.01), independent of clinical measures. The levels of bone erosions and JSN were associated with the
level of the HAQ score in 4 of 5 hand-related HAQ-items (p<0.05). MRI-assessed inflammation was generally not associated with PROs at
remission or relapse.
Conclusion: In patients with established RA MRI-assessed wrist and hand damage, but not inflammation is associated with patient-reported
physical impairment at clinical remission and relapse, and the amount of damage in the wrist and hand is associated with reduced function of
the hand.
HAQ VAS-PtGlobal VAS-Pain
Univariate Multivariable Univariate Multivariable Univariate Multivariable
β (95% β (95% β (95% β (95%
p β (95% CI) p p β (95% CI) p p p
CI) CI) CI) CI)
0.00 -0.39 -0.31
(- 0.97 (- 0.53 (- 0.57

MRI Synovitis 0.03;0.03) 1.63;0.84) 1.37;0.76)
0.00 0.58 0.67
0.77 0.46 0.31
(- (- (-
MRI Tenosynovitis 0.03;0.03) 0.95;2.10) 0.63;1.96)
0.00 0.51 0.21
0.86 0.25 0.59
(- (- (-
MRI Osteitis 0.02;0.03) 0.36;1.38) 0.55;0.97)
0.04 0.06
0.01 0.01
0.001 0.001** 0.52 0.34
(0.00;0.01) (- (-
(0.00;0.01)
MRI Bone Erosion 0.08;0.15) 0.06;0.17)
0.09 0.12
0.01 0.01
0.002 0.001** 0.44 0.32
(- (-
(0.00;0.02) (0.00;0.02)
MRI JSN 0.14;0.33) 0.11;0.35)
0.00 0.08 -0.03
0.83 0.77 0.89
MRI Combined (- (- (-
Inflammation 0.01;0.02) 0.48;0.64) 0.42;0.49)
0.03 0.04
0.004 0.004
0.002 0.001 0.49 0.33
MRI Combined (- (-
(0.000.01) (0.00;0.01)
Damage* 0.05;0.10) 0.04;0.11)
SF-36 PCS SF-36 MCS EQ-5D
Univariate Multivariable Univariate Multivariable Univariate Multivariable
β (95% β (95% β (95% β (95%
p β (95% CI) p p β (95% CI) p p p
CI) CI) CI) CI)
-0.04 0.14 0.00
0.88 0.55 0.88
(- (- (-
MRI Synovitis 0.55;0.46) 0.32;0.60) 0.01;0.01)
-0.04 0.18 0.00
0.91 0.51 0.78
(- (- (-
MRI Tenosynovitis 0.68;0.60) 0.34;0.69) 0.01;0.01)
-0.08 -0.05 0.00
(- 0.67 (- 0.84 (- 0.43

MRI Osteitis 0.46;0.30) 0.52;0.42) 0.01;0.00)
-0.07 -0.08 0.01
0.00
(-0.12;- 0.004 (-0.13;- 0.001** (- 0.75 0.57
(0.00;0.00)
MRI Bone Erosion 0.02) 0.03) 0.05;0.07)
-0.14 -0.16 0.02 0.00
(-0.24;- 0.004 (-0.27;- 0.002** (- 0.78 (- 0.63

MRI JSN 0.05) 0.06) 0.10;0.14) 0.00;0.00)
-0.02 0.06
0.00
MRI Combined (- 0.85 (- 0.63 0.75
(0.00;0.00)
Inflammation 0.25;0.21) 0.20;0.32)
-0.05 -0.06 0.01
0.00
MRI Combined (-0.08;- 0.003 (-0.09;- 0.001 (- 0.76 0.59
(0.00;0.00)
Damage* 0.02) 0.02) 0.03;0.04)
Table 4. Univariate and multivariable general estimating equations (GEEs) for
the association between MRI features and PROs. All analyses were adjusted for
age and sex.
*If combined damage scores had a p-value ≤0.10 in univariate analyses, these
were included in a separate multivariable model with CRP and SJC included in
the model. **This parameter was included in a separate multivariable GEE
model with SJC and CRP, due to co-linearity between bone erosion and JSN.
Abbreviations: HAQ: Health assessment questionnaire, VAS: Visual analogue

scale, PtGlobal: Patient’s assessment of global disease activity, MRI: Magnetic
resonance imaging, JSN: Joint space narrowing, SF-36: Short Form 36, PCS:
Physical component summary, MCS: Mental component summary, EQ-5D:
EuroQol 5 dimensions.
Disclosure: D. Glinatsi, None; C. H. Brahe, None; M. Lund Hetland, None; L. Ørnbjerg, None; S. Krabbe, None; J. Baker, None; M.
Boesen, None; Z. Rastiemadabadi, None; L. Morsel-Carlsen, None; H. Rogind, None; H. S. Jensen, None; A. Hansen, Calgene, 5,Pfizer
Inc, 5,Abvie, 6; J. Nørregaard, None; S. Jacobsen, None; L. Terslev, None; T. Huynh, None; N. Manilo, None; D. V. Jensen, None; J. M.
Møller, None; N. S. Krogh, None; M. Østergaard, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/are-magnetic-resonance-imaging-features-of-the-hand-

associated-with-patient-reported-physical-function-global-assessment-of-disease-activity-pain-and-health-related-quality-of-life-in-
rheumatoid-art
The Discrepancy between the EULAR Response Criteria and Ultrasonography

Assessment for Monitoring Therapeutic Response in Rheumatoid Arthritis
Ryusuke Yoshimi1, Yuichiro Sato1, Natsuki Sakurai1, Takaaki Komiya1, Naoki Hamada1, Hideto Nagai1, Naomi Tsuchida2, Yumiko
Sugiyama1, Yutaro Soejima1, Yosuke Kunishita1, Hiroto Nakano1, Daiga Kishimoto1, Reikou Kamiyama1, Kaoru Minegishi-Takase3, Yohei
Kirino1, Shigeru Ohno4 and Hideaki Nakajima1, 1Department of Hematology and Clinical Immunology, Yokohama City University School of
Medicine, Yokohama, Japan, 2Department of Hematology and Clinical Immunology, Yokohama City University Graduate School of
Medicine, Yokohama, Japan, 3Center for Rheumatic Diseases, Yokohama City University Medical Center, Yokohama, Japan, 4Center for
Rheumatic Disease, Yokohama City University Medical Center, Yokohama, Japan
SESSION INFORMATION
Background/Purpose: Although the European League Against Rheumatism (EULAR) response criteria based on the Disease Activity Score
(DAS) 28 has been widely used for assessment of treatment response in clinical trials for rheumatoid arthritis (RA), it is still unclear whether
it is indeed reflected by the change of synovitis severity. Musculoskeletal ultrasonography (US) is now one of the standard tools for the
diagnosis and monitoring of active synovitis. Here, we investigated the association between the EULAR response criteria and the US
assessment in monitoring RA activity.
Methods: Power Doppler (PD) US was performed in 24 joints, including all PIP, MCP, bilateral wrist and knee joints, as comprehensive
evaluation in 23 RA patients treated with certolizumab pegol (CZP; n = 15) or tofacitinib (TOF; n = 8). Before and after treatment with CZP
or TOF, PD signals and gray-scale (GS) images were scored semiquantitatively from 0 to 3 in each joint. Total PD score-24 and total PD
score-8 were calculated by summing up PD scores of the 24 joints and the selected 8 joints (bilateral second and third MCP, wrist, and knee
joints), respectively. Total GS score-24 and total GS score-8 were also calculated by summing up GS scores of the 24 joints and the selected
8 joints, respectively.
Results: Among the 23 patients, no response was shown in 5, moderate response was in 12, and good response was in 6 patients by EULAR
response criteria. The change of total PD score-24 by treatment with CZP or TOF was significantly different between the patients with no
response and moderate response (1[interquartile range (-2)-(2)] vs -5[(-11)-(-1.75)], p = 0.012) or good response (1[(-2)-(2)] vs -8[(-9.75)-
(-7)], p = 0.0043). The change of total PD score-8 was also significantly different between the patients with no response and moderate
response (1[(-2)-(2)] vs -3.5[(-7.25)-(-1.75)], p = 0.012) or good response (1[(-2)-(2)] vs -6.5[(-7.75)-(-5.25)], p = 0.0022). The change of
total GS score-24 and total GS score-8 were significantly different between the patients with no response and good response (-2[(-2)-(1)] vs
-9[(-16.5)-(-4.5)], p = 0.011, and -1[(-1)-(-1)] vs -6[(-8)-(-4)], 0.0022, respectively). Among the patients with no response, 2 (40%) showed
decrease in total PD score-24 and total PD score-8, and 3 (60%) and 4 (80%) showed decrease in total GS score-24 and total GS score-8,
respectively. Among the patients with moderate response, 2 (17%) showed no improvement in total PD score-24 and total PD score-8, and 3
(25%) and 5 (42%) showed no improvement or even increase in total GS score-24 and total GS score-8, respectively. Thus total 4 (17%)
and 6 (26%) showed discrepancy between EULAR response criteria and 24-joint US assessment.
Conclusion: Although this study indicates the relationship between EULAR response criteria and US assessment as a whole, there are some
cases showing discrepancy between these two assessment methods in monitoring RA activity. Thus the US assessment can be an essential
method for monitoring response to treatment in RA patients.
Disclosure: R. Yoshimi, None; Y. Sato, None; N. Sakurai, None; T. Komiya, None; N. Hamada, None; H. Nagai, None; N. Tsuchida,
None; Y. Sugiyama, None; Y. Soejima, None; Y. Kunishita, None; H. Nakano, None; D. Kishimoto, None; R. Kamiyama, None; K.
Minegishi-Takase, None; Y. Kirino, None; S. Ohno, None; H. Nakajima, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-discrepancy-between-the-eular-response-criteria-and-

ultrasonography-assessment-for-monitoring-therapeutic-response-in-rheumatoid-arthritis
Power Dopper Ultrasonography Detects Superior Efficacy of Non-TNF Biologics

Compared to Cycling of TNF Inhibitors in RA Patients Inadequate Response to First
TNF Inhibitors
Ayako Nishino1,2,3, Shinya Kawashiri2,3, Tamami Yoshitama2, Nobutaka Eiraku2, Naoki Matsuoka2, Yukitaka Ueki2, Akitomo Okada2,
Hiroaki Hamada2, Toshihiko Hidaka2, Shuji Nagano2, Tomomi Tsuru2, Keita Fujikawa2, Yojiro Arinobu2, Yoshifumi Tada2, Yasuhiro
Nagata1 and Atsushi Kawakami2,4, 1Center for Comprehensive Community Care Education, Nagasaki University Graduate School of
Biomedical Sciences, Nagasaki, Japan, 2Kyushu multicenter rheumatoid arthritis ultrasound prospective observational cohort study group,
Nagasaki, Japan, 3Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki,
Japan, 4Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate
School of Biomedical Sciences, Nagasaki City, Japan
SESSION INFORMATION
Background/Purpose: Efficacy of cycling of TNF inhibitors, judged by composite measures, is inferior to non-TNF biologics in patients
with RA inadequate response to previous TNF inhibitors (TNF-IR patients). Ultrasonography (US) is a non-invasive imaging method to
evaluate activity of synovitis more accurately than physical examinations, however, no previous reports have examined comparative efficacy
of alternate TNF inhibitors or non-TNF biologics in RA patients inadequate response to previous TNF inhibitors by US. The aim of this study
is to determine whether US find the difference of efficacy in switching to cycling TNF inhibitors compared to non-TNF biologics in TNF-IR
patients.
Methods: We have investigated the above-mentioned comparison by the administrated RA patients in Kyushu multicenter rheumatoid
arthritis ultrasound prospective observational cohort in which bilateral 22 wrists and finger joints were semi-quantitatively examined every 3
months by grey-scale (GS) and power Dopper (PD) from 0 to 3. US disease activity was determined as sum of GS or PD score (total GS
score or PD score; 0-66, respectively). Among the 223 patients who registered and completed the first 12 months observation, thirty-nine
subjects were classified as switched to alternate TNF inhibitors (N = 11) or non-TNF biologics (N = 28) as second bDMARDs. We
compared the efficacy of alternate TNF inhibitors group with non-TNF biologics group by US for 12 months using LOCF analysis.
Results: The characteristic of both groups at study entry was comparable including DAS28-ESR, duration of diseases, positivity of ACPA or
RF and sum of GS and PD score. Drug retention rate at 12 months was superior in non-TNF biologics group compared to alternate TNF
inhibitors group. Accordingly, sum of US score, especially PD score, clearly decreased in non-TNF biologics group whereas did poorly
change in alternate TNF inhibitors group (Fig. 1). Change of DAS28-ESR was also more prominent in non-TNF biologics group compared to
alternate TNF inhibitors group.
Conclusion: Our data confirm the previous clinical finding by US, especially PDUS, that switching to non-TNF biologics is more effective
than cycling TNF inhibitors as a second choice of bDMARDs in TNF-IR patients.
Disclosure: A. Nishino, None; S. Kawashiri, None; T. Yoshitama, None; N. Eiraku, None; N. Matsuoka, None; Y. Ueki, None; A. Okada,
None; H. Hamada, None; T. Hidaka, None; S. Nagano, None; T. Tsuru, None; K. Fujikawa, None; Y. Arinobu, None; Y. Tada, None; Y.
Nagata, None; A. Kawakami, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/power-dopper-ultrasonography-detects-superior-efficacy-

of-non-tnf-biologics-compared-to-cycling-of-tnf-inhibitors-in-ra-patients-inadequate-response-to-first-tnf-inhibitors
Ultrasound Abnormalities Predict Arthritis Development in ACPA and/or RF Positive

Arthralgia Patients
Annelies Blanken1, Marian van Beers-Tas1, Marlies Meursinge Reynders1 and Dirkjan van Schaardenburg1,2, 1Amsterdam Rheumatology
and immunology Center | Reade, Amsterdam, Netherlands, 2Amsterdam Rheumatology and immunology Center | Academic Medical Center,
Amsterdam, Netherlands
SESSION INFORMATION
Background/Purpose:
Early diagnosis of rheumatoid arthritis (RA) is important for controlling disease activity and preventing joint damage. Individuals positive
for anticitrullinated protein antibodies (ACPA) and/or rheumatoid factor (RF) are at risk of developing RA. In this study we investigated
whether ultrasound (US) can predict development of arthritis in seropositive arthralgia patients.
Methods:
We included ACPA and/or RF positive patients with arthralgia, but without clinical arthritis. US was performed at baseline in 12 joints:
bilateral MCP2-3, PIP2-3, wrist and MTP5. Images were scored semiquantitatively for synovitis and Power Doppler (PD) on a scale of 0-3.
Grades 2 to 3 for synovitis and grades 1 to 3 for PD were regarded as abnormal. The association of ultrasound abnormalities with the
development of arthritis was analyzed using Fisher’s exact test, expressed as odds ratios (OR) with 95% confidence interval (CI). Kaplan
Meier survival analysis with log-rank test and Cox regression analysis were used to assess the timing of arthritis development, expressed as
median time to arthritis and hazard ratios (HR) with 95% CI.
Results:
In total, 169 seropositive arthralgia patients underwent US examination. Mean age was 51 (standard deviation (SD) 11) and 73% was
female. Of these patients, 44 (22%) developed arthritis during a mean follow-up time of 27 (SD 19) months. Thirty seven (84%) patients
developing arthritis satisfied the 2010 ACR/EULAR classification criteria for RA. Synovitis and PD signal in at least one joint was observed
in 14 (8%) and 7 (4%) patients, respectively. The presence of synovitis was associated with arthritis development (OR 8.9, CI 2.6-30.2,
p<.01, Table 1), whereas the presence of PD signal was not (OR 1.1, CI 0.2-6.1, p=1.0). Corresponding positive predictive values were
71% and 29%, respectively. Patients with synovitis or PD in at least one joint developed arthritis earlier than patients without US
abnormalities (synovitis: median time to arthritis 11 versus 14 months, p<0.01; PD: median time to arthritis 5 versus 12 months, p<0.01; Fig
1) with corresponding HRs of 3.5 (CI 1.5-7.9, p<0.01) and 6.9 (CI 1.5-32.2, p<0.02) respectively.
Conclusion:
Synovitis on US predicted arthritis development in seropositive arthralgia patients. This association was not found for PD, however PD
frequency was low and therefore the power to predict arthritis was low. However, when taking into account the time to arthritis development,
both synovitis and PD were associated with an increased hazard on developing arthritis.
Figure 1. Kaplan-Meier survival curve for (A) synovitis and (B) Power Doppler (PD) and arthritis development
Disclosure: A. Blanken, None; M. van Beers-Tas, None; M. Meursinge Reynders, None; D. van Schaardenburg, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/ultrasound-abnormalities-predict-arthritis-development-

in-acpa-andor-rf-positive-arthralgia-patients
Finger Joint Cartilage Thickness Evaluated By Semiquantitative Ultrasound Score in

Patients with Rheumatoid Arthritis
Takehisa Ogura1, Ayako Hirata1, Sayaka Takenaka2, Hideki Ito2, Yuki Inoue1, Chihiro Imaizumi2, Yuto Takakura2, Kennosuke Mizushina1,
Takaharu Katagiri2, Norihide Hayashi2, Rie Kujime1, Munetugu Imamura2 and Hideto Kameda3, 1Department of Rheumatology, Toho
University Ohashi Medical Center, Tokyo, Japan, 2Toho University Ohashi Medical Center, Tokyo, Japan, 3Division of Rheumatology,
Department of Internal Medicine, Toho University Ohashi Medical Center, Tokyo, Japan
SESSION INFORMATION
Background/Purpose: Joint destruction in rheumatoid arthritis (RA) includes both bone and cartilage lesions. By X-ray examination,
cartilage destruction is evaluated as the joint space narrowing (JSN). However, JSN is not a direct evaluation of cartilage. Previously we
have confirmed the usefulness of the direct imaging of finger joint cartilage thickness (FJCT) by ultrasound (US). Then we aimed to evaluate
the FJCT by semiquantitative US score and clarify its clinical significance in patients with RA.
Methods: We enrolled 53 RA patients in low disease activity or clinical remission (DAS28-CRP < 2.7) in this study. The FJCT of
metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of 2nd to 5th fingers was bilaterally visualized and measured at the
middle portion of MCP and PIP joints from a longitudinal dorsal view, with approximately 90 degrees flexion. Furthermore, one US
examiner performed the semiquantitative scoring of the recorded cartilage images in a blinded manner on a scale of 0–2 (0 = normal, 1 =
minimal, and 2 = severe)1). In addition, the JSN of fingers was scored by van der Heijde-modified Sharp method with a hand X-ray obtained
within 2 months of US examination. The relationship among the total FJCT, the semiquantitative FJCT score and the JSN score were assessed
by Spearman’s rank correlation coefficient.
Results: The total FJCT from 8 fingers ranged from 4.0 to 8.8 mm (median 6.7 mm), which was significantly correlated with the
semiquantitative score (rho=-0.681, p<0.001). And both total FJCT and semiquantitative score were significantly correlated with the total
JSN score (rho=-0.684, p<0.001, and rho=0.639, p<0.001, respectively). The semiquantitative score was associated with disease duration
(rho=0.347, p=0.011), especially for MCP joints (rho=0.453, p<0.001), but not for PIP joints (rho=0.071, p=0.614). Age, height and
seropositivity were not associated with semiquantitative FJCT score and JSN score.
Conclusion: A simplified and direct evaluation of cartilage damage by semiquantitative US score is valid and useful in patients with RA.
Reference: 1) #OP0288. Eular2017, Madrid, Spain. doi: 10.1136⁄annrheumdis-2017-eular.4314
Disclosure: T. Ogura, None; A. Hirata, None; S. Takenaka, None; H. Ito, None; Y. Inoue, None; C. Imaizumi, None; Y. Takakura, None;
K. Mizushina, None; T. Katagiri, None; N. Hayashi, None; R. Kujime, None; M. Imamura, None; H. Kameda, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/finger-joint-cartilage-thickness-evaluated-by-

semiquantitative-ultrasound-score-in-patients-with-rheumatoid-arthritis
Histological and Clinical Correlates of Ultrasound Measures of Joint Inflammation:

Analysis of RA Tissue Obtained By Ultrasound Guided Biopsy in Phase 1 of the
Accelerating Medicines Partnership RA Network
Andrew Filer1, Arthur M. Mandelin II2, Edward F. DiCarlo3, Brendan Boyce4, Darren Tabechian5, Ralf G. Thiele6, Stephan Kelly7, Ellen
M. Gravallese8, Diane Horowitz9, Kevin Wei10, Deepak Rao11, Vivian P. Bykerk12 and Jennifer H. Anolik13, 1Institute of Inflammation and
Ageing (IIA), University of Birmingham, Birmingham, United Kingdom, 2Rheumatology, Northwestern University, Chicago, IL, 3Laboratory
Medicine, Hospital for Special Surgery, New York, NY, 4University of Rochester Medical Center, Rochester, NY, 5Medicine, Division of
Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, 6Medicine, University of Rochester
Medical Center, Rochester, NY, 7Queen Mary University of London, London, United Kingdom, 8Lazare Research Bldg, University of
Massachusetts Medical School, Worcester, MA, 9Division of Rheumatology, North Shore - Long Island Jewish Health System, Woodbury,
NY, 10Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA,
11Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Spring, IN, 122-005, Mt Sinai Hospital, Toronto, ON, Canada,
13Medicine- Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY
SESSION INFORMATION
Background/Purpose:
The AMP-RA network applies cutting edge technologies to the study of tissue obtained by ultrasound guided synovial biopsy from patients
with rheumatoid arthritis (RA). Ultrasound provides objective joint level measures of synovial inflammation, including hypertrophy
(greyscale ultrasound, GSUS) and hyperaemia (Power Doppler ultrasound, PDUS). Furthermore, ultrasound joint count assessments enable
higher sensitivity for measurement of systemic disease activity compared to clinical joint assessments alone. We examined the relationship
between joint level ultrasound variables and synovial histology in Phase I patients with active RA. we also validated ultrasound measures
against conventional measures of disease activity.
Methods:
During Phase I of AMP-RA we recruited patients fulfilling clinician RA diagnosis, 1987 or 2010 ACR/EULAR RA criteria with at least one
joint amenable to biopsy. Patients were required to have a CDAI≥10; patients receiving i.a. steroids in the previous 4 weeks, i.m. in the last
8 weeks or oral steroids >10mg were excluded. 12 joint extended ultrasound assessments of 10 MCPs and 2 wrist joints using four point
semiquantitative GSUS and PDUS scales were performed alongside collection of standard RA disease activity measures including
DAS28CRP domains. 12 joint ultrasound indices were calculated by summing 0-3 grades for all joints. GSUS and PDUS measures were also
assessed in the biopsied joint prior to the procedure. Retrieved tissue was fixed, stained and paraffin embedded prior to sectioning and
staining by H&E. Tissues were assessed for quality: Where 50% or more tissue fragments out of a minimum of 4 contained lining layer
histology, tissues were Krenn scored for lining layer and inflammatory infiltrate, and qualitative assessment of tissue pathotype by three
histologists. In parallel, tissues were enzymatically disaggregated and cell yield determined using trypan dye exclusion.
Results:
In 15 tissue samples meeting QC taken from wrist (5), knee (9) and MCP (1) joints, Greyscale ultrasound (GSUS) grade correlated with the
Krenn index of cellular inflammation (p<0.01, r=0.65) and the Krenn lining layer score (p<0.05, r=0.52). Power Doppler Ultrasound (PDUS)
grade failed to correlate with either histological measure (p=0.34, p=0.48 respectively). Tissues with higher USGS, but not USPD scores,
were more likely to show a lymphocyte predominant histological pathotype than other patterns (p<0.05). There was no consistent relationship
between GSUS or PDUS measures of synovitis and cell yield at tissue disaggregation. GSUS extended joint indices correlated with
DAS28CRP, 28 swollen joint and tender joint counts (p<0.05, r=0.70; p<0.01, r=0.78; p<0.05, r=0.65), while PDUS extended joint indices
correlated with DAS28CRP and 28 swollen joint counts (p<0.05, r=0.66; p<0.05 r=0.76).
Conclusion:
Ultrasound measures of synovial hypertrophy correlate with the complexity of joint infiltrates and lining layer thickness. There was an
association between synovial hypertrophy and a lymphocyte predominant pathotype. Extended joint indices demonstrate validity when
compared to existing clinical domains.
Disclosure: A. Filer, None; A. M. Mandelin II, None; E. F. DiCarlo, None; B. Boyce, None; D. Tabechian, None; R. G. Thiele, Amgen,
8,AbbVie, 8,BioClinica, 5,Fujifilm SonoSite, 9; S. Kelly, None; E. M. Gravallese, Abbott Immunology Pharmaceuticals, 2,Lilly, Inc, 2,New
England Journal of Medicine, 3,Up to Date, 7,Lilly Inc., 5,Sanofi/Genzyme, 5; D. Horowitz, None; K. Wei, None; D. Rao, None; V. P.
Bykerk, None; J. H. Anolik, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/histological-and-clinical-correlates-of-ultrasound-

measures-of-joint-inflammation-analysis-of-ra-tissue-obtained-by-ultrasound-guided-biopsy-in-phase-1-of-the-accelerating-medicines-
partnership-ra-ne
Evaluation of Bone Erosions in Rheumatoid Arthritis Patients Using Cone Beam

Computed Tomography, Magnetic Resonance Imaging, and Ultrasound
Jemima Albayda1, Gaurav Thawait2, Wojciech Zbijewski3, Alexander Martin3, Shadpour Demehri4, Jan Fritz4, John Yorkston2, Jeff
Siewerdsen3 and Clifton O. Bingham III5, 1Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, 2Johns Hopkins
University, Baltimore, MD, 3Biomedical Imaging Science, Johns Hopkins University, Baltimore, MD, 4Radiology, Johns Hopkins University,
Baltimore, MD, 5Rheumatology, Johns Hopkins University, Baltimore, MD
SESSION INFORMATION
Background/Purpose: This preliminary study was designed to determine the agreement and reproducibility of a novel cone beam CT
(CBCT) extremity scanner, MRI and ultrasound (US) for detection of erosions in rheumatoid arthritis (RA). For this purpose, we compared
the bone erosion scores for CBCT, MRI, and US in RA patients along with test-retest reproducibility of the CBCT data.
Methods: Ten patients (5 males, 5 females; mean age 58 years, age range 34 – 81 years) with a clinically confirmed diagnosis of RA were
recruited for this institutional review board-approved study. All patients underwent an MRI, CBCT and US scan of the wrist and hand
followed by a second CBCT scan one week later. The MRI was done using a 3T clinical MR scanner with dedicated hand coil; US using a
state-of-the-art machine with an 18 Mhz hockey stick probe; while the CBCT was done using a prototype CBCT extremity scanner. US scans
were performed and read by a rheumatologist with 5 years of experience in musculoskeletal ultrasound, scoring for the presence of absence
of erosion in each joint. A radiologist with 7 years of musculoskeletal imaging evaluated MRI and CBCT images for erosions using RAMRIS
like scoring between 1 to 10 (1 is 0-10% erosion, 2 is 11-20% erosion etc). The 2nd to 5th metacarpophalangeal joints, carpal bones and
distal radius and ulna were assessed. Repeatability and agreement between methods were evaluated with Intraclass Correlation Coefficients
(ICC) and Bland-Altman plots.
Results: Bland-Altman analysis showed agreement of 0.02±3.5, 3.5 to -3.5 (bias ± repeatability coefficient, 95% limits of agreement
interval) with ICC score of 0.77 showing good correlation between MRI, US, and CBCT bone erosion scores. Correlation was higher for
bone erosion scores of MCPs than for wrist joints. Test-retest reproducibility for the CBCT scans showed an excellent ICC score of 0.95.
Conclusion: Good correlation was seen for bone erosions as detected by CBCT, MRI and US, while the prototype extremity CBCT images
showed high test-retest reproducibility. This study provides a good first approximation for evaluation of bone erosions across the three
modalities.
Figure 1. Images of erosions on CBCT, MRI and US in an RA patient
Disclosure: J. Albayda, None; G. Thawait, None; W. Zbijewski, None; A. Martin, None; S. Demehri, None; J. Fritz, None; J. Yorkston,
None; J. Siewerdsen, None; C. O. Bingham III, BMS, 2,BMS, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/evaluation-of-bone-erosions-in-rheumatoid-arthritis-

patients-using-cone-beam-computed-tomography-magnetic-resonance-imaging-and-ultrasound
Tracer Uptake from High Resolution Bone SPECT/CT Is Linked to Response in

Rheumatoid Arthritis Patients
Yasser Abdelhafez 1,2, Felipe Godinez3, Kanika Sood4, Rosalie Hagge2, Ramsey D Badawi2, Robert D Boutin2, Siba P. Raychaudhuri5 and
Abhijit Chaudhari6, 1Nuclear Medicine Unit, South Egypt Cancer Institute, Assiut University, Assiut, Egypt, 2Radiology, Faculty of
Medicine, University of California Davis, Sacramento, CA, 3Biomedical Engineering Department, King’s College London, London, United
Kingdom, 4Rheumatology Section, Sacramento Veterans Affairs Medical Center, Sacramento, CA, 5Rheumatology, VA Sacramento Medical
CenterUC Davis School of Medicine, Mather, CA, 6Radiology, UC Davis School of Medicine, Sacramento, CA
SESSION INFORMATION
Tracer Uptake from High Resolution Bone SPECT/CT is Linked to Response in Rheumatoid Arthritis Patients.
Background/Purpose:
To evaluate the association between response to TNF-_ blockers and tracer uptake from dual-phase technetium-99m methylene
diphosphonate (99mTc-MDP) bone scanning of the hands via a SPECT/CT system in patients with rheumatoid arthritis.
Methods:
Four patients with established rheumatoid arthritis (RA) were enrolled in this IRB-approved prospective pilot study. They were referred for
performing bone scan prior to receiving TNF-_ blockers. Early blood pool (15 minutes after tracer injection, marker of hypervascularity) and
delayed osseous phase (3 hours after the same injection, marker of osteoblastic activity) scans of the hands using 99mTc-MDP were
performed using high-resolution SPECT/CT scanner. A special hand positioning device was designed and used during the scans. Second- to
5th metacarpo-phalangeal joints (MCP) were assessed qualitatively (normal vs. abnormal uptake) and quantitatively (by measuring the
maximum counts). All counts were corrected to the background (defined as the median count from all normal joints). Qualitative and
quantitative data were assessed against response.
Results:
After a median follow-up of 7.8 months (range: 6.9 Ð 21.7), two patients were considered responders and two were non-responders. A total
of 32 joints were assessed. Early and delayed uptake in the 2nd to 5th MCP joints were abnormal in 7 joints, all belong to non-responders;
while it was normal in 25 joints, 16 of them were in responders & 9 in non-responders; P = 0.007.
The median corrected counts from delayed scans were 0.92 (range: 0.49-1.49) in responders vs. 1.14 (range: 0.81-2.93) in non-responders; P
= 0.002.
The median corrected counts from blood pool scans were 0.95 (range: 0.6-1.67) in responders vs. 1.1 (range: 0.55-2.29) in non-responders;
P = 0.2.
Conclusion:
Delayed osseous uptake in metacarpophalangeal joints of rheumatoid arthritis patients, measured from 99mTc-MDP SPECT/CT, performed
prior to treatment with TNF-_ blockers, was significantly higher in non-responders compared to responders, which might reflect higher
baseline osteoblastic activity in non-responders.
Table 1: Ratio of the counts measured on 2nd to 4th metacarpophalangeal joints in responders and non-responders
Non-
Baseline SPECT/CT Responders P
Responders
Median 0.95 (0.6- 1.1 (0.55-
Blood Pool
(Range) 1.67) 2.29) 0.184
Mean±SD 0.98±0.32 1.29±0.57
Delayed Median 0.92 (0.49-

1.38±0.61
Phase (Range) 1.49)
0.002
1.14 (0.81-
Mean±SD 0.88±0.25
2.93)
Figure 1:
Disclosure: Y. Abdelhafez, Philips Healthcare, 2; F. Godinez, Philips Healthcare, 2; K. Sood, Philips Healthcare, 2; R. Hagge, Philips
Healthcare, 2; R. D. Badawi, Philips Healthcare, 2; R. D. Boutin, Philips Healthcare, 2; S. P. Raychaudhuri, Philips Healthcare, 2; A.
Chaudhari, Philips Healthcare, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/tracer-uptake-from-high-resolution-bone-spectct-is-

linked-to-response-in-rheumatoid-arthritis-patients
Rheumatoid Arthritis Imaging on PET-CT Using a Novel Folate Receptor Ligand for
Macrophage Targeting
Nicki Verweij1, Stefan Bruijnen1, Yoony Gent2, Marc Huisman3, Gerrit Jansen2, Carla Molthoff4, Qingshou Chen5, Philip Low5, Albert
Windhorst3, Adriaan Lammertsma3, Otto Hoekstra3, Alexandre Voskuyl2 and Conny van der Laken2, 1Dept. of Rheumatology, Amsterdam
Rheumatology and immunology Center - location VU University Medical Center, Amsterdam, The Netherlands, Amsterdam, Netherlands,
2Department of Rheumatology, Amsterdam Rheumatology and immunology Center - location VU University Medical Center, Amsterdam, The
Netherlands, Amsterdam, Netherlands, 3Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The
Netherlands, Amsterdam, Netherlands, 4Department of Radiology & Nuclear Medicine, Amsterdam Rheumatology and immunology Center -
location VU University Medical Center, Amsterdam, The Netherlands, Amsterdam, Netherlands, 5Department of Chemistry, Purdue
University, West Lafayette, IN, USA, West Lafayette, IN
SESSION INFORMATION
Background/Purpose:
PET imaging with macrophage tracers has been shown promising for detection of (sub)clinical synovitis, making it useful for both early
diagnostics and therapy monitoring in rheumatoid arthritis (RA) patients (1,2). For detection of more subtle arthritis, a previously
investigated macrophage tracer, (R)-[11C]PK11195, was limited in use due to high background uptake in bone and bone marrow.
[18F]fluoro-PEG-folate binds to the folate receptor β, which is expressed on synovial macrophages (3). Preclinical research in arthritic rats
has shown excellent targeting, making it a promising tracer for clinical testing in RA patients (4). In this study, we investigated the value of
[18F]fluoro-PEG-folate PET-CT for imaging of inflamed joints in patients with clinically active RA.
Methods:
Nine RA patients with a minimal of two clinically inflamed hand joints were included. PET-CT scans were performed of the hands, after
intravenous administration of either 185 MBq of [18F]fluoro-PEG-folate (n = 6) or 425 MBq of (R)-[11C]PK11195 (n = 3) for comparison.
Joints with visually marked uptake were further analyzed by calculation of Standardized Uptake Values (SUVs) in Volumes of Interest (VOI),
drawn on top of the PET positive joints. We drew background VOIs on metacarpal bone in order to calculate Target-to-Background (T/B)
ratios.
Results:
None of the patients showed adverse effects, establishing the safety of [18F]fluoro-PEG-folate for use in humans. Arthritic joints were clearly
visualized (Fig 1).. In the patients injected with [18F]fluoro-PEG-folate, 25 positive joints were observed, with a minimum of two joints per
patient. In 10 of these 25 joints, clinical arthritis was confirmed. In the remaining 15 positive joints clinical inflammation was absent,
suggesting the presence of subclinical inflammation. Whilst both [18F]fluoro-PEG-folate and (R)-[11C]PK11195 showed clear uptake in
arthritic joints, [18F]fluoro-PEG-folate demonstrated a significantly lower background uptake than (R)-[11C]PK11195 (SUV of 0.18 vs 0.75;
p < 0.001) respectively. T/B-ratios were significantly higher for [18F]fluoro-PEG-folate (3.60vs 1.72, p = 0.009).
Figure 1: [18F]fluoro-PEG-folate uptake on PET-CT in inflamed hand/wrist joints of a RA patient.
Conclusion:
[18F]fluoro-PEG-folate shows great potential as a macrophage tracer to image both clinical and presumably also subclinical arthritis in RA
patients. The tracer shows improved characteristics compared to the established macrophage tracer (R)-[11C]PK11195 for imaging arthritis,
because of lower background signal.
References:
(1) Gent YY, et al. J Rheumatology. 2014; 41: 2145-52
(2) Gent YY, et al. Arthritis Rheum. 2012; 64: 62-6
(3) Chandrupatla DMSH, Arthritis Res Ther. 2017; 19: 114.
(4) Gent YY, et al. Arthritis Res Ther. 2013; 15: R37
Disclosure: N. Verweij, None; S. Bruijnen, None; Y. Gent, None; M. Huisman, None; G. Jansen, None; C. Molthoff, None; Q. Chen,
None; P. Low, None; A. Windhorst, None; A. Lammertsma, None; O. Hoekstra, None; A. Voskuyl, None; C. van der Laken, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rheumatoid-arthritis-imaging-on-pet-ct-using-a-novel-

folate-receptor-ligand-for-macrophage-targeting
The Clinical Utility of Splenic Fluorodeoxyglucose Uptake for Diagnosis and Prognosis
in Patients with Macrophage Activation Syndrome
Sung Soo Ahn1, Sang Hyun Hwang2, Seung Min Jung1, Sang-Won Lee1, Yong-Beom Park3, Mijin Yun2 and Jason Jungsik Song1, 1Division
of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea, Republic of (South), 2Department
of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Korea, Republic of (South), 3Department of Internal Medicine, Yonsei
University College of Medicine, Seoul, Korea, Republic of (South)
SESSION INFORMATION
Abstract
Background/Purpose: To evaluate splenic glucose metabolism in macrophage activation syndrome (MAS), characterised by overwhelming
systemic inflammation. Splenic 18F-fluorodeoxyglucose (FDG) uptake was compared in patients with MAS and sepsis using positron
emission tomography/computed tomography (PET/CT).
Methods: Clinical and FDG-PET/CT findings from patients with MAS and those with culture-proven sepsis were evaluated. Standardised
uptake value (SUV) for the spleen and liver were measured. The maximum of the spleen to liver SUV ratio (SLRmax) was calculated as
spleen SUVmax/liver SUVmean. Radiological splenic volume was also measured, and splenic metabolic volume (MV) was defined as total
splenic volume with an SLRmean > 1.14. The association between clinical features, laboratory variables, and SLRmax was analysed.
Results: The median SLRmax and splenic MV were significantly higher in patients with MAS (n = 38) than they were in those with sepsis (n
= 15) (SLRmax: 1.51 vs. 1.09, p = 0.001; MV: 346.0 vs. 154.0, p = 0.015) (Figure 1). Multivariate analyses revealed that SLRmax > 1.31
was useful for discriminating between MAS and sepsis (Table 1). SLRmax positively correlated with ferritin and lactate dehydrogenase level
in MAS. Furthermore, MAS patients with high splenic FDG uptake (SLRmax >1.72) had higher in-hospital mortality compared to those with
moderate to low splenic FDG uptake (p = 0.013).
Conclusion: This study was the first to demonstrate that splenic FDG uptake is significantly elevated in patients with MAS compared to those
with sepsis. This may be useful to differentiate between MAS and sepsis, and to predict poor prognosis in patients with MAS.
References
1. Rosado FG, Kim AS. Hemophagocytic lymphohistiocytosis: an update on diagnosis and pathogenesis. American journal of clinical
pathology. 2013;139(6):713-727.
Figure. 1 Comparison of the standardised 18F-fluorodeoxyglucose uptake values (SUV) in patients with macrophage activation syndrome
(MAS; n = 38), patients with sepsis (n = 15), and healthy controls (n = 40) (A) The SUVmax of spleen to liver ratio. (B) The SUVmax of bone
marrow to liver ratio. (C) Spleen radiologic volume. (D) Spleen metabolic volume. (E) Representative 18F-FDG PET/CT images in patient
with MAS (left), patient with sepsis (middle), and healthy control subject (right). ns, not significant. Data are expressed as the median; error
bars indicate the interquartile range.
Disclosure: S. S. Ahn, None; S. H. Hwang, None; S. M. Jung, None; S. W. Lee, None; Y. B. Park, None; M. Yun, None; J. J. Song, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-clinical-utility-of-splenic-fluorodeoxyglucose-uptake-

for-diagnosis-and-prognosis-in-patients-with-macrophage-activation-syndrome
Development and Validation of a Flourescence Optical Imaging Rheumatoid Arthritis

Scoring System for Synovitis in the Wrist and Hand
Mads Ammitzbøll-Danielsen1, Mikkel Østergaard1,2, Lene Terslev3, Sarah Ohrndorf4 and Daniel Glinatsi1, 1Center for Rheumatology and
Spine Diseases, Rigshospitalet, Copenhagen Center for Arthritis Research, Copenhagen, Denmark, 2Center for Rheumatology and Spine
Diseases, Copenhagen Center for Arthritis Research, Copenhagen, Denmark, 3Copenhagen Center for Arthritis Research, Center for
Rheumatology and Spine Diseases, Rigshospitalet, Denmark, Copenhagen, Denmark, 4Rheumatology and Clinical Immunology, Charité-
University Medicine Berlin, Berlin, Germany
SESSION INFORMATION
Background/Purpose : To assess the intra- and inter-reader agreement and responsiveness of a novel scoring system for FOI-assessed
synovitis.
Methods: FOI of were obtained of both wrists and hands of 46 RA patients inducing or escalating anti-rheumatic therapy and who had ≥1
clinically swollen joint in the hand at baseline, after 3 and 6 months’ follow-up. The hands were placed in the FOI-unit and the patient
received a bolus of i.v. ICG-Pulsion (1mg/kg body weight) 10 seconds after starting the examination, which obtained 1 image/second over 6
minutes. The image-sets were anonymized and randomized and were assessed for synovial pathology at the wrist, 1st-5th
metacarpophalangeal (MCP), 1st interphalangeal (IP) and 2nd-4th proximal interphalangeal (PIP) joint levels in both hands by two readers
blinded to patient data but not chronology. The readers performed a calibration session before the exercise. The images of 23 patients were
re-anonymized and were assessed as an intra-reader analysis. The scoring system for synovitis was based on the theory that inflamed tissue
would demonstrate a more rapid enhancement than surrounding tissues. For each joint, the images were assessed sequentially from start of
injection of ICG-Pulsion to peak enhancement. Synovial pathology was defined as a sharply margined enhancement with clear integrity from
surrounding tissues and correct anatomical location lasting ≥3 seconds. The thickness of the pathology fulfilling these criteria were measured
in the transverse plane of the hand at the 3rd second of enhancement and were scored as follows: 0: no enhancement, 1: ˂1/3, 2: ≥1/3 but
˂2/3, 3: ≥2/3 of joint thickness. Descriptive statistics and the Wilcoxon signed-rank test were used to assess change in score over time. Intra-
/inter-reader for status and change scores were assessed using single measure intra-class correlation coefficients (ICC) and smallest
detectable change (SDC, change scores only). Responsiveness was assessed using standardized response mean (SRM).
Results: The median (IQR) change in total synovitis score between baseline and 3/6 months’ follow-up were -5.0 (-10.0;-1.0)/-8.0 (-13.5;-
3.0) (p<0.01). Intra- and inter-reader ICC were good to very good for status and change scores at all joint levels and for total scores (Table
1). The SDC were generally low and for the inter-reader SDC, 56%/60% of the patients had a change larger than the SDC between baseline
and 3/6 months respectively. The mean SRM for total change scores between baseline and 3/6 months’ follow-up were moderate to good
(0.7/0.8).
Conclusion: The novel FOI RA synovitis scoring system showed high reliability and moderate to good responsiveness in the hands. Future
studies should focus on comparing the sensitivity and specificity of FOI with ultrasound and magnetic resonance imaging.
Table 1
3 months’ 6 months’ ΔBaseline – 3 ΔBaseline – 6

Baseline
follow-up follow-up months months
Intra-reader ICC (SDC), reader 1
Total scores 0.90 0.86 0.83 0.87 (6.2) 0.92 (4.9)
Wrist 0.82 0.92 0.62 0.88 (1.4) 0.91 (1.4)
MCP joints 0.86 0.72 0.93 0.76 (4.8) 0.85 (3.6)
PIP joints 0.95 0.96 0.86 0.90 (2.9) 0.90 (3.3)
Intra-reader ICC (SDC), reader 2
Total scores 0.85 0.72 0.16 0.77 0.74
Wrist 0.84 0.77 0.71 0.80 0.78
MCP joints 0.84 0.67 0.47 0.87 0.84
PIP joints 0.94 0.73 0.24 0.73 0.68
Inter-reader ICC (SDC)
Total scores 0.88 0.84 0.60 0.80 (4.8) 0.70 (6.2)
Wrist 0.76 0.72 0.58 0.67 (1.1) 0.65 (1.3)
MCP joints 0.86 0.80 0.76 0.81 (3.1) 0.66 (3.7)
PIP joints 0.91 0.82 0.39 0.79 (2.6) 0.71 (3.6)
Disclosure: M. Ammitzbøll-Danielsen, None; M. Østergaard, AbbVie, BMS, Celgene, Crescendo Bioscience, Janssen, Merck, 2,Abbvie,
BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Novartis, Orion, Pfizer, Regeneron, Roche,
Takeda, and UCB, 8; L. Terslev, None; S. Ohrndorf, None; D. Glinatsi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/development-and-validation-of-a-flourescence-optical-

imaging-rheumatoid-arthritis-scoring-system-for-synovitis-in-the-wrist-and-hand
Near Infrared Indocyanine Green Imaging Reveals Diminished Flow in Basilic

Associated Lymphatic Vessels in the Hands of Rheumatoid Arthritis Patients during
Flare
Richard Bell1, Alicia Lieberman2, Ronald Wood3, Cristy Bell4, Homaira Rahimi5, Edward Schwarz6 and Christopher T. Ritchlin7,
1Orthopedics, University of Rochaester, Rochester, NY, 2Allergy, Immunology and Rheumatology, University of Rochester Medical Center,
Rochester, NY, 3University of Rochester, Rochester, NY, 4Allergy, Immunology & Rheumatology, University of Rochester, Rochester, NY,
5Rheumatology, University of Rochester/Golisano Children's Hosp, Rochester, NY, 6Orthopedeatrics, University of Rochester, Rochester,
NY, 7Division of Allergy, Immunology and Rheumatology, School of Medicine and Dentistry, Division of Allergy, Immunology and
Rheumatology, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA, Rochester, NY
SESSION INFORMATION
Background/Purpose: Near infrared (NIR) imaging studies of subdermal indocyanine green (ICG) in murine models of inflammatory
arthritis established the important contribution of lymphatic vessel (LV) function in joint homeostasis and flare. However, the role of
lymphatic vessel function and altered joint drainage in rheumatoid arthritis (RA) flare is unknown.
Methods: The web spaces in both hands of 7 healthy controls (Ctl) and 2 subjects in RA flare were injected with 0.1ml of 100μM ICG on 2-
4 separate occasions and the NIR fluorescence of the dorsal aspect imaged. Two independent graders counted the total number of fluorescent
LVs crossing the mid-dorsal aspect of the hand, and the number of LVs associated with the basilic and cephalic veins and their tributaries.
Differences between Ctl vs RA were evaluated using Fisher’s Exact Test, pooling left and right hand observations across all visits (n=32
Ctl, n=10 RA). The frequency of lymphatic contractions of these LVs were determined from graphs of region of interest intensity across time
to calculate contractions per minute; differences evaluated using a Wilcoxon Rank Test.
Results: Representative raw images of Ctl and RA hands are presented in Fig 1A-B demonstrating the Mid-Dorsal region (Blue Box),
Basilic (Dark Green Arrows) and Cephalic (Dark Red) associated clusters and their tributaries (Basilic = Light Green, Cephalic = Light
Red). The number of basilic associated LVs crossing the mid dorsal region and the feeding tributaries were decreased in RA subjects
compared to controls (Fig 1C and F, p<0.05). Contour plots generated by stabilizing and averaging all images during the 10min session
show clear anatomic and bulk flow differences (Fig 1 D-E). Note the lack of Basilic LV filled with ICG in RA (circled region in E).
Representative 3D plots of the ROI analysis are shown in Fig 2A and B with scored contractions (Black Arrows) revealing a significant
increase in contraction frequency in the cephalic associated LVs in RA subjects (Fig 2C, p<0.05).
Conclusion: For the first time, we have characterized the lymphatic vessel anatomy of the hands of healthy subjects and RA subject using NIR
ICG imaging. Furthermore, RA patients in flare show a reduced number of fluorescent LVs in the hands compared to Ctl. A decline in the
number of LVs removing inflammatory cells and molecules from the joints and compensatory redirection of flow is likely to play a significant
role in RA flare. Further studies to confirm these initial findings are underway.
Disclosure: R. Bell, None; A. Lieberman, None; R. Wood, None; C. Bell, None; H. Rahimi, None; E. Schwarz, Janssen Pharmaceutica
Product, L.P., 9,Lilly Inc., 9; C. T. Ritchlin, Amgen, Janssen, Pfizer, and UCB, 2,AbbVie, Amgen, Janssen, Lilly, Pfizer, and UCB, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/near-infrared-indocyanine-green-imaging-reveals-

diminished-flow-in-basilic-associated-lymphatic-vessels-in-the-hands-of-rheumatoid-arthritis-patients-during-flare
Validation of Objective Quantification System for Disease Progression in Patients with

Juvenile Idiopathic Arthritis
Olga Kubassova1, N Tzaribachev2, Romiesa Hagoug3 and Mikael Boesen4, 1R&D, Image Analysis Group, London, England, 2University
Medical Center Schleswig-Holstein, Bad Bramstedt, Germany, 3Imaging, Image Analysis Group, London, United Kingdom, 4Radiology,
Copenhagen University Hospital, Bispebjerg and Frederiksberg, Frederiskberg, Denmark
SESSION INFORMATION
Background/Purpose:
Imaging as outcome measure has been studied and extensively used in the assessment of treatment for adult patients with rheumatoid arthritis
(RA)1. In children with juvenile idiopathic arthritis (JIA) similar knowledge is very limited. This abstract presents a novel imaging based
system for the assessment of treatment efficacy in JRA patients and its initial validation against clinical outcome measures.
Methods:
Patients with polyarticular JIA with insufficient (≥3 affected joints) response or intolerance to ≥3 months of Methotrexate, Etanercept were
assessed by imaging. The MCP joints incClinically most affected hand were imaged with Dynamic Contrast Enhanced (DCE)-MRI at
baseline (BL), month 3 and 6 of treatment using a 0.2T scanner. Clinical scores included active joint (AJ) counts. Clinical response was
considered a state of ≤ 3 AJ. A region of interests (ROIs) were placed in DCE-MRI to quantify the synovium in MCPs 2-5. Output
parameters included Dynamic Enhanced MRI Quantification scores (DEMRIQ-Vol) corresponding to the volume of enhancing voxels within
the synovial ROIs alone or multiplied with the mean of the maximum enhancement (ME) or the initial rate of enhancement (IRE), DEMRIQ-
ME and DEMRIQ-IRE. Differences in DEMRIQ-Vol scores between visits were analyzed using t-test (p<0.05* = statistically significant,
p<0.25** = clinically meaningful). Correlation between clinical and DEMRIQ scores were described.
Results:
18 Caucasian patients (12 girls, median age 12,6 years, median disease duration 1,2 years) were included in the study. Two patients
discontinued imaging after BL but continued treatment. In all but 3 of the remaining patients statistically significant and/or clinically
meaningful changes were documented for DEMRIQ ME between visits.
In 4 patients, clinical and DEMRIQ scores showed corresponded changes. In all other patients, clinical and DEMRIQ scores were non-
concordant. Based on DEMRIQ change (irrespective of the clinical scores) the outcome of the patient could be predicted:
in 5 patients, improvement of DEMRIQ scores predicted response to treatment (within 2-6 months after last MRI examination)
in 4 patients, an increase or persistence of a high DEMRIQ predicted non-response to treatment
in 7 patients, increase in DEMRIQ (after initial decrease) or persistence of a high DEMRIQ predicted flare (in 3 of the patients flare
occurred after treatment discontinuation)
In all patients, subclinical disease could be detected on MRI in clinically unaffected joints.
Conclusion:
DEMRIQ scores supported clinical examination by detecting subclinical inflammation. In most patients, the imaging scores were predictive
of the patient outcomes such as response and non-response to treatment and flare, making it a useful outcome measure in clinical practice and
research.
1Kubassova O et al; Eur J Radiol. 2010 Jun;74(3): e67-72.
Disclosure: O. Kubassova, None; N. Tzaribachev, None; R. Hagoug, Image Analysis Group, 3; M. Boesen, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/validation-of-objective-quantification-system-for-

disease-progression-in-patients-with-juvenile-idiopathic-arthritis
Where to Look for Uric Acid Crystals? Results from a Norwegian Ultrasound Study
Hilde B Hammer1, Lars Karoliussen2, Lene Terslev3, Espen A. Haavardsholm4, Tore K Kvien5 and Till Uhlig4, 1Rheumatology, Dept. of
Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, 2Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, 3Copenhagen Center for
Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Denmark, Copenhagen, Denmark, 4Dept. of Rheumatology,
Diakonhjemmet Hospital, Oslo, Norway, 5On behalf of the NOR-DMARD registry, Oslo, Norway
SESSION INFORMATION
Background/Purpose:
Ultrasound (US) has received an increasing attention in detecting uric monosodium urate (MSU) deposits, and is included in the
ACR/EULAR classification criteria for gout. The OMERACT US group has developed definitions for US elementary lesions in gout
including double contour (DC) sign (deposits of crystals on the surface of cartilage), tophus (larger hypo-echoic aggregation of crystals,
usually well delineated), aggregates (small hyper-echoic deposits) and erosions. MSU deposits may be found in many different regions in an
individual with gout but with some predilection sites. The present objective was to asses by US the presence of MSU deposits in a high
number of locations known to be involved, and to identify areas to include when screening for gout by US.
Methods:
This includes baseline data from a prospective observational study where patients with crystal-proven gout who presented after a recent gout
flare were included (117 patients (mean (SD) 56.9 (14.1) years old, 8.5 (7.3) years disease duration, 93.2% men), all with insufficiently
treated serum uric acid level (>360 μmol/L/>6 mg/dl). We performed a systematic extensive assessment with US (GE E9 machine, grey scale
15MHz) to detect MSU deposits, using the OMERACT definitions for DC, tophi and aggregates. The following locations were assessed
bilaterally; radiocarpal joint, MCP 2, insertion of triceps and quadriceps, the patellar tendon (divided into proximal and distal), cartilage of
distal femur (maximal flexed knee) and the talar cartilage of the tibiotalar joint, the MTP 1 joint as well as the Achilles tendon. Sum of sites
with deposits was calculated and correlations were performed by use of Spearman, and frequencies of deposits were calculated as
percentages at each site.
Results:
The mean (SD) serum uric acid level was 488 (88) μmol/L. There was no significant correlation between number of sites with deposits and
uric acid level (r=0.11), but with disease duration (r=0.25, p=0.007). The table shows that DC was primarily found in MTP1, followed by
talar and femoral cartilage. Tophi and aggregates were primarily found in MTP1, followed by distal patellar and triceps tendons. There were
no major differences between right and left side. In 21 patients (17.9%) DC was seen on femoral or talar cartilage, but not in the MTP1
joints.
Conclusion:
There is limited knowledge on the primary locations of MSU deposits, and the present study suggests US examinations of MTP1, distal
patellar and triceps tendons as well as talar and femoral cartilage to be the most important sites to explore for presence of MSU deposits in
patients examined for possible gout.
Double contour Tophus Aggregates
Right Left Right Left Right Left
Wrist 1.7 0 7.7 9.5 7.7 8.6
MCP 2 0 0 3.5 1.8 2.6 1.7
Distal femur 15.3 16.1 NA NA NA NA
cartilage
Talar cartilage 18.8 19.7 NA NA NA NA
MTP 1 36.2 32.5 44.0 45.7 46.5 53.0
Triceps NA NA 18.0 14.5 29.1 30.8
Quadriceps NA NA 6.0 11.9 10.3 19.7
Proximal patellar NA NA 4.3 7.7 10.4 12.0
tendon
Distal patellar NA NA 22.4 17.1 42.2 39.3
tendon
Achilles NA NA 8.7 8.7 11.3 6.1
Disclosure: H. B. Hammer, AbbVie Norway, 2,Abbvie, 8,Novartis Pharmaceutical Corporation, 5,Pfizer Inc, 8,Roche Pharmaceuticals, 8;
L. Karoliussen, None; L. Terslev, None; E. A. Haavardsholm, None; T. K. Kvien, AbbVie, 2,Pfizer Inc, 2,Roche Pharmaceuticals, 2,UCB,
2,BMS, 2,MSD, 2,AbbVie, 5,Pfizer Inc, 5,BMS, 8,MSD, 8,Roche Pharmaceuticals, 8,UCB, 8,AbbVie, 8; T. Uhlig, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/where-to-look-for-uric-acid-crystals-results-from-a-

norwegian-ultrasound-study
An Ultrasonographic Study for Investigating Relationships with the Signs of Uric

Deposition and Bone Erosion in Patients with Hyperuricemia
Ikuko Tanaka1, Takashi Kato2, Motokazu Kai3, Kunikazu Ogawa3, Hisaji Oshima4 and Shigenori Tamaki5, 1NAGOYA Rheumatology
Clinic, Nagoya, Japan, 2Department of Radiology, National Center for Geratrics and Gerontology, Obu, Japan, 3Mie Rheumatology Clinic,
Suzuka, Japan, 4Department of Connective Tissue Diseases, National Tokyo Medical Center, Tokyo, Japan, 5Nagoya Rheumatology Clinic,
Nagoya, Japan
SESSION INFORMATION
Background/Purpose:
Joint ultrasonography (US) is a noninvasive examination that can evaluate arthritis and uric acid deposition at gout attacks.
The purpose of this study was to investigate the progression of gouty arthritis using cross sectional data from the aspect of the joint
sonographic features such as double contour sign (DCS), hyperechoic aggregate (HA), and bone erosion (BE). DCS and HA are signs
showing uric acid deposition.
Methods:
The subjects were 644 consecutive male patients (Age: 45.7±10.7 y.o.) with hyperuricemia and/or gout attack. Seventy one patients (11%)
had experienced neither any attacks nor diagnosis of gout (N group). One hundred eighty seven patients (29%) were diagnosed as the first
attack of gout (1st group), while 386 patients (60%) had their past history of the attacks (His group). They underwent joint US. Observed
rates of DCS, HA, and BE (D: only DCS; H: only HA; B: both DCS and HA; A: DCS or HA; E: BE) in the first metatarsophalangeal (1st
MTP) were compared.
Results:
In the N group, the observed rates of D, H, B, A, and E were 45%, 1%, 0%, 46%, and 1%, respectively. In the 1st group, arthritis on US was
observed in the joints of the first metatarsophalangeal (1st MTP) (72%), ankle (18%), and knee (5%). In the 1st group, the patients of which
attack was at 1st MTP represented that observe rates were D 29%, H 20%, B 38%, A 87%, and E 29%, while the patients of which attack
was at other than 1st MTP were D 20%, H 4%, B 0%, A 24%, and E 0%. In His group, the observed rates were D 16%, H 18%, B 66%, A
100%, and E 57%. Observed frequency of DCS was highest in N group and was decreased along with articular destruction, respectively. In
His group, 100% and more than 50% patients showed sonographic features of ureic acid deposition and bone erosion. Fisher’s exact tests
demonstrated a significant relationship in HA and BE, but not in DCS and BE (p<0.05).
Conclusion:
The results suggested that DCS was the earliest sign of uric acid deposition that was observed in the asymptomatic stage in gount. Even at the
first attack HA was frequently observed that was leading to BE.
Disclosure: I. Tanaka, None; T. Kato, None; M. Kai, None; K. Ogawa, None; H. Oshima, None; S. Tamaki, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/an-ultrasonographic-study-for-investigating-relationships-

with-the-signs-of-uric-deposition-and-bone-erosion-in-patients-with-hyperuricemia
Articular Cartilage of Knee and First MTP Joint Are the Preferred Sites of Urate
Crystal Deposition in Asymptomatic Hyperuricemic Individuals
Danveer Bhadu1, Siddharth K. Das2, Urmila Dhakad3 and Archana Wakhlu4, 1Rheumatology, ALL INDIA INSTITUTE OF MEDICAL
SCIENCES, NEW DELHI, NEW DELHI, India, 2Rheumatology, Prof. and Head, Rheumatology, K.G. Medical University, Lucknow,
Lucknow, India, 3Rheumatology, Asst Professor, K.G. Medical University, Lucknow, India, Lucknow, India, 4Radiology, Senior Resident,
Lucknow, India
SESSION INFORMATION
Background/Purpose: The prevalence of hyperuricemia ranges from 2.6% to 47.2% in various populations [1,2]. Ultrasound evidence of
urate crystal deposition in the form of double contour sign (DCS) and hyperechoic aggregates (HAGs) in asymptomatic hyperuricemic (AH)
individuals has been documented in studies [3]. It has been reported that assessment of one joint (ie, radiocarpal) and two tendons (ie,
patellar and triceps) for HAGs, and three articular cartilages (ie, first metatarsal (1st MTP), talar and second metacarpal/femoral) for DCS
showed the best balance between sensitivity and specificity (84.6% and 83.3%, respectively) in diagnosing intercritical gout[4]. So we
aimed to find the preferred sites of urate crystal deposition among these six sites in AH individuals.
Methods: 24 AH (serum uric acid (SUA) ³7mg/dl) and fifty controls (SUA <7mg/dl) with age more than 18 years were included in this study.
DCS was looked for at three articular cartilage sites (1st MTP, tibiotalar and femoral condyle) whereas HAGs were looked for at one joint
site (radiocarpal joint) and two tendon sites (patellar tendon and triceps tendon). Ultrasound was done using multifrequency linear array
transducer (8–13 MHz) of Logiq E; GE Medical Systems Ultrasound, on B mode gray scale (GS). Settings of machine were as follows:
dynamic range of 40–50 dB, GS frequency of 11–13 MHz and GS gain of 60 dB.
Results: 8 out of 24 AH patients had ultrasound evidence of urate crystal deposition in 1st MTP joint area followed by knee joint area which
was detected in 6 patients. The detection rate of ultrasound abnormalities in AH was 45.8% with two joint area (knee and 1st MTP) and 50%
with six sites assessment. Amongst controls, 16% were found to have these abnormal ultrasound findings by both two joint area and six sites
exams. (Figure: DCS at knee and 1st MTP joint)
Conclusion: The highest predilection of urate crystal deposition in AH patients is the articular cartilage of Knee and 1st MTP joints.
References:
1. Currie W: Prevalence and incidence of the diagnosis of gout in Great Britain, Ann Rheum Dis 38:101, 1979.
2. Klemp P, Stansfield S, Castle B, Robertson M: Gout is on the increase in New Zealand, Ann Rheum Dis 56:22, 1997.
3. Pineda C, Amezcua-Guerra LM, Solano C, Rodriguez-Henr’quez P, Hern‡ndez-D’az C, Vargas A, et al. Joint and tendon subclinical
involvement suggestive of gouty arthritis in asymptomatic hyperuricemia: an ultrasound controlled study. Arthritis Res Ther 2011;13:R4.
4. Naredo E, Uson J, JimŽnez-Palop M, Mart’nez A, Vicente E, Brito E, et al. Ultrasound-detected musculoskeletal urate crystal
deposition: which joints and what findings should be assessed for diagnosing gout? Ann Rheum Dis 2014;73: 1522–1528.
Disclosure: D. Bhadu, None; S. K. Das, None; U. Dhakad, None; A. Wakhlu, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/articular-cartilage-of-knee-and-first-mtp-joint-are-the-

preferred-sites-of-urate-crystal-deposition-in-asymptomatic-hyperuricemic-individuals
Correlations between Clinical and Ultrasound Scores of Peripheral Enthesitis and

Disease Activity Scores in a Cohort of Spondyloarthritis
Assia Haddouche 1, Sabrina Haid2, Siham Bencheikh3, Samy Slimani4, Amina Abdessemed5, Nadjia Brahimi6, Aïcha Ladjouz Rezig6 and
Fella Hanni6, 1of Medicine, Department of Medicine, University of Algiers 1, Algiers, Algeria, 2medicine, Department of Medicine,
University of Algiers 1, Algiers, Algeria, 3EPH HADJOUT, Algiers, Algeria, 4Department of Medicine, University of Batna, Batna, Algeria,
5Medicine, Department of Medicine, University of Algiers 1, Algiers, Algeria, 6Department of Medicine, University of Algiers 1, Algiers,
Algeria
SESSION INFORMATION
Background/Purpose: To look correlations between clinical and ultrasound (US) scores of peripheral enthesitis (PE) and disease activity
scores of SpA
Methods: A prospective study of 208 SpAs meeting SpA ASAS criteria. In the same consultation, 30 enthesitic sites per patient were
examined clinically and 34 sites per patient were examined with US according to the US OMERACT 2014 definition of enthesitis. PE was
assessed by the following clinical scores: Enthesitis Peripheral Score (PES= Sum of symptomatic peripheral entheses sites on clinical
examination), Visual Analog Scale of peripheral enthesitis (VAS), Spondyloarthritis Research Consortium of Canada score (SPARCC) as
well as the following US enthesitis scores: Acute Enthesitis scorev Correlations between clinical scores and ultrasound scores and disease
activity scores were calculated using SPSS software.
Results: A total of 208 patients were included, mainly men (63.5%). The mean age was 40.2 ± 11.7 years. The mean duration of the SpA
was 11.8 ± 8.7 years. Axial radiographic SpA was the most frequent phenotype (69.2%). On examination 64.4% of SpA were NSAIDs and
88.9% had active disease (ASDAS-vs and / or ASDAS-crp> 1.3). Tables (1, 2) summarize the results of correlations between clinical
scores and US scores and disease activity scores. A weak correlation was found between: the acute enthesitis score and two clinical scores
(peripheral enthesitis score, mean score of enthesitic VAS); the global enthesitis score and all clinical enthesitis scores and finally between
the SES score and two clinical enthesitic scores (peripheral enthesitis score, mean score of enthesitic VAS).
A moderate correlation was observed between disease activity scores and all US scores of peripheral enthesitis except for the chronic
enthesitis score for which the correlation was weak.
Table 1
VASm
Scores PES SPARCC
Enthestis
r: 0,15 r: 0,15 r: 0,13
Acute Enthesitis
p: 0,03 p: 0,03 p: 0,06
r: 0,10 r: 0,09 r: 0,09
Chronic Enthesitis
p: 0,15 p: 0,17 p: 0,26
r: 0,16 r: 0,16 r: 0,14
Global Enthesitis
p: 0,02 p: 0,03 p: 0,04
r: 0,06 r: 0,07 r: 0,06
Doppler Enthesitis
p: 0,36 p: 0,32 p: 0,42
r: 0,13 r: 0,13 r: 0,13
MASEI
p: 0,06 p: 0,23 p: 0,07
r: 0,13 r: 0,13 r: 0,13
SES
p : 0,06 p : 0,04 p:0,05
Table 2
ASDAS-vs ASDAS-crp
PES r: 0,41* r: 0,39*
p <0,0001 p <0,0001
VASm Enthestis r: 0,43* r: 0,40*
p <0,0001 p <0,0001
SPARCC r: 0,39* r: 0,38*
p <0,0001 p<0,0001
r: 0,33* r: 0,46*
Acute Enthesitis
P <0,0001 p<0,0001
r: 0,18 r: 0,23
Chronic Enthesitis
p: 0,006 p: 0,002
r: 0,35* r: 0,46*
Global Enthesitis
p <0,0001 p<0,0001
r: 0,29* r: 0,34*
Doppler Enthesitis
p <0,0001 p<0,0001
r: 0,38* r:0,48*
MASEI
p <0,0001 p<0,0001
r: 0,32* r: 0,42*
SES
p <0,0001 p<0,0001
Conclusion: All clinical and US scores, except for the chronic enthesitis score, would be of interest in assessing disease activity of SpA. US
scores are weakly or even uncorrelated to the peripheral enthesitis clinical scores
Disclosure: A. Haddouche, None; S. Haid, None; S. Bencheikh, None; S. Slimani, None; A. Abdessemed, None; N. Brahimi, None; A.
Ladjouz Rezig, None; F. Hanni, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/correlations-between-clinical-and-ultrasound-scores-of-

peripheral-enthesitis-and-disease-activity-scores-in-a-cohort-of-spondyloarthritis
Presence of Bone Marrow Edema and Structural Lesions on Magnetic Resonance

Imaging of the Sacroiliac Joints in Young Military Recruits before and after 6 Weeks of
Intensive Physical Training
Gaëlle Varkas1, Manouk de Hooge2, Thomas Renson3, Sophie De Mits4, Philippe Carron5, Peggy Jacques4, Muriel Moris6, Geert
Souverijns7, Lennart Jans8, Dirk Elewaut9 and Filip van Den Bosch10, 1Laboratory for Molecular Immunology and Inflammation,
Department of Rheumatology, VIB, Ghent University and Ghent University Hospital, Ghent, Belgium, 2VIB, Ghent University and Ghent
University Hospital, Leiden, Netherlands, 3Rheumatology, Ghent University Hospital, GENT, Belgium, 4Ghent University Hospital, Ghent,
Belgium, 5Department of Rheumatology, Ghent University Hospital, Ghent, Belgium, 6Military Hospital Queen Astrid, Neder-Over-
Heembeek, Belgium, 7Jessa Hospital Hasselt, Hasselt, Belgium, 8Department of Radiology, Ghent University Hospital, Ghent, Belgium,
9VIB Inflammation Research Center, University of Ghent, Ghent, Belgium, 10Rheumatology, Ghent University Hospital, Gent, Belgium
SESSION INFORMATION
Background/Purpose:
While MRI of the sacroiliac is a sensitive method for detection of bone marrow edema (BME) and structural lesions in axial
spondyloarthritis (axSpA), there is only limited data regarding the specificity in a non-SpA population. Mechanical stress is considered to be
an important factor in the pathogenesis of SpA. However, currently there are no data on the effect of intensive physical activity on the
sacroiliac joints and how this could impact MRI findings of the sacroiliac joints (MRI-SIJ).
Methods:
Twenty-two military recruits underwent an MRI-SIJ before and after 6 weeks of intense and uniform physical training. Bone marrow edema
(BME) and structural lesions were scored by 3 trained readers, blinded for time sequence and clinical findings. The Spondyloarthritis
Research Consortium of Canada (SPARCC) score was used to assess BME and an adjusted method derived from the SPARCC scoring
method was used to asses structural lesions: sclerosis, erosions, fatty lesions and ankylosis were scored per quadrant on 6 consecutive slices
representing the cartilaginous part of the joint. Additionally, the agreement with the definition of a positive MRI defined by ASAS was
evaluated.
Results:
At baseline, 40.9% (9/22) of recruits already presented with at least one BME lesion, whereas this number increased to 50.0% (11/22) at
week 6 (p=0.625). In subjects displaying BME, the mean number of BME lesions was 2.4 (±0.4) at baseline, compared to 3.7 (±1.3) at week
6. Overall, the mean change in BME lesions over time in all 22 individuals was 0.9 (±0.6) (p=0.109). A positive MRI according to ASAS
was present in 22.7% (5/22) of recruits at baseline, which increased to 36.4% at follow up (p=0.375). Structural lesions were present in
36.4% (8/22) of subjects at baseline, which increased to 50% subjects (11/22) after 6 weeks of intense physical training (p=0.453). There
was a significant increase of MRI lesions over time when combining both structural and inflammatory lesions (p=0.038).
Conclusion:
We found a markedly high prevalence of BME and structural lesions in young, active, healthy volunteers, with almost 23% of them fulfilling
the ASAS definition of a positive MRI. Overall, MRI lesions seem to increase after 6 weeks of intense physical training. Thus, our study
underscores the necessity to interpret MRI findings of the sacroiliac joints in the appropriate clinical context, even in a young active
population.
Disclosure: G. Varkas, None; M. de Hooge, None; T. Renson, None; S. De Mits, None; P. Carron, None; P. Jacques, None; M. Moris,
None; G. Souverijns, None; L. Jans, None; D. Elewaut, Scientific Research Flanders; Research Council Ghent University; Interuniversity
Attraction Pole., 2,Boehringer Ingelheim; Pfizer; UCB; Merck; Novartis; Janssen; Abbvie, 5; F. van Den Bosch, AbbVie Inc., Celgene, Eli
Lilly, Janssen, Merck, Novartis, Pfizer and UCB, 5,AbbVie Inc., Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/presence-of-bone-marrow-edema-and-structural-lesions-
on-magnetic-resonance-imaging-of-the-sacroiliac-joints-in-young-military-recruits-before-and-after-6-weeks-of-intensive-physical-training
Psoriatic Arthritis Sonographic Enthesitis Scores – Systematic Review of the Literature

Ofir Elalouf1, Sibel Bakirci2, Zahi Touma3, Melanie A Anderson4, Gurjit S. Kaeley5, Sibel Z. Aydin6 and Lihi Eder7,8, 1Rheumatology,
Toronto Western Hospital, University of Toronto, Toronto, ON, Canada, 2Fellow in Rheumatology, Antalya, Turkey, 3Rheumatology,
University of Toronto, Division of Rheumatology, Institute of Health Policy, Management and Evaluation, Toronto, ON, Canada, 4Toronto
Western Hospital, University of Toronto, Toronto, ON, Canada, 5University of Florida, Ponte Vedra Beach, FL, 6University of Ottawa,
Ottawa, ON, Canada, 7Medicine, University of Toronto, Toronto, ON, Canada, 8Women's College Research Institute, Women's College
Hospital, Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose:
Enthesitis is a prominent feature of spondyloarthropathy (SpA), including psoriatic arthritis (PsA). The evaluation of enthesitis has
conventionally been conducted by clinical exam, a method with significant limitations mainly its low sensitivity. Ultrasound can image
entheses in high fidelity and may assist in the diagnosis and management of SpA patients. As part of the GRAPPA US sub-committee
"Enthesitis Project" we performed a systematic review of the literature in order to assess the evidence and knowledge gaps in scoring
systems of enthesitis in PsA.
Methods:
A systematic search of Pubmed, Embase and Cochrane was done. The search strategy was constructed to find original publications in English
containing terms related to US, enthesitis, SpA or PsA. Two reviewers screened all abstracts for eligibility. Studies that reported used global
sonographic scoring systems for assessment of enthesitis in patients with spondyloarthritis or their modifications were included. Data was
extracted independently by 2 reviewers. Data extraction focused on the properties of the enthesitis scoring system used in each study.
Specifically, we assessed the following component of the OMERACT filter: reliability of acquisition, feasibility, and construct validity as
related to clinical assessment of enthesitis, biomarkers and imaging of enthesitis by other modalities, discriminative validity and
responsiveness to treatment.
Results:
Fifty-one of 310 identified manuscripts were included. 13 studies used Glasgow Ultrasound Enthesitis Scoring System (GUESS) or its
modifications, 9 used Madrid Sonographic Enthesitis Index Scoring System (MASEI), 6 used D'Agostino scoring system, 5 used Belgrade
Ultrasound Enthesitis Score (BUSES), 3 used Sonographic Enthesitis Index (SEI), 1 used PsASon-Score, and 14 did not use a formal score.
Only one of these scoring systems (PsASon) was developed and validated in patients with PsA. Only 18 (35%) of the studies involved
patients with PsA, while the rest focused on SpA. Concerning the OMERACT filter, construct validity was assessed using biomarkers in 10
(19.6%) studies, only one study (2%) in PsA. Construct validity using clinical examination was assessed by 26 (51%), 11 (21.5%) were in
PsA, only 6 (11.7%) compared US finding to imaging - none of them was performed on PsA. Responsiveness to treatment was assessed in 7
studies, none of them included PsA patients. Six (11.7%) studies evaluated discriminative validity two (4%) of them in PsA.
Conclusion:
Although sonographic indices have been developed for Spondyloarthropathy, only a few have been validated for PsA. None of them fulfilled
all the OMERACT filter criteria in patients with PsA. Additional research is needed to assess the validity or modification of existing scoring
systems in patients with PsA.
Disclosure: O. Elalouf, None; S. Bakirci, None; Z. Touma, None; M. A. Anderson, None; G. S. Kaeley, None; S. Z. Aydin, None; L.
Eder, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/psoriatic-arthritis-sonographic-enthesitis-scores-

systematic-review-of-the-literature
Healing Time and Blood Perfusion By Laser Speckle Contrast Analysis in Patients with
Systemic Sclerosis and Digital Ulcers
Simone Barsotti1,2, Anna d'Ascanio1, Valentina Venturini3, Laura Amanzi4, Silvia Bilia5, Marta Mosca1 and Alessandra Della Rossa6,
1Rheumatology Unit, University of Pisa, Pisa, Italy, 2Department of Medical Biotechnologies, University of Siena, Siena, Italy, 3Pisa
University Hospital, Rheumatology unit, Pisa, Italy, 4Pisa University Hospital, Rheumatology Unit, Pisa, Italy, 5Univerisity of Pisa,
Rheumatology Unit, Pisa, Italy, 6University of Pisa, Rheumatology Unit, Pisa, Italy
SESSION INFORMATION
Background/Purpose:
Digital ulcers (DUs) are a major burden in patients with systemic sclerosis (SSc). Laser speckle contrast analysis (LASCA) is a novel
technique that can analyse blood perfusion (BP) in the fingers and in DU areas. The objective of the present study was to evaluate BP in
patients with SSc and DUs and correlate these values with the treatments and healing time.
Methods:
From February 2016 to March 2017, 23 consecutive Ssc patients presenting with DU at fingertips were enrolled: M:F=2:21; 15 lcSSc and 8
dcSSc; mean age 56±15.8 years. BP was assessed by LASCA in fingers affected by DUs, unaffected fingers, DU area, peri-ulcer area and the
same area of unaffected fingers. DUs were defined infected if local signs of infection were present (swelling, severe pain, erythema,
discharge). The treatment with major vasoactive drugs (iloprost, bosentan, sildenafil), the latency between the appearance of DU and first
evaluation, and the time to DU healing under standard local treatment were collected.
Results:
BP was higher in peri-ulcer area with respect to the DUs area ( 84.1±21.0 vs 60.3±15.1 p<0.001), and no differences were observed
between DUs area and similar area of unaffected fingers.
In patients without infection (n=17), healing time was negatively associated both to DUs BP (r=-0.618 p=0.011) and peri-ulcer BP (r=-0.488
p=0.011). The latency between appearance of DUs and first evaluation in our centre was also negatively correlated to mean healing time
(r=0.36 p=0.036).
Patients with infection (n=6) presented a higher ulcer BP compared to non-infected pts (198.0±112.2 vs 103.3±66 p=0.023) and DUs needed
a longer healing time (mean 130 vs 100 days).
The treatment with bosentan and iloprost was associated with higher BP in the unaffected fingers (respectively p=0.002 and p=0.001) but no
BP changes at DU area or at fingers with DUs were observed. Sildenafil was not associated with significant differences in blood perfusion.
Conclusion:
Our study suggests a potential usefulness of LASCA analysis of BP in the assessment of DUs in SSc patients. Although all DUs are ischaemic
in nature (blood flow is lower than in unaffected area and periulcer area), BP values could help in identifying difficult to heal lesions, either
due to a markedly reduced perfusion (low BP) or to the presence of an infection (higher than expected BP).
Additional data are needed to better define the role of BP as a guide to treatment, ulcer management and prevention in routine clinical
practice.
Disclosure: S. Barsotti, None; A. d'Ascanio, None; V. Venturini, None; L. Amanzi, None; S. Bilia, None; M. Mosca, None; A. Della
Rossa, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/healing-time-and-blood-perfusion-by-laser-speckle-

contrast-analysis-in-patients-with-systemic-sclerosis-and-digital-ulcers
Tracking Digital Ulcers in Systemic Sclerosis: Feasibility Study Assessing Lesion Area
from Patient-Recorded Smartphone Photographs
Graham Dinsdale 1, Tonia Moore2, Joanne Manning2, Andrea Murray1, Ross Atkinson3, Karen Ousey4, Mark Dickinson5, Christopher
Taylor6 and Ariane L. Herrick1,7, 1Division of Musculoskeletal & Dermatological Sciences, University of Manchester, Salford Royal
Hospital NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK, Manchester, United Kingdom, 2Salford
Royal Hospital NHS Foundation Trust, Salford, UK, Salford, United Kingdom, 3School of Health Sciences, Division of Nursing, Midwifery
& Social Work, University of Manchester, Manchester, UK, Manchester, United Kingdom, 4Division of Podiatry and Clinical Sciences,
University of Huddersfield, Huddersfield, UK, Huddersfield, United Kingdom, 5Photon Science Institute, School of Physics and Astronomy,
University of Manchester, Manchester, UK, Manchester, United Kingdom, 6Centre for Imaging Sciences, Division of Informatics, Imaging &
Data Sciences, University of Manchester, Manchester, UK, Manchester, United Kingdom, 7NIHR Manchester Musculoskeletal Biomedical
Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK, Manchester,
United Kingdom
SESSION INFORMATION
Background/Purpose: Approximately 50% of patients with systemic sclerosis (SSc) will develop painful digital (finger) ulcers (DUs) at
some point during their disease course. These lesions can be extremely disabling and are often refractory to treatment, requiring close
monitoring of healing progression. Also, DUs are often the primary outcome measure in clinical trials of SSc-related digital vasculopathy.
Our aims were to: (1) demonstrate the feasibility of patients with SSc taking smartphone photographs of their DUs, and (2) use software
image analysis on collected images to track lesion area as a marker of wound status.
Methods: Patients with SSc and incident DUs were asked to photograph their lesion(s), using their own smartphone, once per day for a
maximum period of 35 days. Patients received normal clinical wound care for the duration of the study, which in most cases was patient self-
management. Image length scales were initially calibrated using a fixed (non-varying) object in each image sequence, allowing relative
length/area tracking throughout a sequence. Using digital planimetry software (developed and successfully tested in previous work on digital
ulcer photographs [1]), lesion area was measured by fitting an elliptical shape to the wound image by a single observer. Areas from each
image were then normalised to the area measured first in the time sequence.
Results: Image sequences describing 7 lesions were collected in-person at the end of the study period from 4 patients. The 7 image
sequences cover median [range] duration of 29 [13-35] days. The relative area time course for each lesion is shown in Figure 1. At sequence
end, relative lesion areas had, on average, reduced to 56% of the area measured on day 1, with 6 out of 7 lesions reducing in size over the
time course.
Conclusion: We have demonstrated the feasibility of patients with SSc collecting images of digital ulcers using smartphone cameras. Images
collected are of sufficient quality to allow software monitoring of wound progression (healing or worsening). Further work to build a
smartphone app for lesion monitoring (for use in both clinical practice and as an outcome measure in clinical trials) is now required.
References
1. Simpson et al. Arthritis Care & Research, 2017, doi:10.1002/acr.23300
Figure 1. Normalised lesion area time course plots (blue squares) for each of seven digital ulcers. Red dashed line equals 100% relative
area, i.e. equal to the value at the start of the sequence. Only lesion 3 showed an increase in area over the course of the study.
Disclosure: G. Dinsdale, None; T. Moore, None; J. Manning, None; A. Murray, None; R. Atkinson, None; K. Ousey, None; M.
Dickinson, None; C. Taylor, None; A. L. Herrick, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/tracking-digital-ulcers-in-systemic-sclerosis-feasibility-

study-assessing-lesion-area-from-patient-recorded-smartphone-photographs
The Use of Positron Emission Tomography (PET)-Scan for the Quantitative Assessment
of Interstitial Lung Disease in Systemic Sclerosis
Daphne Peelen1, Ben Zwezerijnen2, Esther Nossent1, Lilian Meijboom1, Otto Hoekstra3, Conny van der Laken4 and Alexandre Voskuyl4,
1VUmc, Amsterdam, Netherlands, 2Nuclear Medicine, VUmc, Amsterdam, Netherlands, 3Department of Radiology & Nuclear Medicine, VU
University Medical Center, Amsterdam, The Netherlands, Amsterdam, Netherlands, 4Department of Rheumatology, Amsterdam
Rheumatology and immunology Center - location VU University Medical Center, Amsterdam, The Netherlands, Amsterdam, Netherlands
SESSION INFORMATION
Background/Purpose: Interstitial lung disease (ILD) in systemic sclerosis is treated by immunosuppressive drugs (e.g. cyclophosphamide),
aimed at reduction of inflammatory response . Differentiation between inflamed and non-inflamed fibrotic tissue might help to develop
treatment stratification, with the aim of improving the prognosis of (subgroups of) SSc-ILD patients. 18F-Fluoro-Dexoxyglucose Positron
treatment stratification, with the aim of improving the prognosis of (subgroups of) SSc-ILD patients. F-Fluoro-Dexoxyglucose Positron
Emission Tomography (18F-FDG PET) scan might be a promising tool to detect inflamed lung areas, as formerly shown in a semi-
quantitative setting.[1, 2] This study aims to investigate the potential role of 18F-FDG PET –scan for the quantitative assessment of
metabolically active SSc related ILD.
Methods: 18F-FDG PET -scans of 22 patients with systemic auto-immune disease, including 9 with SSc , 9 with systemic lupus
erythematosus (SLE) and 4 with primary Sjögren’s syndrome (pSS) , were retrospectively analyzed. FDG-uptake was quantitatively
measured within 2cm-sized Regions of Interest (ROIs) at apical, medial and basal lung levels. A total of 22 ROI’s were drawn in each
patient. SUVmean values of all ROI’s were corrected by the medial SUVmean bloodpool value. Subsequently, the average of 6 posterior
basal SUVmean values was divided by the average of 6 posterior apical SUVmean values (basal/apical ratio). High Resolution Computed
tomography (HRCT)-scans and Pulmonary Function Tests (PFT) were examined to confirm the diagnosis of ILD and to specify the pattern of
fibrosis.
Results: Mean age of patients was 69.4 (SSc-ILD), 62.5(SSc without ILD), 38.9 (SLE) and, 49.3 (pSS). In SSc patients, the mean disease
duration was 5.0 (SSc-ILD) and 4.4 (SSc without ILD) years. Diffuse cutaneous sclerosis was present in 2 SSc-ILD and 1 SSc without ILD
patients, while other SSc patients were diagnosed with limited cutaneous SSc. ILD was present in 5 out of 9 SSc patients as confirmed by
HRCT and PFT. ILD was active in 3 out of 5 SSc-ILD patients. Posterior basal/apical SUVmean ratios of SSc-ILD patients were
significantly increased compared to SSc patients without ILD (p=0.016), and compared to SLE and pSS patients without ILD (p=0.001 and
p=0.016, respectively), which is shown in Figure 1.
Conclusion: Our findings demonstrate that 18F-FDG PET is potentially useful for the quantitative assessment of active ILD lesions in SSc
patients. The technique may therefore provide opportunities to select the patients with inflammatory regions in ILD that are most likely to
respond to immunosuppression.
References:
1. Uehara, T., et al., Deep-inspiration breath-hold 18F-FDG-PET/CT is useful for assessment of connective tissue disease associated
interstitial pneumonia. Mod Rheumatol, 2016. 26(1): p. 121-7.
2. Jacquelin, V., et al., FDG-PET/CT in the prediction of pulmonary function improvement in nonspecific interstitial pneumonia. A Pilot
Study. Eur J Radiol, 2016. 85(12): p. 2200-2205.
Disclosure: D. Peelen, None; B. Zwezerijnen, None; E. Nossent, None; L. Meijboom, None; O. Hoekstra, None; C. van der Laken,
None; A. Voskuyl, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-use-of-positron-emission-tomography-pet-scan-for-

the-quantitative-assessment-of-interstitial-lung-disease-in-systemic-sclerosis
Prevalence of Echocardiographic Findings in Connective Tissue Diseases – a

Retrospective Cohort Study
Valentin S. Schäfer1, Katharina Weiss2, Andreas Krause2 and Wolfgang A. Schmidt3, 1Immanuel Krankenhaus Berlin, Medical Center for
Rheumatology Berlin-Buch, Berlin, Germany, 2Medical Centre for Rheumatology Berlin-Buch, Immanuel Krankenhaus Berlin, Berlin,
Germany, 3Medical Center for Rheumatology and Clinical Immunology Berlin-Buch, Immanuel Krankenhaus Berlin, Berlin, Germany
SESSION INFORMATION
Background/Purpose: Echocardiography is frequently performed in patients with connective tissue diseases (CTD), mostly to evaluate
cardiac involvement or development of pulmonary arterial hypertension (paH). Despite the application as part of routine clinical follow-up,
there is incomplete data for the range and frequency of findings in different CTD.
Methods: We included all consecutive patients from a tertiary rheumatological referral center with CTD diagnosis and echocardiographic
examination between January 1st 2006 and December 31st 2015 by retrospective chart review. For each echocardiographic finding, the
proportion of patients per diagnosis with a pathological result in at least one examination was calculated. Further, each finding´s frequency in
patients with and without previously documented inflammatory cardiac involvement was compared. For patients with more than one visit, we
recorded how often findings developed or resolved over time.
Results: 1004 patients with different CTD and a total of 1660 performed echocardiographies were identified. Table 1 displays the frequency
of findings in the whole cohort and for each CTD, respectively. The most common findings were mitral, aortic and tricuspid regurgitation,
aortic valve sclerosis, left ventricular dysfunction, and left atrial dilatation. Table 2 shows which findings were significantly more common
in patients with a history of inflammatory cardiac involvement (n=109). 314 patients had consecutive examinations; medium interval
between first and last examination was 40 months (SD: 28, range: 0.9-115). Development and regression of findings during follow-up are
given in table 3. Mitral (24%) or tricuspid regurgitation (21%), aortic valve sclerosis (18%) and left ventricular dysfunction (20%) most
commonly developed.
Conclusion: This study is the first to report echocardiographic findings in a large cohort of different CTD. Abnormal findings are common in
all disease entities. Some pathological findings are more common in patients having suffered from cardiac involvement, these seem to be
disease-related. In follow-up, a change of findings was frequently observed. These results support the role of echocardiography for routine
examination and in follow-up in patients with CTD.
Disclosure: V. S. Schäfer, None; K. Weiss, None; A. Krause, None; W. A. Schmidt, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prevalence-of-echocardiographic-findings-in-connective-

tissue-diseases-a-retrospective-cohort-study
Imaging for Diagnosis, Monitoring and Outcome Prediction of Large Vessel Vasculitis:
A Systematic Review of the Literature and Meta-Analysis Informing the EULAR
Recommendations
Christina Duftner1, Christian Dejaco2, Alexandre Sepriano3, Louise Falzon4, Wolfgang A. Schmidt5 and Sofia Ramiro6, 1Department of
Internal Medicine, Clinical Division of Internal Medicine II, Medical University Innsbruck, Innsbruck, Austria, 2Rheumatology, Hospital of
Bruneck, Bruneck, Italy, 3Rheumatology, Leiden University Medical Center, Leiden, Netherlands, 4Center for Behavioral Cardiovascular
Health, Columbia University Medical Center, New York, NY, 5Medical Center for Rheumatology and Clinical Immunology Berlin-Buch,
Immanuel Krankenhaus Berlin, Berlin, Germany, 6Rheumatology, Department of Rheumatology, LUMC, Leiden, Netherlands, Leiden,
Netherlands
SESSION INFORMATION
Background/Purpose: Modern imaging techniques including ultrasound (US), magnetic resonance imaging (MRI), computed tomography
(CT) and 18F-FDG positron emission tomography (PET) are increasingly studied in large vessel vasculitis (LVV); however, their role in
daily clinical practice remains elusive so far. The aim of this study was to perform a systematic literature review (SLR) to inform the
EULAR recommendations for imaging in LVV on the role of imaging methods on (1) diagnosis, (2) disease monitoring, (3) outcome
prediction and (4) technical aspects in LVV
Methods: A systematic literature search was conducted in the MEDLINE, EMBASE and Cochrane Library databases (untill 10th March
2017) without language restriction. Full research articles of prospective studies enrolling >20 patients and investigating the index test (US,
MRI, CT, PET) in patients with suspicion of (diagnostic studies) and/or established (studies on monitoring or prediction) primary LVV were
selected. The risk of bias for diagnostic accuracy and prognostic studies were evaluated by the QUADAS2 and QUIPS tools, respectively.
Meta-analysis was conducted, whenever possible, to obtain pooled estimates for sensitivity, specificity, positive and negative likelihood
ratios, by fitting random effects models.
Results: Forty-four studies were included [27 diagnosis giant cell arteritis (GCA), 6 outcome prediction GCA, 15 monitoring disease
activity GCA, 5 technical aspects GCA, 2 diagnosis Takayasu arteritis (TAK), 2 monitoring disease activity TAK with some studies
addressing more than one index test/key objective]. The “halo” sign at temporal arteries, as identified by US (8 studies, 605 patients), yielded
a pooled sensitivity of 77% (95% CI: 62-87%) and a pooled specificity of 96% (95% CI: 85-99%) as compared to clinical diagnosis of
GCA. MRI of extra-cranial arteries was found to have a pooled sensitivity of 73% (95% CI: 57-85) and a pooled specificity of 88% (95%
CI: 81-92), when clinical diagnosis (6 studies, 509 patients) was used as gold standard. For both, US and MRI, similar diagnostic
performances were observed when temporal artery biopsy was used as reference standard instead of clinical diagnosis. Only 2 studies (93
patients) addressed the diagnostic accuracy of PET in GCA reporting sensitivities of 67-77% and specificities of 66-100%. Studies
addressing the role of imaging for outcome prediction, monitoring disease activity and technical aspects were very heterogenous. For TAK, 1
MRI (30 patients) and CT angiography study (25 patients) was identified revealing both a sensitivity of 98% and a specificity of 100% in
comparison to conventional angiography. No study on isolated aortitis was identified.
Conclusion: The SLR confirms the good performance of US and MRI for the diagnosis of cranial GCA. Data on outcome prediction,
monitoring and technical aspects of GCA, as well as imaging studies in TAK are limited.
Disclosure: C. Duftner, None; C. Dejaco, None; A. Sepriano, None; L. Falzon, None; W. A. Schmidt, None; S. Ramiro, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/imaging-for-diagnosis-monitoring-and-outcome-

prediction-of-large-vessel-vasculitis-a-systematic-review-of-the-literature-and-meta-analysis-informing-the-eular-recommendations
Use of Positron Emission Tomography for the Diagnosis of Aortitis. a Study of 170
Patients from a Single Center
Lucia C. Domínguez-Casas1, Javier Loricera1, Diana Prieto Peña1, Isabel Martínez-Rodríguez2, Jose Ignacio Banzo2, Monica Calderón
Goercke1, Vanesa Calvo-Río1, Nuria Vegas-Revenga1, MC Gonzalez-Vela3, Jesus Gonzalez- Vela4, José Luis Martín-Varillas1, Belén
Atienza-Mateo1, Jose L. Hernández5, Miguel Angel González-Gay1 and Ricardo Blanco1, 1Rheumatology, Hospital Universitario Marqués
de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain, 2Nuclear Medicine, Hospital Universitario Marqués
de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain, 3Pathology Anatomy, Hospital Universitario Marqués
de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain, 4Hospital Universitario Marqués de Valdecilla.
IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain, 5Internal Medicine, Hospital Universitario Marqués de Valdecilla.
IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain
SESSION INFORMATION
Background/Purpose:
Aortitis is the inflammation of the aortic wall. This entity is often under-recognised because most of its manifestations are non-specific.
PET/CT scan plays an important role in the diagnosis and management of aortitis; however this technique is expensive.
Our aim was to compare the baseline characteristics of patients with a suspicion of aortitis and positive results on PET/CT scan and those
with a negative result in order to search for predictive factors that improve the clinical probability of diagnosis aortitis by this imaging
technique.
Methods:
Retrospective study on 170 patients and PET/CT scans ordered by suspicion of aortitis from a referral center from January 2010 to
December 2016. According to a pre-specified protocol, the baseline epidemiological and clinical variables of patients with positive and
negative PET/CT scans results for aortitis were reviewed. Distributions of categorical variables were compared by the Pearson Chi2 or
Fisher exact test. Quantitative variables were analyzing using the Student t test or Mann-Whitney U test as appropriate.
Results:
In 170 patients, PET/CT scans were performed due to clinical suspicion of aortitis, being positive in 93 (54.7%) cases. Patients
(113W/57M) had a mean age of 67.7±13.1 years (range, 20-90 years). One patient was excluded because missing clinical or laboratory data.
The underlying conditions at the momento of orderinf the PET/CT scan were: giant cell arteritis (GCA) (n=28), spondiloarthropaties (n=7),
conectivopaties (n=6), Takayasu arteritis (n=3), ulcerative colitis (n=3), other condition (n=11) The remaining 111 patiens dud not hace any
underlying condition suggestive of aortitis.
Characteristics of patients with positive and negative PET/CT sacan were shown in the Table. Patients with GCA had a higher percentage of
positive PET/CT scans, whereas the were negative more frequently in patients who did not have any conidition suggestive of underlying
aortitis. Only inflammatory low back pain and polymyalgic syndrome were significantly more frequent in patients with positives PET/CT
scans.
Conclusion:
In this study, we have found the presence of inflammatory low back pain and polymyalgic syndrome, especially in GCA patients, may have
clinical relevance in ordering a PET/CT scan when aortitis was suspected.
TABLE
Positive Negative
PET PET
p
n= 92 n= 77
Age (years), mean±SD 67.4± 11.1 68.1±15.2 0.73
Age ≥ 70 years, n (%) 39 (41.9) 41 (53.2) 0.14
Sex (women), n (%) 62 (67.4) 54 (70.1) 0.63
Underlying condition
Giant cell arteritis, n (%)
24 (26.1) 4 (5.2) 0.0002
Takayasu arteritis, n (%) 3 (3.3) 0 (0) 0.31
Ulcerative colitis, n (%) 2 (2.2) 1 (1.3) 0.87
Conectivopaties, n (%)
3 (3.3) 3 (3.9) 0.86
Spondiloarthropaties, n (%)
3 (3.3) 4 (5.2) 0.79
None, n (%)
54 (58.7) 57 (74.0) 0.03
Other, n (%) 3 (3.3) 8 (10.4) 0.11
Symptoms at the time of requesting PET

Constitutional syndrome, n (%)
30 (32.6) 36 (46.8) 0.06
Fever, n (%) 18 (19.6) 15 (19.5) 0.98
Inflammatory low back pain, n (%)

30 (32.6) 14 (18.2) 0.03
Diffuse lower limbs pain, n (%)

42 (45.7) 28 (36.4) 0.22
Atypical polymyalgia rheumatica,

n (%) 30 (53.6) 13 (38.2) 0.15
Headache, n (%) 18 (19.6) 9 (11.7) 0.16
Polymialgic syndrome, n (%)

56 (60.9) 34 (44.2) 0.03
Laboratory markers at the time of requesting PET

Anaemia, n (%) 18 (20.2) 22 (28.9) 0.19
ESR (mm/1ªh), mean±SD

43.3±34.3 43.5±31.1 0.72
CRP (mg/dl), median [IQR] 0.9 [0.3- 0.9 [0.3-

0.54
2.6] 2.5]
Treatment at the time of requesting PET
Patients with corticosteroids, n
(%) 48 (51.6) 36 (46.8) 0.48
Dosage of prednisone (mg),

10 [7.5-
median [IQR] 10 [5-15] 0.80
15]
Patients with traditional

immunosuppressants, n (%) 11 (12.0) 5 (6.5) 0.21
Disclosure: L. C. Domínguez-Casas, None; J. Loricera, None; D. Prieto Peña, None; I. Martínez-Rodríguez, None; J. I. Banzo, None;
M. Calderón Goercke, None; V. Calvo-Río, None; N. Vegas-Revenga, None; M. Gonzalez-Vela, None; J. Gonzalez- Vela, None; J. L.
Martín-Varillas, None; B. Atienza-Mateo, None; J. L. Hernández, None; M. A. González-Gay, None; R. Blanco, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/use-of-positron-emission-tomography-for-the-diagnosis-

of-aortitis-a-study-of-170-patients-from-a-single-center
Ultrasound CUT-Off in GIANT CELL Arteritis a Solution to Arteriosclerosis Pitfall in

the Halo Sign
Eugenio De Miguel1, Luis M Beltran2, Irene Monjo2, Francesco Deodati2, Wolfgang A. Schmidt3 and Juan García-Puig2, 1Rheumatology,
University Hospital La Paz, IdiPaz, Madrid, Spain, 2Internal Medicine, Hospital Universitario La Paz, MADRID, Spain, 3Immanuel
Krankenhaus Berlin, Med Ctr for Rheumatology Berlin-Buch, Berlin, Germany
SESSION INFORMATION
Background/Purpose: At the age of Giant Cell Arteritis (GCA) atherosclerosis is common. The ultrasonographic (US) appearance of
athermanous plaque is usually easily differentiated from the hypoechoic halo of GCA. However, the US increase of the intima-media-
thickness (IMT) in an atherosclerotic arteries may have a similar appearance as the halo sign (homogenous, hypoechoic wall thickening, well
delineated towards the luminal side, visible in longitudinal and transverse planes). The new US high frequencies probes make possible not
only to see the halo sign but also measure the increase of the intima-media-thickness (IMT), in this sense the aim of this study was to explore
the better cut-off in the IMT of temporal arteries (TA) to minimise the number of false-positive GCA diagnosis caused by atherosclerosis.
Methods: Consecutive non selected patients, ≥50 years-old with high vascular risk according to European Guidelines on cardiovascular
disease prevention, and without signs or symptoms of GCA, were included.
Ultrasonography of carotid artery: Carotid US examinations were performed on a Mylab Seven (Esaote Medical Systems, Italy) with a 4–
13 MHz linear-array. The system employed dedicated software radiofrequency-tracking technology to obtain IMT (QIMT®).
Ultrasonography of temporal superficial artery: A color Doppler ultrasound (CDU) and grey scale measure of the IMT/halo sign in both
TA and its branches was performed by a second experienced sonographer. A Mylab Twice equipment (Esaote, Geneve, Italy) was used, with
a 22 MHz frequency for grey scale and a 12.5 MHz for CDU (color gain of 51, PRF of 2 kHz). The sonographer was blind to the clinical and
carotid ultrasound IMT data.
Results: Forty patients were studied, 28 men (70%), with a mean age of 70.6 ± 6.9 years. Three patients were active smokers and 27 ex-
smokers. Arterial hypertension was present in 39 (97.5%), dyslipidaemia in 34 (85%) and diabetes in 19 (47.5%). The mean erythrocyte
sedimentation rate was 13.6 ± 11.0. Eighty carotids were studied, 50 had plaques and 30 did not with a IMT ranged from 0.528 to 1.480 mm.
A increase in the carotid IMT is associated with an increase in the IMT of the TA with a weak Spearman correlation (parietal branches 0.282
p = 0.012 and frontal branches 0.228 p = 0.048). The table shows that an IMT > 0.30 mm (halo sign) was seen in at least 1 TA branch of 18
patients (45%) with 33 TA branches affected (20.6%). An IMT cut-off > 0.34 mm, was present in 4 patients (10 %). When at least two
affected branches with this measure were required to make the US diagnosis (criteria recommended to improve specificity) only one patient
(2.5%) produced a false-positive halo sign.
Conclusion: Carotid atherosclerosis increase the IMT in TA and is a potential cause of false-positive halo sign. We propose a cut-off of AT
IMT > 0.34 mm in at least two branches to minimise the number of false positives in GCA diagnosis.
Disclosure: E. De Miguel, None; L. M. Beltran, None; I. Monjo, None; F. Deodati, None; W. A. Schmidt, Roche Pharmaceuticals,
8,Roche Pharmaceuticals, 5,Roche Pharmaceuticals, 2,GlaxoSmithKline, 2,GlaxoSmithKline, 5,Bristol-Myers Squibb, 5,Bristol-Myers
Squibb, 8; J. García-Puig, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/ultrasound-cut-off-in-giant-cell-arteritis-a-solution-to-

arteriosclerosis-pitfall-in-the-halo-sign
FDG PET/CT Visualization of Inflammation in Temporal and Maxillary Arteries in

Treatment-Naive GCA Patients
Berit Dalsgaard Nielsen1,2, Ib Tønder Hansen3,4, Kresten Krarup Keller5, Philip Therkildsen6,7, Ellen-Margrete Hauge6,8 and Lars
Christian Gormsen9, 1Rheumatology, Department of Rheumatology, Aarhus University Hospital, Århus C, Denmark, 2Clnical Medicine,
Department of Clinical Medicine, Aarhus University Hospital, Århus N, Denmark, 3Clinical Medicine, Department of Clinical Medicine,
Aarhus University Hospital, Århus N, Denmark, 4Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark,
5Rheumatology, Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark, 6Clinical medicine, Department of Clinical
Medicine, Aarhus University Hospital, Århus N, Denmark, 7Department of Rheumatology, Aarhus University Hospital, Aarhus C, Denmark,
8Department of Rheumatology, Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark, 9Nuclear Medicine and PET
Center, Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Århus C, Denmark
SESSION INFORMATION
Background/Purpose:
Fluorine-18-fluorodeoxyglucose (FDG) PET/CT is increasingly used to diagnose large vessel GCA (LV-GCA), but has previously been
considered unable to reveal inflammation in temporal arteries due to limited spatial resolution. However, the arteritic pattern in GCA is
heterogeneous and additionally may not always uniformly involve the entire vessel, rendering interpretation of the PET images difficult. An
increased FDG uptake in branches of the external carotic artery, i.e. the temporal (TA) and maxillary arteries (MA), may therefore add to
diagnostic specificity.
Methods:
21 patients fulfilling the ACR criteria of GCA were identified from a LV-GCA cohort (table 1). Laboratory tests, temporal artery ultrasound
(US) and FDG PET/CT (Siemens Biograph 64) were performed prior to treatment.
An experienced nuclear medicine physician performed blinded assessment of FDG uptake in TA and MA. FDG uptake was visually scored
on a 4-point scale (a.m. Meller1: 1; ≤ blood pool, 2; > blood pool, ≤ liver, 3; ≥ liver, 4; ≥ 2xliver), where score ≥2 was considered
indicative of inflammation. In addition, mean and max standardized uptake values (SUVmean, SUVmax; 20 hottest interconnected pixels) and
target to background ratio (TBR=SUVmax(artery)/SUVmean(venousblood)) were recorded for each vessel based on volumes of interest
drawn on the PET images.
Correlations were calculated using Spearman’s test. Mann–Whitney U test or Student t test, when applicable, were used for quantitative data.
Associations between two categorical variables were evaluated using Fisher's exact test.
Results:
FDG uptake in cranial arteries was detectable in 20/21 patients; 12/21 TA and 20/21 MA. In 11 patients, at least one of the arteries was
categorized with a Meller score≥2 indicating significant inflammation. SUVs and TBRs are shown in table 1. SUVs and TBR correlated with
Meller scores.
In the 3 patients with negative TA US (n=2 biopsy positive) and in the 2 patients with negative TA biopsies (n=1 US positive), FDG uptake
in TA and MA was either not detectable or with a Meller score of 1. Meller score in the TA correlated with the degree of inflammation
(none, <transmural, transmural) in the TA biopsy (rho=0.64, p<0.01). Patients with a TA or MA Meller score≥2 were more likely to have
severe cranial symptoms (p=0.02), jaw claudication (p<0.02), had a shorter disease duration prior to diagnosis (median 8 vs 17 weeks,
p<0.02) and were younger (median 65 vs 69 years, p<0.01) than patients with Meller score<2. However, they did not differ in gender or
CRP at time of diagnosis.
Conclusion:
Increased FDG uptake in the cranial arteries of GCA patients is frequent, correlated to histological inflammation and subjective symptoms
and detectable by normal PET/CT systems. It may add to the diagnostic accuracy of 18F-FDG PET/CT in GCA and should not be overlooked
by reading physicians.
Table 1
Baseline characteristics of patients fulfilling ACR
criteria for GCA
No. patients 21
Age, median (range) 68 (60-84)
Gender, females no. 13
CRP, mean (95% CI) 82 (65; 104)
Temporal artery biopsy 16/18
positive, no
Temporal artery 18/21
ultrasound positive
Temporal artery PET characteristics
SUVmean 2.18 (1.69; 2.68)
SUVmax 3.10 (2.27; 3.94)
TBR 1.95 (1.47; 2.48)
Maxillary artery PET characteristics
SUVmean 2.21 (1.77; 2.64)
SUVmax 2.86 (2.21; 3.71)
TBR 2.04 (1.49;2.58)
Patients fullfilling ACR criteria for GCA were
identified in a prospective cohort of 24 large-vessel
GCA patients. Inclusion criteria in the cohort were:
Age>50 years, CRP>15 or ESR>40, either cranial
symptoms of GCA, abrupt new-onset of extremity
claudication or weightloss>5kg or fever>38 for more
than 3 weeks and PET proven large vessel
involvement (FDG uptake higher than liver FDG
uptake in aorta and/or supraaortic branches).
References
1. Stellingwerff MD et al. Medicine 2015
Disclosure: B. D. Nielsen, None; I. Tønder Hansen, None; K. K. Keller, None; P. Therkildsen, None; E. M. Hauge, None; L. C.
Gormsen, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/fdg-petct-visualization-of-inflammation-in-temporal-and-

maxillary-arteries-in-treatment-naive-gca-patients
Quantitative Analysis of Vascular Calcification Using a Novel Semi-Automated Software

Shubhasree Banerjee 1, Mohammadhadi Bagheri2, Veit Sandfort3, Ashkan Malayeri4, Mark Ahlman4, David A. Bluemke4, Jianhua Yao2
and Peter C. Grayson5, 1Fellowship and training branch, NIAMS/NIH, Bethesda, MD, 2Radiology and Imaging Sciences, NIH Clinical
Center, Bethesda, MD, 3Clinical Center, Radiology and Imaging Sciences, NIH, Bethesda, MD, 4Radiology and Imaging Sciences, National
Institutes of Health, Bethesda, MD, 5Research, National Institutes of Health, Bethesda, MD
SESSION INFORMATION
Background/Purpose:
Calcification of the coronary arteries, aorta, and branch vessels can occur in both large vessel vasculitis (LVV) and atherosclerosis. The
study objective was to determine 1) the location and amount of vascular calcification in LVV versus hyperlipidemia (HLD) and 2) risk
factors associated with vascular calcification in LVV.
Methods:
Patients with giant cell arteritis (GCA), Takayasu’s arteritis (TAK), and HLD were recruited into an observational cohort. All subjects
underwent computed tomography of the aorta and branch vessels. We developed a novel semi-automated software to compute vascular
calcification in 14 specific arterial territories (ascending aorta, aortic arch, descending thoracic aorta, abdominal aorta, carotids,
subclavians, innominate, iliacs, femorals and coronary arteries). Total amount of calcification throughout the large arteries was quantified by
calculating a cumulative Agatston score. Multivariate linear regression analyses were performed in LVV to determine associations between
total Agatston score and traditional or disease-specific risk factors. Traditional risk factors were age, gender, body mass index, smoking,
statin use and hypertension. Disease-specific risk factors were disease duration, clinical activity status, glucocorticoid dose, inflammatory
markers (ESR, CRP, fibrinogen) and vascular inflammation as measured by positron emission tomography (FDG-PET). Only variables with
p<0.10 in univariate analyses were included in the multivariate models. Frequencies were compared by the chi-squared test. Agatston scores
were compared by Kruskal-Wallis test with post-hoc Dunn’s test.
Results:
A total of 88 subjects, including GCA (n=29, median age=72, %female=79); TAK (n=22, median age=37, %female=73); and HLD (n=37,
median age= 66, %female=43), participated in the study. There were no differences in the location of vascular calcification in the aorta and
branch vessels between LVV and HLD, except coronary artery calcification was more prevalent in HLD compared to both TAK and GCA
(p<0.01). Total Agatston scores were higher in GCA (median 3260, range 25-18138) versus HLD (460.5, 19-17215) (p<0.01) but did not
significantly differ between GCA and TAK (1944, 52-47520) (p=0.53). An Agatston score >1000, consistent with severe calcification
burden, was observed in many patients with GCA (74%), TAK (56%), and HLD (42%). Factors associated with calcification in LVV are
shown in the table.
Conclusion:
We have developed a novel software to quantify calcification in vascular territories. This software could be repurposed to calculate
calcification burden in other regions of interest. Location of vascular calcification was found to be similar between LVV and HLD; however,
the amount of calcification was higher in patients with LVV. Both traditional and disease-specific risk factors are associated with vascular
calcification in LVV.
Table
Variable Univariable Multivariable
Estimate P Value Estimate P value
0.06 0.14
Age 0.01 <0.01
(1.06) (1.15)
Diagnosis
-0.96 4.02
(TAK vs 0.30 0.03
(0.38) (55.70)
GCA)
Prednisone 0.05 0.05
0.08 0.04
dose (1.16) (1.05)
Hypertensive
2.43 1.16
<0.01 0.19
Medication (11.35) (3.19)
Gender
0.12
0.85 (2.3) 0.04 0.90
(Female vs (1.12)
Male)
C-reactive -0.03
0.11
Protein (0.97)
FDG-PET 0.99
0.29
interpretation (2.69)
Statin 1.49
0.17
Medication (4.43)
Treatment
0 (1) 0.53
duration
Not included in
Clinical multivariable model.
0.44(1.55) 0.65
Assessment
Disease
0 (1) 0.74
duration
Body mass 0.02
0.77
index (1.02)
Erythrocyte
0.003
sedimentation 0.89
(1.0)
rate
Disclosure: S. Banerjee, None; M. Bagheri, None; V. Sandfort, None; A. Malayeri, None; M. Ahlman, None; D. A. Bluemke, None; J.
Yao, None; P. C. Grayson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/quantitative-analysis-of-vascular-calcification-using-a-

novel-semi-automated-software
A Novel Method to Assess Subchondral Bone Formation Using Naf-PET in the

Evaluation of Knee Osteoarthritis
Venkata S. Jonnakuti1, William Y. Raynor1, Elena G. Taratuta1, Abass Alavi2 and Joshua Baker3, 1Radiology, University of Pennsylvania,
Philadelphia, PA, 2Department of Radiology/Division of Nuclear Medicine, University of Pennsylvania, Philadelphia, PA, 3Rheumatology,
SESSION INFORMATION
Background/Purpose: Previous studies using 18F-sodium fluoride positron emission tomography (NaF-PET) have quantified the increase in
bone formation associated with osteoarthritic (OA) abnormalities with the maximum standardized uptake value (SUVmax) in user-defined
regions of interest (ROIs). A limitation of this method of quantification is that it assumes that the voxel with the highest SUV within the ROI
represents the overall activity of the affected tissue. To address this limitation, we developed a novel method of global joint analysis to
assess regions of expected bone turnover in articulating joints using NaF-PET in a group of patients at high risk for OA.
Methods: The study population consisted of 18 patients with Rheumatoid Arthritis who underwent static NaF-PET 90 minutes after the
intravenous administration of NaF tracer. The global knee activity was defined as the area-weighted average of the mean NaF tracer uptake
within the ROI. These global assessments at the knee were subsequently adjusted for overall bone formation at a non-articular location by
determining the ratio of tracer uptake at the knee over the uptake at the femoral neck. For comparison, the SUVmax for each ROI was
calculated methods. Standard radiographs of the knee were also obtained from the medical record in 9 patients and scored by a radiologist
using the Kellgren-Lawrence (K/L) grading system.
Results: The average SUVmean score for the knees was 1.48 (SD = 0.68) with a range of 0.54 to 2.96. Patients with greater NaF uptake
demonstrated greater deterioration of the medial and lateral intercondylar tubercles, as evidenced by the larger lesions in the corresponding
NaF-PET/CT scans (Fig. 1). Greater NaF global joint activity was observed among individuals with higher K/L grading scores (_ = 0.69, p
= 0.04). K/L grading was also associated with SUVmax values (_ = 0.93, p = 0.0003).
Conclusion: Both methods were strongly associated with K/L grading of knee OA. The potential advantage of the novel SUVmean method is
that it may be more sensitive at detecting changes in intra-ROI OA progression since new spatially distinct lesions with a lower SUV that
develop within an ROI would not be detected by the SUVmax methodology. Furthermore, the adjustment for fluoride uptake in non-articular
sites is likely important in order to adjust for age-related declines in overall bone turnover. Further study is needed to determine the utility of
this methodology in longitudinal studies.
Disclosure: V. S. Jonnakuti, None; W. Y. Raynor, None; E. G. Taratuta, None; A. Alavi, None; J. Baker, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-novel-method-to-assess-subchondral-bone-formation-

using-naf-pet-in-the-evaluation-of-knee-osteoarthritis
Reliability of an Omeract Semiquantitative Scoring System and Imaging Atlas for the
Assessment of Cartilage in Hand Osteoarthritis
Alexander Mathiessen1, Hilde B Hammer2, Lene Terslev3, George A. W. Bruyn4, Maria Antonietta D'Agostino5, Emilio Filippucci6, Ida
Kristin Haugen7, Marion Kortekaas8, Peter Mandl9, Ingrid Moller10, Esperanza Naredo11, Ruth Wittoek12, Annamaria Iagnocco13 and
Karen Ellegaard14, 1Dept. of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, 2Rheumatology, Dept. of Rheumatology,
Diakonhjemmet Hospital, Oslo, Norway, 3Copenhagen University Hospital at Glostrup, Copenhagen, Denmark, 4Rheumatology, MC Groep,
Loenga, Netherlands, 5Department of Rheumatology, Assistance publique-Hôpitaux de Paris Ambroise Paré Hospital, Boulogne-Billancourt ,
Université Versailles Saint Quentin en Yvelines, Paris, France, 6Rheumatology Unit, Università Politecnica delle Marche, Jesi, Italy,
7Diakonhjemmet Hospital, Oslo, Norway, 8Dept. of Rheumatology, Leiden University Medical Center, Leiden, Netherlands, 9Department of
Internal Medicine III; Division of Rheumatology, Medical University Vienna, Vienna, Austria, 10Instituto de Poal, Barcelona, Spain,
11Rheumatology Department, Hospital Gregorio Marañón, Madrid, Spain, 12Rheumatology, Ghent University Hospital, Ghent, Belgium,
13Academic Rheumatology Unit, Università degli Studi di Torino, Torino, Italy, 14Dept. of Rheumatology, The Parker Institute, Copenhagen,
Denmark
SESSION INFORMATION
Background/Purpose:
Osteoarthritis (OA) is characterized by gradual loss of articular cartilage. Evaluation of cartilage in the small joints of the hands has shown
that ultrasound may differentiate between normal and pathological joint cartilage, whereas semiquantitative scoring is not reliable. These
studies have however assessed the dorsal aspects of the joint, in which osteophytes often limits the acoustic window.
The aim of the present study was to test the reliability of a semiquantitative scoring system for the assessment of palmar finger joint cartilage
by ultrasound in a patient-based exercise of patients with hand OA.
Methods:
Six experienced sonographers participated in a patient-based reliability exercise. Bilateral proximal interphalangeal (PIP) joints of 12
patients with hand OA were assessed twice on the same day by all experts using ultrasound machines (GE Logiq E9) equipped with high-
frequency transducers (18MHz) with presets calibrated for the appropriate assessment of cartilage. The palmar aspects of the joints were
assessed in a transverse view with the fingers fully extended, and the participants had an imaging atlas available during the exercise (figure).
Intraclass correlation coefficient (ICC) values with 95% confidence intervals (CI) were calculated with average-measure for inter-reader
and single-measure for intra-reader reliability. Reliability was defined as poor (<0.5), moderate (0.5–0.75), good (0.75–0.9) and excellent
(>0.90).
Results:
A three-grade semiquantitative was applied: grade 0, normal cartilage (anechoic structure with visible margins of cartilage); grade 1, focal
thinning of cartilage or loss of sharpness of at least one cartilage margin; grade 2, focal or complete loss of cartilage. In total 96 joints were
assessed twice by every sonographer. The inter-reader reliability was excellent (ICC=0.90, 95% CI 0.77–0.97). Intra-reader reproducibility
was excellent (0.95, 0.83–0.98) to moderate (0.56, 0.02–0.85), with a mean ICC value of 0.74.
Conclusion:
A semiquantitative scoring system for the assessment of joint cartilage in palmar aspects of PIP joints by ultrasound showed excellent inter-
and moderate to excellent intra-reader reliability in a patient-based reliability study. Our study demonstrates that ultrasound with a high-
frequency probe is a reliable tool for evaluating cartilage and supports the use of a new semiquantitative scoring system for assessment of
finger cartilage in hand OA patients.
Figure
Disclosure: A. Mathiessen, None; H. B. Hammer, None; L. Terslev, None; G. A. W. Bruyn, None; M. A. D'Agostino, None; E.
Filippucci, None; I. K. Haugen, None; M. Kortekaas, None; P. Mandl, None; I. Moller, None; E. Naredo, None; R. Wittoek, None; A.
Iagnocco, None; K. Ellegaard, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/reliability-of-an-omeract-semiquantitative-scoring-

system-and-imaging-atlas-for-the-assessment-of-cartilage-in-hand-osteoarthritis
Prevalence and Pattern of Hand Osteoarthritis in a Working Population Using

Ultrasound
Mario Giulini1, Hasan Acar2, Ralph Brinks3, Matthias Schneider2, Benedikt Ostendorf4, Oliver Sander5 and Philipp Sewerin6, 1Department
for Rheumatology, Heinrich-Heine-University, Duesseldorf, Germany, 2Policlinic for Rheumatology & Hiller Research Centre for
Rheumatology, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany, 3Department of Rheumatology & Hiller Research Unit,
Heinrich-Heine University, Düsseldorf, Germany, 4Department of Rheumatology, Univ. Duesseldorf, Düsseldorf, Germany, 5Department of
Rheumatology & Hiller Research Unit, Heinrich-Heine-University, Duesseldorf, Germany, 6Department and Hiller-Research-Unit for
Rheumatology, Heinrich-Heine University, Düsseldorf, Germany
SESSION INFORMATION
Background/Purpose: The estimated prevalence of hand osteoarthritis (HOA) varies severely according to the selection of different
diagnostic modalities, items of interest and subject samples. In most studies conventional radiography (CR) was used in this matter. Recently
ultrasound (US) was considered reliable and reproducible, and even more sensitive in detecting HOA signs such as osteophytes. We assumed
that the prevalence of HOA detected by US was higher as described in previous studies. The objectives of this study were to investigate the
prevalence and precise pattern of HOA in a working population by US.
Methods: The study included 427 participants (15.7% women, 84.3% men, mean age 53.5 years). A total of 11,840 images were scored for
synovitis 0-3, synovitis mm, erosions 0-3, osteophytes 0-3, joint space mm and cartilage thickness mm. US assessment was provided for both
hands, scanning 26 finger joints of each participant (CMC 1, MCP 2-5, PIP 2-5 and DIP 2-5) using an Esaote Mylab 25Gold unit with an 18
MHz linear transducer. Gray-scale US was performed on the palmar side with all joints in neutral position. Static images were stored and
evaluated afterwards using Esaote Mylab-Desk software. HOA was defined as present if one or more joints of the participant showed
osteophytes.
Results: The overall prevalence for HOA was nearly 100%. Only one participant had no osteophytes. There is strong evidence to suggest
that the number of osteophytes increase with age (p<0.001). With every additional year, a mean increase of 0.18 (standard error 0.03)
osteophytes has been observed. We found no evidence for an association of the number of osteophytes with sex (p = 0.4, after adjustment of
age p = 0.9). The prevalence rates of osteophytes in the following joints of the right hand were: 8.5% MCP 5, 38.2% PIP 5, 56.8% DIP 5,
18.1% MCP 4, 51.4% PIP 4, 65.6% DIP 4, 28.3% MCP 3, 58.7% PIP 3, 67.4% DIP 3, 19.8% MCP 2, 48.5% PIP 2, 66.7% DIP 2 and
37.5% CMC 1. The prevalence rates of osteophytes in the following joints of the left hand were: 7.3% MCP 5, 34% PIP 5, 47.5% DIP 5,
12.3% MCP 4, 51.5% PIP 4, 56.2% DIP 4, 19.7% MCP 3, 53.2% PIP 3, 67.3% DIP 3, 14.6% MCP 2, 45.8% PIP 2, 59.6% DIP 2 and
40.1% CMC 1. Overall, DIP 3 on the right-hand side was the most frequently affected joint, followed by DIP 3 on the left-hand side, then
right-hand DIP 2 and DIP 4, then left-hand DIP 2.
Conclusion: US detected HOA shows a higher prevalence when compared to studies using CR. This supports prior studies emphasizing that
US is more sensitive than CR in detecting HOA signs such as osteophytes. Nearly all participants showed HOA signs and on average more
than 15% of the MCP joints were affected which could possibly be misinterpreted in the context of accompanying inflammatory joint
diseases. Regarding that, HOA is an underestimated problem in sonographic assessments and has to be more carefully respected when
interpreting US images of hand and finger joints.
Disclosure: M. Giulini, None; H. Acar, None; R. Brinks, None; M. Schneider, None; B. Ostendorf, None; O. Sander, None; P. Sewerin,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prevalence-and-pattern-of-hand-osteoarthritis-in-a-

working-population-using-ultrasound
Musculoskeletal Ultrasound As a Diagnostic Tool for Eosinophilic Fasciitis and

Correlation with MRI Findings
Florentina Berianu1, Neha Narula2 and Andy Abril1, 1Rheumatology, Mayo Clinic Florida, Jacksonville, FL, 2Division of Rheumatology,
Mayo Clinic, Jacksonville, FL
SESSION INFORMATION
Background/Purpose:
Eosinophilic fasciitis (EF) presents with pain and induration of the skin. Currently the clinical diagnosis is based on typical physical findings
along with MRI enhancement of the fascia, and the diagnosis is confirmed by documenting fascial thickening and inflammation on tissue
histology, including eosinophilic infiltrates. A recent case report has suggested fascia thickness can be measured with use of MSK ultrasound.
Changes in compressibility of subcutaneous tissue using a high-frequency probe have been shown to help distinguish it from scleroderma
patients. Objective: To describe a cohort of 7 patients with MSK US finding supporting the diagnosis of eosinophilic fasciitis with
corresponding MRIs findings compared with normal controls.
Methods: 7 patients with suspected EF seen in our rheumatology clinic underwent MSK US of upper or lower extremities that exhibited
findings of induration suggestive of EF. An ultrasound was performed using a 12-18 MHZ linear array transducer to visualize muscle and
fascia in the area of pain and induration. A measurement of fascial thickness was recorded in all patients. MSK US was also performed in 7
healthy controls. Patients subsequently underwent MRI of the same region. Full thickness skin to muscle biopsy to confirm the diagnosis was
performed in 6 out of 7 cases (one patient refused biopsy). Initial labs with serum eosinophils were recorded. None of the patients had
Raynaud’s or showed clinical or laboratory findings of scleroderma.
Results: 4 females and 3 males were included. Mean age: 43.5. Absolute eosinophil values ranged from 1051-4780/microL. The mean
thickness of the fascia was 0.43 cm (ranges 0.21-0.7 cm) versus 0.14 cm in normal controls (ranges: 0.11-0. 19 cm). All patients had MRI
with contrast with evidence of thickened and enhanced fascia of the same region. Diagnosis of EF was confirmed with tissue histology in all
cases in which biopsy was performed.
Conclusion: MSK US may represent a quick, safe, inexpensive and reliable diagnostic method for patient with suspected EF. It can also help
locate the best site for biopsy.
Disclosure: F. Berianu, None; N. Narula, None; A. Abril, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/musculoskeletal-ultrasound-as-a-diagnostic-tool-for-

eosinophilic-fasciitis-and-correlation-with-mri-findings
Applications of Salivary Gland Ultrasonography in Sjögren Syndrome and Sicca

Symptoms: A Single Center Experience
Yen-Po Tsao1,2, Ming-Han Chen3,4, Wei Sheng Chen1,5, Chien Chih Lai1,5 and Chang Youh Tsai1,2, 1National Yang-Ming University,
Taipei, Taiwan, 2Division of Allergy- Immunology- Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei,
Taiwan, 3Division of Allergy- Immunology- Rheumatology, Department of Medicine, Division of Allergy- Immunology- Rheumatology,
Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, 4Faculty of Medicine, School of Medicine, National Yang-Ming
University, Taipei, Taiwan, 5Department of medicine, division of allergy, immunology, rheumatology, Division of Allergy- Immunology-
Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
SESSION INFORMATION
Background/Purpose:
Sjögren’s syndrome is an autoimmune disease that involves salivary and lacrimal gland, which influences life quality of patients. In the recent
classification criteria declared by ACR/EULAR in 2016, salivary gland biopsy remained one of the main diagnostic factors. Salivary gland
ultrasonography (SGUS) has been evaluated recently for diagnosis Sjögren’s syndrome or detection the morphological change of the gland.
SGUS offered a non-invasive, time-consuming way in elucidating the condition of salivary gland. Although SGUS had been used in detection
autoimmune diseases, such as IgG4 disease or sarcoidosis, the usefulness and effectiveness in Sjögren syndrome remained controversial.
Methods:
Total 74 patients were enrolled. SGUS was conducted by a 10MHz-13MHz linear probe at both parotid and submandibular glands. Each
gland was scored from 0 to 4 according to the scoring scale proposed previously. The total maximum score was 16. Minor salivary gland
biopsy results were examined by pathologist with Chisholm-Mason grade. Blood samplings and ESSPRI questionnaires were conducted after
SGUS.
Results:
Total 47 patients with primary Sjögren’s Syndrome, 9 patients with secondary Sjögren’s Syndrome, and 18 patients with sicca symptoms
were examined. SGUS score correlated with serum anti-Ro/SSA (p=0.012), anti-La/SSB (p=0.004), ESSPRI score (p<0.001), and
Chisholm-Mason score of salivary gland biopsy (N=24, p=0.012). Furthermore, dryness scale and fatigue scale correlated with SGUS score
(p=0.001 and 0.002, respectively), but not with pain scale (p=0.199). In patient with primary Sjögren syndrome, the correlations between
ESSPRI and SGUS remained (p=0.024), but it did not exist in patient with secondary Sjögren syndrome (p=0.073) or sicca symptoms
(p=0.074).
Conclusion:
In our study, SGUS score correlated with patients’ self-reporting ESSPRI score and the microscopic biopsy result. It also correlated with
serology markers such as anti-Ro/SSA and anti-La/SSB. SGUS may provide a direct evaluation tool for evaluation the severity of gland
architecture as well as an alternative representative for histological change.
Disclosure: Y. P. Tsao, None; M. H. Chen, None; W. S. Chen, None; C. C. Lai, None; C. Y. Tsai, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/applications-of-salivary-gland-ultrasonography-in-

sjogren-syndrome-and-sicca-symptoms-a-single-center-experience
Prevalence of Pneumococcal Vaccination in Rheumatologic Patients with Community

Acquired Pneumonia. Biobadasar Registry
Gimena Gomez 1, Alejandro Brigante Jr.2, Alejandro Benitez3, Osvaldo Cerda4, Soledad Retamozo5, Ignacio Javier Gandino6, Ana
Quinteros7, Ida Exeni4, Belén Barrios8, Pablo Astesana9, Carolina Sanchez Andia4, María Victoria Collado10, Amelia Granel11, Ana
Cappuccio4, Rosana Quintana12, Eduardo Mussano13, Andrea Smichowski2, Mercedes De La Sota14, Karin Kirmayr15, Edson Javier
Velozo16, Maria Silvia Larroude17, Ana Bertoli18, Santiago Aguero19, Cristina Battagliotti20, Sidney Soares de Souza21, Emilia Cavillon9,
Analia Bohr22, Oscar Luis Rillo2, Eugenia Bedoya23, Eduardo Kerzberg24, Boris Kisluk12, Ingrid Petkovic25, Dora Pereira26, Juan Carlos
Barreira2, Luis Somma2, Ana Carolina Costi27, Belen Virasoro2, Fernando Melo28, Sergio Paira29, Luis Roa Perez2, Leandro Carlevaris
Sr.30, Gustavo Casado4 and María Celina de La Vega4, 1on behalf of BiobadaSar study group, Sociedad Argentina de Reumatologia, Buenos
Aires, Argentina, 2Sociedad Argentina de Reumatologia, Buenos Aires, Argentina, 3Sociedad Argentina de Reumatologia, Berazategui,
Argentina, 4Sociedad Argentina de Reumatologia, CABA, Argentina, 5Sociedad Argentina de Reumatologia, Córdoba, Argentina,
6Reumatologia, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina, 7Sociedad Argentina de Reumatologia, Tucuman, Argentina,
8Section of Rheumatology, Hospital General de Agudos “Dr. E. Tornú”, Buenos Aires, Argentina, Buenos Aires, Argentina, 9Sociedad
Argentina de Reumatologia, Cordoba, Argentina, 10Instituto de Investigaciones, Buenos Aires, Argentina, 11Sociedad Argentina de
Reumatologia, La Plata, Argentina, 12Sociedad Argentina de Reumatologia, Rosario, Argentina, 13Córdoba, Sociedad Argentina de
Reumatologia, Córdoba, Argentina, 14Sociedad Argentina de Reumatologia, Bahia Blanca, Argentina, 15Sociedad Argentina de
Reumatologia, Río Negro, Argentina, 16Rheumatology, Sociedad Argentina de Reumatologia, Entre Rios, Argentina, 17Centro de
Diagnostico Rossi, Buenos Aires, Argentina, 18Instituto Reumatológico Strusberg, Córdoba, Argentina, 19Sociedad Argentina de
Reumatologia, Catamarca, Argentina, 20Sociedad Argentina de Reumatologia, Santa Fe, Argentina, 21Ramallo 1851, Sociedad Argentina de
Reumatologia, CABA, Argentina, 22Rheumatology Department, Hospital de Rehabilitación Manuel Rocca, Buenos Aires, Argentina,
23Sociedad Argentina de Reumatologia, Entre Rios, Argentina, 24Rheumatology Department, Hospital Ramos Mejía, Buenos Aires,
Argentina, 25Sociedad Argentina de Reumatologia, Mendoza, Argentina, 26Rheumatology Department, Hospital Ricardo Gutierrez, Buenos
Aires, Argentina, 27Rheumatology, HIGA General San Martin La Plata, La Plata, Argentina, 28Rheumatology Department, Hospital
Rivadavia, Buenos Aires, Argentina, 29Reumatologia, Hospital J M Cullen, Santa Fe, Argentina, 30Rheumatology, Sociedad Argentina de
Reumatologia, Buenos Aires, Argentina
SESSION INFORMATION
Session Title: Infection-related Rheumatic Disease Poster
Background/Purpose:
Biobadasar is a registry that monitors adverse events in patients who use biological treatments in rheumatologic diseases conducted by the
Argentine Society of Rheumatology. As in others international registries the community acquired pneumonia (CAP) has been detected as one
of the most frequent infectological adverse events. Although all immunosuppressed patients should be vaccinated against streptococcus
pneumoniae, there is a proportion of patients who are not.
Evaluate the prevalence of pneumococcal vaccination in patients with CAP within the Biobadasar database. Assess factors associated with
severe CAP in these patients.
Methods:
A cross-sectional, multicenter study was made in Biobadasar database from 2010 to 2016. In patients who reported CAP data of
demographics, comorbidities and state of pneumococcal immunization was collected.
Microbiological data, treatment and outcome of the event was considered. The severity of CAP was assessed according to the opinion of the
attending physician, hospitalization, risk of life and / or death.
Values are expressed as mean ± standard deviation, median (ranges) and frequencies (percentages), as appropriate. We performed bivariate
and multivariate logistic regression analysis to identify variables associated with the event.
Results:
Of the 4029 patients enrolled in the registry, the cumulative incidence of CAP was 4.2% (n 170), 72.4% (n 123) were women. The mean age
was 57 (SD +/- 14.5). Biological treatment was found in 81.8% (n 139). Patient s that have received the pneumococcal vaccine were 40.6%
(n = 69). Severe CAP was detected in 7.1% with ICU admission requirement in and 31.8% were in general admission. Streptococco
Pneumoniae was the main pathogen isolated in 13% of the cases. Overall mortality was 4.1%. Among the comorbidities of patients with
CAP, the following were found: AHT 31.8%, Osteoporosis 16.5%, Smoking 12.9%, DBT 4.7%, interstitial lung disease 2.9%, CKD 1.8%.
The most frequent rheumatic disease was RA in 74.5%, followed by PAs 6.5% and SLE in 6.5%. The median time to progression of the
underlying disease was 9 years (R: 1-45). A logistic regression was performed to evaluate risk factors in severe CAP. In the univariate
analysis for severe CAP we found statistical significance for Smoking OR 3.88, CI95 1.063-14.22, p= 0.029 and chronic kidney disease
(CKD) OR 31, CI95 2.6-376, p= 0.007. When performing a multiple logistic regression model, only renal failure OR 7.39 CI95 0.003-0.38
p= 0.007 was a predictor of severe CAP. Not significative association with immunosuppressive treatment (p: 0.09), age (p: 0.464), or
vaccination (p: 0.937)
Conclusion:
The annual incidence of CAP in Argentina varies between 0.5 -1.1% while in our cohort it was four times higher. The prevalence of
pneumococcal vaccination was less than 50%, showing that, although the literature and guidelines establish the need for vaccination, this is
not so in the real world. In the multivariate analysis, only CRD was related to severe CAP. Although in the univariate analysis the CKD and
the smoking habit represented factors associated with severity. We must emphasize the medical education in following the international
vaccination guidelines.
Disclosure: G. Gomez, None; A. Brigante Jr., None; A. Benitez, None; O. Cerda, None; S. Retamozo, None; I. J. Gandino, None; A.
Quinteros, None; I. Exeni, None; B. Barrios, None; P. Astesana, None; C. Sanchez Andia, None; M. V. Collado, None; A. Granel, None;
A. Cappuccio, None; R. Quintana, None; E. Mussano, None; A. Smichowski, None; M. De La Sota, None; K. Kirmayr, None; E. J.
Velozo, None; M. S. Larroude, None; A. Bertoli, None; S. Aguero, None; C. Battagliotti, None; S. Soares de Souza, None; E. Cavillon,
None; A. Bohr, None; O. L. Rillo, None; E. Bedoya, None; E. Kerzberg, None; B. Kisluk, None; I. Petkovic, None; D. Pereira, None; J.
C. Barreira, None; L. Somma, None; A. C. Costi, None; B. Virasoro, None; F. Melo, None; S. Paira, None; L. Roa Perez, None; L.
Carlevaris Sr., None; G. Casado, None; M. C. de La Vega, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prevalence-of-pneumococcal-vaccination-in-

rheumatologic-patients-with-community-acquired-pneumonia-biobadasar-registry
HIV Infection and Avascular Necrosis in the Antiretroviral Era

Yasir Abdulqader1, Muhsen Al-ani2 and Konstantinos Parperis3, 1Internal Medicine, Maricopa Integrated health system, Phoenix, AZ,
2Internal Medicine, Maricopa Integrated Health System and University of Arizona College of Medicine, Phoenix Campus, phoenix, AZ,
3Rheumatology, Maricopa Integrated Health System and University of Arizona College of Medicine, Phoenix Campus, phoenix, AZ
SESSION INFORMATION
Background/Purpose:
Infection with the HIV has been associated with an increased risk of developing avascular necrosis (AVN), however there are only few
studies in the US that analyzed the frequency and risk factors of the AVN in HIV patients on antiretroviral therapy (ART). The aim of this
study was to determine the prevalence of AVN in well-controlled HIV-infected patients who were receiving antiretroviral treatment and
evaluate potential risks factors including HIV medications.
Methods:
: A retrospective review of our medical record database over a 6 year period was conducted using ICD-9 and ICD-10 codes. Three thousand
patients with chronic HIV infection on ART that had more than 2 visits in the HIV clinic were identified. Individual electronic patient charts
were reviewed and we identified patients diagnosed with AVN that was confirmed by magnetic resonance imaging studies. We collected
data regarding patient’s demographic characteristics, co-morbidities, T-helper lymphocytes with CD4 cell surface marker count, HIV RNA
viral load and antiretroviral regimen. Two hundred randomly selected HIV-infected patients on ART without a diagnosis of AVN were used
as a control group. Group differences were statistically compared and presented using Mann-Whitney U and Fisher’s exact test.
Results:
Forty two out of 3000 HIV patients (1.4 %) with AVN were identified (mean age of 49.5 years, 87% male). The most commonly involved
joint was the hip (80%, n=34), followed by the glenohumeral (7.5%, n=4), femoral condyle (4.7%, n=2) and ankle (4.7%, n=2). Associated
co-morbidities in patients with AVN included hyperlipidemia (21%, n=9), hypertension (19%, n=8), COPD/asthma(12%,n=5), hepatitis C
(12%,n=5). All the patients with COPD/asthma have been treated with corticosteroids. Ten patients underwent joint replacement (23%), 4
core decompression surgery (9%) and the rest non-operative management.
Compared with the 200 HIV control patients, the patients with AVN were older (mean age of 49.5 vs. 42.7 years; p<0.01), had a history of
COPD treated with corticosteroids (p= 0.02) and had a longer duration of HIV infection (mean duration of 16.8 vs.10.3 years; p<0.01).
Patients who developed AVN were more likely to be receiving integrase strand transfer inhibitors (66%) compare to those who never
received integrase inhibitors (20%; p<0.01). No differences were found between ANV patients and controls with respect to CD4 cell counts
or viral load
Conclusion:
AVN remains one of the most frequent musculoskeletal complication in HIV patients. Potential risk factors associated with the development
of AVN in HIV patients were older age, longer duration of HIV infection, history of COPD/asthma, corticosteroid use and the use of ART
regimens containing integrase strand transfer inhibitors.
Disclosure: Y. Abdulqader, None; M. Al-ani, None; K. Parperis, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/hiv-infection-and-avascular-necrosis-in-the-

antiretroviral-era
The Trend of Incidence Rate, Frequency and HLA Phenotype of Reactive Arthritis and
Uveitis in Japanese Patients with Bladder Cancer Following Intravesical BCG Therapy:
A 20-Year, Two-Center Retrospective Study
Yoshinori Taniguchi1, Satoshi Inotani2, Hirofumi Nishikawa2, Kosuke Inoue3, Taro Horino2, Takashi Karashima4, Yasuhiko Yoshinaga5
and Yoshio Terada3, 1Endocrinology, Metabolism,Nephrology and Rheumatology, Kochi University, Kochi, Japan, 2Endocrinology,
Metabolism, Nephrology and Rheumatology, Kochi Medical School, Nankoku, Japan, 3Kochi University, Nankoku, Japan, 4Urology, Kochi
University, Nankoku, Japan, 5Kurashiki Medical Center, Kurashiki, Japan
SESSION INFORMATION
Background/Purpose: Intravesical instillation of Bacillus Calmette-Guerin (iBCG) is used as an effective immunotherapy of bladder cancer.
However it may have, as adverse event, a reactive arthritis (ReA) and the frequencies are known as about 0.5 to 1 % in Western countries.
Obejective is to evaluate the trend of incidence rate, frequency and HLA phenotype of reactive arthritis (ReA), uveitis and other adverse
events in Japanese patients with bladder cancer following iBCG therapy.
Methods: The clinical findings of Japanese patients who received iBCG (n = 555 [250 and 305 in Kochi Medical School Hospital and
Kurashiki Medical Center, respectively]) for bladder cancer from March 1997 to February 2017 were retrospectively assessed, with specific
attention to patients with ReA and uveitis. HLA phenotypes of patients with ReA were also looked. Moreover, iBCG-induced ReA diagnosed
from 1997 to 2007 were compared with that from 2007 to 2017.
Results: Patients’ mean age was 72 ± 10 years and male/female ratio was 438/117. Fever, haematuria, and dysuria were presented in 91/555
(16.4%), 121/555 (21.8%), and 196/555 (35.3%), respectively of all enrolled patients. Of the 555 cases, ReA and uveitis were revealed in
11/555 (2.0%) and 4/555 (0.7%). The protocol of iBCG therapy was stable over the 20 years. Notably, HLA-B27, -B35, -B39 and -B51
positivity was more frequent in ReA patients (9.1%, 36.3%, 36.3% and 63.6%, respectively) (p<0.05) than in healthy subjects without ReA
(0.3%, 8.3%, 4.0% and 9.1%, respectively). All 4 cases with uveitis had ReA, and showed positive HLA-B27 (25%), -B39 (50%) and –
B51 (25%). Finally, the overall incidence of iBCG-ReA was not different between from 1997 to 2007 and 2007 to 2017.
Conclusion:
The 2.0% iBCG-induced ReA frequency in Japanese patients exceeds that in Western countries, and its incidence has been stable over the
last 20 years. HLA phenotype, especially HLA-B51 and -B39 alleles in addition to -B27, may be a risk factor in iBCG-induced ReA in
Japanese patients.
Disclosure: Y. Taniguchi, None; S. Inotani, None; H. Nishikawa, None; K. Inoue, None; T. Horino, None; T. Karashima, None; Y.
Yoshinaga, None; Y. Terada, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-trend-of-incidence-rate-frequency-and-hla-phenotype-

of-reactive-arthritis-and-uveitis-in-japanese-patients-with-bladder-cancer-following-intravesical-bcg-therapy-a-20-year-two-center-
retrospect
The Difference in the Clinical Characteristics between Cytomegalovirus Disease and

Asymptomatic Cytomegalovirus Reactivation in Rheumatic Diseases
Shunya Kaneshita, Takashi Kida, Hidetake Nagahara, Yuko Kitagawa, Hideaki Sofue, Akiko Kasahara, Risa Sagawa, Takuya Inoue, Amane
Nakabayashi, Yuji Kukida, Kazuki Fujioka, Makoto Wada, Takahiro Seno, Masataka Kohno and Yutaka Kawahito, Inflammation and
Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
SESSION INFORMATION
Background/Purpose:
Cytomegalovirus (CMV) infection is one of the most common opportunistic infections in rheumatic diseases. A definite diagnosis of CMV
infection usually requires histopathological confirmation, but performing biopsy is usually difficult in patients with poor general condition.
The CMV antigenemia test, which detects the virus-specific protein PP65 antigen in polymorphonuclear leukocyte, is widely used to examine
immunocompromised patients with rheumatic diseases and becomes positive (CMV reactivation) regardless of the symptoms. Anti-CMV
agents should not be exclusively and needlessly used for asymptomatic patients with CMV reactivation to avoid side effects and social
burden due to high medication cost. The aim of this study was to determine the difference in the clinical characteristics between patients with
symptomatic and asymptomatic reactivation in rheumatic diseases.
Methods:
We retrospectively examined patients with CMV infection at our department, from January 2008 to December 2016. Patients positive for
CMV reactivation were divided into two groups based on the symptoms they experienced, namely, CMV disease (with any symptoms) and
asymptomatic CMV reactivation (without symptoms). The CMV antigenemia assay was used to assess the difference in the clinical
characteristics between the two groups and their transitions 4 weeks prior to, and during, the first positive diagnosis.
Results:
In 80 patients with CMV reactivation, 31.2% were men and the mean age was 61.0}15.7 years. In the univariate analysis, patients with CMV
disease were mostly men, with oral candidiasis, hypoalbuminemia, low lymphocyte count, and high titer CMV antigenemia count. In the
multivariate analysis, the odds ratios (ORs) are 8.82 (95% confidence interval (CI) 1.64–47.30, P value=0.01), 0.81 (95% CI 0.69–0.95, P
value<0.01), and 1.26 (95% CI 1.05–1.50, P value=0.01) for oral candidiasis, serum albumin, and CMV antigenemia count, respectively
(Table 1). Moreover, the transitionfs ORs 4 weeks prior to the first positive diagnosis using the CMV antigenemia are 1.96 (95% CI 1.09–
3.54, P=0.025) and 2.02 (95% CI 1.07–3.8 P=0.03) for lymphocyte count and serum albumin, respectively (Table 2).
Conclusion:
Patients with CMV reactivation, who have a gradually decreasing serum albumin and lymphocyte count 4 weeks prior to the first positive
diagnosis and who presented with hypoalbuminemia, oral candidiasis, and high CMV antigenemia count during the first positive diagnosis,
are highly at risk for CMV disease in rheumatic diseases.
Disclosure: S. Kaneshita, None; T. Kida, None; H. Nagahara, None; Y. Kitagawa, None; H. Sofue, None; A. Kasahara, None; R.
Sagawa, None; T. Inoue, None; A. Nakabayashi, None; Y. Kukida, None; K. Fujioka, None; M. Wada, None; T. Seno, None; M. Kohno,
None; Y. Kawahito, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-difference-in-the-clinical-characteristics-between-

cytomegalovirus-disease-and-asymptomatic-cytomegalovirus-reactivation-in-rheumatic-diseases
The Risk Factors of Developing Adult T Cell Leukemia (ATL) in Human T Cell
Leukemia Virus Type 1 (HTLV-1) Positive Patients with Rheumatoid Arthritis in
Endemic Area, Japan; A Retrospective Cohort Study
Kunihiko Umekita1, Yayoi Hashiba2, Shunichi Miyauchi1, Kazuyoshi Kubo2, Toshihiko Hidaka2 and Akihiko Okayama1, 1Department of
Rheumatology, Infectious Diseases and Laboratory Medicine, University of Miyazaki, Miyazaki, Japan, 2Institute of Rheumatology, Zenjinkai
Shimin-no-Mori Hospital, Miyazaki, Japan
SESSION INFORMATION
Background/Purpose: Human T cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL). ATL is an
aggressive T-cell malignancy caused by HTLV-1 infection and often occurs in HTLV-1-endemic areas, such as southwestern Japan, the
Caribbean islands, Central and South America, Intertropical Africa, and Middle East. Recent study indicated that the estimated annual
number of new HTLV-1 infection was 4,190 in nationwide blood donor surveillance in Japan. However, it is still not clear that the
prevalence of HTLV-1 infection in patients with RA. Additionally, there are questions as to whether comorbidity of RA and its treatment in
HTLV-1 carriers could increase the risk of developing ATL. The aim of this study is to clarify the prevalence of HTLV-1 infection in RA
patients in HTLV-1 endemic area Miyazaki, Japan. In addition, we investigated the risk factors of developing ATL in HTLV-1 positive RA
patients.
Methods: We established HTLV-1 positive RA cohort study in Miyazaki from 2012. Eight hundred sixty-one patients with RA were
registered in this cohort until 2015. We evaluated blood levels in HTLV-1 proviral load (PVL) samples by real-time PCR, HTLV-1 antibody
titer by particle agglutination assay, and the level of soluble IL-2 receptor (sIL-2R) by ELISA.
Results: The prevalence of HTLV-1 infection in RA patients was 6.0 % in this cohort. The age of HTLV-1 positive RA patients was higher
than in HTLV-1 negative RA patients (p= 0.003). In the distribution of PVL, 20% of HTLV-1 positive RA patients showed highly PVL (>
4%), which was the known risk factor for ATL. The levels of sIL-2R in sera correlated to the levels of PVL, significantly (p=0.01).
Treatment of disease modifying anti-rheumatic drugs (DMARDs) including biologics were administrated in the all patients. No effect to the
levels of PVL and sIL-2R by the treatment with DMARDs was observed. A patient developed chronic type ATL, who were treated with
MTX and anti-TNF inhibitor during 3-years observation periods (121 person-years) in this cohort.
Conclusion: The prevalence of HTLV-1 infection in RA patients in this cohort tended to be higher than that in nationwide surveillance in
Japan. The incidence of ATL in HTLV-1 carriers was estimated to one per 1000 person-years. The incidence of ATL in HTLV-1 positive
RA patients was higher than that in their study, although the sample size was small. A long-term follow-up of HTLV-1 positive RA patients is
required to resolve whether the comorbidity of RA and its treatment increase the risk of developing ATL.
Disclosure: K. Umekita, None; Y. Hashiba, None; S. Miyauchi, None; K. Kubo, None; T. Hidaka, None; A. Okayama, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-risk-factors-of-developing-adult-t-cell-leukemia-atl-

in-human-t-cell-leukemia-virus-type-1-htlv-1-positive-patients-with-rheumatoid-arthritis-in-endemic-area-japan-a-retrospective-cohort-stu
Frequency of Chronic Joint Pain Following Chikungunya Infection: A Colombian

Cohort Study
Aileen Chang1, Liliana Encinales2, Alexandra Porras3, Nelly Pacheco2, St. Patrick Reid4, Karen Martins5, Shamila Pacheco2, Eyda
Bravo2, Marianda Navarno2, Alejandro Rico Mendoza3, Richard Amdur6, Priyanka Kamalapathy6, Gary S. Firestein7, Jeffrey Bethony6 and
Gary Simon6, 1Medicine, George Washington University, Washington, DC, 2Allied Research Society, Baranquilla, Colombia, 3Allied
Research Society, Bogota, Colombia, 4University of Nebraska, Omaha, NE, 5United States Army Medical Research Institute of Infectious
Disease, Frederick, MD, 6George Washington University, Washington, DC, 7Medicine, University of California San Diego, La Jolla, CA
SESSION INFORMATION
Background/Purpose: To estimate the frequency of chronic joint pain after infection with chikungunya virus in a Latin American cohort.
Methods: A cross sectional follow-up of a prospective cohort of 500 Chikungunya patients from Atlántico Department, Colombia clinically
diagnosed with chikungunya during the 2014-2015 Colombian epidemic. Baseline and follow-up (20-months) symptoms were evaluated in
serologically confirmed cases.
Results: Among 500 patients enrolled, 485 cases were serologically confirmed with chikungunya. Patients were predominantly adults (age
49 ± 16 years), female, had a high school or less level of education and were of mestizo ethnicity. The most commonly affected joints were
the small joints including the wrists, ankles and fingers. The initial joint pain lasted a median of 4 days (IQR 3-8). Sixteen percent of
participants reported missing a median of 4 days (IQR 2-7) of school or work. After 20-months, one fourth of the participants had persistent
joint pain. A multivariate analysis indicated that significant predictors of persistent joint pain included college graduate status, initial
symptoms of headache or knee pain, missed work, normal activities affected, 4 or more days of initial symptoms, and 4 or more weeks of
initial pain.
Conclusion: This is the first report to describe the frequency of chikungunya-related arthritis in the Americas after a 20-month follow-up. The
high frequency of chronic disease highlights the importance of development of prevention and treatment interventions.
Disclosure: A. Chang, None; L. Encinales, None; A. Porras, None; N. Pacheco, None; S. P. Reid, None; K. Martins, None; S. Pacheco,
None; E. Bravo, None; M. Navarno, None; A. Rico Mendoza, None; R. Amdur, None; P. Kamalapathy, None; G. S. Firestein, Janssen
Pharmaceutica Product, L.P., 2; J. Bethony, None; G. Simon, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/frequency-of-chronic-joint-pain-following-chikungunya-

infection-a-colombian-cohort-study
Predictive Factors of Cytomegalovirus Infection in Patients with Connective Tissue

Predictive Factors of Cytomegalovirus Infection in Patients with Connective Tissue
Diseases Treated with Immunosuppressive Drugs
Yusuke Yoshida1, Hiroki Kohno2, Katsuhiro Oi3, Tadahiro Tokunaga3, Tatsuomi Kuranobu3, Takaki Nojima4, Shintaro Hirata3 and Eiji
Sugiyama1, 1Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan, 2Hiroshima
Prefectural Hospital, Hiroshima, Japan, 3Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan,
4Clinical Immunology and Rheumatolog, Graduate School of Medicine, Kyoto University, Kyoto, Japan
SESSION INFORMATION
Background/Purpose: Cytomegalovirus (CMV) infections occur frequently in immunocompromised patients. This disease will be fatal if
proper treatment is not done. Therefore, in the treatment of connective tissue disease (CTDs), care should be taken while paying attention to
the onset of cytomegalovirus infection. The purpose of this study is to clarify the predictors of CMV infection that developed in patients
undergoing immunosuppressive treatment.
Methods: All CTD patients who were diagnosed as a CMV infection from January 2009 to March 2017 at our hospital were retrospectively
reviewed. The diagnosis of CMV was made by clinical symptoms, radiological findings, the presence of CMV pp65 antigen in
polymorphonuclear leukocyte (C7-HRP) and pathological findings of organ specimen. We compared the sequential changes in laboratory
data between one month before diagnosis and at diagnosis. The differences in laboratory data between the survivors and non-survivors were
also compared. Statistical analyses were performed using XLSTAT.
Results: A total of 20 patients were diagnosed with CMV infection (12 bone marrow suppression; 4 pneumonia; 2 enteritis; 1 genital ulcer;
and 1 retinitis) and enrolled in this study. The mean age was 67.9 years old and 60% of patients was female. The CTDs of patients as
follows: dermatomyositis (25%), adult-onset Still’s disease (15%), and microscopic polyangiitis (15%). All patients were positive for CMV
pp65 (mean C7-HRP: 287.6 ± 510.0/50,000 WBC), who were treated with a moderate to high dose of glucocorticoids (mean prednisolone
dose: 33.4 ± 15.9 mg/day). When compared laboratory data between one month before diagnosis and at diagnosis, reduction of leukocyte
cells, lymphocytes, platelet counts and IgG levels were predictive for occurring CMV infection. Among them, lymphopenia was critical for
distinguishing between survivors and non-survivors.
Conclusion: The decreased in the leukocyte, lymphocyte, platelet, and IgG levels are important predictive factors for CMV infection in
CTDs. Among them, decreased lymphocytes counts is a critical predictive factor for life threatening condition.
Disclosure: Y. Yoshida, None; H. Kohno, None; K. Oi, None; T. Tokunaga, None; T. Kuranobu, None; T. Nojima, None; S. Hirata, None;
E. Sugiyama, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/predictive-factors-of-cytomegalovirus-infection-in-

patients-with-connective-tissue-diseases-treated-with-immunosuppressive-drugs
Follow-up of Patients with Musculoskeletal Manifestations Related to Chikungunya

Fever
Paula Murari-Nascimento1, Ana Beatriz Vargas-Santos2, Natalia Fortes1, Heruza Zogbi3, Otília Santos3, Patricia Brasil3, Guilherme
Calvet3, Rogério Valls3, Carlos Andrade3, Andre Siqueira3, Geraldo Castelar-Pinheiro2, Letícia Pereira1 and Rodrigo B. Chaves-Amorim4,
1State University of Rio de Janeiro, Rio de Janeiro, Brazil, 2Internal Medicine - Rheumatology, State University of Rio de Janeiro, Rio de
Janeiro, Brazil, 3Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation – FIOCRUZ, Rio de Janeiro, Brazil,
4Universidade do Estado do Rio de Janeiro - UERJ, Rio de Janeiro, Brazil
SESSION INFORMATION
Background/Purpose:
Chikungunya fever (CHIK) has joint involvement as a striking characteristic, which may persist for months. This study aimed to better
understand the clinical impact of this new disease, evaluating the patients of a reference center for infectious disease
(Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation – FIOCRUZ) in Brazil during the 2016 CHIK outbreak.
Methods:
From April 2016 to October 2016, patients who sought care at the FIOCRUZ’s Acute Febrile Disease Outpatient Clinic, with symptoms
suggestive of CHIK (fever, musculoskeletal pain) were evaluated by a team of infectologists and rheumatologists through medical history,
physical exam, clinical questionnaires and diagnostic lab tests. Patients were stratified by symptoms duration at first evaluation, classified as
acute if symptoms present for ≤14 days and subacute/chronic if symptoms present for >14 days. After about 1 year from the initial visit, we
contacted the patients by phone to obtain information about the current clinical status regarding joint pain, swelling and morning stiffness.
Results:
We evaluated 61 patients with suspected CHIK. Diagnosis was confirmed in 41 patients by serology or PCR; in 20 patients, lab results were
not available. Demographic and clinical characteristics of patients with diagnostic confirmation were similar compared to those without lab
results; thus, both groups were analyzed together. There were 36 women and 25 men; none had autoimmune disease. In 18 patients, extra-
articular manifestations (bursitis, tenosynovitis and carpal tunnel syndrome) were described. Baseline characteristics are shown in Table.
At 1 year, we managed to contact 30 patients; 9 of them referred symptoms resolution and 11 presented partial improvement, while 10
patients reported pain level similar to the initial presentation. Most patients had peripheral involvement, mainly hands and feet. Pain was
considered mild in 9 patients, moderate in 9 patients, and intense in 3 patients. Subjects who chronically persisted with similar symptoms had
significantly higher mean HAQ-DI at baseline (HAQ-DI = 2.4, 95% confidence interval (CI) 2.0–2.8) than those who achieved partial
improvement or symptoms resolution (HAQ-DI = 1.5, 95% CI 1.1–2.0, p=0.01).
Conclusion:
Our study showed that CHIK results in dramatic, and often chronic joint involvement, with severe pain, fatigue and functional disability.
Furthermore, the baseline HAQ-DI may predict chronicity of symptoms, although our conclusions are limited by our sample size.
Disclosure: P. Murari-Nascimento, None; A. B. Vargas-Santos, None; N. Fortes, None; H. Zogbi, None; O. Santos, None; P. Brasil,
None; G. Calvet, None; R. Valls, None; C. Andrade, None; A. Siqueira, None; G. Castelar-Pinheiro, None; L. Pereira, None; R. B.
Chaves-Amorim, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/follow-up-of-patients-with-musculoskeletal-

manifestations-related-to-chikungunya-fever
Rheumatic Conditions Appearing De Novo after Infection with Chikungunya Virus in

Venezuelan Patients
Yurilis Fuentes-Silva1, Carlota Acosta2, Luisa Ortega3, Martin A Rodriguez4, Soham Al Snih5, Ivan Amaya6 and Irama Maldonado3,
1Division of Rheumatology/Internal Medicine Department, 1Unidad de Reumatología adscrita al Centro Nacional de Enfermedades
Reumáticas. Complejo Hospitalario Universitario Ruiz y Páez, Ciudad Bolivar, Venezuela (Bolivarian Republic of), 21Unidad de
Reumatología adscrita al Centro Nacional de Enfermedades Reumáticas. Complejo Hospitalario Universitario Ruiz y Páez, Ciudad Bolivar,
Venezuela (Bolivarian Republic of), 3Internal Medicine, 1Unidad de Reumatología adscrita al Centro Nacional de Enfermedades
Reumáticas. Complejo Hospitalario Universitario Ruiz y Páez, Ciudad Bolivar, Venezuela (Bolivarian Republic of), 4Division of
Rheumatology/Internal Medicine Department, Centro Nacional de Enfermedades Reumaticas. Hospital Universitario de Caracas, Caracas,
Venezuela (Bolivarian Republic of), 5University of Texas Medical Branch, Galveston, TX, 6Facultad de Bioanálisis. Universidad de
Oriente, Cudad Bolivar, Venezuela (Bolivarian Republic of)
SESSION INFORMATION
Background/Purpose: It is well known that viral infections can trigger autoimmune rheumatic diseases. In 2,014 there was an outbreak of
Chikungunya (CHIK) virus infection in Venezuela. A majority of infected patients develop a flare of self-limited acute polyarthritis followed
by complete remission. Some patients continue to experience subacute and chronic joint inflammatory symptoms. However, it is not well
known how many of those patients evolve into a well-defined chronic rheumatic condition. The aim of this study was to examine how many
patients with post-CHIK chronic inflammatory rheumatism (CHIK-CIR) evolve into a definite chronic rheumatic disease.
Methods: One hundred and sixty-eight patients seen during the period between 2,014 and 2,016 were included in this study. Post-CHIK CIR
criteria were: 1. A triad of arthritis, fever and rash in presence of musculoskeletal manifestations (N=50, 29.76%) or 2. Musculoskeletal
manifestations with or without the whole triad plus a positive IgM o IgG CHIK serology ELISA test (N=118, 70.23%). In both cases
persistence of the symptoms for more than three months was required. The diagnosis for a definite rheumatic disease was done following the
corresponding American College of Rheumatology (ACR) criteria. Statistical analysis was done by Chi-square and the Exact Fisher´s test. P-
values of < 0.001 were considered statistically significant. All patients signed an informed consent.
Results: A positive CHIK serology test was tested and resulted positive in 70.23% of patients (IgM and IgG in 44 and 117 patients,
respectively). Rheumatoid factor (RF) was positive in 24.13% and anti-citrullinated peptide antibodies (ACPA) in 25.66% of the patients.
Of the total population (168 patients) with post-CHIK-CIR, 89.29% were female, mean age was 55.33 ± 12.72 years, and mean disease
follow-up was 73.9±15.6 months. Forty patients (23.80%) had family history for autoimmunity. Thirty patients (17.85%) evolved into the
following definite rheumatic diseases: rheumatoid arthritis (12.50%), psoriatic arthritis (2.38%), spondyloarthritis (1.79%) and systemic
lupus erythematosus (0.60%). There was a statistically significant association between positivity of RF, ACPA or both with development of
the de novo rheumatic diseases (P < 0.0001 in each case). Other variables studied no related with development of de novo rheumatic disease
were: IgM and IgG serology titers, presence of tenosynovitis and elevation of acute phase reactants.
Conclusion: CHIK virus infection can trigger a chronic autoimmune rheumatic disease, predominantly rheumatoid arthritis. Risk factors are
the appearance of either RF or ACPA, or both.
Disclosure: Y. Fuentes-Silva, None; C. Acosta, None; L. Ortega, None; M. A. Rodriguez, None; S. Al Snih, None; I. Amaya, None; I.
Maldonado, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rheumatic-conditions-appearing-de-novo-after-infection-

with-chikungunya-virus-in-venezuelan-patients
Corticosteroid Use, Biologic Therapy Switching, Smoking and Renal Failure Are
Associated with Serious Infections in Rheumatoid Arthritis Patients Treated with
Biologics: Data from Two Latin-American Registries
Maria de la Vega1, Gustavo Casado2, Gustavo Citera2, Ieda Maria Magalhães Laurindo3, Georges Christopoulos3, Miguel Angel
Descalzo4 and Roberto Ranza5, 1on behalf of BiobadaSar study group, Sociedad Argentina de Reumatologia, Buenos aires, Argentina, 2on
behalf of BiobadaSar study group, Sociedad Argentina de Reumatologia, Buenos Aires, Argentina, 3on behalf of the BiobadaBrasil study
group, Sociedade Brasileira de Reumatologia, São Paulo, Brazil, 4Unidad de Investigación Fundación Piel Sana Academia Española de
Dermatología y Venerología, Madrid, Spain, 5on behalf of the BiobadaBrasil study group, Sociedade Brasileira de Reumatologia,
Uberlandia, Brazil
SESSION INFORMATION
Background/Purpose: Infections are the most frequent and concerning serious adverse events related to rheumatoid arthritis (RA) treatment
with biologic drugs (bDMARDs). Their safety profile might have substantial regional differences. In January 2009 started BiobadaAmerica,
a common platform registry project open to all Latin American countries, focused on safety monitoring of bDMARDs. Purpose of this study is
to present data on factors associated with serious infections (SI) in patients with RA exposed to bDMARDs in two Latin-American not
mandatory registries.
Methods: Data from Argentinian Registry (BiobadaSar) and Brasilian Registry (BiobadaBrazil), both initiated in 2010, were downloaded
on December 31, 2016, merged and analyzed. The same constant monitoring process guaranteed data quality. Patients with rheumatic
diseases were included prospectively when started the first bDMARD. Time of exposure was set from start of the drug to the date of last
administration or censorship. SI incidence rate was calculated per 1000 patient/years with 95%CI
Results: Data from 2591 RA patients were analyzed, for a total of 9300 p/y. Treatments were 3784, 64% aTNF (Adalimumab, Certolizumab,
Etanercept, Golimumab, Infliximab), 36% non-aTNF (Abatacept, Rituximab, Tocilizumab) including Tofacitinib. Females 85%, at baseline
mean age 53 (SD 12.8)yrs , mean disease duration 10(8.5)yrs, mean follow-up 2.7 (2) yrs. The overall incidence rate of SI was 30.54 (CI
27.18-34.30), Comparing patients with (191) and without (2400) SI, age, sex, disease duration, use of concomitants DMARD, presence of
diabetes mellitus or pulmonary chronic disease and a positive history of previous câncer did not differ statistically. Exposition to more than
one bDMARD (p<0.01), corticosteroid use (p=<0.01), smoking (p=0.01) and presence of renal failure (p=0.03) were statistically associated
with SI. Unexpectedly, basal DAS28 was higher in patients without SI (p=0.03).
Conclusion: Corticosteroid use, exposition to more than one biologic, smoking and renal failure are associated with serious infections in RA
patients on bDMARDs.
Disclosure: M. de la Vega, None; G. Casado, None; G. Citera, AbbVie, Bristol-Myers Squibb, Janssen, Novartis, Pfizer Inc, 5,Novartis,
Pfizer Inc, 2,AbbVie, Bristol-Myers Squibb, Janssen, Novartis, Pfizer Inc, 5; I. M. M. Laurindo, None; G. Christopoulos, None; M. A.
Descalzo, None; R. Ranza, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/corticosteroid-use-biologic-therapy-switching-smoking-

and-renal-failure-are-associated-with-serious-infections-in-rheumatoid-arthritis-patients-treated-with-biologics-data-from-two-latin-
american-r
the Usefulness of Cytomegalovirus Infection Strategy in Patients with Connective-Tissue

Disease, Based on the Guidelines of the Japan Society for Hematopoietic Cell
Transplantation 2011
Rika Suzuki1, Yasuyoshi Kusanagi2, Takashi Nakanishi2, Hideyuki Horikoshi3, Fumihiko Kimura1 and Kenji Itoh1, 1Department of
Hematology and Rheumatology, Division of Internal medicine, National Defense Medical College, Saitama, Japan, 2Department of
Hematology and Rheumatology, Division of Internal medicine, National Defence Medical College, Tokorozawa, Japan, 3National Defence
Medical College, Tokorozawa, Japan
SESSION INFORMATION
Background/Purpose: Cytomegalovirus (CMV) infection is a life-threatening complication in immunocompromized hosts. There are no
official guidelines for CMV infection management in patients with connective-tissue diseases (CTD) under immunosuppressive therapy.
CMV infection management according to the guidelines of the Japan Society for Hematopoietic Cell Transplantation (JSHCT) 2011 was
performed in CTD patients and its usefulness and safety were evaluated.
Methods: We retrospectively examined 98 CTD patients who were admitted to the National Defense Medical College Hospital from
October 2012 to March 2017, and were receiving ≥20 mg/day of prednisolone. CMV infection was defined by the detection of CMV pp65
antigenemia. CMV disease was diagnosed by both detection of CMV pp65 antigenemia and the involvement of organs due to CMV
reactivation. We managed the CMV infection according to the guidelines. The primary endpoint was mortality and major organ involvement
due to CMV infection. We also evaluated the risk factors for CMV reactivation and intervention after scoring positive for CMV antigenemia.
Results: Sixty-six cases of positive CMV pp65 antigenemia occurred in the 98 patients. An antiviral drug was administered in accordance
with the JSHCT guidelines in 36 cases (treatment group). The patients in the remaining 30 cases did not receive treatment (observation
group). No patients died due to CMV disease. Four patients in the treatment group died due to renal failure, Pneumocystis pneumonia or
deterioration of adult-onset Stillfs Disease, in observation group none died. Persistent major organ involvement due to CMV infection did not
occur in either groups. The risk factors for CMV reactivation were older age and steroid pulse therapy. The risk factor for CMV disease was
CMV test positivity in the early period (<4 weeks) of steroid therapy. Thrombocytopenia is the most common manifestation of CMV disease.
Conclusion: This study demonstrates the usefulness of CMV infection management according to the JSHCT guidelines for CTD patients
under immunosuppressive therapy.
Disclosure: R. Suzuki, None; Y. Kusanagi, None; T. Nakanishi, None; H. Horikoshi, None; F. Kimura, None; K. Itoh, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-usefulness-of-cytomegalovirus-infection-strategy-in-

patients-with-connective-tissue-disease-based-on-the-guidelines-of-the-japan-society-for-hematopoietic-cell-transplantation-2011
Reasons Why Patients Failed Vaccinations Vs Influenza and Pneumococcus.

Monocentric Cross-Sectional Study.
Maria Chiara Ditto1, Alberto Batticciotto1, Maria Chiara Gerardi1, Federica Rigamonti2, Rossella Talotta1 and Piercarlo Sarzi-Puttini1,
1Rheumatology Unit, ASST Fatebenefratelli - Sacco, L. Sacco University Hospital, Milano, Italy, 2Rheumatology Unit, ASST
Fatebenefratelli - Sacco, L. Sacco University Hospital, Milan, Italy
SESSION INFORMATION
Background/Purpose: immunosuppressive therapies and bDAMRDs expecially, increase the risk of infections. According to the EULAR
guidelines, all patients affected by autoimmune/inflammatory diseases should receive vaccinations against influenza and pneumococcus. The
primary aim of this work is to evaluate the prevalence of flu and pneumococcal vaccinations in a cohort of patients affected by inflammatory
arthritides and SLE treated with biological drugs. The secondary aim was to explore the reason why patients do not receive vaccination.
Methods: we administered a self-reporting questionnaire about both flu and pneumococcal vaccination, to 274 consecutive patients from
February to April 2017 treated with bDMARDs.
Results: the 65.3% of patients declared to have been informed from rheumatologist about the possibility to received vaccinations during
biological treatments but the 19.5% declared to have never been informed about them. The 46% of patients vaccination for influenza was
performed after rheumatology suggestion and the 21% after their general pratictioner suggestion, while the 30.1% has declared to have not
performed it for several reasons: because concerned about adverse events (5.1%), beacause they don't see it as useful (17.4%) or for other
reasons. The injection has been administered for free in the majority of patients (GPs 36.8%, local healthcare 33.5%). The 60.9% would
have undergone vaccination even for a fee. The anti pneumococcal vaccination was administered to the 25.3%, while to the 50.3% has never
been suggested to do it. The 4.4% has declared to have not performed it because concerned about adverse events and the 6.6% because they
don't see it as useful. The injection has been administered for free at local healthcare facilities in the 84% of the patients. The 97.3% would
have undergone vaccination even for a fee. At last the patients have declared to have always been well informed about vaccinations (48,9%),
to have been well informed only about certain vaccinations (9,5%) or to have been informed only after asking (9,1%); The 19.1% was
unsatisfied.
Conclusion: the acquired vaccine rate has been low for the influenza vaccination (<60%) and extremely low for the pneumococcal
vaccination (26%). Even if the reasons of this results are partially attributable to a low patients' compliance (47.5% for the influenza
vaccination, 11% for the anti pneumococcical vaccination), almost 20% has declared not to have ever been informed about vaccinations. So
an additional effort to improve these results is mandatory.
Disclosure: M. C. Ditto, None; A. Batticciotto, None; M. C. Gerardi, None; F. Rigamonti, None; R. Talotta, None; P. Sarzi-Puttini,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/reasons-why-patients-failed-vaccinations-vs-influenza-

and-pneumococcus-monocentric-cross-sectional-study
Direct Medical Costs Associated with the Extrahepatic Manifestations of Hepatitis C

Virus Infection in France
Patrice Cacoub1, Mathieu vautier2, Anne-Claire Desbois3, David Saadoun4 and Zobair Younossi5, 1Department of Internal Medicine and
Clinical Immunology, Groupe Hospitalier Pitié-Salpêtrière, Paris, France, 2Médecine Interne 1, Hôpital Pitié-Salpêtrière, Paris, France,
3Hôpital Pitié-Salpêtrière, Internal Medicine and Clinical Immunology, Paris, France, 4Sorbonne Universités, UPMC Univ Paris 06, UMR
7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75005, Paris, France; INSERM, UMR_S 959, F-75013,
Paris, France; CNRS, FRE3632, F-75005, Paris, France; AP-HP, Groupe Hospitalier, Paris, France, 5Medicine, Inova Fairfax Hospital,
Falls Church, Falls Church, VT
SESSION INFORMATION
Background/Purpose: The economic impact of the extrahepatic manifestations (EHM) of hepatitis C virus (HCV) infection remains unknown
for France. To estimate the prevalence of HCV-EHM and the direct medical costs associated with HCV-EHM in France.
Methods: Estimates of thirteen EHM prevalence were obtained (i) from a retrospective data analysis of HCV-infected patients in
specialized center in France, and the baseline prevalence in the general French population and (ii) from an international systematic review
and meta-analysis. Per-patient-per-year (PPPY) inpatient, outpatient and medication costs to treat EHM in France were obtained from the
literature, national databases, or expert opinion. The impact of achieving SVR after antiviral therapy was applied to the French healthcare
costs.
Results: Using approach (i), increased EHM prevalence rates in HCV patients compared to the general population were observed for most
EHM, including cryoglobulinemia vasculitis (51.5% vs. 1.5%), rheumatoid-like arthritis (47.8% vs. 0.1%) and lymphoma (14.2% vs.
0.24%). The mean PPPY cost of EHM in the French tertiary center was 3,296 € [95% CI 1,829; 5,540]. In France, HCV-EHM amounted to a
total cost of 215 million (M) € per year [144; 299]. Using approach (ii), the mean PPPY cost of EHM in France was estimated to be 1,117 €.
The estimated total cost reduction in France associated with SVR was 13.9 M€ for diabetes, 8.6 M€ for cryoglobulinemia vasculitis, 6.7 M€
for myocardial infarction, 2.4 M€ for end-stage renal disease, and 1.4 M€ for stroke.
Conclusion: Extrahepatic manifestations of HCV infection substantially add to the overall economic burden of HCV infection in France.
Sustained virological response after antiviral therapy is expected to significantly reduce the total costs of managing HCV-EHM in France.
Disclosure: P. Cacoub, None; M. vautier, None; A. C. Desbois, None; D. Saadoun, None; Z. Younossi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/direct-medical-costs-associated-with-the-extrahepatic-

manifestations-of-hepatitis-c-virus-infection-in-france
The Value of Imaging As an Early Noninvasive Test for Prosthetic Joint Septic Arthritis
Kevin Byrne 1, Mary Louise Fowler2, Sarah Lieber3, Robert Shmerling4 and Ziv Paz3, 1Boston University School of Medicine, Boston, MA,
22Boston University School of Medicine, Boston, MA, 3Beth Israel Deaconess Medical Center, Boston, MA, 4Rheumatology, Beth Israel
Deaconess Medical Center, Boston, MA
SESSION INFORMATION
Background/Purpose: Medical imaging is commonly obtained in evaluating patients with suspected prosthetic joint septic arthritis (PJSA);
it may be helpful to detect other pathology in the joint (e.g., chondrocalcinosis), to establish a baseline, or to detect the presence of synovial
fluid. Imaging may even help diagnose PJSA, but there is little data available to evaluate the value of various imaging modalities for the
diagnosis of PJSA.
Objectives: To examine how the use of medical imaging for PJSA has changed over the 17 years of this study and to assess the value of
different imaging modalities in differentiating patients with culture-positive PJSA from patients with culture-negative PJSA.
Methods: We conducted a retrospective study that included all patients ages 18 years and older who were diagnosed with monoarticular
PJSA and underwent surgical intervention at a single, tertiary-care hospital between 1997 and 2014.
Results: Of the 280 patients with diagnosed PJSA, 214 (76.4%) had at least one imaging study during the index admission. Radiographs
were performed in 167 patients (59.6%). The second most common imaging modality was CT scan (17 patients; 6.1%). The most common
imaging findings were joint effusion in 91 (32.5%) patients and soft tissue swelling in 41 (14.6%) patients. Of the 280 patients assigned a
diagnosis of PJSA, 190 (69.3%) were culture-positive. Patients with culture-positive PJSA were less likely to have normal findings in their
plain radiographs (3.7 vs. 13.1%, p=0.007), more likely to have gas/free air (7.4 vs. 1.2%, p=0.043), but no more likely to have joint
effusions (28.9 vs. 25.0%, p=0.56) or soft tissue swelling (13.2 vs. 8.3%, p=0.31). The percentage of patients receiving each imaging
modality remained relatively constant over the course of the study (Figure 1).
Conclusion: Imaging studies—especially radiographs—are commonly ordered to evaluate patients with suspected PJSA. Our study
demonstrates that patients with culture negative PJSA are more likely to have normal findings on imaging, including radiographs. Patients
with culture-positive PJSA were significantly more likely to have radiographic findings of gas or free air. Imaging studies in general and
radiographs in particular demonstrated joint effusions in patients at similar rates among PJSA patients with and without positive cultures.
This study demonstrates that in most cases imaging studies have limited utility among patients with suspected PJSA and cannot be relied upon
to demonstrate specific findings to suggest the diagnosis.
Figure 1: Trend over time for the percentage of patients receiving different modalities of imaging studies. The line labeled “Overall”
indicates the percentage of patients receiving any form of imaging study.
Disclosure: K. Byrne, None; M. L. Fowler, None; S. Lieber, None; R. Shmerling, None; Z. Paz, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-value-of-imaging-as-an-early-noninvasive-test-for-

prosthetic-joint-septic-arthritis
Metabolic Activity Sustains Macrophage Cytokine Production in Rheumatoid Arthritis

and Coronary Artery Disease
Cornelia M. Weyand1, Markus Zeisbrich1, Lukas Brosig2, Barbara Wallis1, Niall Roche3, Janice Lin1 and Jorg Goronzy4, 1Medicine:
Immunology and Rheumatology, Stanford University, Stanford, CA, 2Medicine: Immunology and Rheumatology, Stanford University, Stanfod,
CA, 3The Arthritis Center, Pleasanton, CA, 4Medicine/Division of Immunology & Rheumatology, Stanford University School of Medicine,
Stanford, CA
SESSION INFORMATION
Session Title: Innate Immunity and Rheumatic Disease Poster I
Background/Purpose: Accelerated atherosclerosis has become increasingly recognized as a complication of chronic inflammatory disease,
such as in patients with rheumatoid arthritis (RA). RA patients have a 2-fold increased risk of developing coronary artery disease (CAD)
regardless of traditional risk factors and cardiovascular complications substantially contribute to their increased mortality. The inflammatory
lesions in RA and CAD share the chronicity of tissue-destructive immune responses, with macrophages representing abundant effector cells.
Methods: Patients with RA who fulfilled 2010 ACR/EULAR RA Classification Criteria and patients with CAD (history of at least one
myocardial infarction) were enrolled together with healthy age-matched controls. Monocytes were isolated from peripheral blood and
differentiated into macrophages with macrophage colony-stimulating factor. Macrophages were polarized into M1 cells with IFN-γ and
lipopolysaccharide. Mitochondrial reactive oxygen species (ROS) were quantified by MitoSOX staining and their production was inhibited
with the ROS scavenger mitoTEMPO. Cellular ATP concentrations were quantified by fluorometric assay. Glycolytic rates and oxygen
consumption were measured by Seahorse Flux Analyzer experiments. Relative gene expression was analyzed by quantitative RT-PCR and
adjusted for β-actin transcripts.
Results: Seahorse experiments demonstrated increased glycolytic rates (ECAR) in RA and CAD macrophages compared to age-matched
healthy controls. Key enzymes of glycolysis, HK-1 and PKM-2, were upregulated as well as GLUT-1, the main glucose uptake receptor in
macrophages. The breakdown of glucose resulted in high mitochondrial activity characterized by an increase in mitochondrial membrane
potential and by greater oxygen consumption, with mitochondria from CAD macrophages respiring even more than those from RA
macrophages. Pharmaceutical uncoupling of the electron transport chain was used to measure maximal mitochondrial respiration. Notably,
CAD mitochondria had explicitly more reserve capacity to work against imminent energy deficits and RA mitochondria still showed higher
capacity than healthy ones. A byproduct of enhanced mitochondrial respiration is the generation of mitochondrial ROS, which was confirmed
by MitoSOX staining to be substantially higher in patient-derived macrophages. Production of pro-inflammatory key cytokines of the synovial
joint and the atherosclerotic plaque was directly related to mitochondrial activity, as indicated by the effective inhibition of IL-6, IL-1b, IL-
18, and IL-23 when cells were pretreated with mitoTempo, a ROS-scavenger that specifically targets mitochondria-derived superoxide.
Conclusion: Macrophages from RA and CAD patients share a distinct metabolic profile characterized by upregulated glycolysis and high
mitochondrial activity; fueling excess production of ROS and cytokines. Metabolic activity directly regulates the macrophages’ inflammatory
potential and might contribute to accelerated atherosclerosis in RA patients.
Disclosure: C. M. Weyand, None; M. Zeisbrich, None; L. Brosig, None; B. Wallis, None; N. Roche, None; J. Lin, None; J. Goronzy,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/metabolic-activity-sustains-macrophage-cytokine-

production-in-rheumatoid-arthritis-and-coronary-artery-disease
Liver X Receptor-α (LXRα) Modulates Macrophage Phenotype and Disease Activity in

SLE
Shuhong Han1, Haoyang Zhuang1, Pui Lee2, Stepan Shumyak1, Jingfan Wu1, Chao Xie3, Hui Li3, Lijun Yang3 and Westley Reeves4,
1Medicine, University of Florida, Gainesville, FL, 2Harvard Medical School, Boston, MA, 3Pathology, Immunology and laboratory
medicine, University of Florida, Gainesville, FL, 4Rheumatology & Clinical Immology, University of Florida, Gainesville, FL
SESSION INFORMATION
Background/Purpose: LXRα is an oxysterol-regulated transcription factor that plays a key role in reverse cholesterol transport by inducing
the expression of ATP binding cassette A1 (ABCA1) and other genes. LXRα also promotes macrophage (Mϕ) polarization away from
proinflammatory (classically activated, M1) toward alternatively activated (M2) Mϕ. M1 Mϕ are metabolically dependent on glycolysis,
whereas M2 Mϕ require oxidative metabolism. Hypoxia-inducible factor 1-α (HIF1α), a key regulator of glycolysis, promotes M1 Mϕ
polarization. We have shown that Mϕ depletion prevents diffuse alveolar hemorrhage (DAH) in mice with pristane-induced lupus. The
present study explored the mechanisms involved.
Methods: Murine Mϕ subsets were phenotyped by flow cytometry and the cell subsets were flow-sorted. Gene expression in SLE patients
and mice with pristane-lupus was determined using RNA-Seq and real-time PCR. Cell metabolism was evaluated by extracellular flux
analysis (Seahorse assay). Pristane-treated C57BL/6 mice received daily injections of the synthetic LXR agonist T0901317 (or vehicle) for
14-d after which we assessed DAH.
Results: Peritoneal Mϕ from pristane-treated mice had an M1 phenotype with high CD274, Ly6C, CD86, and TNFa expression and low
CD273, Ym1, and IL-10 vs. mice treated with mineral oil (MO), a control inflammatory oil that does not cause lupus. MO treatment induced
the opposite pattern from pristane, consistent with an M2 phenotype. Glycolytic metabolism (extracellular acidification rate, ECAR) was
higher in pristane-treated mice (M1-like) whereas oxidative metabolism (oxygen consumption rate, OCR) was higher in MO-treated mice
(M2-like). HIF1α and the HIF-regulated gene phosphofructokinase (PFKL) were higher in pristane-treated mice whereas LXRα and the LXR-
regulated gene ABCA1 were higher in MO-treated mice. Similarly, SLE patients’ monocytes exhibited low LXRα/ABCA1 and high
HIF1α/PFKL expression vs. healthy controls consistent with M1 polarization. T0901317 inhibited type I interferon and increased ABCA1 in
vitro in both SLE patients’ monocytes and in mice. In pristane-lupus, T0901317 re-polarized Mϕ to M2, increased Mϕ OCR, and decreased
TNFα. It also completely abolished autoimmune lung disease (DAH).
Conclusion: Mϕ may play a more important role in SLE than previously recognized. Murine and human SLE both are associated with low
LXR activity in Mϕ and monocytes. Our data suggest that high LXRa activity is a marker for the generation of M2 Mϕ, which mediate the
resolution of chronic inflammation, while protecting from end-organ disease in lupus. LXR agonist therapy prevents DAH in mice and raises
ABCA1 expression on patients’ monocytes in vitro, suggesting a possible therapeutic role in SLE.
Disclosure: S. Han, None; H. Zhuang, None; P. Lee, None; S. Shumyak, None; J. Wu, None; C. Xie, None; H. Li, None; L. Yang, None;
W. Reeves, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/liver-x-receptor-%ce%b1-lxr%ce%b1-modulates-

macrophage-phenotype-and-disease-activity-in-sle
Serum Amyloid a Aggravates Rheumatoid Arthritis By Activating NFAT5-Mediated

Migration of Macrophages
Yu-Mi Kim Sr.1, Donghyun Kim Sr.1, Seung-Ah Yoo Sr.2, Jung Hee Koh Sr.2, Jin-Sun Kong Sr.2 and Wan-Uk Kim Sr.3, 1Center for
Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea, Seoul, Korea, Republic of (South), 2The Catholic
University of Korea, Center for Integrative Rheumatoid Transcriptomics and Dynamics, seoul, Korea, Republic of (South), 3The Catholic
University of Korea, Department of Internal Medicine, seoul, Korea, Republic of (South)
SESSION INFORMATION
Background/Purpose: Serum amyloid A (SAA) is an acute phase protein and its serum levels may increase up to 1000-fold over normal
levels during inflammation, triggering perpetual inflammatory responses. The level of SAA has been reported to have a correlation with
rheumatoid arthritis (RA) symptoms. However, the direct role of SAA in the RA pathogenesis remains unclear. In this study, we have
identified that SAA contributes to the activation of macrophages through induction of nuclear factor of activated T cells 5 (NFAT5), resulting
in the aggravation of arthritic symptoms.
Methods: Expression of NFAT5 was examined in the SAA-treated macrophages using Western blot analysis and immunofluochemistry. The
transcriptional activation of NFAT5 was measured by luciferase reporter assay and Matrigel assay. To find the receptor and signaling
pathway involved in the SAA-induced NFAT5 expression, chemical inhibitors and genetically deficient macrophages were used. The cell
migrations were compared between wild type and NFAT5 knock-down or knock-out macrophages by using transwell migration assay,
wound-healing assay and air-pouch mouse model. To confirm the importance of SAA-NFAT5 axis in vivo, we injected SAA into the arthritis
mouse model induced by injection of methylated-bovine serum albumin/interlukin-1β (mBSA/IL-1β).
Results: SAA induced the expression and activation of NFAT5 in macrophages, which is mediated by TLR2 and TLR4 on their surface.
MAPKs and PI3K signaling pathways, especially JNK1/2, were involved in the NFAT5 expression induced by SAA treatment. The induced
NFAT5 contributed to the cytoskeletal rearrangement in macrophages, thereby leading to the cell migration in vitro and in vivo. Moreover,
SAA injection aggravated disease severity, including increased macrophages, in the joints of mBSA/IL-1β-induced arthritis.
Conclusion: Our data show novel findings that SAA could induce the activation and migration of macrophages by stimulating the expression
and activity of NFAT5 through TLR2/4 and MAPKs signaling pathways. Moreover, Increased SAA could contribute to the aggravation of
arthritis symptoms in the mouse model. Thus, targeting SAA-NFAT5 axis may potentially be of therapeutic value in chronic inflammatory
diseases accompanied by elevated SAA levels, such as rheumatoid arthritis.
Disclosure: Y. M. Kim Sr., None; D. Kim Sr., None; S. A. Yoo Sr., None; J. H. Koh Sr., None; J. S. Kong Sr., None; W. U. Kim Sr., the
National Research Foundation of Korea, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/serum-amyloid-a-aggravates-rheumatoid-arthritis-by-

activating-nfat5-mediated-migration-of-macrophages
Anti-TNF Agents Induce Alternative Macrophages

Yannick Degboé 1, Benjamin Rauwel2, Michel Baron2, Jean Frédéric Boyer2, Alain Cantagrel2, Arnaud Constantin3 and Jean-Luc
Davignon2, 1Centre de Physiopathologie Toulouse Purpan, INSERM UMR 1043, Toulouse, France, 2CPTP, INSERM UMR 1043, Toulouse,
France, 3Department of Rheumatology, Purpan Hospital, Toulouse III University, Toulouse, France, Toulouse, France
SESSION INFORMATION
Background/Purpose:
Macrophages contribute to the pathogenesis of rheumatoid arthritis (RA). They can display various states of activation or « polarization »,
characterized by distinct functions and plasticity. M1 polarization corresponds to the “classical”, pro-inflammatory activation as identified in
RA. M2 “alternative” polarizations display immunoregulatory and wound-healing properties. Data concerning the effects of RA anti-cytokine
biological drugs (bDMARDs) on macrophage polarization are scarce.
We aimed to assess in vitro modulation of macrophage polarization by RA bDMARDs.
Methods:
Blood monocytes from 15 healthy controls and 10 RA patients were positively sorted by CD14+ magnetic selection. Macrophages were
Derived from Monocytes (MDM) by 5 days of culture in the presence of MCSF, and activated or not for 24h as M1 pro-inflammatory MDM
(by LPS + IFNγ) or as M2 alternative MDM by IL10 or IL4, respectively M2(IL10) and M2(IL4). M1 MDM were cultured with or without
bDMARDs.
We evaluated 2 anti-TNF agents (etanercept (ETA), adalimumab (ADA)), 1 anti-IL6R agent (tocilizumab (TCZ)), and 1 anti-CD20 agent
(rituximab (RTX)) used as control monoclonal antibody. bDMARDs effects were assessed on M1 activation phase by flow cytometric
analysis of membrane markers. Functional aspects of polarization were assessed by analysis of cytokine production in cell culture
supernatants (cytometric bead array and ELISA) and phagocytosis (flow cytometry).
M1 MDM cultured in the presence of bDMARDs were compared to untreated M1 MDM by a Wilcoxon matched pairs test.
Results:
We validated membrane polarization markers in our culture model: CD40 and CD80 as M1 (LPS + IFNγ) markers; CD16, CD163, MerTK
and CD64 as M2(IL10) markers, CD206 and CD200R as M2(IL4) markers.
When compared to MDM from healthy controls, MDM from RA patients displayed a biased plasticity: they significantly expressed higher
levels of M1 markers after M1 activation and expressed lower levels of CD16 after differentiation or M1 and M2 activations.
Concerning the effect of bDMARDs on surface markers after M1 activation (M1 MDM): in RA patients and healthy controls, anti-TNF
agents induced a significant decrease in M1 markers and a significant modulation in M2(IL10) markers. We observed (i) a decrease in CD40
and CD80, (ii) an increase in CD16, CD163, and MerTK, (iii) a decrease in CD64 with ETA and an increase with ADA. TCZ induced a
slight but significant decrease in CD40 and an increase in CD64. RTX only increased CD64.
Anti-TNF agents led to a significant modulation of cytokines produced by M1 MDM from healthy controls: we observed a decrease in
TNFα, IL6, IL12 and IL10 levels, and an increase in TGFβ. TCZ mainly affected IL6 and TNFα productions with a significant decrease. No
significant effect was observed with RTX.
In healthy controls, phagocytosis was superior in M2(IL10) and M2(IL4) activated MDM than in M1 MDM. Anti-TNF agents, but neither
TCZ nor RTX, induced an increase of phagocytosis in M1 MDM.
Conclusion:
Anti-TNF agents modulate the phenotype of MDM from healthy donors as well as from RA patients. They up-regulate M2 alternative
properties and downregulate M1 inflammatory properties in macrophages.
Disclosure: Y. Degboé, Pfizer Inc, 2; B. Rauwel, None; M. Baron, None; J. F. Boyer, None; A. Cantagrel, None; A. Constantin, Pfizer
Inc, 2; J. L. Davignon, Pfizer Inc, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/anti-tnf-agents-induce-alternative-macrophages
The Rheumatoid Arthritis Susceptibility Gene C5orf30 Is an Immunomodulator in

Macrophages
Emma Dorris1, Karen Creevey1, John Moylett1, Simon Tazzyman2, Munitta Muthana2 and Anthony G. Wilson1, 1UCD School of Medicine
and Medical Science, Conway Institute, University College Dublin, Dublin, Ireland, 2University of Sheffield Medical School, Sheffield,
United Kingdom
SESSION INFORMATION
Background/Purpose: rs26232 in the first intron of C5orf30 has been associated with risk of developing rheumatoid arthritis (RA) and
severity of tissue damage. C5orf30 is highly expressed by RA synovial fibroblasts (RASF) and macrophages. Inhibition of C5orf30 in RASF
results in increased cellular invasiveness and migration in vitro and inhibition in the collagen-induced arthritis model accentuated joint
inflammation and damage. There is no published data on the biological activities of C5orf30 in macrophages.
Methods: Monocyte cell line (THP1) and primary monocyte-derived macrophages (MDM) were used. C5orf30 mRNA was assessed by
qPCR and protein via Western blot. Transcript and protein half-lives were assessed using actinomycin D and cyclohexamide. Polarization to
M1 and M2a phenotypes and stimulation with TNF and LPS on C5orf30 expression were compared. C5orf30 levels were manipulated using
siRNA and functional effects on macrophage biology was assessed using ELISAs, invasion assays, pathogen phagocytosis assays, reactive
oxygen species assays, gene expression and intracellular signalling assays. In vivo, antisense morpholino oligonucleotides were used to
knockdown C5orf30 in zebrafish. Confocal imaging was used to assess the number of invading macrophages.
Results: C5orf30 has a half-life of 3.13 hours, which does not significantly change with the addition of inflammatory (LPS +IFNγ) or anti-
inflammatory (IL-4) stimuli. Protein half-life is 19.54 hours, rising to 22.05 hours when pretreated with LPS+ IFNγ (M1-like) and decreasing
to 15.07 hours when pretreated with IL-4 (M2a-like). Polarization to M2a increased C5orf30 protein expression whereas polarization to M1
resulted in phosphorylation of C5orf30 protein and decreased expression of C5orf30 (p=0.01). Treatment with TNF or LPS reduced C5orf30
expression (TNF p=0.001, LPS p=0.02). LPS phosphorylates C5orf30. Pretreatment of cells with the JNK inhibitor SP600125 retarded the
phosphorylation of C5orf30 in response to LPS in a dose-dependent manner and prevented downregulation of C5orf30 gene expression.
Knockdown of C5orf30 reduced the invasive capacity of macrophages (p=0.003) with an associated decrease in MMP1 (p=0.01), MMP3
(p=0.01) and MMP9 (p=0.03). Decrease in invasion was intensified upon incubation with either TNF (p=0.02) or LPS (p=0.01). C5orf30
knockdown increased phagocytosis when co-stimulated with LPS (p=0.01). C5orf30 knockdown also increased activation of the JNK
pathway. In vivo, tail amputations in zebrafish with C5orf30 deficient embryos showed an increased macrophage infiltration at the wound
site (p=0.01).
Conclusion: Stimulation with inflammatory mediators induces phosphorylation of C5orf30 and downregulates C5orf30 gene expression,
whereas treatment with anti-inflammatory signals increases C5orf30 protein expression. C5orf30 knockdown enhanced the proinflammatory
macrophage phenotypes of phagocytosis and JNK activation whilst diminishing the tissue-clearing (M2-like) phenotype of macrophage
invasion. This data indicates an important role for C5orf30 in the immunomodulatory regulation of macrophages and is consistent with our
previous findings in RASF.
Disclosure: E. Dorris, None; K. Creevey, None; J. Moylett, None; S. Tazzyman, None; M. Muthana, None; A. G. Wilson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-rheumatoid-arthritis-susceptibility-gene-c5orf30-is-

an-immunomodulator-in-macrophages
HDL Modified with Malondialdehyde-Acetaldehyde (MAA) Is Bound and Rapidly

Internalized By Human THP-1 Monocytes
Michael J. Duryee 1, Dahn L Clemens2, Logan M. Duryee2, Karen C. Easterling3, Carlos D. Hunter4, Lynell W. Klassen5, James R. O'Dell6,
Daniel R. Anderson2, Ted R. Mikuls5 and Geoffrey M. Thiele2, 1Research Services, Omaha VA Medical Center, Omaha, NE, 2University of
Nebraska Medical Center, Omaha, NE, 3Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE,
4Internal Medicine Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, 5Veteran Affairs Nebraska-Western
Iowa Health Care System and University of Nebraska Medical Center, Omaha, NE, 6Department of Internal Medicine, University of
Nebraska Medical Center, Omaha, NE
SESSION INFORMATION
Background/Purpose: Rheumatoid arthritis (RA) is associated with an increased cardiovascular disease (CVD) burden, one that appears to
be mitigated by increased concentrations of circulating HDL resulting from effective disease-modifying treatment. Our group has
demonstrated that proteins modified with malondialdehyde-acetaldehyde (MAA), are present in the synovial tissues of RA patients and
atherosclerotic lesions from non-RA patients with CVD. Previous data has also shown that MAA-modified proteins are bound and
internalized by scavenger receptors (SRs) (SRA, SRBI, LOX-1, and CD36) present on immune cells. Therefore, in this study we evaluated
whether HDL is modified by MAA and bound or internalized by monocytes.
Methods: Human HDL was labeled with 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate (DIL-HDL). For MAA
modification DIL-HDL (1 mg/ml) was incubated with 2mM malondialdehyde and 1mM acetaldehyde for 3 days and fluorescence of the
dihydropyridine structure determined. To evaluate receptor mediated binding and internalization, PMA activated THP-1 cells (human
monocytic) were incubated on ice at either 4oC or 37oC (respectively) for 90 minutes with 25 μg/ml of DIL-Albumin, DIL-HDL and DIL-
HDL-MAA. Cells were washed, fixed in paraformaldehyde, and subjected to flow cytometry at 594 nm wavelength. Analysis was
performed using FlowJo V10. Data are expressed as percent positive compared to the DIL-labeled human albumin.
Results: Human HDL was modified at 30,000 fluorescent units (FU), which was greater than the MAA modification observed for human
serum albumin (22,000 FU). As shown in the Figure, THP-1 cells bound HDL (41.73%) at the cell surface significantly better than HDL-
MAA (17.55%; P<0.001). Internalization studies revealed that HDL-MAA (48.9%) was taken up more by the cells than HDL (39.14%)
alone, although this difference did not achieve statistical significance.
Conclusion: These data show that HDL can be modified with the MAA adduct and HDL-MAA is subsequently bound and internalized by
human monocytes. THP-1 cells contain multiple scavenger receptors capable of binding and internalizing altered self-ligands as a normal
clearance mechanism. These results demonstrate that HDL modified with MAA is bound at lower levels that HDL alone, but is internalized
more efficiently by human monocytes Taken together, these results suggest that MAA modification could impact cellular trafficking of HDL,
thus influencing CVD pathogenesis in conditions characterized by oxidative stress and increased MAA adduct formation.
Disclosure: M. J. Duryee, None; D. L. Clemens, None; L. M. Duryee, None; K. C. Easterling, None; C. D. Hunter, None; L. W. Klassen,
None; J. R. O'Dell, Medac, 5,Coherus, 5; D. R. Anderson, None; T. R. Mikuls, BMS, 2,Ironwood Pharm, 2,Pfizer Inc, 5,NIH, VA, 2; G. M.
Thiele, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/hdl-modified-with-malondialdehyde-acetaldehyde-maa-

is-bound-and-rapidly-internalized-by-human-thp-1-monocytes
Characterization of Neutrophil Subsets and Neutrophil Extracellular Traps in Pyogenic

Arthritis, Pyoderma Gangrenosum and Acne (PAPA) Syndrome
Pragnesh Mistry1, Carmelo Carmona-Rivera1, Nickie Seto1, Monica Purmalek1, Amanda Ombrello2, Ivona Aksentijevich2, Daniel L.
Kastner2 and Mariana J. Kaplan1, 1Systemic Autoimmunity Branch, NIAMS/NIH, Bethesda, MD, 2Inflammatory Disease Section,
NHGRI/NIH, Bethesda, MD
SESSION INFORMATION
Background/Purpose: Pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is an autosomal dominant autoinflammatory
disorder caused by mutations in the PSTPIP1/CD2BP1 gene. PAPA syndrome is characterized by recurrent flares of sterile arthritis and
severe skin inflammation in the absence of adaptive immune responses. Mutations in PSTPIP1 likely dysregulate the pyrin inflammasome
leading to exuberant IL-1β production. PAPA patients respond to treatment with cytokine inhibitors, including IL-1 inhibitors. Neutrophils
can undergo a form of cell death called NETosis where dying cells release a meshwork of decondensed DNA decorated with granule
proteins called neutrophil extracellular traps (NETs). NETs have been shown to induce tissue damage in other systemic diseases. While
previous studies have suggested that neutrophils may play critical roles in driving inflammation in PAPA syndrome, the mechanism by which
it happens is still unclear. A subset of proinflammatory neutrophils called low-density granulocytes (LDGs) has been identified in other
autoimmune/autoinflammatory conditions and these cells display an enhanced capacity to form NETs. Here, we aimed to elucidate the role of
neutrophil subsets and NETs in the pathogenesis of PAPA syndrome.
Methods: Normal density neutrophils were isolated by dextran sedimentation from control and PAPA patients. LDGs were isolated by
negative selection from the PBMC fraction. Immunofluorescence (IF) was used to assess the presence of NETs. To assess the effect of serum
in NET formation, control neutrophils were incubated with 10% serum from control or PAPA patients in the presence or absence of the IL-1
receptor anatagonist anakinra for 2 h. Circulating NET remnants were quantified by ELISA against citrullinated histone H3 (citH3)-DNA
complexes. A skin biopsy from a PAPA patient was analyzed by IF, quantitative PCR, and western blot analysis for the presence of NETs
and proinflammatory cytokines.
Results: LDGs were detected in PAPA patients. Neutrophils and LDGs from PAPA patients displayed an enhanced capacity to
spontaneously form NETs when compared to control neutrophils. Serum from PAPA patients induced NET formation in control neutrophils
and this process was inhibited in the presence of IL-1 inhibitor, anakinra. NET products, as measured by cit-H3-DNA complexes in plasma
from PAPA patients, were significantly higher when compared to control plasma. We detected NETs in a skin biopsy from a PAPA patient,
in association with upregulation of tissue IL-1β and IL-8 when compared to healthy skin biopsies. Furthermore, an immature granulocyte
signature was detected in the skin biopsy tissue suggesting the presence of LDGs.
Conclusion: Taken together, neutrophils and LDGs in PAPA patients display dysregulated NET formation as assessed by in vitro
spontaneous NET formation and the presence of circulating NET remnants. Proinflammatory cytokines in serum and affected tissues of PAPA
patients trigger the NET formation. Anakinra ameliorates serum-induced NETosis, suggesting a role of IL-1 signaling in NETosis. The
identification of LDGs in skin tissue from PAPA patients point out a strong myeloid signature in this condition.
Disclosure: P. Mistry, None; C. Carmona-Rivera, None; N. Seto, None; M. Purmalek, None; A. Ombrello, None; I. Aksentijevich, None;
D. L. Kastner, None; M. J. Kaplan, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/characterization-of-neutrophil-subsets-and-neutrophil-

extracellular-traps-in-pyogenic-arthritis-pyoderma-gangrenosum-and-acne-papa-syndrome
A Novel Real-Time Imaging Technique to Quantify Neutrophil Extracellular Traps and

Distinguish Mechanisms of Cell Death in Neutrophils
Sarthak Gupta1, Diana Chan2, Kristien Zaal3, Evelyn Ralston4 and Mariana J. Kaplan2, 1Systemic Autoimmunity Branch, National Institue
of Arthritis, and Musculoskelatal and Skin Diseases/NIH, Bethesda, MD, 2Systemic Autoimmunity Branch, National Institute of Arthritis and
Musculoskeletal and Skin Diseases/NIH, Bethesda, MD, 3Light Imaging Section, Office of Science and Technology, National Institute of
Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 4Light Imaging Section, Office of Science and
Technology, National Institute of Arthritis and Musculoskeletal and Skin Diseases/NIH, Bethesda, MD
SESSION INFORMATION
Background/Purpose: Neutrophils play a key role in host defenses and have recently been implicated in the pathogenesis of autoimmune
diseases by several mechanisms including formation of neutrophil extracellular traps (NETs) through a distinct form of programmed cell
death called NETosis. Techniques to assess and quantitate NETosis in vitro in an unbiased, reproducible and efficient way are lacking,
considerably limiting the advancement of this field. We optimized and validated a new method to automatically quantify the percentage of
neutrophils undergoing NETosis in real time using IncuCyte ZOOM™, a two-color, live-content imaging platform, and the membrane
permeability properties of two different DNA dyes. We also evaluated whether this technology would allow for the differentiation of various
forms of neutrophil cell death.
Methods: Neutrophils were isolated from healthy controls and their nuclei were stained with the membrane permeable DNA binding
NUCLEAR-ID red dye to count all cells. They were then seeded on a 96-well plate and incubated with various stimuli or inhibitors and a
membrane-impermeable DNA dye, Sytox Green, that helped to assess cell death. Images were taken every 10minutes and a processing
definition was devised to automatically count all neutrophils at baseline and neutrophils undergoing cell death based on fluorescence
intensity and stained nuclear area size.
Results: This imaging platform enabled efficient, real-time imaging and quantification of cells undergoing NETosis. Findings were
confirmed with established method of immunofluorescence microscopy and the percentage counts of cells undergoing NETosis correlated
well. The platform’s ability to rapidly measure NETosis and effects of drugs to modulate it was used to test various concentrations of an
inhibitor of NETosis (Akt-inhibitor XI) which showed a dose dependent effect. This method was also able to distinguish between distinct
neutrophil cell deaths. Neutrophils undergoing NETosis induced by phorbol-myristate acetate, bacterial toxin nigericin, calcium ionophore
A23187 or platelet activating factor, exhibited a loss of multi-lobulated nuclei, nuclear decondensation and eventual membrane compromise.
Necrosis induced by freeze-thaw resulted in instantaneous damage to membrane integrity with minimal change to nuclear morphology. In
contrast, apoptotic cells induced by staurosporine showed nuclear condensation and cytoplasmic blebbing.
Conclusion: The IncuCyte ZOOM platform is a novel assay that quantifies NETosis in a rapid, automated and reproducible way, while
retaining the ability to distinguish between different types of neutrophil cell death, and offers a significant advancement in the study of
neutrophils. It is a powerful tool to assess neutrophil physiology and to swiftly develop novel neutrophil targets in autoimmune diseases.
Disclosure: S. Gupta, None; D. Chan, None; K. Zaal, None; E. Ralston, None; M. J. Kaplan, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-novel-real-time-imaging-technique-to-quantify-

neutrophil-extracellular-traps-and-distinguish-mechanisms-of-cell-death-in-neutrophils
Neutrophil Extracellular Traps Are Induced By Adenosine and Stimulate Release of

TNF Alpha from Macrophages in Deficiency of Adenosine Deaminase 2 (DADA2)
Carmelo Carmona-Rivera1, Kyawt W. Shwin2, Jorge A. irizarry-Caro3, Sami S. Khaznadar4, Yudong Liu3, Kenneth A. Jacobson4, Amanda
Ombrello5, Deborah L. Stone5, Wanxia Li Tsai3, Massimo G. Gadina6, Daniel L. Kastner5, Ivona Aksentijevich5, Mariana J. Kaplan3 and
Peter C. Grayson7, 1Systemic Autoimmunity Branch, NIAMS/NIH, Bethesda, MD, 2Division of Rheumatic Diseases, Dallas VA Medical
Center/ UT Southwestern Medical Center, Dallas, TX, 3NIAMS/NIH, Bethesda, MD, 4Molecular Recognition Section, NIDDK-NIH,
Bethesda, MD, 5Inflammatory Disease Section, NHGRI/NIH, Bethesda, MD, 6Translational Immunology Section, Office of Science and
Technology, NIAMS/NIH, Bethesda, MD, 7National Institute of Arthritis, Musculoskeletal and Skin Disease (NIAMS), Bethesda, MD
SESSION INFORMATION
Background/Purpose: Reduction of adenosine deaminase 2 (ADA2) activity due to autosomal recessive loss of function mutations in the
CECR1 gene results in a systemic illness known as DADA2 characterized in part by early-onset stroke, vasculitis, and clinical response to
TNF-inhibitors. Adenosine, which is extracellularly degraded by ADA2, modulates inflammation via four different adenosine receptors
(ARs). Neutrophils and a subset of neutrophils known as low-density granulocytes (LDGs) have been implicated in the pathogenesis of
small-vessel vasculitis through the formation of neutrophil extracellular traps (NETs). The study objective was to determine whether
neutrophils and NETs play a pathogenic role in DADA2.
Methods: Neutrophils and LDGs were isolated from healthy volunteers, patients with DADA2, and their family members. NETs were
quantified and visualized by fluorescence microscopy. Immunofluorescence was performed against citrullinated-histone H4 and macrophage
markers to detect NETs and macrophages in affected tissue from a patient with DADA2. Neutrophils were incubated with adenosine +/-
ADA2 enzyme and resultant NET formation was quantified. Pharmacologic approaches were utilized to determine the specific receptor(s)
and pathways that mediate NET formation by adenosine. ELISA quantified TNF-alpha release in supernatants from macrophages incubated
with NETs.
Results: An abundance of circulating LDGs prone to spontaneous NET formation were observed during active disease in DADA2 and were
significantly reduced after remission induction by anti-TNF therapies. Increased circulating LDGs were identified in unaffected heterozygous
carriers of CECR1 mutations. In vivo evidence demonstrated NETs and macrophages in affected gastrointestinal tissue in a patient with
DADA2. Adenosine triggered NET formation by engaging A1 and A3 adenosine receptors and through ROS- and PAD4- dependent
pathways. Adenosine-induced NETosis was inhibited in the presence of recombinant ADA2, A1/A3 AR antagonists, or an A2A agonist. M1
macrophages incubated with NETs from patients with DADA2 released significantly increased amounts of TNF-alpha. Treatment with IL-
1Ra (anakinra) or an A2A AR agonist decreased nuclear translocation of NFkB and pro-inflammatory cytokines-induced by NETs in
macrophages.
Conclusion: Neutrophils may play a pathogenic role in DADA2. LDGs and NETs are observed during active disease. Adenosine can trigger
NET formation, and deficiency of ADA2 may enhance adenosine-mediated NETosis. M1 macrophages produce TNF-alpha when exposed to
NETs from patients with DADA2, potentially explaining the efficacy of anti-TNF therapies in this disease. Modulation of adenosine-
mediated NET formation may constitute a novel and directed therapeutic approach in the treatment of DADA2.
Disclosure: C. Carmona-Rivera, None; K. W. Shwin, None; J. A. irizarry-Caro, None; S. S. Khaznadar, None; Y. Liu, None; K. A.
Jacobson, None; A. Ombrello, None; D. L. Stone, None; W. L. Tsai, None; M. G. Gadina, None; D. L. Kastner, None; I. Aksentijevich,
None; M. J. Kaplan, None; P. C. Grayson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/neutrophil-extracellular-traps-are-induced-by-adenosine-

and-stimulate-release-of-tnf-alpha-from-macrophages-in-deficiency-of-adenosine-deaminase-2-dada2
Expanded Therapeutic ACPA Utility for Different NET-Driven Human (Autoimmune)

Diseases
Renato G.S. Chirivi1,2, Jos W.G. van Rosmalen1, Kostantinos Kambas3, Gonny Schmets1, Hans Kalisvaart1, Galina S. Bogatkevich4, Tim
Shaw2, Helmuth van Es2 and Jos M.H. Raats1,2, 1ModiQuest BV, Oss, Netherlands, 2Citryll BV, Nijmegen, Netherlands, 3Laboratory of
Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece, 4Division of Rheumatology and Immunology,
Department of Medicine, Medical University of South Carolina, Charleston, SC
SESSION INFORMATION
Background/Purpose:
Aberrant Neutrophil Extracellular Trap (NET) formation contributes to the induction and propagation of inflammation and plays a key role in
causing tissue damage in conditions like sepsis, SLE, RA and vasculitis. Citrullination of proteins is involved in the formation of NETs,
autoimmunity, and the breaking of tolerance in NET-driven autoimmune diseases. In SLE and RA, neutrophils undergo enhanced NETosis,
and NET components are observed in blood, inflamed tissues and joints.
Therapeutic ACPA (tACPA) are first in class NETosis-inhibiting antibodies targeting citrullinated histones 2A and 4, which are being
developed for the treatment of human diseases in which aberrant NET formation adds to the severity of the pathology with an initial focus on
autoimmune diseases.
Here, we demonstrate the utility of tACPA as a NETosis-inhibiting therapy for different NET-based diseases beyond RA, including SLE and
Idiopathic pulmonary fibrosis (IPF).
Methods:
Previously, using two RA animal models, the therapeutic properties of tACPA have been demonstrated (Chirivi et al., 2013). In the current
studies, neutrophils from RA and SLE donors, as well as biological NET-inducing stimuli, such as RA synovial fluid (SF), gout SF and
activated platelets, have been used to demonstrate the NETosis-inhibiting properties of tACPA in different human disease contexts. We have
further expanded tACPA’s therapeutic utility by testing it in a surrogate model for NET-mediated organ damage (sepsis) and idiopathic
pulmonary fibrosis (IPF).
Results:
NETosis in human RA and SLE neutrophils have been induced with a calcium ionophore and could be inhibited by tACPA treatment (40-
100% reduction). Similar results were obtained using RA and gout SF or activated platelets as NETosis inducers in combination with
neutrophils from healthy donors. These observations have been confirmed with multiple NET readouts such as MPO activity, MPO/DNA
ELISA, DNA quantification as well as imaging readouts. In addition, we demonstrated that in an LPS-induced sepsis model 30% of tACPA-
treated mice survived (compared to 0 % in placebo controls), showing protection against organ failure. In a bleomycin-induced IPF mouse
model, tACPA protected mice from the development of lung fibrosis (compared to placebo controls). When determining neutrophil counts in
bronchoalveolar lavage samples, we found that in tACPA-treated mice, neutrophil levels were normal, while levels in placebo-treated mice
were elevated.
Conclusion:
In a sepsis and IPF mouse model, tACPA prevented NET-mediated organ damage, providing evidence that tACPA could be a promising
therapeutic strategy for diseases where NET-mediated endothelial toxicity causes organ damage like SLE, vasculitis and IPF. Central to our
strategy for generating a preclinical data package supporting clinical testing, is to demonstrate that patient NETosis can be significantly
inhibited ex vivo. We will present data that confirm that tACPA can block human SLE NETosis as well as human NETosis induced by
activated platelets or gout SF.
Disclosure: R. G. S. Chirivi, Citryll, 3; J. W. G. van Rosmalen, None; K. Kambas, None; G. Schmets, None; H. Kalisvaart, None; G. S.
Bogatkevich, None; T. Shaw, None; H. van Es, Citryll, 4; J. M. H. Raats, Citryll and ModiQuest, 4.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/expanded-therapeutic-acpa-utility-for-different-net-

driven-human-autoimmune-diseases
DNA Area and Netosis Analysis (DANA): A High-Throughput Method to Quantify

Neutrophil Extracellular Traps in Fluorescent Microscope Images
Ryan Rebernick1, Lauren Fahmy2, Christopher Glover2, Nicole Rademacher2, Hemanth Potluri2, Mandar Bawadekar1, Christie M. Bartels3
and Miriam A. Shelef1,4, 1Department of Medicine, Division of Rheumatology, University of Wisconsin - Madison, Madison, WI,
2University of Wisconsin - Madison, Madison, WI, 3Rheumatology/Medicine, University of Wisconsin - Madison, Madison, WI, 4William S.
Middleton Memorial Veterans Hospital, Madison, WI
SESSION INFORMATION
Background/Purpose: Neutrophil extracellular traps (NETs), extracellular structures composed of decondensed chromatin, are released in a
process called NETosis. NETs, which are part of normal host defense, have also been implicated in multiple rheumatologic diseases
including rheumatoid arthritis, lupus, and vasculitis. Unfortunately, methods for quantifying NETs have limitations involving cost, speed,
bias, and/or ease of use, which constrain the study of NETs in disease. The purpose of this project is to advance the methodology for NET
quantification in order to maximize the ability of investigators to further elucidate the role of NETs in health and disease.
Methods: We created DNA Area and NETosis Analysis (DANA), a novel ImageJ/Java based program which provides a simple, semi-
automated approach to quantify NET-like structures and DNA area for many fluorescent microscope images at once providing data on a per
cell, per image, and per sample basis. To test DANA, 2 different individuals determined the frequency of NET-like structures for fluorescent
microscope images of Sytox-stained human neutrophils by eye followed by running DANA on those images. DANA was then used to analyze
images of neutrophils from rheumatoid arthritis subjects and control subjects. To test the ease of implementing DANA and applicability to
other species and DNA stains, two individuals with no programming background installed DANA and repeated the above experiments using
images of DAPI-stained unstimulated and stimulated murine bone marrow derived neutrophils.
Results: DANA quantified a similar frequency of NET-like structures to the frequency determined by eye, and in a fraction of the time, for
both human Sytox-stained neutrophil images and murine DAPI-stained neutrophil images. Also, as expected, DANA detected increased DNA
area and frequency of NET-like structures in rheumatoid arthritis subjects compared to controls and in stimulated murine neutrophils
compared to unstimulated.
Conclusion: DANA provides a means to quantify DNA decondensation and the frequency of NET-like structures in a reliable, simple, high-
throughput, and cost-effective manner making it ideal to assess NETosis in a variety of conditions.
Disclosure: R. Rebernick, None; L. Fahmy, None; C. Glover, None; N. Rademacher, None; H. Potluri, None; M. Bawadekar, None; C.
M. Bartels, Pfizer Inc, 2; M. A. Shelef, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/dna-area-and-netosis-analysis-dana-a-high-throughput-

method-to-quantify-neutrophil-extracellular-traps-in-fluorescent-microscope-images
Ex Vivo Induced Neutrophil Extracellular Traps Are Intrinsically Different in Anca-

Associated Vasculitis and Systemic Lupus Erythematosus
Laura van Dam1, Tineke Kraaij1, Sylvia Kamerling1, Hans U. Scherer2, Charles Pusey3, Ton Rabelink1, Cees van Kooten1 and Onno
Teng1, 1Nephrology, Leiden University Medical Center, Leiden, Netherlands, 2Rheumatology, Leiden University Medical Center, Leiden,
Netherlands, 3Imperial College, London, United Kingdom
SESSION INFORMATION
- Background/Purpose: Neutrophil extracellular traps (NETs) are immunogenic, extracellular DNA structures that harness important
autoantigens to be recognized by the adaptive immune system. NETs are thought to play a pivotal role in the pathogenesis of ANCA-
associated vasculitis (AAV) and SLE. However it is still unclear how and if NETs can act as a common pathway in the pathophysiology of
these clinically divergent autoimmune diseases. The aim of the present study is to characterize AAV- and SLE-induced NETs.
- Methods: The present study involved 88 AAV patients according to the Chapel Hill consensus definitions of 2012, 59 SLE patients
according to the ACR criteria 1997 and 10 healthy controls. Healthy neutrophils were stimulated with 10% serum of AAV or SLE patients to
induce NETs. Ex vivo NET induction by serum and IgG-depleted serum was measured by a novel, highly-sensitive NET quantification assay
using 3D-confocal microscopy1. Qualitative characteristics of NETs were studied by immunofluorescence to detect NET-related auto-
antigens. Additionally, the morphology and kinetics of AAV- and SLE-induced NETosis were visualized by live cell imaging and electron
microscopy.
- Results: Ex vivo NET induction by AAV sera was 19.36 [9.161 – 73.08], (median [Q1 – Q3]) fold higher than sera of healthy
controls (n=10) and also significantly higher than NET induction by SLE sera 5.56 [2.34 – 14.33] (Figure 1). Depletion of IgG from serum
did not reduce NET induction in AAV, but it decreased NET induction significantly in SLE, indicating that different triggers mediate the
induction of neutrophil extracellular traps in these autoimmune diseases. Additionally, the colocalisation of NET-related auto-antigens was
different: citrullinated histon-3 (CitH3) was predominantly found on AAV-induced NETs, whereas high mobility group box protein-1
(HMGB-1) was exclusively found on SLE-induced NETs. Moreover, live cell imaging demonstrated that the kinetics of SLE-induced NETs
peaked at 60 minutes, while AAV-induced NETs peaked at 4 hours (Figure 2). Intriguingly, SLE sera induced immediate clustering of
neutrophils surrounding NETs whereas AAV sera induced NETs composed of long, thin DNA-fibres through lytic expulsion.
- Conclusion: We demonstrate intrinsically distinct features of AAV- and SLE-induced NETs, indicating that NET formation in AAV
and SLE is based on different mechanisms. Future studies should be directed at unravelling how different NETs are involved in causing SLE-
or AAV-associated glomerulonephritis.
1. T. Kraaij et al. – Autoimmunity Reviews 15 (2016) 577–584

Disclosure: L. van Dam, None; T. Kraaij, None; S. Kamerling, None; H. U. Scherer, None; C. Pusey, None; T. Rabelink, None; C. van
Kooten, None; O. Teng, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/ex-vivo-induced-neutrophil-extracellular-traps-are-

intrinsically-different-in-anca-associated-vasculitis-and-systemic-lupus-erythematosus
A Module of Genes Describing Low Density Granulocytes Can be Identified and

Followed in the Periphery of Lupus Patients
Brian Keggereis1, Michelle Catalina2, Nick Geraci1, Sarah Heuer2, Prathyusha Bachali2, Sushma Madamanchi2, Peter E. Lipsky2 and
Amrie Grammer2, 1AMPELBioSolutions and RILITE Research Institute, Charlottesville, VA, 2AMPEL BioSolutions and RILITE Research
Institute, Charlottesville, VA
SESSION INFORMATION
Background/Purpose:
Lupus is an autoimmune disease characterized by a type I interferon signature thought to be initiated by granulocyte NETosis. The granulocyte
population in the periphery of lupus patients contains abnormal LDGs (low-density granulocytes) that are correlated with SLEDAI and anti-
dsDNA antibodies. The current experiments were carried out to identify LDGs quantitatively by their genomic signature in peripheral and
tissue datasets from lupus patients.
Methods:
Publicly available microarray or RNASeq gene expression profiles from lupus patients were identified in GEO, including those obtained
from from neutrophils, whole blood (WB), PBMC and skin, synovium, and kidney. The raw data were downloaded, normalized, curated and
assessed for differentially expressed (DE) genes. Correlation with clinical or histologic features was carried out by WGCNA and variation
in pathway activity was determined in individual samples and groups of samples by Gene Set Variation Analysis (GSVA). Curated STRING-
based protein-protein interaction analysis was carried out using MCODE in Cytoscape. Functional categories were defined using the BIG-C
clustering algorithm.
Results:
Analysis of control or lupus neutrophil RNA expression datasets as well as lupus LDGs resulted in three WGCNA modules that are
consistent across patient samples. Specifically, modules were identified that were positively correlated with LDGs but negatively correlated
with lupus and normal neutrophils (or vice-versa). Two WGCNA modules were identified in the LDG to neutrophil comparison that were
positively correlated (A,334 genes; B, 92 genes). “A” contains genes related to platelet activation and adhesion. “B” contains genes classic
for neutrophils and granulocytes. One module was negatively correlated (C, 82 genes) and contains genes related to nuclear transport and
translational machinery. The most informative module was “B”. 41/92 of “B” genes have been described to characterize
neutrophils/granulocytes (M2.2)1. 30/92 genes fall under the Neutrophil Granulation GO term and 13 of the 30 genes described by the
Neutrophil Granulation GO term are contained in M2.2. An end goal of this analysis was to identify a group of genes that could be used to
query whole blood, PBMC and tissue datasets for the presence of neutrophils and LDGs. WGCNA modules for whole blood and PBMC
were compared to the LDG modules described above and GSVA was utilized to examine the consistency across patients. Module B
containing LDG genes was found in 3/3 PBMC and 3/3 WB datasets by three measurements (gene overlap LDG module to PBMC or WB
module, eigengene correlation with module “B” and eigengene correlation with clinical traits).
Assessing correlation of the log2 fold change of DE genes in the WGCNA “B” module with the test sets (PBMCs or WB) gives an r range of
0.6-0.8 (p value < 0.05) regardless of disease activity. Genes within modules “A” and “C” were not significantly correlated. This
observation was not found for lupus-affected tissues.
Conclusion:
These results indicate that a discrete LDG module can be identified in the periphery of lupus patients. However, the contribution of these
cells to tissue pathology is uncertain.
Disclosure: B. Keggereis, None; M. Catalina, None; N. Geraci, None; S. Heuer, None; P. Bachali, None; S. Madamanchi, None; P. E.
Lipsky, None; A. Grammer, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-module-of-genes-describing-low-density-granulocytes-

can-be-identified-and-followed-in-the-periphery-of-lupus-patients
Multiplexed Characterization of Circulating and Joint-Derived Human Neutrophils in

Inflammatory Arthritis
Ricardo Grieshaber Bouyer1, Olha Halyabar2, Anais Levescot1, Kacie Hoyt2, Lauren Henderson2 and Peter Nigrovic1,2, 1Division of
Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 2Division of Immunology,
Boston Children's Hospital, Harvard Medical School, Boston, MA
SESSION INFORMATION
Background/Purpose:
Neutrophils are innate immune cells that play a central role in the initiation of inflammatory arthritis as well as mediating tissue damage. We
sought to improve our understanding of the role of neutrophils in joint inflammation using two multiplex discovery modalities. We
characterized simultaneous circulating and transmigrated, joint-derived neutrophils from patients with inflammatory arthritis and blood from
healthy controls via mass cytometry (CyTOF) and RNA-Seq with the goal of gaining new insights into the biology of neutrophils in inflamed
environments.
Methods:
We established a biospecimen pipeline that allowed for both immediate processing as well as cryopreservation of fresh samples. Synovial
fluid and simultaneous peripheral blood samples were obtained from seven consented patients with inflammatory joint disease. Purified
neutrophils were cryopreserved and stained with metal-conjugated antibodies directed against 30 surface proteins including lineage markers,
adhesion molecules, chemokine receptors, Fc- and complement receptors and immune checkpoints. Gene expression of freshly isolated
neutrophils from inflammatory arthritis patients and healthy controls was examined via Smart-seq2. Each gene was modeled as a linear-
mixed combination of donor- and group-specific effects using DESeq2.
Results:
Circulating and transmigrated neutrophils demonstrated fundamentally distinct gene- and surface protein expression. Joint-derived neutrophils
exhibited an activated phenotype reflected by increased surface expression of integrins, adhesion molecules and chemokine receptors and
increased transcription of complement receptor, TNF and CD69 among many others. Intriguingly, joint neutrophils overexpressed the
adaptive immunity regulatory gene PD-L1 – confirmed by CyTOF – suggesting that they might also act to restrain pathological inflammation
by negatively regulating T-cell function. We further identified 11 significantly enriched Gene Sets in joint neutrophils compared to blood,
including TNF-α signaling, IFN-α response, IL-2 and IL-6 signaling. Confirmation studies are ongoing.
Conclusion:
Using multiplex discovery modalities, this study examined both circulating and joint-derived neutrophils in the context of joint inflammation.
The dysregulated pathways identified suggest that neutrophils not only serve as effectors of immunity but also provide feedback that could
potentially regulate adaptive immune responses.
Disclosure: R. Grieshaber Bouyer, None; O. Halyabar, None; A. Levescot, None; K. Hoyt, None; L. Henderson, None; P. Nigrovic,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/multiplexed-characterization-of-circulating-and-joint-

derived-human-neutrophils-in-inflammatory-arthritis
Anabasum (JBT-101) Enhances Resolution of Inflammation in Humans

Madhur Motwani1, Fran Bennett1, Mark Tepper2, Barbara White2, Paul Norris3, Raymond MacAllister1, Charles Serhan3 and Derek
Gilroy1, 1University College London, London, United Kingdom, 2Corbus Pharmaceuticals, Norwood, MA, 3Harvard Medical School,
Cambridge, MA
SESSION INFORMATION
Background/Purpose: Certain rheumatic diseases including systemic sclerosis (SSc) are characterized by chronic activation of innate
immune responses, leading to excessive fibrosis. A normal innate immune response is comprised of an onset phase characterised by
generation of pro-inflammatory lipid mediators, chemokines, adhesion molecules, and tissue infiltration of inflammatory cells. This is
followed by a resolution phase where the balance of lipid mediators shifts from pro-inflammatory mediators to novel Specialized
Pro‑resolving Lipid Mediators (SPMs), pro-inflammatory cytokines and chemokines are inhibited, pathogens and inflammatory cells are
cleared from involved tissues, and active wound healing processes are completed. Persistent inflammation and progressive fibrosis can
reflect an imbalance that favors onset phase over resolution phase. Anabasum (JBT-101) is a cannabinoid receptor type 2 agonist that
showed evidence of clinical benefit on Phase 2 testing in systemic sclerosis. Anabasum activates resolution of skin and lung inflammation in
animal models of SSc. Using a novel in vivo human skin challenge model of an innate immune response, we tested the effect of anabasum on
inflammatory onset and resolution and compared it to prednisolone.
Methods: In this placebo-controlled study, subjects (N = 20) received placebo (n = 5), oral anabasum 5 mg BID (n = 5), anabasum 20 mg
BID (n = 5), or prednisolone 15 mg OD (n = 5) for 4 days. On the 4th day, acute inflammation was triggered by intradermal injection of
ultraviolet light-killed E coli on both the forearms of healthy subjects. Local inflammatory exudate was acquired into a suction blister raised
at 4 hr on one forearm (onset time point) and at 10 hr on the contralateral forearm (resolution time point). Inflammatory exudate was analyzed
for soluble mediators and immune cells. Blood flow to the site of inflammation was monitored by laser doppler.
Results: Anabasum exerted a profound anti-inflammatory effect in this model by accelerating the resolution phase of the innate immune
response. Anabasum: increased blood flow during the resolution phase at 10 hours; reduced IL-8 and neutrophils in blister exudate 10 hours
post-challenge, as did prednisolone; reduced the proinflammatory lipid mediators LTB4, PGF2a, TxB2 and PGE2; increased the SPMs
lipoxins (LXA4, LXB4) and resolvins (RvD1, RvD3, RvD5); and hastened bacterial clearance, whereas prednisolone slowed bacterial
clearance during the resolution phase (resolution toxic).
Mean (SE)
Exudate content Hours Placebo Anabasum 5 mg Anabasum 20 mg Prednisolone 15 mg
BID BID QD
IL-8, pg/ml 4 5931 (923) 3299 (773) 3024 (1235) 4289 (1375)
10 3241 (784) 1679 (602) 2007 (515) 2267 (543)
Neutrophils/ml x 4 262 (71) 55 (17) 66 (16) 72 (25)
103 10 244 (101) 120 (52) 72 (21) 69 (16)
Macrophage 4 705 (244) 1420 (460) 711 (277) 5233 (2145)
CD163 intensity 10 2383 (478) 3610 (968) 3338 (744) 5427 (1381)
Endotoxin, 4 14.6 (4.2) 5.3 (2.0) 6.8 (4.3) 17.2 (5.3)
relative units 10 5.0 (3.3) 6.9 (4.5) 5.9 (2.7) 11.5 (3.2)
Conclusion: Anabasum has novel biologic effects on infection-induced innate immune responses as it exerts a striking anti-inflammatory
effect greater than that of prednisone and leading to timely resolution of inflammation. This activity offers promise for anabasum in the
treatment of SSc.
Disclosure: M. Motwani, None; F. Bennett, None; M. Tepper, Corbus Pharmaceuticals, 1,Corbus Pharmaceuticals, 3; B. White, Corbus
Pharmaceuticals, 1,Corbus Pharmaceuticals, 3; P. Norris, None; R. MacAllister, None; C. Serhan, None; D. Gilroy, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/anabasum-jbt-101-enhances-resolution-of-inflammation-

in-humans
Bik Plays an Important Role of Cell Proliferation Caused By Nitric Oxide in

Rheumatoid Arthritis Synovium
Takeshi Ueha1, Yoshitada Sakai1, Kohjin Suzuki2, Koji Fukuda3, Toshihisa Maeda3, Hanako Nishimoto3, Shinya Hayashi4, Yasushi
Miura4, Ryosuke Kuroda3 and Akira Hashiramoto2, 1Division of Rehabilitation Medicine, Kobe University Graduate School of Medicine,
Kobe, Japan, 2Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan, 3Department of Orthopaedic
Surgery, Kobe University Graduate School of Medicine, Kobe, Japan, 4Orthpaedic Surgery, Kobe University Graduate School of Medicine,
Kobe, Japan
SESSION INFORMATION
Background/Purpose: Nitric oxide (NO), a proinflammatory mediator responsible for various physiological processes, plays a central role
in the pathogenesis of rheumatoid arthritis (RA). As a heme-based sensor for NO, a transcription factor neuronal PAS domain protein 2
(NPAS2) forms a heterodimer with clock gene BMAL1. Using RA fibroblast-like synoviocytes (-FLS), we previously reported the
interaction of clock genes and Bcl-2-interacting killer (BIK) which was known to be an inducer of mitochondrial apoptosis, and the promoter
site of BIK has the NPAS2/BMAL1 heterodimer binding enhanced box sites (E-box sites). In this study, we evaluated the role of NPAS2 in
RA synovium in views of relationship between NO and BIK.
Methods: The synovium were obtained during total knee replacement surgery from patients. Immunohistochemistry was performed to
determine NPAS2 expression in synovial tissue. Cell proliferation was assessed with WST-8 assay in RA-FLS, using varying concentrations
of the NO donor, S-Nitroso-N-acetyl-DL-penicillamine (SNAP) (0-20 nM). To evaluate the relationship between NPAS2 and BIK, NPAS2-
siRNA was used to measure BIK mRNA expression in the absence and presence (5, 20 nM) of SNAP in RA-FLS. Moreover, we cloned the
three BIK promoters (see Figure1), made luciferase assay model, and measured the luciferase activity in the absence and presence of SNAP
in RA-FLS.
Results: NPAS2 expression was observed in RA synovium. Cell proliferation was significantly increased by SNAP. In the presence of
SNAP, BIK mRNA expression was significantly reduced in the control-siRNA group, but not in the NPAS2-siRNA group (Figure 2, *; P <
0.05). In the presence of SNAP, the luciferase activity was significantly reduced in the Bik-E2-promoter group, but not in the Bik-E0-
promoter group (Figure 3, *; P < 0.05).
Conclusion: NPAS2 enhance Bik expression, and NO inhibited Bik expression by NPAS2. These results suggests that NO may inhibit
NPAS2 to bind E-box of Bik promoter. We propose a novel action of NO that inhibits mitochondrial apoptosis of RA-FLS by preventing the
binding between NPAS2 and BIK. Therefore, we suggested that the inhibition of NO and NPAS2 may clinically be potential of anti-
hyperproliferation and anti-bone destruction in RA synovium.
Disclosure: T. Ueha, None; Y. Sakai, None; K. Suzuki, None; K. Fukuda, None; T. Maeda, None; H. Nishimoto, None; S. Hayashi, None;
Y. Miura, None; R. Kuroda, None; A. Hashiramoto, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/bik-plays-an-important-role-of-cell-proliferation-caused-

by-nitric-oxide-in-rheumatoid-arthritis-synovium
The DNA-Binding Protein ARID3a Is Associated with Interferon Alpha Production in

Lupus Patient Plasmacytoid Dendritic Cells and Neutrophils
Michelle Ratliff1, Joshua Garton1,2, Indra Adrianto3, Ambra Pastori4, Courtney Montgomery5, Patrick Gaffney4, Judith A. James3,6 and
Carol Webb1,7,8, 1Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 2Chemistry, University of Oklahoma,
Oklahoma City, OK, 3Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 4Arthritis
and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, 5Arthritis & Clinical Immunology, Oklahoma
Medical Research Foundation, Oklahoma City, OK, 6Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma
City, OK, 7Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 8Microbiology and Immunology, University
of Oklahoma Health Sciences Center, Oklahoma City, OK
SESSION INFORMATION
Background/Purpose: We previously demonstrated over-expression of the DNA-binding protein ARID3a in peripheral blood B
lymphocytes from patients with systemic lupus erythematosus (SLE) compared to healthy controls. In addition, we found that ARID3a is
induced in healthy control blood cells in response to toll receptor signaling, and specifically to CpG stimuli. Furthermore, ARID3a
expression was associated with interferon alpha production in a subset of B lymphocytes from both CpG-stimulated healthy controls and SLE
patients. Therefore we hypothesized that ARID3a might also be associated with interferon alpha production in other cell types that secrete
interferons.
Methods: De-identified peripheral blood samples were obtained via our IRB approved protocol from SLE patients (classified via ACR
criteria) and healthy age-matched control participants of the Oklahoma Rheumatic Diseases Core Center. Peripheral blood mononuclear cells
were isolated over ficoll gradients and either subjected directly to immunofluorescence staining and flow cytometry analyses, or they were
first subjected to magnetic bead enrichment for neutrophils or plasmacytoid dendritic cells (pDCs). Purified pDCs and neutrophils were
subjected to RNA-seq and were evaluated for gene expression patterns in relation to ARID3a levels.
Results: Linear regression analyses demonstrated strong associations between ARID3a expression and interferon production in pDCs and
neutrophils in SLE patients. In addition, ARID3a expression in those cell types was associated with increased SLE disease activity indices.
Surprisingly, interferon subtypes were heterogeneously transcribed in neutrophils and pDCs. Gene expression data show increased
interferon-associated transcripts in patients with increased ARID3a protein expression.
Conclusion: Our data indicate co-expression of ARID3a and interferon in SLE patient blood cells may be linked to interferon signatures
observed in SLE.
Disclosure: M. Ratliff, None; J. Garton, None; I. Adrianto, None; A. Pastori, None; C. Montgomery, None; P. Gaffney, None; J. A.
James, None; C. Webb, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-dna-binding-protein-arid3a-is-associated-with-

interferon-alpha-production-in-lupus-patient-plasmacytoid-dendritic-cells-and-neutrophils
MiR-221-3p Overexpression Impairs Anti-Inflammatory Activity of TLR4-Stimulated

M2-Macrophages
Lilian Quero1,2, Andre Tiaden1,2 and Diego Kyburz2,3, 1Department of Biomedicine, Experimental Rheumatology, University of Basel,
Basel, Switzerland, 2Rheumatology, University Hospital Basel, Basel, Switzerland, 3Department of Biomedicine, Experimental
Rheumatology, University of Basel, 4051 Basel, Switzerland
SESSION INFORMATION
Background/Purpose: MicroRNAs (miRNAs) have been shown to contribute to the inflammatory response in rheumatoid arthritis (RA) and
several of these miRNAs have been found to be dysregulated in synovial tissue, synovial fluid or plasma of RA patients. In addition, also
inflammatory cells such as macrophages, which are infiltrating the synovium and promoting the pannus generation, exhibit an aberrant miRNA
expression. As toll-like receptors (TLRs) play a pivotal role in RA, we conducted a study to explore the role of TLRs in regulating the
expression of miRNAs in macrophages under conditions prone to RA. Based on a miRNA-screen in TLR-stimulated M1-and M2-
macrophages we selected several potential candidates for further studies, among them miR-221-3p. We then compared the release of
inflammatory versus anti-inflammatory cytokines upon miR-221-3p overexpression or inhibition in stimulated M1- and M2-macrophages.
Methods: Monocytes were isolated from buffy coats of 8 healthy donors by CD14 microbead separation and differentiated into M1 and M2
by culturing them in the presence of 50ng/ml GM-CSF and M-CSF, respectively, for 6 to 8 days. Subsequently, cells were stimulated for 8.5
or 24 hours with TLR2/3/4 ligands Pam3, PolyIC or LPS. Cytokine release was measured by ELISA and miRNA expression by qRT-PCR.
For miRNA mimic and inhibition studies, cells were transfected with corresponding pre-miR or antagomir using lipofectamine for 72 hours
prior to the stimulation of M1- and M2-macrophages with TLR ligands.
Results: The general outcome of the miRNA-screen showed that a higher proportion of the tested miRNAs were downregulated in M2
macrophages upon stimulation with TLR ligands Pam3 and LPS. The basal expression level of miR-221-3p was similar in M1- and M2-
macrophages, however, stimulation with LPS and PolyIC resulted in a prominent downregulation of miR-221-3p only in M2-macrophages. In
M1-macrophages LPS caused only a slight decrease of miR-221-3p expression. Since several recent studies detected higher miR-221-3p
levels in serum of RA patients and also in synovium of an induced RA-mouse model, we checked how macrophages respond to aberrant miR-
221-3p levels under inflammatory conditions. Overexpression or inhibition of miR-221-3p showed no effect in unchallenged M1- or M2-
macrophages on the secretion of IL-6, IL-8 or IL-10. However, miR-221-3p overexpression in combination with LPS stimulation, but not
Pam3 or PolyIC, significantly increased IL-6 and IL-8 cytokine secretion in M2 macrophages. In contrast, the same combinatorial treatment
(LPS + miR-221-3p overexpression) significantly decreased the IL-10 secretion in M2 macrophages.
Conclusion: We herein demonstrate that aberrant miR-221-3p expression is significantly downregulating the anti-inflammatory activity of
TLR4-stimulated M2-macrophages by decreasing the ratio of secreted IL-10/IL-6 and IL-10/IL-8. Thus, abundant miR-221-3p might
contribute to promote and sustain the chronically inflammatory conditions apparent in disease settings such as RA synovial tissue by
deregulating the pro-/anti-inflammatory cytokine profile of synovial macrophage subpopulations.
Disclosure: L. Quero, None; A. Tiaden, None; D. Kyburz, None.

View Abstract and Citation Information Online - http://acrabstracts.org/abstract/mir-221-3p-overexpression-impairs-anti-inflammatory-
activity-of-tlr4-stimulated-m2-macrophages
From Monocytes to Macrophages: the Pathogeneses of Spontaneous Inflammatory

Arthritis in CD11c-Flip-KO (HUPO) Mice
Qi Quan Huang1, Renee E. Doyle2, Philip J. Homan1, Harris Perlman3, Deborah R. WInter3 and Richard M. Pope2, 1Division of
Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL,
2Medicine/Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, 3Department of Medicine Division of
Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL
SESSION INFORMATION
Background/Purpose:
We have generated a CD11c-Flip-KO mouse line (HUPO) that spontaneously develops erosive arthritis with incidence 70-80% at age ≥
20 weeks. This study aimed at understanding the role of monocytes in HUPO arthritis and to define the molecular changes during
differentiation to macrophages in the inflamed joint compared with controls.
Methods:
Arthritis was evaluated by clinical score. Cell types from blood and ankle joints are determined by flow cytometry. Cell proliferation are
determined by BrdU incorporation and populations of cells were isolated for RNAseq.
Results:
Circulating monocytes, defined as CD45+CD11b+CD115+F4/80lo, were further characterized as classical (CM), Ly6C+CD62L+, or
non-classical (NCM), Ly6C-CD62L-. CM were markedly increased in HUPO mice with arthritis and positively correlated with arthritis
severity. 70 -90% of CM are also CCR2+ in HUPO mice with arthritis, similar to that in control mice. In contrast, in the HUPO mice
without arthritis, only 0-7% of these cells are CCR2+, and the CM numbers were normal. Monocytes recently recruited into synovium
are defined as CD45+Ly6C+CD64+CD11b+F4/80intLy6C+MHCII-. This population demonstrated reduced CD115 and increase F4/80
compared with CMs. Within 24 hours after BrdU injection, in both HUPO and control mice, >60% of these Ly6C+MHCII-
macrophages incorporated BrdU, comparable to CM and bone marrow monocytes. In contrast, < 1% in NCM incorporated BrdU. In
HUPO mice during further differentiation the macrophages became Ly6C+MHCII+ and then Ly6C-MHCII+, with less BrdU
incorporation in the more differentiated cells. A similar transition was observed in the control mice except the Ly6C+MHCII+
population was not identified. CMs and F4/80int macrophages were isolated for RNAseq. In the controls, clusters of differentially
expressed genes were identified in CMs, and Ly6C+MHCII- and Ly6C-MHCII+ joint macrophages. For example Immune response and
leukocyte activation were increase in CMs while cell cycle and cell division were increased in Ly6C+MHCII- macrophages. There were
differences in these transcriptional profiles of the macrophages subset between HUPO and control mice, including those regulating cell
cycle and differentiation as well as for monocyte differentiation and antigen processing.
Conclusion:
These observations demonstrate that during chronic inflammation, CMs enter the joints and undergo macrophage differentiation during
homeostasis and chronic inflammation. The differences in transcriptional profiles between the control and HUPO mice will provide
important insights into the mechanisms contributing to chronic inflammation.
Disclosure: Q. Q. Huang, None; R. E. Doyle, None; P. J. Homan, None; H. Perlman, None; D. R. WInter, None; R. M. Pope,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/from-monocytes-to-macrophages-the-pathogeneses-

of-spontaneous-inflammatory-arthritis-in-cd11c-flip-ko-hupo-mice
Outcomes after Hip Fracture in the Elderly: Does Social Isolation Matter?
Lisa A. Mandl1, Omar Halawa2, Jackie Szymonifka3, Kirsten Grueter4 and Joseph Lane5, 1Rheumatology, Hospital for Special
Surgery Weill Cornell Medical College, New York, NY, 2Hospital for Special Surgery, New York, NY, 3Rheumatology, Hospital for
Special Surgery, New York, NY, 4Orthopaedic Surgery, Hospital for Special Surgery, New York, NY, 5Orthopaedic Surgery, Hospital
for Special Surgery/Weill Cornell Medicine, New York, NY
SESSION INFORMATION
Session Title: Orthopedics, Low Back Pain and Rehabilitation Poster
Background/Purpose: Hip fractures are a serious public health issue with a significant population burden, especially among those over
65 years old. Social isolation—how integrated a patient is into his/her community—is a novel and potentially modifiable risk factor for
poor health outcomes after low trauma hip fracture. This study evaluates the association of pre-operative social isolation with death,
short-term complications and patient-reported functional recovery in elderly patients 3 months following surgical repair of low-trauma
hip fracture.
Methods: The Lubben Social Networks Scale-18 (LSNS-18), a validated instrument specifically designed to measure social isolation in
the elderly, PROMIS-29, which measures patient-reported outcomes, and the Lower Extremity Activity Scale (LEAS), which measures
physical function, were administered to cognitively intact patients ≥ 65 years old with no active cancer, 2-4 days after surgical repair of
hip fracture. Patients were specifically asked about their pre-fracture status. Patients were contacted 1 and 3 months after surgery and
asked about adverse events and hospitalizations. The LSNS-18, PROMIS-29 and the LEAS were administered again at 3 months.
Results: 109 patients were enrolled, 72.5% female, 92.7% white, 78% college educated with a mean age of 80.7± 8.5 years. 45% of
patients enrolled were socially isolated. Of the 109 patients enrolled, 19 had adverse events including pulmonary emboli, hypotension,
hypoxia, urinary tract infection, peri-prosthetic fracture, CHF exacerbation, cholecystitis, lower extremity cellulitis, falls, wound
dehiscence and duodenal ulcers. 5 patients died within the first 3 months. Of the 76 patients eligible for 3 month follow-up, 63 (83%)
completed 3-month questionnaires. A higher proportion of socially isolated patients died by 3 months (8.2% vs. 1.7%), although this
was not statistically significant (p=0.172). There was no statistically significant difference between socially isolated and non-socially
isolated patients in short-term complications, or PROMIS-29 and LEAS scores 3 months after surgery.
Conclusion: There is a positive trend suggesting social isolation is associated with 3-month mortality in elderly patients undergoing
surgical repair of low trauma hip fracture. There was no association between social isolation and short-term complications or self-
reported short-term functional recovery. Whether social isolation is associated with longer term functional outcomes or mortality is
unknown. Recruitment for this study is ongoing and all subjects will be studied for up to 1 year following surgery.
Disclosure: L. A. Mandl, None; O. Halawa, None; J. Szymonifka, None; K. Grueter, None; J. Lane, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/outcomes-after-hip-fracture-in-the-elderly-does-

social-isolation-matter
Usefulness of Consecutive Doppler Ultrasound Examinations for Detecting Deep

Venous Thrombosis during the Perioperative Period in Patients with Osteoporotic
Fractures of the Proximal Femur
Ken Nakaseko and Norihiro Mayumi, Department of Orthopaedic Surgery and Rheumatology, Kuwana City Medical Center, Kuwana
Mie, Japan
SESSION INFORMATION
Background/Purpose: Deep venous thrombosis (DVT) can lead to a venous thromboembolism and increase the risk of a pulmonary
thromboembolism (PE). PE is one of the most common causes of death in hospitalized surgical patients.Although there have been some
prospective studies regarding the prevalence of DVT on Doppler ultrasound examinations of the lower extremities, there have not been
any prospective studies in which three consecutive Doppler ultrasound examinations were performed to detect DVT during the
perioperative period. The purpose of the present study was to prospectively evaluate the occurrence of DVT in patients with
osteoporotic fractures of the proximal femur, based on the results of examinations involving three consecutive ultrasound scans. In
addition, the usefulness of the D-dimer level as a predictor of DVT was investigated.
Methods: This study was a single-center prospective study. Eighty-seven patients (14 males and 73 females) between the ages of 46
and 95 years with osteoporotic fractures of the proximal femur were enrolled. All patients were asymptomatic in terms of their clinical
DVT findings. Three Doppler ultrasound examinations of the lower extremities were conducted in each case: on admission, one day
before surgery, and one week after surgery. The period from admission to surgery ranged from 2 to 7 days (mean: 5.3 days).The D-
dimer level was measured at one week after surgery and its relationship with the presence/absence of DVT was evaluated by calculating
sensitivity, specificity, positive predictive, and negative predictive values.
Results: DVT was detected in 16 patients (2 patients on admission, 8 patients one day before surgery, and 6 patients one week after
surgery). The overall prevalence of DVT in the perioperative period was 18.4% (16/87). As for the characteristics of the patients that
did and did not develop DVT, there were no significant differences between the two groups.When the D-dimer cut-off level was set at
4.3 μg/ml, the sensitivity and negative predictive value reached 100%, while the specificity was 15.5%, and the positive predictive
value was 21.1%. A receiver operating characteristic (ROC) curve was drawn, and the optimal D-dimer cut-off level was examined. The
ROC curve was closest to the upper left corner when the D-dimer cut-off level was 12.2 μg/ml. At that point, the sensitivity, specificity,
positive predictive value, and negative predictive value were 62.5%, 70.4%, 32.3%, and 89.3%, respectively.
Conclusion: In this prospective study, DVT was detected in 2 patients on admission, 8 patients one day before surgery, and 6 patients
one week after surgery. As DVT can occur at any moment, performing repeated Doppler ultrasound examinations in the perioperative
period is useful for quickly detecting DVT, which can cause PE.As for the D-dimer level, its sensitivity and negative predictive value
reached 100% at a cut-off level of 4.3 μg/ml. Therefore, D-dimer assays could be a useful screening tool for DVT and might be a
suitable substitute for Doppler ultrasound examinations.
Disclosure: K. Nakaseko, None; N. Mayumi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/usefulness-of-consecutive-doppler-ultrasound-

examinations-for-detecting-deep-venous-thrombosis-during-the-perioperative-period-in-patients-with-osteoporotic-fractures-of-the-
proximal-femur
Ultrasonographic Evaluation of the Femoral Cartilage, Achilles Tendon and Plantar

Fascia in Young Women Wearing High-Heeled Shoes
Ayşen Akinci1, Kamal Mezian2, Ayşe Merve Ata1, Murat Kara1, Şule Şahin Onat3, Eda Gürçay4, Aslı Çalışkan1, Maria Ines Taboas
Simoes5 and Levent Özçakar1, 1Hacettepe University Medical School Department of Physical Medicine and Rehabilitation, Ankara,
Turkey, 2Czech Technical University in Prague, Faculty of Biomedical Engineering, Department of Health Care Disciplines and
Population Protection, Kladno, Czech Republic, 3Ankara Physical Medicine and Rehabilitation Training and Research Hospital,
Ankara, Turkey, 4Gaziler Physical Medicine and Rehabilitation Training and Research Hospital, Ankara, Turkey, 5PMR hospitalar
assistant in Centro Hospitalar Entre Douro e Vouga, E.P.E, Portugal
SESSION INFORMATION
Background/Purpose: Wearing high-heeled shoes (HHS) may include structural and functional abnormalities due to repetitive stress
particularly in the knee and forefoot. The aim of this study was to investigate whether the distal femoral cartilage, Achilles tendon and
plantar fascia were different between healthy young women wearing HHS and flat shoes.
Methods: A total of 91 healthy women (aged 20-45 years) participated in this cross-sectional study. Women wearing shoes with a heel
height of >5cm were enrolled in the HHS group, and those wearing shoes with a heel height of <1.4 cm were included in the flat shoes
group. Femoral cartilage from the lateral femoral condyle (LFC), intercondylar area and medial femoral condyle (MFC), and Achilles
tendon and plantar fascia thicknesses were measured by using ultrasound.
Results: There were 34 women (mean age; 31.1±6.4 years, BMI; 21.6±2.3 kg/m2) in the HHS group and 57 women (mean age;
29.5±7.3 years, BMI; 22.5±3.4 kg/m2) in the control group (both p>0.05). In group comparisons, thicker right MFC and left Achilles
tendon were obtained in the HHS group (both p<0.05). Between group comparisons yielded thicker left Achilles tendon in the HHS
group than the flat shoes group (p<0.05). Plantar fascia thicknesses were similar both within and between group comparisons (both
p>0.05). Right Achilles tendon thickness was positively correlated with right (r=0.469, p=0.005) and left (r=0.402, p=0.018) plantar
fascia thicknesses only within the HHS group.
Conclusion: Wearing HHS resulted in thickening of the right MFC and left Achilles tendon in women wearing HHS which might
definitely be interpreted as secondary to chronic overload. Our results may provide an understanding of the morphological changes with
wearing HHS and recommend that this "social" issue that exists in women's lives be investigated further to reveal the musculoskeletal
consequences.
Disclosure: A. Akinci, None; K. Mezian, None; A. M. Ata, None; M. Kara, None; Ş. Şahin Onat, None; E. Gürçay, None; A.
Çalışkan, None; M. I. Taboas Simoes, None; L. Özçakar, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/ultrasonographic-evaluation-of-the-femoral-

cartilage-achilles-tendon-and-plantar-fascia-in-young-women-wearing-high-heeled-shoes
Relationship between Inflammatory Anterior or Posterior Arch MRI Abnormalities

and Clinical Data in Low Back Pain Patients
Helene Braun1, Clement Geniez1, Yannick Degboe2, Arnaud Constantin3, Alain Cantagrel4, Delphine Nigon5, Marie Faruch-Bilfeld1
and Adeline Ruyssen-Witrand4, 1Purpan Hospital, Toulouse, France, 2Department of Rheumatology, Purpan Hospital, Toulouse III
University, Toulouse, France, Toulouse, France, 3Purpan Hospital, toulouse, France, 4Rheumatology, Purpan Hospital, Toulouse III
University, Toulouse, France, 5CHU Purpan, Toulouse, France
SESSION INFORMATION
Background/Purpose: To compare demographic characteristics, characteristics of pain and functional status according to the presence
of inflammatory anterior or posterior arch MRI abnormalities in low back pain (LBP) patients.
Methods: Design: Monocentric cross-sectional study. Patients: Chronic LBP patients with a lumbar spine MRI planned in the Toulouse
Hospital Radiology Center were prospectively selected and filled a standardized questionnaire to get clinical data. MRI: STIR and T1
sagittal images from 3 and 1.5 Tesla MRI going up to T8-T9 stages were reviewed by two experienced rheumatologists, blinded from
the diagnosis and clinical data. Inflammatory anterior arch abnormalities (IAAA: i.e.: MODIC I or II, inflammatory corner lesions) and
inflammatory posterior arch abnormalities (IPAA: i.e.: pedicle edema, transverse and spinous process edema, interspinous process
edema, costo-transverse or zygapophyseal joint arthritis) were collected. Analyses: Clinical data (age, sex, disease duration, ODI, pain
VAS, inflammatory pain, NSAIDs efficacy) were compared according to the presence/absence of IAAA or IPAA by Chi2 or Wilcoxon
tests.
Results: Ninety-five patients were included in this study, 66 have IPAA. Inter and intra-observer agreement was excellent (κ=0.938).
The most prevalent IPAA was zygapophyseal joint arthritis (62.5%), then 31.9% patients have interspinous process edema, 9.7%
pedicle edema and 4.2% spinous process edema. Patients with IPAA had more frequently Modic I and/or II lesions than patients without
IPAA (39.2% versus 9.5%, p=0.01). There was no statistically significant association between IPAA presence and clinical data,
including pain characteristics. IPAA seemed to be more prevalent in women (62.1% versus 41.4%, p=0.06), in patients with longer pain
duration (6 years versus 4.75 years, p=0.22), with morning stiffness more than 30 minutes (42.4% versus 24.1%, p=0.2), and with better
NSAID response (65.9% versus 55%, p=0.35). Furthermore, patients with Modic I had a better response to NSAIDs (90% versus 52%,
p=0.04). Patients with Modic II seemed to be older than patients without Modic (66 years versus 43 years, p=0.0004). Modic I was
often associated with IPAA at the same vertebral stage.
Conclusion: The most prevalent IPAA in patients with LBP was zygapophyseal joint arthritis. Modic I and/or II were more prevalent
when patients have IPAA. There was no significant association between IPPA presence and clinical data. However, NSAIDs had a
better efficacy in patients with Modic I, and Modic I was often associated with IPPA at the same vertebral stage.
Disclosure: H. Braun, None; C. Geniez, None; Y. Degboe, None; A. Constantin, None; A. Cantagrel, None; D. Nigon, None; M.
Faruch-Bilfeld, None; A. Ruyssen-Witrand, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/relationship-between-inflammatory-anterior-or-

posterior-arch-mri-abnormalities-and-clinical-data-in-low-back-pain-patients
Biochemical Intervertebral Disc Alterations in Patients with Low Back Pain and
Radiculopathy
Philipp Sewerin1, Christoph Schleich2, Ruben Sengewein3, Matthias Schneider4 and Benedikt Ostendorf1, 1Department and Hiller-
Research-Unit for Rheumatology, Heinrich-Heine University, Düsseldorf, Germany, 2Dep. for diagnostic and interventional Radiology,
Heinrich-Heine University, Duesseldorf, Germany, 3Department and Hiller Research Unit for Rheumatology, Heinrich-Heine
University, Düsseldorf, Germany, 4Policlinic for Rheumatology & Hiller Research Centre for Rheumatology, Heinrich-Heine-
University Duesseldorf, Duesseldorf, Germany
SESSION INFORMATION
Background/Purpose: To assess the glycosaminoglycan (GAG) content of lumbar intervertebral discs (IVD) in patients with low back
pain (LBP) and radiculopathy using glycosaminoglycan chemical exchange saturation transfer imaging (gagCEST).
Methods: 258 lumbar IVDs of 53 participants, 21 healthy volunteers, 19 patients with LBP and 13 patients with radiculopathy (28
female; 25 male; mean age: 45.5 ± 16.7 years; range: 23 - 83 years), were examined with a 3T MRI scanner. Biochemical gagCEST
imaging was used to determine the GAG content of each nucleus pulposus (NP) and annulus fibrosus (AF).
Results: Significantly reduced gagCEST values of NP were found in patients with LBP and/or radiculopathy (p < 0.0001) compared to
healthy control group. NP gagCEST values were significantly lower in patients with LBP (p < 0.0001) and radiculopathy (p = 0.0005)
compared to healthy volunteers, respectively. We saw an association between pain and GAG loss with significantly lower gagCEST
values in participants with dorsal pain at examination day (p = 0.0004) and higher pain scores (p < 0.0001) compared to participants
without LBP. Participants with body mass index ≥ 25 revealed lower gagCEST values compared to participants with BMI < 25 (p =
0.02).
Conclusion: GagCEST analysis indicated significantly lower GAG values of NP in patients with LBP or radiculopathy, in participants
with elevated BMI, current pain at examination day and elevated pain scores.
Disclosure: P. Sewerin, None; C. Schleich, None; R. Sengewein, None; M. Schneider, None; B. Ostendorf, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/biochemical-intervertebral-disc-alterations-in-

patients-with-low-back-pain-and-radiculopathy
Frequency, Morbidity and Healthcare Utilization of Diffuse Idiopathic Skeletal

Hyperostosis (DISH) Patients at a University Hospital
Maanas Tripathi1, Divya Rajmohan2, Cody Quirk3, Brooke Beckett3, Donseok Choi4, Neha Rich-Garg5 and Atul A. Deodhar4,
1University of Miami, FL, Miami, FL, 2Oregon Health & Sciences University, Portland, OR, 3Radiology, Oregon Health & Science
University, Portland, OR, 4Oregon Health & Science University, Portland, OR, 5Northwest Rheumatology Assoc., Portland, OR
SESSION INFORMATION
Background/Purpose:
DISH is a non-inflammatory condition affecting the spine, and characterized by ossification of paravertebral ligaments. DISH is
traditionally considered asymptomatic, detected incidentally on spine radiographs. We investigated the frequency of DISH diagnosis,
the associated morbidity and healthcare utilization by patients attending our university hospital.
Methods:
Our University’s radiology database was searched from years 2005 to 2015 for the words “DISH” or “diffuse idiopathic skeletal
hyperostosis” in the recorded results of spinal radiographs. Patients from the year 2015 whose spinal radiographs mentioned these
words were selected for further analysis. Their spinal radiographs were re-read by two authors. Patients were divided into those who
fulfilled the Resnick Criteria for DISH (Group A), and those who did not fully meet the criteria but had radiographic features suggestive
of DISH (Group B). Means and proportions were used to describe variables, for group comparisons, T-test and c2 were used. A p-value
less than 0.05 was considered statistically significant. All computations were done in the R statistical program.
Results:
Between 2005-2015, 3439 radiology records had DISH mentioned as a diagnosis. Out of 196 patients diagnosed with DISH In 2015,
153 fulfilled the Resnick criteria (Group A), 41 didn’t fulfill the criteria but were diagnosed as DISH by the radiologists (Group B), and
2 had erroneous diagnoses. The Table shows the comparison between the two groups. Thoracic radiographs where DISH was mentioned
were more likely to fulfill the Resnick criteria than not (35% vs 15%) compared to other radiographs (p < 0.03). Chronic back pain was
very common in both groups, and more often reported in Group B than Group A (81% vs. 63%, p = 0.04). Back pain was the reason for
performing the initial diagnostic radiograph in 45% of Group A and 61% of Group B. A substantial portion of patients required opioid
medications for pain control (51%), spinal surgery (31%), and consultations with various specialists for regional pain (57%). Health
care interventions were similar in both groups.
Conclusion:
DISH is a common diagnosis with significant morbidity, despite being commonly considered to be an asymptomatic condition. Majority
of DISH patients had chronic back pain, required opioid medication, and a large proportion required spinal surgery. Future research is
needed to systematically assess the healthcare utilization by DISH patients.
Table: Comparison of DISH patients: those fulfilling Resnick criteria vs. not fulfilling Resnick criteria but diagnosed by
radiologists (ns = not significant)
Variable Group A: Group B: p
Resnick Resnick
Criteria Criteria not
fulfilled (n fulfilled (n
= 153) = 41)
Age in years 70.6 62.4 p < 0.01
(mean)
Male Gender 110 33 p = ns
(72%) (28%)
BMI 32.34 32.83 p = ns
Chronic Back 96 (63%) 33 (81%) p = 0.04
Pain
Type 2 19 (12%) 3 (7%) p = ns
Diabetes
Mellitus
Hypertension 33 (22%) 8 (20%) p = ns
Hyperlipidemia 19 (12%) 5 (12%) p=ns
Gout 10 (7%) 2 (5%) p = ns
Type of 2 (1%) 1 (3%) p = 0.03
Radiograph
12 (8%) 6 (15%)
Spinal Survey
11 (22%) 0 (NA)
Cervical
53 (35%) 6 (15%)
Thoracolumbar
68 (45%) 26 (66%)
Thoracic
3 (2%) 0 (NA)
Lumbar
Sacroiliac
Reason for X- 5 (3.3%) 0 (NA) Pearson's
ray c2
69 (45%) 25 (61%)
DISH p = ns
78 (51%) 16 (39%)
Pain
Other
Opioid Use 77 (54%) 22 (50%) p = ns
Bisphosphonate 1 (1%) 0 (0%) p =ns
Use
Spinal Surgery 46 (31%) 14 (34%) p = ns
Spinal Pumps 1 (1%) 0 (0%) p =ns
Consultations 8 (6%) 3 (8%) p = ns
Neurology 59 (42%) 23 (59%)
Orthopedics 7 (5%) 2 (5%)
Rheumatology 5 (4%) 1 (3%)
Physical
Medicine and
Rehabilitation
Disclosure: M. Tripathi, None; D. Rajmohan, None; C. Quirk, None; B. Beckett, None; D. Choi, None; N. Rich-Garg, Pfizer Inc,
2; A. A. Deodhar, AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB Pharma, 2,Eli Lilly, Janssen, Novartis,
Pfizer, UCB Pharma, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/frequency-morbidity-and-healthcare-utilization-of-

diffuse-idiopathic-skeletal-hyperostosis-dish-patients-at-a-university-hospital
Compression Assisted Arthrocentesis and Intraarticular Injection

James Bennett1, Tej Bhavsar1, Romy Cabacungan2, Sabeen Yaqub1, Monthida Fangtham3, N. Suzanne Emil1, Roderick Fields4,
Konstantin Konstantinov5, Arthur Bankhurst6, William Hayward7 and Wilmer Sibbitt Jr.3, 1Internal Medicine, Division of
Rheumatology, University of New Mexico Health Sciences Center, Albuquerque, NM, 2Internal Medicine, Division of Rheumatology,
University of New Mexico, Albuquerque, NM, 3Rheumatology, University of New Mexico, Albuquerque, NM, 4Internal Medicine/
Rheumatology, University of New Mexico School of Medicine, Albuquerque, NM, 51 University Of New Mexico, University of New
Mexico, Albuquerque, NM, 6Rheumatology, University of NM Medical Center, Albuquerque, NM, 7Exercise and Sport Sciences, New
Mexico Highlands University, Las Vegas, NM
SESSION INFORMATION
Background/Purpose:
We hypothesized that compression assisted arthrocentesis of the knee would improve arthrocentesis fluid yields and intraarticular
injection outcomes.
Methods:
We performed conventional arthrocentesis on 215 painful knees, both with and without effusions prior to injection. Subsequently a
constant compression device (a commercially available elastomeric brace positioned or modified so classic arthrocentesis portals could
be utilized) was placed and arthrocentesis was performed on 215 painful knees. In all cases, post arthrocentesis, 1mg/kg of
triamcinolone acetonide (60-80 mg total, 80 mg maximum) was injected into each knee. Arthrocentesis fluid yield and time to the next
flare were measured. The data were compared using Student's T-test.
Results:
The demographics of the study groups were similar. Fluid yield for complete arthrocentesis with constant compression was greater (by
230%) than the conventional technique: constant compression 5.3±11.2 ml, conventional 1.6±6.4 ml (difference 3.7 ml, CI of difference
1.9757 <3.7< 5.4243, p<0.00001). Fluid yield was also increased in the effusive knee subgroup (by 166%): constant compression (n =
38) 26.6±113.4 ml, conventional (n=37) 10.0±13.3 ml (p<0.00001)(Figure 1). Time to flare was 35% longer in the subjects treated with
constant compression 6.9±3.5 months as opposed to conventional treatment 5.1±2.7 months (p<0.00001)(Figure 2). The prolonged
effect of constant compression was present in both the effusive knee (30% longer, p<0.02) and the non-effusive knee (38% longer,
p<0.01).
Figure 1:
Figure 2:
Conclusion:
Constant compression of the knee results in greater arthrocentesis fluid yield and improved injection outcomes in both the effusive and
non-effusive knee. We hypothesize that more accurate needle placement, forced extrusion of interstitial fluid and cytokines from
compressed tissues, and more complete removal of fluid decrease inflammatory cells and cytokines and increase intraarticular drug
concentrations, resulting in improved outcomes. Constant compression of the knee is a straightforward and effective quality
improvement intervention for knee arthrocentesis and intraarticular injection.
Disclosure: J. Bennett, None; T. Bhavsar, None; R. Cabacungan, None; S. Yaqub, None; M. Fangtham, None; N. S. Emil, None;
R. Fields, None; K. Konstantinov, None; A. Bankhurst, None; W. Hayward, None; W. Sibbitt Jr., None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/compression-assisted-arthrocentesis-and-

intraarticular-injection
Comparison of Flexed and Extended Knee Arthrocentesis and the Role of Constant
Compression
Sabeen Yaqub1, Tej Bhavsar1, Romy Cabacungan2, James Bennett1, Monthida Fangtham3, N. Suzanne Emil1, Roderick Fields4,
Konstantin Konstantinov5, Arthur Bankhurst6, Luke Haseler7 and Wilmer Sibbitt Jr.3, 1Internal Medicine, Division of Rheumatology,
University of New Mexico Health Sciences Center, Albuquerque, NM, 2Internal Medicine, Division of Rheumatology, University of
New Mexico, Albuquerque, NM, 3Rheumatology, University of New Mexico, Albuquerque, NM, 4Internal Medicine/ Rheumatology,
University of New Mexico School of Medicine, Albuquerque, NM, 51 University Of New Mexico, University of New Mexico,
Albuquerque, NM, 6Rheumatology, University of NM Medical Center, Albuquerque, NM, 7Department of Physiotherapy and Exercise
Physiology, Curtin University, Perth, Australia
SESSION INFORMATION
Background/Purpose: The objective of this study was to determine whether extended versus flexed knee position is superior for
arthrocentesis.
Methods: 55 clinically effusive knees with osteoarthritis underwent arthrocentesis: 20 knees in the extended knee position using the
lateral superior approach, and 35 knees in the flexed knee position using the inferiolateral approach. Conventional arthrocentesis
maneuvers including manual compression were used and fluid yield in milliliters measured. After fluid return ceased in the flexed
knee, constant compression was applied using an elastomeric knee brace on the superior knee and additional fluid yield recorded. The
measurement data were compared using the Student test.
Results: Fluid yield for arthrocentesis with the extended knee was greater (191% greater) than the flexed knee: extended knee:
16.9±15.7 ml, flexed knee 5.8±6.3 ml (difference 11.1 ml, CI 0.91 <8.8< 16.7, p<0.02). After constant compression to the flexed knee
fluid yields were identical (1% different): extended knee: 16.9±15.7 ml, flexed knee 16.7±11.3ml (difference -0.2 ml, 95% CI 11.09
<-2.7< 5.6, p=0.73).
Conclusion: The extended knee lateral approach is superior to the flexed knee approach for conventional arthrocentesis. However,
when constant compression is applied, the two approaches have identical fluid yields. This new flexed knee constant compression
technique is particularly useful for patients who cannot get onto the examining table, who are in wheelchairs, have flexion contractures,
or who cannot otherwise extend their knee.
Figure 1: Fluid yields in extended and flexed knee positions

Figure 2: Arthrocentesis in Extended Knee Position
Figure 3: Arthrocentesis in Flexed Knee Position
Disclosure: S. Yaqub, None; T. Bhavsar, None; R. Cabacungan, None; J. Bennett, None; M. Fangtham, None; N. S. Emil, None;
R. Fields, None; K. Konstantinov, None; A. Bankhurst, None; L. Haseler, None; W. Sibbitt Jr., None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/comparison-of-flexed-and-extended-knee-

arthrocentesis-and-the-role-of-constant-compression
Total Ankle Arthroplasty for Rheumatoid Arthritis Cases in This Biologics Era: Mid
to Long-Term Follow-up
Makoto Hirao1, Jun Hashimoto2, Hideki Tsuboi3, Kosuke Ebina4 and Hideki Yoshikawa5, 1Orthopaedic Surgery, Osaka University,
Graduate School of Medicine, Suita, Japan, 2Rheumatology/Orthopaedics, Osaka-Minami Medical Ctr, Kawachinagano, Japan,
3Orthopaedics/Rheumatology, Osaka Rosai Hospital, Sakai, Japan, 4Orthopaedics, Osaka University Graduate School of Medicine,
Suita, Japan, 5Department of Orthopedics, Osaka University Graduate School of Medicine, Suita Osaka, Japan
SESSION INFORMATION
Background/Purpose: Outcomes after total ankle arthroplasty (TAA) combined with additive techniques (augmentation of bone
strength, control of soft tissue balance, adjustment of the loading axis) for destructive rheumatoid arthritis (RA) cases were evaluated
after mid to long-term follow-up. The influences of biologic treatment on the outcomes after TAA were also evaluated.
Methods: A retrospective observational study was completed involving 50 RA cases [mean follow-up period: 7.1 years] who
underwent TAA. RA foot ankle scales were administered using the Japanese Society for Surgery of the Foot (JSSF) standard rating
system, and a postoperative self-administered foot evaluation questionnaire (SAFE-Q) was also checked at final follow-up.
Radiographic findings were also checked.
Results: This procedure significantly improved the clinical scores of the JSSF RA foot and ankle scales. Of 50 ankles, 48 had no
revision TAA surgery. Prosthesis sinking at the talus side was seen in 8 ankles (6 ankles in biologics group, 2 ankles in non-biologics
group); 2 required revision TAA. The social functioning score of the SAFE-Q scale at final follow-up was significantly higher in the
biologic treatment group than in the non-biologic group. The biologic treatment group showed a significantly lower rate of prednisolone
usage (12%) than the non-biologic treatment group (71%), and disease activity was significantly improved in the biologic treatment
group at final follow-up.
Conclusion: TAA is recommended for RA cases, if disease control, augmentation of bone strength, control of soft tissue balance, and
adjustment of loading axis are taken into account. Withdrawal of the steroid in biologics treatment might have a good effect on the
durability of prostheses in long-term observation in the perspective of bone-mineral structure. Biologics treatment contributed to
increase social activity after TAA in RA cases. So, prevention of talar component sinking for RA cases with such higher social activity
should be further discussed and resolved in this biologics era.
Disclosure: M. Hirao, None; J. Hashimoto, None; H. Tsuboi, None; K. Ebina, Chugai Pharmaceutical, Eisai, Ono Pharmaceutical,
Mitsubishi Tanabe Pharma, UCB Japan, 8; H. Yoshikawa, Chugai Pharmaceutical, Eisai, Ono Pharmaceutical, Mitsubishi Tanabe
Pharma, Phizer, Astellas Pharma, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/total-ankle-arthroplasty-for-rheumatoid-arthritis-

cases-in-this-biologics-era-mid-to-long-term-follow-up
Rates of Total Joint Replacement Utilization in the U.S.: Future Projections to 2020-
2040 Using the National Inpatient Sample
Jasvinder A. Singh and Shaohua Yu, University of Alabama at Birmingham, Birmingham, AL
SESSION INFORMATION
Background/Purpose: To project the future utilization of total hip and knee joint arthroplasty (THA, TKA).
Methods: We used the 2000-2010 U.S. National Inpatient Sample combined with Census Bureau data to develop projections for
primary and revision THA and TKA from 2020 to 2040 using negative binomial regression.
Results: Predicted total annual counts for THA and TKA utilization in the U.S. by 2020, 2025, 2030 and 2040 are (in
thousands): primary THA, 527 (95% CI, 495, 561), 765 (95% CI, 712, 823), 1087 (95% CI, 999, 1184) and 2040 (95% CI, 1828,
2081); primary TKA, 1611 (95% CI, 1531, 1699), 2675 (95% CI, 2516, 2847); 4306 (95% CI, 4008, 4632) and 10314 (95% CI,
9391, 11343); revision THA 56 (95% CI, 51, 61), 68 (95% CI, 61, 76), 82 (95% CI, 72, 93) and 204 (95% CI, 183, 228); and
revision TKA, 153 (95% CI, 140, 168), 250 (95% CI, 226, 279), 399 (95% CI, 353, 452) and 1031 ((95% CI, 939, 1134) (Figures 1
and 2). The utilization is projected to increase for both females and males (Figure 3), all age groups and all race/ethnicities (data not
shown).
Conclusion: Significant increases in THA and TKA utilization are expected in the future. A policy change may be needed to meet
increased demand.
FIGURES
Figure 1. The projected annual total utilization of primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) procedures (in
thousands) in the United States from 2020 to 2040
Figure 2. The projected annual total utilization of revision total hip arthroplasty (THA) and total knee arthroplasty (TKA) procedures (in
thousands) in the United States from 2020 to 2040
Figure 3. The projected annual total utilization of primary total Knee arthroplasty (TKA) procedures in the United States from 2020 to
2040 by sex
Disclosure: J. A. Singh, Takeda and Savient, 2,Savient, Takeda, Regeneron, Merz, Iroko, Bioiberica, Crealta/Horizon and Allergan
pharmaceuticals, WebMD, UBM LLC and the American College of Rheumatology., 5,JAS serves as the principal investigator for an
investigator-initiated study funded by Horizon pharmaceuticals through a grant to DINORA, Inc., a 501 (c)(3) entity., 9,JAS is a
member of the executive of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length
funding from 36 companies., 9,JAS is the editor and the Director of the UAB Cochrane Musculoskeletal Group Satellite Center on
Network Meta-analysis., 9,Jas is a member of the American College of Rheumatology's (ACR) Annual Meeting Planning Committee
(AMPC); Chair of the ACR Meet-the-Professor, Workshop and Study Group Subcommittee., 9,a member of the Veterans Affairs
Rheumatology Field Advisory Committee, 9; S. Yu, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rates-of-total-joint-replacement-utilization-in-the-u-
s-future-projections-to-2020-2040-using-the-national-inpatient-sample
The Effect of Obesity on Walking; Comparison of the Spatiotemporal, Kinematic

and Kinetic Parameters of Young Obese and Non-Obese Healthy Women
Erkan Kilic1, Gamze Kilic2 and Fatma Inanici3, 1Rheumatology Clinic, Afyonkarahisar State Hospital, Afyon, Turkey, 2Pyhsical
Medicine and Rehabilitation, Afyon Kocatepe University, Faculty of Medicine, Afyon, Turkey, 3Pyhsical Medicine and Rehabilitation,
Hacettepe University, Faculty of Medicine, Ankara, Turkey
SESSION INFORMATION
Background/Purpose: Obesity is a risk factor for development of knee osteoarthritis due to altered gait biomechanics. Gait analysis
was performed mostly on older obese adults with knee osteoarthritis. Biomechanics of young obese individuals is unclear. The aim of
this study was to investigate the effect of obesity on gait biomechanics in young women; and the relationship between obesity and
occurrence of knee osteoarthritis.
Methods: 31 healthy normal-weighted and 31 obese women aged between 30-45 years and body mass indexes (BMI) between 30-40
kg/m2 were included in this study. Anthropometric measurements like body weight (BW), height, waist/hip ratios were measured.
Skinfold thickness (SFT) was measured from right side of the body. Isokinetic quadricesps and hamstring muscle strengths were
measured at 60°/s angular velocity and 0-90° joint range of motion. Body composition analyses were determined before breakfast. Gait
analyses were performed by Vicon 612 gait analyses system with the subjects' comfortable walking speed.
Results: Mean age of obese group was 39.4 years and control group was 35.8 years (p˃0.05). Circumferences and SFT, body fat ratio,
fat free mass (FFM) found higher in obese group (p«0. 001) and there was a strong relation between fat ratio and circumferences (r
=0.89), BMI (r=0.85) and SFT (r=0.83). When peak torque were normalized to BW, Isokinetic quadricesps and hamstring muscle
strengths were significantly lower in obese individuals (p<0.001). Walking speed, single support time, step length and stride length were
lower and stance phase, double support time and step width was higher in obese individuals (p<0.001). In obese group we found that
total excursion of pelvic obliquity, hip rotation and knee flexion-extension angle was lower (p<0.001), knee varus moment (p<0.05) and
second peak of vertical ground reaction force was higher in obese group (p<0.001).
Conclusion: In obese subjects, isokinetic quadriceps and hamstring muscles strengths were lower, knee and hip joint range of motion
was diminished. Knee peak varus moment and vertical ground reaction force at the end of stance phase were significantly higher in
obese group. These results suggest that obesity may contribute to knee osteoarthritis. Thus, prospective studies are needed to identify
the influence of higher loading rates on knee osteoarthritis.
Disclosure: E. Kilic, None; G. Kilic, None; F. Inanici, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-effect-of-obesity-on-walking-comparison-of-

the-spatiotemporal-kinematic-and-kinetic-parameters-of-young-obese-and-non-obese-healthy-women
Effects of Exercise on Anxiety in Adults with Arthritis: A Systematic Review with

Meta-Analysis
George Kelley1, Kristi Kelley1 and Leigh F. Callahan2, 1Biostatistics, West Virginia University, Morgantown, WV, 2Thurston Arthritis
Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC
SESSION INFORMATION
Session Title: ARHP Orthopedics, Low Back Pain and Rehabilitation Poster
Background/Purpose: Previous randomized controlled trials have led to conflicting findings regarding the effects of exercise on
anxiety in adults with arthritis and other rheumatic diseases (AORD). The purpose of this study was to use the meta-analytic approach
to try and resolve these discrepancies.
Methods: The a priori inclusion criteria were: (1) randomized controlled trials, (2) exercise (aerobic, strength training, or both) >/= 4
weeks, (3) comparative control group, (4) adults >/= 18 years of age with osteoarthritis, rheumatoid arthritis or fibromyalgia, (5)
published and unpublished studies in any language since January 1, 1981, (6) anxiety as an outcome assessed. Studies were located by
searching 8 electronic databases, cross-referencing and expert review. Dual selection of studies and data abstraction were performed.
Hedge’s standardized effect size (g) was calculated for each result and pooled using the recently developed inverse-heterogeneity
(IVhet) model. Non-overlapping 95% confidence intervals were considered statistically significant. Heterogeneity was estimated using
Q and I2 with alpha values < 0.10 for Q considered statistically significant. Small-study effects were examined using funnel plots and
Egger’s regression test. In addition, the number-needed-to-treat (NNT), percentile improvement, and subgroup analyses were
conducted. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Instrument. Training program characteristics were
reported as mean +/- standard deviation.
Results: Of the 639 citations screened, 14 studies representing 926 initially enrolled participants (539 exercise, 387 control) met the
criteria for inclusion. Length of training averaged 15.8 +/- 6.7 weeks, frequency 3.3 +/- 1.3 times per week and duration 28.8 +/- 14.3
minutes per session. Overall, statistically significant exercise minus control reductions in anxiety were found (g = -0.40, 95% CI, -0.65,
-0.15, tau2 = 0.14; Q = 40.3, p = 0.0004; I2 = 62.8%). The NNT was 6 with a percentile improvement of 15.5% and an estimated 5.3
million inactive US adults with AORD improving their anxiety if they started exercising regularly. Statistically significant small-study
effects were observed (p < 0.0001). No between-group differences in anxiety were observed between type of arthritis and type of
exercise. All studies were considered to be at high risk of bias with respect to blinding of participants to group assignment. Given the
lack of information provided, greater than 50% of studies were at an unclear or high risk of bias with respect to (1) incomplete outcome
reporting (78.6%), (2) allocation concealment (78.6%), and (3) blinding of outcome assessors (57.1%).
Conclusion: Exercise is associated with reductions in anxiety among adults with AORD. However, a need exists for additional, well-
designed, randomized controlled trials on this topic.
Disclosure: G. Kelley, None; K. Kelley, None; L. F. Callahan, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effects-of-exercise-on-anxiety-in-adults-with-

arthritis-a-systematic-review-with-meta-analysis
Efficacy of a Wearable-Enabled Physical Activity Counselling Program for People

with Knee Osteoarthritis
Linda Li1, Eric C. Sayre2, Navi Grewal2, Juliane Chien2, Greg Noonan3, Ryan Falck1, John Best4, Teresa Liu-Ambrose1, Alison
Hoens5, Valerie Gray6, Karen Tsui7, Wendy Watson6 and Lynne Feehan8, 1Department of Physical Therapy, University of British
Columbia, Vancouver, BC, Canada, 2Arthritis Research Canada, Richmond, BC, Canada, 3Mary Pack Arthritis Program, Vancouver
General Hospital, Vancouver, BC, Canada, 4University of British Columbia, vancouver, BC, Canada, 5BC SUPPORT Unit, Vancouver,
BC, Canada, 6OASIS Program, Vancouver Coastal Health Authority, Vancouver, BC, Canada, 7Fraser Health Authority, Surrey, BC,
Canada, 8Rehabilitation Program, Fraser Health Authority, Surrey, BC, Canada
SESSION INFORMATION
Background/Purpose: Current guidelines emphasize an active lifestyle in the management of knee osteoarthritis (OA), but up to 90%
of OA patients are inactive. Several modifiable risk factors are associated with low physical activity participation, including lack of
motivation, doubts about effectiveness of exercise, and lack of health professional advice regarding ways to adjust their activities based
on symptoms. Our study aimed to assess the efficacy of a wearable-enabled physical activity counselling program for improving
activity participation and disease status in people with knee OA.
Methods: Eligible participants had a self-reported knee OA diagnosis, or symptoms of knee OA based on a validated questionnaire.
After baseline assessment and randomization, the Immediate Intervention Group (II) received group education, a Fitbit, and 4 biweekly
phone calls by a physiotherapist to counsel activity goals over a 2-month period. The Delayed Intervention (DI) Group received the
program 2 months later. Participants were assessed at baseline (T0) and the end of 2, 4 and 6 months (T1, 2, and 3). Outcome measures
included: 1) mean moderate/vigorous physical activity (MVPA) time measured with a SenseWear® monitor; 2) mean daily step count;
3) mean sedentary behaviour time; 4) Knee Injury & OA Outcome Score (KOOS). Analysis of covariance (ANCOVA) was used to
evaluate the effect of the group type on the outcome measures at T1, 2, and 3, after adjusting for T0. We assessed three planned
contrasts of changes: 1) compared T0–T1 between the two groups to determine if II was superior to DI (the control); 2) compared T0–
T2 in II against T0–T3 in DI; 3) compared T0–T2 in II against T1–T3 in the DI. The last 2 models assessed whether the two-month
delay had an impact on the effect of the intervention.
Results: In 2015–2016, we recruited 61 participants (II: n=30, 73% women; DI: n=31, 90% women). Both groups were similar in age
(II: 61.3 (9.4) years; DI: 62.1 (SD 8.5)] and body mass index [II: 29.2 (5.5); DI: 29.2 (4.8)]. Figure 1 summarizes the results. Pre-
specified contrast analyses revealed a significant effect whereby the II group improved in the MVPA time at T0–T1 compared to the DI
(contrast coefficient: 25.2; 95% CI 5.5, 44.9; p = 0.01). A significant effect was also found in the mean daily steps at T0–T1 (contrast
coefficient: 1,519; 95% CI 256.2, 2,782.3; p = 0.02). We found no significant effect in any outcome measures in the other contrast
analyses.
Table 1: Results of outcome measures

Immediate Intervention Group Delayed Intervention Group
(n = 30) (n = 31)
T0 T1 T2 T3 T0 T1 T2 T3
Mean 62.1 75.5 62.6 65.6 65.3 49.6 60.1 70.7
MVPA (54.6) (54.3) (56.3) (48.5) (77.4) (46.8) (76.8) (71.9)
time
[mins]
Mean 7,069.2 8,217.4 8,132.5 8,215.1 7,556.6 6,713.6 7,631.9 7,573.6
daily steps (3,375.3) (3,095.5) (3,420.7) (3725.6) (5,054.1) (3,354.3) (4,054.3) (4,477.1)
Mean 464.1 437.6 505.9 435.8 497.4 503.0 508.9 496.9
sedentary (137.7) (133.9) (167.2) (138.8) (200.7) (160.7) (189.0) (179.5)
time
[mins]
KOOS (0-100; higher =
better)
Symptoms 59.8 62.6 62.4 62.1 62.9 61.7 63.4 61.4
(16.1) (15.6) (14.7) (15.3) (17.2) (14.5) (16.7) (19.8)
Pain 66.2 70.9 67.5 68.6 65.1 64.8 66.3 66.2
(17.5) (17.0) (15.5) (17.5) (17.9) (14.6) (15.2) (16.4)
ADL 71.8 76.0 76.6 75.1 74.1 71.0 75.2 73.9
(17.5) (16.1) (17.5) (15.9) (17.6) (16.5) (17.2) (15.8)
Sports & 47.3 49.3 50.0 50.4 52.7 47.0 48.9 49.8
recreation (26.6) (24.9) (25.6) (26.3) (27.7) (23.3) (27.7) (29.2)
Qol 41.0 47.2 45.4 44.9 44.6 42.4 47.5 48.1
(19.8) (18.9) (17.6) (17.9) (16.3) (16.8) (13.6) (19.1)
Conclusion: Our wearable-enabled counselling program improved MVPA time and step counts in people with a diagnosis or symptoms
of knee OA. The finding is important since an active lifestyle is recognized as an important component of successful self-management.
Disclosure: L. Li, None; E. C. Sayre, None; N. Grewal, None; J. Chien, None; G. Noonan, None; R. Falck, None; J. Best, None; T.
Liu-Ambrose, None; A. Hoens, None; V. Gray, None; K. Tsui, None; W. Watson, None; L. Feehan, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/efficacy-of-a-wearable-enabled-physical-activity-

counselling-program-for-people-with-knee-osteoarthritis
Pain, Fatigue and Function in Patients with Ehlers-Danlos Syndrome and

Hypermobility Spectrum Disorder – Relationship with Perceived Benefits and
Barriers to Exercise
Leslie Soever1, Laura Passalent2, Ahmed Omar3 and Medha Soowamber4, 1Toronto General Hospital, Toronto, ON, Canada, 2Allied
Health, Toronto Western Hospital, Toronto, ON, Canada, 3Rheumatology, Toronto Western Hospital, University of Toronto, Toronto,
ON, Canada, 4University Health Network, Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose: The Ehlers-Danlos Syndromes (EDS) are a heritable group of connective tissue disorders with predominant
features including joint hypermobility, skin hyperextensibility and tissue fragility. Hypermobility Spectrum Disorders (HSD) include all
phenotypes presenting with joint hypermobility plus one or more of its secondary manifestations but not satisfying the criteria for EDS
(Castori, 2017). Common symptoms reported by patients with EDS and HSD include pain and fatigue, resulting in decreased function,
including lack of exercise. It has been shown that patients with EDS and HSD overall improve with exercise interventions (Palmer,
2014).The purpose of this study was explore relationships between self-reported pain, fatigue, and function; with perceived benefits and
barriers to exercise.
Methods: A retrospective chart review was completed on 38 consecutive patients with either EDS or HSD to determine if there were
any relationships between the scores for pain (high scores indicate greater pain), fatigue (high scores indicate greater fatigue), and
function (low scores indicate greater function), as per the Multi-Dimensional Health Assessment Questionnaire (MD- HAQ); and the
total score (high scores indicate more positive perception of exercise), benefits score (high scores indicate more positive perception of
exercise), and barriers score (high scores indicate greater perception of barriers to exercise) on the Exercise Benefits and Barriers Scale
(EBBS). These instruments were administered to patients as part of routine care to assist with treatment planning and recommendations.
Descriptive statistics and univariate analysis (Pearson correlation coefficients) were used to determine if relationships existed between
self-reported pain, fatigue and function; and perceived benefits scores, barriers scores, and total EBBS scores reported by patients.
Results: The majority of the sample was female (96 %); and the average age was 33.5 years. According to the 2017 International
Classification for EDS, 23 patients had EDS (hypermobility type n=20; classical type n=1; vascular type n=1; kyphoscoliotic type n=1)
and15 patients had HSD. Overall, EBBS scores indicated high perceived value of exercise. There was no relationship between fatigue (r
= -0.143; p = 0.39) nor pain (r = -0.192; p = 0.25) with total EBBS scores. However, the higher patients reported their level of function,
the higher were their total EBBS scores (r = 0.392; p = 0.015). Similarly, higher function scores, correlated with higher total benefits
scores (r = 0.383; p = 0.018); and patients who reported higher function reported fewer perceived barriers to exercise (r = -0.44; p =
0.006).
Conclusion: These results support previously reported importance of exercise in the management of patients with EDS and HSD; and
further highlight the critical role of programs to educate patients, with EDS and HSD regarding the importance of exercise, who are
experiencing difficulty with function.
Disclosure: L. Soever, None; L. Passalent, None; A. Omar, None; M. Soowamber, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/pain-fatigue-and-function-in-patients-with-ehlers-

danlos-syndrome-and-hypermobility-spectrum-disorder-relationship-with-perceived-benefits-and-barriers-to-exercise
Risk Factors for Blood Transfusions Following Total Joint Arthroplasty in Patients
with Rheumatoid Arthritis
Elizabeth Salt1, Andrew Johannemann1, Amanda T. Wiggins2, Mary Kay Rayens3, Katelyn Brown1, Kate Ekmann1 and Leslie
Crofford4, 1University of Kentucky, Lexington, KY, 2Nursing, University of Kentucky, Lexington, KY, 3College of Nursing, University
of Kentucky, Lexington, KY, 4Rheumatology, Vanderbilt University School of Medicine, Nashville, TN
SESSION INFORMATION
Risk Factors for Blood Transfusions Following Total Joint Arthroplasty in Patients with Rheumatoid Arthritis
Abstract
Background/Purpose: Despite effective therapies, rheumatoid arthritis (RA) can result in joint destruction requiring total joint
arthroplasty to maintain patient function. An estimated 16% to 70% of those undergoing total joint arthroplasty of the hip or knee will
receive a blood transfusion. Few studies have described risk factors for blood transfusion following total joint arthroplasty in patients
with RA. The purpose of this study is to identify demographic and clinical risk factors associated with receiving a blood transfusion
following total joint arthroplasty among patients with RA.
Methods: A retrospective study (N = 3,270) was conducted using de-identified patient health claims information from a commercially-
insured, U.S. dataset (2007-2009). Data analysis included descriptive statistics and multivariate logistic regression.
Results: Females were more likely to receive a blood transfusion (Odds ratio [OR]=1.48; 95% Confidence Interval [CI]: 1.16-1.87;
p=.001). When compared to those in the South, patients residing the Midwest were less likely to receive a blood transfusion following
total joint arthroplasty (OR=0.56, 95% CI: 0.44-0.71). Relative to those receiving total knee arthroplasty, patients who underwent total
hip arthroplasty were more likely to receive a blood transfusion (OR=1.39, 95% CI: 1.14-1.70), and patients who underwent a total
shoulder arthroplasty were less likely to receive a blood transfusion (OR=0.14 and 95% CI: 0.05-0.38; p<.001). Patients with a history
of anemia were more likely to receive a blood transfusion compared to those who did not have this diagnosis (OR=3.30, 95% CI: 2.62-
4.14; p<.001).
Conclusion: Risk factors for the receipt of blood transfusions among RA patients who have undergone total joint arthroplasty were
identified.
Disclosure: E. Salt, None; A. Johannemann, None; A. T. Wiggins, None; M. K. Rayens, None; K. Brown, None; K. Ekmann,
None; L. Crofford, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/risk-factors-for-blood-transfusions-following-total-

joint-arthroplasty-in-patients-with-rheumatoid-arthritis
A Randomized Alendronate-Controlled Trial of Romosozumab: Results of the Phase

3 Active-Controlled Fracture Study in Postmenopausal Women with Osteoporosis at
High Risk
Kenneth Saag1, Jeffrey Petersen2, Maria Luisa Brandi3, Andrew Karaplis4, Mattias Lorentzon5, Thierry Thomas6, Judy Maddox2,
Michelle Fan2, Paul D. Meisner7 and Andreas Grauer2, 1University of Alabama, Birmingham, AL, 2Amgen Inc., Thousand Oaks, CA,
3University of Florence, Florence, Italy, 4McGill University, Montreal, QC, Canada, 5University of Gothenburg and Sahlgrenska
University Hospital, Mölndal, Sweden, 6CHU de Saint-Étienne, Saint-Étienne, France, 7UCB Pharma, Brussels, Belgium
SESSION INFORMATION
Session Title: Osteoporosis and Metabolic Bone Disease – Clinical Aspects and Pathogenesis Poster I
Background/Purpose: The bone forming agent romosozumab (Romo) was previously shown to reduce vertebral and clinical fractures
in postmenopausal women with osteoporosis. Here we report the efficacy and safety results of the ARCH study (NCT01631214).
Methods: This multicenter double-blind study enrolled postmenopausal women age 55–90 years with osteoporosis and high fracture
risk, defined as a BMD T-score ≤‒2.5 at total hip [TH] or femoral neck [FN] and either ≥1 moderate/severe or ≥2 mild vertebral
fractures, or a BMD T-score ≤–2.0 at TH or FN and either ≥2 moderate/severe vertebral fractures or a history of a recent hip fracture.
Subjects were randomized 1:1 to 210mg Romo SC QM or 70mg alendronate (ALN) PO QW for 12 months, followed by open label
70mg ALN PO QW in both groups. Primary endpoints were subject incidence of new vertebral fracture through 24 months and clinical
fracture through the primary analysis (PA). PA was performed when ≥330 clinical fractures had occurred and all subjects had completed
the month 24 visit. Nonvertebral fracture at the PA was a secondary endpoint, as was BMD at the lumbar spine, TH, and FN at months
12 and 24. Hip fracture was evaluated as an additional secondary endpoint.
Results: 4093 women (mean age 74, mean TH T-score –2.8) were randomized to Romo or ALN. 12 months of Romo prior to ALN vs
ALN alone significantly reduced new vertebral, clinical, nonvertebral, and hip fractures (Table). Treatment with Romo also significantly
increased BMD at all sites measured, at months 12 and 24 vs ALN alone (Table). Overall adverse events were balanced between
groups. During the open label ALN period, 6 subjects (2 Romo; 4 ALN) were positively adjudicated for AFF and 2 subjects (1 Romo; 1
ALN) for ONJ. Cardiovascular (CV) serious adverse events (SAEs) were independently adjudicated; at 12 months the subject incidence
was 2.5% in the Romo group vs 1.9% in the ALN group with cardiac ischemic events at 0.8% vs 0.3% and cerebrovascular events at
0.8% vs 0.3%, respectively.
Conclusion: In postmenopausal women with osteoporosis, Romo 210mg QM followed by ALN significantly reduced new vertebral,
clinical, nonvertebral, and hip fracture risk vs ALN alone, suggesting that in osteoporotic patients at high risk for fracture, a treatment
regimen starting with Romo followed by ALN leads to superior fracture risk reduction over ALN alone. An observed imbalance in CV
SAEs compared with ALN was not seen in the previous placebo-controlled 7180-patient FRAME study and is currently being
evaluated.
Disclosure: K. Saag, Amgen, Merck, 2,Amgen, Merck, Radius, 5; J. Petersen, Amgen Inc., 1,Amgen Inc., 3; M. L. Brandi, Abiogen,
Alexion, Amgen, Bruno Farmaceutici, Kyowa Kirin, Shire, SPA, 2,Abiogen, Alexion, Amgen, Bruno Farmaceutici, Kyowa Kirin,
Shire, SPA, 5,Shire, 8; A. Karaplis, Amgen Canada, 2,Amgen Canada, 5,Amgen Canada, 8; M. Lorentzon, Consilient Health, Radius
Health, 5,Amgen, Lilly, Meda, UCB, 9; T. Thomas, Amgen, Chugaï/Roche, HAC-Pharma, LCA, MSD, Novartis, Pfizer, Servier, UCB,
2,Abbvie, Amgen, BMS, Chugaï, HAC-Pharma, Expanscience, Gilead, Lilly, Medac, MSD, Pfizer, Teva, Thuasne, UCB, 5; J.
Maddox, Amgen Inc., 1,Amgen Inc., 3; M. Fan, Amgen Inc., 1,Amgen Inc., 3; P. D. Meisner, UCB Pharma, 1; A. Grauer, Amgen
Inc., 1,Amgen Inc., 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-randomized-alendronate-controlled-trial-of-

romosozumab-results-of-the-phase-3-active-controlled-fracture-study-in-postmenopausal-women-with-osteoporosis-at-high-risk
The Placebo-Controlled Fracture Study in Postmenopausal Women with

Osteoporosis: The Foundation Effect of Rebuilding Bone with One Year of
Romosozumab Leads to Continued Lower Fracture Risk after Transition to
Denosumab
Felicia Cosman1, Daria B Crittenden2, Serge Ferrari3, Aliya Khan4, Nancy E Lane5, Kurt Lippuner6, Toshio Matsumoto7, Cassandra E
Milmont2, Cesar Libanati8 and Andreas Grauer2, 1Helen Hayes Hospital, West Haverstraw, and Columbia University, New York, NY,
2Amgen Inc., Thousand Oaks, CA, 3Geneva University Hospital, Geneva, Switzerland, 4McMaster University, Hamilton, ON, Canada,
5UC Davis Medical Center, Sacramento, CA, 6Osteoporosis Policlinic, Inselspital, Bern University Hospital and University of Bern,
Bern, Switzerland, 7University of Tokushima, Tokushima, Japan, 8UCB Pharma, Brussels, Belgium
SESSION INFORMATION
Background/Purpose: Romosozumab (Romo), a sclerostin antibody, has a dual effect of increasing bone formation and decreasing
bone resorption. In the FRAME study, one year of Romo treatment resulted in large BMD increases at the lumbar spine and total hip
versus placebo (PBO); the differences between groups remained after all subjects transitioned to denosumab (DMAb) during the second
year of the study (Cosman NEJM 2016). Here, we further characterize the BMD gains during the FRAME study and the effect of
building bone with Romo on fracture risk reduction upon transition to DMAb.
Methods: Subjects in FRAME (NCT01575834) were randomized to receive Romo 210 mg QM or PBO for 12 months, after which all
subjects received DMAb 60 mg Q6M for an additional 12 months. Endpoints for the current analysis were mean change from baseline
in BMD T-score, percent of subjects with a BMD gain, and subject incidence of fractures in the second year of the study, including new
vertebral, clinical (nonvertebral plus symptomatic vertebral), and other fracture categories.
Results: There were 7180 subjects in the study (N=3589 Romo, N=3591 PBO). At month 12, mean change from baseline in lumbar
spine BMD T-score was 0.88 for Romo and 0.03 for PBO; at month 24, after both treatment groups received DMAb in the second year,
the mean change from baseline was 1.11 for Romo/DMAb and 0.38 for PBO/DMAb. At the total hip, the mean changes were 0.32 for
Romo and 0.01 for PBO at month 12, with month-24 changes of 0.45 for Romo/DMAb and 0.17 for PBO/DMAb. 99% of subjects in
the Romo group showed some increase in BMD at month 12, with 89% achieving ≥ 6% gains in lumbar spine BMD (Figure).
Administration of Romo during the first year led to relative risk reductions in fractures between groups during the second year, despite
both groups receiving DMAb in year two, with reductions of 81% for vertebral fractures (p < 0.001), 32% for clinical fractures (p =
0.052), and 39% for major osteoporotic fractures (p = 0.034).
Conclusion: Romo resulted in substantial T-score increases after one year; upon transition to DMAb, gains in both groups were similar,
resulting in unprecedented BMD gains after treatment with Romo followed by DMAb. As a result of one year of Romo before transition
to DMAb, fracture rates were substantially reduced during year two, when subjects in both groups received DMAb. The data support
the clinical benefit of rebuilding the skeletal foundation with Romo treatment before transition to DMAb.
Disclosure: F. Cosman, Amgen, Eli Lilly, 2,Merck, Radius, Tarsa, 5,Amgen, Eli Lilly, 8,Amgen, Eli Lilly, Merck, Radius, 9; D. B.
Crittenden, Amgen, 1,Amgen, 3; S. Ferrari, MSD, UCB Pharma, 2,Agnovos, Amgen, Labatec, UCB Pharma, 5,Amgen, Sandoz,
UCB Pharma, 8,Novartis Pharmaceutical Corporation, 9; A. Khan, Amgen, Shire, 2; N. E. Lane, Amgen, 5,Novartis Pharmaceutical
Corporation, 8; K. Lippuner, None; T. Matsumoto, Astellas Pharma, Daiichi-Sankyo, 2,Amgen-Astellas Biopharma, Chugai, Eli Lilly,
Teijin, 5,Ono Pharmaceuticals, 8; C. E. Milmont, Amgen, 1,Amgen, 3; C. Libanati, UCB Pharma, 1,UCB Pharma, 3; A. Grauer,
Amgen, 1,Amgen, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-placebo-controlled-fracture-study-in-

postmenopausal-women-with-osteoporosis-the-foundation-effect-of-rebuilding-bone-with-one-year-of-romosozumab-leads-to-
continued-lower-fracture-risk-after-tran
Teriparatide Compared with Risedronate and the Risk of Clinical Vertebral

Fractures: 2-Year Results of a Randomized, Double-Dummy Clinical Trial
Cristiano A.F Zerbini1, Piet Geusens2, Eric Lespessailles3, Jean-Jacques Body4, Enrique Casado5, Jan Stepan6, David L Kendler7,
Luis Russo8, Susan L. Greenspan9, Salvatore Minisola10, Alicia Bagur11, Peter Lakatos12, Astrid Fahrleitner-Pammer13, Rüdiger
Möricke14, Pedro Lopez-Romero15 and Fernando Marin16, 1Centro Paulista de Investigações Clinicas, São Paulo, Brazil, 2Maastricht
University Hospital, Maastricht, Netherlands, 3Service de Rhumatologie, CHR d'Orléans, Orléans, France, 4CHU Brugmann, Free
University Brussels, Brussels, Belgium, 5Rheumatology, University Hospital Parc Taulí, Sabadell, Spain, 6Institute of Rheumatology,
Faculty of Medicine 1, Charles University, Prague, Czech Republic, 7University of British Columbia, Vancouver, BC, Canada, 8Centro
de Analises e Pesquisas Clínicas LTDA,, Rio de Janeiro, Brazil, 9University of Pittsburgh, Pittsburgh, PA, 10Internal Medicine,
Policlinico Umberto I,, Rome, Italy, 11Centro de Osteopatías Comlit, Buenos Aires, Argentina, 12Department of Medicine, Semmelweis
University, Budapest, Hungary, 13Division of Endocrinology, Medical University, Graz, Austria, 14Institut Präventive Medizin &
Klinische Forschung, Magdeburg, Germany, 15Europe Research Center, Eli Lilly and Company, Madrid, Spain, 16Lilly Research Center
Europe, Madrid, Spain
SESSION INFORMATION
Background/Purpose: The VERO trial was an active-controlled fracture endpoint clinical trial that recruited postmenopausal women
with low bone mass and prevalent vertebral fractures (VFx). We have reported that the risk of new VFx and clinical fractures [a
composite of clinical VFx and non-vertebral fragility fractures (NVFFx)] in patients treated with teriparatide (TPTD) compared with
those treated with risedronate (RIS) was reduced by 56% and 52% respectively (p<.001 for each), with a non-significant reduction in
NVFFx (34%, p=0.099). Here we present the pre-specified exploratory analysis of clinical vertebral fracture (ClinVFx) incidence over
24 months.
Methods: 1,360 postmenopausal women (680/arm; mean age: 72.1 years) with at least 2 moderate or 1 severe VFx and low bone mass
(BMD T-score ≤-1.5) were randomized to TPTD 20 µg sc/day or RIS (35 mg po/week) in a 2-year, double-blind, double-dummy trial.
A ClinVFx was defined as an clinical episode associated with signs and symptoms suggestive of a VFx, such as acute onset of severe
back pain, pain with little or no exertion or pain localised to a specific vertebra and associated with limited back mobility, confirmed
with a new or worsened radiographic VFx (centrally adjudicated). A new vertebral fracture was radiologically defined as a loss of
vertebral body height of at least 20% and 4 mm from the baseline radiograph by quantitative morphometry measurements, confirmed
with a semiquantitative assessment (i.e.; the vertebral body also has an increase of 1 or more severity grade according to the Genant
scale). Cumulative incidences of the first ClinVFx were obtained by Kaplan-Meier, and comparison was based on a stratified long-rank
test. The stratified HR was computed from the log-rank test. Incidence rates, depicted as number of events per 100 patient-years, were
also assessed.
Results: The mean (SD) number of prevalent VFx was 2.7 (2.1), 55.4% of the women had a BMD T-score <-2.5 (lowest value
measured at the lumbar spine or hip), 36.5% a history of ClinVFx within the year before randomization, 27.9% were naïve to
osteoporosis medications, and 57.9% were previously treated with bisphosphonates. A total of 31 women were diagnosed with an
incident ClinVFx over the 24-month study duration: 7 women in the TPTD group (1.1%) compared to 24 women (3.9%) in the RIS
group (hazard ratio: 0.29; 95% CI: 0.14-0.58; p=0.002) (Figure). The incidence rates (95% CI) were 0.58 (0.23-1.18) and 1.97 (1.27-
2.91) events/patient-years in the TPTD and RIS treated subjects, respectively (p=0.004).
Conclusion: In postmenopausal women with severe osteoporosis, TPTD treatment for 24 months significantly reduced by 71% the risk
of new clinical vertebral fractures compared with RIS.
Disclosure: C. A. F. Zerbini, Eli Lilly and Company, 2; P. Geusens, Pfizer, Abbott, Lilly, Amgen, MSD, Roche, UCB, BMS, Novartis,
5; E. Lespessailles, Abbvie, Amgen, Lilly, MSD, UCB., 2; J. J. Body, Eli Lilly and Company, 2; E. Casado, None; J. Stepan, None;
D. L. Kendler, Amgen, Lilly, Astra-Zeneca, Astellas, UCB, 5; L. Russo, None; S. L. Greenspan, Eli Lilly and Company, 2; S.
Minisola, Abiogen, Amgen, Diasorin, Lilly, Italfarmaco, Fujii, MSD, Takeda., 5; A. Bagur, None; P. Lakatos, None; A. Fahrleitner-
Pammer, Amgen, Alexion, BMS, Lilly, Fresenius, 8; R. Möricke, None; P. Lopez-Romero, Eli Lilly and Company, 3; F. Marin, Eli
Lilly and Company, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/teriparatide-compared-with-risedronate-and-the-
risk-of-clinical-vertebral-fractures-2-year-results-of-a-randomized-double-dummy-clinical-trial
A Meta-Analysis of 4 Clinical Trials of Denosumab Compared with Bisphosphonates

in Postmenopausal Women Previously Treated with Oral Bisphosphonates
Paul D Miller1, N Pannacciulli2, J Malouf3, A Singer4, E Czerwinski5, HG Bone6, C Wang2, Rachel B. Wagman2 and JP Brown7,
1Colorado Center for Bone Research, Lakewood, CO, 2Amgen Inc., Thousand Oaks, CA, 3Hospital de la Santa Creu i Sant Pau,
Barcelona, Spain, 4Georgetown University Medical Center, Washington, DC, 5Krakow Medical Center, Krakow, Poland, 6Michigan
Bone and Mineral Clinic, Detroit, MI, 7CHU de Québec Research Centre and Laval University, Québec, QC, Canada
SESSION INFORMATION
Background/Purpose: Four clinical trials have separately shown greater BMD gains with transitioning to denosumab (DMAb)
compared with continuing on bisphosphonates (BP) in subjects previously treated with oral BPs (Kendler JBMR 2010; Recknor Obstet
Gynecol 2013; Roux Bone 2014; Miller JCEM 2016). The aim of this meta-analysis was to improve estimates of effect size and provide
an integrated assessment of safety/efficacy of DMAb vs BPs with different dosing regimens (weekly, monthly, yearly) and
administration routes (oral, intravenous), over 12 months in postmenopausal women pretreated with oral BPs.
Methods: Data were pooled from 4 randomized studies in postmenopausal women with low bone mass or osteoporosis, aged ≥55 years,
and pretreated with oral BPs, who were randomized 1:1 to DMAb (60mg every 6 months) or an oral (alendronate 70mg weekly,
ibandronate 150mg monthly, risedronate 150mg monthly) or intravenous (zoledronic acid 5mg yearly) BP for 12 months. Percentage
(%) change from baseline (BL) in BMD at the lumbar spine, total hip, femoral neck, and 1/3 radius (assessed in 2 studies) at month 12;
% change from BL in serum C-terminal telopeptide of type I collagen (sCTX, in a subset of 1058 subjects) at 1, 6, and 12 months (in 2
of the studies); and safety were assessed. Fractures were collected as adverse events (AEs) and not adjudicated.
Results: A total of 2850 subjects were included (1426 DMAb; 1424 BP). Mean (SD) age was 68 (8) years, mean (SD) lumbar spine
BMD T-score was –2.5 (1.0), and mean (SD) duration of prior oral BP use was 3.8 (3.6) years. BMD % change from BL at month 12
was significantly greater with DMAb vs BPs at all measured skeletal sites (Figure) and independent of length of prior BP use (<2 or ≥2
years) at all sites measured (except for 1/3 radius for those with <2 years of prior BP use). Median sCTX % decrease from BL was
greater with DMAb than BPs at months 1 (–58% vs –12%), 6 (–36% vs –14%), and 12 (–26% vs 8%; all p<0.0001). Overall
AEs/serious AEs were similar between groups. There were no cases of osteonecrosis of the jaw. Three events consistent with the
definition of atypical femoral fracture were observed (2 DMAb; 1 BP). Osteoporosis-related fractures were reported in 47 (3.3%)
DMAb and 43 (3.1%) BP subjects.
Conclusion: This integrated assessment shows greater clinical benefit with increases in BMD and reductions in bone turnover and
similar safety profile in transitioning from oral BPs to DMAb, compared with continuing on or cycling through the same therapeutic
class (from one BP to another).
Disclosure: P. D. Miller, Amgen, Lilly, Merck, Radius Health, Ultragenyx, 2,Amgen, Alexion, Lilly, Merck, Radius Health,
Ultragenyx, 5; N. Pannacciulli, Amgen, 1,Amgen, 3; J. Malouf, None; A. Singer, Amgen, Eli Lilly, Merck, Radius, UCB, 5,National
Osteoporosis Foundation Board of Trustees, 6,Amgen, Eli Lilly, Radius, 8; E. Czerwinski, Amgen, 2; H. Bone, Amgen, Merck, Shire,
2,Amgen, Grünenthal, Merck, Radius, Shire, 5,Amgen, Radius, Shire, 8; C. Wang, Amgen, 1,Amgen, 3; R. B. Wagman, Amgen,
1,Amgen, 3; J. Brown, Amgen, Eli Lilly, 2,Amgen, Eli Lilly, Merck, 5,Amgen, Eli Lilly, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-meta-analysis-of-4-clinical-trials-of-denosumab-

compared-with-bisphosphonates-in-postmenopausal-women-previously-treated-with-oral-bisphosphonates
Safety of Denosumab in a Monocentric Cohort of Kidney Transplant Recipients

Sonia Doddoli, Pierre Lafforgue and Thao Pham, Rheumatology, APHM, Aix Marseille Univ, Marseille, France
SESSION INFORMATION
Background/Purpose:
Safety of denosumab, a fully human monoclonal antibody against RANKL developed for osteoporosis and prevention of fracture
remains unclear in kidney transplanted patients.
A recent placebo-controlled trial has demonstrated its efficacy on bone mineral density (BMD) and bone turnover biomarkers (Bonani
et al. Am J Transplant. 2016). Patients in the denosumab group experienced more episodes of cystitis and asymptomatic hypocalcemia
than patients in the placebo group.
Our aim was to assess the clinical and biological tolerance of denosumab in this specific population.
Methods:
Prospective observational monocentric cohort.
Inclusion criteria: kidney transplant recipient who received at least one subcutaneous injections of 60 mg denosumab; age ≥ 18 years.
Safety outcomes: The following variables were collected every 6 months: infection, reaction at the injection site, plasmatic parameters
of renal function and mineral metabolism (estimated glomerular filtration rate, serum creatinine, calcium, 1–25 [OH], vitamin D, PTH).
Results:
Patients were recruited from April 2014 to September 2015. All patients received immunosuppression therapy including prednisolone ≥
5 mg/d.
The main baseline characteristics of the 37 kidney transplant recipients were the following [mean]: male: 41%, age: 60.5 years, BMI:
24,1, transplantation duration: 7.1 years, osteopenia: 36%, osteoporosis: 64%, total lumbar spine T-score: -2.04 SD, total hip T-score:
-2.7 SD, T-score femoral neck: 0.676 g/cm2, serum creatinine: 132.8 mmol/L, calcium: 2.33 mmol/L, 1–25 [OH] vitamin D: 93.5
nmol/L, PTH 95: ng/l. All patients were prescribed vitamin D and calcium supplementation.
During the mean 12-month follow-up period, there were no unexpected adverse event [AE] or severe adverse event, no graft failure and
no deaths. No patient experienced fracture. Only one patient presented an infectious AE with recurrent cutaneous abscess. Renal
function remained stable with no difference in serum creatinine between baseline and 12 months for the majority of the kidney
transplant recipients. However, 9 recipients experienced a decrease in renal function with a mean increased in serum creatinine of 32.5
micromol/L between baseline and 12 months. Serum calcium was stable, no hypocalcaemia was observed. Among patients with normal
baseline PTH, two presented hyperparathyroidism during the follow-up period. Among the 11 patients with baseline
hyperparathyroidism, 7 had an increased PTH level between baseline and 12 months. None were initiated on cinacalcet. None of them
experienced severe hypercalcemia, nor hypocalcemia.
Conclusion:
Our results suggest that denosumab is safe in kidney transplant recipients. We did not observe an increase in the infection rates, nor
hypocalcemia. However, several patients experienced a decrease in their renal function or an increased hyperparathyroidism.
Disclosure: S. Doddoli, None; P. Lafforgue, None; T. Pham, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/safety-of-denosumab-in-a-monocentric-cohort-of-

kidney-transplant-recipients
Evaluation of Invasive Oral Procedures and Events in Women with Postmenopausal

Osteoporosis Treated for up to 10 Years with Denosumab: Results from a Phase 3
Open-Label Extension Study
Nelson B. Watts1, John T. Grbic2, Neil Binkley3, Peter W. Butler4, Xiang Yin4, Antoniette Tierney4, Rachel B. Wagman4 and Michael
McClung5, 1Mercy Health, Cincinnati, OH, 2Columbia University, New York, NY, 3University of Wisconsin School of Medicine and
Public Health, Madison, WI, 4Amgen Inc., Thousand Oaks, CA, 5Oregon Osteoporosis Center, Portland, OR
SESSION INFORMATION
Background/Purpose: Antiresorptive therapy use is associated with osteonecrosis of the jaw (ONJ), an infrequent but serious adverse
event. Positively adjudicated ONJ in the denosumab (DMAb) clinical trial program is rare (between ≥1 and <10 per 10,000).
Completion of the 7-year FREEDOM Extension study (EXT) permitted an in-depth assessment of the risk factors and observed invasive
oral procedures and events (OPEs; eg, dental implants, tooth extraction, natural tooth loss, scaling/root planing [extensive subgingival
cleaning]) in the clinical trial setting.
Methods: In the randomized, placebo-controlled FREEDOM study, women received DMAb 60mg or placebo SC every 6 months for 3
years. Patients who missed ≤1 dose of investigational product and completed the Year-3 visit were eligible to participate in the 7-year
open-label EXT to receive DMAb, regardless of original treatment assignment in FREEDOM. Women who reached the EXT Year-3
visit were asked to chronicle their history of invasive OPEs since the start of the EXT through Year 2.5, as well as oral events (including
jaw surgery) in the prior 6 months. The oral event questionnaire was then administered every 6 months through the end of the EXT.
Results: During the EXT, the overall ONJ rate was 5.2 per 10,000 patient-years. The majority of women (79%; 3591/4550 patients)
participated in the survey. Over the EXT, 1621 (45.1%) reported at least one invasive OPE; the incidence of five individual OPEs were
similar between groups (Table). There were 12 confirmed cases of ONJ among women who participated in the survey (11 had OPE and
one did not) and one additional case in a woman who did not complete the survey. ONJ incidence was 0.7% (11/1621 patients) in
women reporting invasive OPEs and 0.05% (1/1970 patients) in women reporting no invasive OPEs. Of the 12 ONJ cases with survey
results, one outcome was unknown due to consent withdrawn, one was ongoing at the end of study, and 10 resolved with treatment.
Conclusion: Nearly all cases of ONJ observed in this study occurred after a reported invasive OPE, yet while invasive OPEs were
common in this group of DMAb-treated women with postmenopausal osteoporosis, ONJ incidence was low. The actual number of
invasive OPEs may be underestimated due to limited capture of OPEs in medical charts and possible recall bias in patients with events
that occurred in the first 2.5 years of the EXT. ONJ is an adverse event of interest that continues to be monitored in DMAb
pharmacovigilance activities.
Table: Invasive OPEs during the EXT for patients who completed at least one oral event questionnaire
7-year FREEDOM Extension

Long-
term
Cross-over (N = All
(N = 1731) 1860) (N = 3591)
Age at EXT baseline in years, 74.3 (4.9) 74.4 (4.8) 74.3 (4.8)
mean (SD)
Any invasive oral procedure or 795 (45.9) 826 (44.4) 1621 (45.1)
event, n (%)
Scaling / root planing 503 (29.1) 531 (28.5) 1034 (28.8)
Tooth extraction 434 (25.1) 458 (24.6) 892 (24.8)
Dental implant 100 (5.8) 112 (6.0) 212 (5.9)
Natural tooth loss 72 (4.2) 75 (4.0) 147 (4.1)
Jaw surgery* 16 (0.9) 17 (0.9) 33 (0.9)
N = Number of patients who received ≥1 dose of investigational product in
the EXT and responded to ≥1 oral event questionnaire related to the EXT
n = Number of patients with an OPE
*Collected in the oral event questionnaire every 6 months; therefore, jaw
surgery in the first 2.5 years of the EXT was not captured
Disclosure: N. B. Watts, AbbVie, Sanofi, 5,Amgen, Shire, 8; J. T. Grbic, None; N. Binkley, Amgen, GE Heathcare, Lilly, Merck,
Novartis, Viking, 2,Amgen, Radius, 5; P. W. Butler, Amgen, 1,Amgen, 3; X. Yin, Amgen, 1,Amgen, 3; A. Tierney, Amgen, 1,Amgen,
3; R. B. Wagman, Amgen, 1,Amgen, 3; M. McClung, Amgen, Radius Health, 5,Amgen, Radius Health, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/evaluation-of-invasive-oral-procedures-and-events-

in-women-with-postmenopausal-osteoporosis-treated-for-up-to-10-years-with-denosumab-results-from-a-phase-3-open-label-extension-
study
The Predictors of the Efficacy of Denosumab, a Monoclonal Antibody to RANK

Ligand, on Osteoporosis in Rheumatoid Arthritis Patients from Japanese
Multicenter Study
Kyosuke Hattori1, Yuji Hirano1, Yasuhide Kanayama2, Nobunori Takahashi3, Naoki Ishiguro3 and Toshihisa Kojima3,
1Rheumatology, Toyohashi Municipal Hospital, Toyohashi, Japan, 2Orthopaedic Surgery and Rheumatology, Toyota Kosei Hospital,
Toyota, Japan, 3Orthopaedic Surgery and Rheumatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
SESSION INFORMATION
Background/Purpose: Although early intensive treatment has improved medication of rheumatoid arthritis (RA), treatment for
osteoporosis (OP) in RA patient will be more important. Here, we report 2-year outcome of denosumab (DMB) on OP of RA patients.
This was a multiple center, prospective study (TBCR-BONE) to investigate the efficacy of DMB for 2 years on OP of RA patients and
the predictors for the efficacy in DMB treatment.
Methods: 74 females completed 24-month (m) DMB treatment and were used for the analysis. Bone mineral density (BMD) of lumbar
spine (LS) and total hip (TH) by DEXA, and P1NP and TRACP-5b were measured every 6m.
Results: Mean age was 70.2 years old. Mean RA duration was 17.1 years. Oral PSL was used in 26 cases. Biological agents (BIO) were
used in 17 cases. 33 cases had the past history of fractures. The rate of change in LS-BMD (%LS-BMD) significantly increased as 4.4%
at 6m, 5.8% at 12m, 7.2% at 18m and 7.6% at 24m. %TH-BMD significantly increased as 2.7% at 6m, 3.3% at 12m, 4.6% at 18m and
4.6% at 24m. %P1NP at 24m was -28.1%. %TRACP-5b at 24m was -20.6%. To confirm the predictors for large increase of %LS-BMD
at 24m and %TH-BMD at 24m, all cases were divided into two groups, good outcome group (LS-GO group: n=47, mean %BMD at
24m=11.4% and TH-GO group: n=47, mean %BMD at 24m=6.8%) and no good outcome group (LS-NGO group: n=24, mean %BMD
at 24m=0.18% and TH-NGO group: n=24, mean %BMD at 24m=0.21%) with the cutline of %LS-BMD at 24m (4.0%) and %TH-BMD
at 24m (3.1%) made of each superior two thirds of all cases. We performed multivariate logistic regression analyses and confirmed
large decrease of %TRACP-5b at 12m was associated with large increase of %LS-BMD at 24m [OR (%) 0.97, 95% CI 0.95-0.99], and
concomitant use of BIO was associated with large increase of TH-BMD at 24m (OR 5.8, 95% CI 1.10-30.64). The cutoff value of
%TRACP-5b at 12m for larger increase of %LS-BMD at 24m was -38.7% (AUC of ROC=0.766). We divided all cases into two groups,
large decrease of %TRACP-5b at 12m group (L group: n=36) and small decrease of %TRACP-5b at 12m group (S group: n=37) with
this cutoff value. %LS-BMD at 24m was 8.9% vs. 5.9% (p<0.01), %TH-BMD at 24m was 5.0% vs. 4.2% (n.s.), %P1NP at 24m was
-59.6% vs. 0.6% and %TRACP-5b at 24m was -48.8% vs. 5.6% (L group vs. S group). At last, to evaluate the efficacy of combination
of BIO and DMB, all cases were divided into two groups, BIO used group (B group: n=17) and no BIO used group (NB group: n=57).
%LS-BMD at 24m was 9.7% vs. 7.0% (n.s.), %TH-BMD at 24m was 6.5% vs. 4.0% (p<0.01), %P1NP at 24m was -33.8% vs. -26.5%
and %TRACP-5b at 24m was -26.7% vs. -18.7% (B group vs. NB group).
Conclusion: DMB was effective in OP of RA patients. Large decrease of %TRACP-5b at 12m was a predictor for large increase of
%LS-BMD at 24m. Combination of BIO and DMB was a predictor for large increase of %TH-BMD at 24m. They might suggest that
there are different mechanisms associated with increase of LS-BMD and TH-BMD in DMB treatment for OP of RA patients.
Disclosure: K. Hattori, None; Y. Hirano, None; Y. Kanayama, None; N. Takahashi, None; N. Ishiguro, None; T. Kojima, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-predictors-of-the-efficacy-of-denosumab-a-

monoclonal-antibody-to-rank-ligand-on-osteoporosis-in-rheumatoid-arthritis-patients-from-japanese-multicenter-study
Zoledronic Acid Did Not Impaired Renal Function in Patients with Osteoporosis
Ying-Chou Chen Sr., Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Kaohsiung Chang Gung
Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung County, Taiwan
SESSION INFORMATION
Background/Purpose:
Bisphosphonates are recommended for patients with osteoporosis, however concerns have been raised with regards to their effect on
kidney function. The aim of this study was to investigate the safety of bisphosphonates on renal function in patients with magnetic
resonance imaging-proven acute osteoporotic vertebral fractures after vertebroplasty.
Methods:
This retrospective study enrolled patients with osteoporosis and acute vertebral fractures who underwent vertebroplasty between
January 2001 and December 2015. Their gender, age, body mass index, co-morbidities, and use of zoledronic acid were recorded. The
patients with increased creatinine were defined as having worse renal function. Logistic regression was used to adjust for variables.
Results:
Of the 224 included patients (184 females; mean age, 72.91±9.26 years), 82 took zoledronic acid and the others received other anti-
osteoporotic agents. Fifty-four (65.9%) of the patients who took zoledronic acid had an increased creatinine level, compared to 92
(64.8%) of those who received other anti-osteoporotic agents (p=0.885). After adjusting for confounding variables, zoledronic acid was
not significantly associated with an increase in creatinine (p=0.815; OR: 0.926; 95% CI: 0.487-1.761).
Conclusion:
The use of zoledronic acid did not lead to an increase in creatinine compared to those who used did not use zoledronic acid. However,
further studies are needed to confirm our findings.
Table . Risk of zoledronic acid treatment increasing
creatinine after adjustments for covariates
Regression
coefficient SE P value OR(95CI)
Zoledronic acid -0.076 0.328 0.815 0.926(0.487-1.761)
Age 0.057 0.023 0.012 1.059(1.013-1.107)
BMI -0.023 0.034 0.499 0.977(0.914-1.045)
Gender 0.281 0.469 0.548 1.324(0.529-3.321)
Smoking -0.867 0.859 0.313 0.420(0.078-2.263)
Alcohol 1.577 1.116 0.158 4.838(0.543-43.150)
consumption
Diabetes -0.324 0.334 0.333 0.723(0.376-1.393)
Hypertension 0.285 0.317 0.369 1.329(0.715-2.473)
Neurologic -1.235 0.499 0.013 0.290(0.109-0.773)
disease
Cardiovascular -0.091 0.430 0.832 0.913(0.393-2.120)
disease
Pulmonary 0.147 0.399 0.713 1.158(0.530-2.532)
disease
Gastrointestinal -0.351 0.363 0.334 0.703(0.345-1.435)
disease
Liver disease 0.524 0.465 0.260 1.688(0.679-4.201)
Renal disease 0.930 0.435 0.033 2.534(1.080-
5.950)
Key: CI: confidence interval; OR: odds ratio; SE: standard
error; BMI: body mass index
Disclosure: Y. C. Chen Sr., None;
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/zoledronic-acid-did-not-impaired-renal-function-in-

patients-with-osteoporosis
Osteoporosis and Vertebral Fractures Are Associated with Disease Activity, Low
Vitamin D Levels and Spinal Radiographic Damage in Patients with Axial
Spondyloarthritis
Cintia Romera-López1, Cristina Fernández-Carballido2, Miguel Ángel García-Moreno3 and Teresa Pedraz4, 1Rheumatology, Hospital
Universitario del Vinalopó, Elche, Spain, 2Hospital General Universitario de Elda, Elda, Spain, 3Hosppital Universitario de Elda, Elda,
Spain, 4Hospital Universitario de Elda, Elda, Spain
SESSION INFORMATION
Background/Purpose: Osteoporosis and vertebral fractures are comorbidities of Axial Spondyloarthritis (axSpA). We evaluated the
relationship between disease activity and radiographic damage and bone mineral density (BMD) and vertebral fractures (VF) in patients
with axSpA.
Methods: Cross-sectional study of patients with axSpA (ASAS Criteria). Disease activity variables: Bath AS Disease Activity Index
(BASDAI), ESR, CRP, ASAS-endorsed disease activity scores (ASDAS). Lumbar spine and hip BMD by dual x-ray absorptiometry
(DXA) (187(91%) patients). VF assessed by a semiquantitative method (Genant) in lateral thoracic and lumbar spine X-rays. Risk of
fracture was assessed with FRAX tool. Bivariate analysis performed to investigate the associations with the presence of osteoporosis
and/or VF. Then, binary and multiple logistic regression models applied. SPSS (v23); p-values significant if < 0.05.
Results: We included 206 patients (62 female and 144 male). Mean values: age 51,7±14,1; BASDAI 3,6±2,2; ASDAS-CRP 2,2±0,95;
ASDAS-ESR 2,5±0,99; BASFI 3,3±2,78; mSASSS 20,46±19,14; CRP 4,97±8,97mg/L; ESR 18,2±14,8 mm; 25OHvitD 19,83±9,25
ng/mL. Vitamin D deficiency detected in 85.7% of the patients. Low lumbar BMD was detected in 25,7% (z score) and 28,9% (t score)
of the patients and low femoral neck BMD in 45,2% (z score) and 59,7% (t score). Lumbar osteoporosis was present in 3,2%/6.9% and
hip osteoporosis in 9,1%/13,4% (applying z/t scores respectively). VF were detected in 34% of the patients. Bivariate analysis: ESR,
ASDAS-ESR, age, male sex, low 25OHvitD and radiographic damage(mSASSS) were associated to low BMD. Multivariate models
confirmed an association between disease activity (ASDAS-ESR) [OR 3.32 (IC 2.35–4.55) p=0.016] and 25OHvitD [OR 0.95 (IC95
0.86–0.98) p=0.029] and low hip BMD(z score). Differences between patients with and without fractures shown in table 1. Multivariate
models confirmed the association between CRP [OR2.34 (IC95 1.10-4.98) p=0.027], radiographic damage [mSASS lumbar OR 1.06
(IC95 1.03-1.10) p=0.001], high lumbar BMD [OR 296 (IC95 5.07-12258)p=0.006] and low hip BMD (femoral neck t score) [OR 0.11
(IC95 0.03-0.12)p=0.000] and VF.
Conclusion: In patients with axSpA, low BMD is associated with disease activity and low 25OHvitD. The presence of vertebral
fractures is associated with CRP and low hip BMD (p=0.001). Radiographic damage “falsely” increases lumbar BMD results but is
associated with the presence of fractures.
Table 1. Significative differences between patients without fractures versus patientes with vertebral fractures
Variable No Fractures p value t Student
fractures
CRP (mg/L) 5.10 9.51 p = 0.003 t = -3.503
ESR (mm/h) 15.87 23.12 p = 0.002 t = -3.302
25OHvitD 20.80 18.043 p = 0.049 t = 1.979
(ng/mL)
mSASSS 8.02 13.11 p = 0.002 t = -2.146
cervical
mSASSS 8.93 12.36 p = 0.000 t = -5.271
lumbar
mSASSS total 17.66 27.13 p = 0.000 t = -3.873
BMD lumbar 1.090 1.191 p = 0.002 t = -3.068
BMD femoral 0.912 0.773 p = 0.000 t = 6.589
neck
None: Has no relevant financial relationship to disclose
Disclosure: C. Romera-López, None; C. Fernández-Carballido, Gebro, 2; M. Á. García-Moreno, None; T. Pedraz, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/osteoporosis-and-vertebral-fractures-are-associated-

with-disease-activity-low-vitamin-d-levels-and-spinal-radiographic-damage-in-patients-with-axial-spondyloarthritis
Association of Anti-Cyclic Citrullinated Peptide Seropositivity and Lean Mass Index

with Low Bone Mineral Density in Patients with Rheumatoid Arthritis
Katherine D. Wysham1, Dolores M. Shoback2, Kashif Jafri1, Sarah L. Patterson3, Gabriela Schmajuk4, John B. Imboden Jr.5 and
Patricia P. Katz5, 1University of California, San Francisco, San Francisco, CA, 2Medicine, San Francisco VA Medical Center,
University of California, San Francisco, San Francisco, CA, 3Division of Rheumatology, University of California, San Francisco, San
Francisco, CA, 4San Francisco VA Medical Center, University of California San Francisco, San Francisco, CA, 5Medicine, University
of California, San Francisco, San Francisco, CA
SESSION INFORMATION
Background/Purpose: Osteoporotic fractures are associated with high morbidity and mortality. Persons with rheumatoid arthritis
(RA) have twice the risk of osteoporosis-related fracture than age-matched controls. It is not known, however, which characteristics of
RA or its treatments have the greatest impact on bone mineral density (BMD). We investigated associations of RA characteristics,
medication use, and body composition to low BMD in patients with RA.
Methods: We performed a cross-sectional analysis of an existing longitudinal RA cohort study from years 2007-2009. All patients met
ACR classification criteria for RA. Demographic, clinical, laboratory and functional variables were collected at study visits. Body
composition (fat, lean muscle and BMD) was measured by dual x-ray absorptiometry. We used linear regression to evaluate the
association between predictors and femoral neck BMD. To identify independent predictors of BMD, we performed multivariable linear
regression analyses that included variables significant in the univariable analyses at p<0.10. To determine if there was a linear trend
between anti-cyclic citrullinated peptide (CCP) level and BMD, we repeated the linear regression analysis restricted to anti-CCP
positive participants.
Results: Of the 138 participants (82 women, 56 men), 70% were rheumatoid factor positive, and 55% were anti-CCP positive to a level
3 times the upper limit of normal. Mean disease duration was 19±10.9 years. 44% of participants reported taking prednisone and of
those taking prednisone, the mean dose was 7.1±6.1 mg/day. The mean body mass index (BMI) was 27.2±6.0 kg/m2, and mean
appendicular lean mass index (ALMI) was 6.4±1.2 kg/m2; 59% of the participants were obese based on percent total body fat. 52% had
low BMD based on a T or Z score <=-1 and 27% reported taking osteoporosis medications. Age and anti-CCP positivity were
negatively associated with BMD, even after controlling for other variables (β=-0.003 and -0.055, respectively, p<0.05) (Table). ALMI
had an independent positive association with BMD (β=0.053, p <0.0001). Among anti-CCP positive participants (n=61), higher anti-
CCP level was associated with lower BMD (β for each 20-unit increase in anti-CCP=-0.011, p=0.026) when controlling for age, sex,
disease duration, ALMI and knee flexion strength.
Conclusion: Anti-CCP positivity, ALMI and age were independently associated with BMD in patients with RA. The linear relationship
of anti-CCP levels with lower BMD supports the hypothesis that processes specific to RA negatively impact BMD. In contrast, ALMI
was positively associated with BMD, emphasizing the role of muscle mass as a potentially modifiable risk factor. Our findings highlight
the complicated interplay of RA disease-specific and functional factors and their impact on bone mass.
Disclosure: K. D. Wysham, None; D. M. Shoback, None; K. Jafri, None; S. L. Patterson, None; G. Schmajuk, None; J. B.
Imboden Jr., None; P. P. Katz, Bristol-Myers Squibb, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/association-of-anti-cyclic-citrullinated-peptide-

seropositivity-and-lean-mass-index-with-low-bone-mineral-density-in-patients-with-rheumatoid-arthritis
Secular Trends in the Risk of Fragility Fracture Among Patients with Rheumatoid
Arthritis: A General Population-Based Study
Sarah Keller1, Marcy B. Bolster2, Amar Oza3, Sharan K. Rai4, Leo Lu3, Yuqing Zhang5 and Hyon K. Choi4, 1Rheumatology, Allergy
and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 2Division of Rheumatology, Massachusetts
General Hospital, Harvard Medical School, Boston, MA, 3Allergy, Immunology, and Rheumatology, Massachusetts General Hospital,
Harvard Medical School, Boston, MA, 4Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital,
Harvard Medical School, Boston, MA, 5Department of Rheumatology, Allergy and Immunology, Massachusetts General Hospital,
Harvard Medical School, Boston, MA
SESSION INFORMATION
Background/Purpose: The risk of osteoporotic (OP) fracture among patients with rheumatoid arthritis (RA) is higher than that of the
general population. The worldwide incidence of OP fractures in high-risk individuals is expected to double over the next 40 years. It is
unknown if improvements in the management of RA and OP has decreased the OP fracture risk in patients with RA. To address this
knowledge gap, we compared the risk and incidence of OP fracture among patients with RA to the general population over two
chronologic periods.
Methods: Using an electronic medical record database representative of the United Kingdom general population (The Health
Improvement Network), we identified patients with incident RA and up to five individuals without RA matched for age, sex, and
calendar year of diagnosis between 1999 and 2014. The RA cohort was divided in two sub-cohorts based on the year of RA diagnosis:
the early cohort (1999Ð2006) and the late cohort (2007Ð2014). We identified incident OP fracture using physician diagnosis (READ)
codes. Subjects with previously-diagnosed prevalent fractures were excluded from this analysis. We calculated the period-specific
incidence rates of total OP fracture and hip fragility fracture for each cohort separately. We calculated the hazard ratio (HR) of incident
fracture using a Cox proportional hazard model. In the multivariable model, we adjusted for age, body mass index, smoking status (non-
smokers, ex-smokers, current smokers), alcohol use (non-drinkers, ex-drinkers, current drinkers), comorbidities, medication use, and the
number of PCP visits.
Results: Both the early and late cohorts (N=54,291 and 59,915, respectively) had a similar mean age (60 and 59 years) and sex
proportion (~70 and 69% female), and RA patients showed an increased risk of OP fracture compared with their corresponding
comparison cohort (Table). In both cohorts, the incidence rate of total OP fracture slightly increased, and the corresponding relative risk
(RR) was not significantly different between the two periods (corresponding multivariable HRs=1.23 [95% CI: 1.04 to 1.47] vs. 1.45
[95% CI: 1.26 to 1.68]; p for interaction = 0.21) (Table). Meanwhile, in both cohorts, the incidence rate of hip fragility fracture slightly
declined and the corresponding RR was not significantly different between the two periods (corresponding multivariable HRs=1.68
[95% CI: 1.28 to 2.21] and 1.53 [95% CI: 1.16 to 2.03]; p for interaction = 0.24) (Table).
Conclusion: This general population-based cohort study indicates that RA patients still experience a higher risk of all OP and hip
fragility fractures compared to non-RA patients, and that this difference has not improved over the past several decades despite
advances in RA and OP therapy. This unclosing gap in increased fracture risk among RA patients calls for improved management of
osteoporosis in RA.
Disclosure: S. Keller, None; M. B. Bolster, None; A. Oza, None; S. K. Rai, None; L. Lu, None; Y. Zhang, None; H. K. Choi,
Selecta, Horizon, 5,AstraZeneca, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/secular-trends-in-the-risk-of-fragility-fracture-

among-patients-with-rheumatoid-arthritis-a-general-population-based-study
Factors Associated with Worsening Serum Vitamin D Deficiencies in Japanese

Patients with Rheumatoid Arthritis: Results from the IORRA Cohort Study
Masanori Nakayama1, Takefumi Furuya1, Eisuke Inoue2, Eiichi Tanaka1, Katsunori Ikari1, Ayako Nakajima1, Atsuo Taniguchi1 and
Hisashi Yamanaka1, 1Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan, 2Division of Medical Informatics,
St. Marianna University School of Medicine, Kawasaki, Japan
SESSION INFORMATION
Background/Purpose: In 2011, we evaluated serum vitamin D levels in Japanese patients with rheumatoid arthritis (RA) and reported
the prevalence of, and factors associated with, vitamin D deficiency [1]. Limited data exist in the literature concerning factors that
predispose patients with RA to a worsening vitamin D deficiency. The aim of this study was to investigate predictive factors for a
worsening vitamin D deficiency using our Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort.
Methods: Established in the year 2000, the IORRA cohort is a single institute-based large cohort of Japanese RA patients. Over 120
publications have described various characteristics of Japanese patients with RA using this large cohort. In 2013, fresh serum from
those patients who participated in our first vitamin D study in 2011 was evaluated for 25-hydroxyvitamin D [25(OH)D] levels via
radioimmunoassay. A vitamin D deficiency was defined as serum 25(OH)D levels <20 ng/mL. To determine the predictive factors of a
worsening vitamin D deficiency over a 2-year period, multivariate logistic regression analyses were used.
Results: Among the 2534 patients with RA who participated in our vitamin D studies in 2011 and 2013 (2179 women and 355 men;
mean age 59.6 years), the mean (± standard deviation) serum 25(OH)D level was 18.0 (±5.8) ng/mL, and the prevalence of vitamin D
deficiency was 68.2% in 2013. Via multivariate analysis, younger age, female gender, and a high score for the Japanese version of the
Health Assessment Questionnaire disability index (J-HAQ-DI) were significantly associated with vitamin D deficiency (P<0.05).
Serum vitamin D levels decreased by >5 ng/mL over the 2 years from 2011 to 2013 in 224 (8.8%) patients. For that subset of patients, a
multivariate analysis revealed, younger age, female gender, bisphosphonate disuse, and higher baseline serum 25(OH)D levels were
significantly associated with the decrease in vitamin D levels over the two years (P<0.05) (Table).
Conclusion: In Japanese patients with RA, younger age, female gender, bisphosphonate disuse, and a high baseline serum 25(OH)D
level appear to be associated with serum vitamin D levels that worsen over time.
Table:Factors associated with a further decrease in serum 25(OH)D levels in Japanese patients with RA from 2011 to 2013.
Odds ratio
Variables P
(95% CI)
0.981 (0.964-
Age 0.0338
0.999)
2.190 (1.100-
Female gender 0.0254
4.360)
Bisphosphonate 0.431 (0.201-
0.0308
use 0.925)
Baseline serum
1.310 (1.27-1.35) <0.0001
vitamin D levels
Reference: 1) Clin Rheumatol. 2013; 32: 1081-7.
Disclosure: M. Nakayama, Bristol-Myers Squibb, 8; T. Furuya, UCB, 8,Bristol-Myers Squibb, 8,Takeda, 8,Eisai, 8,Chugai, 8,Pfizer
Inc, 8,Ono, 8,Asahi Kasei, 8; E. Inoue, Merck Serono Co., Ltd., 8; E. Tanaka, Abbvie, 8,Ayumi, 8,Bristol-Myers Squibb, 8,Chugai,
8,Eisai, 8,NIppon Kayaku, 8,Pfizer Inc, 8,Takeda, 8,UCB, 8; K. Ikari, Bristol-Myers Squibb, 8,Abbvie, 8,Eisai, 8,Asahi Kasei,
8,Asttelas, 8,Chugai, 8,Hisamitsu, 8,Janssen Pharmaceutica Product, L.P., 8,Taisho Toyama, 8,Takeda, 8,Santen, 8,Tanabe-Mitsubishi,
8,Kaken, 8; A. Nakajima, Nippon-Kayaku, 5,Bristol-Myers Squibb, 8,Chugai, 8,Novartis Pharmaceutical Corporation, 8,Pfizer Inc,
8,Siemens, 8,Tanabe-Mitsubishi, 8; A. Taniguchi, Pfizer Inc, 8; H. Yamanaka, MSD, 2,Astellas, 2,AbbVie, 2,BMS, 2,Kaken, 2,UCB,
2,Ono, 2,Ayumi, 2,Eisai, 2,Daiichi-Sankyo, 2,Takeda, 2,Tanabe-Mitsubishi, 2,Chugai, 2,NIpponshinyaku, 2,Pfizer Inc, 2,Pfizer Inc,
8,YL biologics, 8,Takeda, 8,NIpponkayaku, 8,Chugai, 8,Tanabe-Mitsubishi, 8,Daiichi-Sankyo, 8,Astellas, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/factors-associated-with-worsening-serum-vitamin-d-

deficiencies-in-japanese-patients-with-rheumatoid-arthritis-results-from-the-iorra-cohort-study
Change in Bone Mineral Density in Patients with Rheumatoid Arthritis: Minimal 10-
Year Follow-up
Hiraku Motomura, Isao Matsushita, Toshihito Hiraiwa and Tomoatsu Kimura, Department of Orthopaedic Surgery, Faculty of
Medicine, University of Toyama, Toyama, Japan
SESSION INFORMATION
Background/Purpose:
To investigate the long-term change in bone mineral density (BMD) in patients with rheumatoid arthritis (RA).
Methods:
In a longitudinal study of 40 patients with RA, we collected clinical data and measured hip BMD by dual-energy X-ray absorptiometry
at baseline and after at least 10 years. BMD of the total hip was measured as the percentage of young adult mean (YAM). We compared
clinical characteristics between patients with osteopenia (BMD < 80% of YAM) and those without (normal group; BMD ³ 80% of
YAM) at baseline. We also analyzed factors associated with a decrease in YAM of >5% during the follow-up period using multivariate
logistic regression analysis.
Results:
The mean patient age was 59.8 years, the mean disease duration was 11.5 years, and the mean follow-up period was 10.4 years. Most of
the patients (90%) were women. At baseline, 22 patients (55%) were being treated with methotrexate (MTX, mean dose 5.4 mg/week),
26 patients (65%) with prednisolone (PSL, mean dose 6.7 mg/day), and one patient (2.5%) with a biologic disease-modifying
antirheumatic drug (DMARD). The antiresorptive drug intervention rate at baseline was 20%. The mean serum C-reactive protein
(CRP) and matrix metalloproteinase-3 (MMP-3) values at baseline were 2.21 mg/dL and 258.6 ng/mL, respectively. At follow-up, the
mean dose of MTX had increased to 7.0 mg/week and the mean PSL dose had decreased to 2.9 mg/day. The antiresorptive drug
intervention rate had increased to 77.5%, and treatment with biologic DMARDs had also increased to 55%. The mean CRP and MMP-3
values had decreased to 0.33 mg/dL and 105.4 ng/ml, respectively. Total hip BMD had decreased from 80.0% YAM at baseline to
76.8% YAM at follow-up. At baseline, 19 patients (47.5%) were classified as osteopenia (BMD < 80% of YAM). The total hip BMD in
this group increased slightly from 67.2% YAM at baseline to 69.7% YAM at follow-up. By contrast, the normal group showed a
significant decrease in BMD from 91.6% YAM at baseline to 83.1% YAM at follow-up. At both baseline and follow-up, the
antiresorptive drug intervention rate was significantly higher in the osteopenia group than in the normal group. No significant
differences were found in age, disease activity, use of MTX, PSL, or biological DMARDs between the osteopenia and normal groups.
Multivariate logistic regression analysis was used to determine individual factors associated with a reduction in BMD (>5% decrease of
YAM). Current use of antiresorptive drugs was strongly associated with a decreased risk for total hip bone loss (odds ratio: 0.04, 95%
confidence intervals: 0.003–0.436, P = 0.009)
Conclusion:
Our findings suggest that osteoporosis treatment and tight control of RA disease activity are important for maintaining total hip BMD
over a 10-year period. Even RA patients without osteopenia should be started on osteoporosis treatment to inhibit the progression of
bone loss.
Disclosure: H. Motomura, None; I. Matsushita, None; T. Hiraiwa, None; T. Kimura, None.

View Abstract and Citation Information Online - http://acrabstracts.org/abstract/change-in-bone-mineral-density-in-patients-with-
rheumatoid-arthritis-minimal-10-year-follow-up
Case Series: Comparison of Repository Corticotropin Injection (H.P. Acthar Gel)

Versus Glucocorticoids on Bone Density in SLE Patients
Anny T. Wu1 and Joshua June2, 1Rheumatology, Franciscan Alliance, Munster, IN, 23394 E Jolly Rd Ste C, Great Lakes Center of
Rheumatology, Lansing, MI
SESSION INFORMATION
Background/Purpose: Repository Corticotropin Injection (RCI) is an adrenocorticotropin hormone in 16% gelatin with a prolonged
release after intramuscular (IM) or subcutaneous injection. Adverse effects of RCI are primarily related to its steroidogenic effects
including decrease in BMD. However, there is recent renewed interest in RCI’s role as an alternative to high dose glucocorticoids and as
last resort therapy for SLE.
Methods: This retrospective case series looks at the bone density changes of 5 adult female patients with mean age of 59 years on RCI
vs. glucocorticoids at a Rheumatology practice. A list of 73 patients on RCI was populated using the EMR. Chart review was performed
and patients were selected with the following criteria: on RCI for at least 6 months, history of SLE, verifiable DXA scan results from
before and after starting RCI. Patients were then excluded if they had been on bone sparing agents during this time interval. The bone
with the lowest density on the DXA report post-RCI is selected for comparison to the pre-RCI BMD. The lowest significant change of
each BMD value is operator dependent and is within 95% confidence interval based on the certified technologist’s past DXAs. The
same technologist performed all of the above DXAs. An example is as follows: for this particular technologist, her range of lowest
significant change (at 95% confidence interval) in measurement of the femoral neck is plus or minus 0.010 gm/cm^2. If the difference
in BMD of the femoral neck falls outside of this range on a latter DXA, then there is indeed a significant change.
Results: Two of the 5 patients had nonsignificant changes to their BMD before and after starting RCI. Two patients had a decrease in
BMD that were significant but were noted to have been on higher doses of Prednisone (10mg and/or 20mg a day) and received more IM
glucocorticoid injections. One patient had an increased BMD, although for her, RCI was started just 3 months prior to her latter DXA.
Her third DXA scan 2 years later did show a significant decrease in BMD but she, too, had received more glucocorticoid IM injections.
Conclusion: These cases illustrate the possibility that RCI by itself does not contribute to significant BMD decrease. Rather, significant
decrease in BMD is seen in those patients who have concurrently received more oral, IM or intra-articular glucocorticoids while on
RCI. Although RCI may be understood to have similar side effects as glucocorticoids, we see a possible difference in side effects such
as BMD decrease as compared to glucocorticoids.
Disclosure: A. T. Wu, None; J. June, Mallinckrodt, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/case-series-comparison-of-repository-corticotropin-

injection-h-p-acthar-gel-versus-glucocorticoids-on-bone-density-in-sle-patients
Serum 25-Hydroxyvitamin D, Acute Phase Reactants and Disease Activity in

Rheumatologic Diseases
María Lorena Brance1,2, Lucas Ricardo Brun3, Maria Larroude4, Mónica Patricia Sacnun5, Carolina Aeschlimann5, Guillermo
Berbotto6, Mariano Palatnik1, Ignacio Chavero1 and Ariel Sánchez7, 1Centro de Reumatología, Rosario, Argentina, 2School of
Medicine. Rosario National University., Bone Biology Laboratory, Rosario, Argentina, 3School of Medicine. Rosario National
University, Bone Biology Laboratory, Rosario, Argentina, 4Centro de Diagnostico Rossi, Buenos Aires, Argentina, 5Hospital
Provincial, Rosario, Argentina, 6Sanatorio Británico, Rosario, Argentina, 7Centro de Endrocrinología., Rosario, Argentina
SESSION INFORMATION
Background/Purpose: Previous evidence indicates an association between vitamin D deficiency and autoimmune diseases. The aim of
this study was to evaluate serum 25-hydroxyvitamin D (25OHD), acute phase reactants and disease activity in patients with
rheumatologic diseases (RD).
Methods: This retrospective study evaluated 173 patients with RD (94 rheumatoid arthritis (RA), 18 spondyloarthropathies (SA), 61
collagenopathies (COL) (systemic lupus erythematosus, vasculitis, scleroderma, undifferentiated disease, superposition syndrome) and
compared them with a control group (CG, n=121) matched by age (CG= 55.0±14.7 years; RD= 53.4±13.6, sex and body mass index
(BMI). All patients were from Rosario (32º52´18´´S) and Buenos Aires (34º36´14´´S) cities. Exclusion criteria: supplementation with
vitamin D, pregnancy, intestinal malabsorption, chronic liver or kidney disease, and cancer. Date are expressed as mean±SEM.
Differences between groups were analyzed using the Mann-Whitney or Kruskal-Wallis tests. Correlations were performed with
Spearman’s correlation test. Univariate linear regression and logistic regression analysis were performed. Contingency tables were
evaluated with χ2 test. The difference was considered significant if p<0.05.
Results: RD patients had significant lower 25OHD levels as a control group (CG= 26.8±1.1 ng/ml; RD= 19.8±0.6 ng/ml; p<0.0001).
Furthermore, all subgroups had lower 25OHD (RA=20.7±0.7 ng/ml, SA= 15.4±1.3 ng/ml, COL= 19.7±1.1 ng/ml). The OR of patients
with RD being vitamin D deficient (25OHD <20 ng/ml) was 2.7 (95%CI 1.6 to 4.4) with a probability of 73%. Consistent with 25OHD
differences, significant lower serum calcium (CG= 9.33±0.04; RD= 9.14±0.08 mg/dl) and higher PTH (CG= 39.72±2.37; RD=
49.93±3.34 pg/ml) levels were found. No differences in serum phosphate, urinary calcium and urinary deoxipiridinoline were observed.
25OHD significantly correlated with erythrocyte sedimentation rate (ERS) [r= -0.28; p=0.0017] as acute phase reactants. No differences
was found in reactive C-protein (RCP). Lower values of 25OHD were found at higher DAS-28 (<3.2= 22.9 ng/ml; 3.2-5.1= 19.8 ng/ml;
>5.1= 19.9 ng/ml; p=0.23) and HAQ-DI (0-1= 22.9 ng/ml; 2= 19.8 ng/ml; 3= 19.9 ng/ml; p=0.001). Activity scores in other RD couldn
´t be analyzed because of the small number of patients. Age, BMI, presence of RD, RCP and HAQ-DI were significantly and inversely
associated with 25OHD levels. BMI, presence of RD, ERS and RCP were significantly associated with vitamin D deficiency.
Conclusion: Patients with RD have a high probability of being deficient in 25OHD. Low 25OHD levels are associated with high acute
phase reactants in the whole group, and with high disease activity scores in RA patients.
Disclosure: M. L. Brance, None; L. R. Brun, None; M. Larroude, None; M. P. Sacnun, None; C. Aeschlimann, None; G. Berbotto,
None; M. Palatnik, None; I. Chavero, None; A. Sánchez, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/serum-25-hydroxyvitamin-d-acute-phase-reactants-

and-disease-activity-in-rheumatologic-diseases
Atypical Femoral Fracture in Patients of a Rheumatology Service: Clinical,

Radiographic and Bone Histomorphometric Data
Mariana O Perez1, Diogo S Domiciano1, Vanda Jorgetti2 and Rosa M R Pereira1, 1Rheumatology Division, Hospital das Clinicas
HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil, 2Nephrology Division, Hospital das Clinicas
HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
SESSION INFORMATION
Background/Purpose: Atypical femoral fractures (AFF) are low energy femoral fractures with a specific radiographic pattern and
subtrochanteric / diaphyseal localization that have been related to long-term bisphosphonate therapy. Glucocorticoid and rheumatic
diseases, mainly rheumatoid arthritis has also been implicated in this comorbidity. Therefore, the aim of this study was to evaluate a
cohort of patients with AFF from a Tertiary Rheumatology Center, including clinical presentation, radiographic data and findings of
bone histomorphometry.
Methods: From January 2007 to May 2017, all patients from the Outpatient Clinic (Osteometabolic Disease) of a Tertiary
Rheumatology Service, Clinics Hospital- School of Medicine who fulfilled the American Society of Bone Mineral Research (ASBMR,
2010) criteria for atypical fracture were included in this study. Clinical-epidemiological data were obtained from electronic chart review.
Anteroposterior radiographs of bilateral hip were analyzed, according to ASBMR. Confirmation of bilateral AFF was performed by
magnetic resonance imaging or scintigraphy. Serum markers of bone remodeling, C-terminal telopeptide of type 1 collagen (CTX) and
alkaline phosphatase (AP) were also evaluated. Iliac crest bone biopsy and static and dynamic bone parameters (compared to reference
values of healthy controls matched by sex and age) were performed by histomorphometric analysis (Osteomeasure® software).
Results: Eighteen patients presented AFF, mostly women (94.4%), Caucasian (72.2%), mean age of 64.9 ± 13.3 years and all had
prodromal pain in the anterolateral region of the thigh before the clinical fracture. Seventeen used bisphosphonate (5.83 ± 2.74 years),
mostly alendronate (83.3%) at the time of fracture. One patient was taking denosumab, but had previously received bisphosphonate for
6 years. Presence of any inflammatory rheumatic disease was observed in 9 (50%) patients: rheumatoid arthritis (n=4), systemic lupus
erythematosus (n=1), Sjögren's syndrome (n=1), Behçet´s disease (n=1), inclusion body myositis (n=1) and adult-onset Still's disease
(n=1). Eight patients (44.4%) were using oral glucocorticoid at a median dose of 5 mg/day (ranged 5-15mg/day). All fractures presented
diaphyseal localization, 16 (88.8%) were complete fracture and 4 (22.2%) bilateral. Bone markers were in the normal range (CTX:
0.28±0.18ng/mL and AP: 76.11± 30.22 U/L). Bone biopsy performed in 6 patients revealed suppression of bone turnover (100%), with
reduction of osteoid tissue, as well as decreasing of resorption, osteoclastic and osteoblastic surfaces and impairment of bone
mineralization. Sixteen patients underwent surgical treatment and 2 only clinical treatment (teriparatide). In total, 14 patients received
teriparatide, 1 strontium ranelate and 3 remained without medication.
Conclusion: Our study alerts the rheumatologist about the possibility of AFF in those patients with bisphosphonate above 5 years,
mainly with inflammatory rheumatic diseases and glucocorticoid use. Bone biopsy revealed a bone turnover suppression. Attention
should be aware of the prodromal thigh or groin pain and subclinical imaging changes in the lateral femur, both associated with AFF.
Disclosure: M. O. Perez, None; D. S. Domiciano, None; V. Jorgetti, None; R. M. R. Pereira, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/atypical-femoral-fracture-in-patients-of-a-

rheumatology-service-clinical-radiographic-and-bone-histomorphometric-data
Comparison of Outcomes in Osteoporosis in Patients on Denosumab between

Standard and Non-Standard Dosing Intervals
Nouman A. Syed, Mohammed Wiqar, Douglas Einstadter and Marina N. Magrey, Case Western Reserve University at MetroHealth
Medical Center, Cleveland, OH
SESSION INFORMATION
Session Title: ARHP Osteoporosis and Metabolic Bone Disease – Clinical Aspects and Pathogenesis Poster
Background/Purpose: Denosumab (Dmab) is an antiresorptive agent with an approximate half-life of 26 days and according to the
prescribing information the recommended dose is 60 mg subcutaneous every 6 months. Although in real world clinical practice, strict
adherence to this dosing regimen is frequently hampered due to delays in prior authorizations, follow up appointment scheduling and
missed visits. We hypothesized that patients who did not adhere to the standard dosing regimen would have impaired efficacy of Dmab.
The objective of this study is to determine whether there is difference in bone mineral density (BMD) after 2 years of therapy in patients
who received Dmab at recommended 6 month intervals as compared with patients who did not.
Methods: All patients between 2009 and 2015 with a primary diagnosis of post-menopausal osteoporosis that had received 4 doses of
Dmab in 2 consecutive years were identified from the electronic data base. Furthermore patients were required to have a baseline DXA
within 2 years prior to Dmab initiation and a follow up DXA within 2-3 years thereafter done on the same GE Lunar machine (least
significant change for hip 0.036 g/cm2). Patient records were reviewed to obtain information on demographics, weight, smoking
history, baseline vitamin D level, Dmab administration and DXA results. Change in BMD at lowest T-score of hip or femoral neck for
each patient was used as the outcome measure. Adherence to therapy was defined as receiving subsequent injections at 6 month ± 4
week intervals. Patients were divided into 3 groups with Group 1 being adherent with all injections. Patients in Group 2 were adherent
with 2 of 3 subsequent injections whereas Group 3 patients received subsequent injections at 8-12 month intervals and were considered
to be non-adherent. Descriptive analysis included continuous variables (means ± SD) and categorical variables (%). Data were
compared by using ANOVA.
Results: 50 patients, all females, with mean age of 75 yrs (± 9.4), 74% were Caucasian, 12% African American, 6% Hispanic and 8%
were of other ethnicities. 60% smokers and 56% had history of fragility fractures. Mean Vitamin D level was 39.3 ng/ml (± 21.5). The
mean lowest BMD at the hip or femoral neck at baseline and follow up were 0.705 g/cm2 (± 0.130) and 0.726 g/cm2 (± 0.130),
respectively. 14% of patients were adherent with all 3 injections whereas 40% were categorized as Group 2. 46% were non adherent.
The mean change in BMD stratified by groups was 0.035 g/cm2 (± 0.061) for Group 1, 0.006 g/cm2 (± 0.035) for Group 2 and 0.031
g/cm2 (± 0.057) for Group 3. There was no significant difference in mean lowest BMD change at the hip or femoral neck between the 3
groups through ANOVA analysis (p=0.2073).
Conclusion: Despite low adherence to the standard dosing regimen for Dmab there was no significant difference in change of BMD in
patients who were not adherent to the current prescribing information.
Disclosure: N. A. Syed, None; M. Wiqar, None; D. Einstadter, None; M. N. Magrey, Amgen, AbbVie, and UCB Pharma, 2,UCB
and Janssen, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/comparison-of-outcomes-in-osteoporosis-in-

patients-on-denosumab-between-standard-and-non-standard-dosing-intervals
Psoriatic Arthritis Patients Who Attain a Very Low Disease Activity State Have a
Minimal Impact of the Disease on Their Lives
Rubén Queiro1, Juan D. Cañete2, Carlos Alberto Montilla-Morales3, Miguel A. Abad4, Susana Gomez Castro5 and Ana Cabez5,
1Rheumatology Department. Hospital Universitario Central de Asturias, Oviedo, Spain, 2Rheumatology Department, Arthritis Unit,
Rheumatology Dpt, Hospital Clinic of Barcelona, Barcelona, Spain, 3Hospital Clínico Universitario de Salamanca, Salamanca, Spain,
4Rheumatology, HU. Virgen del Puerto., Plasencia, Spain, 5Pfizer, Madrid, Spain

SESSION INFORMATION
Session Title: Patient Outcomes, Preferences, and Attitudes Poster I
Background/Purpose:
The target of treatment in psoriatic arthritis (PsA) should be remission or inactive disease. A potential definition that would fit with the
Treat-to-Target Recommendations would be minimal disease activity (MDA) meeting all 7 criteria1, proposed as a definition of very
low disease activity (VLDA) in PsA. Patient reported outcomes (PROs), such as those provided by the novel PsAID questionnaire 2, are
also important to evaluate healthcare interventions and to reflect the impact of PsA on patients’ lives. The aims of this study were to
evaluate the prevalence of VLDA in patients with PsA and how much residual active disease is still present, so as to determine whether
PsAID could be an additional useful tool to assess PsA interventions in clinical practice.
Methods:
This was a sub-analysis of the MAAPs study3. Patients were considered in VLDA when they met all the MDA criteria: tender joint
count ≤1, swollen joint count ≤1, Psoriasis Area Severity index (PASI) score ≤1 or body surface area ≤3%, patient pain visual analog
scale (VAS) score ≤ 15, patient global disease activity VAS score ≤ 20, Health Assessment Questionnaire (HAQ) score ≤ 0.5, and tender
entheseal points ≤ 1. Patient acceptable symptoms state (PASS) is considered a PsAID value <4. Comparisons of qualitative variables
have been made with the chi-square test or Fisher's exact test. Comparisons of quantitative variables were made with the Student's T test
or with non-parametric tests if necessary.
Results: 227 patients from 25 Spanish rheumatology departments were included, and among them, 26 (11.5%) were in VLDA. The
majority (96.2%) of VLDA patients had a PASS situation while 49.2% of non VLDA patients had a PASS, p<0.001.
Variable Non-VLDA (n: VLDA (n: 26) p-values
201)
Age (yrs) 53.1 (12.1) 53.7 (14.4) NS
Sex (male) 52.7% 65.4% NS
Disease duration 9.6 (7.6) 9.5 (9.1) NS

(yr)
13.9% 0% 0.042
Family history
(PsA) 3% 11.5% 0.035
CHD 19.4% 34.6% 0.074
Obesity 3.8 (6.5) 1.9 (1.9) 0.002
CRP (mg/L) 35.8% 42.3% NS
Hand erosive 29.4% 30.8% NS

disease
52.2% 34.6% 0.091
Foot erosive
disease 18.9% 3.8% 0.055
NSAID 77.6% 57.7% 0.027
Corticoids 77.1 (72.2) 38.5 (38.6) 0.051
csDMARDs 47.3% 65.4% 0.082
Duration 46.1 (35.5) 43.9 (30.9) NS

(months)
64.2% 94.2% 0.027
Biologics
0.6 (0.5) 0.06 (0.1) <0.001
Duration
(months) 5.4 (4.5) 1.1 (1.2) <0.001
ETA/ADA 3.0 (2.3) 0.6 (0.6) <0.001
HAQ 3.4 (2.7) 0.6 (1.2) <0.001
PsAID 3.5 (2.5) 0.5 (0.6) <0.001
BASDAI
Pain VAS (0-10)
Pt. disease activity
CHD: coronary heart disease. ETA: etanercept. ADA: adalimumab. PsAID: psoriatic arthritis impact of disease. Pt: patient. Values are
expressed as percentages and mean (SD).
Conclusion:
11.5% of Spanish PsA patients achieved VLDA state in routine clinical practice. PsA patients who reached this state also had a minimal
impact of disease according to PsAID. VLDA state could represent a situation of clinical remission in PsA.
References
1. Coates LC, et al. Ann Rheum Dis 2010; 69(1): 48-53.
2. Gossec L, et al. Ann Rheum Dis 2014; 73(6): 1012-1019.
3. Queiro R, et al. Arthritis Res Ther 2017; 19(1):72.

Disclosure: R. Queiro, None; J. D. Cañete, None; C. A. Montilla-Morales, None; M. A. Abad, None; S. Gomez Castro, None; A.
Cabez, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/psoriatic-arthritis-patients-who-attain-a-very-low-

disease-activity-state-have-a-minimal-impact-of-the-disease-on-their-lives
Patient–Reported Barriers to Achieving Rheumatoid Arthritis Disease Control

Maria I. Danila1, Eric M. Ruderman2, Leslie R Harrold3, Joshua A. Melnick1, Ronan O'Beirne1, Monika M. Safford4, Joel Kremer5
and Jeffrey R. Curtis6, 1University of Alabama at Birmingham, Birmingham, AL, 2Northwestern University Feinberg School of
Medicine, Chicago, IL, 3University of Massachusetts Medical School, Worcester, MA, 4Weill Cornell Medical College, New York, NY,
5Corrona, LLC, Southborough, MA, 6Rheumatology & Immunology, University of Alabama at Birmingham, Birmingham, AL
SESSION INFORMATION
Background/Purpose: Many patients with RA do not achieve guideline-recommended treat-to-target (T2T) goals in clinical practice.
There is a paucity of data regarding the challenges that patients face when attempting to achieve better control of their RA disease
activity. In this study we sought to identify and prioritize patient-perceived barriers to achieving RA disease activity control.
Methods: Participants were recruited from the within the Consortium of Rheumatology Researchers of North America (Corrona)
registry by email and invited to participate in 4 nominal groups. Each group generated a list of barriers that made it challenging for
patients to control their RA disease activity. All generated items were combined in a single dataset and subjected to a card sort
procedure to create common themes. A random sample of patients with RA enrolled in Corrona were invited by email to complete a
compensated online survey and asked to rank their top 3 barriers. A weighted score was assigned for each barrier by considering the
number of respondents who ranked it and the priority rank they assigned. The barriers were sorted into domains. The survey also
included knowledge items about T2T strategy and attitudes about RA treatment.
Results: Four nominal groups with 37 RA patients identified 17 themes to achieving control of RA activity. We sent 1567 email
invitations to complete the survey and 463 patients with RA responded within 3 weeks. Demographic and clinical data was available for
1331 persons, 383 of whom responded to the survey. There were no differences in age, sex, or disease duration between survey-
respondents and non-respondents. A higher proportion of respondents were college-educated. A total of 289 (76%) respondents
considered RA to be a high priority for their health, 193 (51%) reported being familiar with T2T as a treatment strategy, and 233 (75%)
agreed that it is important to accept the risk of side effects now in order to improve the chance of being healthy in the future. Among the
challenges to controlling RA disease activity, the domain that received the highest score was unpredictability of RA and its treatment,
which comprised the following barriers: unpredictability of how RA may progress, medication risk aversion, effectiveness, and
safety/tolerability concerns (Figure). Symptoms and illness burden domain received the second highest score, followed by the health
system domain (Figure).
Conclusion: Important patient-perceived barriers to achieving RA disease control include unpredictability of how RA may progress,
medication risk aversion, cost of RA care and RA physical limitations. Addressing these barriers, when possible, may improve goal-
directed RA care.
Disclosure: M. I. Danila, Pfizer IGLC, 2; E. M. Ruderman, AbbVie, Amgen, BMS, GSK, Janssen, Eli Lilly and Company, Novartis,
Pfizer, Roche/Genentech, 5; L. R. Harrold, Corrona, 1,Pfizer Inc, 2,Roche Pharmaceuticals, 5,Corrona, 3; J. A. Melnick, None; R.
O'Beirne, Pfizer, Inc, 2; M. M. Safford, Amgen, 5; J. Kremer, Abbvie, Amgen, BMS, Genentech, GSK, Eli Lilly and Company,
Novartis,Pfizer, 5,Abbvie, Genentech, Eli Lilly and Company, Novartis, Pfizer, 2,Genentech and Biogen IDEC Inc., 8,Corrona,
1,Corrona, 3; J. R. Curtis, AbbVie, Roche/Genentech, BMS, UCB, Myraid, Lilly, Amgen, Janssen, Pfizer, Corrona, 5,Amgen, Pfizer,
Crescendo Bio, Corrona, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/patient-reported-barriers-to-achieving-rheumatoid-

arthritis-disease-control
Patient-Reported Flares Were Correctly Predicted By an Algorithm Using Machine-

Learning Statistics on Activity Tracker Data on Steps, in a Longitudinal 3-Month
Study of 170 Patients with Rheumatoid Arthritis (RA) or Axial Spondyloarthritis
(axSpA)
Laure Gossec1, Frédéric Guyard2, Didier Leroy3, Thomas Lafargue2, Michel Seiler3, Charlotte Jacquemin1, Anna Molto4, Jeremie
Sellam5, Violaine Foltz1, Frédérique Gandjbakhch1, Christophe Hudry6, Stéphane Mitrovic1, Bruno Fautrel1 and Herve Servy7,
1UPMC University Paris 06, Pitié-Salpétrière Hospital, Paris, France, 2IMT, Orange, Nice, France, 3Healthcare, Orange, Paris, France,
4Hôpital Cochin, Department of Rheumatology, Paris Descartes University, Paris, France, 5Rheumatology, Saint-Antoine Hospital,
Paris, France, 6AP-HP Hôpital Cochin, Paris, France, 7e-health services, Sanoia, Gemenos, France
SESSION INFORMATION
Background/Purpose: The natural history of RA and axSpA comprises periods of low disease activity and flares. However, there are
few data linking patient-reported flares to quantifiable outcomes. We previously indicated in the ActConnect study that flares were
related to a moderate decrease in physical activity (1). Objective: to predict patient-reported flares based on activity-tracker-provided
continuous flows of steps per minute.
Methods: This prospective multi-center observational study (ActConnect) included patients with definite RA (ACR/EULAR criteria) or
axSpA (ASAS criteria), owning a smartphone. Over 3 months, physical activity was sampled continuously (each minute) using an
activity tracker, and flares were self-assessed weekly using a specific flare question. In this reanalysis of the dataset, Machine Learning
statistical methods were used. Physical activity data were first normalized at patient level using each patientÕs mean and standard
deviation of steps for a similar timeframe without flares. Then the data were analysed by multiclass Bayesian methods with a Machine
Learning software belonging to Orange (2). The software was instructed to find the best predictive model of patient-reported flares.
Sensitivities and specificities were calculated. Several sensitivity analyses were performed using different physical activity timeframes,
different definitions of flares.
Results: In all, 170/178 patients (91 RA and 79 axSpA patients; 1228 weekly flare assessments and 24,972 1-hour physical activity
assessment timeframes) were analyzed: mean age 45.5±12.4 years, mean disease duration 10.3±8.7 years; 60 (35.3%) were males and
90 (52.9%) received biologics. Disease was well-controlled (mean DAS28: 2.3±1.2; mean BASDAI: 3.3±2.1) but flares were frequent:
reported in 24% of all the questionnaires. The Khiops generated model detected correctly both flares and absence of flare (Table) with a
sensitivity of 96% and a specificity of 97%. The corresponding positive and negative predictive values were respectively 89% and 99%.
Sensitivity analyses were confirmatory.
Conclusion: Machine Learning methods are useful to deal with repeated data in big datasets. The results confirm objectively the
functional impact of patient-reported flares. Furthermore, the correct detection of flares by the activity tracker and adapted statistics
opens the way for future studies of flares using connected devices with great precision and minimal patient burden.
1 - Jacquemin C et al. Physical activity decreased significantly but moderately during weeks where patients reported flares: A 3-month
study of 170 rheumatoid arthritis (RA) or axial spondyloarthritis (AXSPA) patients wearing an activity tracker, Ann Rheum Dis 2017
(suppl): EULAR congress, poster FRI0700.
2- Khiops software for data mining, PredicSis; accessed 06/01/2017: https://khiops.predicsis.com
Disclosure: L. Gossec, None; F. Guyard, Orange, 3; D. Leroy, Orange, 3; T. Lafargue, Orange, 3; M. Seiler, Orange, 3; C.
Jacquemin, None; A. Molto, None; J. Sellam, None; V. Foltz, None; F. Gandjbakhch, None; C. Hudry, None; S. Mitrovic, None; B.
Fautrel, AbbVIe, Biogen, BMS, Celgene, Hospira, Janssen, Eli Lilly and Company, Novartis, Pfizer, Roche, SOBI Pharma, UCB, 5; H.
Servy, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/patient-reported-flares-were-correctly-predicted-by-

an-algorithm-using-machine-learning-statistics-on-activity-tracker-data-on-steps-in-a-longitudinal-3-month-study-of-170-patients-with-
rheumatoid-ar
Measurement Properties of Paindetect, a Neuropathic Pain Screening Tool, for

Evaluating Pain Phenotype in Patients with Rheumatoid Arthritis: Developing
Neuropathic Pain Scale As a Measure of Treatment Outcome By Applying Rasch
Analysis
Yong Gil Hwang1, Lei Zhu2, Ajay Wasan3 and Larry W. Moreland1, 1Rheumatology & Clinical Immunology, University of Pittsburgh,
Pittsburgh, PA, 2University of Pittsburgh, Pittsburgh, PA, 3Departments of Anesthesiology and Psychiatry, University of Pittsburgh,
Pittsburgh, PA
SESSION INFORMATION
Background/Purpose: Ongoing pain state in rheumatoid arthritis (RA) often persists after the resolution of inflammation, indicating
the transition between the acute inflammatory pain and post-inflammatory persistent pain phenotypes. PainDETECT (PDQ) was
developed as a self-reported neuropathic pain screening tool. We conducted a Rasch analysis to investigate whether measurement
properties of PDQ can be used as an outcome measure.
Methods: For RA subjects enrolled in the University of Pittsburgh Rheumatoid Arthritis Comparative Effectiveness Registry
(RACER), Rasch analysis was conducted for all RACER patients who completed PDQ and PROMIS29 short form. Unidimensionality,
reliability, item difficulty, category functioning, and differential item function were examined using the partial credit model for
polytomous items (WINSTEPS ver. 3.93.2). Differential item function (DIF) analyses for gender and age groups (<60,60-70,>70) were
performed to examine item invariance for different groups.
Results: For the 302 subjects analyzed, age was 63.8 ¡¾ 12.4 (mean ¡¾ SD) years with disease duration of 18.4¡¾11.9 years. Given
misfit and high fit residuals, time course and radiating pain items were removed. Remaining 7-item PDQ fit the Rasch model (Table 1).
Item residuals showed high correlation between the burning and slight pressure items and these items were treated as a testlet. Cold-or-
heat item exhibited marginally disordered threshold but the rescoring did not substantially affect fit (Table 2). DIF analyses for gender
and age groups showed uniform DIF. Person-item distribution showed that PDQ was reasonably targeted (Figure).
Conclusion: Rasch analysis of 7-item PDQ suggests that PDQ may function as an outcome measure and may provide a useful tool to
predict RA treatment outcome for neuropathic pain.
Table 1. Summary statistics for all analyses (*Log-likelihood chi-
squared: The chi-square value is approximately = -2 * log-
likelihood of the active data points, **probability: the probability
that these data fit the Rasch model globally, df: degree of
freedom, SE: Standard Error, RMSR: Root-Mean-Square
Residual, MNSQ: Mean Square)
PainDETECT items 9 items 8 items 7 items 7 items
(testlet)
Global Log_- 5521.44 4863.36 4194.34 3534.94
statistics liklihood chi-
squard*
df 5553 4923 4257 3610
Probability** 0.62 0.72 0.75 0.811
Global 0.88 0.90 0.89 0.88
RMSR with (0.89) (0.89) (0.88) (0.87)
expected
value
Person Measure -1.62 -1.66 -1.71 -1.76
(location,
logit)
SE (logit) 0.54 0.61 0.67 0.73
Infit MNSQ 1.02 1.04 1.06 1.04
Outfit MNSQ 1.06 1.03 1.04 1.03
Separation 1.44 1.32 1.29 1.17
Reliability 0.68 0.63 0.63 0.58
Item Measure 0.00 0.00 0.00 0.00
(location,
logit)
SE (logit) 0.07 0.07 0.07 0.07
Infit MNSQ 0.98 1.02 1.03 1.03
Outfit MNSQ 1.08 1.03 1.04 1.03
Separation 5.15 5.05 5.40 5.74
Reliability 0.96 0.96 0.97 0.97
Table 2. Item difficulty, fit statistics and step difficulties (thresholds)
represented with logit unit of PDQ 7 items with 6-level scaling (SE:
Standard Error, RMSR: Root-Mean-Square Residual, MNSQ: Mean Square,
*: disordering of the step difficulties)
Item Difficulty SE Infit Outfi 0 1 2 3 4 5
(logit) (logit)
MNSQ MNSQ
Burning -0.21 0.06 0.92 0.90 -2.61 -1.47 -1.19 -0.73 0.11 1.26
Tingling -0.08 0.06 0.88 0.89 -2.56 -1.40 -1.26 -0.46 0.20 1.27
Light 0.38 0.07 0.87 0.92 -2.41 -0.97 -0.92 -0.10 0.35 1.47
touch
Sudden -0.14 0.06 1.15 1.18 -2.54 -1.40 -1.10 -0.69 -0.26 1.57
attack
Cold or 0.53 0.08 1.19 1.23 -2.35 -1.03 -0.56 -0.24* -0.34* 1.40
heat
Numbness 0.20 0.07 1.01 0.96 -2.42 -1.10 -0.92 -0.60 0.49 1.45
Slight -0.69 0.06 1.19 1.20 -2.91 -1.68 -1.47 -1.04 -0.35 0.63
pressure
Disclosure: Y. G. Hwang, Pfizer Inc, 2; L. Zhu, None; A. Wasan, None; L. W. Moreland, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/measurement-properties-of-paindetect-a-

neuropathic-pain-screening-tool-for-evaluating-pain-phenotype-in-patients-with-rheumatoid-arthritis-developing-neuropathic-pain-
scale-as-a-measure-of-treatmen
Patients’ Attitudes and Experiences of Transitional Care in Paediatric

Rheumatology: A Systematic Review of Qualitative Studies
Ayano Kelly1,2,3,4, Fiona Niddrie5, David Tunnicliffe4,6, Camilla Hanson4,7, Gabor Major8,9, Davinder Singh-Grewal10,11,12 and
Allison Tong4, 1Rheumatology, The Canberra Hospital, Canberra, Australia, 2School of Medicine, Australian National University,
Canberra, Australia, 3Canberra Rheumatology, Canberra, Australia, 4Centre for Kidney Research, The Children's Hospital at Westmead,
Sydney, Australia, 5Rheumatology, Bone and Joint Institute,John Hunter Hospital, Newcatle, Australia, 6Sydney School of Public
Health, University of Sydney, Sydney, Australia, 7Sydney School of Pubic Health, University of Sydney, Sydney, Australia, 8Medicine,
University of Newcastle, Newcastle, Australia, 9Rheumatology, Bone and Joint Institute, John Hunter Hospital NSW Australia,
Newcastle, Australia, 10Faculty of Medicine, University of New South Wales, Sydney, Australia, 11Department of Rheumatology, The
Sydney Children's Hospital Network, Sydney, Australia, 12Sydney Medical School, University of Sydney, Sydney, Australia
SESSION INFORMATION
Background/Purpose: Despite the increasing number of transition programs available for rheumatology patients moving from
paediatric to adult care, transition continues to pose challenges for patients and leads to poorer health outcomes. We aimed to describe
patients’ attitudes and experiences of transitional care in paediatric rheumatology to capture a deeper understanding of patients’
perspectives and inform the development of patient-centred transitional care programs.
Methods: MEDLINE, Embase, PsycINFO, CINAHL, dissertation databases and reference lists were searched to February 2017 and
thematic synthesis was used to analyse the findings.
Results: We included 18 studies involving 267 patients with paediatric rheumatic conditions (juvenile idiopathic arthritis [n=162],
systemic lupus erythematosus [n=79], mixed connective tissue disease [n=5]). We identified six themes (with subthemes): a sense of
belonging (familial care and community, yearning for friends with shared experiences, comfort and reassurance in age appropriate care,
communication to gain understanding and acceptance); trust in familiarity (emotionally preparing for a new environment, building
connection with continuity, valuing privacy, a supportive point of contact); abandonment and fear of the unknown (abrupt and forced
independence, ill-equipped to transfer medical information, shocking view of future self); depersonalised and discredited (like an object
on a conveyer belt, unmet needs and disjointed priorities, sterile and uninviting environment, sudden loss of validation); quest for
autonomy (refreshingly liberated, ready to leave the nest, freedom to disclose); and needing control of parental involvement
(unintentionally undermined, the guilt of independence, reluctant solitude).
Conclusion: There are limited qualitative studies on transitional care in paediatric rheumatology which focus largely on patients with
juvenile idiopathic arthritis. Available qualitative studies show that successful transition can be nurtured by building trust in familiarity,
creating a sense of belonging and facilitating an adolescent’s quest for autonomy. However, some patients feel de-personalised,
abandoned, ill prepared and out of control of the transition process. The findings of this review highlight important elements to include
into transitional care programs and the need for further research into patients’ needs in transitional care.
Disclosure: A. Kelly, None; F. Niddrie, None; D. Tunnicliffe, None; C. Hanson, None; G. Major, None; D. Singh-Grewal, None; A.
Tong, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/patients-attitudes-and-experiences-of-transitional-

care-in-paediatric-rheumatology-a-systematic-review-of-qualitative-studies
Accessing Positive (but Not Negative) Online Reviews Is Associated with Increased
Willingness to Take Medication
Changchuan Jiang1, Ellen Peters2 and Liana Fraenkel3, 1Yale University, New Haven, CT, 2Decision Research, Eugene, OR,
3Rheumatology, Rheumatology, Yale University School of Medicine, New Haven, CT, New Haven, CT
SESSION INFORMATION
Background/Purpose: Testimonials have been shown to have a strong influence on patient decision-making. Patients are increasingly
accessing the Internet as a source of medical information. In this study, we sought to examine whether the number of positive or
negative reviews accessed influence willingness to take a medication.
Methods: We administered a survey to Mechanical Turk workers (≥ 50 years old) who were not currently taking any medications for
osteoporosis or osteopenia. Participants’ received information describing outcomes using one of three randomly distributed formats:
icon array, icon array followed by narrative reviews, or narrative reviews followed by icon arrays. Subjects in the latter two groups were
included for these analyses. The outcomes in the reviews were purposely composed to match the actual distribution of outcomes
associated with a commonly used osteoporosis treatment. Each review was rated by actual patients on a 5-point scale (illustrated by
stars). Willingness to take medication was measured on a 10-point scale before and after reading the description of the medication and
reviews (in the two groups including testimonials). Reviews could be read by clicking on links. We examined whether ratings and
number of online testimonials accessed influenced change in willingness to take the medication using linear mixed models adjusting for
baseline willingness, age, sex, race, education, numeracy, osteoporosis/osteopenia and previous history of osteoporosis/fracture.
Reviews rated above ‘3” were defined as positive; the rest were defined negative. The influence of positive and negative reviews was
examined in separate models due to their strong collinearity.
Results: 276 participants were randomized to one of the two groups including testimonials. The mean (SD) age was 59 (7), and the
majority were female (61%), white (73%) and college graduates (67%). We found significantly positive associations between the
number of accessed positive testimonials and willingness to take the medication (p=0.015). However, no significant association was
found between the number of accessed negative testimonials and willingness. Education level and numeracy did not modify the
association between reviews accessed and willingness to take the medication (data not shown).
Conclusion: In this study, we found that willingness to take a medication for osteoporosis was positively associated with the number of
positive online testimonials accessed. These results support the need to examine the impact of evidenced-based narratives as decision
support tools.
Table. Association between Positive (Model 1) and Negative (Model2) reviews

with willingness to take a medication for osteoporosis.
Model1 Model2
β p-value β p-value
coefficient coefficient
Willingness Before Reading the 0.669 <.0001 0.669 <.0001
Description
Age -0.027 0.138 -0.025 0.170
Male vs. Female 0.401 0.130 0.376 0.159
White vs. Non-White 0.137 0.644 0.087 0.773
High Numeracy vs. Low 0.521 0.053 0.470 0.088
Education Level College Graduate 0.276 0.294 0.340 0.196
vs. Less
History of Bone Fracture vs. None 0.194 0.615 0.174 0.655
Osteopenia/Osteoporosis vs. None -0.019 0.949 -0.0284 0.927
Number of Positive Reviews 0.027 0.015 N/A N/A
Accessed
Number of Negative Reviews N/A N/A 0.0563 0.218
Accessed
Disclosure: C. Jiang, None; E. Peters, None; L. Fraenkel, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/accessing-positive-but-not-negative-online-reviews-

is-associated-with-increased-willingness-to-take-medication
Understanding Perceptions and Experience of Gout through Linguistic Analysis of

Online Search Activities
Kayla Jordan1, James Pennebaker1, Keith Petrie2 and Nicola Dalbeth2, 1University of Texas at Austin, Austin, TX, 2University of
Auckland, Auckland, New Zealand
SESSION INFORMATION
Background/Purpose: Online search engines are widely used to seek information about disease and management strategies. The aim of
this study was to understand what terms people seeking information about gout use most frequently in their online searches and to
explore the psychological and emotional tone of these searches using a linguistic analysis of their search histories.
Methods: In cooperation with Microsoft Research, a large de-identified dataset of search histories from 200,000 consenting individuals
was obtained from ComScore, a web analytics company, covering a two year period (2011 to 2013). Time-stamped search terms were
logged from all major search engines (e.g., Google, Bing). From the larger dataset, three groups were identified: participants who
searched for gout at least once (n = 1,388), participants who had searched for arthritis (arthritis control group, n = 2,289, matched to the
gout group on age and sex), and a random set of participants matched on age and sex (general control group, n = 2,150). Meaning
Extraction Helper (Boyd, 2016), a word frequency software, was used to calculate search term frequencies from the search history of
each participant. Group membership was correlated with individual word frequencies. Search terms were further analyzed using
Linguistic Inquiry and Word Count (LIWC; Pennebaker, Boyd, Jordan, & Blackburn, 2015), a text analysis software from which
psychological processes can be inferred from the words people use.
Results: The most frequent unique searches in the gout group included gout-related and food-related terms (including uric, kidney,
meats, purine, and atkins). Those who searched for gout were more likely to search for words related to eating or avoidance. In
contrast, those who searched for arthritis were more likely to search for disease or health-related words. In the LIWC analysis,
compared with the general control group, total word count was higher for the gout and arthritis groups, indicating higher information
seeking by both groups. Both the gout and arthritis groups searched more for health (e.g., clinic, flu, pill) and ingest (e.g., dish, eat,
pizza) words, and fewer social (e.g. family, talk, they), leisure (e.g., cook, chat, movie), and sexual (e.g. love, sex) words. Compared
with the general control group, the searches of both the gout and arthritis groups were lower in positive emotion tone and higher in
sadness words. There were very few differences between the gout and arthritis groups in the LIWC analysis, with the exception of
higher use of health words by the arthritis group and higher use of insight words (e.g., know, learn, and means) by the gout group.
Conclusion: People searching about gout or arthritis have high levels of information seeking. The perception of gout as a condition
managed by dietary strategies aligns with online information-seeking about the disease and its management. In contrast, people
searching about arthritis are more focused on searching about medical strategies. Linguistic analysis reflects greater disability in social
and leisure activities and lower positive emotion for those searching for medical conditions such as gout or arthritis.
Disclosure: K. Jordan, None; J. Pennebaker, LIWC, 4; K. Petrie, None; N. Dalbeth, Takeda, AstraZeneca, Abbvie, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/understanding-perceptions-and-experience-of-gout-

through-linguistic-analysis-of-online-search-activities
Health Related Quality of Life Is Comparable in Psoriatic Arthritis and Rheumatoid

Arthritis Patients in Spite of Different Disease Activity. SF-36 Data from a Large
Prospective Observational Multicentre Study
Brigitte Michelsen1,2, Till Uhlig1, Eirik K Kristianslund1, Joseph Sexton1, Elisabeth Lie1, Karen M Fagerli3, Hilde B Hammer4, Glenn
Haugeberg5,6 and Tore K Kvien7, 1Dept. of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, 2Dept. of Rheumatology, Hospital
of Southern Norway Trust, Kristiansand, Norway, 3Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, 4Dept of Rheumatology,
Diakonhjemmet Hospital, Oslo, Norway, 5Martina Hansens Hospital, Bærum, Norway, 6NTNU, Norwegian University of Science and
Technology, Trondheim, Norway, 7Diakonhjemmet Hospital, Oslo, Norway
SESSION INFORMATION
Background/Purpose:
It is well established that RA patients have lower health related quality of life (HRQoL) across several domains compared with the
general population, whereas less is known about PsA patients.
The aim of this study was to compare the Medical Outcomes Survey Short Form-36 (SF-36) Physical and Mental Component
Summaries (PCS, MCS) as well as domain scores between RA and PsA patients from a large prospective observational registry.
Methods:
We included first-time enrolled RA and PsA patients from the prospective observational multicenter NORwegian-Disease Modifying
Anti-Rheumatic Drug (NOR-DMARD) study, starting synthetic and biologic DMARDs between year 2000 and 2012. Continuous
variables were compared using independent t-test or Mann-Whitney U-test, as appropriate. Prespecified ANCOVA analyses adjusted for
age, gender and disease duration were performed to compare the SF-36 domains between RA and PsA patients at baseline and after 3
months follow-up. Spyder diagram was made to visualize the differences in health domains (0 worst, 100 best) between the RA and
PsA patients.
Results:
A total of 3903 RA and 1518 PsA patients were included (mean (SD) age 56.8 (31.6)/ 47.9 (12.6) years, median (25th-75th percentile)
disease duration 1.9 (0.07-11.0)/ 2.0 (0.12-9.6) years, 71.2%/ 50.2% women). Mean (SD) 28-joint Disease Activity Score was higher in
RA vs. PsA patients at baseline (4.9 (1.4)/ 4.2 (1.3)) and at 3 months (3.8 (1.5)/ (3.3 (1.4)) follow-up (p≤0.001). Unadjusted means and
adjusted estimated marginal means of PCS, MCS and domain scores all improved during follow-up (table, figure). In adjusted analyses
PCS and MCS were similar between the RA and PsA patients. However, RA patients had slightly worse physical function and role
emotional domains and PsA patients had slightly worse general health and vitality domains both at baseline and at 3 months. Bodily
pain was similar between RA and PsA patients at baseline, but slightly worse in the PsA patients at 3 months follow-up.
Conclusion:
Levels of HRQoL were comparable across all SF-36 domains and component summary scores between patients with RA and PsA, in
spite of higher levels of joint inflammation in the RA patients.
Table Unadjusted and adjusted analyses of SF-36 component summary and domain scores
Unadjusted analyses, mean (SD) Estimated marginal means (95%CI)
Summary score/ domain p-value1 p-value2
RA PsA RA PsA
Physical Component Summary 31.0 (9.9) 31.8 (9.5) 0.01 31.7 (31.3-32.0) 31.6 (31.1-32.1) 0.88
Mental Component Summary 46.0 (11.4) 46.3 (11.5) 0.31 46.4 (46.0-46.8) 46.3 (45.7-46.8) 0.72
Physical Function 49.7 (25.0) 54.5 (23.4) <0.001 51.6 (50.8-52.4) 53.9 (52.7-55.2) 0.002
Role Physical 20.0 (31.6) 23.7 (34.1) <0.001 21.4 (20.3-22.5) 23.4 (21.8-25.1) 0.04
Bodily Pain 34.5 (19.0) 34.7 (18.2) 0.77 35.4 (34.8-36.1) 34.5 (33.6-35.5) 0.13
Baseline
General Health 51.1 (20.3) 49.4 (20.7) 0.006 51.7 (51.1-52.4) 49.2 (48.2-50.3) <0.001
Vitality 39.2 (20.5) 38.7 (20.9) 0.39 41.1 (40.4-41.8) 38.6 (37.6-39.7) <0.001
Social Functioning 63.9 (26.4) 64.8 (25.8) 0.28 65.5 (64.6-66.4) 64.7 (63.4-66.0) 0.34
Role Emotional 51.4 (42.9) 55.8 (42.9) 0.001 52.3 (50.9-53.8) 55.3 (53.1-57.4) 0.03
Mental Health 70.0 (18.3) 70.6 (17.7) 0.31 71.0 (70.3-71.6) 70.6 (69.7-71.5) 0.52
Physical Component Summary 35.6 (11.1) 36.4 (10.8) 0.06 36.4 (36.0-36.8) 36.1 (35.5-36.7) 0.54
Mental Component Summary 48.1 (10.9) 48.1 (11.3) 0.98 48.2 (47.8-48.6) 48.0 (47.3-48.6) 0.55
Physical Function 57.6 (25.9) 62.1 (24.3) <0.001 59.6 (58.7-60.6) 61.4 (60.0-62.8) 0.04
Role Physical 34.5 (38.9) 38.3 (39.5) 0.003 35.9 (34.4-37.4) 37.5 (35.3-39.7) 0.23
Bodily Pain 49.0 (22.0) 47.9 (21.3) 0.12 49.8 (49.0-50.6) 47.5 (46.3-48.8) 0.002
3 Months
General Health 54.2 (21.2) 53.1 (21.7) 0.14 54.8 (54.0-55.6) 52.9 (51.6-54.1) 0.009
Vitality 46.7 (21.5) 45.0 (21.1) 0.02 48.1 (47.3-48.9) 44.8 (43.6-46.0) <0.001
Social Functioning 71.8 (24.7) 72.2 (24.8) 0.68 73.0 (72.0-73.9) 71.8 (70.4-73.2) 0.19
Role Emotional 59.7 (41.4) 64.0 (40.9) 0.002 60.0 (58.4-61.5) 63.0 (60.7-65.4) 0.03
Mental Health 74.2 (17.3) 74.1 (17.1) 0.84 74.8 (74.2-75.5) 73.9 (73.0-74.9) 0.15
1 Independent t-test; 2ANCOVA adjusted for age, gender and disease duration
Figure Estimated marginal means adjusted for age, gender and disease duration of baseline and 3 months SF-36 domains
Disclosure: B. Michelsen, None; T. Uhlig, None; E. K. Kristianslund, None; J. Sexton, None; E. Lie, AbbVie, Celgene, Hospira and
Pfizer, 8; K. M. Fagerli, None; H. B. Hammer, AbbVie Norway, 2,Abbvie, 8,Novartis Pharmaceutical Corporation, 5,Pfizer Inc,
8,Roche Pharmaceuticals, 8; G. Haugeberg, None; T. K. Kvien, AbbVie, 2,Pfizer Inc, 2,Roche Pharmaceuticals, 2,UCB, 2,BMS,
2,MSD, 2,AbbVie, 5,Pfizer Inc, 5,BMS, 8,MSD, 8,Roche Pharmaceuticals, 8,UCB, 8,AbbVie, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/health-related-quality-of-life-is-comparable-in-

psoriatic-arthritis-and-rheumatoid-arthritis-patients-in-spite-of-different-disease-activity-sf-36-data-from-a-large-prospective-
observational-mul
What Is the Impact of Functional Medicine on Patient Reported Outcomes in

Inflammatory Arthritis?
Nicole Droz1, William Messner2 and M. Elaine Husni3, 1Rheumatology, Cleveland Clinic Foundation, Cleveland, OH, 2Quantitative
Health Sciences, Cleveland Clinic, Cleveland, OH, 3Rheumatology, Cleveland Clinic, Cleveland, OH
SESSION INFORMATION
Background/Purpose: Both RA and PsA patients carry significant morbidity despite advances in treatment. Patients often do not
achieve clinical remission which can be limited by patient’s global assessment of disease (PtGA). Currently utilized disease activity and
functional status assessments do not address all treatment outcomes that are important to patients (such as fatigue, psychological
distress and quality of life). These outcomes drive PtGA and represent important areas of focus to achieve remission in RA and PsA
patients. The Patient Reported Outcome Measurement Information System (PROMIS®) developed by the National Institute of Health,
is a set of patient centric measures evaluating physical, mental and social health and is a precise and reliable way to measure domains
critical to PtGA.
Functional medicine utilizes a patient-centered approach, addressing sleep, exercise, nutrition, stress and other lifestyle factors. The
desire for this approach has led more patients to turn to functional medicine for adjunctive care.
Methods: In this 12 week retrospective study, RA and PsA patients were identified by ICD 10 code. They were included if they were
diagnosed by a board certified rheumatologist and participated in a 12 week functional medicine program adjunctive to their usual care.
PROMIS global physical and mental health and pain scores were collected at baseline and after 12 weeks of enrollment and compared
to patients with similar baseline characteristics who received usual care alone. Changes in PROMIS T score domains in global physical,
global mental health and pain were compared between treatment groups using two-sample t-tests.
Results: 38 patients were identified for inclusion. Both functional medicine + usual care (n=19) and usual care alone (n=19) had similar
baseline characteristics including age, gender, smoking status and seropositivity. Baseline global physical and mental health scores were
similar, however, pain was significantly lower at baseline in the functional medicine group as compared to the usual care group. At 12
weeks, there was no statistically significant difference between groups in any primary outcome, however there was a trend towards
improved physical health scores and pain in the functional medicine group at 12 weeks (Table 1).
Table 1: Change in primary outcome scores from baseline to week 12

Usual Care +
Functional
Total Usual Care Medicine p-
Factor (N=38) (N=19) (N=19) value
Physical Health T- 1.7±4.9 0.58±5.5 2.9±4.0 0.16
Score Change*
Mental Health T- 1.2±3.8 0.99±4.0 1.5±3.7 0.70
Score Change*
Pain Change* 0.05±2.0 0.42±2.0 -0.33±1.9 0.25
*Data not available for all subjects.
Statistics presented as Mean ± SD
p-values computed via two-sample t-tests
Conclusion: Enrollment in an adjunctive functional medicine program did not demonstrate a statistically significant improvement in
pain, functional or mental health scores after 12 weeks but did show trends toward improvement in pain and physical function. Larger,
prospective studies of longer duration are needed to identify the subset of patients who would benefit from a functional medicine
intervention.
Disclosure: N. Droz, None; W. Messner, None; M. E. Husni, Pfizer Inc, 6,Abbvie, 5,PASE questionnaire, 7,Novartis Pharmaceutical
Corporation, 5,Lilly, 5,UCB, 5,Amgen, 5,Janssen Pharmaceutica Product, L.P., 5,Bristol Myers Squibb, 5,Regeneron, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/what-is-the-impact-of-functional-medicine-on-

patient-reported-outcomes-in-inflammatory-arthritis
Real World Clinical Trial Comparing the Patient Reported Outcomes Measurement
Information System Short Forms and Profiles to CDAI Disease Classification in
Rheumatoid Arthritis Patients
Jeffrey R. Curtis1, Sergio Schwartzman2, Shelly Kafka3, Dennis Parenti3, Shawn Black3, Stephen Xu4, Wayne Langholff4 and Clifton
O. Bingham III5, 1Rheumatology & Immunology, University of Alabama at Birmingham, Birmingham, AL, 2Weill Cornell Medical
College, New York, NY, 3Janssen Scientific Affairs, LLC, Horsham, PA, 4Janssen Research & Development, LLC, Spring House, PA,
5Rheumatology, Johns Hopkins University, Baltimore, MD
SESSION INFORMATION
Background/Purpose: Patient (Pt) reported outcomes (PROs) play a role in overall disease evaluation, therapeutic response assessment
and care of rheumatoid arthritis (RA) patients (Pts). The Pt Reported Outcomes Measurement Information System (PROMIS [P])
questionnaires developed by the NIH have been used in clinical practice and observational studies in RA (Bartlett 2015). AWARE
(Comparative and Pragmatic Study of Golimumab Intravenous [IV] Versus Infliximab in RA) is a large, pragmatic multi-center United
States-based, real-world evidence study of golimumab IV (GLM) vs. infliximab (IFX) in RA and will assess infusion reactions, disease
activity, and multiple PROs as outcomes.
Methods: AWARE is a prospective, noninterventional, ongoing study in which 1200 adult Pts will be enrolled on initiation of treatment
with GLM or IFX. Objectives include PRO assessments of Pt response to treatment using the PROMIS-29 Profile v2.0 (P29v2), P Pain
Interference Short Form-6b (PISF) and P Fatigue Short Form-7a (FSF), 36-Item Short Form Health Survey (SF-36v2) and Clinical
Disease Activity Index (CDAI). We report here an interim analysis of 747 pts’ baseline PROMIS questionnaire and CDAI scores, and
their inter-relationships. PROMIS questionnaire results are normalized to the US population and reported as a “T-score” (mean of 50
and standard deviation (SD) of 10) with higher scores indicating more of the trait being measured. PROMIS T-scores were compared
between HDA with MDA, LDA and remission, respectively. Data shown are mean ± SD. Statistical testing compared T-scores across
CDAI categories using ANOVA for this IA of baseline data (before drug administration). Data from GLM and IFX pts are combined.
Results: Overall baseline CDAI score was 32.5 ± 15.4, with 71.7% of pts in high DA (HDA), 22.5% in moderate disease activity
(MDA), 5.2% in low disease activity (LDA) and 0.7% in remission. All P29v2 domains, PISF and FSF scores were significantly worse
in pts with CDAI>22 vs. CDAI≤22 (p < 0.05), as was true for the 8 SF-36 domains (data not shown). PROMIS T-scores (P29v2
domains, PISF and FSF) were compared to the 4 CDAI disease activity categories. As shown below, PROMIS T-scores correlated with
CDAI disease category, with HDA Pt T-scores significantly (*, p<0.05) different from those of MDA, LDA and Remission pts (except
between HDA and remission for Anxiety, Depression and Sleep Disturbance domains).
Mean ± Standard Deviation of PROMIS T-Score of All Patients in Interim Analysis Dataset
and a Comparison of T-Scores of PROMIS-29 Domains, Fatigue Short Form and Pain
Interference Short Form to CDAI Disease Activity Category
All Patients Remission LDA MDA HDA
(n=672-682) CDAI≤2.8 2.8<CDAI≤10 10<CDAI≤22 CDAI>22

(n=526)
(n=5) (n=38) (n=165)
P29-Physical Function 37.9 ± 6.6 47.5 ± 5.7 45.0 ± 7.6 40.0 ± 6.7 36.6 ± 5.9*
P29-Anxiety 55.2 ±
53.8 ± 10.4 45.2 ± 6.7# 47.7 ± 8.6 51.3 ± 10.0
10.3*
P29-Depression 54.0 ±
52.5 ± 10.3 42.6 ± 3.6# 45.9 ± 6.5 49.4 ± 9.8
10.3*
P29-Fatigue 58.8 ± 9.9 42.3 ± 5.4 49.7 ± 9.7 55.6 ± 9.2 60.8 ± 9.4*
P29-Sleep Disturbance 48.2 ±
55.5 ± 8.7 51.5 ± 7.9 53.2 ± 8.4 56.7 ± 8.6*
13.6#
P-29 Ability to
participate in Social 43.2 ± 8.6 57.3 ± 7.6 50.8 ± 8.5 45.9± 8.5 41.6 ± 8.0*
Roles and Activities
P29-Pain Interference 63.5 ± 7.7 46.9 ± 7.2 53.9 ± 8.4 60.1 ± 7.7 65.4 ± 6.5*
Fatigue Short Form 7a 59.3 ± 8.5 46.7± 8.8 51.6 ± 9.0 56.2 ± 7.5 61.0 ± 8.1*
Pain Interference Short
62.5 ± 7.6 45.9 ± 7.5 53.9 ± 9.3 59.3 ± 5.6 64.3 ± 6.4*
Form 6b
P29 Pain Intensity
6.0 ± 2.2 1.6 ± 2.6 3.5 ± 2.3 5.1 ± 2.2 6.6 ± 1.9*
(scored 0-10 scale)
T-scores > 50 indicate worsening of the domain relative to the general population, except
“Physical Function” and “Ability to participate in Social Roles and Activities”, where T-
scores < 50 indicate worsening of these domains relative to the general population. * =
p<0.05 vs respective scores in MDA, LDA and remission DA categories. # = not statistically
different from HDA
Conclusion: Our interim findings demonstrate the feasibility of using PROMIS short forms and profiles to evaluate RA pts in clinical
trials. These results confirm the domain validity of PROMIS measures according to CDAI disease category. PROMIS measures show
the range of impact across multiple domains of physical, emotional, and social health experienced by RA pts. With a fully enrolled
AWARE trial, evaluation of PROs, their responsiveness over time, and comparison with SF36 will provide important additional
validation for their use in clinical trials.
Crescendo Bio, Corrona, 9; S. Schwartzman, AbbVie, Antares, Genentech, Janssen, Lilly, Novartis, Pfizer, Regeneron, Sanofi, UCB,
5,AbbVie, Janssen, Genentech, Pfizer, UCB, Crescendo, Novartis, 8,Crescendo Biosciences, Discus Analytics, National Psoriasis
Foundation, 6; S. Kafka, Janssen, 3,Johnson & Johnson, LLC, 1; D. Parenti, Janssen, 3,Johnson & Johnson, LLC, 1; S. Black, Janssen,
3,Johnson & Johnson, LLC, 1; S. Xu, Janssen, 3,Johnson & Johnson, LLC, 1; W. Langholff, Janssen, 3,Johnson & Johnson, LLC, 1; C.
O. Bingham III, Janssen, 2,Janssen, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/real-world-clinical-trial-comparing-the-patient-

reported-outcomes-measurement-information-system-short-forms-and-profiles-to-cdai-disease-classification-in-rheumatoid-arthritis-
patients
The Patient Experience of Musculoskeletal Imaging Tests for Investigation of

Inflammatory Arthritis: A Mixed Methods Study
Sandra Bourke1,2, Nicola Dalbeth1, William J. Taylor3, Anthony Doyle1 and Merryn Gott1, 1University of Auckland, Auckland, New
Zealand, 2Auckland district health board, Auckland, New Zealand, 3University of Otago, Wellington, New Zealand
SESSION INFORMATION
Background/Purpose: Musculoskeletal (MSK) imaging is widely used in rheumatology for diagnosis and management of arthritis.
Although the technical and performance properties of MSK imaging tests are well recognised, few studies have examined the patient
experience of undergoing these tests. The aim of this study was to understand the patient experience of MSK imaging tests for
investigation of inflammatory arthritis, and factors that contribute to this experience.
Methods: In this mixed methods study, we conducted a thematic analysis of semi-structured interviews with 33 patients who had
undergone a recent peripheral joint conventional radiograph, ultrasound, computed tomography or magnetic resonance imaging scan for
investigation of inflammatory arthritis. Data from these interviews were used to generate an 18-item questionnaire about the experience
of MSK imaging which was posted to rheumatology clinic patients within six weeks of peripheral joint imaging. Variables associated
with the overall patient experience of the test were analysed using stepwise linear regression models.
Results: Analysis of the interviews identified six themes; knowledge about the test, the role of imaging in clinical care, awareness of
potential harm, discomfort, experience of waiting, and ‘seeing is believing’. Patient understanding was informed by the information
they received and previous experience of the test. Patients perceived imaging as part of clinical care and believed the benefits of having
the test outweighed the potential risks. Discomfort was experienced by some patients, both emotional due to negative experiences of
interactions with staff and claustrophobia, and physical due to positioning for the test. Some patients felt anxious about waiting times
for the test and for receiving results. Viewing of the images (particularly during ultrasound) improved understanding of disease and
gave a sense of personal involvement in their arthritis treatment. Completed questionnaires were available from 132 patients. In
regression analysis (Table), a strong negative association was observed between the 'Discomfort during the test’ item and the overall
experience of the test (standardised beta 0.35, p<0.001). ‘Staff made the experience better’ (0.26, p<0.001) and ‘Information provided’
(0.28, p<0.001) were positively associated with the overall experience of the test. For those who viewed their images, ‘looking at the
images with my doctor made me feel more involved in my care’ (0.24, p<0.019) was also associated positively with overall experience.
Conclusion: Factors before, during and after a musculoskeletal imaging test contribute to the patient experience. The overall experience
is most influenced by patient discomfort, interactions with staff during the test, information provided, and viewing images to improve
patient involvement in clinical care.
Table 1. Stepwise linear regression analysis of question items (excluding non-applicable questions)
independently associated with overall experience of the test (all participants)
Dependent variable Predictors Standardized ß R2 change p Model
Overall experience Discomfort during the test -0.35 0.16 <0.001 Adjusted R2 = 0.32
Information provided 0.28 0.11 <0.001 F = 20.0
Staff made the experience better 0.26 0.06 <0.001
P < 0.001
Items included in this analysis: imaging modality and all questionnaire items that did not include a not
applicable response.
Disclosure: S. Bourke, None; N. Dalbeth, Takeda, AstraZeneca, Abbvie, 9; W. J. Taylor, Pfizer Inc, 5; A. Doyle, None; M. Gott,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-patient-experience-of-musculoskeletal-imaging-

tests-for-investigation-of-inflammatory-arthritis-a-mixed-methods-study
What Are We Measuring? Influence of Contextual Factors on RAPID3 Scores in

Psoriatic Arthritis
Alexis Ogdie1, Christine Willinger2, M. Elaine Husni3, Jose U. Scher4, Soumya M. Reddy5 and Jessica A. Walsh6,
1Medicine/Rheumatology and Epidemiology, University of Pennsylvania, Philadelphia, PA, 2University of Pennsylvania, Philadelphia,
PA, 3Cleveland Clinic, Cleveland, OH, 4New York University School of Medicine, New York, NY, 5Department of Medicine, Division
of Rheumatology *contributed equally, New York University School of Medicine, New York, NY, 6Division of Rheumatology,
University of Utah, Salt Lake City, UT
SESSION INFORMATION
Background/Purpose: Patient reported outcomes (PRO) provide valuable insights into patientsÕ perceptions of their disease and
overall health and function, and these perceptions influence management of their disease. The objective of this study was to examine
patient factors (also termed Òcontextual factorsÓ) that may be associated with the Routine Index of Patient Data (RAPID3) score
among patients with psoriatic arthritis (PsA).
Methods: Patients with PsA were enrolled in the Psoriatic Arthritis Research Consortium (PARC) between 2015-2016. PARC is a
longitudinal observational cohort study conducted at four institutions in the United States: University of Pennsylvania, Cleveland
Clinic, New York University, and University of Utah. Only baseline data are included in this cross-sectional analysis. Potential
contextual factors were defined prior to statistical testing. A contextual factor is defined by OMERACT as a Òvariable that is not an
outcome of the study but needs to be recognized and measured in order to understand the study results.Ó We examined the association
between potential contextual factors and RAPID3 scores using univariable linear regression models. Variables significant at the
univariable stage (defined as p<0.05) were included in multivariable linear regression models. A final model to identify factors with an
independent relationship with RAPID3 score after accounting for disease activity (e.g., swollen and tender joint counts, skin global
assessment, enthesitis) was formed using backwards selection.
Results: Among the four centers, 401 patients were enrolled; 55% were female, mean age was 51.3, and 76% identified as Caucasian.
Using RAPID3 cut-offs designed for RA, the mean disease activity (9.0, SD 6.7) would be categorized as Òmoderate.Ó Contextual
factors significantly associated with RAPID3 score were female sex, current alcohol use, body mass index (BMI), depression, education
level, and insurance status. In a multi-variable model insurance status, depression and BMI were most strongly associated with
RAPID3 score, after accounting for PsA disease activity. These factors were similarly associated with the individual components of the
RAPID3 (physical function, global assessment, and pain).
Conclusion: In PsA, the RAPID3 score is influenced by depression, insurance status, and obesity. These factors must be taken into
account when using RAPID3 in clinical practice. Additionally, treating depression and improving obesity may be potential targets for
improving the overall perception of disease in patients with PsA.
Table. Univariable and Multivariable Associations
with RAPID3 scores
Univariable Multivariable*
Beta- Beta-
p- p-
Factor coefficient coefficient
value value
(95%CI) (95%CI)
0.002
Age (-0.05- NS
0.06)
2.39 1.32
Female vs Male (0.92- <0.001 (-0.42- 0.14
3.86) 3.05)
1.22
Smoking (ever vs
(-0.42- NS
never)
2.86)
-2.12
Alcohol (current
(-3.66- 0.01
use)
-0.58)
0.23 0.16
Body Mass Index (0.12- <0.001 (0.04- 0.01
0.34) 0.29)
4.09 2.93
Depression (2.36- <0.001 (0.94- <0.001
5.82) 4.92)
0.89
History of
(-1.34- NS
Diabetes
3.12)
History of 1.85
Cardiovascular (-0.01- NS
disease 3.71)
Race
REF
Caucasian
4.77
Black/African
(-0.62- NS
American
10.16)
2.23
Native American (-7.04- NS
11.5)
-3.01
Asian (-7.43- NS
1.42)
3.45
Hispanic/Latino (-2.44- NS
9.34)
2.59
Other (-1.84- NS
7.01)
Education
REF
No college degree
-2.5
College (-4.88- 0.04
-0.13)
-5.24
Post-graduate (-7.92- <0.001
-2.56)
Insurance
REF
Uninsured
Medicare/medicaid -11.63 0.02 -10.47 0.01
(-20.94- (-18.66-
-2.32) -2.27)
-15.88 -13.78
Private (-25.03- <0.001 (-21.8- <0.001
-6.72) -5.76)
-15.28 -14.62
Both (-24.94- <0.001 (-23.13- <0.001
-5.61) -6.11)
Work
Full Time
2.73 (-0.8-
Part time NS
6.25)
7.26
Disabled/sick
(4.23- <0.001
leave
10.3)
3.83
Student (-1.65- NS
9.31)
0.18
Homemaker (-3.34- NS
3.71)
1.89
Retired (-1.05- NS
4.82)
-2.2
Looking for work (-9.83- NS
5.43)
-0.04
PsA duration
(-0.11- NS
(years)
0.03)
-0.02
PsO duration
(-0.07- NS
(years)
0.03)
0.8 (0.24-
Center 0.01
1.36)
Disease/Outcome
factors
-0.04
Inflam Back Pain (-2.49- NS
2.41)
0.68
ASAS
(-2.05- NS
classification
3.41)
0.72
Skin Physician
(0.36- <0.001
Global
1.07)
2.13
Enthesitis Count (1.09- <0.001
3.17)
0.48
Total swollen 0.74 (0.5-
<0.001 (0.19- <0.001
joints 0.97)
0.77)
0.39
Total tender 0.16 (0-
(0.26- <0.001 0.04
joints 0.31)
0.51)
-1.06
Nail dystrophy (-3.53- NS
1.41)
The β-coefficients can be interpreted as the difference
in the mean PRO score between the two groups. The
95% confidence intervals do not include 0 (no
difference). CIs that do not cross 0 indicate statistical
difference.
Prevalence of obesity was 42%, depression 19%,

diabetes 10% and cardiovascular disease 18%.
Sex was specifically included in the previous model

given others studies reporting an association between
sex and patient reported outcome scores.
*All other items that were not significant in the

multivariable models were removed.
Disclosure: A. Ogdie, Pfizer, Novartis, 2,Takeda, Pfizer, Novartis, 5; C. Willinger, None; M. E. Husni, Celgene, AbbVie, Genentech,
Bristol-Myers Squibb, Pfizer, Novartis, and Janssen, 9; J. U. Scher, NIAMS-NIH, 2; S. M. Reddy, Eli Lilly and Company, 5; J. A.
Walsh, Novartis, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/what-are-we-measuring-influence-of-contextual-

factors-on-rapid3-scores-in-psoriatic-arthritis
Disease Burden at One Academic Rheumatology Routine Care Setting Is Similar in

Osteoarthritis (OA) and Rheumatoid Arthritis (RA) at First Visit but Significantly
Greater in OA at a 6-Month Follow-up Visit
Jacquelin R. Chua1, Shakeel M. Jamal1, Isabel Castrejón1, Najia Shakoor1, Anne-Marie Malfait2, Joel A. Block2 and Theodore
Pincus2, 1Division of Rheumatology, Rush University Medical Center, Chicago, IL, 2Rheumatology, Rush University Medical Center,
Chicago, IL
SESSION INFORMATION
Background/Purpose: Osteoarthritis commonly is regarded as less severe and less debilitating than RA. However, limited data are
available for direct comparison of OA versus RA, in large part because different measures traditionally have been used to assess
patients, primarily a HAQ (Health Assessment Questionnaire) in RA and WOMAC (Western Ontario and McMaster Universities
Osteoarthritis Index) in OA. RAPID3 (Routine Assessment of Patient Index Data) on an MDHAQ (Multi-Dimensional HAQ) is a
composite of 3 patient self-report measures that was developed for RA, but is informative in many other rheumatic diseases, including
OA1. Recent observations from 4 settings indicate that RAPID3 and other MDHAQ scores were similar or higher in OA versus RA
patients2. Those findings were from a cross-sectional convenience sample, and likely were affected by treatment in most patients. We
analyzed MDHAQ/RAPID3 scores in patients with a primary diagnosis of either OA or RA at their first visit to a rheumatology center
and at 6 month follow-up.
Methods: At one academic center, all patients complete an MDHAQ/RAPID3 prior to seeing the rheumatologist. The 2-page
MDHAQ/RAPID3 includes scores for physical function (FN) (0-3 converted to 0-10) and 0-10 visual analog scale (VAS) scores for
pain (PN) and patient global assessment (PATGL), compiled into a 0-30 composite RAPID3. Patients with physician-diagnosed primary
OA or RA were included in the study. Mean FN, PN, PATGL and RAPID3 scores in RA and OA at baseline and 6-month follow-up
(range 3-9 months) were compared for differences between first and second visits using t-tests, as well as between OA and RA adjusted
using MANOVA.
Results: At first visit, RAPID3 was 15.9 in OA vs 15.3 in RA - no meaningful differences in individual measures or index (Table). At
6-month follow-up, in OA, RAPID3 fell from 15.9 to 14.9 (-1.0, p=0.06) vs 15.3 to 11.1 (-4.2, p<0.001) in RA, indicating greater
improvement in RA, resulting in significantly higher disease burden in OA vs RA. These differences remained significant after
adjusting for age, sex, body mass index, and education level.
Mean and standard deviation (SD) at first visit and 6-month follow up visit MDHAQ/RAPID3 of patients with OA and RA seen in
routine care
Measures OA (n=109) RA (n=102) OA vs RA OA vs RA
p value p adjusted*
First visit
Function (0- 3.15 (1.9) 2.89 (2.2) 0.34 0.60
10)
Pain (0-10) 7.01 (2.3) 6.36 (2.9) 0.07 0.49
PATGL (0- 5.69 (2.8) 5.85 (3.0) 0.69 0.30
10)
RAPID3 (0- 15.9 (5.9) 15.3 (7.0) 0.52 0.47
30)
Follow-up visit
Function(0- 2.93 (1.9) 2.24 (2.2) 0.02 0.006
10)
Pain (0-10) 6.36 (2.5) 4.60 (3.0) <0.001 0.03
PATGL (0- 5.62 (2.7) 4.10 (3.2) <0.001 0.001
10)
RAPID3 (0- 14.9 (6) 11.1 (7.6) <0.001 0.001
30)
*adjusted for age, sex, BMI and education
Conclusion: Patients with OA or RA have similar disease burdens at first visit, but OA patients have a considerably higher burden 6
months later, reflecting more effective treatments for RA than for OA. Nonetheless, OA is a severe disease at first visit, suggesting a
need for further research in OA toward improved treatment and outcomes. MDHAQ/RAPID3 is feasible and useful to assess and
monitor clinical status in routine care of patients with different rheumatic diseases.
References: 1. J Clin Rheumatol. 2013;19(4):169-74. 2. RMD Open, 2017, in press.
Disclosure: J. R. Chua, None; S. M. Jamal, None; I. Castrejón, None; N. Shakoor, None; A. M. Malfait, Galapagos, Regeneron,
Ferring, 5; J. A. Block, None; T. Pincus, Theodore Pincus, 7.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/disease-burden-at-one-academic-rheumatology-

routine-care-setting-is-similar-in-osteoarthritis-oa-and-rheumatoid-arthritis-ra-at-first-visit-but-significantly-greater-in-oa-at-a-6-month-
follow-up-v
The Impact of Rheumatoid Arthritis-Sustained Remission on Patient´s Reported

Outcomes Differs Accordingly to Each Particular Outcome
Irazú Contreras-Yáñez1, Guillermo Guaracha2, César Sifuentes-Cantú3 and Virginia Pascual-Ramos4, 1Inmunología y Reumatología,
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico, 2Instituto Nacional de Ciencias Médicas y
Nutrición Salvador Zubirán, Mexico City, Mexico, 3Department of Immunology and Rheumatology, Instituto Nacional de Ciencias
Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico, 4Instituto Nacional de Ciencias Médicas y Nutrició, Mexico City, Mexico
SESSION INFORMATION
Background/Purpose: Sustained remission (SR) is the most desirable status in patients with rheumatoid arthritis (RA). For adoption by
patients, SR should reflect symptom´s resolution and impact patient-report-outcomes (PRO). The study was performed in an inception
cohort of recent-onset RA, initiated in 2004. Objectives of the study were to describe PRO from patients who achieved SR for the first
time, as well as the proportion of those patients who achieved PRO norms, and to describe the pattern of PRO´s normalization.
Methods: In November 2016, the cohort had 145 patients with ≥30 months of follow-up, with complete and regular rheumatic
evaluations that additionally included a patient-pain visual analogue scale (PVAS), a patient-overall disease-VAS (OVAS), the health
assessment questionnaire (HAQ), the Short-Form 36v2 Survey (SF-36) and fatigue assessment. First SR was defined according to
DAS28 cut-offs (DAS28-SR) and to the ACR/EULAR 2011 Boolean definition (B-SR), if maintained for at least 12 months. The
dependent t test and Mc Nemar´s tests were used. The study was approved by IRB and written informed consent was obtained from all
the patients.
Results: At cohort inclusion, patients were primarily middle-aged female with a high frequency of auto-antibodies. Up to SR, 98% of
the patients were on traditional DMARDs and 37-42% were receiving combined low doses of corticosteroids.
An increased number of patients achieved DAS28-SR compared to B-SR (78 vs. 63 patients, respectively). In addition, follow-up to
DAS28-SR was shorter than to B-SR, and the duration of DAS28-SR was longer than the duration of B-SR (p≤0.03 for both).
In general, at SR (either DAS28-SR or B-SR) patients had PRO proxy to normal values (PRO-N); the percentage of patients with PRO-
N varied from 97% for HAQ, but decreased to 50% for absence of fatigue.
In SR patients, we calculated (mean±SD) months of follow-up to achieve each particular PRO-N, and to achieve values within the
normal range of erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) and of overall-disease-physician-VAS. In DAS28-
SR patients, normalization of ESR and CRP was detected at 1.5 and 2.9 months from baseline, respectively, followed by HAQ-N,
PVAS-N, OVAS-N, SF-36-N (achieved between 6 and 7 months of follow-up); absence of fatigue was detected late, at 8.7 months of
follow-up, similar to DAS28-SR, which was achieved at 9.8 months. A similar pattern was observed in B-SR patients (Figure. Pattern
of outcome normalization).
Conclusion: At SR, RA patients achieved PRO proxy to normal values although the percentage of patients with PRO-N varied
depending on each particular outcome. We identified a particular temporal pattern of outcome normalization. PRO provide unique
information that cannot be collected from a physician and aid to complete the clinical picture of RA patients in SR.
Figure.
Disclosure: I. Contreras-Yáñez, None; G. Guaracha, None; C. Sifuentes-Cantú, None; V. Pascual-Ramos, None.

View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-impact-of-rheumatoid-arthritis-sustained-
remission-on-patients-reported-outcomes-differs-accordingly-to-each-particular-outcome
Preferences and Satisfaction in a Pediatric Multidisciplinary Infusion Center

Catherine McDermott &1, Brian Sohl1, Lisa M. McGregor2 and Lisabeth V. Scalzi3, 1Penn State Hershey Medical Center, Hershey,
PA, 2Penn State Hershey Children’s Hospital, Hershey, PA, 3Department of Rheumatology, Penn State Hershey Children’s Hospital,
Hershey, PA
SESSION INFORMATION
Background/Purpose:
Many pediatric rheumatology patients receive infusions in multi-specialty infusion centers (MSICs). There is little data about pediatric
patient satisfaction and preferences within MSICs and no data about their physicians’ perceptions of these preferences. In order to better
understand and improve the patient experience, we studied these concepts.
Methods:
We created and administered a survey containing free response and 5-point Likert scale questions to parents of children receiving
infusion therapy and their respective physicians at our center. We compared means and sums of the scores using t-tests and ANOVA
analyses.
Results:
We surveyed 21 physicians (8 oncologists, 13 non-oncologists) and 174 parents of patients with oncologic (n=66) and non-oncologic
(n=108) diagnoses who were receiving infusions in our MSIC. Our results showed significant differences between family
satisfaction/preference and physician perception (Fig 1).
For all 3 questions, families responded positively towards the multi-specialty nature of the infusion center, though oncology families to
a lesser degree than non-oncology families (respectively, mean=4.5 ±0.07 vs. 4.8 ±0.05; p<0.009).
Rheumatologists had a greater discrepancy than oncologists did in their perceptions of their patients’ preferences, predicting their
patients would be less satisfied receiving care in an MSIC than patients reported (Fig 2). In addition, rheumatologists believed their
patients would prefer to receive infusions in a center specific for children without cancer, despite families not having this preference
(mean = 1.3 ± 0.58 vs. 2.7±0.90; p<0.027, respectively).
Lastly, the majority of families surveyed reported they had increased awareness and empathy from exposure to children with other
diagnoses, reflected in their comments (Table 1).
Conclusion:
Pediatric rheumatology patients are satisfied with their experiences in an MSIC. Patients are significantly more satisfied than their
physicians perceive. As infusion therapy for rheumatologic conditions increases, it is important to understand patient preferences as a
crucial aspect of patient-centered care. Patients are content to receive infusions in an MSIC and find value in their experiences with
families of children with other diagnoses.
Disclosure: C. McDermott &, None; B. Sohl, None; L. M. McGregor, None; L. V. Scalzi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/preferences-and-satisfaction-in-a-pediatric-

multidisciplinary-infusion-center
Patients with Gout Consider Zero Flares over the Previous Six or Twelve Months
Necessary for a Remission State
William J. Taylor1, Nicola Dalbeth2, Kenneth Saag3, Jasvinder A. Singh4, Elizabeth J. Rahn5, Amy S. Mudano6, Yi-Hsing Chen7,
Ching-Tsai Lin8, Paul Tan2, Worawit Louthrenoo9, Janitzia Vazquez-Mellado10, Hansel Hernández-Llinas11, Tuhina Neogi12, Ana
Beatriz Vargas-Santos12, Geraldo Castelar-Pinheiro13, Rodrigo B. Chaves-Amorim13, Till Uhlig14, Hilde B Hammer14, Maxim
Eliseev15, Fernando Perez-Ruiz16, Lorenzo Cavagna17, Geraldine M. McCarthy18, Lisa K. Stamp19, Martijin Gerritsen20, Viktoria
Fana21, Francisca Sivera22 and Angelo L. Gaffo5, 1University of Otago, Wellington, New Zealand, 2University of Auckland,
Auckland, New Zealand, 3Division Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, AL,
4Rheumatology, University of Alabama at Birmingham, Birmingham, AL, 5Department of Medicine, Division of Immunology and
Rheumatology, University of Alabama at Birmingham, Birmingham, AL, 6University of Alabama at Birmingham, Birmingham, AL,
7Taichung Veterans General Hospital, Taichung, Taiwan, 8Division of Allergy, Immunology and Rheumatology, Taichung Veterans
General Hospital, Taichung, Taiwan, 9Div of Rheumatology, Dept of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand,
10Rheumatology, Hospital General de Mexico, Mexico City, Mexico, 11Hospital General de Mexico, Mexico City, Mexico, 12Clinical
Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, MA, 13Universidade do Estado do Rio de
Janeiro - UERJ, Rio de Janeiro, Brazil, 14Dept. of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, 15V. A. Nasonova Research
Institute of Rheumatology, Moscow, Russian Federation, 16Servicio de Reumatología, Vizcaya, Spain, 17Division of Rheumatology,
University and IRCCS Policlinico S. Matteo, Pavia, Italy, 18Div of Rheumatology, Mater Misericordiae University Hospital, Dublin,
Ireland, 19University of Otago, Christchurch, New Zealand, 20Westfries Gasthuis, Hoorn, Netherlands, 21Center for Rheumatology and
Spine Diseases, Rigshospitalet , Glostrup, Copenhagen Center for Arthritis Research (COPECARE), Copenhagen, Denmark, 22Sección
de Reumatología, Hospital General Universitario de Elda., Elda, Spain
SESSION INFORMATION
Background/Purpose: Treatment targets for gout generally focus on serum urate, but patient-centred targets may be equally important.
We seek to determine the relationship between gout flare rates and patient self-classification into 3 disease activity states: remission (no
symptoms of disease), low disease activity (LDA, no symptoms of disease that require additional therapy), and patient acceptable
symptom state (PASS, level of symptoms acceptable to the patient).
Methods: Patients with 2015 ACR/EULAR gout criteria attending rheumatology clinics in 17 countries were asked to recall the number
of flares over the preceding 6 and 12 months. For each time horizon they were asked to consider whether they thought their gout had
gone away (remission), didn’t require any additional or stronger therapy (LDA) or was controlled to their satisfaction (PASS).
Multinomial logistic regression was used to determine the association between being in each disease state, flare count and self-reported
current flare. A distribution-based approach and 3-state analysis of the volume under a ROC surface (VUS) with extended Youden
index identified possible flare count thresholds for each state.
Results: 512 patients were recruited with mean (SD) age 58 (14) years, 89% were male, and disease duration of 12 (10) years. The
states of LDA/PASS were combined since the distribution of recalled flares was very similar for these states. Each recalled flare
reduced the likelihood of self-classified remission by 52% for 6 months and 23% for 12 months, and the likelihood of LDA/PASS by
15% and 5% for 6 and 12 months, respectively (Table). Not currently self-reporting a flare was strongly associated with self-
classification into remission (OR 15.20 for 6 months and 15.13 for 12 months) or LDA/PASS (OR 5.74 for 6 months and 5.13 for 12
months) (Table). The VUS for 6-month flare count was 0.41 (95%CI 0.36 to 0.46) and the thresholds identified from the extended
Youden index were 0 and 3.5; for 12-month flare count, the VUS was 0.38 (95%CI 0.33 to 0.43) and thresholds were 0 and 4.5. A
threshold of 0 flares in preceding 6 and 12 months was associated with accurate classification of remission in 58% and 56% of cases,
respectively.
Conclusion: Recalled flares are significantly associated with patient perceptions of disease activity in gout, supporting flare as an
important target of therapy. Zero flares over prior 6 or 12 months were necessary for most patients to self-categorise as remission.
Current flare is strongly associated with perception of disease activity, independently of the number of prior flares. However, recalled
flare counts alone do not fully predict self-categorised states, suggesting that other factors may also contribute to perception of gout
disease activity.
Table. Association between self-categorized disease state and recalled
flares and current flare.
Disease activity
OR (95% CI)‡ p-value
category*
Considering Remission No. of 0.48 (0.38 to 0.60) <0.001
the previous 6 flares
months Current 15.20 (5.58 to <0.001
flare 41.37)
absent†
LDA/Pass No. of 0.85 (0.79 to 0.90) <0.001
flares
Current 5.74 (3.51 to 9.37) <0.001
flare absent
Considering Remission No. of 0.77 (0.70 to 0.85) <0.001
the previous 12 flares
months Current 15.13 (5.68 to <0.001
flare 40.34)
absent†
LDA/Pass No. of 0.95 (0.92 to 0.97) <0.001
flares
Current 5.35 (3.33 to 8.60) <0.001
flare absent
* The reference category is: Not in any of the 3 low disease activity
states.
† The reference category is: Current flare present
‡ The OR are derived from a multinomial logistic regression model

(separate models for 6 and 12 months), where the dependent variable was
disease activity category and the independent variables were flare count
and presence/absence of current flare
Disclosure: W. J. Taylor, AstraZeneca, Pfizer, Abbvie, Roche, 5; N. Dalbeth, AstraZeneca, 2,Takeda, Pfizer, AstraZeneca, Cymabay,
Crealta, 5,Takeda, AstraZeneca, 9; K. Saag, AstraZeneca, Horizon, Ironwood, SOBI, Takeda, 5; J. A. Singh, Takeda, Savient,
2,Savient, Takeda, Regenron, Merz, Bioiberica, Crealta, Allergan, WebMD, UBM LLC, American College of Rheumatology, 5; E. J.
Rahn, None; A. S. Mudano, None; Y. H. Chen, None; C. T. Lin, None; P. Tan, None; W. Louthrenoo, None; J. Vazquez-Mellado,
None; H. Hernández-Llinas, None; T. Neogi, None; A. B. Vargas-Santos, None; G. Castelar-Pinheiro, None; R. B. Chaves-
Amorim, None; T. Uhlig, None; H. B. Hammer, None; M. Eliseev, None; F. Perez-Ruiz, Ardea Biosciences, AstraZeneca, Cymabay,
Grunenthal, Menarini, 5; L. Cavagna, None; G. M. McCarthy, None; L. K. Stamp, None; M. Gerritsen, None; V. Fana, None; F.
Sivera, AstraZeneca, 5; A. L. Gaffo, SOBI, 5,Amgen, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/patients-with-gout-consider-zero-flares-over-the-

previous-six-or-twelve-months-necessary-for-a-remission-state
Integration of Electronically Captured Patient-Reported Outcomes in a Pediatric

Rheumatology Clinic Visit
Alysha J. Taxter1 and Ajay Dharod2, 1Pediatrics, Brenner Children's Hospital, Wake Forest Baptist Medical Center, Winston-Salem,
NC, 2Internal Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC
SESSION INFORMATION
Background/Purpose: Increasing emphasis has been placed on the use of patient reported outcomes (PROs) in both research and
clinical practice. Capturing this data in clinical practice, however, is often challenging for providers and clinical staff: paper forms are
easily lost and verbal questions may be rushed or skipped in busy clinics. Many electronic medical record systems (EMRs) have
developed patient portal systems with the capacity to electronically administer questionnaires. This study aims to evaluate the use of a
patient portal system for collecting PROs in a pediatric rheumatology clinic.
Methods: Response rates to patient reported outcome questionnaires were compared one month pre- and four months post-
implementation of an electronic data capture system. Pre-implementation, verbal responses were manually entered into the chart by the
physician. Post-implementation, data were captured electronically through our medical record patient portal. Questionnaires were
completed on clinic computers or tablets in the waiting or exam room. Questions examined current physical symptoms, performed
psychiatric screening, reported both patient pain and fatigue on 0-10 ordinal scales, and allowed entry of any concerns. English and
Spanish versions were available. Patients and clinical staff were surveyed about their experiences.
Results:
There were 106 and 307 questionnaires completed pre- and post-implementation, respectively. Post-implementation, the majority of
patients/parent-proxies entered their own data. Patient-portal activation increased from 53% to 88% (p<0.01). Higher response rates
were seen in psychiatric symptoms after electronic questionnaire implementation. Identification of positive responses pre- and post-
electronic questionnaire implementation respectively, are reported: depression increased from 3 to 14% (p<0.01), anxiety increased
from 2 to 27% (p<0.01), and difficulty sleeping increased from 16 to 30% (p<0.01). Questionnaires also revealed themes in parental
concerns, including “When can we reduce medication?” and “What can we do about her pain?” Physician satisfaction surveys estimated
a time savings of 2-5 minutes per visit. Patients reported positive feedback to having portal access and state it allows more time to think
about the questions. Furthermore, it introduces patients and their families to other functions within the portal, such as viewing labs and
communicating with providers. There were 29 patient-portal correspondence messages prior to implementation and mean of 22
messages/month thereafter. Staff reported there was difficulty with activation of proxy accounts and password recovery workflow.
Conclusion: Integration of novel patient electronic data capture systems within pediatric clinics improve recognition and identification
of psychiatric symptoms. It can also save valuable physician time. Improved discrete data capture is necessary to further improve
clinical systems and patient care.
Disclosure: A. J. Taxter, None; A. Dharod, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/integration-of-electronically-captured-patient-

reported-outcomes-in-a-pediatric-rheumatology-clinic-visit
Psychometric Features of a New Methotrexate (MTX)-Specific Adherence Tool for

Use in the Management of Patients with Rheumatoid Arthritis (RA): Preliminary
Results from an Online Patient Community
Elodie de Bock1, Corrado Bernasconi2, Tan P. Pham1, Ana Maria Rodriguez3, Khaled Sarsour4, J. Michael Nebesky2 and Christine de
la Loge1, 1Mapi, Lyon, France, 2F. Hoffmann-La Roche, Basel, Switzerland, 3Patients Like Me (PLM), Cambridge, MA, 4Genentech,
South San Francisco, CA
SESSION INFORMATION
Background/Purpose: F. Hoffmann-La Roche Ltd. and Mapi collaborated to develop a medication adherence measure among RA
patients taking MTX—the Methotrexate Experience Questionnaire (MEQ). The MEQ aims to facilitate communication between
patients and clinicians during consultation to help clinicians identify patients having difficulty with MTX adherence and specific issues
leading to nonadherence. The MEQ was developed in accordance with best psychometric practices, including patient interviews, and
contains several domains providing a comprehensive picture of drivers and descriptors of adherence issues encountered by RA patients
treated with MTX. An observational study was conducted with patients from the PatientsLikeMe (PLM) online community. The aims of
the present analysis were to provide preliminary results regarding the MEQ psychometric features and identify drivers of poor
adherence in a population of PLM online users treated with MTX for RA.
Methods: This was a cross-sectional study where PLM RA subjects treated with MTX (currently or within the past 6 months) were
asked to complete the 4-item Morisky Medication Adherence Scale (MMAS-4) and the MEQ online. The MEQ includes 29 items with
4- or 6-point Likert scale answers. Key psychometric MEQ features were described: acceptability and appropriateness of items (quality
of completion, distribution, floor and ceiling effects), construct validity (multi-trait correlation-based analyses), concurrent validity
(description and comparison of MEQ scores across MMAS-defined adherence and clinical groups). Linear, logistic, and partial least
squares regressions were used to identify drivers of poor adherence.
Results: The population included 217 patients (80.2% aged 40-65 years; 90.8% women) whose mean duration of RA was 9 years (SD
±10.5). The MEQ was well accepted (only 3.2% of completed questionnaires were missing ≥1 MEQ items). Some revisions to the
theoretical structure were proposed in the process toward the development of the MEQ scoring algorithm (5 dimension scores were
proposed: Perceived benefits of MTX, Convenience aspects of MTX, Drivers of nonadherence to MTX, Negative sides of MTX, Patient
information). As expected, convenience and noncompliance scores were highly correlated to MMAS-4 (r=0.661 and 0.661,
respectively), while Patient information and Perceived benefits did not show a significant association. Moreover, MEQ convenience,
noncompliance, and Negative sides scores discriminated between low, moderate, and high adherence groups as defined by the MMAS-4
(p<0.0001). Multiple drivers of poor adherence were identified, including aspects related to convenience, symptom improvement, how
sick the patient felt, patient activities, and patient travel plans.
Conclusion: These preliminary results related to psychometric features of MEQ look promising as the instrument appears to
discriminate between low, moderate, and high adherence as defined from the generic MMAS-4 in an online community of patients with
RA. Future research includes psychometric validation of the MEQ in patients with clinically diagnosed RA against an objective
measure of adherence (prescription claims data).
Disclosure: E. de Bock, F. Hoffmann-La Roche, 5; C. Bernasconi, Roche, 5; T. P. Pham, F. Hoffmann-La Roche, 5; A. M.

Rodriguez, None; K. Sarsour, Genentech, 3; J. M. Nebesky, F. Hoffmann-La Roche, 3; C. de la Loge, F. Hoffmann-La Roche, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/psychometric-features-of-a-new-methotrexate-mtx-

specific-adherence-tool-for-use-in-the-management-of-patients-with-rheumatoid-arthritis-ra-preliminary-results-from-an-online-patient-
community
Patient Experiences of Rheumatoid Arthritis Models of Care: An International

Survey
Cheryl L. Koehn1, Kelly Lendvoy1, Yue Ma2, Linda Li3, Alison Hoens4, Marion Souveton5 and John M. Esdaile4, 1Arthritis
Consumer Experts, Vancouver, BC, Canada, 2Simon Fraser University, Burnaby, BC, Canada, 3Rheumatology, Arthritis Research
Canada, Richmond, BC, Canada, 4Arthritis Research Canada, Richmond, BC, Canada, 5F. Hoffmann-La Roche Ltd, Basel, Switzerland
SESSION INFORMATION
Background/Purpose: Despite the global prevalence of rheumatoid arthritis (RA), there is no single model of care (MoC) and little is
known about the RA patient journey at the population level. 18 RA patient organizations launched a global survey to understand patient
experiences of RA MoCs and identify common challenges, gaps, and opportunities for improvement.
Methods: A short online questionnaire of RA patients recruited by patient organizations from 25 countries in Europe, the Middle East,
and North and South America was conducted by Kantar Health (March 15–June 9, 2017) in 16 languages. The survey include questions
on the patient’s disease journey through 5 key elements of an RA MoC: 1) recognize symptoms/seek care, 2) access to specialist care, 3)
medical management, 4) shared care, and 5) self-care. Countries with >30 respondents were included in this analysis. Data were
analyzed at the global and country levels; descriptive (means, medians, percentages) analyses were conducted using STAR ODEC
version 2.9.13. Global results are presented.
Results: 2690 respondents from 14 countries were included in this analysis (Table 1): 90% women, 71.5% between 35-65 years of age,
and 69.7% from urban communities. Most respondents first heard they had RA from a rheumatologist (66%) (Table 2) and classified
their current RA severity as moderate (59%) or severe (24%). Respondents reported an average of 22 mo (median, 5 mo) to receive an
RA diagnosis and 20 mo (median, 3 mo) for an initial rheumatologist visit after first experiencing RA symptoms. Although 47% waited
<1 mo for their first rheumatologist appointment, 33% had to wait >3 mo. Half (49%) see a rheumatologist once every 3 mo for
management, 32% less frequently, and 9% as needed or do not see a rheumatologist. The majority (92%) have been treated with
methotrexate, hydroxychloroquine, or sulfasalazine; however, most have not taken or did not know whether they have received
biologics (72%) or small molecule treatment (82%). One-third (30%) reported it took from 4 mo to “never” for a first medication
effectiveness assessment. Many respondents (39%) are not completely confident when describing RA to other people (Table 2). Access
to additional information about living with RA and self-care was noted as a need by half (49%).
Conclusion: This large international patient survey highlights self-reported gaps and delays in all 5 key elements of a standardized RA
MoC, including significant delays to diagnosis and specialist access globally, delayed therapy effectiveness assessment, and additional
education/information to increase the level of confidence to describe RA and improve effective self-care practice.
Disclosure: C. L. Koehn, F. Hoffmann-La Roche Ltd, 9; K. Lendvoy, F. Hoffmann-La Roche Ltd, 9; Y. Ma, None; L. Li, None; A.
Hoens, None; M. Souveton, F. Hoffmann-La Roche Ltd, 3; J. M. Esdaile, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/patient-experiences-of-rheumatoid-arthritis-models-

of-care-an-international-survey
Multidomain Functional Assessment in a Cohort of Patients with Systemic Lupus

Erythematosus: A Pilot Study
Laura Plantinga1, Benjamin Tift2, C. Barrett Bowling3, Charmayne M. Dunlop-Thomas4, S. Sam Lim5 and Cristina Drenkard5,
1Department of Medicine, Emory University School of Medicine, Atlanta, GA, 2Edward Via College of Osteopathic Medicine,
Spartanburg, SC, 3Durham Veterans Affairs Medical Center, Durham, NC, 4Emory University School of Medicine, Atlanta, GA,
5Division of Rheumatology, Emory University School of Medicine, Atlanta, GA
SESSION INFORMATION
Background/Purpose: Systemic lupus erythematosus (SLE) is a chronic, complex disease with multiple comorbid conditions and non-
disease-specific manifestations. Consequently, the impact of SLE on both physical and cognitive function may be analogous to what is
seen in the general geriatric population. We used a multidomain functional assessment, commonly performed in geriatric patients but
novel among SLE patients, to better understand the magnitude of the functional impairment in this population.
Methods: We recruited 60 adult (≥20 years old) SLE patients from an ongoing cohort study of Atlanta-area SLE patients for an in-
person visit (10/16-4/17), in which we evaluated physical and cognitive function in several domains shown to be associated with poor
outcomes in geriatric populations: physical performance (by the Short Physical Performance Battery; range on balance, gait speed, and
lower body strength scores, 0-4; higher scores = better performance); cognitive performance (by NIH Toolbox measures of five fluid
cognition domains; reported as adjusted t-scores); and self-reported measures including physical functioning (reported as t-scores),
activities of daily living (ADLs), falls, and life-space mobility, which measures how far, how often, and how much help is needed as
respondents move through their community (scale 0-120; higher scores = greater community mobility).
Results: Balance and gait speed scores were high, while mean lower body strength scores were low (Table). Cognitive performance
was close to average (score=50) in the domains of episodic and working memory, but mean scores for cognitive flexibility, processing
speed, and attention/inhibitory control were ~1 SD below average for healthy individuals of the same age, sex, race, ethnicity, and
education level. Patients reported independence in most basic ADLs but dependence in several instrumental ADLs. Nearly half (45.0%)
of patients reported falling in the prior year, and only 40.0% reported unlimited ability to travel without the help of another person.
Overall, scores did not differ substantially by age, although older patients had slightly lower self-reported physical functioning and
higher cognitive performance scores than younger patients in general.
Conclusion: SLE patients of all ages report a substantial burden of functional impairment across multiple domains, similar to that
among geriatric patients. Because impairment seems to be relatively independent of age in SLE and because greater levels of function
may lead to better clinical and patient-centered outcomes, such as the ability to live independently, the value of functional assessment in
the setting of SLE should be further explored. Further research could help inform potential interventions to improve or prevent further
declines in functioning in this population.
Disclosure: L. Plantinga, None; B. Tift, None; C. B. Bowling, None; C. M. Dunlop-Thomas, None; S. S. Lim, None; C. Drenkard,
No commercial interest, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/multidomain-functional-assessment-in-a-cohort-of-

patients-with-systemic-lupus-erythematosus-a-pilot-study
Perceptions and Outcomes of Pregnancy and Lactation in Patients with Rheumatic

Diseases
Brooke Mills1, Kathryn H. Dao2, Kristen Tecson2, Emily Fishman3, Rachel Tate2 and John J. Cush2, 1Internal Medicine, Baylor
University Medical Center, Dallas, TX, 2Baylor Research Institute, Dallas, TX, 3Texas A&M HSC College of Medicine, Dallas, TX
SESSION INFORMATION
Background/Purpose: Once diagnosed with a rheumatic disease, women often defer or avoid pregnancy or lactation, fearing adverse
outcomes for their offspring or for themselves. Scant data exist regarding the attitudes of women with these diseases toward pregnancy
and lactation. Furthermore, there is an unclear relationship between breastfeeding and disease activity. Our study evaluates the
perceptions of women with rheumatic diseases on pregnancy and lactation while analyzing their outcomes during this period.
Methods: We conducted a single center cohort study of women of childbearing age regarding their attitudes, concerns, and outcomes of
pregnancy and lactation. Information was gathered from chart review, telephone interviews and surveys. Those who completed a
pregnancy and breastfed were queried further regarding their use of disease modifying anti-rheumatic drugs (DMARD) or biologics
while breastfeeding and if their infants had any adverse outcomes.
Results: 154 subjects were included. 51.6% of respondents indicated their diagnosis changed their views on pregnancy. Opinions
differed significantly across the diagnoses of JIA (28.6%), AKS (45.5%), RA (43.1%), and SLE (69.4%) (P=0.04). 65.6% of women
were concerned about medications affecting the baby. 33.6% indicated that their views on breastfeeding changed as a result of their
disease diagnosis. Views on breastfeeding did not differ significantly between diagnoses. 29.7% of respondents said their diagnosis
changed their minds about having children, a sentiment that differed significantly by diagnosis (AKS: 11.1%, JIA: 0.0%, Other: 30.0%,
PSA: 33.3%, RA: 20.4%, SLE: 53.1%; P=0.01). The rates of breastfeeding did not differ significantly for babies born before or after the
mothers’ diagnosis (before: 86.6%, after: 82.2%; P=0.50). Breastfeeding duration did not differ by diagnosis status (P=0.21). After
diagnosis, more women stopped breastfeeding early to start a medication they believed to be contraindicated (before diagnosis: 2, 3.5%;
after diagnosis: 12, 20%; P=0.005). Of the 46 who responded, breastfeeding positively, negatively, or did not affect the mother’s disease
state in 21.7%, 43.5%, and 34.8%, respectively. There were 35.3% (12/34) instances of having to change medical therapy due to disease
worsening while breastfeeding. 18 women breastfed 21 babies on a DMARD or biologic. None of these women reported a delay in their
children’s developmental milestones.
Conclusion: After disease diagnosis, nearly half of women negatively changed their views on pregnancy, and a third of women
negatively changed their views on lactation. Women were concerned that the use of a DMARD or biologic may affect their own health
or their baby’s health. There was no difference in the rates or duration of breastfeeding between women before and after diagnosis,
however after diagnosis, some respondents refrained from or curtailed breastfeeding due to concerns for medications or lack of
information. Disease activity during lactation is variable based on our data; further studies are needed to fully evaluate this issue. This
study highlights an unmet need in patients of childbearing potential for data and education regarding pregnancy and lactation.
Disclosure: B. Mills, None; K. H. Dao, None; K. Tecson, None; E. Fishman, None; R. Tate, None; J. J. Cush, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/perceptions-and-outcomes-of-pregnancy-and-

lactation-in-patients-with-rheumatic-diseases
Preliminary Real World Data on Switching Patterns between Etanercept, Its

Recently Marketed Biosimilar Counterpart and Its Competitor Adalimumab, Using
Swedish Prescription Registry
Rieke Alten1, Petra Neregard2, Heather Jones3, Ena Singh4, Cinzia Curiale5, Thomas Meng6, Lara Lucchese7, Cristiana Miglio7 and
Gudrun Jonasdottir Bergman8, 1Internal Medicine, Rheumatology & Clinical Immunology, Schlosspark-Klinik, University Medicine
Berlin, Berlin, Germany, 2Pfizer, Stochholm, Sweden, 3Inflammation & Immunology Global Medical Affairs, Pfizer, Collegeville, PA,
4Pfizer, Collegeville, PA, 5Pfizer, Rome, Italy, 6Pfizer, Berlin, Germany, 7QuintilesIMS, London, United Kingdom, 8QuintilesIMS,
Solna, Sweden
SESSION INFORMATION
Background/Purpose: The increasing availability of biologic treatments over the past 10 years has revolutionized the management of
rheumatic diseases. In April 2016, the first etanercept biosimilar (EtnBS) was launched in Sweden, representing a cheaper option to its
innovator counterpart and other anti-TNF agents. The objective of this study was to describe the position of etanercept innovator (EtnI)
within the Swedish biologic market for rheumatic diseases, before and after the launch of its biosimilar. The study also provides early
real-world data on the market penetration of EtnBS by evaluating switching dynamics to and from this drug since the date of launch.
Methods: The overall biologic market share across all type of rheumatic diseases was monthly tracked over the last year of available
data in the Swedish Prescription Registry (100% coverage). The proportion of patients receiving a rheumatologists’ prescription for any
biologic in each month, from November 2015 to March 2017, was recorded. In addition, switching dynamics of patients initiating
EtnBS treatment between April 2016 and March 2017 were studied. The proportion of patients receiving no biologic treatment (naïve)
and of those on treatment with EtnI, adalimumab and other biologic agents in the 12 months prior to initiate EtnBS was reported.
Further, the proportion of patients who switched from EtnBS back to EtnI or adalimumab and the median time to this second switch
were also evaluated.
Results: EtnI and adalimumab dominate the biologic market for rheumatic diseases in Sweden, holding the 40% and 28% of market
share, respectively, up to April 2016. However, in the 11 months after EtnBS was launched, the share of EtnI decreased constantly,
dropping to 22% in March 2017. Since April 2016, we identified in total 5,387 patients receiving first prescription of EtnBS by a
rheumatologist. Of these, 1,845 (34%) were naïve to treatment, 2,938 (55%) had prior treatment with EtnI, 235 (4%) with adalimumab,
369 (7%) with other biologics. Among the patients who changed to EtnBS from prior EtnI, 11% switched back to EtnI after a median
time of 55 days. Similarly, of those who were on previous adalimumab treatment, 5% switched back to adalimumab after, median time,
67 days.
Conclusion: Many patients changed from EtnI to its biosimilar treatment since its launch in Sweden. However, this study showed that
11% of these patients switch back to their original treatment after short time. Despite the change from a brand biologic to the biosimilar
is very likely made for economic reasons, the reasons for switching back to the innovator are not clear and may imply patients’
preference or clinical reasons. Interestingly, the same pattern is observed for patients changing from adalimumab to EtnBS. Longer-term
studies are required to confirm these early observations and investigate the reasons for switching back.
These results were presented at EULAR, Madrid 14-17 June 2017
Disclosure: R. Alten, None; P. Neregard, None; H. Jones, Pfizer Inc, 1,Pfizer Inc, 3; E. Singh, None; C. Curiale, None; T. Meng,
None; L. Lucchese, None; C. Miglio, None; G. J. Bergman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/preliminary-real-world-data-on-switching-patterns-

between-etanercept-its-recently-marketed-biosimilar-counterpart-and-its-competitor-adalimumab-using-swedish-prescription-registry

Determinants of Patient and Physician Disagreement on Presence of a Gout Flare
Aprajita Jagpal1, Nicola Dalbeth2, William J. Taylor3, Kenneth Saag1, Jasvinder A. Singh4, Amy S. Mudano5, Elizabeth J. Rahn6 and
Angelo L. Gaffo6, 1Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL,
2University of Auckland, Auckland, New Zealand, 3University of Otago, Wellington, New Zealand, 4Rheumatology, University of
Alabama at Birmingham, Birmingham, AL, 5University of Alabama at Birmingham, Birmingham, AL, 6Department of Medicine,
Division of Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL
SESSION INFORMATION
Background/Purpose:
Flare is a central feature of gout and patient self-report of flare was found to be an important element in a gout flare definition for
research. However, patients may disagree with the clinicians on presence of a flare. In this study, we investigated factors impacting the
concordance and discordance between investigators with expertise in gout and their patients, on presence of a gout flare.
Methods:
We used gout patient data collected at 21 international sites from a gout flare definition study published in 2012 and its ongoing
validation study. Information on demographics, gout flares, and anatomical location of swelling and warmth during a flare were
collected during routine clinic visits. We performed Chi-square and t-test comparisons of these variables in patients who agreed with the
investigator on the presence of a flare (concordant) versus those who disagreed with the investigator on the presence of a flare
(discordant). We also made comparisons within the discordant group (when investigator diagnosed a flare but patient disagreed versus
when patient self-reported a flare and the investigator disagreed).
Results:
Concordant and discordant flares were noted in 187 and 81 cases, respectively. There were no differences between groups in age, sex, or
disease duration. Compared to the discordant group, the concordant group had higher pain scores, increased patient global assessment
of disease severity, greater proportions of patients with lower extremity joint (knee, ankle, or foot joints) involvement, and lower
proportion of patients with tophi (Table). Fewer patients in the discordant group had either swollen or warm joint (patient reported)
compared to the patients with concordant flares (76.5% vs 97.9%, p <0.0001). Within the discordant group, 70.4% of flares were patient
determined and not endorsed by the investigators. All patients with an investigator-determined flare where patients disagreed had at
least one swollen joint (100%) compared to only 57.9% in flares that were patient-determined but the investigator disagreed with
(p<0.0001).
Conclusion:
We identified factors associated with agreement and disagreement among patients and investigators on the presence of a gout flare.
Lower extremity involvement, higher patient global assessment of disease, less tophaceous disease, higher pain scores, and presence of
at least one swollen or warm joint is associated with concordance. Having a swollen joint was a determinant in all the investigator-
defined flares when patients disagreed, however it was much less important in patient-determined gout flares.
Table: comparison between patients in discordant flare group to concordant group

Variable Discordant Concordant P value
flare flare
N=81 N=187
Age in years; Mean (SD) 54.7 (13.8) 53.8 (14.0) 0.65
Male sex; n (%) 75 (93.8) 165 (88.7) 0.20
Disease duration in years; Mean (SD) 11.8 (8.1) 11.8 (10.3) 0.98
Presence of tophi; n (%) 50 (61.7) 87 (46.8) 0.0246
Lower extremity involvement in a 48 (59.3) 157 (84.0) <0.0001
flare; n (%)
PGA (0-10); Mean (SD) 4.3 (3.3) 6.6 (2.5) <0.0001
Pain at rest (0-10); Mean (SD) 4.1 (3.3) 6.9 (2.5) <0.0001
Patient- reported 62 (76.5) 183 (97.9) <0.0001
Any swollen or warm joint (%)

Any Swollen (%) 57 (70.4) 178 (95.2) <0.0001
Any warm (%) 38 (46.9) 153 (81.8) <0.0001
SD= standard deviation, PGA = patient global assessment of disease severity
Disclosure: A. Jagpal, None; N. Dalbeth, AstraZeneca, 2,Takeda, Pfizer, AstraZeneca, Cymabay, Crealta, 5,Takeda, AstraZeneca, 9;
W. J. Taylor, AstraZeneca, Pfizer, Abbvie, Roche, 5; K. Saag, AstraZeneca, Horizon, Ironwood, SOBI, Takeda, 5; J. A. Singh,
Takeda, Savient, 2,Savient, Takeda, Regenron, Merz, Bioiberica, Crealta, Allergan, WebMD, UBM LLC, American College of
Rheumatology, 5; A. S. Mudano, None; E. J. Rahn, None; A. L. Gaffo, SOBI, 5,Amgen, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/determinants-of-patient-and-physician-

disagreement-on-presence-of-a-gout-flare
Patients and Physicians Have Different Perceptions of the Relative Bother of the
Symptoms and Impacts on Daily Activities in Psoriasis and Psoriatic Arthritis
M. Elaine Husni1,2, Anthony Fernandez1, Rakesh Singh3, Brett Hauber4, Jessie Sutphin4, Joshua Posner4 and Arijit Ganguli3,
1Cleveland Clinic, Cleveland, OH, 2Rheumatology Dept A50, Cleveland Clinic Foundation, Cleveland, OH, 3AbbVie Inc., North
Chicago, IL, 4RTI Health Solutions, Research Triangle Park, NC

SESSION INFORMATION
Background/Purpose: Psoriasis and psoriatic arthritis arise from the same immune system response but result in different symptoms
and impacts on daily activities. A patient with both conditions may be treated by a dermatologist, rheumatologist, or both. Our objective
was to assess patient, dermatologist, and rheumatologist perceptions of the bother of individual psoriatic outcomes in 3 separate areas:
skin and joint symptoms and impacts on daily activities.
Methods: We developed a set of 7 skin symptoms, 7 joint symptoms, and 6 impacts on daily activities of psoriatic disease from existing
validated measures. To measure perceived relative bother, we created an online best-worst scaling survey in which patients,
dermatologists, and rheumatologists in the US, recruited through internet panels, indicated which of 5 items from the full set of 20 was
most and least bothersome in each of 16 questions determined by an experimental design. We used these data to rank perceived relative
bother in skin symptoms, joint symptoms, and daily activities for each respondent group.
Results: We surveyed 200 patients with self-reported physician diagnosis of both psoriasis and psoriatic arthritis with mean (SD) age of
42 (14) years. On a scale from 0 (none) to 10 (severe), patients had mean self-reported skin symptoms of 6.8 (2.5) and joint symptoms
of 6.4 (2.6). Patients, dermatologists (n=150), and rheumatologists (n=150) differed on the most bothersome skin symptom (Table 1).
All respondent groups ranked joint pain, soreness, or tenderness as the most bothersome joint symptom and discomfort while doing
everyday tasks as the most bothersome impact on daily activities. Among skin symptoms, embarrassment was ranked highest (most
bothersome) by dermatologists, while painful skin was ranked higher than embarrassment by patients and rheumatologists. Among joint
symptoms, patients and physicians ranked the relative burden of eye problems differently. Among daily activities, patients and
physicians ranked the relative bother of difficulty sleeping differently.
Conclusion: The perception of the bother of psoriatic disease outcomes differs among patients, dermatologists, and rheumatologists.
Greater communication among these groups is warranted and may help patients and physicians better address patient needs.
Disclosure: M. E. Husni, AbbVie, Genentech, Bristol-Myers Squibb, Pfizer, Novartis, and Janssen, 9; A. Fernandez, Mallinkrodt,
Roche, AbbVie, 2,AbbVie, 5,Celgene, AbbVie, 8; R. Singh, AbbVie, 3,AbbVie, 1; B. Hauber, RTI, which has received consulting fee
from AbbVie to partner on this research, 3; J. Sutphin, RTI, which has received consulting fee from AbbVie to partner on this research,
3; J. Posner, RTI, which has received consulting fee from AbbVie to partner on this research, 3; A. Ganguli, AbbVie, 3,AbbVie, 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/patients-and-physicians-have-different-perceptions-

of-the-relative-bother-of-the-symptoms-and-impacts-on-daily-activities-in-psoriasis-and-psoriatic-arthritis
Nurse Telephone Education for Promoting a Treat-to-Target Approach in Recently

Diagnosed Rheumatoid Arthritis Patients – a Preliminary Review
Bonita Libman1, Siobhan Farley1, Melinda Edwards1, Carl Possidente2 and Amanda Kennedy3, 1Medicine/Rheumatology, University
of Vermont Medical Center, Burlington, VT, 2Medical Affairs, Pfizer, Inc., Jericho Center, VT, 3Internal Medicine, University of
Vermont, Burlington, VT
SESSION INFORMATION
Background/Purpose: A successful Treat-to-Target approach to managing Rheumatoid Arthritis (RA) requires shared decision making
with patients and healthcare providers. However patients may not have the education they need around the time of a new diagnosis to
effectively partner with their providers in their RA care. Educational efforts must focus on interventions that are feasible, sustainable,
and available to all RA patients as part of their rheumatology care. The purpose of this project was to implement a pragmatic nurse
telephone education program for patients with recently diagnosed RA that promotes shared decision making and a treat-to-target
approach.
Methods: This was a pilot project of newly diagnosed adult RA patients between November 2015 and December 2016. Rheumatology
clinic nurses telephoned patients to offer disease education, targeting no more than 20 minutes per call. A shared decision making
toolkit was mailed to the patient. Demographic data included patient age, sex, and zip code. RA-specific data included date of RA
diagnosis, prescribed RA medications, routine assessment of patient index data 3 (RAPID3) scores if recorded, and date of next visit
with the rheumatologist. Process measures included median call attempts, median call time, and a qualitative description of the free text
notes. Outcome measures included the results from the satisfaction survey and proportion of patients who adhered to their next
rheumatology visit. Data were analyzed descriptively and qualitatively.
Results: Twenty-six patients participated in the nurse calls. Most patients were female (65%), with a median age of 54 years (range 22-
78). Median call length was 14.5 minutes with a range of 8-23 minutes. Qualitative notes indicate patients overwhelmingly support the
nurse calls. Five patients returned the survey. All five patients indicated they would like calls from a nurse more than once per year.
Twenty-three patients had follow-up visits at the time of this report. Sixteen patients (69.5%) were adherent to their follow-up visit.
Conclusion: This preliminary review successfully implemented an educational program that included a nurse-facilitated, RA-specific,
telephone call and toolkit. The strength of our approach was designing our educational program with the goal of long-term sustainability
and generalizability. This educational program could be a model for similar educational efforts by other rheumatology clinics.
Disclosure: B. Libman, Novartis Pharmaceutical Corporation, 2,Pfizer, Inc, 9; S. Farley, None; M. Edwards, None; C. Possidente,
Pfizer, Inc., 1,full time employee Pfizer, Inc., 3; A. Kennedy, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/nurse-telephone-education-for-promoting-a-treat-to-

target-approach-in-recently-diagnosed-rheumatoid-arthritis-patients-a-preliminary-review
Evaluation of the Educational Needs in Argentinian Patients with Rheumatoid

Arthritis Using the SpENAT Questionnaire
Silvana Karina Pérez1, Maria Julia Santa Cruz1, María Alejandra Medina1, Diana Klajn2, Silvia Beatriz Papasidero1, Jose Angel
Caracciolo1, Gisela Pendón3, Federico Giordano4, Dora Pereira5, Damaris Alvarez6, Valeria Astudillo6, Eduardo Kerzberg6, Adriana
Perez Davila7, Analia Bohr7, Fernando Melo8, Nicolas Lloves8, Marta Mamani9, Claudia Hartvig10, Gabriela Sanchez10, Monica
Sacnun10, Yamila Chichotky11, José Velasco Zamora11, Mariana Benegas12, Javier Rosa13, Maria Victoria Garcia14, Laura Raiti15,
Vanesa Cruzat15, Rosana Quintana16, Bernado Pons-Estel17, Karin Kirmayr18, Andrea D'Orazio19, Cinthya Retamozo20, Olga
Romano21, Rodolfo Perez-Alamino21, María de los Angeles Correa22, Gustavo Citera23, Oscar Rillo24, María Marta Zalazar24, Ana
Carolina Costi25, Mercedes Argentina García25, Graciela Gómez26 and Hernán Maldonado Ficco27, 1Rheumatology Department,
Hospital General de Agudos Dr. Enrique Tornú, Buenos Aires, Argentina, 2Research Committee, Hospital General de Agudos Dr.
Enrique Tornú, Buenos Aires, Argentina, 3Hospital Ricardo Gutierrez, La Plata, Argentina, 4Rheumatology Department, Hospital
Ricardo Gutierrez, La Plata, Buenos Aires, Argentina, 5Rheumatology Department, Hospital Ricardo Gutierrez, Buenos Aires,
Argentina, 6Rheumatology Department, Hospital Ramos Mejía, Buenos Aires, Argentina, 7Rheumatology Department, Hospital de
Rehabilitación Manuel Rocca, Buenos Aires, Argentina, 8Rheumatology Department, Hospital Rivadavia, Buenos Aires, Argentina,
9Rheumatology Department, Hospital Bernardino Rivadavia, Buenos Aires, Argentina, 10Rheumatology Department, Hospital
Provincial de Rosario, Santa Fe, Argentina, 11Rheumatology Department, Reumatologia al sur, Buenos Aires, Argentina,
12Rheumatology Department, Sanatorio de la Providencia, Buenos Aires, Argentina, 13Rheumatology Unit, Internal Medicine Service,
Hospital Italiano de Buenos Aires, CABA, Argentina, 14Rheumatology Department, Hospital Italiano de Buenos Aires, Buenos Aires,
Argentina, 15Rheumatology Department, Clinica Bessone, Buenos Aires, Argentina, 16Rheumatology Department, Sanatorio Parque,
Rosario, Santa Fe, Argentina, 17GLADEL, Rosario, Santa Fe, Argentina, 18Rheumatology Department, Sanatorio San Carlos,
Bariloche, Argentina, 19Rheumatology Department, Hospital Interzonal Dr. José Penna, Bahia Blanca, Buenos Aires, Argentina,
20Rheumatology Department, Centro Especializado Diabetes y Reumatologia, Salta, Argentina, 21Rheumatology Department, Hospital
de Clínicas Pte. Dr. Nicolás Avellaneda, Tucumán, Argentina, 22Section Rheumatology, Instituto de Rehabilitación Psicofísica, Buenos
Aires, Buenos Aires, Argentina, 23Rheumatology Department, Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina,
24Rheumatology Department, Hospital General de Agudos Dr. Ignacio Pirovano, Buenos Aires, Argentina, 25Rheumatology
Department, Hospital Interzonal General de Agudos Gral. José de San Martín, La Plata, Buenos Aires, Argentina, 26Rheumatology
Department, Instituto de Investigaciones Medicas Alfredo Lanari, Buenos Aires, Argentina, 27section of Rheumatology, Clinica
Regional del Sud, Córdoba, Argentina, Córdoba, Argentina
SESSION INFORMATION
Background/Purpose: The SpENAT, a Spanish version of the Educational Needs Assessment Tool, is a self-completed questionnaire
that assesses educational needs (ENs) with the purpose of providing tailored and patient-centered information. It consists of 39
questions grouped into the 7 following domains: Pain management, Movement, Feelings, Arthritis process, Treatments, Self-help
measures and Support system. The objective of the study was to describe the educational needs of RA patients using the SpENAT and
to determine the main sources of information that these patients consult.
Methods: Multicenter, observational, cross-sectional study. We included consecutive patients ≥ 18 years with diagnosis of RA (ACR-
EULAR 2010). Socio-demographic data, disease characteristics and clinimetric measurements were recorded. All patients completed
the SpENAT and were asked about the sources employed to obtain information about their disease. Statistical analysis: Population
characteristics were described. ENs were determined as percentages of the highest possible score for each domain. Needs for each
domain according to sex, years of education, duration of disease, use of biologicals and functional capacity were analyzed by means of
Anova test, and bivariate comparisons were made with Student's T test and Bonferroni correction. Correlation between domains was
determined with Spearman's test. ENs were described by geographic region. We compared patients’ age by source of information with
Student's t-test.
Results: We included 496 patients from 20 centers across the country. More ENs were observed in Movement, Feelings and Arthritis
process domains (Table). Patients with higher educational level (> 7 years) reported more ENs in Arthritis process and Self-help
measures domains. A higher functional impairment (HAQ-A ≥0.87) was associated with more ENs in every domains. Patients with high
activity showed more ENs than those in remission in Managing Pain, Movement, Feelings, Treatments and Support system domains;
and also than those with low activity in Self-help measures and Support system domains. Patients with moderate activity showed more
ENs in Managing pain domain compared to patients in remission. All SpENAT domains showed positive correlations with each other (p
<0.0001), being the most important Managing pain/ Movement and Treatments/ Arthritis process (r≥0.7). The most consulted source of
information was the rheumatologist (93.95%); those who made use of internet were on average younger (p = 0.0004).
Conclusion: RA Patients were very interested in knowing more about their disease. ENs were higher in Movement, Arthritis process
and Feelings domains. High functional impairment was associated with more ENs. Patients with high disease activity had higher EN
levels in almost every domain. The rheumatologist was the main source of information of the patient with RA.
EN in RA patients according to the domain (N=496)

Pain Movement Feelings Arthritis Treatments Self- Support
management process help system
Median 79.17 90 81.25 89.29 78.57 75 75
(IQR) (70.83-91.67) (75-95) (75-100) (75-100) (71.43-100) (70.83- (62.5-

93.75) 93.75)
Disclosure: S. K. Pérez, None; M. J. Santa Cruz, None; M. A. Medina, None; D. Klajn, None; S. B. Papasidero, None; J. A.
Caracciolo, None; G. Pendón, None; F. Giordano, None; D. Pereira, None; D. Alvarez, None; V. Astudillo, None; E. Kerzberg,
None; A. Perez Davila, None; A. Bohr, None; F. Melo, None; N. Lloves, None; M. Mamani, None; C. Hartvig, None; G. Sanchez,
None; M. Sacnun, None; Y. Chichotky, None; J. Velasco Zamora, None; M. Benegas, None; J. Rosa, None; M. V. Garcia, None; L.
Raiti, None; V. Cruzat, None; R. Quintana, None; B. Pons-Estel, None; K. Kirmayr, None; A. D'Orazio, None; C. Retamozo,
None; O. Romano, None; R. Perez-Alamino, None; M. D. L. A. Correa, None; G. Citera, Novartis, Pfizer Inc, 2,AbbVie, Bristol-
Myers Squibb, Janssen, Novartis, Pfizer Inc, 5; O. Rillo, None; M. M. Zalazar, None; A. C. Costi, None; M. A. García, None; G.
Gómez, None; H. Maldonado Ficco, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/evaluation-of-the-educational-needs-in-argentinian-

patients-with-rheumatoid-arthritis-using-the-spenat-questionnaire
Multi-National Observational Patient Diary Study to Assess Disease Burden of

Periodic Fever Syndromes (PFS), Including Colchicine-Resistant Familial
Mediterranean Fever (crFMF), TNF-Receptor Associated Periodic Syndrome
(TRAPS) and Mevalonate Kinase Deficiency (MKD)
Jasmin B. Kuemmerle-Deschner1, Pierre Quartier2, Shai Padeh3, Isabelle Koné-Paut4, Veronique Hentgen5, Katherine A. Marzan6,
Fatma Dedeoglu7, Helen J. Lachmann8, Tilmann Kallinich9, Norbert Blank10, Seza Ozen11, Yelda Bilginer12, Jonathan S.
Hausmann7,13, Arturo Diaz13, Ravi Degun14, Nina Marinsek14, Jill Gregson15, Kathleen G. Lomax16 and Avi Livneh17, 1Pediatrics,
University Hospital Tübingen, Tübingen, Germany, 2Necker-Enfants Malades Hospital, Paris, France, 3Sheba Medical Center, Tel-
Hashomer, Israel, 4Bicêtre Hospital, APHP, Univeristy Paris Sud, Paris, France, 5Versailles Hospital, CEREMAI, Le Chesnay, France,
6Division of Rheumatology, Children's Hospital Los Angeles, Los Angeles, CA, 7Boston Children's Hospital, Boston, MA, 8UCL
Division of Medicine, UK National Amyloidosis Centre, London, United Kingdom, 9Charité, Humbolt University Medicine Berlin,
Berlin, Germany, 10UniversitätsKlinikum Heidelberg, Heidelberg, Germany, 11Department of Pediatrics, Hacettepe University, Ankara,
Turkey, 12Department of Pediatrics, Division of Rheumatology, Hacettepe University Faculty of Medicine, ANKARA, Turkey, 13Beth
Israel Deaconess Medical Center, Boston, MA, 14Life Sciences, Navigant Consulting, London, United Kingdom, 15Novartis Pharma
AG, Basel, Switzerland, 16Novartis Pharmaceuticals Corporation, East Hanover, NJ, 17Sheba Medical Center, Ramat-Gan, Israel
SESSION INFORMATION
Background/Purpose:
Periodic fever syndromes (PFS) are a group of autoinflammatory disorders characterized by recurrent bouts of fever and severe
localized inflammation which, if not treated, can result in severe complications such as amyloidosis. Flares can last for several days to
weeks and are typically associated with high symptom burden. Due to the rarity of these conditions detailed analysis of the patient
experience with PFS is lacking. HEROES (Hereditary Periodic Fevers Burden of Illness Observational Patient Diary Study) is the first
international study to document the nature and extent of the humanistic and economic burden experienced by patients (pts) and their
families during and between flares.
Methods:
Eligible pts had diagnosis of TRAPS (TNF-receptor associated periodic syndrome), MKD/HIDS (mevalonate kinase
deficiency/hyperimmunoglubulinemia D syndrome) or crFMF (colchicine-resistant FMF), were expected to flare at least once every 6
months despite current treatment and be of sufficient severity to be eligible for (or currently receiving) biologic therapy. Investigators
provided background information including treatment history and response to colchicine for crFMF pts. Disease burden was captured
through participant completion of an electronic diary. Diaries were completed by adult pts (≥18 years old) or caregivers for younger pts;
adolescent pts (13-17 years old)provided input into the daily questionnaire. Baseline questionnaire collected background information
including demographics, disease history, treatment satisfaction and long-term impact of PFS. Daily and weekly on and off flare forms
focused on patient function, emotional/social wellbeing and pain. Quality of life measures by SF-12v2, SF-10v2 and Sheehan Disability
Scale version 3 (SDSv3) were quantified. Disease activity was assessed using patient/parent’s global assessment of disease activity
(PPGA).
Results: The study enrolled 67 pts across 10 sites in France, Germany, Israel, the UK and the US, including 49 crFMF, 11 MKD/HIDS,
and 7 TRAPS pts. Of these, 24 were children (2-12 years old), 11 were adolescents, and 32 were adults. All pts received drug therapy
for their PFS. At least one flare was recorded in 58 (87%) pts. Fourteen (40%) children/adolescents reported that PFS impacted their
education. Twenty-five (78%) adult pts reported that condition impacted their work achievements. Of the 35 caregivers participating in
the study, 71% reported that their child’s PFS impacted their employment. All caregivers not working full-time reported that their
child’s PFS was at least one, if not the main reason for reduced working hours. A large proportion (64% and 43%) of pts had at least
one hospital or ER visit related to their PFS in the last year, respectively. The vast majority (86% and 88%) of pts and caregivers,
respectively, report that PFS interfered with their social activities.
Conclusion:
Severe PFS have a very broad impact on the lives of pts and their families, including work productivity and educational attainment.
Therapeutic interventions that reduce the flare burden and long term complications of severe PFS, as well as psychosocial support for
pts and caregivers, are needed.
Disclosure: J. B. Kuemmerle-Deschner, Novartis Pharmaceutical Corporation, 2,Novartis Pharmaceutical Corporation, 5; P.

Quartier, Novartis Pharmaceutical Corporation, 2,Novartis Pharmaceutical Corporation, 6; S. Padeh, None; I. Koné-Paut, Chugai,
2,Navigant, Novartis, SOBI, PFIZER, Abbvie, Novimmune, LFB, Roche, 5; V. Hentgen, Novartis Pharmaceutical Corporation,
2,Novartis Pharmaceutical Corporation, 5; K. A. Marzan, Novartis Pharmaceutical Corporation, Abbvie, 2; F. Dedeoglu, Novartis
Pharmaceutical Corporation, 5; H. J. Lachmann, Novartis, GSK, SOBI, 5; T. Kallinich, None; N. Blank, None; S. Ozen, Novartis
Pharmaceutical Corporation, R-Pharm, 5,Roche Pharmaceuticals, 8; Y. Bilginer, None; J. S. Hausmann, None; A. Diaz, None; R.
Degun, Novartis Pharmaceutical Corporation, 5; N. Marinsek, Novartis Pharmaceutical Corporation, 5; J. Gregson, Novartis
Pharmaceutical Corporation, 3; K. G. Lomax, Novartis Pharmaceutical Corporation, 3,Novartis Pharmaceutical Corporation, 1; A.
Livneh, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/multi-national-observational-patient-diary-study-to-

assess-disease-burden-of-periodic-fever-syndromes-pfs-including-colchicine-resistant-familial-mediterranean-fever-crfmf-tnf-receptor-
associate
Patients’ Experiences and Attitudes about Non-Medical Switching of Biologics:

Results from an Online Patient Survey
Amanda Teeple1, Lorie A. Ellis2, Laura Huff3, Chuck Reynolds3, Seth D. Ginsberg4, Leah McCormick Howard5, Danielle Walls6 and
Jeffrey R. Curtis7, 1Janssen Scientific Affairs, LLC, Horsham, PA, 2Health Economics & Outcomes Research, Janssen Scientific
Affairs, LLC, Horsham, PA, 3Benfield | Arthur J. Gallagher & Co., Webster Groves, MO, 4Global Healthy Living Foundation,
CreakyJoints, Upper Nyack, NY, 5National Psoriasis Foundation, Portland, OR, 6BDJ Solutions, Melrose, MA, 7Division of Clinical
Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL
SESSION INFORMATION
Background/Purpose: Health insurance plan designs often have benefits that result in highly prescriptive patient (pt) treatment options
that can result in switching of patient’s medications for non-medical (economic) reasons.
Methods: An online pt survey was conducted in pts recruited from advocacy organizations (Global Healthy Living Foundation,
National Psoriasis Foundation) and a research panel (Research Now). Pts were eligible if they were ≥18 years of age, resided in United
States; had a diagnosis for one of the following: rheumatoid arthritis, Crohn’s disease, ulcerative colitis, psoriasis or psoriatic arthritis;
were currently taking a biologic; and consented to participate. Pts who met these criteria answered follow up questions about their
experiences related to a possible non-medical switch (NMS) of their biologic medication. Descriptive statistics (n%, mean, SD) were
used to summarize responses.
Results: A total of 1,696 pts completed the 20-minute survey; 993 were from advocacy groups and 703 from a research panel. Of the
1,696 patients that were asked about their perceptions to a possible biologic NMS, 90% expressed that they wouldn’t want to switch
biologics if their current medication was helping my disease. 71% indicated they would not risk switching to another biologic. Only
29% would switch if the new biologic was cheaper. 86% of patients expressed concern that switching may cause more side effects, and
81% worried that switching would increase their stress. 74% were concerned that switching would cause them to lose their copay
support. 20% (n=337) of patients had received notification their biologic insurance coverage was changing and they should consider
switching biologics to avoid paying a higher cost. Of these, 79% took at least one action to avoid a NMS, most often asking their
doctors’ offices to appeal the switch; 56% did not make the switch. Of pts that agreed to a NMS (n= 150), 67% did so to avoid paying a
higher cost for their current biologic medication; most often pts switched to a biologic with the same mode of administration.
Additionally, of patients that reported a NMS, 67% indicated that the biologic they were previously taking worked well for them, and
70% didn’t want to switch to another biologic. More than half (56%) went without therapy for administrative reasons during the period
of transition from the old biologic to the NMS treatment.
Conclusion: Pts reported multiple concerns about NMS that would impact treatment outcomes, and many of the pts who non-medically
switched in this survey missed treatments. Future studies should be conducted on real world pt experience with NMS to understand the
impact on treatment persistency and pt outcomes.
Disclosure: A. Teeple, Janssen, 3,Johnson & Johnson, LLC, 1; L. A. Ellis, Janssen, 3,Johnson & Johnson, LLC, 1; L. Huff, Janssen
Scientific Affairs, LLC, 5; C. Reynolds, Janssen Scientific Affairs, LLC, 5; S. D. Ginsberg, None; L. McCormick Howard, Janssen
Scientific Affairs, LLC, 5; D. Walls, Janssen Scientific Affairs, LLC, 5; J. R. Curtis, Janssen Scientific Affairs, LLC, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/patients-experiences-and-attitudes-about-non-

medical-switching-of-biologics-results-from-an-online-patient-survey
Work Productivity Benefit in Patients with Rheumatoid Arthritis Initiating

Etanercept in the United States
Mahdi Gharaibeh1, Bradley S. Stolshek2, Alex Mutebi3, Amy M. Sainski-Nguyen4, David Collier5 and Emily Durden4, 1Amgen Inc.,
Thousand Oaks, CA, 2Amgen, Inc., Thousand Oaks, CA, 3Amgen, Thousand Oaks, CA, 4Truven Health Analytics, Ann Arbor, MI,
5Amgen, Inc, Terni, Italy
SESSION INFORMATION
Background/Purpose:
Rheumatoid arthritis (RA) is a chronic inflammatory disease that can progress to joint destruction, functional impairment and disability
that can lead to work productivity losses. Biologics are generally prescribed when conventional disease modifying agents are no longer
effective or following disease progression. Treatment with etanercept (ETN), either as monotherapy or in combination with
methotrexate (MTX), has been shown to improve functioning and work productivity in clinical and observational studies. The aim of
this study was to assess the productivity benefit of treating RA patients with ETN compared to MTX.
Methods:
In this retrospective administrative claims analysis using the MarketScan Health and Productivity Management and the Commercial
Claims and Encounters databases, adults diagnosed with RA who were treated with ETN, ETN+MTX, or MTX between January 1,
2007 and December 31, 2013 were identified. The index date was the date of the earliest qualifying ETN or MTX pharmacy or medical
claim. Patients were continuously enrolled with medical and pharmacy benefits 12 months prior to and 12 months following the index
date. Patients who switched to or added another biologic during the post-index period were excluded. Patients diagnosed with other
autoimmune diseases or had evidence of pregnancy or childbirth at any time during the study period were excluded. The proportions of
patients with any workplace absence (ABS) or short-term disability (STD) in the 12 months prior to and following the index date were
evaluated. Multivariable logistic regression was used to compare the odds of work loss during follow-up for the ETN and ETN+MTX
groups relative to the MTX group, adjusting for demographic and baseline clinical characteristics including but not limited to age,
gender, additional RA-related medications, and baseline RA-related costs.
Results:
For the work loss due to ABS analysis, 34 patients on ETN monotherapy, 49 patients on ETN+MTX, and 308 patients on MTX
monotherapy were identified. For the STD analysis, 207 patients on ETN, 274 patients on ETN+MTX, and 1,620 patients on MTX
were identified. The proportions of patients with at least one event of ABS during the pre-index period for the ETN, ETN+MTX, and
MTX cohorts were 82.4%, 73.5%, and 85.4%, respectively. In the post-index period, the proportions of patients with at least one event
of ABS for the ETN, ETN+MTX and MTX cohorts were 85.3%, 75.5%, and 87.0%, respectively.
The proportion of patients with at least one event of STD during the pre-index period for the ETN, ETN+MTX and MTX cohorts were
8.7%, 13.9%, and 11.5%, respectively. In the post-index period, the proportion of patients with at least one event of STD for the ETN,
ETN+MTX and MTX cohorts were 7.7%, 8.4%, and 11.7%, respectively. After adjusting for potential confounders, the odds (95%CI)
of losing a day due to ABS in the ETN and ETN+MTX groups relative to the MTX group were 0.61(0.19-1.98) and 0.33(0.13-0.85),
respectively. The odds (95%CI) of having STD in the ETN and ETN+MTX groups relative to the MTX group were 0.61(0.35-1.07) and
0.50(0.30-0.84), respectively.
Conclusion:
Adding ETN to MTX reduces the probability of ABS from work by 67% and the probability of STD by 50% compared to those on
MTX alone.
Disclosure: M. Gharaibeh, Amgen, 1,Amgen, 3; B. S. Stolshek, Amgen, 1,Amgen, 3; A. Mutebi, Amgen, 1; A. M. Sainski-Nguyen,
Amgen, 5; D. Collier, Amgen, 1,Amgen, 3; E. Durden, Amgen, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/work-productivity-benefit-in-patients-with-

rheumatoid-arthritis-initiating-etanercept-in-the-united-states
Canakinumab First or Second Choice in Systemic Juvenile Idiopathic Arthritis –

Experience from Clinical Practice
Gerd Horneff1, Ivan Foeldvari2, Klaus Tenbrock3, K Minden4 and Jasmin B. Kuemmerle-Deschner5, 1Asklepios Clinic, Sankt
Augustin, Germany, 2Kinder- und Jugenrheumatologie, Hamburger Zentrum Kinder-und Jugendrheumatologie, Hamburg, Germany,
3University Aachen, Aachen, Germany, 4Charité – University of Medicine Berlin, Berlin, Germany, 5Pediatrics, University Hospital
Tübingen, Tübingen, Germany
SESSION INFORMATION
Session Title: Pediatric Rheumatology – Clinical and Therapeutic Aspects Poster I: Autoinflammatory Disorders and Miscellaneous
Background/Purpose: Canakinumab (CAN) has demonstrated its efficacy and safety in systemic juvenile idiopathic arthritis in clinical
trials. We report on the experience with CAN in the clinical practice.
Methods: Surveillance of patients exposed to biologics is performed by the BIKER registry. Data on patients’ and disease
characteristics, disease activity and safety reports until Dec. 2016 were analysed.
Results: Until June 2017, 39 JIA patients were registered in the German BIKER registry in whom CAN was started, representing 59.2
PY of exposure. In 14 patients CAN was used as first biologic agent. 25 patients were pretreated with other biologics, 14 received 1, 7
two, 3 three and 1 four biologics. 15 had been treated with Tocilizumab, 11 with Anakinra, 9 with Etanercept and 9 with Adalimumab.
Of interest, 3 patients in the pre-exposed cohort had experienced a macrophage activation syndrome. Patient’s and disease
characteristics comparison of biologics naïve and preexposed patients are given below.
Patients pretreated were older, had a longer disease duration and more comorbidities (Macrophage activation syndrome, pericarditis,
pleuritic organomegaly and Cushing’s) than naïve patients. The proportion of patients with active arthritis, active systemic features and
both were comparable.
Disease activity at baseline (number of active joints, Patient’s and physicians’ global, ESR, CRP and the JADAS) was higher in the
biologic naïve cohort suggesting some clinical benefit from pretreatment in the exposed cohort. Dosing of CAN was comparable
(3.9+/-0.4 vs. 3.5+/-0.7 mg/kg) as well as the median treatment duration.
Treatment efficacy at 6 month of treatment was stronger in the naïve cohort with more patients reaching a PedACR50/90 response, CRP
normalisation, normal CHAQ, physician global indicating no activity (p=0.05) JADAS remission (p=0.02). Treatment with CAN was
discontinued by 42% in the naïve cohort and 48% in the exposed cohort. Reasons for withdrawals were inefficacy (n=7; 19%),
intolerance (n=2; 5%) and remission (n=7; 19%) of the disease and other (n=2;5%).
Conclusion: First experience with CAN for treatment of systemic JIA in clinical practice is presented. A high proportion of patients
gained significant response to treatment. JADAS remission was reached in significantly more biologics naïve patients while few
patients discontinued treatment in remission so far. Intolerance was rare. The further long term surveillance of patients exposed to
biologics is intended by the registry.
Table 1: Baseline characteristics in the comparison groups
Biologics naive Biologics pre-exposed

N ( female gender) 14 (28%) 25 (52%)
Age at JIA onset (years); Median
3.3 (2.7-5.2) 3.7 (2.6-7.1)
(IQR)
Disease duration (years); Median
0.7 (0.2-5.6) 1.9 (0.6-8.7)
(IQR)
Concomitant treatment at baseline:
7 (50%) 10 (40%)
NSAIDS
Steroids 6 43%) 11 (44%)
MTX 3 (21%) 6 (24%)
Patients with active joints 8 (57%) 10 (40%)
Patients with active systemic features 9 (64%) 10 (40%)
Active joint count; Median (IQR) 2.5 (0-3) 0 (0-3)
Physician global VAS (0-10); Median
5.2+/-2.8; 6.2 (3.2-7.2) 3.8+/-3m.4 ; 3.7 (0.7-6.3)
(IQR)
Patient Global VAS (0-10); Median
4.8+/-2.9; 4.6 (2.7-7) 3.3+/-2.9; 2.6 (0.6-5.1)
(IQR)
0.65+/-0.84; 0.25 (0-
CHAQ-DI (0-3); Median (IQR) 0.5 (0.38-1.24)
1.22)
ESR (mm/h); Median (IQR) 28 (10-55) 9 (4-18.5)
CRP (mg/l); Median (IQR) 43 (25-109) 3 (1-11)
JADAS10; Median (IQR) 15.2 (14-20.9) 9.5(5.5-11.8)
Disclosure: G. Horneff, Pfizer Inc, 2; I. Foeldvari, None; K. Tenbrock, None; K. Minden, Pfizer, Abbvie, Roche, 2,Abbvie, Pfizer,
Pharm-Allergan, Roche, 5; J. B. Kuemmerle-Deschner, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/canakinumab-first-or-second-choice-in-systemic-

juvenile-idiopathic-arthritis-experience-from-clinical-practice

Canakinumab Treatment in Patients with Still’s Disease: A Pooled Analysis of
Systemic Juvenile Idiopathic Arthritis Data By Age Groups
Eugen Feist1, Pierre Quartier2, Bruno Fautrel3, Rayfel Schneider4, Paolo Sfriso5, Petros Efthimiou6, Luca Cantarini7, Karine
Lheritier8, Karolynn Leon9 and Antonio Speziale8, 1Department of Rheumatology and Clinical Immunology, Charité-
Universitätsmedizin, Berlin, Germany, 2Necker-Enfants Malades Hospital, Paris, France, 3UPMC University Paris 06, Pitié-Salpétrière
Hospital, Paris, France, 4University of Toronto and The Hospital for Sick Children, Toronto, ON, Canada, 5University of Padova,
Padova, Italy, 6Medicine/Rheumatology, New York University School of Medicine/NYU Langone Health, New York, NY, 7University
of Siena, Siena, Italy, 8Novartis Pharma AG, Basel, Switzerland, 9Novartis Pharmaceuticals Corporation, East Hanover, NJ
SESSION INFORMATION
Background/Purpose: Still’s disease presents in pediatric and adult patients as a disease continuum with similar symptoms and
pathophysiology.1,2 The objective of this analysis was to evaluate the efficacy and safety of canakinumab, a selective human anti-IL1 β
monoclonal antibody, in systemic juvenile idiopathic arthritis (SJIA) patients from pooled data across three age groups: children,
adolescents and adults (the latter representing adult-onset Still’s disease [AOSD] population).
Methods: Data of canakinumab treated patients were pooled from 4 SJIA studies (NCT00426218, NCT00886769, NCT00889863,
NCT00891046). Canakinumab was administered at 4 mg/kg every 4 weeks in majority of the patients. Efficacy parameters (adapted
American College of Rheumatology [aACR] pediatric responses, juvenile idiopathic arthritis [JIA] ACR responses, patients with
inactive disease), C-reactive protein (CRP) levels over 12 weeks and safety were assessed by age groups. One study (NCT00426218)
was excluded for efficacy outcomes.
Results: 216 children (2–<12 years), 56 adolescents (12–<16 years) and 29 adults (≥16 years) were analyzed for efficacy outcomes.
The efficacy parameters across the three age groups were comparable (Table 1). The safety profile of canakinumab was similar across
age groups (Table 2). One patient from the adolescents group died because of pulmonary hypertension that was associated with
macrophage activation syndrome. Clinical, laboratory and immunogenicity data showed no notable differences between the age groups.
Table 1. Efficacy: responses by age group and time point

Age group % aACR pediatric; n/N (%) JIA ACR; n/N (%)
Day 15 Day 85 Day 15 Day 85
Children ≥30 158/216 90/133 169/216 (78.2 93/133 (69.9)
(73.1) (67.7)
≥70 109/216 77/133 111/216 (51.4) 77/133 (57.9)
(50.5) (57.9)
≥100 46/216 42/133 47/216 (21.8) 42/133 (31.6)
(21.3) (31.6)
Adolescents ≥30 47/56 (83.9) 20/27 (74.1) 47/56 (83.9) 20/27 (74.1)
≥70 33/56 (58.9) 18/27 (66.7) 33/56 (58.9) 18/27 (66.7)
≥100 15/56 (26.8) 8/27 (29.6) 15/56 (26.8) 8/27 (29.6)
Adults ≥30 25/29 (86.2) 15/18 (83.3) 25/29 (86.2) 15/18 (83.3)
≥70 19/29 (65.5) 13/18 (72.2) 19/29 (65.5) 12/18 (66.7)
≥100 4/29 (13.8) 4/29 (13.8) 4/18 (22.2) 4/18 (22.2)
Inactive disease; n/N (%) CRP, median; mg/L (n/N)
Age group Day 15 Day 85 Day 15 Day 85
Children 40/216 32/133 12.00 9.75 (168/216)
(18.5) (24.1) (211/216)
Adolescents 18/56 (32.1) 10/27 (37.0) 10.00 (55/56) 8.40 (45/56)
Adults 6/29 (20.7) 8/18 (44.4) 4.50 (26/29) 7.80 (23/29)
aACR, adapted American College of Rheumatology; CRP, C-reactive protein; JIA,
juvenile idiopathic arthritis
Table 2. Safety: adverse events

Children, n (%) Adolescents, n Adults, n (%)
N = 233 (%) N = 31
N = 60
AEs (at least one) 202 (86.7) 53 (88.3) 27 (87.1)
AEs leading to study 26 (11.2) 10 (16.7) 6 (19.4)
drug discontinuation
AEs most
common/special interest
Infections and 176 (75.5) 42 (70.0) 23 (74.2)
infestations
Gastrointestinal disorders 122 (52.4) 32 (53.3) 18 (58.1)
Musculoskeletal and 119 (51.1) 33 (55.0) 16 (51.6)
connective tissue
disorders
Opportunistic infections 3 (1.3) 4 (6.7) 1 (3.3)
Neutropenia 11 (4.7) 2 (3.3) 0
SAEs (at least one) 81 (34.8) 25 (41.7) 9 (29.0)
AEs, adverse events; SAEs, serious adverse events
Conclusion: Pooled analyses indicate similar efficacy of canakinumab across all the age groups of children, adolescents and adult SJIA
patients. There were no meaningful differences in safety profiles across the different age groups. These analyses suggest similar efficacy
of canakinumab in AOSD patients as observed in the SJIA patients.
References: 1. Jamilloux. Immunol Res 2015;61:53-62. 2. Nirmala. Pediatric Rheumatol 2015;13:50.
Disclosure: E. Feist, Novartis, 2,Novartis, 9; P. Quartier, AbbVie, Novartis, Pfizer, and Chugai-Roche, 2,AbbVie, Novartis, Sobi, and
Roche, 8,AbbVie, Novartis, Pfizer, Sobi, Roche, Novimmune and Sanofi, 9; B. Fautrel, AbbVie, MSD, and Pfizer, 2,AbbVie, Biogen,
BMS, Celgène, Hospira, Janssen, Lilly, MSD, Nordic Pharma, Pfizer, Roche, Sobi, and UCB, 9; R. Schneider, Novartis, 2,Novartis,
Novimmune and Sobi, 9; P. Sfriso, Novartis, 9; P. Efthimiou, Novartis, 9; L. Cantarini, Sobi, Novartis, and AbbVie, 9; K. Lheritier,
Novartis, 3; K. Leon, Novartis, 3; A. Speziale, Novartis, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/canakinumab-treatment-in-patients-with-stills-
disease-a-pooled-analysis-of-systemic-juvenile-idiopathic-arthritis-data-by-age-groups
Short-Term Outcomes in Patients with Systemic-Onset Juvenile Idiopathic Arthritis

Treated with Either Tocilizumab or Anakinra in a Real-World Setting in the United
Kingdom
Lianne Kearsley-Fleet1, Diederik De Cock1, Eileen Baildam2, Michael W. Beresford3, Helen E. Foster4, Taunton R. Southwood5,
Wendy Thomson6,7 and Kimme L. Hyrich1,6, 1Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester
Academic Health Science Centre, Manchester, United Kingdom, 2Clinical Academic Department of Paediatric Rheumatology, Alder
Hey Children's NHS Foundation Trust, Liverpool, United Kingdom, 3Alder Hey Children's NHS Foundation Trust Hospital, Institute of
Translational Medicine (Child Health), University of Liverpool, Liverpool, United Kingdom, 4Institute of Cellular Medicine and
Paediatric Rheumatology, Newcastle University and Great North Children's Hospital, Newcastle Upon Tyne, United Kingdom,
5Institute of Child Health, University of Birmingham and Birmingham Children's Hospital, Birmingham, United Kingdom, 6National
Institute of Health Research Manchester Musculoskeletal Biomedical Research Centre, Central Manchester NHS Foundation Trust,
Manchester Academic Health Science Centre, Manchester, United Kingdom, 7Arthritis Research UK Centre for Genetics and
Genomics, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
SESSION INFORMATION
Background/Purpose: Juvenile idiopathic arthritis (JIA) comprises 7 ILAR categories, but systemic-onset JIA (sJIA) appears to be
distinct in genetic background and pathogenesis from the other categories of JIA. The aim of this study is to investigate real-world
therapeutic short-term responses in patients with sJIA starting tocilizumab (TCZ) or anakinra (ANK), the 2 most common biologics
used currently for this ILAR category.
Methods: This analysis included patients with sJIA enrolled in the UK Biologics for Children with Rheumatic Diseases (BCRD) study
starting TCZ or ANK from 01/01/2010 (study start date), with data available at baseline, 6 months and 1 year by 31/12/2016. Disease
activity was assessed at baseline, 6 months and 1 year, including outcomes; minimal disease activity (MDA), clinically inactive disease
(CID) and ACRPedi90. Univariable logistic regression was used to identify baseline characteristics associated with the outcomes.
Multiple imputation was used to account for missing data.
Results: A total of 78 sJIA patients were included (54 TCZ; 24 ANK) (Table); 55% were female and 70% received this drug as their
first biologic. Patients starting ANK had a shorter disease duration (0 vs 2 years; p=0.003), and more had a history of macrophage
activation syndrome (MAS) (38% vs 8%; p=0.002). Response rates between the 2 drugs were similar. In the whole group, at 1 year,
54% achieved ACRPedi90, 47% MDA and 33% CID (Table). Mean JADAS-71 change was -14 (p<0.001). No baseline characteristics
were associated with achieving response. Nineteen (24%) patients stopped their biologic treatment by 1 year (Figure), for reasons
including remission (N=1), inefficacy (N=6), adverse events (N=10, including one case of MAS in patient receiving TCZ) and unknown
(N=2). Treatment survival was better with TCZ (87% at 1 year vs 50% ANK), with 4 children stopping for injection-related problems.
Conclusion: In this real-world cohort of children with sJIA receiving TCZ or ANK, approximately half the patients achieved a
significant clinical short-term response, and one-third achieved inactive disease within 1 year. Although numbers in this analysis are
low, reflecting the rarity of sJIA, it is important to report these reassuring real-world outcomes and similarities in response with other
JIA categories. As this UK JIA study continues to develop, future analyses investigating longer term tolerability and safety will be
possible.
Table: Baseline characteristics and one year outcomes of 78 systemic JIA patients; 54 tocilizumab and 24 anakinra.
Anakinra (IL- Tocilizumab (IL-
Total
1) 6)
p-value
N=78
N=24 N=54
Female, n (%) 15 (63%) 28 (52%) 43 (55%) P=0.4
First Biologic, n (%) 19 (86%) N=22 34 (63%) 53 (70%) N=76 P=0.04
Age (years), median (IQR) 6 (2, 13) 7 (4, 11) 7 (3, 12) P=0.8
Disease Duration (years),
0 (0, 1) N=23 2 (1, 3) 1 (0, 2) N=77 P=0.003
median (IQR)
Systemic Features Present, n
13 (81%) N=16 24 (53%) N=45 37 (61%) N=61 P=0.05
(%)
History of Macrophage
8 (38%) N=21 4 (8%) N=49 12 (17%) N=70 P=0.002
Activation Syndrome, n (%)
Concomitant Oral Steroids,
15 (63%) 36 (67%) 51 (65%) P=0.7
n (%)
Concomitant Methotrexate,
20 (83%) 44 (81%) 64 (82%) P=0.8
n (%)
Disease Activity, median
(IQR)
Active Joints (0-71) 4 (1, 11) N=19 4 (1, 8) N=48 4 (1, 9) N=67 P=0.9
Physician Global of Disease
3 (2, 6) N=16 4 (2, 6) N=34 3 (2, 6) N=50 P=0.8
(0-10cm VAS)
Parent Global of Wellbeing (0-
4 (1, 5) N=18 4 (2, 7) N=34 4 (1, 7) N=52 P=0.9
10cm VAS)
0.9 (0.4, 1.8)
Childhood Health Assessment 1.0 (0.4, 2.0) 0.9 (0.4, 1.8)
P=0.8
Questionnaire (0-3) N=15 N=49
N=34
Erythrocyte sedimentation 55 (27, 86) 35 (11, 67)
26 (10, 58) N=49 P=0.1
rate, mm/hr N=19 N=68
19 (7, 27)
JADAS-71 18 (6, 29) N=12 20 (11, 26) N=22 P=0.7
N=34
Six Month Outcomes*, %
-10.7
Mean JADAS-71 change -10.4 (p=0.1) -10.8 (p<0.001) P=0.9
(p<0.001)
ACR Pedi 90 51% 58% 56% P=0.7
Minimal disease activity
45% 50% 49% P=0.7
(MDA)
Clinically inactive disease
15% 20% 19% P=0.7
(CID)
Twelve Month Outcomes*,
%
-13.6
Mean JADAS-71 change -13.3 (p<0.001) -13.7 (p<0.001) P=0.7
(p<0.001)
ACR Pedi 90 37% 62% 54% P=0.1
Minimal disease activity
41% 49% 47% P=0.5
(MDA)
Clinically inactive disease
22% 38% 33% P=0.2
(CID)
*Using imputed data.
Interquartile range (IQR), visual analogue scale (VAS), 71-joint juvenile arthritis disease
activity score (JADAS-71), American college of rheumatology paediatric criteria for 90%
improvement (ACR Pedi 90).
Disclosure: L. Kearsley-Fleet, None; D. De Cock, None; E. Baildam, None; M. W. Beresford, None; H. E. Foster, None; T. R.
Southwood, None; W. Thomson, None; K. L. Hyrich, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/short-term-outcomes-in-patients-with-systemic-

onset-juvenile-idiopathic-arthritis-treated-with-either-tocilizumab-or-anakinra-in-a-real-world-setting-in-the-united-kingdom
Interleukin-1 Receptor Antagonist Is a Potential Treatment for Undifferentiated

Autoinflammatory Syndromes
Ananta Subedi1, Daniella Schwartz2, Karyl Barron3, Daniel L. Kastner4 and Amanda Ombrello5, 1National Institute of Arthritis,
Musculoskeletal and Skin Disease (NIAMS), Bethesda, MD, 2NIAMS - Rheumatology, National Institutes of Health, Bethesda, MD,
3National Institutes of Health, Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, MD,
4Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD,
5Inflammatory Disease Section, NHGRI/NIH, Bethesda, MD
SESSION INFORMATION
Background/Purpose: The autoinflammatory diseases (AIDs) are a group of disorders of the innate immune system characterized by
seemingly unprovoked inflammation1. A variety of genetic alterations are attributed to the clinical and pathological manifestations of
these conditions; however, many of the patients presenting with clinical features of AIDs do not have a pathogenic mutation to be
classified under one of the monogenic AIDs2. These patients are referred to as having an undifferentiated autoinflammatory syndrome.
Blocking of the interleukin 1 (IL-1) pathway is defined as a treatment modality in some of the AIDs (FMF, CAPS, TRAPS and MVK);
but, there is limited data on their use in undifferentiated autoinflammatory syndromes.
Aim: We aim to review the treatment effects of the IL-1 receptor antagonist, anakinra, in pediatric undifferentiated autoinflammatory
syndrome patients.
Methods: We identified the pediatric patients enrolled in the protocol 94-HG-0105 “Genetics and Pathophysiology of Familial
Mediterranean Fever and Related Disorders” who were prescribed Anakinra between October 2010 and October 2016. Patients who
tested positive for known genetic mutation to cause periodic fever syndromes (FMF, CAPS, TRAPS, MKD, PAPA, DIRA, HA20and
DADA2) by commercially available methods were excluded. Medical records were reviewed to identify the response to treatment with
Anakinra. Clinical response was determined based on the patient reported outcome. Laboratory data ((White Blood Cell Count (WBC),
ESR and CRP)) were compared before and after the treatment. Statistical tests were done using RStudio (http://www.R-project.org).
Clinical response to treatment were presented as frequency diagram. Laboratory data before and after the use of Anakinra was
compared using the Wilcoxon signed rank test.
Results: We identified 75 patients who met the pre-specified criteria. Among the 75 patients, the majority of the patients were male
(65%). The disease was predominantly seen among Caucasians (84%). Anakinra was prescribed as needed (PRN) for 56% of the
patients, 44% required a daily dose. 59% of the patients were responders, 9% were partial responders and 17% did not have clinical
response to the treatment. 13% of the patients were non-compliants, 1% could not tolerated and 1% of the patient did not have a follow
up. Among the patients who had clinical response to treatment, we found a statistically significant decrease in ESR after treatment with
anakinra (p-value = 0.01416, 95 percent confidence interval: 1.000085 8.999991).
Conclusion: The management of pediatric undifferentiated autoinflammatory syndromes is challenging. We found anakinra a very
effective treatment option for use on both an intermittent and continuous basis. Anakinra has the potential to significantly improve the
quality of life of such patients.
Refrences:
1. Kastner, Daniel L. "Hereditary periodic fever syndromes." ASH Education Program Book 2005.1 (2005): 74-81.
2. Rigante, Donato, et al. "The hereditary autoinflammatory disorders uncovered." Autoimmunity reviews 13.9 (2014): 892-900.
Disclosure: A. Subedi, None; D. Schwartz, None; K. Barron, None; D. L. Kastner, None; A. Ombrello, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/interleukin-1-receptor-antagonist-is-a-potential-

treatment-for-undifferentiated-autoinflammatory-syndromes
Evaluation of Efficacy and Safety of Opocalcium Colchicine, and Anti-IL1 Treatment

in Childhood Colchicine-Resistant Familial Mediterranean Fever
Kenan Barut, Amra Adrovic, Sezgin Sahin, Asli Kaplan and Ozgur Kasapcopur, Pediatric Rheumatology, Istanbul University,
Cerrahpasa Medical School, Department of Pediatric Rheumatology, Istanbul, Turkey
SESSION INFORMATION
Background/Purpose:
The colchicine-resistant FMF (crFMF) is defined as 6 or more polyserositis attacks in the last year despite the regular usage of
colchicine in the highest tolerable dose. IL-1 receptor antagonists have been shown to be efficient in crFMF. We tried to define the
efficacy of opocalcium colchicine (OC), anakinra and canakinumab by FMF50 scores, complete and partial clinical responses.
Methods:
Patients who were under OC, anakinra and canakinumab are considered to be resistant to standard colchicine treatment. The FMF50
score is used to define the response to treatment. Complete clinic and laboratory response is characterized by an absence of clinical
features and normal laboratory findings. The partial clinical and laboratory response include 30 % improvement in clinical and
laboratory features.
Results:
A total of 839 FMF patients has been assessed and 49/839(5,8%) of them has been considered colchicine resistant. FMF50 response has
been obtained in 4/49(8.2%) patients under standard colchicine treatment; in 14/30 (46.7%) patients treated with OC, in 5/6 (83.3%)
with anakinra and in 12/13(92.3%) patients with canakinumab. The FMF50 response significantly differed according to treatment
modality (p<0.005). Clinical remission has been achieved in 10/30(33.3%), 5/6(83.3%) and in 11/13(84.6%) patients treated with OC,
anakinra and canakinumab, respectively. Patients treated with OC significantly differed from those treated with anti IL-1 according to
complete clinical remission (p<0.002). Laboratory remission has been obtained in 7/30(23.3%), 4/6(66.7%) and 11/13(84.6%) patients
treated with OC, anakinra and canakinumab, respectively. The laboratory remission was significantly different between patients treated
with OC and with anti IL-1 (p<0.0001).
The most common adverse effect was diarrhea in 17/49(34.6%), transaminases elevation in 3/49(6%) patients and leukopenia in 1
patient. Diarrhea was seen in 3/30(10%) patients under OC treatment. Local allergic reactions were seen in 3/6(50%) anakinra patients.
One patient developed pneumonia while on canakinumab treatment; upper respiratory tract infection has been registered in 3/13(23%)
patients and acute gastroenteritis in one patient. None of the patients developed severe adverse effect.
Conclusion:
The FMF50 response has not been achieved in majority of patients under OC treatment, although their drug compliance was better
comparing to standard colchicine compound in our country. Complete clinical remission has been obtained in minority of patients
treated with OC. In contrary, FMF50 response, complete clinical and laboratory response have been detected in most of patients treated
with anakinra and canakinumab. Both of anti IL-1 agents were safe and effective in crFMF patients.
References
1. Ozen S, Demirkaya E, Duzova A, et al. FMF50: a score for assessing outcome in familial Mediterranean fever. Ann Rheum Dis
2014;73:897-901.
2. Gul A, Ozdogan H, Erer B, Ugurlu S, Kasapcopur O, Davis N, Sevgi S. Efficacy and safety of canakinumab in adolescents and
adults with colchicine-resistant familial Mediterranean fever. Arthritis research & therapy 2015;17:243.
Disclosure: K. Barut, None; A. Adrovic, None; S. Sahin, None; A. Kaplan, None; O. Kasapcopur, Novartis Pharmaceutical
Corporation, 8,Roche Pharmaceuticals, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/evaluation-of-efficacy-and-safety-of-opocalcium-

colchicine-and-anti-il1-treatment-in-childhood-colchicine-resistant-familial-mediterranean-fever
Hepatitis A Virus Vaccination in Juvenile-Onset Systemic Lupus Erythematosus

Sevinc Mertoglu1, Sezgin Sahin1, Omer Faruk Beser2, Amra Adrovic1, Kenan Barut1, Pelin Yuksel3, Soner Sazak4, Bekir Kocazeybek5
and Ozgur Kasapcopur1, 1Pediatric Rheumatology, Istanbul University, Cerrahpasa Medical School, Department of Pediatric
Rheumatology, Istanbul, Turkey, 2Pediatric Gastroenterology, Department of Pediatrics, Okmeydani Education and Training Hospital,
Istanbul, Turkey, 3Microbiology, Istanbul University, Cerrahpasa Medical School, Department of Microbiology, Istanbul, Turkey,
4Pediatrics, Department of Pediatrics, Okmeydani Education and Training Hospital, Istanbul, Turkey, 5Istanbul University, Cerrahpasa
Medical School, Department of Microbiology, Istanbul, Turkey
SESSION INFORMATION
Background/Purpose:
Various infections play significant roles in flares of systemic lupus erythematosus (SLE). Hepatitis A virus is one of these infectious
agents that has high endemicity particularly in developing countries. Hence, immunization via vaccination against this infectious agent
would provide a better management of the disease. However, both immunosuppressive drugs and the disease itself are believed to
impair the normal functioning of immune system. Little is known regarding the safety and immunogenicity of vaccinations in SLE
patients. Moreover, to the best of our knowledge safety and efficacy of hepatitis A vaccination were not studied in children with SLE.
In the present study, we aimed to compare the antibody titers and seropositivity rates in juvenile SLE and healthy subjects after hepatitis
A vaccination. Besides, we examined the effect of immunosuppressive drugs and disease activity on antibody responses.
Methods:
Sixty-nine juvenile SLE patients were enrolled in the study. Initially, we evaluated anti-HAV IgM and anti-HAV IgG titers in juvenile
SLE patients. Of the 69 subjects, 37 patients were seronegative and eligible for hepatitis A vaccination. Among them, 7 juvenile SLE
patients refused to participate to the study. Finally, anti-HAV Ig G negative 30 patients and 39 healthy subjects were vaccinated with
two doses of hepatitis A vaccine (at 0 months and at sixth months). After vaccinations, anti-HAV Ig G titers were measured and
compared between two groups.
Results:
Anti-HAV Ig G concentrations were measured after vaccination in 30 patients with juvenile SLE and 39 control subjects. Anti-HAV Ig
G titer of the juvenile SLE patients was significantly lower than that of the healthy controls (median 4.6 versus 11.9 IU/L, p=0.02).
Although the rate of seropositivity was lower in juvenile SLE patients (n=24/30, 80%) compared to healthy controls (n=33/39, 84.6%);
this was not statistically significant (p=0.6). No adverse reaction was reported after vaccination.
Conclusion:
Although anti-HAV Ig G antibody titers after vaccination have found to be somewhat lower than that of the healthy subjects, significant
portion of juvenile SLE patients were seropositive. According to these results, we conclude that hepatitis A vaccine is adequately
immunogenic and quite safe in juvenile SLE patients.
References:
1. Borgia RE, Silverman ED. Childhood-onset systemic lupus erythematosus: an update. Curr Opin Rheumatol 2015; 27: 483-92.
2. Zandman-Goddard G, Shoenfeld Y. Infections and SLE. Autoimmunity 2005; 38: 473–85.
3. Melhem NM, Talhouk R, Rachidi H, Ramia S. Hepatitis A virus in the Middle East and North Africa region: a new challenge.
Journal of viral hepatitis 2014; 21(9): 605-615.
4. Aytac MB, Kasapcopur O, Aslan M, Erener-Ercan T, Cullu-Cokugras F, Arisoy N. Hepatitis B vaccination in juvenile systemic lupus
erythematosus. Clin Exp Rheumatol 2011; 29: 882-6.
Disclosure: S. Mertoglu, None; S. Sahin, None; O. F. Beser, None; A. Adrovic, None; K. Barut, None; P. Yuksel, None; S. Sazak,
None; B. Kocazeybek, None; O. Kasapcopur, Novartis Pharmaceutical Corporation, 8,Roche Pharmaceuticals, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/hepatitis-a-virus-vaccination-in-juvenile-onset-

systemic-lupus-erythematosus
Validation of 2016 ACR/EULAR Classification Criteria of Macrophage Activation

Syndrome Complicating Systemic Juvenile Idiopathic Arthritis in Japanese Patients
Masaki Shimizu1, Mao Mizuta1, Takahiro Yasumi2, Naomi Iwata3, Yuka Okura4, Noriko Kinjo5, Hiroaki Umebayashi6, Tomohiro
Kubota7, Yasuo Nakagishi8, Kenichi Nishimura9, Masato Yashiro10, Junko Yasumura11, Kazuko Yamazaki12, Hiroyuki Wakiguchi13,
Nami Okamoto14 and Masaaki Mori15, 1Department of Pediatrics, Graduate School of Medical Sciences, Kanazawa University,
Kanazawa, Japan, 2Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan, 3Department of
Immunology and Infectious Diseases, Aichi Children’s Health and Medical Center, Obu, Japan, 4Department of Pediatrics, KKR
Sapporo Medical Center, Sapporo, Japan, 5Department of Pediatrics, Faculty of medicine, University of the Ryukyus, Nakagami-gun,
Japan, 6Department of Rheumatics, Miyagi Children’s Hospital, Sendai, Japan, 7Department of Pediatrics, Kagoshima University
Graduate School of Medical and Dental Sciences, Kagoshima, Japan, Kagoshima, Japan, 8Department of Pediatric Rheumatology,
Hyogo Prefectural Kobe Children’s Hospital, Kobe, Japan, 9Department of Pediatrics, Yokohama City University Graduate School of
Medicine, Yokohama, Japan, 10Department of Pediatrics, Okayama University Hospital, Okayama, Japan, 11Department of Pediatrics,
Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan, 12Department of Pediatrics, Saitama
Medical Center, Saitama Medical University, Kawagoe, Japan, 13Department of Pediatrics, Yamaguchi University Graduate School of
Medicine, Ube, Japan, 14Department of Pediatrics, Osaka Medical College, Takatsuki, Japan, 15Department of Lifetime Clinical
Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
SESSION INFORMATION
Background/Purpose: To validate the 2016 ACR/EULAR classification criteria of macrophage activation syndrome (MAS)
complicating systemic juvenile idiopathic arthritis (s-JIA) in Japanese patients.
Methods: A combination of expert consensus and analysis of real patient data was conducted by a panel of 15 paediatric
rheumatologists. Eighty-three profiles comprised 25 patients with s-JIA–associated MAS and 58 patients with active s-JIA without
evidence of MAS. From these profiles, 19 points for full-blown MAS, 16 points for MAS onset and 58 points for acute s-JIA without
MAS were evaluated.
Results: Evaluation of the classification criteria to discriminate full-blown MAS from acute s-JIA without MAS showed a sensitivity
of 0.947 and specificity of 1.000 at the time of full-blown MAS. Sensitivity was 0.438 and specificity 1.000 at the time of MAS onset.
The number of measurement items that fulfilled the criteria increased in full-blown MAS compared to that at MAS onset. At MAS
onset, the positive rates of patients who met the criteria for platelet counts and triglycerides were low, whereas those for aspartate
aminotransferase and fibrinogen were relatively high. At full-blown MAS, the number of patients who met the criteria for each
measurement item increased.
Conclusion: The classification criteria for MAS complicating s-JIA had a very high diagnostic performance. However, the diagnostic
sensitivity for MAS onset was relatively low. For the early diagnosis of MAS in s-JIA, the dynamics of laboratory values during the
course of MAS should be further investigated.
Disclosure: M. Shimizu, None; M. Mizuta, None; T. Yasumi, None; N. Iwata, None; Y. Okura, None; N. Kinjo, None; H.
Umebayashi, None; T. Kubota, None; Y. Nakagishi, None; K. Nishimura, None; M. Yashiro, None; J. Yasumura, None; K.
Yamazaki, None; H. Wakiguchi, None; N. Okamoto, None; M. Mori, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/validation-of-2016-acreular-classification-criteria-

of-macrophage-activation-syndrome-complicating-systemic-juvenile-idiopathic-arthritis-in-japanese-patients
Longer Term Outcomes of Chronic Relapsing Multifocal Osteomyelitis in a UK

Tertiary Adolescent and Young Adult Rheumatology Centre
Kristina E.N. Clark1, Francesca Josephs2, Nicola Daly3, Claire Louise Murphy3 and Debajit Sen4, 1Rheumatology, University college
London Hospitals, London, United Kingdom, 2rhuematology, UCL, London, United Kingdom, 3Rheumatology, University College
London Hospital, London, United Kingdom, 4Adolescent Rheumatology Department, University College London Hospital NHS Trust,
London, United Kingdom
SESSION INFORMATION
Background/Purpose:
Chronic relapsing multifocal osteomyelitis (CRMO) is a rare autoinflammatory bone condition presenting primarily in children &
adolescents. It characteristically affects the epiphysis & metaphysis of long bones & presents with bony pain, local swelling & warmth.
The aim of this study was to collate our centre’s experience of managing patients with CRMO & establish their longer term outcomes.
Methods:
Our Centre provides a tertiary service for adolescents & young adults >13 years. We performed a retrospective case note review of all
patients known to our service with a diagnosis of CRMO.
Results:
We identified 17 (10 female) patients with CRMO presenting between 1999 & 2015. The median age of initial symptoms & age of
presentation was 12 years. Median follow up duration 4.75 years (range 1-16.5 years).
On review of long term outcomes, several patients evolved into a different disease phenotype: 3 SAPHO (synovitis, acne, pustolosis,
hyperostosis, osteitis), 3 ERA (enthesitis related arthritis) & 2 oligoarticular juvenile idiopathic arthritis (OJIA). The clinical phenotype
of patients with SAPHO was predominantly multifocal (involving wrists, jaw, ankle & ribs), with one patient having disease of only the
sternoclavicular joints. Of the ERA patients, 2 had sacro-iliac & clavicle involvement, 1 had initial femur involvement which has
progressed to ERA around the hips. All patients with OJIA had ankle involvement, with 1 developing knee synovitis as well & 1 wrist
& shoulder inflammatory arthritis.
Unifocal osteomyelitis was seen in 35% of patients & 65% multifocal as confirmed by whole body MRI. 70.5% patients had recurrent
episodes of inflammation, while 29.5% had only one flare & then remitted (either clinical or confirmed with MRI). 15 patients had their
diagnosis confirmed with biopsy, 2 did not due to site of disease being close to the growth line (diagnosis based on clinic impression &
typical radiographic findings).
Multiple sites of disease have been confirmed in our patients & include lower limbs (70%), upper limbs (35%), clavicle (29.4%),
mandible (17.6%) & spine/pelvis (23.5%).
All patients were treated with NSAIDs. During the course of the disease at any point 76% have been on methotrexate; 47% had one
pamidronate infusion & 23% more than 1. Other medications include sulfasalazine, azathioprine, risedronate &anti-TNFs.
On last clinic review, 35% of patients have evidence of ongoing active disease
Conclusion:
The perceived wisdom is that CRMO is a self-limiting disease which eventually goes into remission. However our Centre’s experience
is that nearly 50% of our patients have a disease which evolves into another systemic autoimmune disease (SAPHO, OJIA or ERA).
This is more frequent in those with multifocal CRMO. Previous case series have suggested only 0-30% of patients’ disease evolves. Our
findings may be a reflection of our older cohort of patients.
The majority of patients have a recurrent and multifocal disease. The most common site of disease was in the lower limbs. All patients
were treated with NSAIDS, a combination of DMARDS, bisphosphonates & biologic agents have been used, which has resulted in
remission of disease in the majority of patients.
Disclosure: K. E. N. Clark, None; F. Josephs, None; N. Daly, None; C. L. Murphy, None; D. Sen, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/longer-term-outcomes-of-chronic-relapsing-

multifocal-osteomyelitis-in-a-uk-tertiary-adolescent-and-young-adult-rheumatology-centre
Phenotype of Chronic Recurrent Multifocal Osteomyelitis in a Tertiary Referral

Centre: The Great Ormond Street Hospital Experience
Kulsoom Riaz1 and Sandrine Lacassagne2, 1Paediatric Rheumatology/Gastroenterology, Great Ormond Street Hospital, London,
United Kingdom, 2Paediatric Rheumatology, Great Ormond Street Hospital, London, United Kingdom
SESSION INFORMATION
Background/Purpose:
Recurrent Multifocal Osteomyelitis (CRMO) is an aseptic inflammatory bone disease that typically affects the metaphases of the long
bones. It affects children, adolescents and young adults. The main presenting feature is local bone pain and/or swelling. It has a
protracted course for years with exacerbations and improvement with treatment. The diagnosis of CRMO can be made on clinical
presentation and confirmed by magnetic resonance imaging (MRI) and bone biopsy. On MRI examination there are mostly multifocal,
and symmetrical lesions (especially in the metaphysics of tubular long bones, flat bones and spine). CRMO can be associated with skin,
gut involvement and other rheumatological conditions.
Methods:
We reviewed reports of whole body MRI scans of 300 children, done in last 5 years between January 2012 and December 2016. Patients
with MRI scan results consistent with CRMO were included in the study. Retrospective analysis of electronic clinical records of these
patients was done and we recorded their clinical symptoms at presentation, any associated illnesses and Family history.
Histopathological/ microbiological findings of bone biopsies were reviewed to rule out haematological, infectious or malignant causes.
Results:
Twenty three patients were included in the study.Five were male and eighteen female. These children were 8-18 years old with median
age of 15 years. The clinical features of CRMO at first presentation are as under.All patients presented with musculoskeletal symptoms
like backache, clavicular involvement, or joint pain.Five patients (21%) presented with abdominal pain and blood in stool. These
patients were diagnosed as Inflammatory bowel disease(IBD) on the endoscopic and histopathological findings. Three patients
presented with gut symptoms first and later on they developed joint pain and swelling. However one patient presented with joint pain to
start with and diagnosed as CRMO. This patient later on developed gut symptoms. One patient presented with simultaneous onset of
diarrhoea, blood in stool, abdominal pain and joint pain with swelling.There is significantly more raised inflammatory markers in the
IBD/CRMO group than in the CRMO alone groupHistory of trauma was present in 13% of patients who presented with musculoskeletal
symptoms.Hyper mobility was present in four patients. Juvenile idiopathic arthritis was an associated diagnosis in three patients. One
patient was diagnosed as Enthesitis related arthritis (ERA) and CRMO overlap. Psoriasis, palmoplantar pustulosis , acne, atopic
dermatitis, dermatitis artefacta were the skin conditions associated with CRMO but not in IBD/CRMO overlap group.There was family
history of connective tissue disorders in six (26%) out of 23 patients, including systemic lupus erythematosus, ankylosing spondylitis,
Crohn’s disease, rheumatoid arthritis, antiphospholipid syndrome and psoriasis. Only one patient (4%)out of 23 was HLAB27 positive.
Conclusion:
CRMO has a varied presentation. We identified that CRMO is associated with IBD in 21% of the patients. Further studies are needed to
identify whether the CRMO/IBD overlap group has a separate phenotype.
Disclosure: K. Riaz, None; S. Lacassagne, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/phenotype-of-chronic-recurrent-multifocal-

osteomyelitis-in-a-tertiary-referral-centre-the-great-ormond-street-hospital-experience
a Retrospective Study of Clinical Factors Influencing the Development of

Overlapping Disease Features in Pediatric Patients with Chronic Recurrent
Multifocal Osteomyelitis (CRMO) and Spondyloarthropathies (SpA)
Lillian Lim1, Jyoti Panwar2, Jennifer Stimec3, Shirley M.L. Tse4, Brian M. Feldman5 and Ronald M. Laxer6, 1Paediatrics, The
Hospital for Sick Children, Toronto, ON, Canada, 2Christian Medical College, Vellore, India, Vellore, India, 3The Hospital for Sick
Children, Toronto, ON, Canada, 4Rheumatology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada,
5Rheumatology, The Hospital for Sick Children, Toronto, ON, Canada, 6Div of Rheumatology, The Hospital for Sick Children, Toronto,
ON, Canada
SESSION INFORMATION
Background/Purpose:
Some studies have suggested that chronic recurrent multifocal osteomyelitis (CRMO) and spondyloarthropathies (SpA) fall on a
spectrum of disease, as they have been noted to share overlapping radiographic and clinical features. Most studies examining the link
between inflammatory bone lesions and SpA have involved adult patients with SAPHO syndrome, with limited pediatric data. This
study was done to test whether gender, HLA-B27 positivity, or age at onset of disease, influence whether and when pediatric CRMO
and SpA patients develop overlapping features. Understanding of the clinical factors influencing overlap may have implications for
earlier diagnosis, risk stratification, and treatment options.
Methods:
This was a retrospective inception cohort study of SickKids hospital charts. Eligible pediatric patients diagnosed with either CRMO or
SpA between January 2000 and December 2016 were collected using the SickKids Rheumatology patient database. Using a secure web
application (REDCap), we collected and compared the clinical, laboratory, and radiographic data of 40 randomly sampled patients from
each of the CRMO and SpA groups. The MRIs were re-read by a radiologist. A patient was considered to have an overlap diagnosis if
they had radiologic and clinical features of both CRMO and SpA.
Results:
7 patients (17.5%) and 8 patients (20.0%) from the CRMO and SpA groups, respectively, developed overlap. The median time to
overlap was 36.0 months and 31.5 months, respectively. A survival (time-to-event) analysis, using the Kaplan-Meier approach, was
used to show the proportion of patients without overlap features, since time of symptom onset. 28% of the entire sample population was
HLA-B27 positive. Multivariable regression models using the Cox Proportional Hazards regression technique showed that the overall
likelihood ratio test was not statistically significant (p=0.59), with hazard ratios of 1.11, 0.91, and 1.17 for each of male gender, HLA-
27 positivity, and age at symptom onset, respectively.
Conclusion:
Patient gender, HLA-B27 positivity, and age of symptom onset did not appear to increase the risk of developing overlap features of
CRMO and SpA in our sample population. Nonetheless, overlap of clinical and radiologic features was found in approximately 20% of
our patients. CRMO and SpA may represent two diseases on the same spectrum, though prospective studies with longer follow up are
needed. Our study was limited by the small sample size and retrospective design, as it is unknown whether overlap may occur in the
time exceeding clinical follow-up. Study of their clinical overlap is important to allow a better understanding of how to recognize and
treat these rare diseases.
Disclosure: L. Lim, None; J. Panwar, None; J. Stimec, None; S. M. L. Tse, None; B. M. Feldman, None; R. M. Laxer, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-retrospective-study-of-clinical-factors-

influencing-the-development-of-overlapping-disease-features-in-pediatric-patients-with-chronic-recurrent-multifocal-osteomyelitis-
crmo-and-spondyloarthropat
A Pilot Study of Infrared Thermal Imaging to Detect Active Bone Lesions in

Children with Chronic Nonbacterial Osteomyelitis
Yongdong Zhao1, Ramesh Iyer2, Lucas Reichley1, Assaf Oron3, Averi Kitsch4, Seth Friedman5, Savannah Partridge4 and Carol A
Wallace1, 1University of Washington, Department of Pediatrics, Seattle, WA, 2Division of Radiology, University of Washington, Seattle
Children’s Hospital, Seattle, WA, 3Center for Clinical and Translational Research, Seattle Children’s Research Institute, Seattle, WA,
4Department of Radiology, University of Washington, Seattle, WA, 5Division of Radiology, University of Washington, Seattle
Children's Hospital, Seattle, WA
SESSION INFORMATION
Background/Purpose: Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease. For detection of active bone
lesions, bone scintigraphy and magnetic resonance imaging (MRI) are much more sensitive than radiographs, but are more expensive
and often require sedation for young children. A rapid and noninvasive imaging tool, infrared thermal imaging, was evaluated for its
utility to detect active CNO lesions in extremities of children with CNO.
Methods: Children with suspected or established diagnosis of CNO in their lower extremities were enrolled. All subjects underwent
infrared thermal imaging of both entire legs with four views each (anterior, posterior, medial, and lateral) and MRI examinations of their
lower extremities. Relevant demographic, laboratory and clinical data were collected. Infrared thermal data were analyzed using
custom software. Lower legs were divided equally into three segments longitudinally, and distal thigh was defined as the same length of
proximal lower leg (Figure 1). Median and 95th percentile temperatures were recorded for each leg segment. MRI examinations were
graded by a blinded pediatric musculoskeletal radiologist to determine the presence of bone edema as confirmation of inflammation
within each segment. Temperature differences between inflamed and uninflamed extremities were evaluated using mixed-effects
regression models.
Results: Nineteen children with MRI-confirmed CNO in their lower extremities were enrolled, Table 1. Overall, 26 distal, 2 mid
(excluded from analysis), 18 proximal lower leg and 12 distal thigh lesions were detected on MRI. Inflamed distal lower leg segments
had significantly higher median and 95th percentile temperatures than uninflamed counterparts (p<0.01 in all views). The mean
difference between two groups ranged from 0.70C to 1.70C, with the greatest difference from medial view (Figure 2). Distal thigh and
proximal lower leg temperatures did not differ between inflamed and uninflamed legs from any view.
Conclusion: Children with active CNO lesions in the distal lower leg exhibited higher regional temperatures versus healthy limbs.
Further research is needed to evaluate infrared thermal imaging as a convenient and cost-effective tool to identify patients needing
additional evaluation by MRI.
Disclosure: Y. Zhao, None; R. Iyer, None; L. Reichley, None; A. Oron, None; A. Kitsch, None; S. Friedman, None; S. Partridge,
None; C. A. Wallace, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-pilot-study-of-infrared-thermal-imaging-to-detect-

active-bone-lesions-in-children-with-chronic-nonbacterial-osteomyelitis
Controlled Discontinuation of Colchicine Therapy in Familial Mediterranean Fever

Patients with Single MEFV Mutation
Yonatan Butbul Aviel1, Shafe Fahoum2 and Riva Brik3, 1Department of Pediatrics B Pediatric Rheumatology Service, Ruth Rappaport
Children's Hospital, Rambam Medical Center, Haifa, Israel, Haifa, Israel, 2Department of Pediatrics B,, , Ruth Children's Hospital,
Rambam Medical Center, Haifa, Israel, Pediatric Rheumatology Service, .Rappaport Faculty of Medicine, Technion-lsrael Institute of
Technology, Haifa, Israel, 3Pediatrics, Rambam Medical Center, Haifa, Israel
SESSION INFORMATION
Background/Purpose:
Familial Mediterranean fever (FMF) traditionally has been considered an autosomal recessive disease; however, the diagnosis remains
predominantly clinical, since mutations cannot always be identified on both alleles.
The aim of our study was to evaluate cessation of colchicine therapy in selected group of patients with FMF who possess only 1 or none
demonstrable MEFV mutation.
Methods:
We performed a prospective controlled study evaluated cessation of colchicines therapy in patients that were previously diagnosed and
treatd for FMF based on clinical features and did not carry any common MEFV mutation or were heterozygote for one of the mutations
.
Patients were included in the study if they were between the age of 2-18 years and were treated with colchicine, had a normal level of
serum amyloid A (SAA )and had at least 6 months free of FMF attacks.
SAA levels were evaluated before colchicine cessation and at 3 and 6 months following cessation. Colchicine therapy was resumed in
case of FMF attacks reappeared during this period.
Results:
thirteen patients ages 10.6±4 years enrolled in the study. Prior to entering the study patients were treated with colchicine for an average
of 36.3 month ( 7-141 months median 31 months ). The average time with no FMF attacks before enrolment into the study was
12.8±8.6 months and the average follow up after stopping colchicine therapy was 16.3±6 months . Five patients were heterozygote for
the M694Vmutation four patients were heterozygote for E148Q two patients had other mutations and two patients had no mutations .
Five patients (41.6%) had an FMF attack during follow up and needed to renew colchicine therapy, the average time to renew
colchicine therapy was 5.3 months (range 1.5-11.4 months) 3 of them (60%) carried the M694V mutation.
There were no differences between the groups of patients that did not relapse and the groups that needed to renew therapy regarding age
(10.7±1.6 vs 10.6±6.3 p- 0.97) or levels of SAA at time of enrolment (4±3.6 vs 3.3±2.4 p-0.7). Length of colchicine therapy prior to
enrolment showed tendency that didn't reach significance towards longer time in the patients needed to resume therapy (22.3±12.6 vs
53±51 months p-0.18) .
Conclusion:
Cessation of colchicine therapy in selected group of patients who are not homozygous for the common MEFV mutation should be
considered. Monitoring SAA levels every 3 months could not predict FMF attacks following cessation of colchicine therapy.
Disclosure: Y. Butbul Aviel, None; S. Fahoum, None; R. Brik, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/controlled-discontinuation-of-colchicine-therapy-in-

familial-mediterranean-fever-patients-with-single-mefv-mutation
Improvement of Disease Activity in Patients with Colchicine-Resistant FMF,

Hids/Mkd and TRAPS Assessed By Autoinflammatory Disease Activity Index
(AIDAI): Results from a Randomized Phase III Trial
Isabelle Koné-Paut1, Michaël Hofer2, Susanne Benseler3, Jasmin B. Kuemmerle-Deschner4, Annette Jansson5, Itzhak Rosner6,
Raffaele Manna7, Sara Murias8, Omer Karadag9, Lori Tucker10, Ilonka Orban11, Vincent Tormey12, Maria Alessio13, Huri Ozdogan14
and Fabrizio De Benedetti15, 1Bicêtre Hospital, APHP, Univeristy Paris Sud, Paris, France, 2Unité romande d’immuno-rhumatologie
pédiatrique, CHUV, University of Lausanne, Genova, Italy, 3Alberta Children's Hospital, Calgary, AB, Canada, 4University Hospital
Tuebingen, Tuebingen, Germany, 5Ludwig Maximilian University, Munich, Germany, 6Bnai-Zion Medical Center, Haifa, Israel,
7Department of Internal Medicine, Università Cattolica Sacro Cuore, Rome, Italy, 8Hospital Infantil La Paz, Madrid, Spain, 9Hacettepe
University Faculty of Medicine, Ankara, Turkey, 10BC Children's Hospital, Vancouver, BC, Canada, 11Orszagos Reumatologial es
Fizioterepias, Budapest, Hungary, 12University College Hospital Galway, Galway, Ireland, 13A Osped-Universit Policlinico Federico II,
Univ degli Studi di Napoli, Napoli, Italy, 14Rheumatology, Istanbul University, Cerrahpasa Medical Faculty, Division of Rheumatology,
Istanbul, Turkey, 15Istituto Giannina Gaslini - Pediatria II, Reumatologia - PRINTO, Genoa, Italy
SESSION INFORMATION
Background/Purpose: AIDAI is a novel, validated tool for the assessment of disease activity across a wide spectrum of
autoinflammatory diseases including recurrent fever syndromes such as familial Mediterranean fever (FMF), hyper-IgD
syndrome/mevalonate kinase deficiency (HIDS/MKD) and TNF receptor-associated periodic syndrome (TRAPS).1 Canakinumab
(CAN), a fully human anti-interleukin-1β monoclonal antibody, has demonstrated efficacy in resolving flares and preventing new flares
in RFS patients (pts) through CLUSTER study (NCT02059291).2 Here we evaluate AIDAI scores over 16 weeks (wks) of CAN
treatment in pts from CLUSTER study and assess correlation between AIDAI and disease/response characteristics.
Methods: CLUSTER study consisted of 3 cohorts (crFMF, HIDS/MKD and TRAPS).2 AIDAI was calculated as the sum of 12 items
(Yes=1 or No=0)1 for 30 consecutive days. AIDAI score was calculated if the first score was recorded before ≥29 days. Missing AIDAI
scores between first and last assessments were imputed with ‘No’. Missing items beyond last evaluable measurement were imputed by
last observation carried forward (LOCF). Proportion of pts with inactive disease (ID; AIDAI score <9) was calculated at Wk 16.
Correlation analysis of AIDAI with C-reactive protein (CRP), serum amyloid A (SAA), physician global assessment (PGA), Sheehan
disability score (SDS), child health questionnaire–psychological/physical (CHQ–PsCS/PCS) and short form 12–physical/mental
component summaries (SF12–PCS/MCS) were performed at baseline and Wk 16, with significance set at p<0.05.
Results: Overall, 181 (crFMF, N=63; HIDS/MKD, N=72; TRAPS, N=46) pts were randomized to CAN 150 mg or placebo every 4
wks. Median AIDAI scores in all 3 cohorts decreased from baseline to Wk 16 (Figure 1). The proportion of pts with ID at Wk 16 was
52% in crFMF, 40% in HIDS/MKD and 46% in TRAPS cohort. AIDAI at Wk 16 correlated significantly with: SDS in all 3 cohorts;
PGA in HIDS/MKD and TRAPS; SF12–MCS in crFMF and HIDS/MKD (Table 1). CRP and SAA did not correlate with AIDAI.
Conclusion: Decrease in AIDAI scores over 16 weeks in crFMF, HIDS/MKD and TRAPS patients treated with canakinumab
corroborates rapid and sustained disease control with canakinumab in CLUSTER study. At Week 16, approximately half of the crFMF
and TRAPS patients, and 40% of the HIDS/MKD patients had inactive disease. AIDAI improvements at Week 16 correlated with
patient and physician driven evaluations (PGA, SF12–MCS and SDS). CRP and SAA are indicators of response to treatment rather than
a disease activity parameter.
1Piram M, et al. Ann Rheum Dis. 2014;73:2168-73.
2De Benedetti F, et al. Ann Rheum Dis. 2016;75:615-6.

.
Table 1. Correlation between AIDAI and disease activity/response variables at Week 16

Correlation coefficient (95% CI)
crFMF HIDS/MKD TRAPS
N=63 N=72 N=46

CRP -0.12 (-0.36; 0.14) 0.23 (-0.01; 0.45) 0.12 (-0.19; 0.42)
SAA -0.01 (-0.27; 0.25) -0.05 (-0.30; 0.21) 0.06 (-0.26; 0.37)
PGA 0.23 (-0.02; 0.46) 0.35§ (0.12; 0.55) 0.73* (-0.54; 0.85)
CHQ–PsCS -0.18 (-0.56; 0.26) -0.25 (-0.55; 0.11) -0.33 (-0.72; 0.22)
CHQ–PCS -0.33 (-0.66; 0.11) -0.46§ (-0.70; -0.14) -0.48 (-0.80; 0.04)
SF12–PCS -0.26 (-0.57; 0.11) -0.23 (-0.68; 0.35) -0.52‡ (-0.81; -0.03)
SF12–MCS -0.45‡
(-0.70; -0.10) -0.55‡ (-0.84; -0.03) 0.09 (-0.43; 0.56)
SDS 0.47† (0.22;
0.67) 0.37§ (0.10; 0.59) 0.41‡ (0.06; 0.67)
† § ‡
*p<0.0001; p<0.001; p<0.01; p<0.05
Disclosure: I. Koné-Paut, Novartis, SOBI and Roche, 2,Novartis, SOBI, Pfizer, AbbVie and Roche, 5; M. Hofer, Novartis and
AbbVie, 5; S. Benseler, Novartis, SOBI and AbbVie, 5; J. B. Kuemmerle-Deschner, Novartis, 2,Novartis, SOBI and Baxalta, 5; A.
Jansson, Novartis, 2; I. Rosner, None; R. Manna, Novartis, 2; S. Murias, None; O. Karadag, None; L. Tucker, Novartis, 2; I.
Orban, None; V. Tormey, None; M. Alessio, None; H. Ozdogan, Novartis, 5; F. De Benedetti, Novartis, Roche, Pfizer, SOBI,
AbbVie, Novimmune, BMS, Sanofi, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/improvement-of-disease-activity-in-patients-with-

colchicine-resistant-fmf-hidsmkd-and-traps-assessed-by-autoinflammatory-disease-activity-index-aidai-results-from-a-randomized-
phase-iii-trial
Novel Insights into Periodic Fever Syndromes

Tiffany Hoang1, Shreya Shrestha1 and Daniel Albert2, 1Dartmouth Medical School, Lebanon, NH, 2Medicine/Rheumatology,
Dartmouth-Hitchcock Med Ctr, Lebanon, NH
SESSION INFORMATION
Background/Purpose: The Periodic Fever Syndromes (PFS) are a rapidly expanding group of disorders primarily of the innate
immune system that often affect the inflammasome. In our previous report (ACR 2014 Annual Meeting), we detailed 30 patients with
about 1/3 with Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenopathy (PFAPA), 1/3 with a genetically defined PFS, and 1/3
unclassifiable. We now report with improved genetic testing (Medical Neurogenetics NextGen PFS Panel – 37 genes) novel phenotypic
expressions of genetically determined PFS in 15 patients.
Methods: Case acquisition was performed by three methods: 1) review of ICD 9/10 coded records for Familial Mediterranean Fever
(ICD 9 277.31); 2) laboratory test records for PFS genetic screening; and 3) clinic records between 1/1/2011 and 12/31/2017 after
receiving approval from the Institutional Review Board for a de-identified retrospective case analysis.
Results: Twenty seven cases (12 female and 15 male) were obtained that underwent extensive clinical evaluation including PFS genetic
screening. Clinical diagnoses included FMF (10), Muckle Wells (2), TRAPS (4), and HIDS (1). Other diagnoses included Crohn’s (1),
SoJIA (1), FUO (1), PFAPA (6), and cold induced urticaria (1). Of these 27 cases, 15 were subsequently associated with a genetic cause.
Seven of the 10 FMF cases were confirmed genetically, all of whom were either heterozygous or compound heterozygotes. Both cases
of Muckle Wells had non classical genetics – one was a compound heterozygote for CIAS 1, and the other had a mutation in the NOD
gene. Both TRAPS cases were atypical – one was asymptomatic, and the other developed SLE. Two patients had novel syndromes. One
TRAPS patient had a mutation in the TNFRSF-1A gene who eventually remitted with IVIG after failing multiple drugs. The other had
SoJIA with a mutation in the LPIN 2 gene but responded to colchicine. Only 1 of the 15 genetically proven cases had a classical
presentation and classical genetics (HIDS secondary to a mutation in the MVK gene).
Conclusion: Most patients presented atypically both from a clinical and genetic standpoint, making treatment challenging and difficult.
Genetic testing with PFS screen was helpful in over ½ of the cases to develop therapeutic treatment plans. Given the atypical clinical
presentations seen with genetically determined PFS, extensive genetic testing is indicated for all patients presenting with a PFS except
those with a classical PFAPA syndrome.
Disclosure: T. Hoang, None; S. Shrestha, None; D. Albert, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/novel-insights-into-periodic-fever-syndromes
Musculoskeletal Features in Copa Syndrome

William B. Lapin1, Monica Marcus2, Andrea A. Ramirez3, Marietta M. de Guzman3 and Levi B. Watkin4,5, 1Department of Pediatrics,
Division of Immunology, Allergy and Rheumatology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, 2Pediatric
Immunology, Allergy and Rheumatology, Texas Children's Hospital, Houston, TX, 3Immunology, Allergy and Rheumatology, Baylor
College of Medicine, Texas Children's Hospital, Houston, TX, 4Department of Pediatrics, Division of Immunology, Allergy and
Rheumatology, Baylor College of Medicine, Houston, TX, 5Texas Children's Hospital, Center for Human Immunobiology, Houston, TX
SESSION INFORMATION
Background/Purpose:
COPA syndrome is a newly discovered primary immunodeficiency resulting in immune dysregulation showing autosomal dominant
inheritance with incomplete penetrance. Its name is derived from the mutation of the gene encoding for the alpha subunit of the
coatomer complex-I that is responsible for transportation of molecular cargo from the Golgi to the Endoplasmic Reticulum. Previously,
studies have elucidated the molecular mechanisms responsible for the disease phenotype. Clinical features of COPA syndrome primarily
included pulmonary disease (interstitial lung disease, pulmonary hemorrhage), musculoskeletal (MSK) manifestations, autoantibody
formation and renal disease. Here we aim to review and describe the MSK features of this newly defined disorder.
Methods:
After IRB approval, we reviewed the MSK manifestations of patients with COPA mutation, as to characteristic nature, physical findings
and diagnostic features. The clinical course of a family from this cohort, that was followed at our institution, was described.
Results:
The previously reported cohort included 21 patients with 62% female. The mean age at presentation was 3.5 years with a range of 6
months to 22 years. Joint pain was present in 24% of patients at initial presentation and joint complaints were mostly intermittent in
nature. Findings of arthritis were described in 95% of patients involving both small and large joints along the clinical course, often with
polyarticular disease. Most commonly affected joints included the knees, and the interphalangeal joints of the hands. Two patients had
osteonecrosis along the femur, patella and tibiofibula. Fatty necrosis was noted in one patient. Notably, presence of autoantibodies was a
prominent feature of this disorder: rheumatoid factor (43%), ANA (67%), and ANCA/MPO/PR-3 (71%).
The most common diagnosis included Rheumatoid Arthritis, Juvenile Idiopathic Arthritis and undifferentiated arthritis. Arthralgia
exacerbation was found to mirror pulmonary disease flare. Joint manifestation had varying response to NSAID, steroids, methotrexate
and anti-TNF therapy. Multimodal anti-inflammatory, immunolytic and immunomodulatory therapy indicated for the severe pulmonary
and renal features did not provide prolonged remission of arthritis.
Table 1: COPA patients from single family carrying the R235H mutation
Patient Sex Age at Age at Ethnicity MSK Type of
disease arthritis features at arthritis
onset onset (y) presentation
(y)
1 M 2 4 Caucasian Knee Polyarticular
arthritis
2 F 1.25 Unknown Caucasian Ankle, Polyarticular
wrist
arthritis
3 M 12 12 Caucasian Shoulder Polyarticular
arthritis
4 F 4 9 Caucasian Wrist, ankle Polyarticular
arthritis
Conclusion:
Musculoskeletal manifestations are a prominent and important feature of COPA syndrome. Due to similarities in clinical features it is
difficult to differentiate COPA arthritis from other inflammatory arthropathies of systemic immune mediated disorders.
Disclosure: W. B. Lapin, None; M. Marcus, None; A. A. Ramirez, None; M. M. de Guzman, None; L. B. Watkin, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/musculoskeletal-features-in-copa-syndrome
H Syndrome: Five New Cases from the United States with Novel Features and
Responses to Therapy
Jessica Bloom1, Clara Lin2, Lisa F. Imundo3, Stephen Guthery4, Shelly Stepenaskie5, Csaba Galambos6, Amy Lowichik7 and John F.
Bohnsack8, 1Pediatrics, Children's Hospital Colorado, Aurora, CO, 2Pediatric Rheumatology, Children's Hospital Colorado, Aurora,
CO, 3Pediatrics, Columbia University Medical Center, New York, NY, 4Department of Pediatrics,, University of Utah, Salt Lake City,
UT, 5Pathology and Dermatology, University of New Mexico, Albuquerque, NM, 6Pathology, Children's Hospital Colorado, Aurora,
CO, 7Pathology, University of Utah, Salt Lake City, UT, 8Division of Allergy, Immunology and Pediatric Rheumatology, University of
Utah, Salt Lake City, UT
SESSION INFORMATION
Background/Purpose: H Syndrome is an autosomal recessive disorder characterized by cutaneous hyperpigmentation, hypertrichosis,
and induration with numerous systemic manifestations. The syndrome is caused by mutations in SLC29A3, a gene located on
chromosome 10q23, which encodes the human equilibrative transporter 3 (hENT3). Less than 100 patients with H syndrome have been
described in the literature, with the majority being of Arab descent, and only a few from North America. Here we report five pediatric
patients from three medical centers in the United States who were identified to have H syndrome by whole exome sequencing as well as
their response to treatment.
Methods: All five patients presented to pediatric rheumatologists prior to diagnosis and include two of Northern European descent,
bringing the total number of Caucasian patients described to three. Cases were discussed and compared in order to gather more data on
H Syndrome and optimize treatment regimens.
Results: The patients were found to share many of the characteristics previously reported with H syndrome, including
hyperpigmentation, hypertrichosis, short stature, insulin-dependent diabetes mellitus, arthritis and systemic inflammation, as well as
some novel features, including selective IgG subclass deficiency and autoimmune hepatitis. They share genetic mutations previously
described in patients of the same ethnic background, as well as a novel mutation. In two patients, treatment with prednisone improved
inflammation, however both patients flared once prednisone was tapered. In one of these patients, treatment with tocilizumab alone
resulted in marked improvement in systemic inflammation and growth. The other had partial response to prednisone, azathioprine, and
TNF inhibition; thus, his anti-TNF biologic was recently switched to tocilizumab due to persistent polyarthritis. Another patient
improved on Methotrexate, with further improvement after the addition of tocilizumab.
Conclusion: H syndrome is a rare autoinflammatory syndrome with pleiotropic manifestations that affect multiple organ systems and is
often mistaken for other conditions. Rheumatologists should be aware of this syndrome and its association with arthritis. Some patients
respond to treatment with biologics alone or in combination with other immune suppressants; in particular, treatment of systemic
inflammation with IL-6 blockade appears to be promising. Overall, better identification and understanding of the pathophysiology may
help devise earlier diagnosis and better treatment strategies.
Disclosure: J. Bloom, None; C. Lin, None; L. F. Imundo, None; S. Guthery, None; S. Stepenaskie, None; C. Galambos, None; A.
Lowichik, None; J. F. Bohnsack, Various, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/h-syndrome-five-new-cases-from-the-united-states-

with-novel-features-and-responses-to-therapy
Treatment Outcomes of Down Syndrome Arthropathy

Jordan T. Jones1, Leena Danawala2, Nasreen Talib3 and Mara L Becker4, 1Rheumatology Division, Children's Mercy Kansas City,
Kansas City, MO, 2University of Missouri-Kansas City School of Medicine, Kansas City, MO, 3General Pediatrics, Children's Mercy
Kansas City, Kansas City, MO, 4Rheumatology, Children's Mercy Kansas City, Kansas City, MO
SESSION INFORMATION
Background/Purpose: Crude prevalence estimates indicate Down syndrome arthropathy (DA) is 3-8 times more common than juvenile
idiopathic arthritis (JIA), however, DA is still largely under recognized, and has a 2 year average delay from onset of symptoms to
diagnosis. The majority of patients with DA present with greater than 5 affected joints, with small joints affected more predominantly.
Additionally, treatment can be challenged by lack of efficacy and intolerance. Further, gaps in literature exist around optimal treatment
approach and outcomes. The objective of this study was to investigate treatment approach and outcomes of DA at our institution.
Methods: In a retrospective chart review, potential DA patients were identified through electronic medical record system (EMR) from
January 1, 1995 to December 31, 2015. ICD-9-CM codes were used to identify patients (less than 18 years of age) with both Down
Syndrome (DS; 758.0) and JIA (714.3, 714.31, 714.32, 714.33). Individual charts were then manually reviewed to confirm diagnosis of
DS and JIA. Chart review included analysis of all documents found in the EMR, including clinical visits and treatment data.
Results: Of 26 identified patients, (3 did not have DS and 2 had incomplete records) 21 met inclusion criteria and were analyzed.
Patients were 62% female with polyarticular, RF negative presentation at diagnosis and had a mean (SD) follow-up of 4 (±4) years.
There was a 19 month (±16) mean delay in diagnosis of arthritis from symptom onset, and at diagnosis of arthritis, 71% had morning
stiffness with an average of 14 (±10) active joints, 12 (±10) limited joints, and mean physician global of disease activity (MD PGA) of
4.9 (±2). All patients were started on nonsteroidal anti-inflammatory drugs (NSAIDs) at diagnosis with 33% simultaneously starting a
disease modifying antirheumatic drug (DMARD), and 5 % a Biologic. Over the course of disease, 62% used a DMARD (57% MTX)
and 48% used a biologic (90% etanercept). Six patients (29%) had at least one change in DMARD and another six patients had at least
one change in biologic therapy (Table 1). Compared to diagnosis, at the last recorded visit there was a significant decrease in mean (SD)
active joints: 3 (± 4), limited joints: 5 (± 6) and MD PGA: 1.7 (± 1.6) (p<0.01 respectively). Of those on DMARD therapy 54% had
drug discontinuation due to side effects and 56% had an inadequate response to first-line biologic therapy.
Conclusion: Down syndrome arthropathy remains under recognized despite reports of higher prevalence compared with JIA. Although
treatment approach is unclear, DA patients have significant improvement in the number of active and limited joints with NSAID,
DMARD, and biologic therapies. Other barriers that inhibit optimal treatment and outcomes are DMARD toxicity and lack of anti-TNF
effectiveness. More research is needed to determine the timing and choice of optimal therapy in patients with Down syndrome.
Disclosure: J. T. Jones, None; L. Danawala, None; N. Talib, None; M. L. Becker, Bristol Myers Squibb, 2,Sobi, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/treatment-outcomes-of-down-syndrome-arthropathy
Down’s Arthritis (DA) – Clinical and Radiological Features of Arthritis in Children

with Trisomy 21
Charlene Foley, Emma Jane Mac Dermott and Orla Killeen, National Centre for Paediatric Rheumatology, Our Lady's Children's
Hospital Crumlin, Dublin, Ireland
SESSION INFORMATION
Background/Purpose: Down's Arthritis (DA) was first reported in the literature in 1984. Crude estimates suggest higher incidence and
prevalence rates of DA compared with Juvenile Idiopathic Arthritis (JIA), (JIA prevalence 1/1000, estimated DA prevalence 8.7/1000).
Despite this fact, there remains a paucity of data on this condition. DA is rarely recognised at onset, & remains under-diagnosed. As a
direct consequence children with DA are presenting with significant joint damage and disability at diagnosis. Our aim was to perform a
musculoskeletal examination on children with Trisomy 21 (T21) aged 0-20 years, looking specifically for features of undiagnosed
arthritis. We also wanted to better define the disease in terms of it's clinical and radiological features.
Methods: Children with T21 were invited to attend a screening clinic. Screening involved completion of a health questionnaire and a
comprehensive musculoskeletal examination. DA cases detected were investigated & managed as per normal clinical practice. Data on
a convenience sample of 33 newly diagnosed children with JIA was collected to create a comparison group.
Results: 503 children with T21 were screened for DA and 22 new cases identified. All of these children had poor language skills or
were non-verbal. Only 11% of the parents suspected that their child may have arthritis prior to attending our screening clinics, and this
was only after reading our recruitment literature. In total, we now have 33 children attending our centre with DA (combining cases
attending pre-dating the start date of the study). This suggests the prevalence of DA in Ireland is 18-21/1000.
The majority of children presented with a polyarticular RF negative pattern of disease. No cases of uveitis have been observed to date.
Small joint involvement of the hands was observed in 88% of the DA cohort, significantly higher than in the JIA comparison group
(43%, p<0.01). Erosive changes were reported on X-Ray in 29.2% of the DA cohort (9.5% in the JIA Cohort). Methotrexate-associated
nausea was a significant barrier to treatment with this DMARD in DA. There was a significant delay in diagnosis of DA, 1.7 years (0.2-
4.9yrs) versus 0.7 years (0..2-2.4yrs) in the JIA cohort.
Conclusion: Children with T21 are at increased risk of developing arthritis. There is a lack of awareness of this risk among health care
professionals & the general public at large. This almost certainly contributes to poor recognition of the disease and a delay in diagnosis.
The predominant pattern of disease is polyarticular small joint arthritis. Treatment with standard protocols used in JIA is complicated by
drug-associated side effects in children with T21. However, a good response to treatment with steroid intra-articular joint injections and
anti-TNF therapy has been observed. Our study has raised a number of questions. Our on-going research aims to accurately define this
disease in terms of its immunological, histopathological and genetic basis, & identify best practice with regards to treatment. We
advocate that all children with T21 should have an annual musculoskeletal examination as part of their health surveillance programme.
Disclosure: C. Foley, None; E. J. Mac Dermott, None; O. Killeen, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/downs-arthritis-da-clinical-and-radiological-

features-of-arthritis-in-children-with-trisomy-21
Radiological Features Identified in the Hands of Children with Down Syndrome and
Inflammatory Arthritis
Charlene Foley1, Emma Jane Mac Dermott1, Aisling Snow2 and Orla G Killeen1, 1National Centre for Paediatric Rheumatology, Our
Lady's Children's Hospital Crumlin, Dublin, Ireland, 2Radiology, Our Lady's Children's Hospital Crumlin, Dublin, Ireland
SESSION INFORMATION
Background/Purpose: Down’s Arthritis (DA) is an inflammatory joint condition affecting children with Down syndrome (DS). It is
18-21 times more common than JIA in the general paediatric population (JIA prevalence 1/1000). Children with DA usually present
with a poly-articular, RF negative pattern of disease, with predominance in the small joints of the hands & wrists. Despite it’s higher
prevalence, a significant delay in diagnosis is frequently observed. Joint laxity & hypotonia are almost universal in children with DS,
contributing to an increased risk of a number of musculoskeletal disorders & degenerative joint disease. Clinical signs & symptoms may
not always help differentiate between inflammatory joint disease & joint hypermobility. We aim to report the radiological features
described by a Paediatric Musculoskeletal Radiologist (PMR) when reviewing hand & wrist radiographs in a cohort of children with
DA.
Methods: A retrospective review of all hand & wrist radiographs in a convenience sample of 19 children with DA was undertaken by a
PMR. Bone age, carpal & metacarpal bone abnormalities were documented, as were corresponding clinical findings following
musculoskeletal examination by a Paediatric Rheumatologist. Wrist MRIs were performed on 4 of the 19 children. The results of these
studies were also included in our report.
Results: 18/19 children (10/19 (53%) Female; Average Age 13yrs (0.8-19yrs); 100% Full Trisomy 21 genetics) had radiographs of their
hands & wrists. Bone age was below chronological age in 5 (28%) of the cohort imaged. Time to DA diagnosis from symptom onset
was known in 8/19 children & on average was 1.8 years (0.14-4.9 years). Over half (63%) of the cohort were detected through a
musculoskeletal screening programme offered to children with DS & not from direct referral to the Tertiary Rheumatology Centre. On
musculoskeletal examination the most commonly affected joints, 95% of cases, were the PIP joints, followed by the wrists (68%), knees
(58%), toes (37%) & MCP joints (32%). The average joint hypermobility score using the Beighton system was 2 (0-6).
Radiograph & MRI review highlighted a range of carpal & metacarpal bone abnormalities. The most common abnormality was
crowding of the carpal bones with associated degenerative disease (63%). The earliest sign of degenerative disease was observed in a
child aged 10 months whose MRI with gadolinium contrast demonstrated synovial enhancement of the proximal carpal row. The second
most common finding (42%) was scalloping of the base of the first metacarpal. Other less frequent features identified (5% of cohort)
included carpal pits, tuft irregularity & dactylitis. Bone erosions were evident on plain film in 50% of the cohort.
Conclusion: Radiographic carpal & metacarpal bone changes appear to be prevalent in DA & do not always correspond to clinical
signs & symptoms. Undetected, these features can have a significant functional impact. If detected & managed in a timely &
appropriate manner, irreversible joint damage & long-term sequelae could be avoided. These results support the importance of access to
a specialist PMR & MRI. Our plan now is to compare these results with two separate cohorts; children with JIA & children with DS
with no evidence of inflammatory arthritis.
Disclosure: C. Foley, None; E. J. Mac Dermott, None; A. Snow, None; O. G. Killeen, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/radiological-features-identified-in-the-hands-of-

children-with-down-syndrome-and-inflammatory-arthritis
Immunogenicity of 13 Valent Pneumococcal Vaccine in Children with Lupus: Single

Center Experience in South Texas
Elissa Gonzalez, Joe Cole and Mark Gorelik, Pediatrics, Baylor College of Medicine/Children's Hospital of San Antonio, San Antonio,
TX
SESSION INFORMATION
Background/Purpose: Pneumococcal vaccination is an important part of the care of pediatric and adult patients with systemic lupus
erythematosus, and is recommended as a quality indicator for management of children with SLE. Literature on the immunogenicity of
pneumococcal vaccines in children is scant. As part of a quality improvement project to increase the rates of pneumococcal vaccination
in our center, we sought to evaluate immunogenicity to the 13-valent pneumococcal vaccine in our patients with lupus, and also to
identify patients that may be at higher risk of infection due to non response.
Methods: Patients undergoing vaccination with 13-valent pneumococcal vaccine had pre-vaccination antibody levels to serotypes
obtained when possible, and then post-vaccination antibody levels were obtained 4 weeks after vaccination. The percentage and number
of patients with pre and post vaccination protective levels (defined as >70% serotypes >/= 1.3 mcg/dl) were evaluated. Medication
status, disease activity and demographic information was obtained from these patients as well.
Results: 15 patients had pre and post pneumococcal antibody levels avaialble for evaluation, and a further 5 had post pneumococcal
antibody levels only. 5 of 15 patients had pre-vaccination protective levels of pneumococcal antibody despite no known previous
vaccination. 8 of 10 patients with both pre and post pneumococcal antibody levels available demonstrated conversion to protective
status, while 2 did not; a further 3 of the 5 patients who had post pneumococcal levels only available did not demonstrate achievement
of protective levels. Thus in total, 15 of 20 patients achieved protected status. Patients not achieving protected status had a higher rate of
recent rituximab or higher dose mycophenolate treatment, while patients with previous cytoxan exposure generally achieved protected
status.
Conclusion: While the 13-valent pneumococcal vaccine achieves protective status for a majority of pediatric lupus patients, a
significant number of these patients do not achieve this status after this vaccine. Further evaluation for responses after 23-valent
vaccination is ongoing, but these results suggest that patient responses to vaccination may be important to evaluate in order to identify
patients that are at higher risk of future infection.
Disclosure: E. Gonzalez, None; J. Cole, None; M. Gorelik, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/immunogenicity-of-13-valent-pneumococcal-

vaccine-in-children-with-lupus-single-center-experience-in-south-texas
Protection Against Hepatitis B in Immunocompromised Pediatric Rheumatology and

Gastroenterology Patients
Najla Aljaberi1, Emily A. Smitherman2, Enas Ghulam3, Allen Watts2, Dana MH Dykes4 and Jennifer L. Huggins5, 1Pediatric
rheumatology, Pediatric Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2Pediatric Rheumatology,
Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 3Environmental health and biostatistics, Department of Environmental
Health, University of Cincinnati, Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center,
Cincinnati, OH, 4Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH,
5Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
SESSION INFORMATION
Background/Purpose:
Hepatitis B infection remains a significant public health challenge, particularly for patients on chronic immunosuppressive therapy, due
to a considerable mortality risk associated with hepatitis B reactivation. Serologic screening for immunocompromised patients should
include hepatitis B surface antibodies (anti-HBsAb) to assess for immunity, hepatitis B core antibodies (anti-HBcAb) and hepatitis B
surface antigen (HBsAg) to evaluate for acute or chronic infection. Our primary aim was to determine the burden of non-immunity
against hepatitis B, provide insight into factors leading to lack of immunity against hepatitis B and establish the basis for the need for
universal screening of these patients. Secondarily, we determined serologic response to a single hepatitis B vaccination booster.
Methods:
Subjects are patients seen at the rheumatology and inflammatory bowel disease (IBD) clinics who are immunocompromised. We use a
clinical algorithm as part of standard practice to check hepatitis B serology in immunocompromised patients, offer a booster vaccination
if needed, and then repeat serology to determine the response. The results of anti-HBsAb are reported as positive, negative or
indeterminate. Immunity is defined as a positive result for anti-HBsAb. An indeterminate or negative result for anti-HBsAb is non-
immune. A retrospective chart review was performed to collect demographic and clinical factors as well as serology results. Descriptive
statistics were calculated for all variables. R software was used to perform all analyses. For continuous variables, mean and standard
deviation are reported, and comparisons were calculated using two-sample t-tests. For categorical variables, frequency and percentage
are reported, and comparisons were calculated using chi-square tests.
Results:
A total of 502 patient charts of immunocompromised patients were reviewed, 280 rheumatology and 222 IBD. Out of the 502 patients,
70% were non-immune (anti-HBsAb negative/indeterminate) (see Table). The highest portion of non-immune patients were those
between the ages of 16-20 years (p=0.005) There was no clinically significant difference between immune and non-immune patients
with regards to diagnosis (p=0.69), age at the start of treatment (p=0.72) or type of medications. A total of 196 non-immune patients
received a booster dose of hepatitis B vaccine and 61 (72%) of those re-screened developed a positive anti-HBsAB. Of note, one patient
was identified with a previously unknown chronic hepatitis B infection (anti-HBcAb positive).
Conclusion:
A majority of patients had non-immune hepatitis B serology. Lack of serologic immunity is highest at 16-20 years. A majority of
patients developed positive anti-HBsAb following booster vaccination. Results support serologic screening for hepatitis B in
immunocompromised patients.
Disclosure: N. Aljaberi, None; E. A. Smitherman, None; E. Ghulam, None; A. Watts, None; D. M. Dykes, None; J. L. Huggins,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/protection-against-hepatitis-b-in-

immunocompromised-pediatric-rheumatology-and-gastroenterology-patients
Reliable Implementation of a Hepatitis B Serology Screening and Vaccination

Process for Immunocompromised Pediatric Rheumatology Patients
Emily A. Smitherman1, Adam Furnier2, Allen Watts1, Sandra Kramer1, Elizabeth Joy Baker1, Dana MH Dykes3, Rebecca Brady4 and
Jennifer L. Huggins5, 1Pediatric Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2James M. Anderson
Center for Health Systems Excellence, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 3Gastroenterology, Hepatology,
and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 4Infectious Diseases, Cincinnati Children's Hospital
Medical Center, Cincinnati, OH, 5Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
SESSION INFORMATION
Background/Purpose: Vaccine-preventable infections, including reactivation of hepatitis B virus, are a leading cause of morbidity and
mortality in immunocompromised patients. Guidelines recommend that all immunosuppressed patients should be screened with
hepatitis B serologies for active or chronic infection as well as need for repeat vaccination. Previously at our center, we have
implemented hepatitis B serology screenings for patients on intravenous biologics and pneumococcal vaccines for all
immunocompromised patients. The aim of this intervention was to adapt these processes to hepatitis B serology screenings and
vaccinations for all immunocompromised pediatric rheumatology patients.
Methods: The Model for Improvement was used to form a team, map the process, construct a key driver diagram, and develop an
algorithm (Figure 1). Eligible patients included those over 7 years identified as immunocompromised using a validated algorithm in the
electronic health record (EHR). A series of Plan-Do-Study-Act (PDSA) cycles were performed to test and implement the multi-step
process. After building an electronic order-set in the EHR, we adopted the process of clinic staff pending needed orders during pre-visit
planning. We also provided education and developed “talking points” for clinic staff and providers. Results were tracked on a statistical
process control chart weekly, and failures were identified through Pareto analysis.
Results: The intervention began in December 2016 at a tertiary care pediatric rheumatology clinic. Prior to start, a subset of patients
had previously received screenings and vaccines due to an initial process for patients on intravenous biologics. However, by
systematically adopting interventions, we were able to rapidly and reliably achieve our goal performance (Figure 2). There were few
failures for the serology screenings from orders not signed. Failures for vaccine administration included deferred, primary care
preference, refusal, leaving before vaccine, and vaccine orders not signed. To date, we have screened 862 patients and administered 302
booster vaccines.
Conclusion: By adapting processes that were previously successful in our clinic setting, we were able to reliably implement a hepatitis
B serology screening and vaccination program over a short time-frame. Next steps include sustainability planning and spread to other
clinics with immunocompromised patients. The results of this project support the importance of adoption and spread of successful
processes in order to expedite improvement in quality of care.
Disclosure: E. A. Smitherman, None; A. Furnier, None; A. Watts, None; S. Kramer, None; E. J. Baker, None; D. M. Dykes, None;
R. Brady, Pfizer Inc, 2; J. L. Huggins, Pfizer Inc, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/reliable-implementation-of-a-hepatitis-b-serology-

screening-and-vaccination-process-for-immunocompromised-pediatric-rheumatology-patients
Analysis of the Effectiveness of Immunization with Pneumococcal Polysaccharide

Vaccine in Children with Juvenile Idiopathic Arthritis
Ekaterina Alexeeva1,2, Tatiana Dvoryakovskaya1, Rina Denisova1, Olga Lomakina1, Ksenia Isaeva1, Margarita Soloshenko1, Anna
Karaseva1, Nikolay Mayansky3, Irina Zubkova3, Darija Novikova4, Anna Gayvoronskaya4, Natalia Tkachenko4, Marika Ivardava4,
Firuza Shakhtakhtinskaya4 and Marina Fedoseenko4, 1Reumatology department, Federal State Autonomous Institution"National
Scientific and Practical Center of Children's Health"Of the Ministry of Health of the Russian Federation, Moscow, Russian Federation,
2Pediatrics, The Federal State Autonomous Educational Institution of Higher Education The First Moscow State Medical University
named after I.M. Sechenov Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russian Federation, 3Clinical
laboratory, Federal State Autonomous Institution"National Scientific and Practical Center of Children's Health"Of the Ministry of
Health of the Russian Federation, Moscow, Russian Federation, 4Department of Vaccine Prevention, Federal State Autonomous
Institution"National Scientific and Practical Center of Children's Health"Of the Ministry of Health of the Russian Federation, Moscow,
Russian Federation
SESSION INFORMATION
Background/Purpose: Juvenile idiopathic arthritis (JIA) is one of the most frequent and most disabling rheumatic diseases in
childhood. Children suffering from JIA receiving immunosuppressive and genetically engineered biological agents belong to the
high risk group for the development of bacterial and viral infections, including those managed by vaccine preventive means.
Objectives: To evaluate the effectiveness of vaccination of 13-valent pneumococcal polysaccharide vaccine (PPV) in children
with JIA for the level of specific anti-pneumoconve antibodies (anti-SPP) IgG for Streptococcus pneumonia in the blood serum
in patients with JIA before and after vaccination, as well as by recording the number of infections of the upper respiratory tract
and pneumonia.
Methods: In a prospective, open comparative study, the effectiveness of vaccination was determined by the level of specific anti-
pneumoconve antibodies (anti-SPP) IgG to Streptococcus pneumonia in serum in patients with JIA, as well as by the number of
adverse events, the number of infections of the upper respiratory tract and pneumonia. An open prospective comparative study
was conducted, which included 42 children with JIA: 21 children with JIA in the active stage of the disease, 21 - in remission of
the disease. Vaccination with 13-valent conjugated PPV vaccine was carried out once in a dose (0.5 ml) subcutaneously, against
the background of therapy of the underlying disease with methotrexate or etanercept, or 3 weeks before the appointment of
methotrexate or etanercept.
Results:
The study included 42 children with JIA: 21 with JIA in the active stage of the disease, 21 - in remission of the disease. As a
result of vaccination of all patients, an increase in the level of anti-pneumococcal antibodies (anti-SPP) IgG in children with JIA
in the active stage was observed from 23.9 to 51.6 mg /l, with JIA in the remission phase from 26.1 to 73.0 mg /l (p = 0.005).
Episodes flare of of JIA were not detected in any subject patient. Analysis of the frequency of ENT organs infections (otitis,
rhinitis, sinusitis, tonsillitis, adenoiditis) and lower respiratory tract before and 12 months after vaccination showed a
statistically significant decrease in the incidence rate. In the JIA group at the stage of remission of the disease, this index was 4
(3, 7) cases per year, after vaccination, it was reduced to 2 (1; 2) (p = 0.001). A similar situation was observed in the group of
children with exacerbation of the disease: before the vaccination, the median number of cases of infection with ENT organs was
4 (3; 4); within 12 months after the vaccination, the index decreased to 1 (1, 2) cases (p = 0.001). Pneumonia and / or bronchitis
for 1 year after vaccination are not registered in any patient. Serious adverse events were not recorded during the study.
Conclusion: Thus, vaccination of 13-valent PPV of 13 PPV of children with JIA in the remission phase receiving MT or
etanercept and children in the acute stage prior to the initiation of immunosuppressant or GIBP is highly effective, and is not
accompanied by exacerbation / increase in the activity of the disease and the development of serious undesirable phenomena.
Disclosure: E. Alexeeva, Roche Pharmaceuticals, 2; T. Dvoryakovskaya, Roche Pharmaceuticals, 2; R. Denisova, None; O.

Lomakina, None; K. Isaeva, None; M. Soloshenko, None; A. Karaseva, None; N. Mayansky, None; I. Zubkova, None; D.
Novikova, None; A. Gayvoronskaya, None; N. Tkachenko, None; M. Ivardava, None; F. Shakhtakhtinskaya, None; M.
Fedoseenko, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/analysis-of-the-effectiveness-of-immunization-with-

pneumococcal-polysaccharide-vaccine-in-children-with-juvenile-idiopathic-arthritis
F4/80hi Synovial Macrophages in the Pathogeneses of Spontaneous Inflammatory

Arthritis in CD11c-Flip-KO (HUPO) Mice
Qi Quan Huang1,2, Renee E. Doyle2, Philip J. Homan1, Harris Perlman3, Deborah R. WInter4 and Richard M. Pope2, 1Division of
Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL,
2Medicine/Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, 3Medicine, Northwestern University
Feinberg School of Medicine, Chicago, IL, 4Department of Medicine Division of Rheumatology, Northwestern University Feinberg
School of Medicine, Chicago, IL
SESSION INFORMATION
Session Title: Rheumatoid Arthritis – Animal Models Poster I
Background/Purpose:
Synovial tissue macrophages (STMs) are critical in the pathogenesis of rheumatoid arthritis (RA). During homeostasis, the majority of
murine synovial tissue resident macrophages (TRMs) are MHCII-Ly6C- and TRMs in other tissues are F4/80hi. In our novel CD11C-
Flip-KO (HUPO) mouse model of RA, erosive, progressive arthritis develops spontaneously. This study examined the F4/80hi subsets
of ankle macrophages from HUPO mice with arthritis and littermate controls.
Methods:
Arthritis was evaluated by clinical score. Cell types within the ankle joints were determined by flow cytometry. STMs were defined as
CD45+CD11b+CD64+F4/80+, which were further grouped into subsets according to the expression of F4/80, MHCII and Ly6C. Subsets
of F4/80hi STMs were isolated for RNAseq.
Results:
All STMs that are F4/80hi were also Ly6C- in both HUPO and control mice. In the controls mice, under homeostatic conditions, ~80%
of the Ly6C-F4/80hi STMs were MHCII- and 20% MHCII+, and those that are MHCII- were considered TRMs. In contrast, in HUPO
mice with arthritis the F4/80hiMHCII+ macrophages are greatly increased representing >90%, while the F4/80hi MHCII- macrophages
were markedly reduced (<10%), and this reduction was inversely correlated with arthritis severity and duration. In HUPO mice, by flow
cytometry, IL-6 expressing cells are increased in both MHCII+ and - subsets, while IL-10 expressing cells were reduced, compared with
controls. The F4/80hi STM populations were further analyzed by RNAseq. From over 5,000 differentially expressed genes, a similarity
analysis demonstrated limited correlation between HUPO and control F4/80hi STMs. Further, functionally distinct clusters were
identified between HUPO and controls. For both MHCII+ and- subsets, cell differentiation and cell morphogenesis pathways were
reduced, while pathways for innate immunity and inflammation were increased in the HUPO mice. In contrast, differences between the
MHCII+ and the MHCII- subsets were observed for antigen processing and presentation and the regulation of hematopoiesis in the
control mice, while metabolic processes and for tRNA and ntRNA regulation were differentially expressed in the HUPO mice.
Conclusion:
These observations demonstrate that F4/80hi STMs are markedly different under homeostatic and inflammatory conditions. The
reduction of TRMs and an increase of inflammatory F4/80hiMHCII+ macrophages contribute to the pathogenesis of HUPO arthritis.
Further studies on the regulation of macrophage biology under homeostatic and chronic inflammatory conditions will help inform the
pathogenesis of RA.
Disclosure: Q. Q. Huang, None; R. E. Doyle, None; P. J. Homan, None; H. Perlman, None; D. R. WInter, None; R. M. Pope,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/f480hi-synovial-macrophages-in-the-pathogeneses-

of-spontaneous-inflammatory-arthritis-in-cd11c-flip-ko-hupo-mice
Induction of Anti-Citrullinated Protein Antibodies By Peptidyl Arginine Deiminase

Immunization: A New Model for the Development of Anti-Citrullinated Protein
Antibodies in Rheumatoid Arthritis
Fanny Arnoux1,2, Nathalie Lambert1,3, Nathalie Balandraud1,2,4, Jean Roudier1,3,5 and Isabelle Auger1,2, 1Aix Marseille University,
Marseille, France, 2INSERM UMRs 1097, Marseille, France, 3Arthrites auto-immunes, INSERM UMRs 1097, Marseille, France,
4APHM, Marseille, France, 5Rheumatology dept, APHM, Marseille, France

SESSION INFORMATION
Background/Purpose:
The most important immunological event in rheumatoid arthritis (RA) is the development of anti-citrullinated protein autoantibodies
(ACPAs). ACPAs are present in 2/3 of patients. The mechanisms leading to the production of ACPAs are unknown. ACPAs are
produced in the absence of identified T cell responses specific for each citrullinated protein. Peptidyl arginine deiminase 4 (PAD4),
which binds numerous proteins and citrullinates them is the target of autoantibodies in early RA. This suggests a model for the
emergence of ACPAs in the absence T cells specific for each citrullinated antigen: anti-citrullinated protein autoantibodies could arise
because PADs are recognized by T cells which help the production of autoantibodies to proteins being citrullinated by PADs, according
to a “hapten/carrier” model. Here, we tested this model in mice.
Methods:
We used C3H mice which express a particular IEbk whose third hypervariable region is highly homologous to that of RA-associated
HLA-DRB1*04:01 allele and DBA/2 mice whose IEbdis similar to that of non RA-associated HLA-DRB1*04:02. Mice were
immunized subcutaneously with PADs or phosphate buffered saline (PBS) in Freund’s complete adjuvant (CFA). Three booster
injections of PAD or PBS in Freund’ incomplete adjuvant (IFA) were given subcutaneously 15, 35 and 55 days later. Sera from primed
mice were: 1) tested for anti-PAD antibodies by ELISA. 2) tested for T cell responses to native or citrullinated fibrinogen 65 days after
PAD immunization. 3) tested for anti-citrullinated fibrinogen antibodies by ELISA using fibrinogen peptides under citrullinated and
native form.
Results:
C3H mice immunized with human PAD2 or PAD4 developed antibodies and T cells to PADs and IgG antibodies to citrullinated
peptides from fibrinogen, in the absence of T cell response to fibrinogen. To test whether the observed hapten carrier effect applies to
immunization with self-proteins, we immunized C3H mice with murine PAD2 or PAD4 and looked for antibodies to peptides from
fibrinogen under native or citrullinated form. The hapten carrier effect also occurred in the self-situation. Finally, to analyze the effect of
the MHC background on hapten carrier immunization, we immunized DBA/2 mice whose IEbdis similar to that of non RA-associated
HLA-DRB1*04:02. DBA/2 mice failed to develop antibodies to citrullinated fibrinogen peptides.
Conclusion:
T cell immunization to PAD proteins triggers ACPAs through a hapten carrier mechanism in which the carrier is PAD which performs
citrullination and the hapten any protein being citrullinated by PAD.
Disclosure: F. Arnoux, None; N. Lambert, None; N. Balandraud, None; J. Roudier, None; I. Auger, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/induction-of-anti-citrullinated-protein-antibodies-

by-peptidyl-arginine-deiminase-immunization-a-new-model-for-the-development-of-anti-citrullinated-protein-antibodies-in-
S-110483 a New Potent EP4 Receptor Antagonist with Immunomodulatory and

Analgesic Activities
Takashi Maeda1, Toshitaka Ochiai2, Toshie Nagayasu-Tanaka1, Yuta Morisaki1, Haruka Takizawa1, Seiji Ishihara1, Shigeo
Kurokawa1, Kiyoharu Ukai1 and Masahiro Suda1, 1Pharmacology Department, Kaken Pharmaceutical Co., LTD, Kyoto, Japan, 2Kaken
Pharmaceutical Co., LTD, Kyoto, Japan
SESSION INFORMATION
Background/Purpose: Prostaglandin (PG) E2 is known to enhance the expansion of T helper 17 (Th17) cell population via EP4
receptor (EP4) in the early phase of rheumatoid arthritis (RA). Furthermore, EP4 signals are involved in inflammatory hyperalgesia.
Therefore, EP4 antagonists would be useful disease modified anti-rheumatic drugs (DMARDs) with analgesic effect. On the basis of
this concept, pharmacological characteristics of S-110483, our novel potent and selective EP4 antagonist, were compared with existing
EP4 antagonists; in addition, evidence regarding the immunomodulatory/analgesic potential of S-110483 is provided using an RA
model.
Methods: The antagonistic activities of S-110483 and existing EP4 antagonists were evaluated in mammalian cells overexpressing rat,
mouse, or human EP4. The effects of S-110483 on the production of PGE2 and PGI2 were evaluated using human umbilical vein
endothelial cells (HUVEC) stimulated with IL-1β. For estimating the effects on the Th17 expansion, inhibition of IL-23 release from
mouse dendritic cells was measured. The anti-edema and analgesic effects of S-110483 were evaluated by using rat adjuvant-induced
arthritis (AIA) models as follows. Rats received intradermal injections of adjuvant suspension on their left hind paw (day 0). S-110483
(0.003–3 mg/kg) or celecoxib (0.003–3 mg/kg) were orally administered once a day on days 9–20. On day 18, anti-hyperalgesia effects
were evaluated by measuring the vocalization threshold. Anti-edema effects were evaluated by paw volume of day 8, day 14, and day
18.
Results: S-110483 showed potent antagonistic activities for the rat/mouse/human EP4 with IC50 of 10.9/9.0/5.4 nmol/L, respectively.
S-110483 (10–1000 nmol/L) did not inhibit PGE2 and PGI2 production from HUVEC. S-110483 dose-dependently inhibited IL-23
release from activated mouse dendritic cells. The in vitro evaluation including the EP4 antagonistic activity revealed that S-110483 is
the most potent and effective antagonist among existing EP4 antagonists. In the AIA models, S-110483 (0.3 mg/kg) had considerable
analgesic and anti-inflammatory effects. Compared to celecoxib, S-110483 showed the maximum anti-hyperalgesic effects starting at
dose that was 10 times lower.
Conclusion: Our studies demonstrated that S-110483 is the best in class among EP4 receptor antagonists, and it shows not only
immunomodulatory effects but also anti-inflammatory and analgesic effects without inhibiting PGE2 and PGI2 production. These
findings suggested that S-110483 could become a superior therapeutic option in RA patients.
Disclosure: T. Maeda, None; T. Ochiai, None; T. Nagayasu-Tanaka, None; Y. Morisaki, None; H. Takizawa, None; S. Ishihara,
None; S. Kurokawa, None; K. Ukai, None; M. Suda, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/s-110483-a-new-potent-ep4-receptor-antagonist-

with-immunomodulatory-and-analgesic-activities
S-110483, a Novel and Selective EP4 Receptor Antagonist with Anti-Bone

Destruction Activities
Toshitaka Ochiai1, Takashi Maeda2, Toshie Nagayasu-Tanaka2, Jun Anzai1, Daiki Kato1, Yuta Morisaki2, Kiyoharu Ukai2 and
Masahiro Suda2, 1Kaken Pharmaceutical Co., LTD, Kyoto, Japan, 2Pharmacology Department, Kaken Pharmaceutical Co., LTD,
Kyoto, Japan
SESSION INFORMATION
Background/Purpose: S-110483 is our novel potent and selective EP4 receptor (EP4) antagonist. In addition to the well-known fact
that EP4 antagonists have anti-inflammatory effects, it has recently been shown that the prostaglandin E2-EP4 signal is involved in
osteoclastogenesis through RANKL expression in osteoblasts. Therefore, EP4 antagonists are expected to become useful DMARDs
with anti-inflammatory and anti-bone destruction effects. The objective of this study is to clarify the usefulness of S-110483 as a novel
DMARD, and it consists of the following experiments. (1) To evaluate the effects of S-110483 on the osteoclastogenesis and RANKL
expression as well as (2) to evaluate the therapeutic potentials of S-110483 as a novel DMARD using rat arthritis models.
Methods: 1. Osteoclastogenesis: Mice bone-marrow cells were stimulated with M-CSF/RANKL and the numbers of differentiated
osteoclasts were counted. 2. RANKL expression on osteoblasts: Mice preosteoblast cell line (MC3T3-E1) was stimulated with IL-1β
and RANKL expression was evaluated. 3. The therapeutic effects of S-110483 and DMARDs on an adjuvant-induced arthritis (AIA)
model: Rats were orally administered S-110483 or DMARDs for 25 days starting immediately after the adjuvant injection. Paw
volumes were measured regularly. Twenty-five days after the adjuvant injection, rats were sacrificed and the wet weight of the thymus
was measured. Furthermore, bone condition was evaluated by using X-ray and micro CT analysis. 4. Therapeutic effects of S-110483
and celecoxib on collagen-induced arthritis (CIA) model: DA rats were immunized with type-II collagen in CFA, and arthritis score and
the paw volume were measured regularly. S-110483 or celecoxib was administered orally once a day from arthritis onset. Sixteen days
after arthritis onset, bone condition was evaluated.
Results: 1. S-110483 (1–10 µmol/L) inhibited the osteoclastogenesis and its effect was more potent than tofacitinib and MTX. 2. S-
110483 (1–10 µmol/L) also inhibited RANKL expression of osteoblast as well as DMARDs. 3. In the AIA model, anti-edema and anti-
bone destruction effects of S-110483 were comparable with those of MTX (1 mg/kg), and were more potent than those of tofacitinib (10
mg/kg) and iguratimod (10 mg/kg). Furthermore, S-110483 showed the inhibitory effect on inflammation-related bone formation, unlike
DMARDs, suggesting that S-110483 possessed excellent inhibitory effects on joint deformity. Interestingly, S-110483 improved thymus
atrophy, an index of immunosuppression, unlike MTX and tofacitinib. 4. In the CIA model, while anti-edema effect of S-110483 was
comparable to that of celecoxib (10 mg/kg), the anti-bone destruction effect of S-110483 was significantly more potent than that of
celecoxib (10 mg/kg).
Conclusion: Our novel EP4 antagonist, S-110483, has not only anti-inflammatory effects but also has direct effects on osteoclasts and
osteoblasts, similar to DMARDs. Furthermore, the anti-edema and anti-bone destruction effects of S-110483, without strong
immunosuppressive effect, are comparable to those of DMARDs. These findings would support the excellent potential of S-110483 as a
clinically useful DMARD.
Disclosure: T. Ochiai, None; T. Maeda, None; T. Nagayasu-Tanaka, None; J. Anzai, None; D. Kato, None; Y. Morisaki, None; K.
Ukai, None; M. Suda, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/s-110483-a-novel-and-selective-ep4-receptor-

antagonist-with-anti-bone-destruction-activities
Defective Glucose and Lipid Metabolism in Rheumatoid Arthritis Is Determined By

Chronic Inflammation in Metabolic Tissues
Nuria Barbarroja1, Ivan Arias de la Rosa2, Sergio Rodriguez-Cuenca3, Yolanda Jiménez-Gómez1, Patricia Ruiz-Limon2, Carlos
Perez-Sanchez1, Maria Carmen Abalos-Aguilera2, Irene Cecchi2, Rafaela Ortega-Castro1, Jerusalem Calvo-Gutierrez1, Rocio Guzman-
Ruiz4, Maria del Mar Malagon5, Eduardo Collantes-Estévez1, Antonio Vidal-Puig3, Alejandro Escudero-Contreras2 and Chary Lopez-
Pedrera1, 1Rheumatology service, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Spain, 2Rheumatology Service,
IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Spain, 3Metabolic Research Laboratories, Wellcome Trust-MRC
Institute of Metabolic Science, Addenbroke’s Hospital, University of Cambridge, Cambridge, United Kingdom, 4Department of Cell
Biology, Physiology, and Immunology,, IMIBIC/University of Córdoba/Reina Sofía University Hospital, Cordoba, Spain, 5Department
of Cell Biology, Physiology, and Immunology,I, IMIBIC/University of Córdoba/Reina Sofía University Hospital, Cordoba, Spain
SESSION INFORMATION
Background/Purpose: Rheumatoid arthritis (RA) patients are at higher risk for insulin resistance (IR). The association between RA
and IR, and its role on the different characteristics of the disease, such as duration and activity have not been well defined. In addition,
there is a gap of knowledge regarding the link between systemic/local inflammation and insulin sensitivity and lipid metabolism in RA
patients.Objective: To explore the effects of the inflammation on the glucose and lipid metabolism in the RA context, following three
strategies: RA patients, collagen induced arthritis (CIA) mouse model and in vitro treatment of 3T3L1 adipocytes.
Methods: Human study: 150 RA patients and 40 healthy donors were included. IR was quantified using the homeostatic model
assessment of IR (HOMA-IR). Mouse model: 20 CB57J/BL mice were used; 5 mice were used as non-diseased group, and 15 were
used in CIA modelling: sorted in low and high activity of the disease based on the number of inflamed digits depending on the duration
of the disease. Plasma, leukocytes, skeletal muscle, liver and adipose tissue were collected. Treatment of adipocytes with serum from
RA patients: 3T3L1 adipocytes were treated with serum 10% of RA patients and healthy donors for 24h. The expression of genes and
proteins involved in inflammation, lipid metabolism and insulin signalling was analysed in all the tissues and cells.
Results: Percentages of obesity, hypertension, atherogenic risk, metabolic syndrome and IR were significantly increased in the RA
group. Although mean time of evolution was 7 years, no association between IR and the duration of the disease was found. Levels of
HOMA-IR significantly correlated with DAS28 and C-reactive protein levels, suggesting a link between the degree of systemic
inflammation and the development of IR in these patients. These results were strengthened by observing that the induction of arthritis in
mice resulted in a global inflammatory state characterized by defective carbohydrate and lipid metabolism in leukocytes, liver, muscle
and adipose tissue, consistent with defects in insulin signaling. Adipose tissue was the organ most susceptible to the RA-induced
metabolic alterations, which were observed from early stages of the disease. These metabolic effects were recapitulated in 3T3-L1
adipocytes treated with serum from RA patients.
Conclusion: 1) IR was closely associated with an increase in disease activity and systemic inflammation in RA patients. 2) Induction of
arthritis in mice promoted an increase in inflammation in skeletal muscle, adipose tissue and leukocytes, accompanied by alterations in
metabolic pathways favouring the development of insulin resistance on these tissues. 3) The inflammatory mediators in RA are the
direct responsible for the metabolic alterations observed in adipose tissue. Altogether, our results show the direct effect of RA-
associated chronic inflammation mediating the alterations occurred in glucose and lipid metabolism associated with this disorder. Thus,
therapeutic strategies aimed to inhibit inflammation targeting proinflammatory cytokines might be an excellent option to normalize the
metabolic alterations associated with RA. Funded by ISCIII-FIS (CP15/00158)
Disclosure: N. Barbarroja, None; I. Arias de la Rosa, None; S. Rodriguez-Cuenca, None; Y. Jiménez-Gómez, None; P. Ruiz-
Limon, None; C. Perez-Sanchez, None; M. C. Abalos-Aguilera, None; I. Cecchi, None; R. Ortega-Castro, None; J. Calvo-
Gutierrez, None; R. Guzman-Ruiz, None; M. D. M. Malagon, None; E. Collantes-Estévez, None; A. Vidal-Puig, None; A.
Escudero-Contreras, None; C. Lopez-Pedrera, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/defective-glucose-and-lipid-metabolism-in-

rheumatoid-arthritis-is-determined-by-chronic-inflammation-in-metabolic-tissues
Effects of Synthetic Dmards on the Insulin Resistance and Obesity Associated with
Rheumatoid Arthritis: An Obese Mouse Model of Arthritis
Nuria Barbarroja1, Ivan Arias de la Rosa2, Miriam Ruiz-Ponce1, Sergio Rodriguez-Cuenca3, Maria Carmen Abalos-Aguilera2,
Yolanda Jiménez-Gómez1, Patricia Ruiz-Limon2, Carlos Perez-Sanchez1, Eduardo Collantes-Estévez1, Antonio Vidal-Puig3, Alejandro
Escudero-Contreras2 and Chary Lopez-Pedrera1, 1Rheumatology service, IMIBIC/Reina Sofia Hospital/University of Cordoba,
Cordoba, Spain, 2Rheumatology Service, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Spain, 3Metabolic Research
Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbroke’s Hospital, University of Cambridge, Cambridge,
United Kingdom
SESSION INFORMATION
Background/Purpose: Numerous studies have demonstrated the closely association between rheumatoid arthritis (RA) and metabolic
complications such as obesity and insulin resistance (IR). Thus, there is an urgent need for the use of therapies targeting both the
activity of the disease and such metabolic disorders. Yet, the beneficial/negative effect of conventional synthetic DMARDs (disease-
modifying antirheumatic drugs) on the metabolic complications associated with cardiovascular disease prominent in RA patients is
unknown yet. Objective: To analyze and compare the effects of methotrexate (MTX), leflunomide (LFN) and hydroxychloroquine
(HDQ) on the obesity and IR in an obese collagen-induced arthritis (CIA) mouse model.
Methods: CIA was developed in obese-induced by high fat diet (HFD) and lean mice. 55 C57Bl/6 mice (4-5 weeks) were used. Groups
of study: 5 non-diseased lean mice, 9 CIA lean mice, 5 non-diseased OB mice, 9 OB-CIA mice, 9 OB-CIA mice treated with LFN, 9
OB-CIA mice treated with MTx and 9 OB-CIA mice treated with HDQ for 15 days. Mice were weighted and the number of total
swollen digits was recorded daily. After treatment, glucose tolerance test (GTT) was performed. HOMA-IR was calculated in all
groups. Serum, plasma and adipose tissue were collected. Gene and protein expression of molecules involved in inflammation, insulin
signaling and lipid metabolism.
Results: HFD promoted an early development of arthritis onset, however fat overloading did not affect the CIA effector phase. In
contrast, the development of arthritis had not effect on body weight. Although the disease overcome was unaffected, obese CIA mice
were more insulin resistant and display an elevated inflammatory state and an alteration of adipokines (at serum/plasma and adipose
tissue levels) compared to lean CIA mice and non-arthritic obese mice. After 15 days of treatment, the therapies more effective on the
disease progression were HDQ and MTX. Only the treatment with HDQ significantly reduced the body weight and improved insulin
sensitivity at systemic level (HOMA-IR and area under the curve-GTT). Although systemic and adipose tissue high inflammatory status
was reverted by the three DMARDs, MTX and HDQ, these were able to restore the metabolic alterations observed on adipose tissue.
Thus, these DMARDs increased the expression of genes involved in insulin signaling (IRS-1 and 2, GLUT4 and AKT), lipid
accumulation (DGAT, PLIN), and adipogenesis (PPARg, SREBP1 and INSIG1) and modulate the expression of leptin and adiponectin.
Conclusion: 1) Lipid overloading accelerates the disease onset in CIA mice. Although disease overcome was unaffected, the induction
of arthritis in an obese state aggravates the metabolic alterations, suggesting that inflammation associated with RA strongly contributes
to the development of metabolic complications. 2) MTX and HDQ can reduce the metabolic abnormalities induced by arthritis,
modulating glucose and lipid metabolism and favoring the improvement of insulin sensitivity. Thus, they can be used as an excellent
therapeutic strategy in patients with metabolic complications related to RA. Funded by ISCIII-FIS (CP15/00158) and Roche Pharma
S.A
Disclosure: N. Barbarroja, None; I. Arias de la Rosa, None; M. Ruiz-Ponce, None; S. Rodriguez-Cuenca, None; M. C. Abalos-
Aguilera, None; Y. Jiménez-Gómez, None; P. Ruiz-Limon, None; C. Perez-Sanchez, None; E. Collantes-Estévez, None; A. Vidal-
Puig, None; A. Escudero-Contreras, None; C. Lopez-Pedrera, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effects-of-synthetic-dmards-on-the-insulin-

resistance-and-obesity-associated-with-rheumatoid-arthritis-an-obese-mouse-model-of-arthritis
The Role of Follicular Helper 17 T Cells in Glucose-6-Phosphate Isomerase Induced

Arthritis
Izumi Kurata, Isao Matsumoto, Atsumu Osada, Hiroshi Ebe, Hoshimi Kawaguchi, Yuya Kondo, Hiroto Tsuboi and Takayuki Sumida,
Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
SESSION INFORMATION
Background/Purpose: Follicular helper T (Tfh) cell is a novel T cell subset which promotes follicular B cell activation, differentiation
to plasma cell and antibody production. Recently, circulating Tfh has been reported to be increased in RA and other autoimmune
diseases. Some reports have showed the existence of Tfh subsets which share same characteristics as conventional Th subsets, but their
function in RA has been still unclear. The aim of this study was to explore the role of Tfh subsets in glucose-6-phosphate isomerase
(GPI) induced arthritis (GIA), which mouse model was dependent on CD4+ T cells, B cells and IL-17.
Methods:
1) The fluctuation in numbers of Tfh, the subsets and germinal center (GC) B cell in draining lymph nodes from GIA were analyzed by
FACS during the course of arthritis.
2) The localization of Tfh and the subsets were analyzed by IF staining of the draining lymph nodes.
3) Anti-GPI antibody titers of sera from GIA were measured by ELISA. To assess Tfh function, Tfh and plasmablasts from GIA were
co-cultured and the antibody titers of the culture supernatant were also measured.
Results:
1) Tfh cell population was increased after the immunization of GPI. The increase was peaked on day 7, just at the onset of the arthritis,
then gradually subsided. The subset analysis revealed the specific increase of IL-17 producing Tfh (Tfh17) at the same phase. The
increased population of GC B cells was also observed through the course of arthritis. Its increase started on day 7 in response to Tfh,
and peaked on day 14.
2) The IF staining showed that Tfh17 cells were accumulated in the T cell zone of GC and physically contacted with GC B cells in the
draining lymph nodes of GIA (Figure).
3) Anti-GPI antibody was detected from day 7 in the sera from GIA, and the titers were gradually elevated over time. The titers of anti-
GPI antibody in the culture supernatant were significantly increased compared with those from non-Tfh CD4+ cells and plasmablasts
co-culture.
Conclusion:
Tfh, particularly Tfh17, might have a crucial role in the development of arthritis via B cell activation and anti-GPI antibody production
in GIA. We are now elucidating the function of Tfh17 in the generation of GIA.
Disclosure: I. Kurata, None; I. Matsumoto, None; A. Osada, None; H. Ebe, None; H. Kawaguchi, None; Y. Kondo, None; H.
Tsuboi, None; T. Sumida, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-role-of-follicular-helper-17-t-cells-in-glucose-6-

phosphate-isomerase-induced-arthritis
Female Tumor Necrosis Factor Transgenic Mice Have More Severe Arthritis Than
Males and Supporessed Levels of Bifidobacterium Pseudolongum in Their Gut
Microbiome
Emily Wu1, Richard Bell2, Alex Grier3, Steven Gill4, Edward Schwarz5 and Homaira Rahimi6, 1Department of Immunology,
Microbiology, and Virology, University of Rochester, Rochester, NY, 2Center for Musculoskelatal Research, University of Rochester,
Rochester, NY, 3Rochester Genomics Center, University of Rochester, Rochester, NY, 4Genomics Research Center, University of
Rochester, Rochester, NY, 5Orthopedeatrics, University of Rochester, Rochester, NY, 6Rheumatology, University of Rochester/Golisano
Children's Hosp, Rochester, NY
SESSION INFORMATION
Background/Purpose: Rheumatoid arthritis (RA) has an increased prevalence and severity in women compared to men, yet the
underlying etiology of this sexual dimorphism is unknown. Similar sex differences in the tumor necrosis factor-transgenic (TNF-Tg)
mouse model of RA have been reported. Most notably, female TNF-Tg mice die earlier than males, with the majority dying between 6-7
months of age, while male mice die sporadically between 5-12 months of age. Recent studies have suggested that the gut microbiota
significantly contribute to the pathogenesis of RA. This has been supported by the K/BxN mouse model of arthritis, which only
develops arthritis when colonized with commensal bacteria. Based on this influence of microbiome on arthritis, we hypothesize that a
sexually dimorphic microbiome exists in TNF-Tg mice, which is associated with disease severity.
Methods: An initial pilot study was performed to assess beta-diversity in male vs. female TNF-Tg mice (n=10), by 16S rRNA
sequencing of fecal pellets. We also performed a principal coordinate analysis (PCoA) on these data. Based on significant findings, we
collected samples from 4 separately housed cohorts of mice at 5.5 months of age, when TNF-Tg females have advanced disease and
males have moderate disease. Cohorts were formed for the purpose of comparing TNF-Tg vs. WT and female vs male gut microbiome
profiles (n=6 per cohort). 16S rRNA sequencing was performed on all samples.
Results: We found that female TNF-Tg mice had a significantly decreased beta-diversity (p<0.05) compared to their male counterparts.
PCoA demonstrated a clear spatial separation between male and female samples, suggesting distinct gut microbiome profiles. Follow up
studies demonstrated that female TNF-Tg mice had enriched levels of several Bacteroidetes and Firmicutes species, as well as
suppressed levels of Bifidobacterium pseudolongum, a known commensal bacterium with noted immunosuppressive properties.
Conclusion: Here, we have shown for the first time that the TNF-Tg model of RA demonstrates both a disease-associated dysbiosis, as
well as a sexually dimorphic microbiome profile within the TNF-Tg population. We have also shown that the female TNF-Tg
microbiome was enriched in certain Bacteroidetes and Firmicutes species compared to the male cohort. The greatest disparity was with
the bacterium Bifidobacterium pseudolongum, which multiple studies have suggested has an immunosuppressive phenotype and was
greatly suppressed in female TNF-Tg mice. Further research is needed to investigate its role in inflammatory environments and whether
active manipulation of the gut microbiome with probiotics may alter the disease state.
Disclosure: E. Wu, None; R. Bell, None; A. Grier, None; S. Gill, None; E. Schwarz, Janssen Pharmaceutica Product, L.P., 9,Lilly
Inc., 9; H. Rahimi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/female-tumor-necrosis-factor-transgenic-mice-have-

more-severe-arthritis-than-males-and-supporessed-levels-of-bifidobacterium-pseudolongum-in-their-gut-microbiome
Pharmacological and Safety Profiles of Cyclin-Dependent Kinase 4/6 Inhibitor,

Candidate for Development As Rheumatoid Arthritis Therapeutic Option
Johji Nomura1, Shunsuke Tsujimoto2, Kei Tamura2, Wataru Yamamoto2, Hiroshi Takahashi2, Kyohei Horie2, Toshiya Mashiko2,
Naoki Hase2 and Tsunefumi Kobayashi2, 1Teijin Institute for Bio-medical Research, TEIJIN PHARMA LIMITED, Tokyo, Japan,
2TEIJIN PHARMA LIMITED, Tokyo, Japan
SESSION INFORMATION
Background/Purpose: The pathogenesis of rheumatoid arthritis (RA) is characterized by the infiltration of immune cells into the
synovial tissues and the excessive proliferation of synovial fibroblasts, resulting in synovial hyperplasia (pannus formation) and
subsequent destruction of the bones and joints. Therapeutic strategies to inhibit pro-inflammatory cytokines or immune cells with
methotrexate and biologics are the mainstay in the current treatment of RA. However, they cannot induce complete clinical remission in
all of the patients. Cyclin-dependent kinase (CDK) 4/6 are key regulators in cell cycle, and its inhibitors have been reported to attenuate
the proliferation of synovial fibroblasts and the progression of arthritis without inhibiting acquired immune responses in mouse RA
models. To provide novel therapeutic option to inhibit the synovial hyperplasia, we performed the screening for CDK4/6 inhibitors and
found out Compound X with high potency and selectivity for CDK4/6. Here we show the pharmacological and safety profiles of
Compound X.
Methods: In vitro activities of Compound X were examined in kinase assays to determine the inhibitory activity against CDK4/6 and
the selectivity to other kinases. In vivo efficacies of Compound X were examined in collagen-induced arthritis (CIA) of mice.
Combination efficacy of Compound X and etanercept was examined in anti-collagen antibody-induced arthritis (CAIA) of mice.
Adjuvant-induced arthritis (AIA) in rats was performed to determine the safety margin of Compound X. Compound X was orally
administrated twice daily for 19 days in mice and once daily for 3 weeks in rats, respectively. A toxicological profiling of Compound X
was conducted with 4-week repeat dose studies in rats and monkeys. Telemetry study in monkeys and proarrhythmia study in human
iPS cell-derived cardiomyocytes were conducted to evaluate the risk of the cardiovascular system.
Results: Compound X showed dose-dependent inhibition of the progression of arthritis and bone destruction in the CIA mice. The
serum MMP-3 level was decreased by Compound X, which is consistent with the finding that inhibition of MMP-3 secretion by
Compound X in synovial fibroblasts from RA patients. Furthermore, combination of Compound X with etanercept suppressed arthritic
score and MMP-3 level more than monotherapy with Compound X or etanercept at the most effective dose. Whereas myelosuppression
was observed at 120 mg/kg of Compound X in the AIA rats, the best efficacy in arthritic score was observed at 15 mg/kg. Four-week
general toxicity studies in rats and monkeys demonstrated that Compound X is well-tolerated and has no critical concerns. In addition,
telemetry study in monkeys and proarrhythmia study using human iPS-derived cardiomyocytes revealed a low risk of the cardiovascular
system.
Conclusion: Compound X is an orally available CDK4/6 inhibitor and a promising candidate for development for RA treatment.
Disclosure: J. Nomura, TEIJIN PHARMA LIMITED, 3; S. Tsujimoto, TEIJIN PHARMA LIMITED, 3; K. Tamura, TEIJIN
PHARMA LIMITED, 3; W. Yamamoto, TEIJIN PHARMA LIMITED, 3; H. Takahashi, TEIJIN PHARMA LIMITED, 3; K. Horie,
Kyohei Horie, 3; T. Mashiko, TEIJIN PHARMA LIMITED, 3; N. Hase, TEIJIN PHARMA LIMITED, 3; T. Kobayashi, TEIJIN
PHARMA LIMITED, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/pharmacological-and-safety-profiles-of-cyclin-

dependent-kinase-46-inhibitor-candidate-for-development-as-rheumatoid-arthritis-therapeutic-option
Phospho-STAT1 Inhibition Is the Initial Step after Tofacitinib Treatment in Rabbits

with Severe Chronic Synovitis
Sandra Pérez-Baos, Paula Gratal, Juan Ignacio Barrasa, Ana Lamuedra, Gabriel Herrero-Beaumont and Raquel Largo, Bone and Joint
Research Unit, IIS-Fundación Jiménez Díaz UAM, Madrid, Spain
SESSION INFORMATION
Background/Purpose: Tofacitinib (TOFA) is a Janus Kinase (Jak) inhibitor approved for the treatment of rheumatoid arthritis (RA) 1.
It has recently been shown to selectively inhibit the expression of several chemokines in the synovium of RA patients that were treated
over 28 days, without modifying the expression of various pro-inflammatory cytokines, nor the histopathological synovial
inflammation, including macrophage infiltration 2. Despite being the synovium the main articular tissue affected by RA, to date there
are very limited data regarding the early modulation of synovial cytokines by this Jak inhibitor. In this sense, animal models may allow
a better understanding of the consequences of Jak inhibition in chronic arthritis (CA). Our aim was to develop a rabbit model of CA
which mimicked severe human RA in early phases of treatment, in order to evaluate early tissue changes rather than the final
therapeutic effect.
Methods: Twenty-four male, New Zealand white rabbits were randomly assigned to two groups: control (n=8) and CA (n=16). CA was
induced over six weeks via intra-dermal ovalbumin sensitization and four subsequent intra-articular injections on a weekly basis. After
the second intra-articular injection, eight CA rabbits were treated with TOFA (10mg/kg/day).
Results: CA animals showed reduced weight gain compared to controls, which TOFA tended to increase (weight gain, kg; Control:
0.8±0.05; CA: -0.09±0.06*; CA+TOFA: 0.18±0.1*#; *p<0.05 vs Control; #p=0.07 vs CA). A substantial increase in serum C-reactive
protein (CRP) was found both in CA and CA+TOFA animals. CA animals showed a severe synovitis that was partially prevented by
TOFA (Krenn Score; Control: 0.9±0.3; CA: 7.6±0.2*; CA+TOFA: 6.6±0.2*#; p<0.05 *vs. control; # vs. CA), and exhibited an
augmented macrophage infiltration which was not modified by this inhibitor. TOFA effectively reduced the synovial expression of
matrix metalloproteinases MMP-1 (93% inhibition, p<0.05) and MMP-3 (83% inhibition p<0.05), the C-C Motif Chemokine Ligand 2
(CCL2, 74% inhibition, p<0.05) as well as the pro-inflammatory cytokines Interleukin-6 (IL-6, 42% inhibition, p<0.05) and Tumor
Necrosis Factor-α (TNFα, 55% inhibition, p<0.05). However, IL-1β was not modified with this Jak inhibitor. Signal Transducer and
Activator of Transcription (STAT) -1 and -3, and Nuclear Factor-κB (NF-κB) were activated during CA, but TOFA was only able to
diminish STAT-1 phosphorylation.
Conclusion: In a synovial tissue with an intense inflammatory activity, TOFA treatment initially blocked STAT-1 phosphorylation,
whereas phospho-STAT-3 levels remained unchanged. This Jak inhibitor induced a partial decrease in the synovitis score along with a
marked reduction of the expression of MMPs and, to a lesser extent, other pro-inflammatory mediators. These data suggest a key role of
STAT-1 in the initial changes occurring in the synovium after TOFA treatment.
References: 1. Elkan, A. C. et al. Arthritis Res. Ther. 11, R37 (2009); 2. Boyle, D.L. et al. Ann Rheum Dis 74, 1311–1316 (2015)
Disclosure: S. Pérez-Baos, None; P. Gratal, None; J. I. Barrasa, None; A. Lamuedra, None; G. Herrero-Beaumont, None; R.
Largo, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/phospho-stat1-inhibition-is-the-initial-step-after-

tofacitinib-treatment-in-rabbits-with-severe-chronic-synovitis
Anti-Fractalkine Monoclonal Antibody Ameliorates Joint Destruction in Collagen-

Induced Arthritis Model through Suppression of Osteoclast Precursor Cell Survival
and Migration
Yoshikazu Kuboi1, Kana Hoshino-Negishi1, Masayoshi Ohkuro2, Wataru Ikeda1, Tomoya Nakatani1, Naoto Ishii1, Toshihiko
Yamauchi1, Nobuyuki Yasuda1 and Toshio Imai3, 1KAN Research Institute, Inc., Chuo-ku, Kobe-shi, Japan, 2Research Project
Promotion Group, EA Pharma Co., Ltd., Kawasaki-ku, Kawasaki-shi, Japan, 3KAN Research Institute, Inc., Kobe, Japan
SESSION INFORMATION
Background/Purpose: In the Phase 1/2 clinical study, E6011, a novel humanized anti-fractalkine (FKN) mAb demonstrated a
promising efficacy in active RA patients who were inadequately controlled by MTX and/or TNF-α inhibitors. In RA joint tissue,
increased expression of FKN and abundant infiltration of CX3CR1-positive cells were observed. However, the precise mechanism(s) of
FKN-CX3CR1 axis in RA, especially on joint destruction remains to be elucidated. FKN is expressed on endothelial cells and
fibroblast-like synoviocytes in synovium and also expressed on osteoblasts. CX3CR1 is expressed on monocytes/macrophages and
osteoclast precursor cells (OPCs). Therefore, FKN-CX3CR1 interaction could play pivotal roles in migration, differentiation and
activation of those cells. Thus, we examined the roles of FKN-CX3CR1 axis in joint destruction, particularly focused on osteoclast
precursor cells in in vitro and in vivo by using anti-mouse FKN mAb (anti-mFKN mAb).
Methods: DBA/1J mice were immunized with intradermal injections of bovine type II collagen to induce arthritis. Anti-mFKN mAb or
control IgG were intraperitoneally injected twice a week. The clinical arthritis score was monitored, and joint destruction was evaluated
by soft X-ray and histopathology. Blood parameters were measured using ELISA. In in vitro, effect of immobilized FKN on RANK
ligand (RANKL)-induced osteoclast differentiation was examined. Cell survival of bone marrow-derived OPCs without or with
immobilized FKN was also assessed by FACS. In in vivo, OPCs were labeled by fluorescein and transferred to CIA mice to evaluate
migration of OPCs into inflamed synovium. Anti-mFKN mAb or control IgG were injected before the cell transfer. The number of
fluorescein-labeled OPCs that migrated into the CIA joint tissue were counted.
Results: In both prophylactic and therapeutic treatments, anti-mFKN mAb clearly reduced the clinical arthritis score, soft x-ray score
and histopathological changes (synovitis, bone erosion and cartilage destruction). The number of TRAP-positive cells in the joint was
clearly decreased with anti-mFKN mAb treatment. Interestingly, anti-mFKN mAb suppressed plasma levels of COMP and MMP-3
without affecting those of IL-6, TNF-α and SAA. In in vitro, RANKL-induced osteoclast differentiation was enhanced by immobilized
FKN, and anti-mFKN mAb suppressed FKN-dependent enhancement of osteoclast formation. FKN enhanced cell survival of OPCs and
eventually increased the number of OPCs. In in vivo, fluorescein-labeled OPCs migrated into inflamed joint tissues, and anti-mFKN
mAb clearly abrogated their migration into synovium.
Conclusion: Anti-mFKN mAb remarkably ameliorated the joint destruction with the marked reduction of osteoclasts by the inhibition
of both OPC survival and OPC migration in inflamed joint tissues without affecting systemic inflammatory parameters. These results
strongly indicate that inhibition of FKN-CX3CR1 axis by a humanized anti-FKN mAb, E6011, is an attractive and affected joints-
selective therapeutic strategy for the treatment of both inflammatory synovitis and joint destruction in RA patients.
Disclosure: Y. Kuboi, None; K. Hoshino-Negishi, None; M. Ohkuro, None; W. Ikeda, None; T. Nakatani, None; N. Ishii, None; T.
Yamauchi, None; N. Yasuda, None; T. Imai, KAN Research Institute, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/anti-fractalkine-monoclonal-antibody-ameliorates-

joint-destruction-in-collagen-induced-arthritis-model-through-suppression-of-osteoclast-precursor-cell-survival-and-migration
An on-Demand Drug Delivery System for the Treatment of Inflammatory Arthritis

Jing Yan1, Nitin Joshi2, Seth Levy2, Sachin Bhagchandani2, Kai Slaughter2, Nicholas Sherman1, Julian Amirault2, Xueyin He2, Tan
Shi Rui2, Michael Valic2, Praveen Vemula3, Oscar Miranda2, Oren Levy2, Antonios Aliprantis4, Joerg Ermann1 and Jeffrey Karp2,
1Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, 2Brigham and Women's Hospital,
Boston, MA, 3Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bangalore, India, 4Rheumatology/Immunology,
Brigham and Women's Hospital, Boston, MA
SESSION INFORMATION
Background/Purpose: Many types of inflammatory arthritis (IA) are treated with systemic therapy. In situations where only one or a
few joints are active, intra-articular drug administration may offer distinct advantages over starting or escalating systemic therapy by
increasing drug bioavailability locally and reducing the potential for drug-induced systemic toxicity. However, local delivery of
therapeutics is limited by short intra-articular half-lives. A drug delivery method that generates a local drug depot and titrates drug
release to arthritis activity would represent an attractive solution to this problem. We investigated the utility of hydrogels generated
from a generally recognized as safe (GRAS) compound for inflammation-responsive local drug delivery in a mouse model of IA.
Methods: Hydrogels were generated from triglycerol monostearate (TG-18) and loaded with triamcinolone acetonide (TA) or a
fluorescent dye (DiR). TA-loaded hydrogels were incubated in vitro with defined enzymatic activities or human synovial fluid. TA
release was measured using high performance liquid chromatography. IA was induced in C57BL/6 mice by two i.p. injections of K/BxN
serum. DiR-loaded hydrogels were injected into the right hindpaw prior to disease induction and fluorescence signal decay was
measured by IVIS imaging. To test therapeutic efficacy, TA-loaded hydrogel, blank hydrogel or free TA were injected into the right
hindpaw immediately after disease induction, and disease severity was assessed by measuring paw thickness with calipers and clinical
scoring.
Results: TG-18 hydrogels efficiently and stably encapsulate TA. In vitro, TA-loaded hydrogels released drug on-demand upon exposure
to enzymes including matrix metalloproteases or synovial fluid from patients with rheumatoid arthritis. In mice with K/BxN serum
transfer arthritis, locally injected DiR-hydrogels demonstrated loss of fluorescence over time due to hydrogel disassembly that
correlated with arthritis severity. Moreover, a single dose of TA-loaded hydrogel but not the equivalent dose of locally injected free TA
reduced arthritis activity in the injected paw.
Conclusion: Our results suggest that an inflammation-responsive hydrogel as self-titrating on-demand drug delivery system can offer
improved therapeutic benefit in IA.
Disclosure: J. Yan, None; N. Joshi, None; S. Levy, None; S. Bhagchandani, None; K. Slaughter, None; N. Sherman, None; J.
Amirault, None; X. He, None; T. S. Rui, None; M. Valic, None; P. Vemula, None; O. Miranda, None; O. Levy, None; A. Aliprantis,
None; J. Ermann, Novartis Pharmaceutical Corporation, 5,UCB, 5,Takeda, 5,SPARTAN/GRAPPA, 9; J. Karp, Alivio Therapeutics, 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/an-on-demand-drug-delivery-system-for-the-

treatment-of-inflammatory-arthritis
Therapeutic Effect of Rosiglitazone-Mediated Dendritic Cells in Established

Arthritis in Mice
Jin Jung Choi1, Sang-Yoon Jung2, Kyung-Su Park3, Chong-Hyeon Yoon4 and Dae-Seog Lim5, 1Rheumatology, CHA University
Medical Center at Bundang, Sungnam, Korea, Republic of (South), 2Internal Medicine, Bundang CHA Medical Center, Seongnam,
Korea, Republic of (South), 3Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea, Republic of
(South), 4Rheumatology, The Catholic University of Korea, Uijeongbu St. Mary's Hospital, Uijeongbu, Korea, Republic of (South),
5Department of biotechnology, CHA University, Sungnam, Korea, Republic of (South)
SESSION INFORMATION
Background/Purpose:
Rosiglitazone is a selective ligand for peroxisome proliferator-activated receptor-gamma (PPAR-γ), which is expressed by antigen
presenting cells (APCs) and plays a fundamental role in immune responses. Tolerogenic dendritic cells (tDCs) are professional APCs
with antigen-specific immune regulation to induce autoimmune tolerance, suggesting the potential as antigen-specific immunotherapy
for autoimmune diseases. The aim of this study was to investigate therapeutic effects of rosiglitazone-mediated DC (Rosi-DC) in a
collagen-induced arthritis (CIA) mouse model.
Methods:
Rosi-DCs were generated by treating immature DCs with TNF-α, type II collagen, and rosiglitazone. CIA mice then received
subcutaneously two injections of Rosi-DCs. The severity of arthritis was then assessed three times until Day 50 post-primary
immunization. The phenotypes of the DC and regulatory T (Treg) cell populations in CIA mice were determined by flow cytometry and
the effect of Rosi-DCs on the secretion of autoimmunity-inducing cytokines was examined by ELISA.
Results:
Rosi-DCs expressed lower levels of DC-related surface markers (CD80, CD86, CD40 and CD54) than mature DCs. Rosi-DCs produced
lower levels of pro-inflammatory cytokines (IL-1β, IL-6, and IL-12p70) than mDCs. Upon the co-culture of DCs and T lymphocytes,
Rosi-DCs markedly increased FoxP3+CD4+CD25+ Treg cell population and reduced the Th1/Th17 cell population.
Histopathological examination revealed that the degree of inflammation in the paws of Rosi-DC-treated mice was much lower than that
in the paws of PBS-treated CIA mice. In vivo, the percentage of Treg cells in the spleens and inguinal lymph nodes of mice vaccinated
with type II collagen-pulsed Rosi-DCs was markedly higher than that in mice injected with Ag-mismatched (myosin pulsed) or Ag-
unpulsed Rosi-DCs and PBS-treated CIA mice. Treatment with type II collagen-pulsed Rosi-DCs resulted in a reduction in the
percentage of Th1 and Th17 cells within the splenocyte population.
Conclusion:
In this study, these results clearly show that rosiglitazone-mediated DCs ameliorate CIA, most likely via the induction of antigen-
specific Treg cells.
Disclosure: J. J. Choi, None; S. Y. Jung, None; K. S. Park, None; C. H. Yoon, None; D. S. Lim, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/therapeutic-effect-of-rosiglitazone-mediated-

dendritic-cells-in-established-arthritis-in-mice
Combination of the Collagen-Induced Arthritis and Organic Dust-Induced Airway

Inflammation Models As a Model of Interstitial Lung Disease in Rheumatoid
Arthritis
Katherine Janike1, Jill Poole1, Geoffrey M. Thiele2, Michael J. Duryee3, Lynell W. Klassen4, Amy Nelson5, Kristi Warren6, Benjamin
Swanson7 and Ted R. Mikuls8, 1Medicine, University of Nebraska Medical Center, Omaha, NE, 2Int Med/Sec of Rheum/Immun, Univ
of NE Medical Ctr, Omaha, NE, 3Internal Medicine Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE,
4Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 5Department of Medicine, University of
Nebrasa Medical Center, Omaha, NE, 6Department of Medicine, University of Nebraska Medical Center, Omaha, NE, 7Department of
Pathology, University of Nebraska Medical Center, Omaha, NE, 8Internal Medicine, Division of Rheumatology, University of Nebraska
Medical Center, Omaha, NE
SESSION INFORMATION
Background/Purpose: Rheumatoid Arthritis (RA) is characterized by extra-articular involvement including interstitial/inflammatory

lung disease (ILD). Whereas the coexistence of RA and ILD is known, mechanisms linking the two conditions are poorly understood.
The objective of this study was to combine an established organic dust extract (ODE) inhalation injury model with the collagen-induced
arthritis (CIA) murine model to assess lung and bone/joint inflammatory outcomes.
Methods: Using an established intranasal inhalation protocol, DBA/1J mice were treated with saline or organic dust extract (ODE)
daily for 5 weeks. CIA arthritis was induced with collagen emulsified in Freund’s complete adjuvant and injected on Days 1 and 21.
Mice (9-10/group; 2 independent experiments) were assigned to 1of 4 groups: 1-Sham (saline injection/saline inhalation); 2-CIA
(CIA/saline inhalation); 3-ODE (saline injection/ODE inhalation); 4-CIA+ODE (CIA/ODE inhalation). Arthritis inflammatory scores
were calculated weekly (0-4 range) based on swelling and redness of the hind paw. Five hours following final ODE, mice were
euthanized. Bones, bronchoalveolar lavage fluid (BALF), and lung tissues were collected.
Results: Table depicts experimental outcome results. Arthritis and histologic inflammatory scores and were increased in
CIA+ODE>CIA alone>ODE alone as compared to Sham. Trabecular bone micro-CT analysis showed loss of bone mineral density,
volume and deterioration of bone micro-architecture and mechanical strength to be most pronounced in CIA+ODE. Evidence of bone
deterioration was also found in the CIA, but not ODE or Sham animals. In contrast, ODE-induced airway neutrophil influx and
cytokine/chemokine (TNF-α, IL-6, CXCL1, CXCL2) in BALF were greater in ODE as compared to ODE+CIA. Similarly, lung
pathology showed ODE-induced lymphoid aggregates and alveolar inflammation were increased in ODE>ODE+CIA. By flow
cytometry, ODE increased lung tissue neutrophils and activated CD11c+CD11bhi macrophages to Sham. Comparable trends, but to a
lesser degree, were demonstrated in CIA+ODE. CIA increased lung activated CD11c+CD11bhiairway macrophages as compared to
Sham.
Conclusion: This is the first study to explore the interaction between a repetitive inhalant injury and arthritis induction with findings
supporting a compartmentalized immune response. The combined exposures (CIA+ODE) resulted in the greatest degree of arthritis and
diffuse bone loss. However, data support a suppression of the lung inflammatory response in the setting of arthritis. Activation of the
lung macrophage during arthritis induction may be responsible for this paradoxical finding. Finally, this co-exposure model could be
exploited further and in other murine strains to better understand the pathogenesis and response to potential treatments for RA-ILD.
Sham CIA ODE CIA+ODE
Final Arthritis 0 (0) 1.33 (0.19) 0.70 (0.13) 1.60 (0.22)
Inflammatory Score
(range: 0-4) *** *** ***, ##
Bone mineral density, 0.14 (0.006) 0.11 (0.008) 0.15 (0.009) 0.09 (0.01)
g/cm3
* **, ##
BALF neutrophil count, 8.2 (1.3) 9.0 (3.3) 524 (79) 246 (67)
x 103
***, ### ***
BALF IL-6, pg/ml 0 (0) 0 (0) 246 (26) 130 (31)
***, ## **
BALF TNF-α, pg/ml 0.7 (0.7) 0 (0) 35 (7) 13 (5)
**,# *
BALF CXCL2, pg/ml 59 (14) 52 (11) 142 (15) 69 (9)
***, # **
BALF CXCL1, pg/ml 237 (142) 225 (53) 474 (54) 254 (41)
**,##
Lung tissue neutrophil 6.1 (2.0) 11.1 (2.0) 30.3 (7.5) 19.8 (1.2)
count, x104
***,## **
Lung tissue activated 1.3 (0.4) 3.1 (0.7) 12.6 (3.1) 7.7 (0.9)
macrophage
(CD11c+CD11bhi) count, * ** **
x10 4
Statistical significance denoted as asterisks (*p<0.05; **p<0.01, ***p<0.001)
vs. Sham. Statistical difference of ODE vs. CIA +ODE denoted as #p<0.05;
##p<0.01, ###p<0.001.
Disclosure: K. Janike, None; J. Poole, None; G. M. Thiele, None; M. J. Duryee, None; L. W. Klassen, None; A. Nelson, None; K.
Warren, None; B. Swanson, None; T. R. Mikuls, BMS, 2,Ironwood Pharm, 2,Pfizer Inc, 5,NIH, VA, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/combination-of-the-collagen-induced-arthritis-and-

organic-dust-induced-airway-inflammation-models-as-a-model-of-interstitial-lung-disease-in-rheumatoid-arthritis
Cigarette Smoking Dose-Dependently Facilitates the Onset of Arthritis and

Aggravates Arthritis in Female Experimental Arthritis Mice
Ji-Won Kim1, Jennifer Lee2, Yeon-Sik Hong3, Sung-Hwan Park2 and Ji Hyeon Ju2, 1Medicine, Division of Rheumatology, Department
of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of
(South), 2Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic
University of Korea, Seoul, Korea, Republic of (South), 3Division of Rheumatology, Department of Internal Medicine, College of
Medicine, The Catholic University of Korea, Seoul, Korea, Republic of (South)
SESSION INFORMATION
Background/Purpose: Smoking is an important epidemiological factor for development of rheumatoid arthritis (RA). However, the
mechanism of proarthritic role of smoking is not well understood. The purpose of this study is to precisely explore the arthritic role of
smoking in two experimental arthritis models including collagen induced arthritis (CIA) and IL-1 receptor antagonist (Ra) knockout
(KO) mice. Cigarette smoking was challenged by two routes of inhalation and drinking.
Methods: To deliver elaborate dosage of smoking, we utilized good laboratory product (GLP)-grade closed inhalation chamber system
which is equipped in Korea Institute of Toxicology. Smoke was generated by routine analytic cigarette-smoking machine (ISO standard
3308). Tobacco produce-3R4F cigarette (9.4mg tar/0.7mg nicotine) was chosen by ISO standard 3402 for atmosphere conditioning and
testing. This study was strictly followed by OECD guidelines for the testing of chemicals section 4 health effects test No.412 Subacute
inhalation toxicity. CIA was induced in a total of 60 mice (negative control (n=10), CIA control (n=10), smoke control (n=10), and
cigarette smoke (n=30)). After 1st collagen immunization, three different doses (T1~T3) of smoke were delivered to collagen induced
mice (T1 dose 150 ug/L (n=10), T2 dose 300 ug/L (n=10), T3 dose 600 ug/L (n=10)). It is known that concentration of smoke exposure
possibly ranges from 50 to 800 ug/L in real world. Cigarette smoke delivery was done 1 hour once a day, 5 days/week, for 4 weeks in
close ventilation system. As a second smoking study, cigarette smoke extract (CSE) was delivered per oral to IL-1RaKO mice arthritis
model.
Results: Cigarette smoking facilitated the onset arthritis. Twenty percent of mice in cigarette smoke group developed arthritis less than
a week after 1st immunization, while control CIA mice showed 20% incidence of arthritis on four weeks after immunization. Time
points of 60% arthritis incidence was on 3 weeks after 1st immunization, 4 weeks, and 6 weeks in high dose (T3), low dose (T1) and
control CIA group, respectively (p<0.05). Higher dose of smoke challenge induced more lymphocyte infiltration in subpleural area of
lung. Citrullination was dose dependently increased in smoking inhaled groups. Splenic Th17 popluation increased dose dependently in
smoking groups. In contrary to smoking experiment, CSE drinking did not affect the arthritis development in experimental arthritis
model. However, interestingly CSE aggravated arthritis score in female group as a subgroup analysis.
Conclusion: In this study, we revealed cigarette smoking facilitated the onset of arthritis and aggravated arthritis score in a dose-
dependent manner. Smoking may play a role in advancing the onset of arthritis in those who are at risk of cigarette smoke exposure and
contribute to developing RA. Female also can be more vulnerable to cigarette challenge. More precise, large scale epidemiological
study may help to verify these observations.
Disclosure: J. W. Kim, None; J. Lee, None; Y. S. Hong, None; S. H. Park, None; J. H. Ju, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/cigarette-smoking-dose-dependently-facilitates-the-

onset-of-arthritis-and-aggravates-arthritis-in-female-experimental-arthritis-mice
Alteration of the Intestinal Microbiome in the Preclinical Phase of Experimental

Arthritis and the Efficacy of Microbiota Modulation in Established Arthritis in Mice
Rebecca Rogier1, Heather Evans-Marin2, Julia Manasson3, Peter M. van der Kraan4, Wim B. van den Berg5, Marije I. Koenders4, Jose
U. Scher6 and Shahla Abdollahi-Roodsaz7,8, 1Experimental Rheumatology, Radboud University Medical Center, Nijmegen,
Netherlands, 2Division of Rheumatology, New York University School of Medicine, New York, NY, 3Department of Medicine,
Division of Rheumatology, New York University School of Medicine, New York, NY, 4Experimental Rheumatology, Radboud
university medical center, Nijmegen, Netherlands, 5Rheumatology Research and Advanced Therapeutics, Radboud University Medical
Center, Nijmegen, Netherlands, 6New York University School of Medicine, New York, NY, 7Department of Medicine, Division of
Rheumatoogy, New York University School of Medicine, New York, NY, 8Rheumatology, Radboud University Medical Center,
Nijmegen, Netherlands
SESSION INFORMATION
Background/Purpose:
The composition of intestinal microbiota is perturbed in patients with new-onset and chronic rheumatoid arthritis (RA). However, it is
not known whether the changes in the intestinal microbiome precede the development of arthritis or are rather a consequence of the
inflammatory processes. Furthermore, while both germ-free condition and administration of oral antibiotics prevent arthritis in mice, it
is unclear whether modulation of the intestinal microbiota after the onset of arthritis may still suppress the disease. We aimed to identify
alterations of the intestinal microbiome in the preclinical phase of inflammatory arthritis, and evaluate the efficacy of microbiota
modulations in the treatment of established arthritis in mice.
Methods:
We sequenced fecal bacterial 16S rRNA genes of mice immunized for the induction of collagen-induced arthritis (CIA) prior to the
onset of arthritis compared with naïve condition. To assess the efficacy of microbiota modulation during arthritis, mice with ongoing
CIA were treated with oral antibiotics to partially eliminate the intestinal microbiota. T cell differentiation and production of cytokines
in intestinal lamina propria and joint-draining lymph nodes were assessed by flow cytometry and Luminex. Arthritis was assessed
macroscopically and by histology. K/BxN serum-transfer arthritis was used to assess the role of microbiota in T cell-independent
arthritis.
Results:
The preclinical phase of arthritis in mice was characterized by marked changes in the intestinal microbiome, represented by a significant
increase of the phylum Bacteroidetes and a decrease of Firmicutes and Proteobacteria. Among the most abundant bacterial families,
S24-7 and Staphylococcaceae were expanded, whereas Lachnospiraceae were reduced during the early immune-priming phase of CIA.
Several operational taxonomic units associated with S24-7 family increased, while those assigned to Lachnospiraceae and
Ruminococcaceae decreased in the intestinal microbiota before the clinical onset of arthritis. The abundance of intestinal lamina propria
Th17 cells significantly correlated with the severity of CIA; however, lamina propria Th1 cells were not correlated with arthritis.
Elimination of intestinal microbiota during established arthritis specifically suppressed intestinal Th17 cell differentiation without
affecting Th1 and regulatory T cells. Importantly, elimination of intestinal microbiota suppressed Th17 cell differentiation and IL-17
production in joint-draining lymph nodes, and reduced the severity of established CIA. In contrast, the T cell-independent serum-
transfer arthritis was not affected by this strategy.
Conclusion:
These observations suggest that perturbations of the intestinal microbiome precede the development of inflammatory arthritis. Similar
studies are warranted in human pre-RA or at-risk individuals to shed light on the potential relevance of the microbiome in the
preclinical phase of RA. Our studies also suggest that modulation of the intestinal microbiota after the onset of arthritis may still
provide opportunities to treat inflammatory arthritis.
Disclosure: R. Rogier, None; H. Evans-Marin, None; J. Manasson, None; P. M. van der Kraan, None; W. B. van den Berg, None;
M. I. Koenders, None; J. U. Scher, NIAMS-NIH, 2; S. Abdollahi-Roodsaz, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/alteration-of-the-intestinal-microbiome-in-the-

preclinical-phase-of-experimental-arthritis-and-the-efficacy-of-microbiota-modulation-in-established-arthritis-in-mice
Cardiac Immune Cells in SKG Mice with Inflammatory Arthritis before and after
Myocardial Infarction
Christine Hsieh1, Isabella Imhof2, Luyi Li3, Erene Niemi1, Matthew Bell1, Joel Karliner4 and Mary Nakamura5, 1Medicine,
SFVA/UCSF, San Francisco, CA, 2Medicine, SFVA/NCIRE, San Francisco, CA, 3SFVA/UCSF, San Francisco, CA, 4Medicine,
SFVA/UCSF, San, CA, 5Department of Medicine, Division of Rheumatology, UCSF/SFVA, San Francisco, CA
SESSION INFORMATION
Background/Purpose:
Cardiovascular disease is a major cause of morbidity and mortality in patients with rheumatoid arthritis (RA). RA patients have an
increased incidence of both myocardial infarction (MI) and congestive heart failure. Cardiac immune cells have been demonstrated to
influence cardiac remodeling post infarction and our study examined the effect of inflammatory arthritis on cardiac immune cells using
a mouse model of myocardial infarction in SKG mice, a model of inflammatory arthritis.
Methods:
Arthritis was induced in female SKG mice (BALB/c ZAP-70W163C-mutants) with a single injection of zymosan at 12 weeks age and
were examined after development of athritis at 4 weeks. Wild type Balb/c mice, SKG mice, and SKG mice with arthritis (4 weeks post-
zymosan) with MI underwent permanent left anterior descending coronary artery ligation. Cardiac leukocytes were evaluated at day 1
and 6 post-infarction, following harvest with cardiac perfusion, disaggregation of the heart, collagenase digestion, cellular isolation and
antibody staining for multicolor flow cytometry. Cells were analyzed using a FACS Aria and FlowJo software (hearts were analyzed
individually, 5 mice per group) using lineage markers (CD90/CD19/NK1.1/Ly-6G) to evaluate T cells, B cells, NK cells, granulocytes
and myeloid markers CD11b, F4/80, Ly-6C.
Results:
Hearts isolated from SKG mice without arthritis showed a slight increase in the number of cardiac neutrophils compared with wild type
Balb/c, that was increased by 3-4 fold in SKG mice with arthritis. At baseline SKG mice with arthritis also had a 2-3 fold increase in
inflammatory macrophages (Ly6C+) compared with either SKG or Balb/c mice. Hearts isolated from SKG mice with arthritis 1 day
post MI, showed a 5-6 fold increase in Ly6G+ cells (neutrophils) and Ly6C+/CD11b (monocyte/macrophages) cells compared to the
basal numbers seen in hearts isolated from wild-type Balb/c mice. At day 6, SKG mice and SKG mice with arthritis both showed a
persistent increase in Ly-6C+ macrophages compared with the decrease in these cells observed in Balc/c mice at the same time point.
Functional outcomes post-MI correlated with these changes are currently being evaluated.
Conclusion:
We found that inflammatory arthritis induces changes in the number and phenotype of cardiac immune cells in mice both before and
after myocardial infarction which likely influences cardiac repair and ventricular remodeling post-MI contibuting to detrimental cardiac
outcomes with inflammatory arthritis.
Disclosure: C. Hsieh, None; I. Imhof, None; L. Li, None; E. Niemi, None; M. Bell, None; J. Karliner, None; M. Nakamura, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/cardiac-immune-cells-in-skg-mice-with-

inflammatory-arthritis-before-and-after-myocardial-infarction
Gut Microbiota Modify Inflammatory Arthritis through Autoantibody Generation

and Mucosal Cytokines Alteration
Widian Jubair1, Sumitra Adhikari2, Nirmal Banda2 and Kristine Kuhn3, 1Rheumatology, University of Colorado, Aurora, CO,
2Division of Rheumatology, UC Denver School of Medicine, Denver, CO, 3Division of Rheumatology, University of Colorado School
of Medicine, Aurora, CO
SESSION INFORMATION
Background/Purpose:
The pathogenesis of rheumatoid arthritis (RA) is thought to be influenced by a combination of genetic and environmental factors.
Observations of microbial dysbiosis in patients with RA have raised interest in studying microbial-mucosal interactions as a potential
trigger of RA. Using the murine collagen-induced arthritis (CIA) model, which is dependent upon generation of T and B cell reactivity
to CII as well as complement activation, we hypothesized that microbiota are required for the development of robust autoimmune
arthritis.
Methods:
Male 6-week old DBA/1j mice were immunized with bovine type II collagen (CII) in Complete Freund’s Adjuvant (CFA) on days 0 and
21. Microbiota depletion was performed by continuous administration of broad spectrum antibiotics in drinking water early (7 days
preceding and throughout the study) or late (starting after day 21 throughout the study) in the disease process. Microbial depletion was
confirmed by quantifying bacterial 16S rRNA by qPCR in feces. Sera were collected every 7 days during the study for autoantibody and
cytokine testing. Mice were euthanized on day 35 and intestinal tissues were harvested for cytokine analyses by ELISA. Disease
severity starting at day 21 was assessed by assigning a score for the degree of paw swelling.
Results:
Depletion of the microbiota prior to the induction of CIA resulted in ~50% reduction in disease severity associated with significantly
reduced serum inflammatory cytokines and anti-CII antibodies. In intestinal tissue, we observed delayed IL-17A and IL-22 responses.
Unexpectedly, microbial depletion during the late, effector phase of CIA resulted in >90% decrease in disease severity and 50%
reduction in prevalence. In these mice, anti-CII antibodies were mildly reduced, but were significantly impaired in their ability to
activate complement. In addition to reduced systemic inflammatory cytokines and intestinal IL-17A and IL-22, IL-23 was significantly
reduced, suggesting it may link mucosal immune responses with systemic autoantibody effectivity. Studies are now aimed at
understanding this mechanism.
Conclusion:
While future studies are needed to solidify the role of the microbiota in driving CIA, our data supports a model in which intestinal
dysbiosis triggers mucosal immune responses that stimulate systemic B cell activities that are key for the development of inflammatory
arthritis. Understanding the pathway by which microbiota and mucosal immune responses modulate systemic autoantibody production
is pivotal, as targeting the microbiota during the preclinical, seropositive phase of RA may have potential for disease prevention.
Disclosure: W. Jubair, None; S. Adhikari, None; N. Banda, None; K. Kuhn, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/gut-microbiota-modify-inflammatory-arthritis-

through-autoantibody-generation-and-mucosal-cytokines-alteration
Dynamics of Transcriptional Signatures from Purified Synovial Macrophage Subsets

during Acute and Chronic Murine Models of Inflammatory Arthritis
Philip J. Homan, Salina Dominguez, Harris Perlman, Deborah R. WInter and Carla Cuda, Department of Medicine Division of
Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL
SESSION INFORMATION
Background/Purpose: Rheumatoid arthritis (RA) manifests in persistent synovial inflammation, cellular infiltration and pro-
inflammatory cytokine production, resulting in progressive joint destruction. Macrophages have been implicated in RA progression and
persistence through production of degradative enzymes, cytokines, and chemokines. However, the mechanisms underlying these
activities are not fully elucidated. We previously demonstrated that naïve mouse joints contain both MHC II+ (monocyte-derived) and
MHC II- (tissue-resident) macrophages. Interestingly, we have shown that the monocyte-derived macrophages drive inflammation,
while the tissue-resident macrophages are involved in resolution based on an acute model of inflammatory arthritis. Thus, we have
optimized a multi-parameter flow cytometry protocol to isolate synovial macrophage subsets to perform subset-specific transcriptomic
analysis.
Methods: We used 3 mouse model of arthritis: the acute inducible K/BxN serum transfer-induced arthritis (STIA) model, and chronic
inducible collagen induced arthritis (CIA) model, and the spontaneous KRN/Ag7 mice. STIA and CIA was induced in 10-12 week old
female C57BL/6 mice. Flow cytometric analysis was employed to delineate macrophage subsets via expression of MHC II and
CX3CR1 to obtain 4 distinct macrophage populations. These populations were sorted throughout the course of arthritis by FACS. RNA
was extracted from sorted macrophage populations and processed for RNA-seq using Quantseq 3’ mRNA library preparation. The
RNA-seq libraries were sequenced on an Illumina NextSeq 500 to an average depth of 5 million reads. The reads were aligned and
mapped to genes using STAR and HTseq respectively.
Results: We observe by flow cytometry that the predominance of individual synovial macrophage subsets shift throughout the
initiation, progression and resolution phases of arthritis and eventually return to their steady-state phenotype. PCA analysis of
macrophage subsets in a naïve mouse show distinct transcriptional profiles. Analysis of the transcriptional profiles over the course of
arthritis reveals that each macrophage subset responds differently at each phase of inflammation. K-means clustering of specific
synovial macrophage subsets have identified distinct gene clusters and cellular processes that are differentially regulated to dictate their
function during arthritis. Synovial macrophage populations from each arthritic model display a similar response to inflammation,
suggesting that the transcriptional signatures and function of macrophages are consistent in inflammatory arthritis.
Conclusion: We conclude that fluctuations in the synovial macrophage populations over the course of arthritis coincide with the
different phases of joint inflammation. These dynamics indicate that the specific macrophage subsets have different function during the
course of disease as evidenced by their distinct transcriptional profiles. These high-throughput genomic approaches applied to
macrophage subsets from models of both acute and chronic inflammatory arthritis allows us to comprehensively map their role in
disease, thereby providing insight into potentially useful targets for therapy.
Disclosure: P. J. Homan, None; S. Dominguez, None; H. Perlman, None; D. R. WInter, None; C. Cuda, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/dynamics-of-transcriptional-signatures-from-

purified-synovial-macrophage-subsets-during-acute-and-chronic-murine-models-of-inflammatory-arthritis
Mapping Changes in Monocyte and Macrophage Populations in the Synovium: An

Aging Study in Arthritic KRN Ag7 Mice
Anna B Montgomery1, Carla Cuda2, Philip J. Homan3, Harris Perlman2 and Deborah R. WInter2, 1Division of Rheumatology,
Northwestern University Feinberg School of Medicine, Chicago, IL, 2Department of Medicine Division of Rheumatology,
Northwestern University Feinberg School of Medicine, Chicago, IL, 3Division of Rheumatology, Department of Medicine,
Northwestern University Feinberg School of Medicine, Chicago, IL
SESSION INFORMATION
Background/Purpose: Rheumatoid arthritis (RA) is an autoimmune disease of the joints associated with accelerated aging and
increased mortality. Further, RA is linked with a number of co-morbidities including cardiovascular disease, which accounts for 40% of
RA mortality. Synovial macrophages are a key effector cell in joint inflammation, and a reduction in sublining synovial macrophages is
the only current reproducible biomarker for successful response to therapy. Thus, characterization of synovial macrophages during
disease could provide insight into progression of RA and increased mortality upon aging. To that end, the aim of this study was to use
KRN Ag7mice that develop spontaneous arthritis and atherosclerosis to monitor changes in the cellular composition of arthritic
synovium in parallel with non-diseased C57Bl/6 controls.
Methods: KRN Ag7 and C57Bl/6 mice were bred in house and euthanized at desired timepoints (1, 3, 6, 9, 12, and 18 months) when
ankles were collected for extraction of synovium. Single cell suspensions were prepared from synovial tissue and stained with an
antibody cocktail designed to identify monocyte and macrophage populations, which were sorted from single cell suspensions using BD
FACSAria 4-Laser. Statistical analysis was carried out in Flowjo v9 and Prism7. Statistical significance was defined P ≤ 0.05.
Results: KRN Ag7 mice displayed arthropathy from birth, and 20% increased mortality compared to C57Bl/6 at 12 months. Flow
cytometry analysis of synovial tissue showed a trend towards an overall reduction in CD11b+ leukocytes in KRN Ag7 mice, which
became statistically significant from 6 months. Further analysis of KRN Ag7 synovium identified two phases of disease, an
inflammatory phase from months 1-3 and an attempted resolution phase from 6 months. The inflammatory phase was characterized by
significant increases in eosinophils and neutrophils and a decrease in dendritic cells compared to C57Bl/6. During resolution phase
levels of these three populations trended towards C57Bl/6 levels, but remained significantly different. Levels of neutrophils in KRN
Ag7 mice also correlated with Ly6clo monocytes, which are required for neutrophil recruitment. Levels of CD11b+CD64+Ly6clo
macrophages in KRN Ag7 synovium peaked in inflammation phase but remained lower than those of C57Bl/6 at all time points.
Subdivision of macrophages into 4 populations based on expression of MHCII and CX3CR1 identified populations associated with both
phases of disease. MHCII+CX3CR1- and MHCII-CX3CR1+ macrophages were significantly higher and lower respectively than
C57Bl/6 during inflammation, but during initial resolution at 6 months reached comparable levels to those of C57Bl/6. However this
was not maintained, and levels of both populations returned to baselines by 18 months. Neither MHCII+CX3CR1+ nor MHCII-
CX3CR1- macrophages significantly changed.
Conclusion: Using KRN Ag7 mice, that best recapitulate human disease, we have characterized the cellular dynamics in arthritis upon
aging, which are distinct from those observed in non-arthritic mice. By identifying the critical populations, and further characterization
of their transcriptional profile, we can provide insight into RA progression with age.
Disclosure: A. B. Montgomery, None; C. Cuda, None; P. J. Homan, None; H. Perlman, None; D. R. WInter, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/mapping-changes-in-monocyte-and-macrophage-

populations-in-the-synovium-an-aging-study-in-arthritic-krn-ag7-mice
Selective Inhibition of Tfh Cells By a Small Molecule Inhibitor Abrogates

Progression of Experimental Inflammatory Arthritis
Frank Migliore1, Sedrick Bradley1, Linh Hellmers1, Quretul Quresh2, Jerald M. Zakem3, William E. Davis3, Tamika Webb-Detiege1,
Zongbing You4, Robert Quinet2 and Xin Zhang5, 1Ochsner Clinic Foundation, New Orleans, LA, 2Rheumatology, Ochsner Medical
Center, New Orleans, LA, 3University of Queensland School of Medicine, Brisbane, Australia, 4Tulane University Health Science
Center, New Orleans, LA, 5Laboratory of Cellular Immunology, Institution of Translational Research, Ochsner Medical Center, New
Orleans, LA
SESSION INFORMATION
Background/Purpose:
Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease characterized by progressive infiltration of the joints by T
cells and other leukocytes, production of mediators of inflammation, and the eventual destruction of joints. T follicular helper (Tfh)
cells are a unique subset of CD4+ T cells, predominantly located in B cell follicles, and regulate the survival of B cells and antibody
production in germinal centers. Our previous studies have showed that circulating Tfh cells were significantly increased in active RA
patients, correlating with the percentage of plasmablasts, anti-CCP antibody titer, and disease activity in active RA patients, indicating
that Tfh cells may play an important role in RA pathogenesis. The purpose of this study is to investigate the therapeutic potential of a
small molecule inhibitor targeting Tfh cells in mice with collagen-induced arthritis (CIA).
Methods:
CIA was induced in twenty-four DBA/1 mice by immunization with chicken type II collagen. Following the onset of clinical arthritis,
mice were treated with a small molecule inhibitor (SMI-Tfh) selective blockage of Tfh cell signature transcription factor Bcl-6. Disease
progression was monitored daily and recorded by arthritis severity scores weekly. Blood, spleen, and affected paws were collected at the
end of the study. Tfh cells in spleen and blood were defined by their signature surface markers (CD4+CXCR5+ICOS+) via flow
cytometry and analyzed using FlowJo software. The immune cells were further confirmed in mice spleen by immunohistochemistry
staining. Statistical analysis was carried out using GraphPad Prism software and the significance was evaluated by t test.
Results:
Mice developed arthritis four weeks after immunization with type II collagen. Treatment with SMI-Tfh (50mg/kg) significantly reduced
the disease progression/activity(as measured by paw swelling) in mice with CIA. SMI-Tfh significantly inhibited the frequency of Tfh
cells in spleen (P<0.01), but not the frequency of circulating Tfh cells in CIA mice (P>0.05). In addition, SMI-Tfh also inhibited B cell
proliferation induced by Tfh cells and antibody production in vitro.
Conclusion:
The small molecule inhibitor SMI-Tfh selectively inhibits Tfh cells and abrogates progression/activity of inflammatory arthritis in CIA
mouse model. Treatment with our small molecule SMI-Tfh in CIA mice provides a potential strategy for joint protection and may be
beneficial in RA patients. This is first report that a small molecule targeting Tfh cells in RA may be an approach worth further
investigation in RA.
Disclosure: F. Migliore, None; S. Bradley, None; L. Hellmers, None; Q. Quresh, None; J. M. Zakem, None; W. E. Davis, None; T.
Webb-Detiege, None; Z. You, None; R. Quinet, None; X. Zhang, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/selective-inhibition-of-tfh-cells-by-a-small-

molecule-inhibitor-abrogates-progression-of-experimental-inflammatory-arthritis
CR6086 Is Highly Effective and Improves Methotrexate Effect in a Mouse Model of

Gianfranco Caselli1, Flora Ferrari1, Eleonora Comi1, Marco Perrella1, Camilla Recordati2, Adriana Grotti1, Rosanna Cavagnoli1,
Marco Lanza1 and Lucio C. Rovati3, 1Rottapharm Biotech, Monza, Italy, 2Mouse & Animal Pathology Lab,, Fondazione Filarete,
Milano, Italy, Milano, Italy, 3Clinical Research Department, Rottapharm Biotech, Monza, Italy
SESSION INFORMATION
Background/Purpose: CR6086, a selective EP4 antagonist, dose-dependently improves disease features in rheumatoid arthritis (RA)
models in rodents. Indeed, recent studies highlight the role of the EP4 receptor in modulating autoimmunity and in counteracting bone
erosion. Aim of the present study was to test CR6086 as an add-on medication with methotrexate (MTX).
Methods: DBA/1 male mice were immunized with bovine type II collagen (BCII) in CFA. On arthritis onset, animals were assigned to
the following experimental groups: vehicle, oral CR6086 30 mg/kg/day, MTX 1 or 3 mg/kg/three times a week alone or in combination
with daily CR6086 30 mg/kg. Edema measurement and clinical scores were blindly determined daily before drug administration. After
2 weeks of treatment, mice were sacrificed and serum BCII antibodies measured. Paw joints were blindly scored for histological
features. Data were analyzed by ANOVA or by Kruskal-Wallis test followed by appropriate post-hoc comparison test.
Results: CR6086 strongly and significantly reduced score and edema within the first week of treatment compared to vehicle. MTX 3
mg/kg modestly reduced clinical signs over the second week of treatment, while MTX 1 mg/kg was inactive. CR6086/MTX combined
treatments significantly reduced clinical score and edema within the first week of treatment. Figure 1 reports the AUC analysis of the
whole treatment. Post-hoc pairwise comparisons showed that combined treatments were significantly superior to each single treatment
(P<0.05 and P<0.01 vs. CR6086 and MTX alone, respectively).
Histological features showed a similar treatment pattern (Fig.2), but the effects of CR6086 were so strong when given alone that we
could not show a significant synergism with MTX but only a trend.
All treatments, but MTX 1 mg/kg, decreased BCII antibodies serum levels (Fig. 3).
Conclusion: In a widely used animal model for RA, CR6086 was effective on all parameters examined both alone and combined with
MTX. The superior overall efficacy of CR6086 vs. a classical immunosuppressant as MTX, at equally effective doses on BCII
antibodies, outlines that CR6086 independently controls various pathological RA pathways. Moreover, the fact that CR6086 improved
MTX effect strengthens its use in early RA in DMARD naïve patients, as presently investigated in clinical trials.
Disclosure: G. Caselli, Rottapharm Biotech, 3; F. Ferrari, Rottapharm Biotech, 3; E. Comi, Rottapharm Biotech, 3; M. Perrella,
Rottapharm Biotech, 3; C. Recordati, Rottapharm Biotech, 5; A. Grotti, Rottapharm Biotech, 3; R. Cavagnoli, Rottapharm Biotech, 3;
M. Lanza, Rottapharm Biotech, 3; L. C. Rovati, Rottapharm Biotech, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/cr6086-is-highly-effective-and-improves-

methotrexate-effect-in-a-mouse-model-of-rheumatoid-arthritis
An Evaluation of Absolute Neutrophil Count As a Biomarker of Inflammatory and

Clinical Disease Activity in Baricitinib-Treated Patients
Iain B. McInnes1, Lee S. Simon2, Robert J. Moots3, Vipin K. Arora4, John D. Bradley4 and David Muram4, 1University of Glasgow,
Glasgow, United Kingdom, 2SDG LLC, Cambridge, MA, 3University of Liverpool, Liverpool, UK, Liverpool, United Kingdom, 4Eli
Lilly and Company, Indianapolis, IN
SESSION INFORMATION
Session Title: Rheumatoid Arthritis – Clinical Aspects Poster I: Treatment Patterns and Response
Background/Purpose: Rheumatoid arthritis (RA) patients (pts) tend to have higher absolute neutrophil count (ANC) values compared
to healthy individuals.1 Baricitinib (BARI), an oral, selective Janus kinase (JAK)1/JAK2 inhibitor,2 reduced disease activity levels in
RA pts with an inadequate response (IR) to methotrexate (MTX).3 BARI also reduced neutrophil counts in these pts.3 Herein we
assessed the association between changes in ANC and the reduction in inflammation, as determined by high-sensitivity C-reactive
protein (hsCRP) levels, and by inference clinical responses in pts receiving BARI 4-mg in the RA-BEAM trial.
Methods: RA-BEAM was a 52 week (wk) Phase 3 trial with RA pts randomized to placebo, BARI 4-mg once daily, or adalimumab 40-
mg biweekly. Primary end-point of the trial was the proportion of pts achieving ACR20 at wk 12. This post hoc analysis evaluated the
changes in observed ANC in BARI 4-mg treated pts with either ≤15% or ≥70% reduction in hsCRP from baseline to wk 12. Proportion
of pts achieving low disease activity (LDA), as determined by Clinical Disease Activity Index (CDAI) ≤10, or DAS28-hsCRP <2.6 at
12 wks was evaluated as a function of percent change in ANC from baseline to wk 8, at which time a peak decline in ANC was
observed (Figure 1).
Results: Of the 487 pts in the BARI 4-mg treatment arm of the RA-BEAM study, 78 pts demonstrated ≤15% reduction in hsCRP and
298 pts had ≥70% reduction in hsCRP at 12 wks. The mean neutrophil count at wk 8 in pts with ≤15% reduction in hsCRP was higher
when compared to pts with ≥70% reduction (Figure 2), suggesting that the decline in ANC was associated with reduction in the
inflammatory process. The reduction in ANC was associated with an improved clinical response as demonstrated by the proportion of
pts achieving LDA (CDAI ≤10) or DAS28-hsCRP <2.6 at 12 wks. In contrast, a smaller proportion of pts achieved LDA when an
increase in ANC was observed (Figure 3). These observations were similar regardless of the use of concomitant oral corticosteroids.
Conclusion: The decline in ANC is associated with a reduction in the overall inflammatory process and may also be associated with
disease activity.
References: 1.Syed KM J Clin Rheumatol (1996) 2. Fridman JS J Immunol (2010) 3.Taylor PC et al N Engl J Med (2017)
Disclosure: I. B. McInnes, Eli Lilly and Company, Abbvie, Pfizer, Novartis, Roche, Janssen, 2,Eli Lilly and Company, Abbvie, Pfizer,
Novartis, Roche, Janssen, 5; L. S. Simon, Affinergy, Astrazeneca, Abraxxis, Alpha Rx, NuvoResearch, Roche, Pfizer, Novartis, PLx
Pharma, Hisamatsu, Dr Reddys, Avanir, Cerimon, Leerink Swann, Alimera, Nomura, Luxor, Paraexel, Antares, Bayer, Rigel, Chelsea,
Regeneron, Eli Lilly and Company, 5,Fidelity, Extera, Wyeth, Asahi, Sammuded, Metabolex, Shire, Anthera, Antares, Vical, Daiichi
Sankyo, Flexion, AcelRx, Inotek, Gilead, Puretechventures, White Mountain Pharma, Abbott, Omeros, Jazz, Takeda, Teva, Zydus,
Proprius, Alder, Cephalon, Purdue, 5,XTL, Inmedix, Nicox, EMDSerono, Altea, Talagen,Tigenix, Agenus, Forest, Genzyme, CaloSyn,
pSivida, Horizon, Pozen, Eicos Sciences, Analgesic Solutions, Bayer, Kowa, Array, JRX Biopharm, Imprimis, Dara, Genco, Neos,
Durect, Sanofi, Idera, Medac, Remedy, 5; R. J. Moots, None; V. K. Arora, Eli Lilly and Company, 1,Eli Lilly and Company, 3; J. D.
Bradley, Eli Lilly and Company, 1,Eli Lilly and Company, 3; D. Muram, Eli Lilly and Company, 1,Eli Lilly and Company, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/an-evaluation-of-absolute-neutrophil-count-as-a-

biomarker-of-inflammatory-and-clinical-disease-activity-in-baricitinib-treated-patients
Association between Anti-Citrullinated Protein Antibody Status and the Incidence of

Erosive Disease in Patients with RA
Leslie R Harrold1, Heather J. Litman2, SE Connolly3, E Alemao3, Sabrina Rebello4, W Hua2 and Joel Kremer5, 1University of
Massachusetts Medical School, Worcester, MA, 2Corrona, Southborough, MA, 3Bristol-Myers Squibb, Princeton, NJ, 4Corrona, LLC,
Southborough, MA, 5Albany Medical College and The Center for Rheumatology, Albany, NY
SESSION INFORMATION
Background/Purpose: RA is characterized by the production of autoantibodies including anti-citrullinated protein antibodies

(ACPAs).1 ACPAs are considered a prognostic indicator for more severe RA and more rapid disease progression.2,3 Little is known
regarding the incidence of erosions overall in a contemporary cohort of patients with access to biologics or the association with ACPA
status. This analysis aimed to characterize the incidence of erosive disease and its association with ACPA serological status in patients
with RA.
Methods: We identified patients aged ≥18 years with RA disease duration ≤2 years who were enrolled in the Corrona Registry (October
2001 to June 2016) with ACPA status available at or before their enrollment visit and no evidence of erosions on their first visit at
which radiographic information was reported. To assess incidence of erosions, we followed patients until their first radiograph showed
evidence of erosions or their last follow-up visit, whichever came first. The primary outcome was the incidence of erosions (calculated
as the total number of first erosions divided by the total radiographic follow-up time), overall and by ACPA status (negative anti-cyclic
citrullinated peptide [CCP] <20 vs positive anti-CCP ≥20), unadjusted and adjusted (for age and baseline disease activity using the
CDAI). Cox proportional hazards modeling was used to assess the hazard ratio (HR) (with 95% CIs) of erosive disease.
Results: In total, 693 patients (452 ACPA positive and 241 ACPA negative) met the inclusion criteria. Most were women (70.6%),
middle-aged (mean [SD] 55 [13.3] years), with moderate disease activity based on the CDAI (13.9 [13.0]). Prior use of ≥1
biologic/targeted synthetic DMARD had occurred in 29.3% of patients. In total, 187 first erosions over 1344.27 person-years of
radiographic follow-up time were recorded with an incidence rate of 13.9 erosions/100 person-years of follow-up. The incidence of
erosions among ACPA-positive patients was 14.8/100 person-years vs 12.2/100 person-years in those who were ACPA negative
(unadjusted HR 1.21; 95% CI 0.88, 1.67; p=0.23; Table). In adjusted analyses, ACPA status was associated with the incidence of
erosions (HR 1.30; 95% CI 0.94, 1.80; p=0.11), although the estimate included unity (Table).
Table. Incidence Rate Overall and by ACPA Status
Total Total number Incidence Unadjusted Adjusted*
number of of person- rate of HR (95%
first years of erosions CI) HR (95%
erosions radiographic (per 100 CI)
follow-up time person-
years)
Overall 187 1344.27 13.9
By ACPA status
ACPA+ 1.21 (0.88, 1.30 (0.94,
1.67) 1.80)
132 893.60 14.8
p=0.23 p=0.11
ACPA– 55 450.67 12.2 reference reference
*Adjusted for baseline CDAI score (0–10, >10–22, >22) and baseline age
(18–<45, 45–<55, 55–<65, 65–90 years)
ACPA=anti-citrullinated protein antibody; HR=hazard ratio
Conclusion:
In this contemporary cohort of patients with early RA, incident erosions were common. Our findings suggest further exploration of the
association of ACPAs and the incidence of erosions is needed, and whether medications including biologic/targeted synthetic DMARDs
influence the relationship.
1. Scott DL, et al. Lancet 2010;376:1094–108.
2. Hecht C, et al. Ann Rheum Dis 2015;74:2151–6.
3. Aletaha D, et al. Arthritis Res Ther 2015;17:229.
Disclosure: L. R. Harrold, Corrona, 1,Pfizer Inc, 2,Roche Pharmaceuticals, 5,Corrona, 3; H. J. Litman, Corrona, 3; S. Connolly,
Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1; E. Alemao, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1; S. Rebello, Corrona,
3; W. Hua, Corrona, 3; J. Kremer, Corrona, 1,AbbVie, BMS, Genentech, Lilly, Novartis, Pfizer, 2,Corrona, 3,Genentech and Biogen
IDEC Inc., 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/association-between-anti-citrullinated-protein-

antibody-status-and-the-incidence-of-erosive-disease-in-patients-with-ra
Factors That Drive Treatment Recommendation during Rheumatoid Arthritis

Patient´s Follow-up, Differ According to Physician Experience
César Sifuentes-Cantú1, Irazu Contreras-Yañez2, Lina Saldarriaga Rivera3, Ana Cecilia Lozada4, Marwin Gutierrez5 and Virginia
Pascual-Ramos1, 1Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador
Zubirán, Mexico City, Mexico, 2Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán,
Mexico, Mexico, 3Instituto Nacional de Rehabilitación, Mexico, Mexico, 4Division of musculoskeletal and rheumatic diseases, Instituto
Nacional de Rehabilitación, Mexico City, Mexico, 5Rheumatology, Instituto Nacional de Rehabilitación, Mexico City, Mexico
SESSION INFORMATION
Background/Purpose:
The management plan for rheumatoid arthritis (RA) might be a relatively simple task if only disease activity is considered but might
become more complex when additional factors are considered.
Previously, in a real clinical setting of RA outpatients, we explored the impact of musculoskeletal ultrasound, added to clinical
evaluations in the treatment decision; we found that ultrasound had a greater impact in the trainee (TR) than in the senior
rheumatologist (SR).
The aim of the present study was to investigate which factors impact the treatment recommendation in RA outpatients and to detect
potential differences among 2 rheumatologists categorized by their experience, TR vs. SR.
Methods:
Eighty-five consecutive and randomly selected RA outpatients underwent 170 assessments, 85 each by the SR and the TR. Initially,
both physicians performed a complete rheumatic assessment which included disease activity as per DAS28 and recommended a
treatment. Then, the patients underwent a musculoskeletal evaluation by an independent rheumatologist. In the final step, the TR and
the SR integrated ultrasound findings with their previous evaluation and reviewed their recommendations. In addition, immediately
after each patient encounter, both physicians were instructed to select and rate, which among the following factors were determinant in
the final treatment proposal: clinical assessments, ultrasound findings, comorbidities, treatment related adverse events,
costs/availability, patient«s preference and DMARD maximum dose. In all the instances, the SR and the TR were blinded to each other
assessments. Data were obtained on standardized formats. Descriptive statistics were used. The study was approved by the local IRB
and all the patients signed informed consent.
Results:
Patients were primary middle-aged (mean±SD: 45.1 ± 12.4 years) female (91.4%) and had disease duration of 7.5±3.9 years. The
majority of the patients were in DAS28 remission (<2.6) and 24 (28.2%) showed some disease activity. All the patients were on
DMARDs and 48% had additional low doses of oral corticosteroids.
Clinical assessments were rated as determinants in the totality of the clinical scenarios, followed by ultrasound findings in 84.7%,
DMARD maximum dose in 41.2%, comorbidities in 23%, DMARD cost/availability in 21.2%, DMARD-related adverse events in 20%
and finally, patient preference was rated as determinant in 14.1% of the clinical scenarios. Interestingly, the SR and the TR differed in
the selection of the factors they considered determinant for the treatment proposal (Figure).
Conclusion:
Disease activity drives the treatment decision during RA patients follow-up, although additional factors may be considered.
Considerable variation was observed in how doctors rated those factors and these variations depended on physician«s experience.
Figure
Disclosure: C. Sifuentes-Cantú, None; I. Contreras-Yañez, None; L. Saldarriaga Rivera, None; A. C. Lozada, None; M.
Gutierrez, None; V. Pascual-Ramos, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/factors-that-drive-treatment-recommendation-

during-rheumatoid-arthritis-patients-follow-up-differ-according-to-physician-experience
Baseline Values for Plantar Pressure and Background Characteristics As Indicators

for the Limit of Conservative Treatment of Rheumatoid Forefoot Deformity
Hyunho Lee1, Hajime Ishikawa1, Asami Abe1, Yumi Nomura1, Eriko Hasegawa1, Chinatsu Takai1, Daisuke Kobayashi1, Hiroshi
Otani1, Satoshi Ito1, Takanobu Sumino2, Takao Ishii2, Shu Saito3, Yasuaki Tokuhashi4, Kiyoshi Nakazono1 and Akira Murasawa1,
1Department of Rheumatology, Niigata Rheumatic Center, Shibata, Japan, 2Department of Orthopaedic Surgery, Kawaguchi Municipal
Medical Center, Kawaguchi, Japan, 3Department of Orthopaedic Surgery, Nihon University School of Medicine, Itabishi, Japan,
4Department of Orthopaedic Surgery, Nihon University School of Medicine, Itabiashi, Japan
SESSION INFORMATION
Background/Purpose: Forefoot deformities are commonly seen in patients with RA. It has been reported that nearly 90% of the
patients have foot problems.1,2 Patients with RA often suffer from callosity or metatarsalgia in the rheumatoid foot. Forefoot surgery is
often necessitated in cases of painful forefoot deformities in which conservative treatment proves to be insufficient.3,4 The purpose of
this study is to investigate the differences in plantar pressure and background characteristics between the patients without scheduled
forefoot surgery (group N) and the patients with scheduled forefoot surgery (group S), and to identify those characteristics that might be
useful as indicators for conservative treatment.
Methods: Patients with RA were divided into 2 groups: group N and group S. The former consisted of 250 feet in 141 patients, and the
latter consisted of 125 feet in 72 patients. DAS28, hallux valgus angle (HVA), the angle between the first and the second metatarsal
bone (M1/2), the angle between the first and the fifth metatarsal bone (M1/5) and distribution of the site of callosity were evaluated as
background characteristics. Distribution of peak pressure as plantar pressure was measured in 9 sections, including the first
interphalangeal joint, the first through the fifth metatarsophalangeal joints (MTPJ), the medial and lateral midfoot, and the hindfoot. In
addition, maximum peak pressure (MAXPP), minimum peak pressure (MINPP) and the difference value between MAXPP and MINPP
(Δ pressure) were also measured. The MAXPP and MINPP indicates the highest and lowest peak pressure value found among the peak
pressure measurements of all 9 sections, respectively. Finally, cut-off values were calculated from the receiver operating characteristic
curve for each item which differed significantly between the 2 groups.
Results: In groups N and S, the mean DAS was 3.7 and 3.0 (p<0.001), the mean HVA was 19.4° and 34.5° (P<0.001), the mean M1/2
was 11.5° and 14.1° (P<0.001), and the mean M1/5 was 30.3° and 33.1°, respectively. Callosities were seen at the second and third
MTPJ in half of all patients in group S. The mean peak pressure of group S at the first, second, third MTPJ, medial midfoot and
hindfoot was significantly higher than that of group N (P <0.001, 0.05, 0.01,0.05 and 0.01). Significant differences between the 2
groups were also seen in MAXPP, MINPP and Δ pressure (P <0.001, 0.05 and 0.001). The cut-off values were 24.9° for HVA, 4.81
kg/cm2 for MAXPP and 4.51 kg/cm2 for Δ pressure. At the cut-off values, sensitivities were 76.0%, 69.6% and 67.4%, and specificities
were 71.2%, 57.2% and 60.8%, respectively. Assessing HVA and MAXPP in combination, sensitivity was 46.4%, and specificity was
90.8%.
Conclusion: The combined assessment of HVA and MAXPP appeared to be useful as an indicator for conservative treatment of
rheumatoid forefoot deformity. It is important to keep MAXPP under 4.81 kg/cm2 through drug treatment, orthotic treatment and
physical treatment, in order to avoid forefoot surgery.
References:
1. Vainio K. Ann Chir Gynaecol Fenn Suppl. 1956;45(1):1-107.

2. Thould AK, et al. Ann Rheum Dis. 1966;25(3):220-8.
3. Helal B, et al. J Bone Joint Surg Brit Vol. 1984;66(2):213-7.
4. Niki H, et al. J Bone Joint Surg Brit Vol. 2010;92(3):380-6.
Disclosure: H. Lee, None; H. Ishikawa, None; A. Abe, None; Y. Nomura, None; E. Hasegawa, None; C. Takai, None; D.
Kobayashi, None; H. Otani, None; S. Ito, None; T. Sumino, None; T. Ishii, None; S. Saito, None; Y. Tokuhashi, None; K.
Nakazono, None; A. Murasawa, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/baseline-values-for-plantar-pressure-and-

background-characteristics-as-indicators-for-the-limit-of-conservative-treatment-of-rheumatoid-forefoot-deformity
Economic Burden Associated with Anti-Cyclic Citrullinated Peptide Antibody

Positivity in Patients Newly Diagnosed with RA
J An1, Z Bider2, J Kang1, E Alemao3, SE Connolly3 and TC Cheetham1, 1Western University of Health Sciences, Pomona, CA,
2Southern California Permanente Medical Group, Pasadena, CA, 3Bristol-Myers Squibb, Princeton, NJ
SESSION INFORMATION
Background/Purpose: Anti-cyclic citrullinated peptide (anti-CCP) antibody positivity has been suggested as a strong predictor of joint
erosion as well as a potential biomarker for guiding treatment decisions. There are limited data evaluating the economic burden of anti-
CCP positivity. We investigated the association between anti-CCP positivity and healthcare expenditures in newly diagnosed patients
(pts) with RA.
Methods: A retrospective cohort study was conducted in adult pts with RA in Kaiser Permanente Southern California (Jan 2007 to Dec
2014). Individuals were followed from their first RA diagnosis (index) for 12 months. Pts were required to have two International
Classification of Diseases, Ninth Revision, RA diagnosis codes of 714.0–714.8, a DMARD prescription, and continuous eligibility for
12 months prior to and after index date. Pt demographics, anti-CCP status, co-morbidity and healthcare resource utilization during the
study period were collected. Nationally recognized direct medical costs were assigned to healthcare utilizations to calculate healthcare
costs in 2015 US dollars. Difference-in-difference (DID) propensity score analyses were conducted to determine the association
between anti-CCP positivity and 12-month cost outcomes. A generalized linear regression model with recycled prediction methods was
used to quantify the differences of changes in costs (ddd) between the anti-CCP-positive (anti-CCP+) and anti-CCP-negative (anti-
CCP–) groups.
Results: A total of 2448 newly diagnosed pts with RA were identified with a mean (SD) age of 55.5 (14.3) years; 75.7% were female.
At baseline, 65.8% of pts were anti-CCP+ and 34.2% were anti-CCP–, where anti-CCP+ pts had fewer co-morbidities (median
Elixhauser co-morbidity scores: 3 vs 4; p<0.001) versus anti-CCP– pts. During follow-up, more anti-CCP+ pts received ≥1 biologic
DMARD (22.6 vs 12.9%; p<0.001) and had more frequent rheumatologist visits (median number: 5 vs 4; p<0.001) versus anti-CCP–
pts. During the 12-month follow-up, median (interquartile range) total healthcare expenditure for anti-CCP+ and anti-CCP– pts was
$6200 ($3563–13,260) and $7022 ($3885–12,995), respectively. For the DID, when considering baseline costs, pt demographics and
co-morbidities, anti-CCP positivity was significantly associated with higher prescription (ddd=$2499; p<0.001), laboratory testing
(ddd=$183; p<0.001) and rheumatologist visit costs (ddd=$76; p<0.001). Total incremental cost associated with anti-CCP positivity was
estimated as $2163 (p=0.001; Figure). No statistical differences were found in hospitalizations or emergency department-related costs.
Conclusion: In newly diagnosed pts with RA, the higher economic burden for anti-CCP+ pts was mainly driven by pharmacy costs.
Future pt-reported outcomes and/or disease progression associated with the early economic burden may help guide treatment decisions.
Disclosure: J. An, Bristol-Myers Squibb, Pfizer, 2; Z. Bider, None; J. Kang, None; E. Alemao, Bristol-Myers Squibb, 3,Bristol-
Myers Squibb, 1; S. Connolly, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1; T. Cheetham, Bristol-Myers Squibb, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/economic-burden-associated-with-anti-cyclic-

citrullinated-peptide-antibody-positivity-in-patients-newly-diagnosed-with-ra
Multi-Biomarker Disease Activity and Autoantibody Status Lead to Cost Effective

Tapering Algorithms in Rheumatoid Arthritis Patients in Sustained Remission
Melanie Hagen1, Matthias Englbrecht2, Judith Haschka3, Michaela Reiser4, Arnd Kleyer5, Axel J. Hueber6, Bernhard Manger7,
Camille Figueiredo8, Jayme Fogagnolo Cobra9, Hans-Peter Tony10, Stefanie Finzel11, Stefan Kleinert12, Joerg Wendler13, Florian
Schuch13, Monika Ronneberger13, Martin Feuchtenberger14, Martin Fleck15,16, Karin Manger17, Matthias Schmitt-Haendle18, H.-M.
Lorenz19, HG Nüßlein20, Rieke Alten21, Joerg C. Henes22, Klaus Krüger23, Georg Schett2 and Juergen Rech24, 1University of
Erlangen-Nuremberg, Erlangen, Germany, 2Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen,
Germany, 3Medical Department II, St. Vincent Hospital, the VINFORCE Study Group, Academic Teaching Hospital of Medical
University of Vienna, Vienna, Austria, Vienna, Austria, 4Department of Medicine 3, Rheumatology and Immunology, University of
Erlangen-Nuremberg, Erlangen, Germany, 5Dept of Medicine 3, Rheumatology and Clinical Immunology, Department of Internal
Medicine 3 – Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany, 6Department
of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, 7Dept of
Medicine 3, Rheumatology and Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, 8Institution de
Rheumatologia, Sao Paolo, Brazil, 9Instituto de Reumatologia de Sao Paolo, Sao Paolo, Brazil, 10Rheumatology/Clinical Immunology,
University of Würzburg, Würzburg, Germany, 11University of Freiburg, Freiburg, Germany, 12Rheumatologische Schwerpunktpraxis
Erlangen, Erlangen, Germany, 13Schwerpunktpraxis Rheumatologie, Erlangen, Germany, 14Rheumatologie/Klinische Immunologie,
Kreiskliniken Altötting-Burghausen, Burghausen, Germany, 15Department of Rheumatology and Clinical Immunology, Asklepios
Medical Center Bad Abbach, Bad Abbach, Germany, 16Internal Medicine I, University Medical Center of Regensburg, Regensburg,
Germany, 17Rheumatology Practice Bamberg, Bamberg, Germany, 18Rheumatology Practice, Bayreuth, Germany, Bayreuth, Germany,
19Rheumatology, University Heidelberg, Heidelberg, Germany, 20Rheumatology Practice Nuremberg, Nuremberg, Germany,
21Schlosspark-Klinik, University Medicine Berlin, Berlin, Germany, 22Department of Internal Medicine II, Division of Rheumatology,
University Hospital Tuebingen, Tuebingen, Germany, 23Praxiszentrum St.Bonifatius, Munich, Germany, 24Friedrich-Alexander-
University Erlangen-Nürnberg (FAU), Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum
Erlangen, Erlangen, Germany., Erlangen, Germany
SESSION INFORMATION
Background/Purpose:
Achieving remission is the ultimate treatment goal in patients with rheumatoid arthritis (RA). With the development and wider use of
highly effective disease modifying anti-rheumatic drugs (DMARD) about half of RA patients reach the disease remission state (1),
raising the question about tapering or stopping anti-rheumatic treatment and appropriate predictors (2). The purpose was to analyse the
effect of a risk-stratified DMARD tapering algorithm based on multiple-biomarker disease activity (MBDA) score and anti-citrullinated
protein (ACPA) status for successful DMARD tapering and treatment cost reduction in RA patients in sustained remission enrolled in
the prospective randomized controlled RETRO study (3,4).
Methods: MBDA scores and ACPA status were determined in the baseline samples of 146. A patients in sustained remission. Patients
either continued DMARDs (arm1), tapered dose by 50% (arm 2) or stopped DMARDs after tapering (arm 3) for one year according to
the RETRO study protocol. Direct treatment costs (including testing costs at baseline) were evaluated every three months. MBDA and
ACPA status were used as predictors creating a risk-stratified tapering algorithm based on relapse rates.
Results: RA patients with a low MBDA score (<30) and negative ACPA showed lowest relapse risk (19%). With either single positivity
for ACPA or moderate/high MBDA scores (>30) relapse risk increased and was high in double-positive patients (61%). In MBDA
negative (<30) and MBDA single-positive (>30) groups, DMARD tapering appears feasible. Considering only patients that did not
flare, costs for synthetic and biologic DMARDs in the MBDA-negative and single-positive groups (n=41) would have been
123.751,29€ for full-dose treatment over one year. Tapering and stopping DMARDs in this low-risk relapse groups allowed a reduction
of 92.821,50€ (-75%) of DMARD costs. Average reduction of DMARD costs per patient were 2.350,08€ in the double negative
(MBDA- /ACPA-) and single negative (MBDA- /ACPA+) group and 1.761,43€ in the MBDA single positive (MBDA+ /ACPA-) group.
Conclusion: Combining MBDA score and ACPA status allows risk stratification for successful DMARD tapering and cost-effective
use of biologic DMARD. Given that previous data of the RETRO have shown that patients relapsing after tapering their DMARDs
respond well to their reintroduction, a stratified tapering and stopping of DMARDs is not only a cost economic but also clinically
feasible strategy.
Disclosure: M. Hagen, None; M. Englbrecht, None; J. Haschka, None; M. Reiser, None; A. Kleyer, None; A. J. Hueber, None; B.
Manger, None; C. Figueiredo, None; J. F. Cobra, None; H. P. Tony, None; S. Finzel, None; S. Kleinert, None; J. Wendler, None; F.
Schuch, None; M. Ronneberger, None; M. Feuchtenberger, None; M. Fleck, None; K. Manger, None; M. Schmitt-Haendle, None;
H. M. Lorenz, None; H. Nüßlein, None; R. Alten, None; J. C. Henes, None; K. Krüger, None; G. Schett, None; J. Rech, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/multi-biomarker-disease-activity-and-autoantibody-
status-lead-to-cost-effective-tapering-algorithms-in-rheumatoid-arthritis-patients-in-sustained-remission
Baricitinib Reduces GlycA Levels in Phase 2 and Phase 3 Clinical Trials in Patients
with Moderate to Severe Rheumatoid Arthritis
Joel Kremer1, Paul Emery2, Margery A. Connelly3, James D. Otvos4, Steven H. Zuckerman5, Giacomo Ruotolo5, Lei Chen5, Maher
Issa5, William L. Macias5 and Iain B. McInnes6, 1Albany Medical College, Albany, NY, 2Leeds MSK Biomed/Chapel Allerton
Hospital, Leeds, United Kingdom, 3Laboratory Corporation of America Holdings (LabCorp), Morrisvile, NC, 4Laboratory Corporation
of America Holding (LabCorp), Morrisville, NC, 5Eli Lilly and Company, Indianapolis, IN, 6University of Glasgow, Glasgow, United
Kingdom
SESSION INFORMATION
Background/Purpose: Baricitinib (bari) is an oral selective inhibitor of Janus kinase (JAK) 1/JAK2.1 In the European Union, bari is
approved for the treatment of moderate to severe RA in adults. GlycA, a measure of glycosylated acute phase proteins, is an emerging
inflammatory marker that may be useful for assessment of disease activity and is associated with subclinical cardiovascular (CV)
disease in patients with RA.2,3 The objective of this analysis was to assess GlycA levels in a Phase 2 and 3 (RA-BEAM) study in
patients (pts) with RA treated with bari.
Methods: In the Phase 2 study, 301 pts were randomized 2:1:1:1:1 to placebo (PBO) or bari (1, 2, 4, or 8 mg) once daily (QD) for 12
weeks (wks). At Wk 12, pts initially assigned to PBO or bari 1 mg were rerandomized 1:1 to bari 2 mg twice daily or bari 4 mg QD; pts
initially assigned to bari 2, 4, or 8 mg QD continued that treatment. In RA-BEAM, 1305 pts were randomized 3:3:2 to PBO, bari 4 mg
QD, or adalimumab (ADA) 40 mg every 2 wks. GlycA levels were evaluated with nuclear magnetic resonance spectroscopy at baseline
and Wks 12 and 24. In these post hoc analyses, change from baseline to week 12 in GlycA levels were compared between treatment
groups without adjustment for multiple comparisons.
Results: Treatment with bari resulted in dose-dependent decreases in GlycA levels from baseline to Wk 12 in the Phase 2 study (-7.7%
to -14.4% in the 1- and 8-mg treatment groups, respectively), with similar results at Wk 24 (Figure). In RA-BEAM at Wk 12, GlycA
levels in pts treated with bari decreased significantly compared to PBO or ADA (Table 1). There were similar reductions in GlycA with
bari regardless of baseline statin use (Table 2).
Conclusion: Bari decreases GlycA in a dose-dependent manner; reductions were seen regardless of baseline statin treatment. With
recent studies suggesting GlycA as a marker for CV risk, these reductions in Phase 2 and 3 studies in an RA population may portend a
reduction in overall CV risk. Further long-term data will be required to assess the possibility.
References: 1Fridman JS et al. J Immunol 2010;184:5298-307; 2Ormseth MJ et al. Arthritis Research & Therapy 2015;17:117; 3Joshi
AA et al. Circulation Research 2016;119:1242-53
Table 1. GlycA levels in the Phase 3 RA-BEAM study
Placebo Baricitinib 4 mg Adalimumab
(N=488) (N=487) (N=330)

Baseline, µmol/L 508.9 (104.6) 517.2 (114.4) 513.9 (106.4)
Week 12, µmol/L 496.9 (104.3) 404.3 (91.9) 416.3 (105.0)
Change from
-13.6 (3.8) -110.9 (3.8)***† -98.7 (4.7)***
baseline to Week 12
Absolute data are mean (standard deviation); change from baseline data
are least-squares mean (standard error) ***p≤0.001 vs placebo †
p≤0.05 vs adalimumab
Table 2. Change in lipid and GlycA levels from baseline to Week 12 according to baseline statin
use in the Phase 3 RA-BEAM study
Baricitinib 4 Baricitinib 4 mg Adalimumab vs
Placebo Adalimumab
mg vs Placebo Placebo
Baseline Statin Use
(N=488) (N=330)
(N=487)
LSM (SE) LSMD (95% CI)
GlycA, µmol/L
No (n=389) -96.0 (-107, -86.0 (-98,
-13.5 (4.0) -109.5 (4.0) -99.5 (4.9)
-85)*** -74)***
Yes (n=37) -116.7 (-157, -79.9 (-123,
-14.3 (14.1) -131.0 (14.3) -94.2 (16.3)
-77)*** -37)***
Total cholesterol,
mg/dL
No (n=412) 26.8 (23.4, 12.9 (9.0,
-1.3 (1.3) 25.5 (1.2) 11.6 (1.5)
30.3)*** 16.8)***
Yes (n=37) 40.4 (22.0, 16.2 (-3.9, 36.3)
-5.7 (6.7) 34.7 (6.4) 10.5 (7.6)
58.7)***
LDL cholesterol,
mg/dL
No (n=404) 17.7 (14.8, 9.8 (6.5,
-2.2 (1.1) 15.5 (1.0) 7.6 (1.3)
20.6)*** 13.0)***
Yes (n=37) 25.0 (10.1, 11.2 (-5.1, 27.6)
-4.6 (5.4) 20.5 (5.2) 6.7 (6.2)
40.0)**
**p≤0.01, ***p≤0.001 vs placebo CI=confidence interval; LDL=low-density lipoprotein;
LSM=least-squares mean; LSMD=least-squares mean difference, SE=standard error
Disclosure: J. Kremer, Corrona, LLC, 1,Corrona, LLC, 3,AbbVie, Amgen, BMS, Genentech, Lilly, Regeneron, Sanofi, Pfizer,
5,AbbVie, Genentech, Lilly, Novartis, Pfizer, 2; P. Emery, Pfizer,MSD,Abbvie,BMS,UCB,Roche,Novartis,Samsung, Sandoz, Eli Lilly
and Company, 5; M. A. Connelly, Laboratory Corporation of America Holdings, 3; J. D. Otvos, Laboratory Corporation of America
Holdings, 3; S. H. Zuckerman, Eli Lilly and Company, 1,Eli Lilly and Company, 3; G. Ruotolo, Eli Lilly and Company, 1,Eli Lilly
and Company, 3; L. Chen, Eli Lilly and Company, 1,Eli Lilly and Company, 3; M. Issa, Eli Lilly and Company, 1,Eli Lilly and
Company, 3; W. L. Macias, Eli Lilly and Company, 1,Eli Lilly and Company, 3; I. B. McInnes, Eli Lilly and Company, Abbvie, Pfizer,
Novartis, Roche, Janssen, 2,Eli Lilly and Company, Abbvie, Pfizer, Novartis, Roche, Janssen, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/baricitinib-reduces-glyca-levels-in-phase-2-and-

phase-3-clinical-trials-in-patients-with-moderate-to-severe-rheumatoid-arthritis
The Impact of Therapy on Anti-Carbamylated Protein Antibody Isotypes and

Serostatus in Patients with Early RA Treated with Abatacept and MTX
LA Trouw1, SE Connolly2, A Johnsen2, J Ye2, MA Maldonado2, REM Toes1 and TWJ Huizinga1, 1Leiden University Medical Center,
Leiden, Netherlands, 2Bristol-Myers Squibb, Princeton, NJ
SESSION INFORMATION
Background/Purpose: Maturation of autoantibody responses has been suggested to be a proxy for disease maturation. Autoantibody
responses against post-translationally modified antigens are present in autoimmune diseases and antibodies directed against
carbamylated proteins (anti-CarP antibodies) are a marker of RA. Anti-CarP antibody analysis in patients (pts) with early RA offers the
opportunity to estimate whether specific intervention during such early stages of autoantibody development may have an impact on the
maturation of the anti-CarP antibody response. We assessed the relationship between changes in anti-CarP isotypes and rates of
seroconversion to negative (–ve) in pts with early RA. Methods: In the AVERT study (NCT01142726), pts with early RA were treated
with abatacept (ABA)+MTX, ABA monotherapy or MTX alone.1 Pts were anti-cyclic citrullinated peptide-2 positive (+ve) at baseline
for study entry.1 In this post hoc analysis, concentrations of anti-CarP isotypes were measured using custom ELISAs. Anti-CarP
ELISAs for immunoglobulin (Ig)G, IgM or IgA isotypes were performed in pt serum at baseline, and at Days 85 and 365 on treatment.
Baseline levels of each anti-CarP antibody isotype and % seropositivity were comparable across treatment arms. Adjusted mean change
from baseline was calculated using a longitudinal repeated measures model. Results: At baseline, 51.3, 42.5 and 29.3% of all pts with
serum available in AVERT were +ve for IgG, IgM (indicative of an ongoing immunoresponse) and IgA anti-CarP isotypes, respectively.
Overall, ~65% of pts were +ve for ≥1 anti-CarP antibody isotype. Median % change from baseline (25%, 75%) for anti-CarP isotype
levels from baseline to Days 85 and 365 are shown (Table). Analyzing pts who were +ve at baseline for each of the isotypes, we
observed that 19/48 (40%), 16/43 (37%) and 11/48 (23%) of pts +ve for the IgG isotype became –ve on ABA+MTX, ABA and MTX,
respectively, at 1 year. For the IgM isotype, 26/48 (54%), 14/36 (39%) and 15/38 (39%) became –ve on ABA+MTX, ABA and MTX,
respectively. For the IgA isotype, 12/26 (46%), 10/23 (43%) and 13/31 (42%) became –ve on ABA+MTX, ABA and MTX,
respectively.
Conclusion: Concentrations of all anti-CarP isotypes (IgM, IgA, IgG) were numerically reduced by abatacept+MTX therapy compared
with MTX or abatacept alone. Abatacept+MTX trended towards higher rates of seroconversion to –ve for all isotypes over 1 year of
treatment. These results indicate that the extent of the anti-CarP antibody response can be modulated by intervention with abatacept on
background MTX in anti-citrullinated protein antibody +ve pts with early RA.
1. Emery P, et al. Ann Rheum Dis 2015;74:19–26. Original abstract © EULAR/BMJ. First presented at EULAR 2017 and published in
Ann Rheum Dis 2017;76 (Suppl 2):1135. Any reprints, promotional options, education material etc have to be done through the original
source (ARD/BMJ).
Table. Median % Change from Baseline (25%, 75%) for Anti-CarP Isotypes
Day 85 Day 365
IgG IgM IgA IgG IgM IgA
Abatacept –17.3 (– –26.3 (– –6.8 (– –31.2 (– 26.0 (-81.2, –26.7 (–
55.7, 0.0) 57.9, 0.0) 35.1, 0.0) 67.4, 0.0) 0.0) 72.9, 13.0)
MTX –19.3 (– –35.7 (– –27.2 (– –17.7 (– –38.3 (– –21.9 (–
53.6, 0.0) 54.4, –6.9) 42.4, –3.9) 65.1, 0.0) 63.7, 0.0) 50.3, 0.0)
Abatacept+ –44.2 (– –41.3 (–
MTX –38.8 (– 59.5, – 54.9, – –55.7 (– –45.7 (– –46.4 (–
62.3, 0.0) 13.8) 28.3) 76.7, 0.0) 72.5, –0.2) 66.7, 0.0)
CarP=carbamylated proteins; Ig=immunoglobulin
Disclosure: L. Trouw, None; S. Connolly, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1; A. Johnsen, Bristol-Myers Squibb,
1,Bristol-Myers Squibb, 3; J. Ye, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; M. Maldonado, Bristol-Myers Squibb, 1,Bristol-
Myers Squibb, 3; R. Toes, None; T. Huizinga, Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Crescendo Bioscience, Novartis
Pharmaceuticals Corporation, Pfizer Inc, Roche, sanofi-aventis, Schering-Plough, UCB, Eli Lilly, 5,METEOR Board, 6,EU & Dutch
Arthritis Foundation, 2,Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Novartis Pharmaceuticals Corporation, Pfizer Inc,
Roche, sanofi-aventis, Schering-Plough, 8,Abbott Laboratories, Roche, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-impact-of-therapy-on-anti-carbamylated-

protein-antibody-isotypes-and-serostatus-in-patients-with-early-ra-treated-with-abatacept-and-mtx
Improvement in Overall Work Productivity Among Biologic-NaïVe Patients with

Rheumatoid Arthritis Treated with Tocilizumab Subcutaneous Injection: A
Prospective, Real World, Observational Study in Japan
Yoshiya Tanaka1, Hideto Kameda2, Kazuyoshi Saito3, Yuko Kaneko4, Eiichi Tanaka5, Shinsuke Yasuda6, Naoto Tamura7, Keishi
Fujio8, Takao Fujii9, Toshihisa Kojima10, Tatsuhiko Anzai11, Chikuma Hamada12, Yoshihisa Fujino13, Shinya Matsuda13 and Hitoshi
Kohsaka14, 1The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan,
2Division of Rheumatology, Department of Internal Medicine, Toho University Ohashi Medical Center, Tokyo, Japan, 3Tobata General
Hospital, Fukuoka, Japan, 4Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo,
Japan, 5Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan, 6Department of Rheumatology, Endocrinology
and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan, 7Department of Internal
Medicine and Rheumatology, Juntedo University School of Medicine, Tokyo, Japan, 8Department of Allergy and Rheumatology, The
University of Tokyo, Tokyo, Japan, 9Department of Rheumatism and Collagen Disease, Wakayama Medical University, Wakayama,
Japan, 10Nagoya Univ. Grad. Schl. of Med., Nagoya, Japan, 11Data Science Division, Statistics Analysis Department 1, EPS
Corporation, Tokyo, Japan, 12Department of Information and Computer Technology, Tokyo University of Science, Tokyo, Japan,
13Department of Preventive Medicine and Community Health, University of Occupational and Environmental Health, Japan,
Kitakyushu, Japan, 14Department of Rheumatology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
SESSION INFORMATION
Background/Purpose: This is the first study assessing the effect of subcutaneous tocilizumab (TCZ-SC) and/or conventional synthetic
DMARDs (csDMARDs) on work productivity and activity impairment (WPAI) in paid workers (PWs) and homeworkers (HWs) among
Japanese patients with RA.
Methods: FIRST ACT-SC was a real-world, prospective, observational study (Jan 2014 to Sep 2015 at 82 centers). Biologic-naïve
patients receiving ≥1 csDMARD, both PWs and HWs, and with moderate/high disease activity were enrolled and treated with TCZ-SC
+/− csDMARDs or csDMARDs alone. The primary endpoint was the percentage change in overall work impairment (OWI; assessed
using the WPAI questionnaire) from baseline to 52 weeks among PWs. Inverse probability of treatment weighting using propensity
score was used to adjust for patient background to compare the 2 groups. Depending on the patientsf symptoms during the observation
period, change of dose, change to another csDMARD, or addition of another csDMARD was allowed.
Results: In total, 377 and 347 patients were enrolled in the TCZ-SC +/− csDMARD and csDMARD-alone groups, respectively, of
which 321 (mean}SD age, 57.7}14.0 years; female, 81.6%) and 307 (60.1}12.8 years; 85.7%) patients, respectively, were included in
the modified intent-to-treat population. Of these, 233 (72.6%) and 224 (73.0%) patients, respectively, completed 52 weeks of follow-up.
The primary and secondary endpoint results are summarized in the Table 1. Although disease activity (DAS28, SDAI, CDAI, etc.) and
HAQ-DI improvements were better in the TCZ-SC group compared to the csDMARD group, the weighted percentage change in OWI
from baseline was only −0.189 in the TCZ-SC group at 52 weeks, and there was no difference between the 2 groups (weighted
treatment difference, 0.003; 95% CI, −0.062 to 0.068; P = 0.929). In contrast, the improvement in percentage activity impairment in
HWs and the overall group was significantly better in the TCZ-SC group compared to the csDMARD group at week 52 (P = 0.005 and
P = 0.003, respectively). TCZ-SC-treated HWs also showed significant improvement in overall quality of life (QOL), including EQ-5D,
J-HAQ, and K6.
Conclusion: There was no significant difference in OWI between the 2 treatment groups. However, activity impairment, disease
activity, and QOL in HWs and the overall group were significantly improved with TCZ-SC than with csDMARDs alone. Taken
together, improvement in work productivity/activity impairment is determined by differences in TCZ-SC +/− csDMARDs and
differences in PWs and HWs at baseline.
Role of the Study Sponsor: This study was supported by funding from Chugai Pharmaceutical Co., Ltd.
Acknowledgments: Medical writing assistance was provided by Mami Hirano, M.S., of Cactus Communications. Support for study
management was provided by EPS Corporation.
Disclosure: Y. Tanaka, Abbvie, Astellas Pharma, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi-Sankyo, Eisai, Kyowa Hakko
Kirin, Mitsubishi-Tanabe Pharma, MSD, Ono Pharmaceutical, Pfizer, and Takeda Pharmaceutical., 2,Asahi Kasei Pharma, Astellas
Pharma, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Mitsubishi-Tanabe
Pharma, Teijin Pharma, Pfizer, Sanofi, UCB, and YL Biologics., 8; H. Kameda, AbbVie, Astellas Pharma, Chugai Pharmaceutical,
Eisai, Mitsubishi-Tanabe Pharma, Takeda Pharmaceutical, 2,AbbVie, Eli Lilly, Novartis, 5,AbbVie, Astellas Pharma, Bristol-Myers
Squibb, Chugai Pharmaceutical, Eisai, Eli Lilly, Janssen, Mitsubishi-Tanabe Pharma, Novartis, Pfizer, Sanofi, Takeda Pharmaceutical,
8; K. Saito, None; Y. Kaneko, AbbVie, Eisai, Daiichi-Sankyo, Sanofi, 2,Bristol-Myers Squibb, Eli Lily, Janssen, 5,AbbVie, Eisai,
Astellas Pharma, Chugai Pharmaceutical, UCB, Pfizer, Bristol-Myeres Squibb, Janssen, Mitsubishi-Tanabe Pharma, 8; E. Tanaka,
AbbVie, Ayumi Pharmaceutical, Bristol Myers Squibb, Chugai Pharmaceutical, Eisai, Nippon Kayaku, Pfizer, Takeda Pharmaceutical,
UCB Pharma., 5; S. Yasuda, Bristol-Myers Squibb, MSD, 2,Chugai Pharmaceutical, Mitsubishi-Tanabe Pharma, Bristol-Myers Squibb,
Astellas Pharma, 8; N. Tamura, Astellas Pharma, Asahi Kasei Pharma, AYUMI Pharmaceutical, Chugai Pharmaceutical, Eisai, Takeda
Pharmaceutical, 2,Janssen, Bristol-Myers Squibb, Mitsubishi-Tanabe Pharma, 8; K. Fujio, Bristol-Myers Squibb, Chugai
Pharmaceutical, 2,Integrated Development Associates, Bristol-Myers Squibb, 5,Chugai Pharmaceutical, 7,Astellas Pharma, Bristol-
Myeres Squibb, Chugai Pharmaceutical, Daiichi-Sankyo, Eisai, Janssen, Mitsubishi-Tanabe Pharma, Pfizer, Santen Pharmaceutical,
Takeda Pharmaceutical, Taisho Toyama Pharmaceutical, UCB, 8; T. Fujii, Eisai, Mitsubishi-Tanabe Pharma, Ono Pharmaceutical,
Daiichi Sankyo, Pfizer, 2,AbbVie, Mitsubishi-Tanabe Pharma, Ono Pharmaceutical, Pfizer, 8; T. Kojima, Chugai Pharmaceutical,
Mitsubishi-Tanabe Pharma, Novartis Pharma, Nippon Kayaku, 2,Ayumi Pharmaceutical, Bristol-Myers Squibb, Chugai Pharmaceutical,
Eli Lilly, Ono Pharmaceutical, Pfizer, Takeda Pharmaceutical, 8; T. Anzai, EPS Corporation, 3; C. Hamada, Chugai Pharmaceutical, 5;
Y. Fujino, None; S. Matsuda, None; H. Kohsaka, AbbVie, Asahi Kasei Pharma, Astellas Pharma, Ayumi Pharmaceutical, Chugai
Pharmaceutical, Eisai, Eli Lilly, Japan Blood Products Organization, Mitsubishi-Tanabe Pharma, Novartis, Ono Pharmaceutical, Pfizer,
Takeda Pharmaceutical, and Teijin Pharma., 2,Bristol-Myers Squibb, Daiichi Sankyo, and GlaxoSmithKline., 5,AbbVie, Asahi Kasei
Pharma, Astellas Pharma, Ayumi Pharmaceutical, Chugai Pharmaceutical, Japan Blood Products Organization, Mitsubishi-Tanabe
Pharma, MSD, Nippon Kayaku, Ono Pharmaceutical, and Takeda Pharmaceutical., 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/improvement-in-overall-work-productivity-among-

biologic-naive-patients-with-rheumatoid-arthritis-treated-with-tocilizumab-subcutaneous-injection-a-prospective-real-world-
observational-study-in-japa
Exploratory Analysis to Identify Factors Associated with Risk of Structural

Progression, Defined As Change from Baseline
Désirée van der Heijde1, Patrick Durez2, Georg Schett3, Esperanza Naredo4, Mikkel Østergaard5, Gabriella Meszaros6, Pedro Lopez-
Romero7, Francesco de Leonardis6 and Roy Fleischmann8, 1Leiden University Medical Center, Leiden, Netherlands, 2UCL-Saint Luc,
Bruxelles, Belgium, 3Department of Internal Medicine III, Institute for Clinical Immunology,, Friedrich-Alexander-University
Erlangen-Nuremberg (FAU), Erlangen, Germany, 4Hospital Universitario Fundación Jimenez Diaz, Madrid, Spain, 5Glostrup Hospital,
Rigshospitalet, Glostrup, Denmark, 6Eli Lilly and Company, Indianapolis, IN, 7Europe Research Center, Eli Lilly and Company,
Madrid, Spain, 8University of Texas Southwestern Medical Center, Dallas, TX
SESSION INFORMATION
Background/Purpose: Baricitinib (BARI), an oral inhibitor of Janus kinase (JAK)1 and JAK2, is being developed for the treatment of
RA. RA-BEGIN (NCT01711359) was a phase 3, double-blind, three-arm, multicenter study of BARI administered as monotherapy or
in combination with methotrexate (MTX) to patients with early active RA who had no or limited treatment with MTX; MTX
monotherapy was the active comparator. This analysis was conducted to identify factors associated with risk of radiographic
progression in an early RA population after 52 weeks of treatment with BARI 4mg monotherapy, MTX monotherapy, or a combination
of the two drugs.
Methods: Radiographic progression was defined as change from baseline (CFB) greater than the smallest detectable change (SDC) in
van der Heijde-modified total Sharp score (mTSS) at week 52. The SDC in mTSS in the RA-BEGIN modified intent-to-treat population
at week 52 was 1.4. Missing mTSS data at week 52 were imputed using linear extrapolation based on baseline data and the most recent
radiographic data before the missed radiograph. Data for 39/584 patients with completely missing radiographic data were omitted from
the analysis. The association of different baseline factors with radiographic progression was assessed using a multivariate logistic
regression model including: treatment, age, gender, BMI, ACPA (≤10U/ml negative; >10U/ml positive), RF (≤14IU/ml negative;
>14IU/ml positive), presence of joint erosions (yes/no), smoking habit (yes/no), hsCRP, HAQ-DI, mTSS, RA duration, CDAI, and
geographic location.
Results: Radiographic progression at week 52 was seen in 21.9% (MTX), 14.9% (BARI 4mg) and 10.1% (BARI 4mg plus MTX) of
patients. Female gender, smoking habit, higher hsCRP at baseline (Fig), higher CDAI at baseline (Fig) and lower BMI at baseline were
significantly associated with an increased risk of radiographic progression (Tab).
Conclusion: In patients with early RA and no or limited previous use of MTX who were treated with MTX, Bari 4 mg, or Bari 4mg
plus MTX, risk factors for radiographic progression can be identified. After multivariate adjustment, female gender, smoking, baseline
hsCRP, CDAI and BMI showed a statistically significant association with radiographic progression.
Disclosure: D. van der Heijde, AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boeringer Ingelheim, Celgene,Daiichi, Eli-Lilly,
Galapagos, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, UCB, 5; P. Durez, Eli Lilly and Company, 5; G. Schett, None; E.
Naredo, Abbvie, Roche, BMS, Pfizer, UCB, Novartis, Lilly, Janssen, 5; M. Østergaard, Abbvie, BMS, Boehringer-Ingelheim,
Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-
Plough, Roche, Takeda, UCB, and Wyeth, 5; G. Meszaros, Eli Lilly and Company, 3; P. Lopez-Romero, Eli Lilly and Company, 1,Eli
Lilly and Company, 3; F. de Leonardis, Eli Lilly and Company, 3; R. Fleischmann, AbbVie, Amgen, Astra Zeneca , Bristol-Myers
Squibb, Celgene, Janssen, Eli Lilly and Company, Novartis, Roche, Sanofi-Aventis, Pfizer, UCB, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/exploratory-analysis-to-identify-factors-associated-

with-risk-of-structural-progression-defined-as-change-from-baseline
Abatacept Initiation in Chilean Patients with Long Lasting Rheumatoid Arthritis.

Hospital Padre Hurtado Experience
Omar Valenzuela1, María Paz Poblete2, Claudia Mardones2, Sebastián Ibáñez1, Katherine Mogollones2, Francisco Silva1 and María
José Villar2, 1Rheumatology department, Hospital Padre Hurtado, Santiago, Chile, 2Hospital Padre Hurtado, Santiago, Chile
SESSION INFORMATION
Background/Purpose: Since the year 2016 Rheumatoid Arthritis (RA) patients in the Chilean public health system can access biologic
treatment if they have active disease refractory to non biologic DMARDs (see inclusion criteria). At first only Abatacept was available
as first line biologic. The first patients that initiated biologic treatment in our center were those who had a long lasting active disease.
Our main objective was to evaluate the response to treatment with Abatacept in the patients from our center.
Methods: RA patients (ACR 2010 criteria), 18 years old or older, that had a DAS28 ESR > 5.1 in two different occasions separated by
at least one month despite the use of at least 3 DMARDs, including methotrexate or leflunomide, for at least 6 monts, were included.
Patients with any contraindication to use Abatacept were excluded. Information about work status, gender, age, years since diagnosis,
comorbidities, and medications used was collected. The patients were followed for 6 months and the DAS28 ESR was measured at
baseline and end of follow-up, and the EULAR response criteria was calculated. Changes from baseline to end of follow-up were
analyzed using T-test for paired variables or Wilcoxon signed-rank sum test, and associations between variables were assessed using T-
test, Mann-Whitney U test and Chi-Squared test or Fisher's exact test, as appropiate
Results: 44 patients were included. Baseline characteristics are described in table 1. Of note, 37.2% had a disability pension and the
median years with disease were 13 (IQR 7-17). The improvement of DAS28 ESR and its variables was statistically significant (table 2).
According to the EULAR response criteria 22.7% of the patients achieved a good response, 52.3% achieved a moderate response and
25% had no response to treatment with Abatacept. 4 of the 10 patients with good response achieved remision (DAS28 ESR <2.6).
Gender, age, years since diagnosis, use of Metothrexate or other DMARDs, prenisone or NSAIDs use, comorbidities, tobacco use and
basal DAS28 ESR did not influence the response to treatment. No adverse events were reported.
Conclusion: In our group of patients, with prolonged disease refractory to treatment with at least 3 DMARDs, 75% achieved at least a
moderate response according to the EULAR response criteria whitout adverse events, but less than one quarter achieved a good
response. This probably reflects that in these patients the window of opportunity to initiate a suitable treatment to achieve remission was
lost. We believe that it is necessary to allow the inclusion of patients with lower DAS28 among the possible beneficiaries of biological
therapy in the public health system of our country.
Table 1. Disease characteristics
Number of
44
patients
Age (mean, SD) 53.9 (10.29)
Female (%) 88.6%
Years since
diagnosis 13 (7-17)
(median, IQR)
Metothrexate use 77.3%
(%)
Sulfasalazine use 52.3%
(%)
Hidroxicloroquine 65.9%
use (%)
Leflunomide use 50%
(%)
Prednisone use 95.5%
(%)
NSAIDs use (%) 86.4%
Tramadol use (%) 50%
Work:
With contract (%) 14%
Independent (%) 7%
Home activities
30.2%
(%)
Retirement (%) 11.6%
Disability pension
37.2%
(%)
Comorbidities:
Diabetes (%) 29.5%
Hypertension (%) 58.1%
Dislipidemia (%) 15.9%
Smokers (%) 16.7%
Latent
11.4%
tuberculosis (%)
HIV, Hepatitis C
0%
or B (%)
Intersticial lung
6,8%
disease (%)
Months of follow-
6.4 (2.6)
up (mean, SD)
Table 2. Comparison from baseline to end of follow-up
Characteristics Basal (44 Follow-up P
patients) (44 patients)
Tender joints 12 (10-17) 5 (3-10) <0.001
(median, IQR)
Swollen joints 8 (5-9.5) 2.5 (1-4) <0.001
(median, IQR)
VAS for pain 80 (70-80) 40 (20-60) <0.001
(median, IQR)
ESR (median, 28 (18-40) 19.5 (13.5- 0.007
IQR) 28.5)
DAS28 ESR 6.11 (0.66) 4.37 (1.25) <0.001
(mean, SD)
Disclosure: O. Valenzuela, None; M. P. Poblete, None; C. Mardones, None; S. Ibáñez, None; K. Mogollones, None; F. Silva, None;
M. J. Villar, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/abatacept-initiation-in-chilean-patients-with-long-

lasting-rheumatoid-arthritis-hospital-padre-hurtado-experience
Machine Learning in Rheumatology: Development and Validation of a Predictive

Model for Rheumatoid Arthritis Mortality Using Random Survival Forests
Luis Rodriguez-Rodriguez1, José M Lezcano-Valverde2, Fernando Salazar3, Leticia León2, Esther Toledano4, Juan A Jover Jover5,
Eduardo Soudah3, Benjamín Fernández-Gutiérrez5, Isidoro Gonzalez-Alvaro6 and Lydia A Alcazar1, 1Rheumatology Department and
Heath Research Institute (IdISSC), Hospital Clinico San Carlos, Madrid, Spain, 2Rheumatology Department, Hospital Clínical San
Carlos, and IdISSC, Madrid, Spain, 3International Centre for Numerical Methods in Engineering (CIMNE), Madrid, Spain,
4Rheumatology, Hospital Clínical San Carlos, Madrid, Spain, 5Rheumatology, Hospital Clínico San Carlos, Madrid, Spain,
6Rheumatology Department, Hospital Universitario la Princesa, IIS-Princesa, Madrid, Spain
SESSION INFORMATION
Background/Purpose: Rheumatoid arthritis (RA) is associated with increased mortality. Traditional survival techniques used to
identify mortality risk factors, such as the Cox proportional hazards model (CPH), have several limitations, such as reliance on
restrictive assumptions. To overcome these limitations, machine learning methods have been developed. Random survival forest (RSF),
a non-parametric ensemble tree method, was proposed as an alternative approach to CPH. Our aim is to develop and validate (internally
and externally) a predictive model for RA mortality using RSF.
Methods: Retrospective longitudinal study involving 2 independent RA cohorts from Madrid (Spain): the Hospital Clínico San Carlos
RA Cohort (HCSC-RAC: 1,461 patients diagnosed between 2001 and 2011, followed-up until death or September 2013; used for model
development), and the Hospital Universitario de La Princesa Early Arthritis Register Longitudinal study (PEARL: 280 patients
diagnosed between 2001 and 2014, followed-up until death or January 2017; used for external validation). Demographic and clinical-
related variables collected during the first two years after disease diagnosis were used. RSF models were developed with the
randomForestSRC R package, based on 1,000 trees. 100 iterations of each model were performed to measure the mean and standard
deviation of the prediction error. Based on the predicted mortality estimated by the RSF model, mortality risk groups were established
through a survival tree created with the R package rpart.
Results: 148 and 21 patients from the HCSC-RAC and the PEARL died during a median follow-up time of 4.3 and 5.0 years,
respectively. Age at diagnosis, median erythrocyte sedimentation rate, and number of hospital admissions in the first 2 years after RA
diagnosis showed the higher predictive capacity. The prediction errors of our model in the training and in the validation cohorts were
0.187, and 0.233, respectively. The survival tree analysis identified 5 risk groups. After combining those three with intermediate risk,
we observed that the intermediate and the high risk groups were significantly associated with higher mortality risk compared with the
low risk, both in the HCSC-RAC and PEARL cohorts (Figures 1 and 2).
Conclusion: We developed and externally validated a clinical prediction model for RA mortality using RSF.
Figure 1: Kaplan Meier curves for the observed mortality of patients from the HCSC-RAC, grouped in mortality risk categories
Figure 2: Kaplan Meier curves for the observed mortality of patients from the PEARL, grouped in mortality risk categories
Disclosure: L. Rodriguez-Rodriguez, None; J. M. Lezcano-Valverde, None; F. Salazar, None; L. León, None; E. Toledano, None;
J. A. Jover Jover, None; E. Soudah, None; B. Fernández-Gutiérrez, None; I. Gonzalez-Alvaro, None; L. A. Alcazar, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/machine-learning-in-rheumatology-development-

and-validation-of-a-predictive-model-for-rheumatoid-arthritis-mortality-using-random-survival-forests
Serum Calprotectin Is Not Predictive for Successful Dose Reduction or

Discontinuation of TNF Inhibitors in RA Patients with Low Disease Activity
Nathan den Broeder1, Lieke Tweehuysen1, Noortje van Herwaarden1, Thomas Vogl2, F.H.J. van den Hoogen1, Rogier Thurlings3 and
Alfons A Den Broeder1, 1Rheumatology, Sint Maartenskliniek, Nijmegen, Netherlands, 2University of Muenster, Muenster, Germany,
3Rheumatology, Radboudumc, Nijmegen, Netherlands
SESSION INFORMATION
Background/Purpose: Dose reduction and discontinuation of TNF inhibitors (TNFi) have been shown feasible in a large proportion of
RA patients with low disease activity.1 To date, no predictors for successful dose reduction or discontinuation have been identified.2
Calprotectin (a heterodimer of S100A8/S100A9) might be a promising biomarker in this context.3,4
Objectives: To investigate the predictive value of baseline serum calprotectin for successful TNFi dose reduction or discontinuation in
RA patients with low disease activity.
Methods: Data was derived from the intervention arm of the DRESS (Dose REduction Strategies of Subcutaneous TNFi) study, which
showed non-inferiority of a dose reduction strategy of adalimumab or etanercept compared to usual care.1 TNFi dose interval was
reduced stepwise every 3 months until flare (DAS28-CRP increase >1.2 or >0.6 if current DAS28-CRP ≥3.2) or discontinuation.
Patients were classified at 18 months as being successfully dose reduced, discontinued or not able to reduce the TNFi dose. At baseline,
quantification of calprotectin was carried out on serum samples using ELISA. Calprotectin levels were compared between each group
and receiver-operator-characteristic (ROC) curves were created. In addition, calprotectin was correlated cross-sectionally with several
clinical markers for disease activity.
Results: Calprotectin levels were available from 102 of 121 patients randomised to the intervention group; 61% were women, 63%
received etanercept and 37% received adalimumab. Overall, 46% of patients successfully reduced the TNFi dose, 19% of patients
successfully discontinued TNFi and 35% of patients could not reduce the TNFi dose. In these groups, median calprotectin levels were
599 ng/ml (p25-p75: 473-965), 629 ng/mL (p25-p75: 453-896) and 624 ng/mL (p25-p75: 514-931) (p=0.801) (Figure 1). The area
under the ROC-curve was 0.52 (95% CI: 0.40-0.63) for predicting successful TNFi dose reduction, 0.53 (95% CI: 0.38-0.67) for
successful TNFi discontinuation and 0.54 (95% CI: 0.42-0.66) for no dose reduction possible. Calprotectin levels were weakly
correlated with C-reactive protein (CRP) levels with a Spearman ρ of 0.21 (p=0.03). No significant correlation was found between
calprotectin and age, gender, DAS28-CRP, rheumatoid factor or ACPA positivity.
Conclusion: Serum calprotectin is not predictive for successful TNFi dose reduction or discontinuation in RA patients with low disease
activity, and calprotectin was only weakly correlated to CRP levels. These results might be caused by the lack of variability in
calprotectin levels at baseline as all patients were in low disease activity state.
Figure 1 Calprotectin levels per outcome
References:
1 van Herwaarden et al. BMJ 2015;350:h1389
2 Tweehuysen et al. Arthritis Rheumatol 2017;69(2):301-308
3 Hammer et al. Ann Rheum Dis 2010;69(1):150-4
4 Choi et al. Ann Rheum Dis 2015;74(3):499-505
Disclosure: N. den Broeder, None; L. Tweehuysen, None; N. van Herwaarden, None; T. Vogl, None; F. H. J. van den Hoogen,
Biogen Idec, 5,Celltrion, 5,Janssen Pharmaceutica Product, L.P., 5,Mundipharma, 5,Sandoz, 5; R. Thurlings, None; A. A. Den
Broeder, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/serum-calprotectin-is-not-predictive-for-successful-

dose-reduction-or-discontinuation-of-tnf-inhibitors-in-ra-patients-with-low-disease-activity
No Added Predictive Value of Serum Calprotectin for Treatment Response to

Adalimumab or Etanercept in RA Patients
Lieke Tweehuysen1, Nathan den Broeder1, Leo .A.B. Joosten2, Thomas Vogl3, F.H.J. van den Hoogen4, Rogier Thurlings5 and Alfons
A Den Broeder1, 1Rheumatology, Sint Maartenskliniek, Nijmegen, Netherlands, 2Internal Medicine, Radboud University Medical
Center, Nijmegen, Netherlands, 3University of Muenster, Muenster, Germany, 4Rheumatology, Rheumatology Centre Sint
Maartenskliniek and Radboud university medical center, Ubbergen (Nijmegen), Netherlands, 5Rheumatology, Radboudumc, Nijmegen,
Netherlands
SESSION INFORMATION
Background/Purpose: To date, no clinically useful baseline biomarkers have been found to predict response to TNF inhibitor (TNFi)
treatment .1 Calprotectin was shown to be predictive for treatment response to adalimumab (ADA) while no difference in calprotectin
levels was found between responders and non-responders in RA patients treated with etanercept (ETN) and methotrexate.2,3
Objectives: To assess the added predictive value of serum calprotectin for clinical response after 6 months treatment with ADA or
ETN in RA patients.
Methods: RA patients starting treatment with ADA or ETN in the BIO-TOP study (a prospective cohort study) were included. Patients
who discontinued TNFi treatment within 2 months were excluded from analysis. Serum calprotectin was measured at baseline using
ELISA. EULAR response was measured at 6 months (good versus moderate/no response). Discontinuation of TNFi before 6 months
was regarded as non-response (in case of lack of effect) and clinical response at 3 months was carried forward (when stopped for other
reasons). First calprotectin levels were correlated cross-sectionally with several clinical baseline markers. Thereafter, receiver-operator-
characteristic (ROC) curves were created for ADA and ETN separately. Finally logistic prediction models were created using backward
selection, including baseline characteristics and calprotectin levels to examine the added predictive value of calprotectin.
Results: Calprotectin levels and EULAR response were available for 125 patients (ADA (n=50), ETN (n=75)), with 40% of patients
achieving EULAR good response. Responders showed significantly higher baseline calprotectin levels: 985 ng/mL (p25-p75: 558-
1417) versus 645 ng/mL (p25-p75: 415-973) (p=0.04). Calprotectin levels were significantly correlated to DAS28-CRP (Spearman
ρ=0.32, p<0.01) and C-reactive protein (CRP) levels (Spearman ρ=0.57, p<0.01) and significantly higher in rheumatoid factor positive
patients (p=0.03). No significant correlation was found between calprotectin and age, gender or ACPA positivity. The area under the
curve (AUC) for calprotectin in the ADA and ETN group were 0.68 (95% CI: 0.49-0.88) and 0.49 (95% CI: 0.35-0.63), respectively.
The basic model (selected variables: baseline DAS28-CRP and medication used (ADA vs ETN)) showed an AUC of 0.73 (95% CI:
0.64-0.82). The calprotectin added model performed similarly with an AUC of 0.76 (95% CI: 0.67-0.84) (p=0.27).
Conclusion: Serum calprotectin is modestly predictive for EULAR good response to ADA but not ETN treatment after 6 months in RA
patients. However, calprotectin does not provide additional predictive value over a basic clinical prediction model.
References
1 Cuppen et al. Rheumatology (Oxford) 2016;55(5):826-39
2 Choi IY et al. Ann Rheum Dis 2015;74(3):499-505
3 Obry A et al. PLoS One 2014;9(12):e115800
Disclosure: L. Tweehuysen, None; N. den Broeder, None; L. A. B. Joosten, None; T. Vogl, None; F. H. J. van den Hoogen, Biogen
Idec, 5,Celltrion, 5,Janssen Pharmaceutica Product, L.P., 5,Mundipharma, 5,Sandoz, 5; R. Thurlings, None; A. A. Den Broeder, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/no-added-predictive-value-of-serum-calprotectin-
for-treatment-response-to-adalimumab-or-etanercept-in-ra-patients
Refractory Pain in Spite of Inflammation Control after Start of Anti-TNF Therapy

in RA: Observational Data from Southern Sweden
Tor Olofsson1, Johan K Wallman2, Maria EC Schelin3, Anna Jöud4 and Jon Lampa5, 1Lund University, Department of Clinical
Sciences Lund, Rheumatology, Lund, Sweden, Lund, Sweden, 2Department of Clincial Sciences Lund, Rheumatology, Lund University,
Lund, Sweden, 3Lund University, Department of Clinical Sciences Lund, Oncology, Lund, Sweden, Lund, Sweden, 4Lund University,
Department of Laboratory Medicine Lund, Division of Occupational and Environmental Medicine, Lund, Sweden, Lund, Sweden,
5Karolinska Institute, Department of Medicine, Rheumatology Unit, Stockholm, Sweden, Stockholm, Sweden
SESSION INFORMATION
Background/Purpose: Pain is a dominant and debilitating feature of RA, but while a lot of focus has been put on the occurrence and
management of inflammatory pain, less is reported on pain despite low inflammation. The aim of this study was therefore to investigate
the prevalence of refractory pain in spite of inflammation control after start of a first anti-TNF therapy in RA patients and its relation to
EULAR treatment response.
Methods: RA patients starting a first anti-TNF therapy 2004-2010 were identified in the prospective, observational South Swedish
Arthritis Group register (n=1166; 76% women; >95% fulfillment of 1987 ACR criteria) with mean age 56 years and mean disease
duration 10 years. Unacceptable pain (>40 mm on a Visual Analogue Scale, VAS; scale 0-100 mm)1 and unacceptable pain in spite of
inflammation control (VAS pain>40 mm combined with CRP<10 mg/L,2 and ≤1 swollen joint) were assessed 1.5, 3, 6, and 12 months
after treatment start. Furthermore, analyses were performed in relation to EULAR treatment response after 3 months (good response,
moderate, no). Differences in pain measures between treatment response groups were estimated by logistic regression.
Results: At start of first anti-TNF therapy, 79.6% of the RA patients had unacceptable pain (VAS pain>40) which declined to 39.8%
after 3 months, and then remained stable during the first treatment year, whereas the frequency of patients with unacceptable pain in
spite of inflammation control increased from 4.0% at treatment start to 12.3% after 3 months, and then stabilized (Figure 1).
Unacceptable pain at 3 months was strongly related to EULAR response (14.1% of good responders vs. 70.5% of non-responders;
p<0.001). In contrast, the frequency of unacceptable pain in spite of inflammation control was largely similar in patients with good
response and those with no response (10.9% vs. 14.4%; p=0.23). Among EULAR good responders, unacceptable pain despite
inflammation control constituted 78% of all unacceptable pain at 3 months (Figure 2).
Conclusion: A substantial proportion of RA patients starting anti-TNF therapy have refractory, unacceptable pain in spite of good
inflammation control during the first treatment year. In the present study, this pain status was as common in EULAR good responders as
in non-responders. These data are in line with insufficient effects of biologics on a subgroup of patients with inflammation-independent
pain, and strongly warrants alternative treatment strategies in these patients.
1) Tubach et al. Arthritis Care Res 2012;64:1699-72. 2) Lourdudoss et al. Arthritis Care Res 2017 doi 10.1002/acr.23245
Disclosure: T. Olofsson, None; J. K. Wallman, Abbvie, Celgene, Novartis, UCB, 5; M. E. Schelin, None; A. Jöud, None; J. Lampa,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/refractory-pain-in-spite-of-inflammation-control-

after-start-of-anti-tnf-therapy-in-ra-observational-data-from-southern-sweden
Re-Establishment of Efficacy of Tofacitinib, an Oral Janus Kinase Inhibitor, in

Rheumatoid Arthritis Patients after Temporary Discontinuation
Jeffrey Kaine1, John Tesser2, Ryan DeMasi3, Liza Takiya3, Lisy Wang4, Mark Snyder3, Haiyun Fan4 and Jürgen Wollenhaupt5,
1Sarasota Arthritis Research Center, Sarasota, FL, 2Arizona Arthritis & Rheumatology Associates, Glendale, AZ, 3Pfizer Inc,
Collegeville, PA, 4Pfizer Inc, Groton, CT, 5Schön-Klinik Hamburg-Eilbek Teaching Hospital of the University of Hamburg, Hamburg,
Germany
SESSION INFORMATION
Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We assessed
tofacitinib efficacy and safety after temporary discontinuation and reinitiation of therapy in patients (pts) with RA.
Methods: Data were from a randomized, parallel-group (grp), controlled, open‑label vaccine sub-study in pts with RA participating in a
long-term extension study (NCT00413699). Pts were aged ≥18 years with active RA and had received tofacitinib 10 mg twice daily
(BID) for ≥3 months. The sub-study included 2 treatment (tx) grps: ‘continuous tx’ (tofacitinib 10 mg BID ± methotrexate [MTX]) and
‘interrupted tx’ (tofacitinib withdrawn for 2 weeks post-randomization [Day 1–15; Visits 1–3], then tofacitinib 10 mg BID reinitiated ±
MTX at Visit 3); randomization was stratified by MTX use. All pts received pneumococcal and influenza vaccines on Day 8 (Visit 2;
vaccine titers reported previously1). Blood samples were taken on Days 8, 15 (Visit 3), and 43 (Visit 4). Efficacy endpoints included
change from baseline (CFB) in CRP, HAQ‑DI, and DAS28-4(ESR) at each visit. A mixed-effects model with repeated measures was
used to evaluate treatment effect at each visit. Efficacy analyses were exploratory, with no multiplicity adjustments. P<0.05 was
considered as statistically significant.
Results: Of the 199 pts in this analysis (continuous, n=100; interrupted, n=99), 117 received concomitant MTX. At study baseline (BL)
in the continuous and interrupted grps, respectively: 81.8/83.8% of total pts were white, 84.8/86.9% were female, and mean age was
55.0/53.9 years. CRP, HAQ-DI, and DAS28-4(ESR) BL values were generally similar between groups. At Day 8, mean CRP and
DAS28-4(ESR) significantly increased from BL for pts receiving interrupted vs continuous tx; HAQ-DI values were similar between
grps (Figure). At Day 15, mean CRP, HAQ-DI, and DAS28-4(ESR) significantly increased from BL for pts receiving interrupted vs
continuous tx. After tofacitinib reinitiation for 28 days (Day 43), CFB in CRP, HAQ-DI, and DAS28-4(ESR) were similar between grps
and approached BL levels. Adverse events (AEs) were experienced by 35.4% and 49.5% of pts receiving interrupted and continuous tx,
respectively. The most frequent treatment-emergent AEs were bronchitis and upper respiratory tract infection (each AE: 6 pts) and
vaccination-related immunisation reaction, myalgia, and rash (each AE: 5 pts). Serious AEs occurred in 3 pts (3%) in each grp. In total,
1 pt (1%) in the interrupted grp discontinued due to study drug-related AEs; no pts discontinued due to disease flare.
Conclusion: Efficacy of tofacitinib 10 mg BID can be re-established following a temporary (2 weeks) tx discontinuation in pts with
RA. Pts receiving continuous tx maintained efficacy throughout the study. Further investigations are required.
Reference:
1. Winthrop KL et al. Ann Rheum Dis 2016; 75: 687-695.
Disclosure: J. Kaine, Pfizer Inc, Bristol-Myers Squibb, 8; J. Tesser, Pfizer Inc, 2,Pfizer Inc, 5,Pfizer Inc, 8; R. DeMasi, Pfizer Inc,
1,Pfizer Inc, 3; L. Takiya, Pfizer Inc, 1,Pfizer Inc, 3; L. Wang, Pfizer Inc, 1,Pfizer Inc, 3; M. Snyder, Pfizer Inc, 1,Pfizer Inc, 3; H.
Fan, Pfizer Inc, 1,Pfizer Inc, 3; J. Wollenhaupt, Pfizer Inc, 1,Pfizer Inc, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/re-establishment-of-efficacy-of-tofacitinib-an-oral-
janus-kinase-inhibitor-in-rheumatoid-arthritis-patients-after-temporary-discontinuation
Efficacy of Monotherapy of the Biologic Dmards in Patients with Rheumatoid

Arthritis: Real Life Data from the Hong Kong Biologics Registry
Chi Chiu Mok, Ting Hung Wan and Lai Shan Fong, Medicine, Tuen Mun Hospital, Hong Kong, Hong Kong
SESSION INFORMATION
Background/Purpose:
To report the prevalence and efficacy of biologic DMARD (bDMARD) monotherapy in real life treatment of rheumatoid arthritis (RA).
Methods:
RA patients registered in the Hong Kong Biologics Registry who were receiving bDMARD monotherapy (without concomitant
conventional synthetic DMARDs [csDMARDs] except low dose prednisolone) were identified. The efficacy (clinical response and drug
retention rate) of bDMARD monotherapy was compared with bDMARD combination therapy (with csDMARDs) using statistical tests.
Results:
From December 2007 to April 2017, 2123 courses of bDMARDs/tsDMARDs were used in 1250 RA patients (83% women, mean age
at therapy 53.8±12.7 years). Among 1881 courses of therapies with complete data, 164 (8.7%) was monotherapy at baseline. Low dose
prednisolone (<10mg/day) was used in 56% of these courses. In the combination group, the commonest csDMARDs used in
combination with bDMARDs were methotrexate (79%), sulphasalazine (27%), hydroxychloroquine (25%) and leflunomide (21%). The
bDMARDs/tsDMARDs most frequently used as monotherapy were tofacitinib (14.3%), tocilizumab (11.6%) and abatacept (11.2%).
Overall, the non-TNF was more commonly used as monotherapy (11.2%) than the anti-TNF bDMARDs (7.4%). At 6 months of
bMDARD/tsDMARD therapy, the DAS remission rate was non-significantly higher in the combination than monotherapy group (11%
vs 5%; p=0.42). The change in DAS28 score was also non-significantly greater in the combination group (-1.95±1.26 vs -1.68±1.56;
p=0.30). The difference in 6-month efficacy between the combination and monotherapy groups was greater in anti-TNF users. The
overall cumulative withdrawal rate of the bDMARDs/tsDMARDs due to either inefficacy or serious adverse events (SAEs) was 0.55 at
3 years and 0.47 at 5 years. The anti-TNF biologics had a significantly higher withdrawal rate than the non-TNF biologics (hazard ratio
[HR] 1.83[1.56-3.14]; p<0.001). In Cox regression models, monotherapy of the bDMARDs was not significantly associated with drug
withdrawal due to inefficacy (HR 0.95 [0.53-1.71]; p=0.87) or SAEs (HR 1.27 [0.51-3.19]; p=0.61) after adjustment for age, sex, anti-
TNF (vs non-TNF) biologic use, previous use of bDMARDs (vs first time use) and DAS28 at baseline. Separate analyses of the anti-
TNF and non-TNF biologics again did not reveal a significant relationship between monotherapy of the biologics with the drug
withdrawal due to inefficacy or SAEs after adjustment for age, sex, previous use of bDMARDs and disease activity at baseline (HR
1.002 [0.56-1.80]; p=0.99 for anti-TNF and HR 1.20 [0.47-3.08]; p=0.70 for non-TNF biologics, respectively).
Conclusion:
Monotherapy of bDMARD/tsDMARD was used in 8.7% of our RA patients in real life practice, probably due to intolerance, inefficacy
or non-compliance to the csDMARDs. Short-term efficacy tended to be better with bDMARDs/csDMARDs combination, especially in
the anti-TNF biologics, but the long-term drug retention rate was similar between bDMARD monotherapy and combination therapy
with the csDMARDs.
Disclosure: C. C. Mok, None; T. H. Wan, None; L. S. Fong, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/efficacy-of-monotherapy-of-the-biologic-dmards-in-

patients-with-rheumatoid-arthritis-real-life-data-from-the-hong-kong-biologics-registry
Serum Levels of the Anti-TNF Biologics Correlate with Clinical Efficacy in Patients
with Inflammatory Arthritis
Chi Chiu Mok1, Lai Shan Fong1, Ling Yin Ho2 and Chi Hung To3, 1Medicine, Tuen Mun Hospital, Hong Kong, Hong Kong, 2Dept of
Medicine, Tuen Mun Hospital, Hong Kong SAR, Hong Kong, 3Medicine, Pok Oi Hospital, Hong Kong, Hong Kong
SESSION INFORMATION
Background/Purpose:
To study the correlation between levels of the anti-TNF biologics and clinical efficacy in patients with inflammatory arthritis
Methods:
Adult patients who fulfilled the criteria for rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PSA) and were
commenced on standard dosing regimens of the anti-TNF biologics were recruited. Stored serum samples at baseline, month 6 and 12
were assayed for the trough levels of the biologics (± anti-drug antibodies) retrospectively. Patients were followed longitudinally and
efficacy analyses were conducted at 3-month intervals without the knowledge of the drug levels. Biologics would be discontinued from
6 months onwards according to protocol-based improvement criteria for each disease. Clinical efficacy of the anti-TNF biologics was
compared among patients with different levels of the drug by statistical analyses.
Results:
112 patients were studied (58 RA, age 51.2±10.9 years, disease duration 72.9±67 months; 41 SpA, age 39.1±9.9 years, disease duration
74.3±81.6 months; 13 PSA, age 53.5±10.7 years, disease duration 44.3±35.4 years). The number of patients treated with infliximab
(IFX), adalimumab (ADM), golimumab (GLM) and etanercept was 3, 31, 36 and 42, respectively. At month 12, neutralizing antibodies
against IFX, ADM and GLM were present in 2 (67%), 14 (45%) and 1 (3%) of the patients, respectively. In ADM users, the drug level
was significantly lower in those with antibodies than those without (1.81±2.63 vs 8.02±4.14 ug/ml; p<0.001). Antibody titer against
ADM correlated negatively with the levels of ADM (Rho -0.72; p<0.001). Patients were stratified into 3 tertiles for each biologic
according to the trough levels of the drugs. Low drug concentrations were defined as levels ≤1.30 ug/ml, 0.05 ug/ml and 0.60 ug/ml in
ADM, ETN and GLM users, respectively. In patients with RA/PSA (N=71), patients with the lowest anti-TNF drug level group (N=30)
had a trend of less improvement in DAS28, CDAI scores at month 12 when compared to others (N=41). However, significantly more
patients withdrew treatment due to inefficacy at month 12 in this group compared to others (67% vs 7.3%, p<0.001). In patients with
SpA (N=41), patients with lowest anti-TNF drug levels stratum (N=9) had significantly less improvement in ASDAS compared with
others at month 12 (N=32) (-0.57±0.63 vs -1.93±1.28; p=0.003). The proportion of patients who achieved an ASAS20 response was
also significantly lower in this group of patients (33% vs 75%; p=0.04). In all the 112 patients studied, the cumulative withdrawal rate
of the anti-TNF biologics at month 12 (by Kaplan-Meier’s analysis) was significantly higher in those with low drug levels when
compared to others with higher drug levels (26.1% vs 54.6%; p<0.001 log rank test).
Conclusion:
The presence of neutralizing antibodies to the anti-TNF monoclonals is associated with lower trough levels of the drugs. Trough level of
the anti-TNF biologics is useful for optimizing the clinical efficacy of the drugs in patients with inflammatory arthritis.
Disclosure: C. C. Mok, None; L. S. Fong, None; L. Y. Ho, None; C. H. To, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/serum-levels-of-the-anti-tnf-biologics-correlate-

with-clinical-efficacy-in-patients-with-inflammatory-arthritis
Do We Treat Men and Women Differently, and Is This a Good Thing?

Sytske Anne Bergstra1, Cornelia F Allaart1, Sofia Ramiro2, Arvind Chopra3, Candida A. Silva4, Nimmisha Govind5 and Robert B.M.
Landewé6,7, 1Department of Rheumatology, LUMC, Leiden, Netherlands, Leiden, Netherlands, 2Rheumatology, Department of
Rheumatology, LUMC, Leiden, Netherlands, Leiden, Netherlands, 3Center for Rheumatic Diseases, Pune, India, Pune, India, 4Instituto
Português de Reumatologia, Lisbon, Portugal, Lisbon, Portugal, 5Department of Rheumatology, University of the Witwatersrand,
Johannesburg, South-Africa, Johannesburg, South Africa, 6Zuyderland Medical Center, Heerlen, Netherlands, Heerlen, Netherlands,
7Amsterdam Rheumatology & Immunology Center, Netherlands, Amsterdam, Netherlands
SESSION INFORMATION
Background/Purpose: Men seem to respond better to antirheumatic treatment than women with RA. In daily practice, expectations
towards responsiveness may influence rheumatologists when making treatment choices. We investigated whether male and female RA
patients are treated differently and whether they respond differently to treatment in daily clinical practice.
Methods: DMARD naive RA patients with symptom duration ≤5 years, ≥3 months follow-up, available data regarding medication use
and baseline DAS≥1.6 were selected from the international observational METEOR database. Patients starting biologic DMARD
treatment were excluded due to low numbers. Follow-up visits were selected until the first medication switch or the end of follow-up.
Missing data were imputed using multiple imputation. Linear mixed model (LMM) analyses were performed to assess whether
differences in treatment between men and women lead to differences in DAS or HAQ over time within each treatment group. If an
added interaction between gender and treatment was statistically significant (p<0.05), models were stratified for treatment. Analyses
were adjusted for potential confounders.
Results: Women (n 4393) more often started treatment with HCQ (HCQ monotherapy, MTX + HCQ and HCQ + glucocorticoid, but
not more often with MTX + SSZ + HCQ), whereas men (n 1142) more often started treatment with SSZ and/or MTX (SSZ
monotherapy, MTX + SSZ and MTX + glucocorticoid, table 1).
Mean (SD) baseline DAS and HAQ for women and men were DAS 3.7 (1.0) vs 3.5 (1.1) and HAQ 1.1 (0.7) vs 1.0 (0.7). LMM
analyses showed that in general women improved less on initial treatment over time than men: DAS [β (95% CI) 0.16 (0.12; 0.20)] and
HAQ [β (95% CI) 0.13 (0.10; 0.16)]. A statistically significant interaction was only found between female gender and initial HCQ
[DAS β (95% CI) -0.17 (-0.33; -0.0045) and HAQ -0.12 (-0.23; -0.0047)] and between female gender and initial MTX + HCQ + SSZ
for the outcome HAQ [β (95% CI) -0.19 (-0.38; -0.0048)]. Results were therefore stratified for individual DMARDs and for
combination therapy with csDMARDs (table 2). It was found that women had a worse response than men to MTX monotherapy, MTX
+ HCQ and SSZ + HCQ (for DAS and HAQ) and for SSZ monotherapy and MTX + SSZ (for DAS). For patients using HCQ
monotherapy or MTX + HCQ + SSZ there were no gender differences over time.
Conclusion: Women more often started treatment with HCQ, as monotherapy or in combination with MTX or a glucocorticoid,
whereas men more often started treatment with MTX and/or SSZ. In general women had worse response to treatment than men, but we
found no gender differences in response to HCQ monotherapy or to combination of MTX + HCQ + SSZ.
Disclosure: S. A. Bergstra, None; C. F. Allaart, Abb Vie, 5,UCB, 5,Schering-Plough, 5,Centocor, Inc., 5,MSD, 5,Roche
Pharmaceuticals, 5,Mitsubishi Tanabe, 5,Pfizer Inc, 5; S. Ramiro, None; A. Chopra, None; C. A. Silva, None; N. Govind, None; R. B.
M. Landewé, Abbott/Abb Vie, Ablynx, Amgen, Astra-Zeneca, Bristol Myers Squibb, Celgene, Janssen, Galapagos, Glaxo-Smith-
Kline, Novartis, Novo-Nordisk, Merck, Pfizer, Roche, Schering-Plough, TiGenix, UCB, Wyeth, 5,Abbott, Amgen, Centocor, Novartis,
Pfizer, Roche, Schering-Plough, UCB, Wyeth, 2,Director of Rheumatology Consultancy BV, 4,Board Member Merit Foundation, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/do-we-treat-men-and-women-differently-and-is-

this-a-good-thing
Impact of Smoking Cessstion Advise in Patients with Rheumatoid Arthritis to Help

Quit Smoking
Shama Khan1, Ahmad Butt1, Emmett Brennan2, Ausaf Mohammad1 and Killian O Rourke3, 1Rheumatology, Midlands Regional
Hospital, Tullamore, Ireland, 2Tullamore, Midlands Regional Hospital, Tullamore, Ireland, 3Rheumatology, Midlands Regional
Hospital, Tullamore, Co Offaly, Ireland
SESSION INFORMATION
Background/Purpose:
Smoking is associated with an increased risk of comorbidities in rheumatoid arthritis (RA) and may reduce the efficacy of anti-
rheumatic therapies. Smoking cessation is therefore critically important in RA management and may lead to a reduced comorbid burden
(1,2). The aim of this pilot study was to investigate whether smoking cessation rates are increased following a smoking cessation advice
for people with RA.
Methods:
We conducted a prospective study of one hundred and eighty RA patients fulfilling the 1987 American College of Rheumatology
classification criteria, from October 2016 to March 2017, attending our rheumatology services. Ethics approval was obtained.
Information on demographics and cigarette smoking status was collected through patients’ interviews and medical notes review. Current
smokers were given advice on quitting smoking through face-to-face advice, handout, and nicotine replacement. Subjects were re-
interviewed at 6-months to ascertain smoking status. The primary outcome was smoking cessation at 6 months.
Results:
180 current smokers with RA were included: mean age 56± 11.9 years and 76% were females. Overall, 64% of subjects stopped
smoking at 6 months, and remainder RA smokers were thinking about quitting. More female subjects quit smoking as compared to
males (74% vs. 26%). Those who quit smoking were younger (49 years vs. 57 years), had higher BMI (28.7 ± 3.6 vs. 26.7 ± 3.6), and
had aggressive disease, DAS28-CRP (4.9 ± 0.9 vs. 2.9 ± 0.9) (P < .05). Subjects who stopped smoking stated “healthy life style” as
motivation to quit.
Conclusion:
In our study significant proportion of RA patients stopped smoking when given advice on quitting. Smoking cessation advice was very
beneficial in motivating them to quit smoking. There should be a structured plan in place to educate RA patients on smoking cessation,
both in verbal and written form.
Disclosure: S. Khan, None; A. Butt, None; E. Brennan, None; A. Mohammad, None; K. O Rourke, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/impact-of-smoking-cessstion-advise-in-patients-

with-rheumatoid-arthritis-to-help-quit-smoking
Repair of Joint Damage Is Rare in Newly Diagnosed Rheumatoid Arthritis Patients

and Appears Not to Relate to Previous Suppression of Inflammation
Joy A. van der Pol1, Gulsah Akdemir1, Marianne van den Broek1, Linda Dirven1, Pit J.S.M. Kerstens2, Willem F. Lems3, Iris M.
Markusse1, Cornelia F Allaart1 and Tom W.J. Huizinga1, 1Department of Rheumatology, LUMC, Leiden, Netherlands, Leiden,
Netherlands, 2Department of Rheumatology, Reade, Amsterdam, Netherlands, 3Department of Rheumatology, VU Medical Center,
Amsterdam, Netherlands, Amsterdam, Netherlands
SESSION INFORMATION
Background/Purpose: Joint damage in RA is thought to be irreparable. We hypothesized that in patients in whom inflammation is
persistently well suppressed, repair may be possible.
Objectives: To investigate whether reversal of erosions and joint space narrowing (JSN) in RA occurs and whether clinical variables
predict repair.
Methods: In the BeSt study, patients with active early RA were randomized to 4 treatment strategies, each with the aim to induce and
maintain suppression of disease activity by adjusting medication based on three-monthly calculations of the 44-joint Disease Activity
Score (DAS), target ≤2.4. Radiographic joint damage was assessed yearly, using the Sharp/van der Heijde score (SHS). In this analysis,
8-years data of the study were used. Repair of erosions or JSN was defined at the individual joint level as a reduction of ≥1 SHS point
compared to the previous available X-ray, present in ≥2 consecutive visits and with ≥3 out of 4 independent scorers agreeing.
Radiographs were scored in random order per patient, blind for patient identity and treatment arm. Multiple logistic regressions were
applied at the patient level for associations between achieving repair and maximum duration of previous remission, mean DAS until
repair, previous prednisone use, previous infliximab use, ACPA, gender, age and randomization arm. All models were adjusted for mean
joint damage over time in the group with repair. In the group without repair, the models were corrected for mean damage over time until
mean time point of repair in the group with repair.
Results: Seven out of 508 patients did not have any X-ray images taken in the study. Of the remaining 501 patients, 320 had damage in
at least 1 joint and thus could potentially show repair. In total, 2395 X-rays were available, on average 7.5 per patient (range 2-9).
Median SHS after 8 years in these patients was 13 (IQR 4-21, range 0.67-255), and mean (SD) DAS from month 3 was 2.00 (0.67).
Repair was seen in 17 out of 320 patients, 5.3%; 10 had reduction of JSN, 7 of erosions. In 14 patients repair was seen in 1 joint, in 3
patients repair was seen in 2 joints (same time point). Mean (SD) time to repair was 44.1 (20.1) months. Ten of 17 patients (59%) had
previously achieved DAS-remission, compared to 100% of the patients who at a matching time point showed no repair. Adjusted for
mean SHS until repair, we found a trend for less repair with longer baseline symptom duration and for less repair in the arm with initial
infliximab. There were no associations with repair for duration of remission, mean DAS until repair, gender, age, presence of ACPA, or
previous exposure to prednisone or infliximab (table 1).
Conclusion: In this early RA cohort, during 8 years treated to target DAS ≤2.4, repair of JSN and erosions was seen in 17 patients
(5.3%). Repair does not seem to relate to previous inflammation or other predictors in this cohort.
Disclosure: J. A. van der Pol, None; G. Akdemir, None; M. van den Broek, None; L. Dirven, None; P. J. S. M. Kerstens, None; W.
F. Lems, Pfizer, MSD, Eli Lilly, Abbvie, 8; I. M. Markusse, None; C. F. Allaart, Abb Vie, 5,UCB, 5,Schering-Plough, 5,Centocor,
Inc., 5,MSD, 5,Roche Pharmaceuticals, 5,Mitsubishi Tanabe, 5,Pfizer Inc, 5; T. W. J. Huizinga, Janssen and Abbvie, 2,Merck, from
UCB, from Bristol Myers Squibb, from Pfizer, from Novartis, from Roche, from Sanofi-Aventis, from Abbott, from Crescendo
Bioscience, from Nycomed, from Boeringher, from Takeda, from Epirus and from Eli Lilly., 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/repair-of-joint-damage-is-rare-in-newly-diagnosed-

rheumatoid-arthritis-patients-and-appears-not-to-relate-to-previous-suppression-of-inflammation
Implementation of a Treat-to-Target Remission Strategy for Rheumatoid Arthritis in

Australian Public and Private Rheumatology Clinics – Identification of Clinician and
Patient Barriers
Helen Benham1, Hedva Chiu2, Joanne Tesiram3, Peter Landsberg4, Andrew A. Harrison5, Peter Nash6, Ranjeny Thomas7 and Mieke
van Driel8, 1The University of Queensland Faculty of Medicine, Brisbane, Australia, 2The University of Queensland Faculty of
Medicine, Woolloongabba, Australia, 3Rheumatology, Princess Alexandra Hospital, Woolloongabba, Australia, 4Princess Alexandra
Hospital, Woolloongabba, Australia, 5Department of Medicine, University of Otago Wellington, Wellington, New Zealand, 6University
of Queensland, Brisbane, Australia, 7Diamantina Institute, Diamantina Institute University of Queensland, Brisbane, Australia,
8Primary Care Clinical Unit, The University of Queensland Faculty of Medicine, Herston, Australia
SESSION INFORMATION
Background/Purpose: Treat-to-target in rheumatoid arthritis (RA-T2T) improves outcomes for people living with RA. Implementing
T2T in routine clinical practice however presents many challenges and an evidence practice gap has emerged.
Methods: Cross-sectional surveys were undertaken in parallel: A survey of RA patients and Australian rheumatologists. Agreement
was measured using a 10-point Likert scale for RA-T2T recommendations and 5-point for use in daily practice. Questions related to
willingness to alter practice, education and patient perceptions were included with free-text comments and thematic analysis
undertaken.
Results: 85 rheumatologists and 107 patients responded. Surveys show the majority of patients have no knowledge of RA-T2T (91%)
but report high levels of agreement with the recommendations (8.61 to 9.51). Patients are willing to try a T2T approach (88%) and
would be specifically willing to increase blood tests (96%), have joint counts performed (87%) and use a patient-reported-outcome tool
(83%). They are less willing to have more frequent appointments (66%) and to spend additional time discussing RA-T2T (69%). 48%
of patients feel their RA treatment could be improved and 28% would like to be more involved in treatment decision making. For
rheumatologists the mean level of agreement scores ranged from 7.32 to 9.33. Lowest level of agreement was with the recommendation
that a disease activity score is required to guide care in routine practice (7.32). 50% of rheumatologists reported they very often/often
use a score in daily practice. 44% do not think RA-T2T is necessary for every RA patient. Rheumatologists are willing to schedule more
visits (88%), perform joint counts (84%), use a PRO for shared decision-making (76%) and spend time discussing RA-T2T (85%).
They are less willing to calculate a disease activity score (64%). Free text identified four thematic barriers to implementation of RA-
T2T identified by rheumatologists: time, patient acceptance and adherence to medication change, lack of appointment availability and
the lack of a rheumatology nurse in the clinic.
Conclusion: RA-T2T is an evidence-based intervention and is recommended for the management of RA. Agreement with some aspects
of RA-T2T and uptake in routine clinical practice by Australian rheumatologists is low and the majority of patients are unaware of RA-
T2T. Significant clinician and patient barriers exist and an implementation strategy utilizing an electronic and patient-driven
knowledge-translation tool, for use at the point of care, is being created and tested for usability in Australian rheumatology clinics.
Disclosure: H. Benham, AbbVie, 2,AbbVie, 8; H. Chiu, None; J. Tesiram, None; P. Landsberg, None; A. A. Harrison, AbbVie, 8;
P. Nash, None; R. Thomas, Janssen Pharmaceutica Product, L.P., 2,Janssen Pharmaceutica Product, L.P., 5; M. van Driel, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/implementation-of-a-treat-to-target-remission-

strategy-for-rheumatoid-arthritis-in-australian-public-and-private-rheumatology-clinics-identification-of-clinician-and-patient-barriers
Post-Marketing Surveillance of Tofacitinib in Japanese Patients with

Rheumatoid Arthritis: An Interim Report of Safety Data
Tsuneyo Mimori1, Masayoshi Harigai2, Tatsuya Atsumi3, Masataka Kuwana4, Syuji Takei5, Naoto Tamura6, Takao Fujii7, Hiroaki
Matsuno8, Shigeki Momohara9, Kazuhiko Yamamoto10, Takeshi Kokubo11, Yutaka Endo11, Naonobu Sugiyama11, Tomohiro Hirose11,
Yosuke Morishima11 and Noritoshi Yoshii11, 1Kyoto University, Kyoto, Japan, 2Division of Epidemiology and Pharmacoepidemiology
of Rheumatic Diseases, Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan, 3Hokkaido University, Sapporo,
Japan, 4Nippon Medical School, Tokyo, Japan, 5Kagoshima University, Kagoshima, Japan, 6Juntendo University, Tokyo, Japan,
7Wakayama Medical University, Wakayama, Japan, 8Matsuno Clinic for Rheumatic Diseases, Toyama, Japan, 9Hakkeikai Inc Medical
Institution, Shizuoka, Japan, 10University of Tokyo, Tokyo, Japan, 11Pfizer Japan Inc, Tokyo, Japan
SESSION INFORMATION
Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Efficacy and safety
of tofacitinib have been shown in patients (pts) with RA in global Phase (P) 2, P3 (one of which included Japanese pts) and a long-term
extension (LTE) study and in two P2 and one LTE study in Japanese pts. We evaluated safety of tofacitinib following drug approval in
Japanese pts with RA using all-case post-marketing surveillance (PMS) data.
Methods: PMS is a regulatory requirement in Japan; an interim analysis of safety data from an ongoing 3-year PMS study was
conducted (4 Mar 2017 data-cut). All Japanese pts with RA receiving tofacitinib were consecutively and prospectively registered in the
PMS study and were monitored. Follow-up surveillance after discontinuation of tofacitinib was implemented for 3 years for all adverse
events (AEs) from the date of treatment initiation with tofacitinib. A 6-month interim analysis of all AEs and serious AEs (SAEs) was
conducted. For AEs of special interest, all-period data was used to calculate cumulative incidence rates (IRs) over time (IRs: pts with
events /100 pt-years [pt-yrs]) for herpes zoster (HZ) and serious infection events (SIEs) during treatment +28 days, and for
malignancies during the observational period.
Results: Overall, 2882 tofacitinib-treated pts were enrolled and included in the 6-month interim safety analysis: 79.9% were female,
mean age 62.6 yrs, with 32.0% pts ≥70 yrs and 1241.4 pt-yrs of exposure. Of these, 686 pts (23.8%) discontinued treatment, mainly due
to AEs (276 pts; 9.6%) or lack of effectiveness (260 pts; 9.0%; multiple reasons allowed). At least one AE was observed in 965 pts
(33.5%); infections were observed in 367 pts (12.7%); the most frequent AEs were HZ (98 pts; 3.4%) and hepatic function abnormal
(48 pts; 1.7%). SAEs occurred in 221 pts (7.7%); the most frequent SAEs were pneumonia (20 pts; 0.7%), HZ (16 pts; 0.6%),
interstitial lung disease (14 pts; 0.5%) and condition aggravated (12 pts; 0.4%); serious infections occurred in 101 pts (3.5%).
Malignancy (all causality) was reported in 21 pts (0.7%); ovarian cancer, pancreatic carcinoma, lung neoplasm, colon cancer, breast
cancer, diffuse large B‑cell lymphoma and lymphoproliferative disorder all occurred in 2 pts (0.07%) each. There were 16 deaths (0.6%)
during the 6-month observed period; the most common causes of death (including pts with multiple causes listed) were infection (5
cases, all respiratory infections), malignancy (4 cases) and interstitial lung disease (3 cases). For AEs of special interest from all-period
data during treatment +28 days, the IR of HZ (serious and non-serious) was 6.43/100 pt-yrs (160 pts; 2489.5 pt-yrs) and SIEs 5.96/100
pt-yrs (150 pts; 2517.0 pt-yrs), and during the observational period IR malignancy was 1.39/100 pt-yrs (42 pts; 3014.1 pt-yrs).
Conclusion: For this interim analysis, AEs during the initial 6-month treatment period from PMS reports of tofacitinib in Japanese pts
did not reveal any new or unexpected safety signals vs the tofacitinib RA clinical program. Final results from this PMS study are
awaited in order to make definitive conclusions on the safety profile of tofacitinib in these pts.
Disclosure: T. Mimori, Astellas, Ayumi, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi Tanabe, MSD, Sanofi, Taisho Toyama, 2,Astellas,
Bristol-Myers Squibb, Chugai, Eisai, Mitsubishi-Tanabe, 8; M. Harigai, Eisai, Takeda, Teijin, 2,Bristol-Myers Squibb, Chugai,
Janssen, Pfizer Inc, 5; T. Atsumi, Alexion, Astellas, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Sanofi,
2,AbbVie, Astellas, Chugai, Eisai, Mitsubishi-Tanabe, Pfizer Inc, Takeda, UCB Japan, 8,Bayer, Daiichi-Sankyo, Takeda, 9; M.
Kuwana, Chugai, Eisai, Mitsubishi-Tanabe, Ono, Pfizer Inc, Santen, 2,Astellas, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Ono, Pfizer
Inc, UCB, 8; S. Takei, Chugai, Eisai, Mitsubishi-Tanabe, Takeda, 2,Asahi-kasei, Ayumi, Chugai, Mitsubishi-Tanabe, Ono, 8; N.
Tamura, AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Takeda, 2,AbbVie, Astellas, Bristol-
Myers Squibb, Eisai, Janssen, Mitsubishi-Tanabe, 8; T. Fujii, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, Ono, Pfizer Japan Inc,
2,AbbVie, Mitsubishi-Tanabe, Ono, Pfizer Japan Inc, 8; H. Matsuno, Ayumi, Meiji Seika, Mochida, Nichi-Iko, 5; S. Momohara,
AbbVie, Bristol-Myers Squibb, Eisai, Janssen, Mitsubishi-Tanabe, Ono, Pfizer Japan Inc, Takeda, 8; K. Yamamoto, AbbVie, Astellas,
Ayumi, Chugai, Eisai, Mitsubishi Tanabe, Nippon Kayaku, Pfizer, Taisho Toyama, Takeda, TEIJIN UCB, 2,Asahikasei, AstraZeneca,
Ayumi, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer Inc, Sanofi, Sumitomo
Dainippon, Taisho Toyama, Takeda, TEIJIN, Toyama Chemical, UCB, 8; T. Kokubo, Pfizer Japan Inc, 3; Y. Endo, Pfizer Inc, 1,Pfizer
Japan Inc, 3; N. Sugiyama, Pfizer Inc, 1,Pfizer Japan Inc, 3; T. Hirose, Pfizer Inc, 1,Pfizer Japan Inc, 3; Y. Morishima, Pfizer Inc,
1,Pfizer Japan Inc, 3; N. Yoshii, Pfizer Inc, 1,Pfizer Japan Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/post-marketing-surveillance-of-tofacitinib-in-

japanese-patients-with-rheumatoid-arthritis-an-interim-report-of-safety-data
ACPA and RF As Predictors of Sustained Clinical Remission in Rheumatoid

Arthritis Patients: Data from a Rheumatoid Arthritis Cohort
Janet E. Pope1, Emmanouil Rampakakis2, Mohammad Movahedi3, Angela Cesta3, John S. Sampalis4 and Claire Bombardier3,
1Department of Medicine, Division of Rheumatology, University of Western Ontario, St Joseph's Health Care, London, ON, Canada,
2JSS Medical Research, Montreal, QC, Canada, 3Toronto General Hospital Research Institute, University Health Network, Toronto,
ON, Canada, 4McGill University, Montreal, QC, Canada

SESSION INFORMATION
ACPA and RF as Predictors of Sustained Clinical Remission in Rheumatoid Arthritis Patients: Data From a Rheumatoid
Arthritis Cohort
Background/Purpose: Positive serology for anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) are included among
the criteria for definitive RA diagnosis as per the 2010 ACR/EULAR classification criteria for rheumatoid arthritis (RA). Previous
studies have shown that autoantibodies are positive predictors of response in rheumatoid arthritis (RA) patients treated with some
biologics. The purpose of this study was to evaluate the interaction of RF and ACPA in predicting sustained clinical response in a large
observational cohort of RA patients followed in routine clinical care. Methods: RA patients enrolled in the Ontario Best Practices
Research Initiative (OBRI) registry, with active disease (≥1 swollen joint), available autoantibody information, and at least 1 follow-up
assessment were included in the analysis. Sustained clinical remission was defined as CDAI ≤ 2.8 in at least 2 sequential visits
separated by at least 3 and maximum of 12 months. Time to sustained remission was assessed with Kaplan-Meier survival analysis and
multivariate cox regression. Results: A total of 970 patients were included in the analysis, of whom 262 (27%) were anti-
CCPneg/RFneg, 60 (6.2%) anti-CCPpos /RFneg, 117 (12.1%) anti-CCPneg /RFpos, and 531 (54.7%) anti-CCPpos /RFpos. At baseline,
significant differences were observed between groups in age (p=0.02), CDAI (p=0.03), tender joint count (p=0.02), and HAQ
(p=0.002), with anti-CCPpos /RFpos and anti-CCPpos /RFneg patients being youngest and having the lowest disease activity and
disability. No differences were observed in terms of biologic use which occurred in 15.9% of patients. Sustained remission was
achieved by 43.5% of anti-CCPpos /RFpos patients, 43.3% of anti-CCPpos /RFneg patients, 31.6% of anti-CCPneg /RFpos patients and
32.4% of anti-CCPneg/RFneg patients (p=0.01). Significant (for RF, borderline non-significant) differences were observed in the time to
achieving sustained clinical response based on anti-CCP status (p<0.001), RF status (p=0.06), and both (p=0.004) (Figure 1).
Multivariate cox regression adjusting for baseline CDAI score, age and sex also showed differences between groups which reached
statistical significance in anti-CCPpos /RFpos vs. anti-CCPneg/RFneg patients (HR [95%CI]: 1.30 [1.01-1.67]; p=0.03). Conclusion:
These results suggest that anti-CCP but not RF positivity may be associated with improved response to anti-rheumatic medications in
RA patients.
Figure 1: Time to Sustained Clinical Response by Autoantibody Status
Disclosure: J. E. Pope, AbbVie, Amgen, Bayer, BMS, Celtrion, Eli Lilly and Company, Merck, Novartis, Pfizer, Roche, UCB,
5,Amgen, Bayer, BMS, GSK, Merck, Novartis, Pfizer, Roche, UCB, 2; E. Rampakakis, Janssen Inc., 9; M. Movahedi, None; A.
Cesta, None; J. S. Sampalis, None; C. Bombardier, Canada Research Chair in Knowledge Transfer for Musculoskeletal Care, 6,Pfizer
Research Chair in Rheumatology, 6.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/acpa-and-rf-as-predictors-of-sustained-clinical-

remission-in-rheumatoid-arthritis-patients-data-from-a-rheumatoid-arthritis-cohort
Predictors of Earlier Biologic Initiation Among Patients with Rheumatoid Arthritis

Starting Methotrexate
Michael D. George1, Brian Sauer2, Chia-Chen Teng, MS2, Grant Cannon2, Bryant R. England3, Gail S. Kerr4, Ted R. Mikuls5 and
Joshua Baker6, 1Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, 2Salt Lake City VA Medical Center and
University of Utah, Salt Lake City, UT, 3Division of Rheumatology & Immunology, Department of Internal Medicine, Nebraska-
Western IA VA Health Care System & University of Nebraska Medical Center, Omaha, NE, 4VAMC, Georgetown University,
Washington, DC, 5Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, 6Rheumatology,
SESSION INFORMATION
Background/Purpose: Biologic therapy for the treatment of RA has increased dramatically and has substantially increased costs of
care. This study aimed to identify factors associated with initiation of biologic use, including previous methotrexate (MTX) adherence
and dose.
Methods: We used U.S. Veteran’s Affairs administrative databases to identify RA patients receiving a first-ever prescription of MTX
between 2005 and 2014 with at least 6 months of prior baseline data. Patients with prior biologic therapy use or those initiating biologic
therapy within 30 days of starting MTX were excluded. Multivariable Cox analysis assessed factors associated with biologic therapy
initiation within 2 years of MTX start, censoring at death. To assess impact of MTX adherence and dose on biologic use, we examined a
subset of patients who received MTX continuously for at least 6 months with no biologic initiation during this time. In this population
we evaluated associations between PDC (proportion of days covered) in the first 6 months and MTX dose at 6 months with subsequent
biologic initiation.
Results: 17,634 patients met inclusion criteria contributing 29,350 person years of follow-up. 3,263 initiated biologic therapy within 2
years (incidence 11.1%/year). CCP positivity, later calendar year, and concurrent use of glucocorticoids, leflunomide, or sulfasalazine
were associated with a greater likelihood of biologic initiation (Table 1). Factors associated with a lower rate of biologic initiation
included advancing age, non-white race, greater comorbidity (Charlson score), congestive heart failure, and malignancy (Table 1,
Figure 1). Among the smaller cohort of 9,851 patients remaining on methotrexate continuously for 6 months, methotrexate adherence
(PDC ≥ 0.8) was not associated with likelihood of subsequent biologic initiation [aHR 1.00 (0.89-1.13), p = 0.94]. Higher methotrexate
dose was associated with greater likelihood of initiating biologic therapy (Table 2).
Conclusion: Biologic therapy is initiated less frequently in elderly patients and those with comorbidities, possibly reflecting safety
concerns. Future studies should evaluate whether these concerns lead to under-treatment of these populations. Surprisingly, low
methotrexate adherence and dose were not associated with increased biologic use; the impact of reduced methotrexate effectiveness
could be masked by differences in disease severity, follow-up, or medication preferences in these patients.
Disclosure: M. D. George, Bristol Myers Squibb, 2; B. Sauer, Amgen, 2; C. C. Teng, MS, Amgen, 2; G. Cannon, Amgen, 2; B. R.
England, None; G. S. Kerr, Janssen, BMS, Genetech, Pfizer, 2; T. R. Mikuls, BMS, 2,Ironwood Pharm, 2,Pfizer Inc, 5,NIH, VA, 2; J.
Baker, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/predictors-of-earlier-biologic-initiation-among-

patients-with-rheumatoid-arthritis-starting-methotrexate
Factors Associated with Treatment Adherence in Rheumatoid Arthritis: A

Systematic Literature Review
Ee Teng Goh1, Alvin Jian Xiong Soo1, James Galloway2, Sam Norton3 and Elena Nikiphorou4, 1UCL Medical School, University
College London, London, United Kingdom, 2King's College, and King´s College Hospital, London, United Kingdom, 3Academic
Rheumatology, King´s College London, London, United Kingdom, 4Academic Rheumatology Department, King's College London,
London, United Kingdom
SESSION INFORMATION
Background/Purpose: Nonadherence to treatment in rheumatoid arthritis (RA) has been shown to negatively impact on treat to target
goals and disease outcomes. Identifying and targeting potential factors influencing nonadherence is therefore crucial in optimising
patient management. This review aims to determine factors associated with nonadherence in patients with RA.
Methods: An electronic search was performed by two independent reviewers using MEDLINE and focusing on articles published from
inception to January 2017. The search strategy combined the thesaurus (MeSH) and expanded keyword searches of two concepts: RA
and treatment adherence. Inclusion criteria included observational studies and clinical trials examining potential factors associated with
nonadherence. Exclusion criteria included articles not in English or without online access and those with a focus on forms of therapy
other than medication. Agreement between raters at the screening stage was high (94.6%, kappa=.88).
Results: The primary search yielded 1411 papers, from which 70 were eventually identified as suitable for full review (Figure). Of the
70 papers, 62 were based on observational studies and eight on clinical trials. Factors associated with nonadherence were broadly
categorized into patient-related factors (demographics, socioeconomic factors, patient perceptions[beliefs/knowledge/attitudes]),
disease-related factors (disease duration, disease activity, comorbidities, functional disability) and treatment-related factors (drug type,
method of administration, concurrent treatment, side effects, cost). Many studies (74.3%) looking at beliefs, attitudes and patient
knowledge reported significant associations between these factors and nonadherence. Adherence was found to be positively associated
with stronger beliefs in the necessity of treatment, positive outlooks on disease control and medication, greater knowledge as well as
greater self-efficacy. Studies reported greater comorbidities (n=8) including poorer mental health (n=5) to be implicated in
nonadherence. Disease duration was largely non-significant in treatment adherence, although a few studies reported a negative
correlation (n=3). The use of biologics was significantly associated with greater adherence. One study identified polypharmacy to be
negatively associated with adherence. Drug side effects were associated with nonadherence (n=3).
Conclusion: Patient-related factors including personal perceptions were among key contributors to nonadherence to medication in RA
patients. This highlights the need for addressing patient-driven perceptions, along with disease and treatment related factors as part of
individualised patient care, to minimise the risk of nonadherence.
Figure showing flowchart of study selection process
Disclosure: E. T. Goh, None; A. J. X. Soo, None; J. Galloway, MSD, 5,UCB, 5,Bristol Myers Squibb, 5,Pfizer Inc, 5,Celgene, 5; S.
Norton, None; E. Nikiphorou, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/factors-associated-with-treatment-adherence-in-

rheumatoid-arthritis-a-systematic-literature-review
Characteristics of Rheumatoid Arthritis Patients Who Have a DMARD Interruption

and the Impact of Using a Bridging Medication on Clinical and Patient Reported
Outcomes
Christine Iannaccone1, Michelle Frits2, Taysir G. Mahmoud3, Gabriela Maica4, Jonathan Coblyn5, Michael Weinblatt2 and Nancy A.
Shadick6, 1Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, 2Rheumatology, Immunology and
Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 3Division of Rheumatology, Immunology and
Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 4Department of Rheumatology, Allergy, and
Immunology, Brigham and Women's Hospital, Boston, MA, 5Department of Rheumatology, Brigham & Womens Hospital, Boston,
MA, 6Rheumatology Immunology & Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
SESSION INFORMATION
Background/Purpose: It is common for RA patients to interrupt their DMARD use due to events like infection, surgery, or pregnancy.
Many RA patients may need to manage their symptoms during these times. Little is known about the characteristics of patients who
have a break in their DMARD regimen and whether the use of a bridging medication produces better clinical and patient reported
outcomes.
Methods: Clinical and patient reported data were collected from a prospective RA cohort. Data included whether patients reported
DMARD interruption for any duration of time in the past 6 months and if they used a bridging medication (corticosteroid and/or
NSAID) during the DMARD break. All data were collected at the time of survey. The outcomes (VAS Pain, fatigue, and patient global)
were also collected at a study visit approximately 6 months prior and DAS28-CRP3 collected approximately 1 year prior. In univariate
analyses, clinical and demographic characteristics of patients who had a DMARD interruption and used of a bridging medication were
compared to patients who did not use of a bridging medication. The outcomes were evaluated in stepwise multiple linear regression
models, adjusting for potential covariates of univariate significance (p<0.15) to assess the impact of a bridging medication (Figure).
Results: The study surveyed 503 RA patients, of which 112 (22%) reported a DMARD interruption in the last 6 months. Patients who
reported a DMARD interruption had a median age of 59 (IQR 49.5, 68), were 85% female, and had median disease duration of 15 years
(IQR 9, 25). Patients who used a bridging medication during a DMARD interruption (n=39) had higher disease activity (p=0.0002),
fatigue (p=0.03), and pain (p<0.001) at the time of the survey compared to patients who did not use a bridging medication. In the final
stepwise regression models evaluating the outcomes, comparing patients who did versus did not use a bridging medication, pain,
fatigue, and patient global were no better with a bridging medication even after adjustment for baseline outcome severity (Figure). Use
of a bridging medication was associated with a worse DAS28-CRP3 (p=0.008) after adjusting for covariates and baseline DAS28-CRP3
level (Figure).
Conclusion: In this study, nearly one quarter of RA patients reported an interruption of their DMARD regimen in the past 6 months and
one third used an NSAID and/or corticosteroid to manage their symptoms during the break. Use of a bridging medication was not
associated with better patient reported outcomes and patients had worse disease activity after the break. Better treatments for patients
who need to manage symptoms during a DMARD interruption may be warranted.
Disclosure: C. Iannaccone, None; M. Frits, None; T. G. Mahmoud, None; G. Maica, None; J. Coblyn, None; M. Weinblatt,
Amgen, BMS, Crescendo Bioscience, UCB, Genzyme, 2,Amgen, Abbvie, BMS, Eli Lilly and Company, Gilead, Merck, Pfizer,
Novartis, Roche, UCB, Crescendo Bioscience, Genzyme, Samsung, 5; N. A. Shadick, Mallinckrodt, 2,Amgen, 2,Bristol-Myers Squibb,
2,UCB, 2,DxTerity, 2,Sanofi, 2,Crescendo Biosciences, 2,Bristol-Myers Squibb, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/characteristics-of-rheumatoid-arthritis-patients-who-

have-a-dmard-interruption-and-the-impact-of-using-a-bridging-medication-on-clinical-and-patient-reported-outcomes
Baseline Anemia As a Predictor of Radiographic Progression in Tofacitinib-Treated

Rheumatoid Arthritis Patients: Post Hoc Analyses from Two Phase 3 Trials
Burkhard Moeller1, Axel Finckh2, Godehard Scholz1, Harry Shi3, Carol A Connell4 and Sander Strengholt5, 1Department for
Rheumatology, Immunology and Allergology, University Hospital of Bern, Bern, Switzerland, 2University Hospital of Geneva, Geneva,
Switzerland, 3Pfizer Inc, Collegeville, PA, 4Pfizer Inc, Groton, CT, 5Pfizer Inc, Capelle aan den IJssel, Netherlands
SESSION INFORMATION
Background/Purpose: Anemia in patients with rheumatoid arthritis (RA) can help to identify those with more rapid erosive disease.1,2
Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. In this post hoc analysis, we explored whether anemia was a
predictor of radiographic progression in patients with RA who were treated with tofacitinib.
Methods: Data were from two 24-month, Phase 3 randomized controlled trials in methotrexate (MTX)-naïve (ORAL Start
[NCT01039688]) or MTX-inadequate responder (IR) patients (ORAL Scan [NCT00847613]). Patients received either tofacitinib 5 or
10 mg twice daily (as monotherapy or with background MTX), placebo or MTX. Radiographic progression was evaluated by modified
Total Sharp Score (mTSS) at baseline (BL), Month (M)6, M12, and M24. Anemia was defined as lower normal hemoglobin limits of 12
g/dL for women or 13 g/dL for men. We used a linear mixed model with repeated measure analysis to analyze the impact of BL anemia
on change in radiographic joint damage (ΔmTSS), adjusting for treatment, age, gender, disease duration, and BL mTSS, autoantibody
status, DAS28, corticosteroid, and non-steroidal anti-inflammatory drug (NSAID) use. Analyses were performed on observed data
without linear extrapolation on missing data.
Results: Anemia was present at BL in 312/956 MTX-naïve patients (32.6%), RA duration ranged from 2.7–3.4 (mean) and from 0.7–
0.8 (median) years, and in 321/797 MTX-IR patients (40.3%), RA duration ranged from 8.9–9.2 (mean) and from 6.0–7.7 (median)
years. In MTX-naïve patients, anemia at BL was significantly associated with additional ΔmTSS from BL to M6 only (difference in
ΔmTSS with and without BL anemia = 0.40; p<0.001) and increased ΔmTSS was also observed at M6 for patients receiving tofacitinib
(0.25; p<0.05) or MTX monotherapy (0.95; p<0.005) (Figure 1A). There were no differences in ΔmTSS observed at M12 or M24 for
either treatment group according to anemia status (data not shown). No associations between BL anemia and ΔmTSS were observed for
MTX-IR patients overall or in either treatment group at M6 (Figure 1B), M12, or M24.
Conclusion: BL anemia was associated with radiographic progression at M6 in MTX-naïve patients, regardless of treatment received
(tofacitinib or MTX monotherapy) but not at later time points (M12/M24). These data support the evidence that anemia at BL is a
predictive parameter for joint damage progression in MTX-naïve patients, at least up to M6.
References:
1. Moller B et al. Ann Rheum Dis 2014; 73: 691-696.
2. van Steenbergen HW et al. Ann Rheum Dis 2013; 72: e16.
Figure 1. Association between baseline anemia and change in radiographic progression at Month 6 in A) MTX-naïve and B) MTX-IR
patients
Disclosure: B. Moeller, None; A. Finckh, AbbVie, 8,A2BIO, 8,BMS, 8,Eli-Lilly, 8,MSD, 8,Pfizer Inc, 8,Roche, 8; G. Scholz, None;
H. Shi, Pfizer Inc, 1,Pfizer Inc, 3; C. A. Connell, Pfizer Inc, 1,Pfizer Inc, 3; S. Strengholt, Pfizer Inc, 1,Pfizer Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/baseline-anemia-as-a-predictor-of-radiographic-
progression-in-tofacitinib-treated-rheumatoid-arthritis-patients-post-hoc-analyses-from-two-phase-3-trials
Recruitment of RA Trials in the Modern Era: Are United States-Based Trials Still
Feasible?
Carla Maldini1,2, Alfred Mahr3, David T. Felson4,5 and Michael P. LaValley6, 1Internal Medicine, Hospital Saint-Louis, Paris, France,
2Rheumatology, Hospital Córdoba, Cordoba, Argentina, 3Internal Medicine, University Hospital Saint-Louis, Paris, France, 4Clinical
Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, MA, 5Arthritis Research UK Centre for
Epidemiology, Institute of Inflammation and Repair, University of Manchester, Manchester, United Kingdom, 6Biostatistics, Boston
University School of Public Health, Boston, MA
SESSION INFORMATION
Background/Purpose: Timely recruitment of patients into interventional trials is necessary for their successful completion. The aim of
this study was to evaluate recruitment rates of interventional trials in RA with clinical centers in the United States (US).
Methods: We searched the ClinicalTrials.gov registry in May 2017 to identify trials in RA. Inclusion criteria were: phase 3 trials,
starting enrollment in 2005 to 2016, adult RA patients, at least one center in the US, an intervention to modify RA activity, and a
clinical evaluation (DAS28, ACR20, or other) as the primary endpoint. Exclusion factors were: if patients with other diseases were
included, trials carried out only in specific RA subgroups, trials terminated early, trials which had not completed enrollment, and trials
with insufficient data to calculate the recruitment rate. The recruitment rate was defined as the average number of patients enrolled per
center per month during the recruitment period, with the recruitment period defined as the time between enrollment start date and date
of enrollment of the last patient. As the registry only provides the “Primary Completion Date”, this was used as the proxy for date of
enrollment of the last patient. Recruitment rate and other trial characteristics were compared in two calendar year periods (2005-2010
and 2011-2016) using the Wilcoxon rank sum test and chi-square test. Negative binomial regression was used to evaluate the
relationship between the percent of US centers and recruitment rate.
Results: 179 trials were identified using our search strategy. 111 trials were excluded: 35 included other diseases, 24 did not complete
recruitment (6 were terminated because low enrollment or sponsor decision), 40 did not use a clinical evaluation primary endpoint, and
12 started enrollment before 2005 or after 2016. Besides, 1 trial was excluded due to inconsistency on reported data. The ACR20
criteria was the most widely used outcome measure (70%). Most trials evaluated efficacy of biological therapies (97%), and only 2
evaluated efficacy of non-biological drugs. 8 trials (12%) assessed the efficacy of biosimilars. All trials but one were industry
sponsored. Number of recruitment centers increased more than 25% in the second period (117 [77–154] vs 148 [111–186]; P = 0.058).
Conversely, percent of US centers slightly decreased in the same period (35% vs 31%; P = 0.492). The recruitment rate per center per
month was lower in the most recent time period (0.11 [0.08–0.16] vs 0.08 [0.05–0.11]; P = 0.02). Percentage of US centers was not
related to recruitment rate (P = 0.295) in regression analysis.
Conclusion: The recruitment rate per center has decreased in recent years, accompanied by a non-significant rise in the number of
centers per trial. While US-based trials remain feasible, understanding the reasons for declining enrollment trends is needed to improve
the efficiency and performance of RA trials.
Table 1. Main characteristics of all 67 studies and by calendar year periods
(2005-2010 and 2011-2016)
Over period Period Period
2005-2016 2005-2010 2011-2016 P-value
n=67 n=37 n=30

No. of patients enrolled
637 (456–897) 643 (461–990) 590 (468–710) 0.194
per trial
No. of centers per trial 136 (88–180) 117 (77–154) 148 (111–186) 0.058
No. of U.S. centers per
45 (30–65) 41 (21–67) 46 (38–59) 0.492
trial
ACR20 outcome measure,
47 (70.1) 28 (75.7) 19 (63.3) 0.272
n (%)
Recruitment rate per 12.9 (8.5– 12.9 (9.1– 12.2 (8.2–
0.512
month 15.4) 15.5) 15.1)
Recruitment rate per 0.10 (0.06– 0.11 (0.08– 0.08 (0.05–
0.020
center per month 0.14) 0.16) 0.11)
Results are expressed as median and interquartile range unless otherwise noted.
Disclosure: C. Maldini, None; A. Mahr, None; D. T. Felson, None; M. P. LaValley, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/recruitment-of-ra-trials-in-the-modern-era-are-

united-states-based-trials-still-feasible
High Multi-Biomarker Disease Activity Score Is Associated with High Risk of

Radiographic Progression in Six Cohorts
Jeffrey R. Curtis1, Cecilie Heegaard Brahe2, Mikkel Østergaard3, Merete Lund Hetland2, Karen Hambardzumyan4, Saedis
Saevarsdottir4, Xingbin Wang5, Eric H. Sasso5 and Tom W.J. Huizinga6, 1Division of Clinical Immunology and Rheumatology,
University of Alabama at Birmingham, Birmingham, AL, 2Copenhagen Center for Arthritis Research, Copenhagen, Denmark,
3Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Denmark, Copenhagen,
Denmark, 4Karolinska Institute and Karonlinska University Hospital, Stockholm, Sweden, 5Crescendo Bioscience Inc., South San
Francisco, CA, 6Rheumatology, Leiden University Medical Center, Leiden, Netherlands
SESSION INFORMATION
Background/Purpose: The multi-biomarker disease activity (MBDA) test uses a validated algorithm with 12 serum protein biomarkers
to assess disease activity in patients with RA. The MBDA score has previously been found to be a predictor of risk for radiographic
progression (RP). We evaluated data from 6 cohorts and performed a meta-analysis to collectively establish the relationship between
the MBDA score and risk for RP.
Methods: Clinical, MBDA score and radiographic data were analyzed for 6 cohorts with N>100: Leiden, SWEFOT Year 1, SWEFOT
Year 2, OPERA Year 1, and AMPLE Year 1 (abatacept and adalimumab arms). Analyses used data on file when published data were not
available (ie, for Leiden and for OPERA CRP analyses). Frequency of RP over 1 year was determined by category of MBDA score
(low, moderate, high on a scale of 1−100) at the start of the year, as reported for 4 cohorts and at the end of the year as reported for the 2
AMPLE cohorts. RP was defined using the threshold for change in modified total Sharp score (ΔmTSS) specific to each study (2 to >5
TSS units). Positive and negative predictive values (PPV and NPV) were determined for each study by comparing patients with high
MBDA score (>44), DAS28-(ESR/CRP) (>5.1 or >4.09) or CRP (>3 mg/dL) vs those in a low/moderate category. Relative risk (RR)
for RP was determined for each study. RR values were integrated in a meta-analysis that included only the 3 non-overlapping cohorts
that had reported radiographic analyses using MBDA scores at the start of the year. Results of published multivariate analyses and
analyses that combined MBDA score with other risk factors for RP were summarized.
Results: The 6 study cohorts included patients receiving csDMARDs alone or with a biologic. Overall rates of RP were 10−26%. In
each study, RP was most frequent among patients with a high vs low/medium MBDA score (>44 vs ≤44). For high MBDA scores,
NPVs were 93−97% and PPVs were 18−32%, with RR values of 3.6−9.5 (P=0.002 to <0.0001) (Figure). In a meta-analysis of the
Leiden, SWEFOT Year 1 and OPERA Year 1 cohorts, RR was 5.1 (P<0.0001) for MBDA categories, and 1.4 (P=0.23) and 1.6 (P=0.01)
for categories of DAS28-CRP or CRP, respectively. Published multivariate analyses in the Leiden and SWEFOT Year 1 cohorts showed
MBDA score was an independent predictor of RP after accounting for the effect of other predictors. In the Leiden cohort, MBDA score
was the strongest predictor and high MBDA score discriminated between high and low risk for RP among patients with high SJC (>5)
or high DAS28-CRP, with PPV as high as 57%.
Conclusion: High MBDA scores were associated with increased risk for RP in 6 study cohorts, including patients treated with
csDMARDs, TNFi and abatacept. Based on high NPVs (≥93%), the MBDA score used alone had clinical value for identifying patients
with little or no risk of RP. Combining the MBDA score with clinical measures yielded PPVs approaching 60%, suggesting that
biomarkers can help stratify patients by their risk for RP.
Disclosure: J. R. Curtis, Crescendo Biosciences, 2,Crescendo Biosciences, 5; C. H. Brahe, None; M. Østergaard, AbbVie, BMS,
Celgene, Crescendo Bioscience, Janssen, Merck, 2,Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira,
Janssen, Merck, Novartis, Orion, Pfizer, Regeneron, Roche, Takeda, and UCB, 5; M. Lund Hetland, AbbVie, Biogen, BMS,
CelltrionRoche, Crescendo Bioscience Inc., Eli Lilly, MSD, Pfizer, UCB, 2,Orion, 8; K. Hambardzumyan, None; S. Saevarsdottir,
None; X. Wang, Myriad Geneitcs, Inc., 1,Crescendo Bioscience Inc., 3; E. H. Sasso, Myriad Genetics, Inc., 1,Crescendo Bioscience
Inc., 3; T. W. J. Huizinga, Merck, UCB, Bristol Myers Squibb, Biotest AG, Pfizer, GSK, Novartis, Roche, Sanofi-Aventis, Abbott,
Crescendo Bioscience Inc., Nycomed, Boeringher, Takeda, Zydus, Epirus, Eli Lilly, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/high-multi-biomarker-disease-activity-score-is-

associated-with-high-risk-of-radiographic-progression-in-six-cohorts
Analysis of Rheumatoid Arthritis Patients That Did Not Achieve the Treatment Goal
By the Treat-to-Target Strategy in Daily Practice
Hideshi Yamazaki and Tetsuo Takanashi, Center for Rheumatic Disease, Marunouchi Hospital, Matsumoto, Japan
SESSION INFORMATION
Background/Purpose: Although the goal of rheumatoid arthritis (RA) treatment is to achieve remission or low disease activity with the
treat-to-target (T2T) strategy, some patients do not achieve the goal in daily clinical practice. This study was performed to determine the
reasons why these patients do not achieve the treatment goal.
Methods: A total of 504 patients with RA that were treated with the T2T strategy using electronic medical record system in 2014 –
2015 were investigated retrospectively. The patients had an average age of 63.7 years, and average disease duration of 15.9 years. A
total of 144 patients were evaluated with moderate or high disease activity according to the simple disease activity index (SDAI) in
2014. After 1 year, 84 patients achieved the treatment goal, i.e., remission or low disease activity, while 60 patients still showed more
than moderate disease activity and did not achieve the goal. In these patients, each item of SDAI, patient background, and treatment
content were investigated.
Results:
In 2014, the patients that did not achieve the treatment goal in 2015 had significantly higher age, disease activity, tender joint count,
patient global assessment, and HAQ-DI than the patients that did achieve the goal. In the patients that achieved the goal, all items of
SDAI were significantly improved. In the patients that did not achieve the goal, swollen joint count and physician global assessment
were significantly improved. As disease activity did not decrease, 21 patients were considered to have been treated insufficiently with
the T2T strategy. Twenty-one patients had joint pain without arthritis. Eighteen patients were not treated sufficiently for complications,
including six elderly patients, respiratory complications in eight patients, and others.
Conclusion:
Although the treatment goal of the T2T strategy in RA is remission or low disease activity, this goal is often not achieved in daily
clinical practice. The patients that do not achieve the goal have higher disease activity or are not treated sufficiently with complications.
It may be possible for these patients to achieve the goal by refining the treatment strategy or providing palliative treatment for pain.
Additional T2T is necessary.
Disclosure: H. Yamazaki, None; T. Takanashi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/analysis-of-rheumatoid-arthritis-patients-that-did-

not-achieve-the-treatment-goal-by-the-treat-to-target-strategy-in-daily-practice
Rheumatoid Arthritis Patient´s Journey: Delay in Diagnosis and Treatment

Aurelia Luissi1, Florencia Pierini1, Maria Victoria Garcia1, Mirtha Sabelli1, Marina Scolnik1, Santiago Ruta1, Javier Rosa1 and
Enrique R Soriano2, 1Rheumatology Unit, Internal Medicine Service, Hospital Italiano de Buenos Aires, CABA, Argentina, 2Argentina,
Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
SESSION INFORMATION
Background/Purpose: there is a wide variation in the time elapsed between first symptoms and diagnosis of RA, ranging from 1 month
to 10 years in different studies; data from Latin America populations are scarce.
Objective: to establish the lag times between articular symptoms onset and first rheumatologist consultation, Rheumatoid Arthritis (RA)
diagnosis and treatment with disease-modifying antirheumatic drugs (DMARDs), and to assess the impact of delay on radiologic
structural damage.
Methods: electronic Medical Records of a cohort of RA adult patients, attending a Private Health Care System (PHCS) between
01/01/1996 and 31/12/2016, were retrospectively reviewed. Clinical and demographic data, and dates of first disease symptoms,
diagnosis of RA and starting treatment with DMARDs were obtained. Physical function was assessed by Health Assessment
Questionnaire (HAQ). Radiologic structural damage was assessed by Sharp score modified by van der Heijde (SvdH score). For the
logistic multivariable analysis, radiologic structural damage was defined as the presence of any value greater than 0 on SvdH score.
Results: 246 patients (81% female), with a mean age of 67.25 (SD:14.53) years, were included. Rheumatoid factor was positive in
82.5% and anti–citrullinated peptide antibodies in 91% of patients.
At the end of follow-up (mean: 7 years, SD: 3.8), median HAQ and SvdH were 0.125 (IQR: 0-0.87) and 15 (IQR: 6-33), respectively.
Mean lag time between first disease symptom and rheumatologist consultation was 9.2 months [(SD:20) (median: 3 months)], mean lag
time to RA diagnosis was 14.2 months [(SD: 24) (median: 4.8 months)] and was16.9 months [(SD: 25.4) (median: 7 months)] for
starting treatment with DMARDs (Table).
Table. Delay times in consultations, diagnosis and treatment with DMARDs in RA patients.
Mean Median
(SD) (IQR)
Time elapsed from the beginning 8.5 1.8
of symptoms to first health
professional consultation (21.6) (0.6-5.1)
(months)
Time elapsed from the beginning 9.2 3
of symptoms to first
rheumatologist consultation (20.5) (1.2-7.1)
(months)
Time elapsed from the beginning 14.2 4.8
of symptoms to RA diagnosis
(months) (24) (2.4-13)
Time elapsed from the beginning 16.9 7
of symptoms to starting
DMARDs therapy (months). (25.4) (3-17)
More radiologic structural damage was observed in patients with more than 12 months delayed diagnosis of RA (mean SvdH score:
30.9 vs. 21.3, p = 0.0325). The presence of radiologic structural damage was associated with more than 12 months delayed diagnosis in
logistic multivariable analysis (OR: 1.7 CI 95% 1.3-4.9, p=0.04).
Conclusion: in this cohort of RA patients from a PHCS there was a significant delay to achieve RA diagnosis and starting DMARDs
therapy. A delay greater than12 months was associated with radiologic structural damage during the follow-up period.
Disclosure: A. Luissi, None; F. Pierini, None; M. V. Garcia, None; M. Sabelli, None; M. Scolnik, None; S. Ruta, None; J. Rosa,
None; E. R. Soriano, AbbVie, Janssen, Novartis, Pfizer Inc, UCB, 2,AbbVie, Janssen, Novartis, Pfizer Inc, UCB, 5,AbbVie, Bristol-
Myers Squibb, Janssen, Novartis, Pfizer Inc, Roche, UCB, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rheumatoid-arthritis-patients-journey-delay-in-

diagnosis-and-treatment
Social Media Based, Direct-to-Patient Study Designed for Development of “from

Home” Testing for Rheumatoid Arthritis Patients Is Feasible and Engaged
Individuals with Distinct Clinical Characteristics
Kristen Warren1, Olga Derbeneva1, Francisco Flores1, Michelle Frits2, James Healy1, Christine Iannaccone3, Omar Khalid1, Krishna
Morampudi1, Nancy Shadick4, Michael Weinblatt4, Hemani Wijesuriya1 and Robert Terbrueggen1, 1DxTerity, Rancho Dominguez,
CA, 2Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA,
3Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, 4Brigham and Women's Hospital and Harvard
Medical School, Boston, MA
SESSION INFORMATION
Background/Purpose: Physicians equipped with low cost, patient-administered, “from home” genomic tests for monitoring disease
activity and therapy response could revolutionize treatment for rheumatoid arthritis (RA) by enabling treat-to-target strategies,
minimizing the use of ineffective therapies, and detecting changes in disease activity before a flare occurs. However, development of a
“from home” strategy for patient care requires rigorous testing in the intended use cohort. In addition, the costs associated with
recruiting and analyzing a patient cohort of sufficient size are formidable and further compounded by the possible confounding effects
of concomitant RA therapies. Here, we investigated the feasibility of recruiting a patient cohort entirely through social media at
minimal cost and cohort metrics were compared with clinical data of patients enrolled in a traditional, clinically managed study.
Methods: A cohort of self-reported RA participants were recruited under an IRB-approved, HIPAA compliant, Direct-to-Patient
observational study entitled Baseline Rheumatoid Arthritis Verification and Outcomes (BRAVO; www.bravostudy.com). Participants
were asked to complete 3 rounds of disease monitoring over a one month period, which included a short disease history questionnaire
with RAPID3 ePRO and a self-collected 100 µL fingerstick blood sample returned through the US mail. Total RNA (50 ng) was
isolated from the self-collected blood samples and sequenced using a custom 1200-gene pan-immunity Ampliseq panel on the Ion S5.
Patient cohort metrics were compared with clinical data from the multi-center, longitudinal observational, 14-year, 1,400+ patient
Brigham Women’s Rheumatoid Arthritis Sequential Study (BRASS; www.brassstudy.org).
Results: BRAVO participants (n = 109) were recruited over a 12-week period through social media platforms. Most participants (80%)
enrolled and completed the questionnaires using a mobile device, and 84% of patient samples yield at least 100ng of isolated RNA with
an average RIN of 7.1. Comparison of cohort attributes at baseline between BRAVO and BRASS individuals (Table) exhibited
significant similarities between mean age, disease duration, and range of medications. However, the BRAVO cohort tended to have
higher disease activity, lower use of biologic and non-biologic DMARDS, higher use of narcotic/opioid pain meds and increased
ethnicity.
Conclusion: Social media and molecular analysis of patient-collected fingerstick samples are viable and cost-effective methods to
examine efficacy of direct-to-patient testing for RA affected individuals. Cohorts however differed significantly on the basis of critical
clinical parameters indicating that a direct-to-patient approach has the power to add depth to the complex RA patient population that can
be effectively monitored.
Disclosure: K. Warren, DxTerity, 3; O. Derbeneva, DxTerity, 3; F. Flores, DxTerity, 3; M. Frits, None; J. Healy, DxTerity,
1,DxTerity, 3,DxTerity, 6; C. Iannaccone, None; O. Khalid, DxTerity, 3; K. Morampudi, DxTerity, 3; N. Shadick, None; M.
Weinblatt, None; H. Wijesuriya, DxTerity, 3; R. Terbrueggen, DxTerity, 1,DxTerity, 3,DxTerity, 4,DxTerity, 6.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/social-media-based-direct-to-patient-study-

designed-for-development-of-from-home-testing-for-rheumatoid-arthritis-patients-is-feasible-and-engaged-individuals-with-distinct-
clinical

Early Treatment with Hydroxychloroquine Is Associated with Better Long-Term
Outcomes in a Group of Hispanic Patients with Rheumatoid Arthritis
Franchesca Cruz-Pérez1, Mariangelí Arroyo-Ávila1, Ruth Fred-Jiménez2, Naydi Pérez-Ríos3, Noelia Rodríguez-Pérez1, Grissel Ríos4
and Luis M. Vilá5, 1Department of Medicine, Division of Rheumatology, University of Puerto Rico Medical Sciences Campus, San
Juan, PR, 2Division of Rheumatology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico, 3Puerto Rico
Clinical and Translational Research Consortium, University of Puerto Rico Medical Sciences Campus, San Juan, PR, 4Rheumatology,
University of Puerto Rico Medical Sciences Campus, San Juan, PR, 5Department of Medicine, Division of Rheumatology, University of
Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
SESSION INFORMATION
Background/Purpose: Hydroxychloroquine (HCQ) has a disease-modifying effect in rheumatoid arthritis (RA) patients but also it is
associated with improved lipid profile, and decreased risk for diabetes and cardiovascular events. However, the impact of early HCQ
treatment in the long-term outcomes of RA is not well established. Therefore, we sought to determine the clinical manifestations,
incident comorbidities, and functional status in a group of Hispanic patients with RA who received early therapy with HCQ.
Methods: A cross-sectional study was performed in a cohort of RA patients (per American College of Rheumatology classification
criteria). Demographic features, health-related behaviors, cumulative RA manifestations, disease activity (per Disease Activity Score 28
[DAS-28]), functional status (per Health Assessment Questionnaire), incident comorbidities, and pharmacologic treatment were
determined. Patients who received early treatment (within the first year from the onset RA symptoms), late treatment (>1 year from the
onset of RA symptoms) or no treatment with HCQ were compared. All patients who were treated with HCQ received at least one year
of therapy. Data were examined using bivariate and multivariate (logistic regression) analyses.
Results: A total of 419 patients were studied. The mean (SD) age of the study population was 56.0 (13.8) years and 87.3% were
woman. The mean (SD) disease duration was 14.7 (9.1) years. Seventy-four (17.7%) patients received early treatment with HCQ, 131
(31.3%) late treatment with HCQ, and 214 (51.0%) patients did not receive therapy with HCQ. In the multivariate analysis adjusted for
age and disease duration, those who received early treatment had lower HAQ scores (OR 0.59, 95% CI 0.41 – 0.85) and were less likely
to have joint replacement surgeries (OR 0.15, 95% CI 0.03 – 0.67) than those who were not exposed to HCQ. These differences were
not observed between patients who had late treatment and those who did not received HCQ treatment. No significant differences were
observed between the three groups in terms of sex, lifestyle behaviors, joint deformities/contractures, extra-articular manifestations,
current disease activity, incident comorbidities (arterial hypertension, diabetes mellitus, dyslipidemia, and cardiovascular events), and
exposure to corticosteroids or other disease-modifying anti-rheumatic drugs (synthetic or biological).
Conclusion: In this group of Hispanic RA patients, those receiving early treatment with HCQ had better long-term outcomes, having
less functional impairment and joint replacement surgeries than those who received late or no HCQ therapy. This study highlights the
importance of early treatment with HCQ to prevent disease damage in RA.
Disclosure: F. Cruz-Pérez, None; M. Arroyo-Ávila, None; R. Fred-Jiménez, None; N. Pérez-Ríos, None; N. Rodríguez-Pérez,
None; G. Ríos, None; L. M. Vilá, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/early-treatment-with-hydroxychloroquine-is-

associated-with-better-long-term-outcomes-in-a-group-of-hispanic-patients-with-rheumatoid-arthritis
Methotrexate Treatment Strategies in an Early Rheumatoid Arthritis Cohort

Sasha Bernatsky1, Orit Schieir2, Cristiano S. Moura3, Marie-France Valois4, Susan J. Bartlett5, Carol A Hitchon6, Janet E. Pope7,
Gilles Boire8, Boulos Haraoui9, Edward C. Keystone10, Diane Tin11, Carter Thorne12 and Vivian P. Bykerk13, 1Divisions of
Rheumatology and Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, QC, Canada, 2Dalla
Lana School of Public Health, University of Toronto, Toronto, ON, Canada, 31Division of Clinical Epidemiology, McGill University
Health Centre, Montreal, QC, Canada, 4McGill University, Montreal, QC, Canada, 5Division of Rheumatology, Johns Hopkins
University School of Medicine, Baltimore, MD, 6University of Manitoba, Winnipeg, MB, Canada, 7Department of Medicine, Division
of Rheumatology, University of Western Ontario, St Joseph's Health Care, London, ON, Canada, 8Rheumatology Division, Centre
Hospitalier Universitaire de Sherbrooke and Universite de Sherbrooke, Sherbrooke, QC, Canada, 9Institute de Rheumatologie,
Montreal, QC, Canada, 10Rheumatology, Mount Sinai Hospital, Toronto, ON, Canada, 11The Arthritis Program, Southlake Regional
Health Centre, Newmarket, ON, Canada, 12University of Toronto, Newmarket, ON, Canada, 132-005, Mt Sinai Hospital, Toronto, ON,
Canada
SESSION INFORMATION
Background/Purpose: Methotrexate (MTX) is recommended as part of initial therapy in early RA, but practices range widely. The
objective of this analysis was to describe MTX treatment in an early RA cohort, beginning with initial therapy and assessing time to
treatment failure across various treatment strategies.
Methods: We studied adult patients from a prospective multicenter early arthritis cohort (enrolled 2007-2017 within one year of
symptom onset) who fulfilled ACR/EULAR RA criteria. RA patients were eligible for our analyses if they initiated MTX (+/-other
DMARDs) within 90 days of cohort entry. The first analyses determined time until ‘failure’ of that initial MTX-based therapy, from the
time of first initiation, left-censored at cohort entry. Treatment failure definition included: change of route for MTX monotherapy,
adding or stopping a DMARD/biologic, and changing dose/frequency of a DMARD or biologic, due to inefficacy or a serious adverse
event.
Results: We studied 1,484 early RA patients, the majority initiating either MTX monotherapy (oral or subcutaneous) or MTX plus a
second agent (Table 1). At the time of entry into the early arthritis cohort, their mean (standard deviation, SD) age was 54 (15) years,
their mean symptom duration was 5.6 months (2.8), their mean DAS28 scores were 5.3 (1.4), and one third (38%) were on oral steroids.
Overall, 911/1464 (61%) had a treatment failure, primarily due to inefficacy (Table 1).
Table 1: Distribution of initial treatment and reasons for treatment failure

Length of time Any Failure
remaining on initial Drug stopped Serious
treatment (months)* due to adverse Any side
Treatment Frequency % Median Range inefficacy effect effect§
Oral MTX 398 26.8 6.0 0.3 to 95.9 313 (79%) 13 (3.3%) 0 (0%) 70 (17.6%)
monotherapy
Subcutaneous MTX 328 22.1 13.1 0.4 to 106.1 146 (45%) 1 (0.3%) 0 (0%) 61 (18.6%)
monotherapy
MTX plus a second 642 43.3 9.3 0.3 to 107.8 375 (58%) 23 (3.6%) 0 (0%) 168 (26.2%)
DMARD
MTX-HQN-SSZ 116 7.8 9.8 0.3 to 96.8 77 (66%) 7 (6.0%) 1 (0.9%) 58 (50.0%)
Total 1484 100.0 9.0 0.3 to 107.8 911 (61%) 44 (3.0%) 1 (0.1%) 357 (24.1%)
§ The variable reason to stop, serious adverse events and any side effects are MD recorded.
The multivariate cox regression (Table 2) for the first analyses showed that, compared to oral MTX monotherapy, all MTX strategies
had longer time to failure.
Table 2: Adjusted hazard rations (HR) for drug changes after time zero* compared to oral MTX monotherapy (the reference)
Treatment at time zero Adjusted HR 95% CI
MTX subcutaneous monotherapy 0.91 0.61, 1.35
MTX + another DMARD 0.87 0.62 1.22
MTX+SSZ+HCQ 0.64 0.44, 0.94
Biologics+/- DMARDs including MTX 0.31 0.20, 0.49
Non MTX DMARDs only 1.26 0.89, 1.77
*Adjusting for baseline characteristics: age, sex, co-morbidities, symptom duration, race, education, smoking, erosions, DAS-28,
disease activity, corticosteroids, NSAIDs, and COXIBs.
Conclusion: Our data in early RA patients initially exposed to MTX suggest that compared to oral MTX, all other MTX strategies had
longer time to failure. These data do not confirm clear differences in outcomes with respect to methotrexate DMARD combinations, as
the width of confidence intervals precludes definitive conclusions in this regard.
Disclosure: S. Bernatsky, None; O. Schieir, None; C. S. Moura, None; M. F. Valois, None; S. J. Bartlett, PROMIS, 6,Pfizer Inc,
UCB, Lilly, 5; C. A. Hitchon, None; J. E. Pope, AbbVie, Amgen, Bayer, BMS, Celtrion, Eli Lilly and Company, Merck, Novartis,
Pfizer, Roche, UCB, 5,Amgen, Bayer, BMS, GSK, Merck, Novartis, Pfizer, Roche, UCB, 2; G. Boire, None; B. Haraoui, AbbVie,
Amgen, BMS, Celgene, Eli Lilly, Janssen, Merck, Pfizer, Roche, Sandoz, 6,AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, and UCB;,
2,Pfizer, and UCB, 8; E. C. Keystone, Abbott Laboratories, Amgen Inc., AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, F.
Hoffmann-La Roche Inc, Janssen Inc, Lilly Pharmaceuticals, Novartis Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, UCB,
2,Abbott Laboratories, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Crescendo Bioscience, F. Hoffmann-La Roche
Inc, Genentech Inc, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, UCB, 5,Amgen, Abbott Laboratories,
Astrazeneca LP, Bristol-Myers Squibb Canada,, 8; D. Tin, None; C. Thorne, AbbVie, Amgen, Celgene, Lilly, Novartis, Pfizer, Sanofi,
and UCB; has served as a consultant for AbbVie, Amgen, Celgene, Centocor, Genzyme, Hospira, Janssen, Lilly, Medexus/Medac,
Merck, Novartis, Pfizer, Sanofi, and UCB, 2,Medexus/Medac, 8; V. P. Bykerk, Amgen, Bristol-Myers Squibb Company, Gilead,
Sanofi-Genzyme/Regeneron, Pfizer Pharmaceuticals, UCB, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/methotrexate-treatment-strategies-in-an-early-

rheumatoid-arthritis-cohort
Do Rheumatoid Arthritis Clinical Disease Activity Index Based Treat-to-Target

Treatment Decisions Always Correspond to Usual Care Treatment Decisions at Point
of Care?
Rajesh Gopalarathinam1, Maryann Kimoto2 and Tarun S. Sharma3, 1Internal Medicine, Allegheny General Hospital- Allegheny
Health Network, Pittsburgh, PA, 2Internal Medicine, Allegheny General Hospital - Allegheny Health Network, Pittsburgh, PA,
3Rheumatology, Lupus Center of Excellence, Allegheny Health Network, Pittsburgh, PA
SESSION INFORMATION
Variables Concordant Discordant PtGA >50%
decisions (71%, decisions of CDAI
n=22) (29%, n=9) calculation
(68%, n=21)
Age (mean, years) 49 51 48
Sex (%, females) 77 77 86
Ethnicity (% 86 89 86
Caucasians)
> College education 63 (n=19) 50 (n=6) 66
(%)
>1 MSK co- 32 67 43
morbidity (%)
Duration of RA 6.7 9.8 3
(median, years)
RF and/or CCP 95 87.5 94
positive (%)
DMARD treatment 100 100 100
(%)
Glucocorticoid ≥ 22.7 22.2 18
5mg daily (%)
CDAI score 8.5 7 7
(median)
PtGA score (median) 5 4 4
PtGA score ≥ 50% of 68 67 29%
CDAI calculation discordant
(%) decisions
T2T target remission 86 100 90
(%)
Table 1 : Comparison between the concordant and discordant treatment decision groups. 3rd
column shows details of 21 patients in whom PtGA > 50% of CDAI calculation. MSK =
musculoskeletal co-morbidities, PtGA = Patient Global Assessment of Disease Activity, CDAI
= Center For Disease Activity Index, T2T = Treat to Target, RF = Rheumatoid Factor, CCP =
Cyclic Citrullinated Peptide, DMARD = Disease Modifying Anti Rheumatic Drugs.
Background/Purpose: The American College of Rheumatology strongly recommends using a treat-to-target (T2T) strategy because it
has demonstrated improved outcomes compared to a non-targeted approach in RA. The crux of a T2T based strategy is accurate disease
activity measurement using a composite disease activity tool like Clinical Disease Activity Index (CDAI) and then adapt therapy as
necessary until the clinical target is met. The aim of our study is to measure concordance between usual care-treatment decisions and
CDAI-based T2T treatment decisions and to identify reasons for discordance, if any. This is a crucial step in our internal validation of
CDAI and development of a T2T-based treatment pathway.
Methods: Adult RA patients in our tertiary care rheumatology clinic during the period of 5/20/16 to 5/20/17 were prospectively
identified. First, as part of the usual care treatment approach currently used at our clinic, a shared treatment decision was made after
consideration of all patient, disease, and treatment related factors. Then a T2T based mutual disease target was established with the
patient and a CDAI was scored to determine if the patient has met target or not. The ideal T2T strategy based treatment decision was
recorded for study purposes to compare with the usual care decision. We measured concordance between the T2T and usual care
treatment decisions, compared characteristics of concordant and discordant groups, and of those where the Patient Global Assessment
of Disease Activity (PtGA) contributed to ≥ 50% of the total CDAI score. We recorded patient, disease and treatment related data at
each visit.
Results: Patient demographic, RA disease and treatment related data can be found in Table 1. Of the total 40 patients, 9 patients were in
remission and were excluded from the analysis as there was low likelihood of discordance. Of the remaining 31 patients, there were 9
instances (29%) of discordance between T2T and usual care treatment decisions. There were higher number of patients with ≥ 1
musculoskeletal comorbidity (osteoarthritis, bursitis, etc) -67% in the discordant group vs 32% in concordant group. There were slightly
higher numbers of patients with ≥ college education in the concordant group (63%) than in the discordant group (50%). PtGA
contributed to ≥ 50% of total CDAI score in 21 patients of the cohort (68%), and of these 43% had ≥ 1 musculoskeletal comorbidity.
Conclusion: In our small group of 40 RA patients, we found 29% discordance between the T2T and usual care treatment decisions, and
the PtGA contributed to ≥ 50% of the total CDAI score in 68% patients. As accurate disease activity measurement is central in any T2T
strategy, we believe that this deeper understanding of variation in CDAI, PtGA scores and T2T decisions is very useful. We have
accordingly started using PtGA as a patient education opportunity and plan to repeat this study with a new amended CDAI
questionnaire.
Disclosure: R. Gopalarathinam, None; M. Kimoto, None; T. S. Sharma, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/do-rheumatoid-arthritis-clinical-disease-activity-

index-based-treat-to-target-treatment-decisions-always-correspond-to-usual-care-treatment-decisions-at-point-of-care
FLARE-RA Instrument Detects RA Flares Independent of Disease Activity

Taysir G. Mahmoud1, Michelle Frits2, Christine Iannaccone3, Gabriela Maica4, Vivian P. Bykerk5, Michael Weinblatt6 and Nancy A.
Shadick7, 1Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston,
MA, 2Brigham and Women's Hospital, Boston, MA, 3Rheumatology, Immunology and Allergy, Brigham and Women's Hospital,
Boston, MA, 4Department of Rheumatology, Allergy, and Immunology, Brigham and Women's Hospital, Boston, MA, 52-005, Mt Sinai
Hospital, Toronto, ON, Canada, 6Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical
School, Boston, MA, 7Rheumatology Immunology & Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston,
MA
SESSION INFORMATION
Background/Purpose: Clinicians often associate the occurrence of a recent rheumatoid arthritis (RA) flare with an increase in overall
disease activity. However, previous studies have shown that patients with RA in low disease states still report flares. The goal of this
study is to examine if having a recent flare is independent from disease activity overall, using the FLARE-RA instrument.
Methods: Data were collected from a prospective RA registry including patient reported and clinical outcomes, such as flare frequency
and the FLARE-RA instrument. FLARE-RA asks patients to rate 11 statements about their disease on a 0-10 scale (not true to
absolutely true). The statements are about patient and physician identified flare features covering the following: morning stiffness, joint
pain, joint swelling, sleep disturbance, pain killer or NSAID use, fatigue, decrease in physical activity, irritability, depression,
withdrawal, and increased need for help. The score is the mean of all 11 items, where a higher score suggests a recent flare. Disease
Activity Score 28 joint with CRP (DAS) was dichotomized into low/remission and moderate/high disease. Flare recency (presence of a
flare in the past 6 months) was coded into 3 categories; no flare, at least 1 flare, and currently flaring. Nonparametric tests were
performed to examine possible covariates in relation to the FLARE-RA score. A multiple regression model with FLARE-RA score as
the outcome included covariates that had a p<0.15 in the univariate analyses.
Results: 503 participants were surveyed; 85% were female with a mean (SD) age of 61 (13), 75% had a college degree or higher, and
the median disease duration was 16 (IQR 9, 26) years. The median DAS28-CRP3 was 2.1 (1.6, 2.8) and the median FLARE-RA score
was 2 (0.5, 4.4). In univariate analyses, a linear trend between DAS category, flare recency, and FLARE-RA was seen (Figure). The
regression model found that having a recent flare is associated with a higher FLARE-RA score independent of DAS category, while
adjusting for gender, education, and disease duration. Additionally, flare recency had a higher effect size than DAS on total FLARE-RA
score.
Conclusion: Having a current or recent flare drives the FLARE-RA score more than a patient’s current disease activity suggesting that
this instrument is able to detect patients’ self report of flare. This instrument may be useful in detecting flares even in patients with low
disease activity which could provide an additional rationale for treatment change.
Disclosure: T. G. Mahmoud, None; M. Frits, None; C. Iannaccone, None; G. Maica, None; V. P. Bykerk, None; M. Weinblatt,
Amgen, BMS, Crescendo Bioscience, UCB, Genzyme, 2,Amgen, Abbvie, BMS, Eli Lilly and Company, Gilead, Merck, Pfizer,
Novartis, Roche, UCB, Crescendo Bioscience, Genzyme, Samsung, 5; N. A. Shadick, Mallinckrodt, 2,Amgen, 2,Bristol-Myers Squibb,
2,UCB, 2,DxTerity, 2,Sanofi, 2,Crescendo Biosciences, 2,Bristol-Myers Squibb, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/flare-ra-instrument-detects-ra-flares-independent-of-

disease-activity
Methotrexate Use and Fatigue in Rheumatoid Arthritis Patients: Results from a

National Patient Registry
Huifeng Yun1, Shuo Yang2, W. Benjamin Nowell3, Cooper Filby1, Lang Chen1 and Jeffrey R. Curtis4, 1University of Alabama at
Birmingham, Birmingham, AL, 2Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham,
Birmingham, AL, 3Global Healthy Living Foundation, Upper Nyack, NY, 4Division of Clinical Immunology and Rheumatology,
University of Alabama at Birmingham, Birmingham, AL
SESSION INFORMATION
Background/Purpose: Methotrexate (MTX), a synthetic disease-modifying antirheumatic drug (DMARD), is the most commonly used
medication for rheumatoid arthritis (RA). Considerable variations between patients taking MTX exist due to its potential adverse effects
and tolerability issues. Although patient reported outcomes have been used for evaluating effectiveness of RA treatments in clinical
trials, much less is understood from real-world settings. This study evaluated the association between MTX use and fatigue in the
PCORI-funded Patient Powered Research Network for adult rheumatologic conditions, ArthritisPower.
Methods: Patients in the ArthritisPower registry were invited to provide medication information and PROs including the RAPID3 and
4 PROMIS instruments (pain interference, physical function, fatigue, and sleep disturbance) plus disease-specific information via a
mobile application (App) on their smartphone or computer. Patients who used selected RA medications of interest (glucocorticoids,
non-biologic DMARDs, biologics) and answered ≥ 1 instrument were eligible this study. We calculated the mean and standard deviation
(SD) of RAPID3 and the 4 PROs across different RA treatments cross-sectionally. Multivariable regression analysis with repeated
measures was used to evaluate the association between MTX use and fatigue.
Results: As of June 2017, ArthritisPower had recruited 5,830 patients; approximately 57% had RA. A total of 469 participants had RA
medication use and answered relevant PROMIS instruments, with mean (SD) age of 48.3 (11.5) years; 32.0% used glucocorticoids,
83.2% used non biologic DMARDs, and 62.5% used biologics. The mean score for pain interference was 62.7 (SD: 7.3), physical
function 38.0 (6.9), sleep disturbance 56.9 (8.4), fatigue 62.3 (8.5), and RAPID3 14.7 (5.7). Among different RA treatments, patients on
biologic monotherapy had the highest scores for pain interference, sleep disturbance, fatigue, and RAPID3, whereas MTX monotherapy
had the lowest. In contrast, MTX monotherapy had the highest physical function score whereas biologic monotherapy had the lowest
(Table). Using fatigue as an example, MTX use is associated with 2.29 (95% confidence interval: -3.2, -1.4) units of lower fatigue score
after adjusting for age, gender, race, insurance, employment and concurrent RA medications and medical conditions.
Conclusion: PROMIS measures are feasible to capture from patients with Smartphone and Web Apps. Despite potential concerns
related to fatigue associated with use of MTX, these results suggest that on average, MTX is associated with lower fatigue scores. RA
patients on MTX might be associated with better PROs, especially when it was combined with biologics use. More longitudinal data
analyses are needed to better understand the relationship.
Table: Mean of PROMIS instruments on different RA medications
N Pain Physical Sleep Fatigue RAPID3
interference function disturbance
Treatments Observations Mean Mean Mean Mean Mean (SD)
(patients) (SD) (SD) (SD) (SD)

Methotrexate monotherapy 196 (60) 59.3 (9.1) 41.3 (7.1) 54.9 (8.5) 59.3 (8.3) 11.7 (6.9)
Methotrexate + other non-biologic 133 (51) 60.8 (7.9) 40.1 (7.7) 56.5 (8.9) 60.4 (9.6) 13.8 (6.1)
DMARDs
Biologic monotherapy 150 (69) 64.1 (6.4) 36.0 (6.7) 58.9 (8.6) 64.7 (8.8) 16.3 (5.8)
Biologic + methotrexate 703 (172) 63.0 (7.0) 37.5 (6.6) 57.8 (8.3) 63.0 (8.4) 15.2 (5.6)
Biologic + other non-biologic 154 (42) 62.9 (7.7) 37.2 (8.4) 58.0 (8.6) 64.2 (10.6) 15.4 (6.1)
DMARDs
Disclosure: H. Yun, BMS, 2; S. Yang, None; W. B. Nowell, Global Healthy Living Foundation, 3; C. Filby, None; L. Chen, None; J.
R. Curtis, UCB Pharma, Janssen-Cilag, Amgen, Roche, Myriad Genetics, Lilly, Novartis, BMS, Pfizer, 2,UCB Pharma, Janssen-Cilag,
Amgen, Roche, Myriad Genetics, Lilly, Novartis, BMS, Pfizer, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/methotrexate-use-and-fatigue-in-rheumatoid-

arthritis-patients-results-from-a-national-patient-registry
Tocilizumab Had Acceptable Retention Rate in Both Randomized Controlled Trials

and Observational Studies: Systematic Review of Rheumatoid Arthritis
Levent Kilic1, Orhan Kucuksahin2, Zeynep Ozbalkan3, Cemal Bes4, Veli Yazisiz5, Ayten Yazici6, Dilek Solmaz7, Timucin Kasifoglu8
and Umut Kalyoncu9, 1Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey, 2Rheumatology, Yildirim Beyazit
University Faculty of Medicine, Ankara, Turkey, 3Rheumatology, Ankara Numune Education and Research Hospital, Ankara, Turkey,
4Rheumatology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey, 5Rheumatology, Akdeniz University
Faculty of Medicine, Ankara, Turkey, 6Department of Rheumatology, Kocaeli University, Faculty of Medicine, Kocaeli, Turkey,
7Rheumatology, Katip Çelebi University Faculty of Medicine, İzmir, Turkey, 8Rheumatology, Eskisehir Osmangazi University Faculty
of Medicine, Eskişehir, Turkey, 9Department of Internal Medicine, Divison of Rheumatology, Hacettepe University Faculty of
Medicine, Ankara, Turkey
SESSION INFORMATION
Background/Purpose: In general, retention rate in biological DMARDs represent both efficacy and safety. Tocilizumab (TOC) is a
humanized monoclonal antibody that binds to the interleukin-6 receptor. So far, TOC was used in randomized controlled trials (RCTs)
and longitudinal observational studies (LOSs), as well. The aim of this study was to assess the retention rate of TOC for the treatment of
RA patients in RCTs and LOS.
Methods: In January 2017, a systematic Review (SR) was performed in PUBMED MEDLINE. Publications were identified using the
MeSH terms: (‘‘rheumatoid arthritis and Tocilizumab’’) with a limitation to ‘‘humans’’, ‘‘all adults: 19+ years’’, ‘‘English’’ and
‘‘clinical trials’’. All available studies describing the retention rate of TOC were recruited to SR. Retention rate of TOC were calculated
according to route (SC or IV), dosage (4 mg/kg vs 8 mg/kg), monotherapy or combination with methotrexate. Of the 662 publications
identified by the literature search, 42 were recruited in the analysis. Retention rates of TOC at 12-16 weeks, 24-32 weeks, 48-52 weeks,
2. Years, 3. Years and 5. years were analyzed. Open label extension period of RCTs included to LOS. The causes of withdrawals of
TOC were recorded as inefficacy, adverse event, and others.
Results: Of the 42 studies, 11 (26.2%) were RCTs and 31 (73.8%) were LOSs. Totally 20590 patients (15574 (75.6%) female) were
pooled to analysis that 4817 patients (23.4%) were from RCTs. The mean age was 56.2 years and mean disease duration was 10.1 years.
Seropositivity was 75.0% for rheumatoid factor and 76.5% for ACPA. Overall, 8934 (44.4%) of patients were biologic-naïve. TOC was
used as monotherapy (5111/16323, 31.3%), or concomitant with methotrexate (11976/19522, 61.4%). Available baseline DAS-28 score,
CDAI, SDAI, and HAQ-DI score were 5.8, 30.4, 32.5, and 1.46 respectively. Retention rates of TOC intravenous 8 mg/kg at 48-52
weeks, 2. year, 3. year and 5. year were 75.5 - 85.2%, 48.4 - 76.1%, 69.9%, 66.2%, respectively. Retention rate and causes of
withdrawal of TOC according to study type were shown in Table 1.
Conclusion: Both RCTs and LOSs, withdrawal of TOC was particularly well known in 24-32. weeks. TOC intravenous 8 mg/kg also
had satisfactory retention rate in 48-52 weeks, 2. year, 3. year and 5. year. Moreover, retention rate of TOC in LOSs was comparable
with other biologic DMARDs, as well.
Table 1: Retention Rate of Tocilizumab in Randomized Controlled Trials and Observational Studies
Durations (weeks) Study Patients Route and Continue of TOC Causes of Withdrawals (%)
Type number dosage (%)
Inefficacy Adverse event Others
12-16 w RCTs 102 iv, 8 mg/kg 85.3 20.0 53.3 26.7
103 iv, 4 mg/kg 82.5 33.3 50.0 16.7
LOS 551 iv, 8 mg/kg 88.0 27.5 31.4 41.2
24-32 w RCTs 3198 iv, 8 mg/kg 92.7 13.8 67.7 25.2
377 iv, 4 mg/kg 85.9 NA NA NA
1242 sc, 162 mg 92.2 19.7 46.5 33.8
LOS 12488 iv, 8 mg/kg 83.3 29.0 44.1 27.0
48-52 w RCTs 209 iv, 8 mg/kg 85.2 25.8 38.7 35.5
LOS 3761 iv, 8 mg/kg 74.5 34.4 31.5 34.1
2. years RCTs 209 iv, 8 mg/kg 76.1 26.0 38.0 38.0
LOS 649 iv, 8 mg/kg 48.4 - - -
3. years LOS 114 iv, 8 mg/kg 69.9 20.0 10.0 40.0
5. years LOS 240 iv, 8 mg/kg 66.2 7.4 61.7 30.9
TOC:Tocilizumab, RCT: Randomized Controlled Trials, LOS: Long Observational Studies, iv: intravenous, sc:subcutaneous
Disclosure: L. Kilic, Roche Pharmaceuticals, 5; O. Kucuksahin, Roche Pharmaceuticals, 5; Z. Ozbalkan, Roche Pharmaceuticals, 5;
C. Bes, Roche Pharmaceuticals, 5; V. Yazisiz, Roche Pharmaceuticals, 5; A. Yazici, Roche Pharmaceuticals, 5; D. Solmaz, Roche
Pharmaceuticals, 5; T. Kasifoglu, Roche Pharmaceuticals, 5; U. Kalyoncu, Roche Pharmaceuticals, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/tocilizumab-had-acceptable-retention-rate-in-both-

randomized-controlled-trials-and-observational-studies-systematic-review-of-rheumatoid-arthritis
Predicting Remission at 6 Months in Early Rheumatoid Arthritis Treated with

Conventional Synthetic Dmards
Michael D Wiese1, Robert Metcalf2, Mihir D Wechalekar3, Llew Spargo2, Leah McWilliams4, Michael James4,5, Catherine Hill6 and
Susanna Proudman7, 1School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia, 2Rheumatology
Unit, Royal Adelaide Hospital, South Australia, Adelaide, Australia, 3Royal Adelaide Hospital, Adelaide, Australia, 4Department of
Rheumatology, Royal Adelaide Hospital, Adelaide, Australia, 5Department of Medicine, University of Adelaide, Adelaide, Australia,
6The Queen Elizabeth Hospital, Adelaide, Australia, 7University of Adelaide, Adelaide, Australia
SESSION INFORMATION
Background/Purpose: Initial treatment of RA with triple csDMARD therapy can achieve remission in a proportion of patients. Others
respond poorly yet must wait at least 6 months to access publically funded bDMARDs in Australia, although they may benefit from
earlier introduction of bDMARDs. The purpose of this study was to identify disease activity thresholds after 3 months of csDMARDs
that were associated with ACR/EULAR remission after 6 months of therapy.
Methods: Consecutive patients >18 years with treatment-naïve RA (1987 ACR or 2010 ACR/EULAR criteria) and ≥ 6 months of
follow up were included. Unless contraindicated, participants received triple DMARD therapy of methotrexate, sulfasalazine and
hydroxychloroquine according to a treat-to-target approach, and if these failed, leflunomide was added. At baseline, 3 and 6-months,
DAS28, SDAI and CDAI were determined. Remission after 6 months was defined by ACR/EULAR 2011 definition of SDAI ≤ 3.3
without initiation of leflunomide. The sensitivity and specificity of disease activity measures at 3 months to predict the 6 month
remission rate were determined by a Receiver Operated Characteristics Curve, and the magnitude of association between the optimal
point on the curve and remission rate was determined. Both percentage and absolute reductions in disease activity scores were
examined.
Results: Median baseline DAS28, CDAI and SDAI were 5.4, 27.7 and 30.0 respectively and 89% were initiated on triple DMARD
therapy. Absolute rather than relative changes in disease activity metrics after 3 months of DMARDs were more strongly associated
with RA remission after 6 months of treatment. Optimal SDAI and CDAI scores at 3 months had a stronger association with 6 month
remission compared to DAS28 (Table).
Association between Optimal Cut-Off Points and Remission Rate after 6 Months of
DMARDs
Disease Activity Cut-Off Proportion Remission Odds Ratio
n
Point after 3-Months Reaching cut-point Rate (95% CI)
45% Reduction in DAS28
259 0.24 0.19 8.8 (4.4-17.5)
from Baseline
65% Reduction in CDAI
258 0.28 0.18 12.3 (5.9-25.6)
from Baseline
65% Reduction in SDAI
250 0.26 0.18 8.5 (4.2-17.3)
from Baseline
DAS28 <3.4 261 0.39 0.19 10.8 (4.9-23.5)
CDAI <8.0 265 0.28 0.18 16.7 (7.8-35.7)
SDAI <8.6 259 0.27 0.19 18.1 (8.4-39.1)
Conclusion: CDAI or SDAI scores at 3 months of csDMARD treatment in early RA are highly predictive of remission after 6 months
and could be useful in predicting those who may ascertain long-term remission with conventional agents, and equally in identifying
those who may benefit from early bDMARD initiation. In practical terms, CDAI has the advantage of providing an immediate score
compared with SDAI where the results of CRP levels are required.
Disclosure: M. D. Wiese, None; R. Metcalf, None; M. D. Wechalekar, None; L. Spargo, None; L. McWilliams, None; M. James,
None; C. Hill, None; S. Proudman, Actelion Pharmaceuticals US, 2,GlaxoSmithKline, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/predicting-remission-at-6-months-in-early-

rheumatoid-arthritis-treated-with-conventional-synthetic-dmards
Medical Bugs for Pain Relief in Patients with Rheumatoid Arthritis, a Systematic
Review
Rongqiang Zhang1, Puwei Yuan2, Jia Li3, Bo Dong1, Wulin Kang3, Stephanie Hyon4, Raveendhara R. Bannuru5, William F. Harvey4
and Chenchen Wang4, 1Shaanxi University of Chinese Medicine, Xianyang 712046, China, Xianyang, China, 2Shaanxi University of
Chinese Medicine, Xianyang 712046, China, XianYang, China, 3Shaanxi University of Chinese Medicine, Xianyang, China,
4Rheumatology, Center of Integrative Medicine and Division of Rheumatology, Tufts Medical Center, Boston, MA, Boston, MA,
5Center of Integrative Medicine and Division of Rheumatology, Tufts Medical Center, Boston, MA, Boston, MA
SESSION INFORMATION
Background/Purpose: Medical bugs, a term used to describe insects and arthropods for medical treatment, have been widely used in
the past centuries for pain relief. The treatment is believed to include biologically active substances that induce anti-inflammatory
effects. Previous trials have shown that medical bugs may reduce the need for analgesic intake of people with rheumatoid arthritis (RA).
However, few studies have been conducted to evaluate the effect of medical bugs on musculoskeletal disease. The aim of this
systematic review was to evaluate the pain relief of commonly used medical bugs in RA patients to better understand its benefits and
inform clinical practice.
Methods: A comprehensive search on PubMed and Chinese databases (CNKI, Wan Fang and VIP) and the Cochrane Library was
conducted through May 1, 2017. Only randomized controlled trials (RCTs) using medical bug (including ant, centipedes, scorpions and
others) therapy for adult RA patients who met diagnostic by the 1995 ACR criteria or 2002 Traditional Chinese Medicine criteria were
included. The effects of medical bugs were evaluated with a tender joint count and pain score of joints. The differences between
treatment groups were reported as mean difference (P-value) across the studies. The methodologic quality of the studies was assessed
with the Jadad instrument. The heterogeneity of the studies, including varying comparison methods, and methodologic limitations,
precluded a formal meta-analysis.
Results: Ten RCTs with a total of 1,176 RA patients (age range = 38-62 years, 59% female, disease duration range = 1 month-30 years)
met the eligibility criteria. Studies were conducted between 2002 and 2015 in China. Outcomes included the Chinese pain score and
Visual Analogue Scale (VAS). Medical bugs were either used singly or in combination with other Chinese herbs. The overall quality of
trials was modest (mean Jadad score = 2). Table 1 summarizes the information from the included studies. All 10 studies utilizing
medical bugs either alone or in combination with other Chinese herbs showed efficacy in pain relief for RA. No adverse events were
reported in either treatment or control groups.
Conclusion: Medical bug therapy appears to relieve pain in patients with RA. These studies did not evaluate disease modifying effects,
and the use of combination treatments makes it difficult to ascertain which ingredient may induce the effect. Still, the potential of
medical bug treatment and its non-pharmacologic properties may have value and deserve further study. Rigorously designed and well-
controlled multicenter RCTs of biological active compounds of medical bugs for RA symptom relief need to be conducted in future
studies.
Table 1. Randomized Clinical Trials Evaluating Medical Bugs for Joint Pain in Rheumatoid Arthritis
Author N a Diagnostic Medical bugs Control Duration Effect on Tender Joint
(Ageb) Criteria (Weeks) Count or Joint Pain
Year Score
(mean changes)c
Yang 280 Chinese criteria 20 herbs including centipede Tripod, 2tablets*twice/day 12 #2.40 e
(ND) and scorpion, 9g/day
2002 2002 (P< 0.05)
Huang 76 ACR 1995 and 18 herbs including centipede 1g Glucosidorum Tripterygll 8 #1.79 e
(38y) Chinese criteria and Steleophaga 5g, once/day; Totorum, 1mg/kg/day
2005 2002 (P< 0.05)
Methotrexate, 10mg/week;
Penicillamine, 250mg*twice/day
Shen 85 ACR 1995 16 herbs including centipede 2g Tripterygium polyglycoside 24 #1.80 d
(39y) and scorpion 3g, tablets, 20mg*3 times/day
2004 250ml*twice/day (P< 0.01)
Huang 82 Chinese criteria 14 herbs including centipede Diclofenac Sodium Sustained 8 #7.18 e
(39y) 0.35g, 6 Tablets*3times/day; Release Tablets,
2014 2002 75mg*twice/day (P< 0.05)
Diclofenac Sodium Sustained
Release Tablets,
75mg*twice/day
Liu 120 ACR 1995 Prednisone adequate dose for 4 Methotrexate, 14 #0.40 e
(ND) weeks; 10mg*once/week;
2003 (P< 0.05)
14 herbs including scorpion 10g, Indometacin Tablets,
250ml*twice/day 150mg/day;
Prednisone, 30mg/day
Cheng 79 ACR 1995 10 herbs including scorpion, 2-3 Fenbid, 600mg *twice/day 8 #0.81 e
(38y) times/day
2003 (P< 0.05)
Liu 66 ACR 1995 12 herbs including scorpion 3g, Methotrexate, 10mg/week; 12 #1.10 d
(49y) 250ml*twice/day;
2009 Meloxicam, 7.5mg*twice/day (P< 0.05)
Methotrexate, 10mg/week;
Meloxicam, 7.5mg*twice/day
Liu 80 ACR 1995 3 herbs including scorpion 5g, 2 herbs not including 12 ^0.25
(49y) 150 ml*3 times/day scorpion, 150ml*3 times/day
2011 (P< 0.05)
Feng 100 Chinese criteria 14 Herb including 1 centipede Methotrexate, 5mg*3 3 #1.20 e
(62y) and 1 scorpions, times/day
2015 2002 200g*twice/day; (P< 0.05)
6 herbs hot pack for 30-50 min,

once or twice/day
Dai 208 ACR 1995 15 herbs including ant 30g, Ibuprofen, 300mg*3 5 #2.59 d
(39y) 150ml*twice/day times/day
2007 (P< 0.01)
a N= number of patients included; b Age reported in years as a mean;c Meandifference was calculated between groups; d Severity of
e
joint pain was scored 0, 1, 2, 3, respectively measured by physicians; Chinese pain score: lower score = better outcome.
Chinese criteria: Guiding Principles of Clinical Research on Traditional Chinese Medicine, including main symptoms: joint swelling
and pain and four of the following secondary symptoms: joint tenderness, limited flexion and extension, morning stiffness, joint cold,
aggravated pain in nights, hand and foot cold, fatigue, aggravated pain in rainy days, pale tongue, heavy and soft pulse.
#: indicate decrease, ^: indicate increase.

Disclosure: R. Zhang, None; P. Yuan, None; J. Li, None; B. Dong, None; W. Kang, None; S. Hyon, None; R. R. Bannuru, None; W.
F. Harvey, None; C. Wang, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/medical-bugs-for-pain-relief-in-patients-with-

rheumatoid-arthritis-a-systematic-review
Disease Duration and Withdrawal of Biologic Agents Predict Radiological

Progression in a Cohort of Rheumatoid Arthritis Patients in Latin America. a Real
World Study
Rocio V. Gamboa-Cardenas1,2, Manuel Ugarte-Gil3, Francisco Zevallos4, Mariela Medina4, Claudia Elera-Fitzcarrald4, Victor
Pimentel-Quiroz4, Cristina Reategui-Sokolova4, Omar Sarmiento-Velasquez4, Zoila Rodriguez-Bellido4, José Alfaro4, Mariano Cucho-
Venegas4, Cesar A. Pastor-Asurza4 and Risto Perich-Campos5, 1Rheumatology, Hospital Guillermo Almenara, EsSalud, Lima, Peru,
2Universidad Nacional Mayor de San Marcos, Lima, Peru, 3Peru, GLADEL, Lima, Peru, 4Rheumatology, Hospital Guillermo Almenara
Irigoyen. EsSalud, Lima, Peru, 5Rheumatology, Hospital Guillermo Almenara Irigoyen, Lima, Peru
SESSION INFORMATION
Background/Purpose: Optimal management of Rheumatoid Arthritis (RA) based in identification of patients with risk factors for Joint
Damage (JD) progression, is a main strategy, but there is scarce evidence regarding this aspect in Latin-America (LA).Objective: To
determine factors associated with JD and predictors of radiographic progression (RP) in a RA cohort
Methods: Prospective analysis of Hospital Almenara RA cohort (Lima-Perú). JD and RP were determined with Sharp-VDH score. A
single reader evaluated all X-ray films. Age, gender, ethnicity, socioeconomic level(Graffar), education, age at diagnosis, disease
duration, diagnosis delay, tobacco, comorbidities(Charlson), current/past DMARDs, biologic and corticosteroids, biologic withdrawal
,DAS28, EULAR-remission, AntiCCP, JD (Sharp-VDH score) and disability (MHAQ) at baseline were analyzed as RP predictors. We
applied a multivariate linear regression elimination model (p <0.05) and SPSS-21.0. Results: 313 patients from the 432 subjects of the
hospital Almenara RA cohort were included , 91.4% women, 98.4% Mestizos, disease duration was 14.94 (12.79) and diagnosis delay
1.71 (2.59) years. Baseline Sharp-VDH was 94.53 (95.81). Most patient were using DMARDs (92%), but only 11.5% biologics. Current
(B=42.86, CI: 6.49-79.24, p=0.021) or past (B=45.76, IC: 6.42-85.09, p=0.023) corticosteroids, current biologic (B=28.63, CI: 4.86-
52.40, p=0.018) and longer disease duration (B=3.62, CI: 3.02-4.22, p<0.01) were associated with baseline JD. One hundred and
eighty-four patients were prospectively followed, in this group the rate of RP total/erosion was 4.41(9.24) and 2.17(5.74)/year
respectively, there was a DMARDs prescription delay of 6.56(8.02) years and 176 (95.7%) subjects without remission-EULAR criteria.
Predictors of RP (erosions) were a longer disease duration (B=0.14, CI 0.01-0.27, p=0.04) and withdrawal of biologic (B=8.63 CI 2.28-
14.98 p=0.008)
Conclusion: This cohort had a high disease duration and delay of DMARD introduction. Disease duration and biologic withdrawal
predicted RP. Carefully biologic withdrawal in these patients could be a good strategy to prevent adverse results in our population
Disclosure: R. V. Gamboa-Cardenas, None; M. Ugarte-Gil, None; F. Zevallos, None; M. Medina, None; C. Elera-Fitzcarrald,
None; V. Pimentel-Quiroz, None; C. Reategui-Sokolova, None; O. Sarmiento-Velasquez, None; Z. Rodriguez-Bellido, None; J.
Alfaro, None; M. Cucho-Venegas, None; C. A. Pastor-Asurza, None; R. Perich-Campos, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/disease-duration-and-withdrawal-of-biologic-

agents-predict-radiological-progression-in-a-cohort-of-rheumatoid-arthritis-patients-in-latin-america-a-real-world-study

A Matrix Risk Model for Prediction of Radiographic Progression in Early
Rheumatoid Arthritis Based on Treatment Response at 3 Months
Pooneh S. Akhavan1, Daming Li1, Sahar Tabatabvakili1 and Edward C. Keystone2, 1Mount Sinai Hospital, Toronto, ON, Canada,
2University of Toronto, Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose: The present study aimed to develop a matix to predict risk of radiographic progression in patients with early
rheumatoid arthritis. The focus of this analysis was to identify a threshold for routine disease activity measures at 3 months i.e. response
to initial treatment that is associated with the lower risk of future joint damage.
Methods: Using data from the PREMIER study, radiographic progression (RP) was defined as a change in modified Sharp/van der
Heijde score (SHS) of ≥3.5 U/year. Patients enrolled into the control arm of the study who received methotrexate only were analyzed.
Baseline characteristics and disease activity measures at 3 months were used to predict the risk of RP at 12 months. Logistic regression
was used to identify the predicators and to calculate the probability of RP. Significant predicators were categorized in order to make the
models more practical to use in daily practice. The results were combined into a matrix model including significant predictors of RP.
Results:
A total of 205 patients were included in this analysis with a mean (sd) baseline age 52.0 (13.1) years, disease duration 0.8 (0.8) year, 28
swollen joint count 14.7 (5.7), 28 tender joint count 17.1 (6.4), mean sharp score (MTSS) 21.4 (21.2) and CRP 4.0 (4.1). Logistic
regression models identified month 3 SJC and CRP as significant predicators of radiographic damage progression at 1 year. These
variables were categorized into three groups based on the variable distribution and clinical relevance. The matrix model showed that the
SJC < 5 at 3 months was associated with a significantly lower damage progression rate at any given CRP category (Table-1).
CRP at 3 months
<1 1-2 >2
<5 0.15 (0.08, 0.36 (0.20, 0.50 (0.29,
0.27) 0.57) 0.70)
SJC at 3
months 5 - 10 0.30 (0.18, 0.58 (0.35, 0.70 (0.49,
0.46) 0.77) 0.85)
> 10 0.35 (0.22, 0.63 (0.42, 0.75 (0.57,
0.52) 0.81) 0.87)
Conclusion: The disease activity state at 3 months has a significant impact on future radiographic damage. Patients with less than 5
swollen joints at this time point have lower risk of radiographic damage at 1 year. Further testing in other populations and with different
therapies is needed to obtain a definitive risk model that will guide rheumatologists in making treatment decisions for early RA patients.
Disclosure: P. S. Akhavan, None; D. Li, None; S. Tabatabvakili, None; E. C. Keystone, Abbott Laboratories, Amgen Inc.,
AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Janssen Inc, Lilly Pharmaceuticals, Novartis
Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, UCB, 2,Abbott Laboratories, AstraZeneca Pharma, Biotest, Bristol-Myers
Squibb Company, Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer
Pharmaceuticals, UCB, 5,Amgen, Abbott Laboratories, Astrazeneca LP, Bristol-Myers Squibb Canada,, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-matrix-risk-model-for-prediction-of-radiographic-

progression-in-early-rheumatoid-arthritis-based-on-treatment-response-at-3-months
Time to First Treatment Is Associated with a Refractory Course of

Manuel Bécède1, Farideh Alasti2, Lukas Haupt3, Lisa Hütter3, Andreas Kerschbaumer4, Uriel Landesmann1, Gabriela
Supp4, Josef S. Smolen4,5 and Daniel Aletaha6, 1Department of Internal Medicine III, Division of Rheumatology, Medical
University of Vienna, Vienna, Austria, 2Rheumatology, Medical University of Vienna, Vienna, Austria, 3Department of
Medicine, Hietzing Hospital, Vienna, Austria, 4Medical University Vienna, Division of Rheumatology, Department of
Internal Medicine III, Vienna, Austria, 5Department of Internal Medicine, Hietzing Hospital, Vienna, Austria, 6Department
of Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Austria
SESSION INFORMATION
Background/Purpose:
It is an ongoing matter of research, whether the course of rheumatoid arthritis (RA) can be altered by an early intervention,
a concept historically referred to as the window of opportunity. So far, only short-term disease outcomes have been
investigated, which are, however, inherently affected by the unknown rate of underlying rate of self-limiting disease. It is
unclear, whether the disease course is really affected by the timing of initial treatment.
Methods:
Patients were identified from a clinical database at the Medical University of Vienna. We used stringent criteria to define
refractory RA (reRA): >=3 treatment courses (>=1 biological) over >=18 months since diagnosis without reaching low
disease activity (LDA) or remission (REM) defined by a Clinical Disease Activity Index (CDAI, >=10). In contrast, we
defined treatment amenable RA (taRA) as patients reaching LDA, or REM within the first 2 treatment courses.
We first matched patients with reRA and taRA 1:1 for time of inception in our database to avoid bias by secular trends in
management over time. Using the reRA or taRA status as the dependent variable, we performed logistic regression
analysis. Furthermore, we performed the same analyses in an unselected group of all-comers at baseline regarding their
probability of developing reRA.
Results:
We identified 412 patients who had their last clinic visit at or after July 1st, 2016: 70 reRA and 102 taRA patients were
identified; 240 patients fulfilled neither definition. In the reRA group, female gender was more frequent, age of disease
onset lower, and CDAI higher at first presentation. Remarkably, the time to first DMARD treatment was significantly
delayed between reRA and taRA (table 1).
In the matched multivariate model, treatment delay (p=0.047), female gender (p=0.038) and higher disease activity
(p<0.001) were significant. In the logistic regression analysis of the 412 patients treatment delay was significant
univariately (p<0.001) and after adjustment for other significant predictors (p=0.007; table 2). We then conducted a matrix
model based on this analysis with predicted probabilities of developing reRA (figure).
Conclusion:
Our data suggest that delay to initial treatment affects the long-term course of RA. Earlier treatment initiation thus may
change the severity of RA.
Disclosure: M. Bécède, None; F. Alasti, None; L. Haupt, None; L. Hütter, None; A. Kerschbaumer, None; U.
Landesmann, None; G. Supp, None; J. S. Smolen, None; D. Aletaha, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/time-to-first-treatment-is-associated-

with-a-refractory-course-of-rheumatoid-arthritis
The Therapy with Tocilizumab Is Not Associated with Periarticular

Demineralisation and Finger Joint Space Narrowing in Rheumatoid Arthritis
Alexander Pfeil1, Ottar Gadeholt2, Joachim Böttcher3, Diane Renz4, Peter Oelzner1 and Gunter Wolf1, 1Department of
Internal Medicine III, Jena University Hospital, Jena, Germany, 2Rheumatology/Immunology, Medical Clinic II, University
Clinic Wuerzburg, Wuerzburg, Germany, 3Institut of Interventional and Diagnostic Radiology, SRH Waldklinikum Gera,
Gera, Germany, 4Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Jena, Germany
SESSION INFORMATION
Background/Purpose:
Digital X-ray Radiogrammetry (DXR) and Computer-Aided Joint Space Analysis (CAJSA) are established computer based
techniques for the quantification of metacarpal bone mineral density and finger joint space width. Tocilizumab as
humanized anti-interleukin-6 receptor antibody is a successful therapy strategy in rheumatoid arthritis (RA). The aim of
this study was the evaluation metacarpal bone mineral density finger joint space width in RA-patients treated with
tocilizumab or methotrexate.
Methods:
The multi-center study includes a retrospective analysis of 44 patients with RA in two matched groups which were treated
with methotrexate or tocilizumab. All patients consist of radiographs at baseline and after 2.4 years in the follow-up. DXR
was measured to quantify cortical thickness (CT), metacarpal index (MCI) and bone mineral density (BMD) of the
metacarpal bones. The CAJSA-technique quantified joint space distance of the metacarpophalangeal joints (JSD-MCP) and
proximal interphalangeal joints (JSD-PIP).
Results:
For the methotrexate group a significant change of BMD (-6.16%, p<0.05), CT (-7.05%, p<0.05), MCI (-4.74%, p<0.5),
JSD-MCP (-4.51%, p<0.05) and JSD-PIP (-12.29%, p<0.05) was observed between baseline and follow-up. The
tocilizumab group no significant difference was detected for BMD (-0.20%, p=n.s), CT (-0.70%, p=n.s.), MCI (-2.05%,
p=n.s.), JSD-MCP (-0.76%, p=n.s.) and JSD-PIP (0%, p=n.s.).
Conclusion:
The study presented an absence of periarticular demineralisation and finger joint space narrowing in the treatment with
tocilizumab, which highlights the effective treatment strategy of a biologic target in RA as well as the detailed computer
based analysis of periarticular minerlisation and finger joint space width by DXR and CAJSA.
Disclosure: A. Pfeil, None; O. Gadeholt, None; J. Böttcher, None; D. Renz, None; P. Oelzner, None; G. Wolf, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-therapy-with-tocilizumab-is-not-

associated-with-periarticular-demineralisation-and-finger-joint-space-narrowing-in-rheumatoid-arthritis

Soluble Urokinase Plasminogen Activator Receptor (suPAR) Correlates with
Disease Activity in Early Rheumatoid Arthritis and Reflects Joint Damage
over Time
Helena Enocsson1, Alf Kastbom1, Tanja Lukic1, Christopher Sjöwall2, Thomas Skogh1 and Jonas Wetterö1,
1Rheumatology, Division of Neuro and Inflammation Sciences, Department of Clinical and Experimental Medicine,
Linköping University, Linköping, Sweden, Linköping, Sweden, 2Department of Clinical and Experimental Medicine,
Linköping University, Sweden, Linköping, Sweden
SESSION INFORMATION
Background/Purpose:
The urokinase plasminogen activator receptor (uPAR) is expressed on various cell types and plays important roles in
proteolysis, migration and adhesion. Receptor shedding yields a soluble form (suPAR) that has been intensively studied as a
potential biomarker in several inflammatory diseases and malignancies. The previous few studies on suPAR in rheumatoid
arthritis (RA) have shown an association with inflammation and swollen joints, but data on changes in suPAR levels in
relation to early disease course are lacking. This study investigates whether suPAR levels predict or reflect disease activity
and/or joint damage in early RA.
Methods:
Serum suPAR was measured by ELISA at disease onset (0 months), after 3 months and after 36 months in 252 RA patients
from the Swedish early RA cohort TIRA-2. suPAR levels were compared with disease activity (defined by DAS28) and
joint damage (Larsen score) at baseline and up to 36 months after disease onset. Healthy individuals (n=100) served as
controls.
Results:
Circulating levels of suPAR were higher in RA patients at all three time points compared to healthy controls (mean suPAR
= 3.62 ng/mL; p<0.001). The highest suPAR among patients was found at 3 months (mean = 8.47 ng/mL) and the lowest at
36 months (mean = 7.14 ng/mL). suPAR at inclusion correlated with baseline DAS28 (p<0.001, rho=0.25) whereas suPAR
levels at 36 months correlated with Larsen score at 36 months (p=0.001, rho=0.24), and 24 months (p=0.002, rho=0.25),
but not with DAS28 at any time point. No correlation was found between baseline suPAR and joint damage at any time
point. Categorization of baseline DAS28 revealed higher baseline suPAR at high DAS28 (Fig. 1) whereas Larsen score at
36 month reveled higher suPAR (measured at 36 months) among patients with a high score (>5) compared to those with a
low score (<2) (Fig. 2).
Conclusion:
suPAR levels associate with disease activity in early untreated RA, but at later stages rather reflect joint damage. Since
suPAR levels seem to increase at or after damage accrual, we speculate that suPAR reflects active inflammation and
ongoing processes in the joint, rather than being a causative agent.
Figure 1. Serum levels of suPAR and in different categories of disease activity (DAS28) at study inclusion. P-values are
from One-way ANOVA with Tukey’s post hoc test. Error bars indicate 95% confidence interval.
Figure 2. Serum levels of suPAR and the degree of joint damage (Larsen score) 36 months after study inclusion. P-values
are from One-way ANOVA with Tukey’s post hoc test. Error bars indicate 95% confidence interval.
Disclosure: H. Enocsson, None; A. Kastbom, None; T. Lukic, None; C. Sjöwall, None; T. Skogh, None; J. Wetterö,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/soluble-urokinase-plasminogen-

activator-receptor-supar-correlates-with-disease-activity-in-early-rheumatoid-arthritis-and-reflects-joint-damage-over-time
Analysis of Real-World Treatment Patterns in a Matched Sample of

Rheumatology Patients with Continuous Infliximab Therapy or Switched to
Biosimilar Infliximab
Lorie A. Ellis1, Ismail Simsek2, Lin Xie3, Adesuwa Ogbomo3, Dennis Parenti4, Kavitha Goyal4 and Yusuf Yazici5,
1Janssen HECOR Immunology, Horsham, PA, 2Guven Hospital, Ankara, Turkey, 3STATinMED Research Inc., Ann Arbor,
MI, 4Janssen Scientific Affairs, LLC, Horsham, PA, 5New York University School of Medicine, New York, NY
SESSION INFORMATION
Background/Purpose: Biosimilar infliximab (CT-P13) was first approved in Europe in 2013.This study compared
treatment (tx) patterns of Turkish pts with a diagnosis of rheumatoid arthritis(RA) who initiated originator IFX(IFX) &
either continued IFX or switched to CT-P13.
Methods: Adult pts with ≥1 RA diagnosis code & IFX claim were identified in a national Turkish healthcare database.
Eligible pts initiated & continued IFX (Continuer cohort; CC) or initiated IFX & switched to CT-P13 (Switch cohort; SC)
during the study period (01DEC2010-01JUN2016). The index date was defined as CT-P13 switch date for SC or a random
IFX date during period of CT-P13 availability for CC. Cohorts were matched on age,sex,&number of IFX prescriptions
during baseline(BL). Discontinuation (d/c) was defined as a switch to another biologic or no index biologic for ≥120 days
without censoring. Pt demographics, d/c & switching were summarized with descriptive statistics.
Results: A total of 697 pts initiating IFX were studied; 87%(N=605) continued IFX throughout the study period; 13%
(N=92) switched to CT-P13. BL & clinical characteristics are shown in Table. Mean duration of IFX therapy during BL
period was 422 days(CC) & 438 days(SC). Average duration of post-index follow-up was 16 months(CC) & 15
months(SC). During the combined BL & post-index periods, median time on any IFX therapy was 1080 days(CC)&540
days(SC)(Figure).D/c post-index occurred in 19%(CC) & 87%(SC); mean time from index to IFX d/c /censoring was 276
days(CC) while mean time from index to CT-P13 d/c /censoring was 132 days.While switching from IFX to CT-P13
occurred in 13% all IFX initiators on the index date; an additional 10% of the CC switched to a non-IFX anti-TNF post-
index. The majority of SC(82%) switched again post-index (off CT-P13) & 88% of those re-initiated IFX. Regional
variation in switching was noted. Switching from IFX to CT-P13 occurred most frequently in Central Anatolia (26% of 154
IFX initiators).Switching from CT-P13 occurred in >75% of SC pts in all regions except for Aegean(44% switched from
CT-P13 to another biologic, predominantly IFX).
Conclusion: In Turkey, RA pts maintained on IFX had greater tx persistence than those who initiated IFX & switched to
CT-P13. CT-P13 d/c resulted in IFX re-initiation in the majority of pts. Reasons for d/c are unknown, however regional
differences in practice patterns were observed.
Table Demographics and Treatment Patterns for Continuer and
Switcher Cohorts
Continuers Switchers
Cohort Cohort
(N=605) (N=92)
N/Mean %/SD N/Mean %/SD
Age (Mean) (years) 41 10.3 43 11.8
Sex
Women 309 51% 48 52%
Baseline Concomitant Disease
Ankylosing Spondylitis 102 18% 27 13%
Psoriatic Arthritis 48 8% 11 5%
Crohn’s Disease 244 42% 114 56%
Ulcerative Colitis 42 7% 9 4%
Average Length of Follow-up Period
(months) 16 2 15 2
Post-Index Concomitant Disease
Ankylosing Spondylitis 363 60% 58 63%
Psoriatic Arthritis 102 17% 13 14%
Crohn’s Disease 48 8% 3 3%
Ulcerative Colitis 33 5% 4 4%
Switching
N and % of patients with ≥1 switch 115 19% 75 82%
N and % Primary Switches from CT-
P13 to IFX NA NA 66 88%
Geographical Distribution of Patients
with ≥ 1 switches (n=115 vs. 75)
East Anatolia 6 5% 1 1%
South Eastern Anatolia 10 9% 9 12%
Marmara 39 34% 9 12%
Aegean 4 3% 4 5%
Mediterrane 19 17% 16 21%
Black sea 9 8% 1 1%
Central Anatolia 28 24% 35 47%
Discontinuation
N of Patients with Confirmed
Discontinued 205 34% 80 87%
Time to confirmed discontinuation
(days) 117 78 98 60
Time to any discontinuation or
censoring (days) 276 124 132 104
N: Number; %: Percentage; IFX: Infliximab; SD: Standard Deviation; NA: Not available.
Figure Kaplan Meier (KM) curve for any Infliximab Use for the Switcher and Continuers Cohorts during the
Baseline and Follow up Period.
Disclosure: L. A. Ellis, Janssen, 3,Johnson & Johnson, LLC, 1; I. Simsek, Janssen Scientific Affairs, LLC, 2; L. Xie,
Janssen Scientific Affairs, LLC, 5; A. Ogbomo, Janssen Scientific Affairs, LLC, 5; D. Parenti, Janssen, 3,Johnson &
Johnson, LLC, 1; K. Goyal, Janssen, 3,Johnson & Johnson, LLC, 1; Y. Yazici, Yusuf Yazici, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/analysis-of-real-world-treatment-

patterns-in-a-matched-sample-of-rheumatology-patients-with-continuous-infliximab-therapy-or-switched-to-biosimilar-
infliximab
Time from First Symptom Onset to First Advanced Therapy Amongst RA

Patients in Latin America
Ivanio Pereira1, Valderilio F Azevedo2, Wilson Bautista-Molano3, Julio Casasola4, Generoso Guerra5, David Vega-
Morales6, Enrique R Soriano7, Diana Rocio Gil8, José Antonio Maldonado-Cocco9, Leandro Aldunate10 and Steve
Lobosco11, 1Rheumatology, Universidade Federal de Santa Catarina, Hospital Universitário, Divisão de
Reumatologia.Brazil, Florianopolis, Brazil, 2Adjunct Professor of Rheumatology, Federal University of Paraná; Brazil,
Curitiba, Brazil, 3School of Medicine, Universidad Militar Nueva Granada and Rheumatology Department Hospital Militar.
Colombia, Bogotá, Colombia, 4Rheumatology, Hospital General de Mexico, Mexico, Mexico, 5Centro Médico Paitilla
Internal Medicine and Rheumatology Department. Panama, Panama City, Panama, 6Universidad Autónoma de Nuevo
León. Rheumatology Service, Internal Medicine Department, Hospital Universitario "Dr. José Eleuterio González".
Mexico, Monterrey, Mexico, 7Argentina, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina, 8ART Medica -
Hospital Universitario Mayor MEDERI Internal Medicine and Rheumatology. Colombia., Bogota, Colombia, 9Buenos
Aires University, Consulting Professor of Rheumatology, Buenos Aires University. Argentina, Buenos Aires, Argentina,
10Immunology, Janssen Latin America, Buenos Aires, Argentina, 11Adelphi, Immunology Director- Adelphi Group,
Manchester, United Kingdom
SESSION INFORMATION
Background/Purpose: To understand the RA patient pathway in Latin America from first symptom onset; including time
to diagnosis and to first advanced treatment.
Methods: Data from the 2015 RA Disease Specific Programme (DSP), a cross-sectional, multi-national survey of patients
and rheumatologists conducted in Brazil, Argentina, Mexico, Colombia, Venezuela were analyzed against 2014 DSP data
from the US and 5EU. Rheumatologists (n=188 Latin America, n=113 US, n=340 EU) completed forms containing patient
demographics, age at first RA symptoms, age at RA diagnosis, age at csDMARD initiation and age at bDMARD initiation.
Continuous data were tested using t tests.
Results: A total of 801 Latin America, 843 US and 2536 EU RA patients were included in this analysis. Current mean age
across Latin America was 51.9 years and 82.8% female. Mean age of patients at RA symptom onset was 40.6 years, with
age at diagnosis 42.6 years; resulting in a 2.2 year (3.9 SD) wait from first experiencing symptoms to receiving a confirmed
diagnosis. Patients in Latin America waited 2.6 years (5.7 SD) from the point of RA diagnosis to initiation of first
csDMARD vs. 1.0 years US (3.2 SD) and 1.1 years EU (3.0 SD) (both p<0.001), and 6.4 years (7.4 SD) from RA diagnosis
to initiation of first bDMARD therapy vs. 3.9 years US (5.6 SD) and 5.2 years EU (5.7 SD) (both p<0.001).
Conclusion: RA patients in Latin America wait over 2 years from symptom onset to diagnosis and significantly longer
than their US and EU counterparts to receive csDMARD and Biologic therapy. This highlights a clear need to shorten RA
diagnosis times and time to treatment initiation.
Disclosure: I. Pereira, None; V. F. Azevedo, AbbVie, Eli Lilly, Genentech, GSK, Pfizer Inc, UCB, 2,AbbVie, Merck-
Serono, Novartis, Pfizer Inc, 5,AbbVie, Janssen, Merck-Serono, Novartis, Pfizer Inc, Sanofi, 8; W. Bautista-Molano,
None; J. Casasola, None; G. Guerra, None; D. Vega-Morales, None; E. R. Soriano, AbbVie, Janssen, Novartis, Pfizer
Inc, UCB, 2,AbbVie, Janssen, Novartis, Pfizer Inc, UCB, 5,AbbVie, Bristol-Myers Squibb, Janssen, Novartis, Pfizer Inc,
Roche, UCB, 8; D. Rocio Gil, None; J. A. Maldonado-Cocco, None; L. Aldunate, Janssen Pharmaceutica Product, L.P.,
3; S. Lobosco, Adelphi, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/time-from-first-symptom-onset-to-first-

advanced-therapy-amongst-ra-patients-in-latin-america
Levels of Satisfaction with RA Treatment and Associated Alignment between

Rheumatologists and Their Patients across Latin America
Enrique R Soriano1, José Antonio Maldonado-Cocco2, David Vega-Morales3, Diana Rocio Gil4, Ivanio Pereira5,
Generoso Guerra6, Wilson Bautista-Molano7, Julio Casasola8, Valderilio F Azevedo9, Leandro Aldunate10 and Steve
Lobosco11, 1Rheumatology Unit, Internal Medicine Service, Hospital Italiano de Buenos Aires, CABA, Argentina,
2Buenos Aires University, Consulting Professor of Rheumatology, Buenos Aires University. Argentina, Buenos Aires,
Argentina, 3Universidad Autónoma de Nuevo León. Rheumatology Service, Internal Medicine Department, Hospital
Universitario "Dr. José Eleuterio González". Mexico, Monterrey, Mexico, 4ART Medica - Hospital Universitario Mayor
MEDERI Internal Medicine and Rheumatology. Colombia., Bogota, Colombia, 5Rheumatology, Universidade Federal de
Santa Catarina, Hospital Universitário, Divisão de Reumatologia.Brazil, Florianopolis, Brazil, 6Centro Médico Paitilla
Internal Medicine and Rheumatology Department. Panama, Panama City, Panama, 7School of Medicine, Universidad
Militar Nueva Granada and Rheumatology Department Hospital Militar. Colombia, Bogotá, Colombia, 8Rheumatology,
Hospital General de Mexico, Mexico, Mexico, 9Adjunct Professor of Rheumatology, Federal University of Paraná; Brazil,
Curitiba, Brazil, 10Immunology, Janssen Latin America, Buenos Aires, Argentina, 11Adelphi, Immunology Director-
Adelphi Group, Manchester, United Kingdom
SESSION INFORMATION
Background/Purpose: To assess levels of rheumatologist and patient satisfaction with RA treatment across Latin America
and any disconnects that may exist between the two in real world clinical practice.
Methods: Data from the 2015 RA Disease Specific Programme (DSP), a cross-sectional, multi-national survey of patients
and rheumatologists conducted in Argentina, Mexico, Colombia and Venezuela were analyzed. Rheumatologists (n=141)
completed forms containing patient demographics, patient disease severity and treatment satisfaction. Patients self-reported
their level of treatment satisfaction and disease severity.
Results: A total of 555 RA patients from across Latin America were included in this analysis. Current mean age across
Latin America was 51.9 years and 82.3% female. Proportions of rheumatologists and patients reporting satisfaction with
treatment were statistically highly similar (79% and 83% respectively), however current disease severity reporting differed
between rheumatologists and patients (mild 70% / moderate-severe 30% rheumatologists vs. 51% mild / 49% moderate-
severe patients; p<0.001). When assessed for alignment, 21% of rheumatologists and patients disagreed on the level of
satisfaction, driven mainly by rheumatologists over-stating dissatisfaction (13%) vs. their patient (8%) (p=0.031). For
current disease severity, 36% of rheumatologists and patients disagreed, driven mainly by patients (28%) over-stating their
severity vs. their rheumatologist (8%) (p<0.001). Of those patients for whom their rheumatologist was satisfied with
treatment, 20% were classified as having moderate to severe RA by that same physician.
Conclusion: Despite many rheumatologists and their patients in Latin America reporting high levels of satisfaction with
treatment, patients frequently remain moderate to severe and disconnected from their physician. There is a need to improve
physician / patient engagement as a means to improving clinical control.
Disclosure: E. R. Soriano, AbbVie, Janssen, Novartis, Pfizer Inc, UCB, 2,AbbVie, Janssen, Novartis, Pfizer Inc, UCB,
5,AbbVie, Bristol-Myers Squibb, Janssen, Novartis, Pfizer Inc, Roche, UCB, 8; J. A. Maldonado-Cocco, None; D. Vega-
Morales, None; D. Rocio Gil, None; I. Pereira, None; G. Guerra, None; W. Bautista-Molano, None; J. Casasola, None;
V. F. Azevedo, AbbVie, Eli Lilly, Genentech, GSK, Pfizer Inc, UCB, 2,AbbVie, Merck-Serono, Novartis, Pfizer Inc,
5,AbbVie, Janssen, Merck-Serono, Novartis, Pfizer Inc, Sanofi, 8; L. Aldunate, Janssen Pharmaceutica Product, L.P., 3; S.
Lobosco, Adelphi, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/levels-of-satisfaction-with-ra-treatment-

and-associated-alignment-between-rheumatologists-and-their-patients-across-latin-america
Improving Knowledge of Rheumatoid Arthritis Clinical Trial Results Among

Rheumatologists: Effect of an Online Educational Intervention
Edward Jackson and Piyali Chatterjee-Shin, Medscape Education, LLC, New York, NY
SESSION INFORMATION
Background/Purpose: While major medical conferences provide the most up-to-date evidence regarding diseases and
treatments, time demands and financial constraints are often cited as reasons for non-participation. A study was conducted
to determine whether an online educational activity could effectively address a knowledge gap in awareness of emerging
trial results as presented at a major rheumatology conference in the field of rheumatoid arthritis (RA).
Methods: An online educational intervention focusing on key abstracts in RA presented at the American College of
Rheumatology Annual Meeting 2016 was developed and made available online. The education consisted of 3 video-based
expert discussions covering both trial outcomes and associated clinical implications, for the intended audience of practicing
rheumatologists. The educational impact was assessed by comparing participants’ responses to 3 identical paired pre- and
post-assessment questions. Pairing of responses allows each learner to act as his/her own control. Data representing a
statistical sampling of the overall learner population were collected from December 22, 2016 through January 31, 2017.
Statistical analysis comprised a paired 2-tailed t-test comparing mean pre-assessment and post-assessment scores,
McNemar’s χ2 statistic for measuring changes in responses to individual questions, and probability values (P values) for
both t-test and χ2 statistics. This analysis considers P < .05 as meeting statistical significance. Cramer’s V was used to
calculate the overall effect size of the intervention.
Results: For the rheumatologists who participated in the online activity, comparison of pre- and post-assessment responses
demonstrated statistically significant improvements (n = 59; P <.05) in knowledge and a robust overall effect (V = 0.307).
As a result of participating in this educational program, significant absolute percentage increases in correct responses were
observed (all P <.05):
• 25% increase (44% vs 69%) in those who identified the trial design of an open-label extension of the MOBILITY trial
regarding the 3-year efficacy of a specific IL-6 inhibitor
• 36% increase (10% vs 46%) in those who recognized the association between different types of disease flare and
progression of joint damage as reported in a post hoc analysis of the PRESERVE trial
• 31% increase (44% vs 75%) in those who identified that tumor necrosis factor alpha therapy allowed patients to reduce or
discontinue methotrexate or corticosteroid therapy as reported in a 10-year open-label extension of the PREMIER and
DE019 trials
Conclusion: Participation in video-based expert discussions of clinical trial data from current and emerging agents resulted
in significant improvement in knowledge of rheumatologists. A need for further education was also identified regarding the
most up-to-date clinical information regarding management of RA as presented at major medical conferences.
Disclosure: E. Jackson, None; P. Chatterjee-Shin, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/improving-knowledge-of-rheumatoid-

arthritis-clinical-trial-results-among-rheumatologists-effect-of-an-online-educational-intervention
Disease Course in Seronegative RA Patients Classified According to the 2010

ACR/EULAR Criteria
Lena Bugge Nordberg1, Siri Lillegraven2, Anna-Birgitte Aga2, Inge C Olsen3, Elisabeth Lie4, Hilde B Hammer2, Till
Uhlig2, Désirée van der Heijde5, Tore Kvien6 and Espen A. Haavardsholm2, 1Departement of Rheumatology,
Diakonhjemmet hospital, oslo, Norway, 2Dept. of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, 3Department of
Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, 4Rheumatology, Diakonhjemmet Hospital, Oslo, Norway,
5Rheumatology, Leiden University Medical Center, Leiden, Netherlands, 6Diakonhjemmet Hospital, Oslo, Norway
SESSION INFORMATION
Background/Purpose:
The development of the 2010 classification criteria for rheumatoid arthritis (RA) has led to a redefinition of the patient
population, including classification of seropositive versus seronegative patients (1). In our recently published study of early
RA patients fulfilling the 2010 ACR/EULAR criteria, we found seronegative patients to have markedly higher disease
activity at time of diagnosis, compared to seropositive patients (2). There is very limited information about the disease
course of seronegative patients classified according to the new criteria. Our aim was to examine the disease course of
seronegative RA patients fulfilling the 2010 ACR/EULAR criteria.
Methods:
In the treat-to-target ARCTIC trial, DMARD-naive RA patients classified according to the 2010 EULAR/ACR criteria
were randomised 1:1 to follow-up with or without ultrasound. Patients in both arms were treated according to the same
DMARD escalation strategy. Patients were assessed at 13 visits during two years of follow-up (3).
We stratified the patients as seropositive (rheumatoid factor (RF)+, anti-citrullinated peptide antibody (ACPA)+, or both) or
seronegative (RF- and ACPA-). At baseline and 24-month follow-up, disease activity measures were compared across
groups using independent t-test or Mann-Whitney U test as appropriate. We also compared the change in disease activity
measures from 0-24 months across groups.
Results:
A total of 230 patients were included. Mean (SD) age was 51.4 (13.7) years and 61.3 % were female; 34 patients (14.8%)
were seronegative. Mean age (SD) was 55.4 (2.7)/ 50.8 (0.9) years (p=0.07), mean (SD) disease duration was 7.7 (6.8)/7.0
(5.1) months (p=0.46), and 56/62 % were females (p=0.48) in the seronegative/seropositive groups.
At baseline disease activity measures and radiographic joint space narrowing were higher in seronegative compared to
seropositive patients. At 24-month follow-up, measures of disease activity were similar between groups (table). There was
a tendency towards more radiographic damage in terms of joint space narrowing in the seronegative patients.
Seronegative patients had a greater reduction (0-24 months) in disease activity measures in terms of DAS, swollen joints,
physician global and ultrasound scores (table).
Conclusion:
In this study of early RA patients, seronegative patients had more inflammatory activity at baseline and a tendency to more
radiographic damage, but disease activity after two years of treat-to-target therapy was similar to the seropositive patients.
Our findings suggest that seronegative patients classified according to the new criteria respond to modern
treatment strategies, with similar rates of patients reaching remission compared to seropositive patients.
1. Aletaha, D., et al. 2010;ARD 2010;69: 1580-1588.
2. Nordberg LB et al. ARD 2017;76:341-345
3. Haavardsholm EA et al., BMJ 2016;354:i4205
Disclosure: L. B. Nordberg, None; S. Lillegraven, None; A. B. Aga, None; I. C. Olsen, Pfizer Inc, 5; E. Lie, AbbVie,
Celgene, Hospira and Pfizer, 8; H. B. Hammer, None; T. Uhlig, None; D. van der Heijde, None; T. Kvien, AbbVie,
Biogen, BMS, Boehringer Ingelheim, Celltrion, Eli Lilly, Epirus, Janssen, Merck-Serono, MSD, Mundipharma, Novartis,
Oktal, Orion Pharma, Hospira/Pfizer, Roche, Sandoz, and UCB., 5,AbbVie, Biogen, BMS, Boehringer Ingelheim,
Celltrion, Eli Lilly, Epirus, Janssen, Merck-Serono, MSD, Mundipharma, Novartis, Oktal, Orion Pharma, Hospira/Pfizer,
Roche, Sandoz, and UCB, 8; E. A. Haavardsholm, AbbVie, Pfizer, Roche, Eli Lilly, Celgene, UCB, 5,AbbVie, Pfizer,
Roche, MSD, UCB, 2,AbbVie, Pfizer, Roche, Eli Lilly, Celgene, UCB, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/disease-course-in-seronegative-ra-

patients-classified-according-to-the-2010-acreular-criteria
Usefullness of Serum Angiogenic and Proinflammatory Cytokines to

Discriminate between 6 Sets of Remission Criteria and Biomarkers of
Radiographic Progression and Clinical Flare in RA in Clinical Remission.
Pre-Eliminary Results of a Study of 5 Years of Follow-up
Julio Ramírez1, Andrea Cuervo2, Raquel Celis3, Virginia Ruiz-Esquide1, M. Victoria Hernández4, Raimon Sanmarti5 and
Juan D. Cañete6, 1Rheumatology Service, Hospital Clínic de Barcelona, Barcelona, Spain, 2Arthritis Unit. Rheumatology
Dpt, Arthritis Unit, Rheumatology Dpt, Hospital Clinic of Barcelona and IDIBAPS, Barcelona, Spain, 3Rheumatology,
Arthritis Unit, Barcelona, Spain, 4Hospital Clinic. Barcelona. Spain, Barcelona, Spain, 5Arthritis Unit, Rheumatology Dpt,
Hospital Clinic of Barcelona, Barcelona, Spain, 6Rheumatology Department, Arthritis Unit, Rheumatology Dpt, Hospital
Clinic of Barcelona, Barcelona, Spain
SESSION INFORMATION
Background/Purpose:
The primary aim of this study was to analyse serum levels differences of angiogenic and inflammatory biomarkers between
SDAI, CDAI, ACR, DAS28 and sonographic remission in patients with RA. As secondary objective, we tried to find
clinical, serological or ultrasound biomarkers of radiographic progression and clinical flares in RA patients in clinical
remission.
Methods:
We selected patients with RA in clinical remission (defined as DAS28-ESR<2.6 for > 6 months) tested by two independent
rheumatologists. Clinical, epidemiological, demographic and serological data were analyzed. PDUS of knees and hands
was performed by a sonographer with an ultrasound scanner with a linear probe of 8-12 MHz. Serum levels of biomarkers
of inflammation/angiogenesis were determined by Quantibody® Human Array. Patients were classified according to 6 sets
of remission criteria: SDAI (<3.3), CDAI (<2.8), ACR/EULAR, DAS28-ESR (<2.6), Doppler (score Doppler=0) and
UdAS (ultrasound defined active synovitis: no joints with SH>2+PD). A clinical and radiographic follow-up of the patients
was done along 5 years. Clinical flare was defined as the loss of remission (DAS28-ESR>2.6) and change on the baseline
treatment for RA. Radiographic progression was defined as the new appearance of erosions in hands or feet.
Results:
60 patients with RA were collected. 76% female, aged (mean) 53 years; disease duration 110 months. Sixteen (26%)
patients were taking oral prednisone (<5 mg/day), 47 (76%) conventional synthetic disease modifying anti-rheumatic drugs
(csDMARDs), and 27 (45%) biological therapies. At baseline, 67% of patients had PD signal and 48% fulfilled criteria for
previously defined UdAS. Although patients in sonographic remission (both Doppler and UdAS) had lower levels of
inflammatory biomarkers such as IL-6, IL-17 or IL-23, no significant differences were found between the 6 sets of
remission criteria. Angiogenic biomarkers such as CXCL6 (0.039), ENA78 (0.007), SDF1 (0.047) and VEGF-R1 (0.025)
were significantly lower in patients fulfilling CDAI remission. Patients with no PD signal (0.009) and no UdAS (0.006) had
significantly lower levels of bFGF. After 5 years of follow-up, 12 patients (20%) flared and 14 (23.3%) had radiographic
progression. No significant differences were found in flares or X-ray progression between the 6 sets of remission criteria.
Patients fulfilling UdAS but not those with only PD, had more radiographic progression (p=0.014). Patients on biological
therapy had less clinical flares along the 5 years of follow-up (p=0.049). Finally, patients with more CD20 + cells infiltrates
in sinovial membrane had also more radiographic progression (p=0.033).
Conclusion:
RA patients in CDAI remission had significantly-lower levels of angiogenic cytokines. Remission according to DAS28-
ESR did not show worse clinical or radiographic progression after 5 years of follow-up. Noteworthy, UdAS and CD20+
cells infiltrates were both significant factors of radiographic progression.
Disclosure: J. Ramírez, Gebro, 2; A. Cuervo, None; R. Celis, None; V. Ruiz-Esquide, None; M. V. Hernández, None;
R. Sanmarti, None; J. D. Cañete, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/usefullness-of-serum-angiogenic-and-

proinflammatory-cytokines-to-discriminate-between-6-sets-of-remission-criteria-and-biomarkers-of-radiographic-
progression-and-clinical-flare-in-ra-in-clinical-remis
Additions to Methotrexate with Conventional and Biologic Dmards in

Rheumatoid Arthritis: Are There Differences in Subsequent Time to
Treatment Failure?
Sasha Bernatsky1, Orit Schieir2, Cristiano S. Moura3, Marie-France Valois4, Susan J. Bartlett5, Carol A Hitchon6, Janet E.
Pope7, Gilles Boire8, Boulos Haraoui9, Edward C. Keystone10, Diane Tin11, Carter Thorne12 and Vivian P. Bykerk13,
1Divisions of Rheumatology and Clinical Epidemiology, Research Institute of the McGill University Health Centre,
Montreal, QC, Canada, 2McGill University, Montreal, ON, Canada, 31Division of Clinical Epidemiology, McGill
University Health Centre, Montreal, QC, Canada, 4McGill University, Montreal, QC, Canada, 5Department of Medicine,
Division of ClinEpi, Rheumatology, Respirology, McGill University, Montreal, QC, Canada, 6University of Manitoba,
Winnipeg, MB, Canada, 7Department of Medicine, Division of Rheumatology, University of Western Ontario, St Joseph's
Health Care, London, ON, Canada, 8Rheumatology Division, Centre Hospitalier Universitaire de Sherbrooke and
Universite de Sherbrooke, Sherbrooke, QC, Canada, 9Institut de Rhumatologie de Montréal, Montreal, QC, Canada,
10University of Toronto, Toronto, ON, Canada, 11The Arthritis Program, Southlake Regional Health Centre, Newmarket,
ON, Canada, 12University of Toronto, Newmarket, ON, Canada, 132-005, Mt Sinai Hospital, Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose: Our objective was to compare RA treatment strategies with conventional and biologic DMARDs
after an initial MTX strategy was ineffective or associated with a severe adverse event.
Methods: We studied adults from a multicenter early arthritis cohort (enrolled from 2007- 2017 within one year of
symptom onset). RA patients were eligible for our analyses if they initiated MTX (+/-other DMARDs) within 90 days of
cohort entry and subsequently changed therapy (changed MTX route, lowered or stopped MTX or other DMARD, or added
another DMARD or biologic). For this analyses, the time of medication change formed the time zero for a survival analyses
of the second treatment approach. Patients were followed from time zero to assess discontinuations of, or additions to, their
therapy. Multivariable survival models were used to compare outcomes. We generated hazard ratios (HRs) and 95%
confidence intervals (CI), comparing each of the treatment groups to oral methotrexate monotherapy.
Results: We included 911 RA patients initially exposed to MTX who had a first treatment failure. At time zero (time of
initial failure), the most common second treatment strategies were MTX+ another DMARD (32.9%) and non MTX
DMARDs (26.1%) (Table 1).
Table 1 Distribution of treatment approaches after a first MTX failure

Time to discontinuation Frequency of Serious
(in months)1 any failure* Loss of adverse Any side
Frequency efficacy2 effect2 effect2
Treatment N % Median Range N (%) N (%) N (%) N (%)
MTX oral 58 6.4 7.8 0.3 to 69.5 39 (67%) 6 (10.3%) 0 (0%) 11 (19.0%)
MTX 89 9.8 9.1 0.3 to 89.8 58 (65%) 4 (4.5%) 0 (0%) 17 (19.1%)
subcutaneous
MTX + another 300 32.9 6.8 0.3 to 83.9 196 (65%) 23 (7.7%) 1 (0.3%) 100 (33.3%)
DMARD
MTX+SSZ+HCQ 126 13.8 12.0 0.3 to 83.0 82 (65%) 7 (5.6%) 0 (0%) 48 (38.1%)
Biologics+/- 100 11.0 12.9 0.4 to 95.7 37 (37%) 11 (11.0%) 0 (0%) 22 (22.0%)
DMARDs
including MTX
Non MTX 238 26.1 4.5 0.3 to 73.9 182 (76%) 6 (2.5%) 0 (0%) 45 (18.9%)
DMARDs only
Total 911 100.0 6.9 0.3 to 95.7 594 (65%) 57 (6.3%) 1 (0.1%) 243 (26.7%)
1 Estimated by Kaplan-Meier curves
2As reported by the treating MD
The multivariable Cox regression analysis for the 911 RA patients suggested that those on biologics and those on triple
therapy had a longer time to failure, compared to the group taking MTX oral monotherapy. (Table 2)
Table 2 Adjusted hazard rations (HR) for drug changes after time zero*
Treatment at time zero HR 95% CI
MTX subcutaneous monotherapy 0.91 0.61, 1.35
MTX + another DMARD 0.87 0.62 1.22
MTX+SSZ+HCQ 0.64 0.44, 0.94
Biologics+/- DMARDs including MTX 0.31 0.20, 0.49
Non MTX DMARDs only 1.26 0.89, 1.77
*Adjusting for baseline characteristics: age, sex, co-morbidities, symptom duration, race, education, smoking, erosions,
DAS-28, disease activity, corticosteroids, NSAIDs, and COXIBs
Conclusion: Our data suggest that, in those who fail initial MTX, RA patients given biologics or triple therapy remain on
that treatment longer without further changes, versus those taking augmented MTX oral monotherapy. These data do not
confirm clear differences in outcomes with respect to MTX(dual or triple) combinations, but width of confidence intervals
precludes definitive conclusions in this regard.
Disclosure: S. Bernatsky, None; O. Schieir, None; C. S. Moura, None; M. F. Valois, None; S. J. Bartlett, PROMIS,
6,Pflizer, UCB, Lilly, 5; C. A. Hitchon, None; J. E. Pope, AbbVie, Amgen, Bayer, BMS, Celtrion, Eli Lilly and Company,
Merck, Novartis, Pfizer, Roche, UCB, 5,Amgen, Bayer, BMS, GSK, Merck, Novartis, Pfizer, Roche, UCB, 2; G. Boire,
None; B. Haraoui, None; E. C. Keystone, Abbott Laboratories, Amgen Inc., AstraZeneca Pharmaceuticals LP, Bristol-
Myers Squibb, F. Hoffmann-La Roche Inc, Janssen Inc, Lilly Pharmaceuticals, Novartis Pharmaceuticals, Pfizer
Pharmaceuticals, Sanofi-Aventis, UCB, 2,Abbott Laboratories, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb
Company, Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Janssen Inc, Lilly Pharmaceuticals, Merck,
Pfizer Pharmaceuticals, UCB, 5,Amgen, Abbott Laboratories, Astrazeneca LP, Bristol-Myers Squibb Canada,, 8; D. Tin,
None; C. Thorne, AbbVie, Amgen, Celgene, Lilly, Novartis, Pfizer, Sanofi, and UCB; has served as a consultant for
AbbVie, Amgen, Celgene, Centocor, Genzyme, Hospira, Janssen, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi,
and UCB, 2,Medexus/Medac, 8; V. P. Bykerk, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/additions-to-methotrexate-with-

conventional-and-biologic-dmards-in-rheumatoid-arthritis-are-there-differences-in-subsequent-time-to-treatment-failure
ABP 710: Matching Critical Biological Functions with Infliximab

Robert Sandrock1, Palanisamy Kanakaraj2 and Scott Kuhns1, 1Amgen, Inc., Thousand Oaks, CA, 2Amgen, Inc.,
Cambridge, MA
SESSION INFORMATION
Background/Purpose:
ABP 710 is being developed as a biosimilar to infliximab, a recombinant chimeric monoclonal antibody that binds tumor
necrosis factor alpha (TNFa) and inhibits the TNF receptor-mediated downstream pro-inflammatory signaling cascade.
Although ABP 710 and infliximab reference product have the same primary amino acid sequence differences in production
cell line and the manufacturing process can impact product quality attributes that may be critical for in vivo efficacy,
pharmacokinetics and immunogenicity. To demonstrate that ABP 710 is similar to the reference product, we performed a
comprehensive comparative biological characterization of ABP 710 with infliximab reference product.
Methods:
The functional similarity assessment of ABP 710 and infliximab reference product included: 1) binding to soluble (s) TNFa
by ELISA, 2) binding to membrane-bound (mb) TNFa by a competitive imaging cytometry-based assay, 3) inhibition of
sTNFa-induced apoptosis in the U937 cell line, and 4) reverse signaling via induction of apoptosis in mbTNFa-expressing
Jurkat cells. To confirm similarity of Fc-mediated functions, antibody-dependent cell-mediated cytotoxicity (ADCC) was
assessed using cells expressing mbTNFa as target cells and NK92-M1 cells expressing FcγRIIIa (158V) as effector cells. In
addition, complement-dependent cytotoxicity (CDC) was assessed using rabbit complement and cells expressing mbTNFa.
Data from at least three lots of ABP 710 and infliximab reference product sourced from the US (IFX-US) and infliximab
reference product sourced from the EU (IFX-EU) were assessed as described.
Results:
Relative binding of ABP 710 to sTNFa (ABP 710 =93-105%; IFX-US =88-101%; IFX-EU =93-104%) and mbTNFa (ABP
710 =101-109%; IFX-US =99-106%; IFX-EU =105-113%) were similar between ABP 710 and infliximab reference
product. Relative inhibition of apoptosis in U937 cells (ABP 710 =87-112%; IFX-US =78-115%; IFX-EU =89-114%), and
to induce apoptosis in Jurkat cells expressing mbTNFa (ABP 710 =99-105%; IFX-US =90-114%; IFX-EU =96-107%)
were also similar between ABP 710 and infliximab reference product. Fc-mediated functions, ADCC (ABP 710=102-
133%; IFX-US =91-169%; IFX-EU =100-166%) and CDC (ABP 710 =96-110%; IFX-US =93-136%; IFX-EU =98-135%)
were similar as well between ABP 710 and infliximab reference product.
Conclusion:
As one aspect of the “totality of evidence” approach to support similarity, results from this assessment demonstrate that
ABP 710 is functionally similar to infliximab reference product in multiple sensitive biological characterization assays.
Disclosure: R. Sandrock, Amgen, 1,Amgen, 3; P. Kanakaraj, Amgen, 1,Amgen, 3; S. Kuhns, Amgen, 1,Amgen, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/abp-710-matching-critical-biological-

functions-with-infliximab

Certolizumab Pegol for Fatigue in Chronic Inflammatory Rheumatic
Diseases: A Meta-Analysis
Yesim Ozguler1, Sinem Nihal Esatoglu1, Guzin Karatemiz1, Ali Ugur Unal2, Gul Guzelant1, Elif Dincses3, Mustafa
Erdogan1, Sema Kaymaz Tahra2 and Gulen Hatemi1, 1Istanbul University, Cerrahpasa Medical Faculty, Department of
Internal Medicine, Division of Rheumatology, Istanbul, Turkey, 2Departement of Internal Medicine, Division of
Rheumatology, Marmara University, Istanbul, Turkey, 3Istanbul University, Cerrahpasa Medical Faculty, Department of
Internal Medicine, Division of Rheumatology, İstanbul, Turkey
SESSION INFORMATION
Background/Purpose: Fatigue is an important problem that impairs life quality in patients with rheumatic diseases.
Although fatigue is often associated with disease activity, only a modest effect of anti-TNFs on fatigue was observed in
patients with RA (1). We aimed to determine the efficacy of different doses of certolizumab pegol (CZP) in chronic
inflammatory rheumatic diseases by a meta-analysis of randomized controlled trials.
Methods: A systematic literature search including patients with rheumatic diseases who received CZP was performed. We
searched PubMed for all randomized controlled trials with CZP up to May 2017 without any restrictions. Studies that
assessed fatigue in any rheumatic disease using the fatigue assessment scale (FAS) and reported the FAS score and/or the
proportion of patients who met the minimum clinically important difference (MCID) for FAS score were included. The
MCID for FAS is 1 over a scale of 0 to 10 where higher scores show increased severity of fatigue. The CZP 200 mg and
CZP 400 mg arms of trials were pooled for comparison with the placebo arms.
Results: The literature search yielded 68 articles. 55 articles were excluded after evaluating the title and abstract, 5 were
excluded after reading the full-text. Among the 8 RCTs that were selected , the study population was RA in 6 RCTs, and
psoriatic arthritis and axial spondyloarthritis in 1 RCT each. Overall, there were 2964 patients treated with CZP and 1056
with placebo. Table summarizes the included studies.
An improvement in the FAS score and an increase in the proportion of patients who met the MCID for FAS were observed
in all the included trials regardless of the underlying disease (Figure-1, 2). The pooled results showed that CZP
significantly improved fatigue compared to placebo (FAS: MD = -1.50, 95% CI:-1.71- -1.29, p <0.0001, MCID: RR=2.53,
95% CI: 1.74-3.68).
Conclusion: This meta-analysis showed that CZP may be an effective treatment modality for fatigue in rheumatic diseases.
Reference:
1) Druce KL, Bhattacharya Y, Jones GT, Macfarlane GJ, Basu N. Most patients who reach disease remission following
anti-TNF therapy continue to report fatigue: results from the British Society for Rheumatology Biologics Register for
Rheumatoid Arthritis. Rheumatology (Oxford). 2016 Oct;55(10):1786-90
Table 1. Characteristics of randomized controlled studies included in the meta-analysis
First author, Disease Inclusion Intervention Comparator arm Number of patients Study
year state criteria arm duration
(M/W) (weeks)
CZP 400 CZP 200 Placebo
Fleischman, RA Active disease CZP 400 Placebo every 4 111 NA 109 24
2017 despite ≥1 weeks (24/87) (12/97)
DMARD
Furst, RA Active disease CZP 400 Placebo every 2 70 70 69 34

despite MTX weeks
2015 CZP 200 (12/58) (23/49) (14/56)
Pope, RA Active disease CZP 200 Placebo every 2 NA 851 221 12
despite ≥1 weeks
2015 DMARD (NR) (NR)
Smolen, RA Low/moderate CZP 200 Placebo every 2 NA 96 98 24
active despite weeks
2017 ≥1 DMARD (15/81) (23/75)
Strand, RA Active disease CZP 400 Placebo every 2 390 393 199 52
despite MTX weeks
2009 CZP 200 (64/326) (69/324) (32/167)
Strand, RA Active disease CZP 400 Placebo every 2 246 246 127 24
despite MTX weeks
2011 CZP 200 (54/192) (42/206) (20/107)
Gladman, pSA Active disease CZP 400 Placebo every 2 135 138 136 24
despite ≥1 weeks
2014 DMARD* CZP 200 (62/73) (64/74) (57/79)
Sieper, axial SpA Active disease CZP 400 Placebo every 2 107 111 107 24
despite ≥1 weeks
2015 NSAID* CZP 200 (68/39) (67/44) (65/43)
*An history of an anti-TNF failure was not an exclusion criterion
DMARD: disease modifying anti-rheumatic drug; pSA; psoriatic arthritis; SpA: spondyloarthritis; MTX methotrexate,
NSAID: non-steroidal anti-inflammatory drugs; CZP: certolizumab pegol; NA: not applicable; NR: not reported
Disclosure: Y. Ozguler, None; S. N. Esatoglu, None; G. Karatemiz, None; A. U. Unal, None; G. Guzelant, None; E.
Dincses, None; M. Erdogan, None; S. Kaymaz Tahra, None; G. Hatemi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/certolizumab-pegol-for-fatigue-in-

chronic-inflammatory-rheumatic-diseases-a-meta-analysis
Value of Matrix Metalloproteinase-3 Regarding Prediction for Joint

Destruction at 1 Year Is Different between Sexes in Patients with Rheumatoid
Arthritis
Yutaro Yamada1, Kentaro Inui2, Tadashi Okano3, Yuko Sugioka1, Kenji Mamoto4, Kazuki Orita5, Tatsuya Koike6,
Masahiro Tada7 and Hiroaki Nakamura3, 1Orthopedic surgery, Osaka City University Graduate School of Medicine, Osaka,
Japan, 2Orhopedic surgery, Osaka City University Graduate School of Medicine, Osaka, Japan, 3Orthopaedic Surgery,
Osaka City University Graduate School of Medicine, Osaka, Japan, 4Orthopedic Surgery, Osaka City University Graduate
School of Medicine, Osaka, Japan, 5Orthopedics, Shirahama hamayu Hospital, Shirahama, Japan, 6Center for Senile
Degenerative Disorders, Osaka City University Medical School, Osaka, Japan, 7Orthopedic Surgery, Osaka City General
Hospital, Osaka, Japan
SESSION INFORMATION
Background/Purpose: Serum level of MMP-3 rises by synovial inflammation in patients with rheumatoid arthritis (RA). It
destroys articular cartilage such as proteoglycans so that it has been used as a clinical biomarker of joint destruction. Also it
has been reported as a predictor for radiographic progression. The purposes of this study are to confirm a relation between
baseline MMP-3 and radiographic progression at 1 year and to examine the association of the MMP-3 level with
ultrasonography (US) findings.
Methods: A total of 259 (213 women) consecutive patients with RA were enrolled in this study. Their baseline data
including age, sex, disease duration, use of glucocorticoid (GC) or DMARDs, disease activity (DAS28), laboratory data
(MMP-3, CRP, RF and ACPA), radiographic assessment (modified total Sharp score; mTSS) and the power doppler score
(PD) in US assessment at digits and wrists were collected. Baseline MMP-3 level was analyzed in association with the
baseline PD value and changes in mTSS (ƒ¢mTSS), erosion score (ƒ¢ERN), joint space narrowing (ƒ¢JSN) at 1 year from
baseline using Pearsonfs correlation method. Correlations between ƒ¢MMP-3 and ƒ¢mTSS, or ƒ¢PD were also analyzed.
Multiple regression analysis was performed with ƒ¢mTSS as the outcome for baseline variables. Statistical analysis was
performed separately by sex because the upper normal limits of MMP-3 is different between male and female.
Results: There was no correlation between baseline MMP-3 and disease duration, GC use, DAS28, RF, CRP and mTSS.
There was moderate correlations between baseline MMP-3, ƒ¢MMP-3, ƒ¢mTSS and ƒ¢JSN at 1 year only in men. There
was also a weak correlation between the baseline MMP-3 and baseline PD score only in men. However, MMP-3 could not
predict joint destruction at 1 year in women. Multiple regression analysis revealed that the baseline MMP-3 level correlated
independently with the ƒ¢mTSS only in men (p= 0.0031), whereas the baseline PD score was correlated independently with
the ƒ¢mTSS in women (p= 0.0003).
Conclusion: The baseline MMP-3 level was a good predictor for deterioration of the mTSS at 1 year in male patients with
RA, but not in female patients. On the other hand, the baseline PD score was a useful predictor of joint destruction in
female patients with RA.
variables correlation confidence p
coefficient interval
Male patients
Baseline ƒ¢mTSS 0.501a [0.246, 0.691] <0.001
MMP-3 ƒ¢ERN 0.336b [0.051, 0.571] 0.022
ƒ¢JSN 0.542a [0.299, 0.719] <0.0001
baseline- 0.228b [-0.074, 0.492] 0.136
PD
ƒ¢MMP-3 ƒ¢mTSS -0.435a [-0.644, -0.165] 0.003
ƒ¢ERN -0.325b [-0.562, -0.038] 0.028
ƒ¢JSN -0.436a [-0.645, -0.167] 0.002
ƒ¢PD 0.134 [-0.170, 0.414] 0.387
Female patients
Baseline ƒ¢mTSS 0.0011 [-0.130, 0.132] 0.987
MMP-3 ƒ¢ERN 0.0188 [-0.113, 0.150] 0.780
ƒ¢JSN -0.0148 [-0.146, 0.117] 0.826
baseline- 0.0985 [-0.040, 0.233] 0.163
PD
ƒ¢MMP-3 ƒ¢mTSS -0.0344 [-0.165, 0.098] 0.610
ƒ¢ERN -0.0485 [-0.179, 0.083] 0.472
ƒ¢JSN -0.0127 [-0.144, 0.119] 0.851
ƒ¢PD 0.134 [-0.0058, 0.060
0.270]
ƒ¢: difference in values from baseline to 1 year; MMP-3: matrix metalloproteinase; mTSS: modified total Sharp score;
ERN: erosion score; JSN: joint space narrowing; PD: power Doppler.
a: Moderate correlation, b: Weak correlation., Statistical analysis was performed using Pearsonfs correlation.
Disclosure: Y. Yamada, None; K. Inui, None; T. Okano, None; Y. Sugioka, None; K. Mamoto, None; K. Orita, None;
T. Koike, None; M. Tada, None; H. Nakamura, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/value-of-matrix-metalloproteinase-3-

regarding-prediction-for-joint-destruction-at-1-year-is-different-between-sexes-in-patients-with-rheumatoid-arthritis
Basement Membrane Remodeling in Rheumatoid Arthritis Associates with

Disease Activity, Response to IL-6 Inhibitor Treatment and Radiographic
Progression: Analysis of Two Phase III Clinical Trials
Natasja Stæhr Gudman1, Pernille Juhl1, Christian S. Thudium2, Peter Junker3, Anne Sofie Siebuhr4, Inger Byrjalsen1,
Morten Karsdal5 and Anne C. Bay-Jensen4, 1Nordic Bioscience, Herlev, Denmark, 2Biomarkers and Research, Nordic
Bioscience, Herlev, Denmark, 3Department of Rheumatology C, Odense University Hospital, Odense, Denmark,
4Rheumatology, Nordic Bioscience, Herlev, Denmark, 5Biomarkers and Reseacrh, Nordic Bioscience, Herlev, Denmark
SESSION INFORMATION
Background/Purpose:
Rheumatoid arthritis (RA) is associated with neovascularization of the synovial membrane and increased risk of
cardiovascular co-morbidity. The extra cellular matrix below the endothelial cells is referred to as the basement membrane,
embedding and protecting the cells. Altered remodeling of basement membrane proteins, including type IV collagen is a
core characteristic in persistent chronic inflammation. We aimed to investigate the association of type IV collagen turnover
with RA disease activity, response to IL-6 inhibition and radiographic progression.
Methods:
The study was based on patients participating in LITHE (NCT00106522, n=687) and RADIATE (NCT00106535, n=217),
phase III, double blinded, placebo controlled studies testing 4 and 8 mg/kg tocilizumab (TCZ) on top of methotrexate.
Basement membrane turnover was assessed at baseline and subsequently for up to 52 weeks using ELISA for quantification
of circulating C4M, an MMP generated collagen IV fragment in serum. We calculated correlations between C4M and
disease activity measures, treatment response and imaging findings.
Results:
Baseline C4M was significantly correlated with clinical disease parameters in both study populations, including DAS28,
HAQ score and VASpain (all p<0.00001). TCZ lowered C4M by 11%-40% in a dose dependent manner and the likelihood
of achieving an ACR20 response by week 16 was associated with C4M suppression exceeding the median decrease at week
4 (p<0.0001). C4M at baseline correlated significantly with change in JSN (p=0.001) and Sharp score (p=0.00002) at 52
weeks.
Conclusion:
Basement membrane remodeling as assessed by C4M was associated with disease activity and radiographic progression in
RA. This remodeling was persistently suppressed by TCZ in a dose dependent manner. These findings probably reflect that
RA synovitis suppression and slowing of erosive progression are at least in part attributable to angiostatic effects by
tocilizumab
Disclosure: N. S. Gudman, Nordic Bioscience Diagnostic, 3; P. Juhl, Nordic Bioscience Diagnostic, 3; C. S. Thudium,
Nordic Bioscience Diagnostic, 3; P. Junker, None; A. S. Siebuhr, Nordic Bioscience Diagnostic, 3; I. Byrjalsen, Nordic
Bioscience Diagnostic, 3; M. Karsdal, Symic Bio, 1; A. C. Bay-Jensen, Nordic Bioscience Diagnostic, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/basement-membrane-remodeling-in-

rheumatoid-arthritis-associates-with-disease-activity-response-to-il-6-inhibitor-treatment-and-radiographic-progression-
analysis-of-two-phase-iii-clinical-trials
Plasma Cytokines at Diagnosis May Predict Non-Response to Methotrexate

in Patients with Early Rheumatoid Arthritis
Martin Pelletier1, Paul R. Fortin1,2, Marie-Pier Longchamps1, Geneviève Parent1, Hadrien Benk-Fortin1, Anne-Sophie
Julien3, Nathalie Amiable1, Emmanuelle Rollet-Labelle1, Laetitia Michou2, Louis Bessette2 and Philippe A. Tessier1,
1Infectious Diseases and Immunity Research Division, CHU de Québec-Université Laval Research Center, Québec, QC,
Canada, 2Division of Rheumatology, Department of Medicine, CHU de Québec-Université Laval, Québec, QC, Canada,
3Clinical Research Platform, CHU de Québec-Université Laval Research Center, Québec, QC, Canada

SESSION INFORMATION
Background/Purpose: Methotrexate (MTX) is the first line treatment for patients with rheumatoid arthritis (RA). For over
30% of patients, MTX fails to diminish DAS28 score in a timely and satisfactory manner. The challenge is to find a way to
identify these non-responders at the time of diagnosis. The aims of this study were to determine whether plasma cytokines
could be used as biomarkers of early RA and of therapeutic response to MTX.
Methods: Thirty RA patients receiving MTX (mean age 58 ± 12 y.o. with symptom duration of 6 ± 3 mo.) from the Group
for Early Arthritis Research (GEAR) / CHU de Québec SARD Biobank Data Repository (SBDR). Patients were evaluated
clinically at baseline and 6 mo., and classified as responders to MTX or non-responders according to the DAS28CRP
EULAR Classification (good response vs moderate/none). Plasma cytokines were measured at baseline by multiplex assay
or ELISA and compared to age- and sex-matched healthy controls. Patients were Bivariate logistic regression was used to
identify RA patients and non-responders based on cytokine concentration or detection, with Firth bias correction when
needed. Optimal cut points were found using distance criteria and their predictive performance was assessed.
Results: Plasma concentrations of IL-1RA, CCL11/Eotaxin, CXCL10/IP-10, CCL2/MCP-1, CCL4/MIP-1β,

CCL5/RANTES, CXCL12a/SDF-1α and calprotectin were significantly different in RA patients compared to controls. IL-
21, IL-22, IL-1α, CXCL1/GROα were detected differently in RA plasma (Table 1). IL-1RA and CCL4/MIP-1β were good
predictors of RA with sensitivity and specificity of approximately 95% when dichotomized with cut points of 280 and 124,
respectively. Thirty-five percent of patients were non-responders to MTX. IL-1α, IL-18, IL-17A and IL-27 were less
frequently detected in non-responders (Table 2).
Conclusion: Several cytokines differentially expressed in plasma are associated with early RA. Absence of detection of IL-
1α, IL-17A and IL-27 and low concentration of IL-18 was associated with non-response to MTX. We propose that these
cytokines could be used as predictors of MTX response in RA.
Acknowledgements: This work was partly funded by CIHR. We thank Pfizer, Amgen, BMS, Abbvie, Roche, Sanofi-
Genzyme and Merck & Co. for unrestricted financial contribution to the SBDR.
Table 1: Plasma cytokine concentrations significantly different between RA patients and healthy controls at
baseline.
Cytokine Controls (n=30) RA (n=30) Odds Ratios (95% Pvalue
CI) (Wald)
IL-1RA 92 (56-174) 1561 (1175-2607) 1.01(1.00-1.01) 0.0065
CCL11/Eotaxin 23 (17-33) 32 (25-38) 1.08(1.02-1.15) 0.0083
CXCL10/IP-10 10 (8-12) 30 (23-47) 1.30(1.16-1.52) <0.0001
CCL2/MCP-1 19 (15-27) 37 (26-49) 1.07(1.03-1.13) 0.0034
CCL4/MIP-1β 22 (19-27) 180 (166-209) 1.03(1.02-1.05) <0.0001
CCL5/RANTES 24 (20-27) 56 (42-67) 1.04(1.01-1.07) 0.0075
CXCL12a/SDF-1α 396 (349-423) 629 (482-754) 1.01(1.00-1.02) 0.0010
Calprotectin 1398 (1082-1915) 2675 (2171-3968) 1.00(1.00-1.00) 0.0006
IL-21 3(10) 11(37) 5.21(1.41-25.39) 0.0213
IL-22 14 (47) 1(3) 0.04(0.00-0.22) 0.0028
IL-1α 6(20) 16(53) 4.57(1.51-15.35) 0.0094
CXCL1/GRO-α 25(83) 4(13) 0.03(0.01-0.12) <0.0001
Values are presented as median in pg/ml (Quartile 1 – Quartile 3) or N(%)
Table 2: Plasma cytokines less frequently detected in RA patients non-responding to MTX

Cytokine Responders (N=19) Non-responders Odds Ratios (95% P-value (Wald)
CI)
(N=10)
IL-18 24 (15-30) 16 (0-20) 0.93 (0.86-1.00) 0.0745
IL-1α 13(68) 2(20) 0.12 (0.01-0.63) 0.0205
IL-17A 7(37) 0(0) 0.08 (0.00-0.79) 0.12
IL-27 7(37) 0(0) 0.08 (0.00-0.79) 0.12
Values are presented as median in pg/ml (Quartile 1 – Quartile 3) or N(%)
Disclosure: M. Pelletier, None; P. R. Fortin, None; M. P. Longchamps, None; G. Parent, None; H. Benk-Fortin, None;
A. S. Julien, None; N. Amiable, None; E. Rollet-Labelle, None; L. Michou, None; L. Bessette, Amgen, BMS, Janssen,
Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Lilly, Novartis, Sanofi, 8,Amgen, BMS, Janssen, Roche, UCB, AbbVie,
Pfizer, Merck, Celgene, Lilly, Novartis, Sanofi, 5,Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene,
Lilly, Novartis, Sanofi, 2; P. A. Tessier, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/plasma-cytokines-at-diagnosis-may-

predict-non-response-to-methotrexate-in-patients-with-early-rheumatoid-arthritis
Smoking and Opioid Use Is Associated with Symptom Severity in

Angela Karellis1,2, Emmanouil Rampakakis3, John S. Sampalis1,4, Martin Cohen5, Michael Starr5, Peter Ste-Marie6,
Yoram Shir6, Mark Ware6 and MaryAnn FitzCharles6,7, 1JSS Medical Research, St-Laurent, QC, Canada, 2Department
of Surgery, McGill University, Montreal, QC, Canada, 3JSS Medical Research, Montreal, QC, Canada, 4McGill University,
Montreal, QC, Canada, 5Rheumatology, McGill University Health Centre, Montreal, QC, Canada, 6Alan Edwards Pain
Management Unit, McGill University Health Centre, Montreal, QC, Canada, 7Rheumatology, McGill University, Montreal,
QC, Canada
SESSION INFORMATION
Smoking and Opioid Use Is Associated with Symptom Severity in Rheumatoid Arthritis
Background/Purpose: Cigarette smoking, both current and past, is a risk for incident rheumatoid arthritis (RA), even for
those with low exposure rates of 1-10 pack years. As smoking is associated with opioid use in patients with chronic pain,
the aim of the current analysis was to examine disease status for RA patients and the relationship between current cigarette
smoking and opioid use.
Methods: As part of a study to evaluate cigarette and marijuana smoking in rheumatic disease patients, 1000 consecutively
attending rheumatology patients completed an anonymous self-administered questionnaire including: pain severity on
visual analog scale (VAS), patient global assessment (PtGA) and cigarette or marijuana smoking status. Concomitant
physician recorded information included: diagnosis, sociodemographics, co-morbidities, treatments for RA and physician
global assessment (PGA). Patients were categorized according to current smoking status and opioid use. Patient
characteristics were compared between groups with one-way ANOVA.
Results: 248 patients were diagnosed with RA [mean (SD) age = 62.4 (14.3) years and 77.4% female] stratified by
smoking status and opioid use: 9 patients were current smokers and opioid users, 186 patients non-smokers and non-opioid
users, and 53 patients current smokers or opioid users (Table 1). Unemployment/ disability was statistically different
between groups (current smokers & opioid users vs. non-smokers & non-opioid users vs. current smokers or opioid users:
11.1% vs. 3.3% vs. 13.5%; p = 0.015). Current smokers and opioid users reported significantly worse disease, including
higher PGA (p < 0.001), PtGA (p = 0.021) and pain VAS (p = 0.001), followed by current smokers or opioid users. In
regard to medication use, current smokers and opioid users took significantly more medications for disease management (p
< 0.001), specifically NSAIDs (p = 0.019) and anti-epileptics (p = 0.020) with a trend towards more antidepressant use (p =
0.088).
Conclusion: Current smoking and opioid use is significantly associated with increased disease severity and other
medication use, indicating that RA patients who smoke experience greater symptom severity and may use chemical coping
methods to alleviate symptoms.
Table 1. Patient Profile by Smoking Status and Opioid Use
Non-
Current smokers & Current
smokers or
All patients smokers & non-opioid
opioid users p-value
(N=248) opioid users users
(n = 9) (n = 53)
(n = 186)
Age, years, mean (SD) 62.4 (14.3) 59.6 (11.8) 62.9 (15.2) 61.3 (11.3) 0.656
Female gender, n (%) 192 (77.4%) 7 (77.8%) 147 (79.0%) 38 (71.7%) 0.530
Employment
Full-time, n (%) 83 (33.9%) 3 (33.3%) 61 (33.2%) 19 (36.5%)
Part-time, n (%) 8 (3.3%) 0 (0.0%) 4 (2.2%) 4 (7.7%)
Student, n (%) 2 (0.8%) 0 (0.0%) 2 (1.1%) 0 (0.0%)
Demo- 0.116
Unemployed, n (%) 3 (1.2%) 0 (0.0%) 2 (1.1%) 1 (1.9%)
graphics
Disabled, n (%) 11 (4.5%) 1 (11.1%) 4 (2.2%) 6 (11.5%)
Retired, n (%) 119 (48.6%) 4 (44.4%) 94 (51.1%) 21 (40.4%)
Homemaker, n (%) 19 (7.8%) 1 (11.1%) 17 (9.2%) 1 (1.9%)
Employment: unemployed/disabled
Yes, n (%) 14 (5.7%) 1 (11.1%) 6 (3.3%) 7 (13.5%) 0.0151
No, n (%) 231 (94.3%) 8 (88.9%) 178 (96.7%) 45 (86.5%)
Cardiovascular, n (%) 74 (29.8%) 3 (33.3%) 57 (30.6%) 14 (26.4%) 0.816
Pulmonary, n (%) 14 (5.6%) 1 (11.1%) 10 (5.4%) 3 (5.7%) 0.767
Gastrointestinal, n (%) 25 (10.1%) 0 (0.0%) 22 (11.8%) 3 (5.7%) 0.249
Neurological, n (%) 4 (1.6%) 0 (0.0%) 3 (1.6%) 1 (1.9%) 0.917
Comorbid
Endocrine, n (%) 50 (20.2%) 1 (11.1%) 38 (20.4%) 11 (20.8%) 0.787
conditions
Mood disorder, n (%) 26 (10.5%) 2 (22.2%) 18 (9.7%) 6 (11.3%) 0.475
Other psychiatric disorder, n (%) 1 (0.4%) 0 (0.0%) 1 (0.5%) 0 (0.0%) 0.846
Lipid disorder, n (%) 31 (12.5%) 2 (22.2%) 21 (11.3%) 8 (15.1%) 0.508
Other comorbid condition, n (%) 17 (6.9%) 1 (11.1%) 14 (7.5%) 2 (3.8%) 0.556
Number of medication types for rheumatic
2.0 (1.1) 3.6 (1.3) 1.8 (1.0) 2.3 (1.1) < 0.001
disease, mean (SD)
Non-steroidal anti-inflammatory drug use, n
110 (44.4%) 7 (77.8%) 74 (39.8%) 29 (54.7%) 0.019
(%)
Medica- Disease-modifying anti-rheumatic drug use, n 184 (74.2%) 7 (77.8%) 134 (72.0%) 43 (81.1%) 0.398
tions for (%)
rheumatic Biologic use, n (%) 70 (28.2%) 2 (22.2%) 48 (25.8%) 20 (37.7%) 0.216
diseases Opioids use, n (%) 23 (9.3%) 9 (100.0%) 0 (0.0%) 14 (26.4%) < 0.001
Tranquilizer use, n (%) 3 (1.2%) 0 (0.0%) 3 (1.6%) 0 (0.0%) 0.603
Antiepileptic use, n (%) 12 (4.8%) 2 (22.2%) 6 (3.2%) 4 (7.5%) 0.020
Antidepressant use, n (%) 14 (5.6%) 2 (22.2%) 9 (4.8%) 3 (5.7%) 0.088
Steroid use, n (%) 73 (29.4%) 3 (33.3%) 60 (32.3%) 10 (18.9%) 0.163
Physician Global Assessment (PGA) (0-10),
2.7 (2.3) 4.4 (1.6) 2.3 (2.2) 3.8 (2.4) < 0.001
mean (SD)
Disease
Patient Global Assessment (PtGA) (0-10),
assessment 3.2 (2.7) 4.5 (2.5) 2.9 (2.6) 3.9 (2.8) 0.021
mean (SD)
Pain, VAS cm, mean (SD) 4.0 (2.9) 6.6 (2.0) 3.7 (2.7) 4.9 (3.1) 0.001
n (%) 145 (58.5%) 9 (100.0%) 89 (47.8%) 47 (88.7%) < 0.001
Past cigarette use Years, mean (SD)2 26.5 (13.6) 40.0 (13.2) 21.9 (11.4) 32.5 (13.5) < 0.001
Cigarette
use Cigarettes/day, mean (SD)2 15.3 (8.0) 21.1 (12.4) 15.6 (7.7) 13.6 (7.1) 0.042
Current cigarette n (%) 46 (18.7%) 9 (100.0%) 0 (0.0%) 37 (72.5%) < 0.001
use Cigarettes/day, mean (SD)2 13.2 (9.7) 20.1 (12.9) NA 11.5 (8.1) 0.015
Herbal Recreational Ever use, n (%) 35 (14.2%) 3 (33.3%) 22 (11.9%) 10 (19.2%) 0.101
cannabis herbal cannabis
Table 1. Patient Profile by Smoking Status and Opioid Use
Non-
Current smokers & Current
All patients smokers & non-opioid smokers or
(N=248) opioid users opioid users p-value
users
(n = 9)
(n = 53)
(n = 186)
use3 use Current use, n (%) 3 (8.6%) 0 (0.0%) 3 (13.6%) 0 (0.0%) 0.379
Ever use, n (%) 4 4 (1.6%) 0 (0.0%) 2 (1.1%) 2 (3.8%) 0.363
More than 10 times, n (%)4 2 (50.0%) NA 1 (50.0%) 1 (50.0%) > 0.999
Medical herbal Current medical use, n (%)4 2 (50.0%) NA 1 (50.0%) 1 (50.0%) > 0.999
cannabis use If never used, consider
medical herbal cannabis use, 75 (36.2%) 6 (75.0%) 52 (33.5%) 17 (38.6%) 0.055
n (%)5
Current use, n (%) 4 (11.1%) 0 (0.0%) 3 (13.6%) 1 (9.1%) 0.755
Daily grams used, mean (SD) 2.0 (2.8) NA 2.0 (2.8) NA 0.667
Monthly grams used, mean
38.0 (64.1) NA 38.0 (64.1) NA6 0.667
Current herbal (SD)
cannabis use Method of herbal cannabis use
(any reason)7 Smoke, n (%) 4 (100.0%) NA 3 (100.0%) 1 (100.0%) NC
Vaporize, n (%) 1 (25.0%) NA 1 (33.3%) 0 (0.0%) > 0.999
Eat, n (%) 1 (25.0%) NA 1 (33.3%) 0 (0.0%) > 0.999
Rub, n (%) 0 (0.0%) NA 0 (0.0%) 0 (0.0%) NC
Current medical Relief of symptoms, mean
herbal cannabis 6.6 (1.6) NA 7.7 (NC) 5.5 (NC) NC
(0-10) (SD)8
use
NA, not applicable; NC, non calculable.
Significant (p<0.05) p-values indicated in bold. Statistical trends (0.05 < p < 0.15) indicated in italics.
1Between unemployed/disabled and full-time/part-time/student/retired/homemaker patients.
2Among smokers.
3Patients may have used more than one method of herbal cannabis.
4Denominator of this proportion represents the total number of patients who have used herbal cannabis for medical
reasons (n=2).
5Denominator of this proportion represents the total number of patients who have never used herbal cannabis for medical
reasons (n=212).
6Patient reported no daily amount of herbal cannabis, though reported ‘1 gram’ as monthly usage. This was omitted from
the description of the results.
7Proportions and p-values are based on the number of patients currently using herbal cannabis for any reason (All
patients: n=4; Current smokers and opioid users: n=0; Non-smokers and non-opioid users: n=3; Current smokers or
opioid users: n=1).
8Among patients using herbal cannabis for medical reasons. Minimum (0) represents ‘no relief’ and maximum (10)
represents ‘maximum relief”.
Disclosure: A. Karellis, None; E. Rampakakis, None; J. S. Sampalis, None; M. Cohen, None; M. Starr, None; P. Ste-
Marie, None; Y. Shir, None; M. Ware, None; M. FitzCharles, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/smoking-and-opioid-use-is-associated-
with-symptom-severity-in-rheumatoid-arthritis
Initiation of Biologic Disease Modifying Antirheumatic Drug Therapy and

Associated Changes in Disease Activity Measures in Routine Clinical
Practice: Findings from a Large Contemporaneous Real World Cohort
Zhaohui Su1, Tom Brecht1, Anna Lafontant1, Costas Boussios1, Francis O’Donovan2, Charles Kekeh2, Kathryn Starzyk1,
Richard Gliklich3 and Vandana Menon1, 1Research, OM1, Inc, Cambridge, MA, 2Data Science, OM1, Inc, Cambridge,
MA, 3OM1, Inc, Cambridge, MA
SESSION INFORMATION
Background/Purpose:
While many clinical trials provide direct comparisons between biologic disease modifying antirheumatic drugs (bDMARD)
and nonbiologic DMARD (nDMARD), there is a need for additional evidence on the effectiveness of these therapies in
routine clinical practice. We evaluated changes in disease activity measures associated with bDMARD therapy, in a large
cohort of patients with RA, under conditions of routine clinical practice.
Methods:
The OM1 platform collects, links, and leverages, structured and unstructured data from electronic medical records (EMR)
and other sources in an ongoing and continuously updating manner. The OM1 RA Cohort includes data on >75,000 patients
treated by rheumatologists. This analysis included patients who were treated with nDMARD between January 2013 and
April 2017, had not received prior treatment with bDMARD, and either added or switched to another nDMARD or initiated
bDMARD during the observation period (date of change in therapy is the index date). Established American College of
Rheumatology cutpoints for standard disease activity measures (RAPID-3, CDAI, DAS28) were used to define remission.
Advanced natural language processing was used to impute missing disease activity categories. Drug eras were defined
using Observational Medical Outcomes Partnership (OMOP) definitions. Survival analyses were conducted to evaluate
time to initial remission and confirmed remission defined as 2 consecutive scores denoting remission. To reduce the impact
of subsequent treatment changes, data were censored at 12 months. Patients who switched or added nDMARD but
subsequently initiated bDMARDs within 6 months after the index date were excluded in sensitivity analyses. To reduce the
bias that more frequent disease activity measures may be associated with shorter time to remission, we matched the two
groups on average number of disease activity measures per patient.
Results: The analysis cohort included 4,957 patients who met study inclusion criteria, none of whom were in
remission at index date; 1,334 added or switched to another nDMARD and 3,623 added or switched to a bDMARD.
There were an average of 4.2 disease activity measures per patient and a total of 20,605 disease activity measures
during the 12 month study period. A larger proportion of patients in the bDMARD group achieved initial remission
(18% versus 16%, p<0.05) and confirmed remission (13% versus 11%, p<0.05) compared to the nDMARD group.
Time to remission was significantly shorter in the bDMARD group (mean±SD=5.2±3.4 months) compared to the
nDMARD group (5.7±3.2 months, p<0.05). These results were unchanged in the sensitivity analysis.
Conclusion: Disease activity improved with changes in DMARD therapy; however, the addition of bDMARDs were
associated with significantly shorter time to remission. This study uses novel data collection techniques to replicate
findings from prior observational studies in a much larger and contemporaneous cohort of patients under
conditions of routine clinical practice.
Disclosure: Z. Su, None; T. Brecht, None; A. Lafontant, None; C. Boussios, None; F. O’Donovan, None; C. Kekeh,
None; K. Starzyk, None; R. Gliklich, None; V. Menon, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/initiation-of-biologic-disease-

modifying-antirheumatic-drug-therapy-and-associated-changes-in-disease-activity-measures-in-routine-clinical-practice-
findings-from-a-large-contemporaneous-real-world-c
Effect of Patient Involvement in Treatment Decision Making on Disease

Outcomes in Rheumatoid Arthritis in the USA
Richard Hutchings1, Shailja Panchal2 and Elizabeth Baynton1, 1Ipsos Healthcare, London, United Kingdom, 2Ipsos
Healthcare, New York, NY
SESSION INFORMATION
Background/Purpose: ACR guidelines for treating Rheumatoid Arthritis (2015) suggest that treatment decisions should be
made by physicians and patients through a shared decision-making process taking into account patients’ values,
preferences, and comorbidities. Identifying the impact of patient involvement on disease outcomes in biologic patients
would provide further evidence which could support ACR guideline recommendations and be used to inform optimal
disease management.
Methods: A multi-center medical chart review study of patients with RA was conducted in Q4 2016 among physicians in
hospitals and private practices to collect de-identified data on patients who were recently treated with a biologic as part of
usual care in the USA. Physicians were screened for duration of practice (3-30yrs) and patient volume (≥2 RA biologic
patients/week) and recruited from a large access panel to be geographically representative of the country. Eligible patient
charts (≥5) were randomly selected from among the patients visiting each center/practice during the screening period.
Physicians abstracted date of diagnosis, treatment patterns/dynamics, and symptomatology/disease status. Physicians
identified the level of patient involvement in treatment decision making using a 7 point scale, and patient records were
segmented into low-medium involvement (1-4/7) and high involvement (5-7/7). Sites waived local ethics review owing to
collection of retrospective de-identified data. High involvement versus low involvement patients were compared using
descriptive statistics.
Results: 517 biologic RA patients were assessed; overall, Highly involved: 409 (79%), Low-mid involved: 108 (21%).
Patient characteristics (Highly involved/Low-mid involved) included: age (in years) 50/54; full time employment status
57%/42%; co-existing conditions: obesity (14%/28%), dyslipidemia (19%/33%), depression (19%/28%), none (45%/24%).
Time since diagnosis (in months): 52.2/48.3. Among patients with available data, current lab measures included:
ESR(mm/h) 20.3/24.0; CRP(mg/l) 2.8/3.8; rheumatoid factor(positive) 89%/84%; anti-CCP(positive) 80%/72%; measures
of disease severity included: disease severity per physician judgment: mild (72%/53%), moderate (25%/40%), severe
(3%/7%); disease under control 80%/69%; remission 63%/52%; mean DAS 28 2.7/3.2; mean tender joint count 3.4/3.6;
mean swollen joint count 2.3/2.4.
Conclusion: In this cohort of RA patients in the USA, majority of patients with high involvement were seen to be younger,
healthier patients who were full time employees. These patients were significantly more likely to be considered as mild
disease severity (physician judgement) with a higher proportion in remission. Lab measures indicated lower disease burden
with low hematology scores for highly involved patients. Further investigation of the influence of socioeconomic status,
insurance type, and other demographics on patient involvement in treatment may warrant further research.
Disclosure: R. Hutchings, None; S. Panchal, None; E. Baynton, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effect-of-patient-involvement-in-

treatment-decision-making-on-disease-outcomes-in-rheumatoid-arthritis-in-the-usa
Clinical Response to the First Biologic in Rheumatoid Arthritis Patients with

Moderate Disease in a Real World Clinical Cohort
Xiuying Li, Angela Cesta, Mohammad Movahedi and Claire Bombardier, Toronto General Hospital Research Institute,
University Health Network, Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose:
While most randomized trials assess the effectiveness of biologic DMARDs (bDMARDs) in rheumatoid arthritis (RA)
patients with high disease activity, in the real world or routine care, patients with moderate disease activity are often treated
with bDMARDs as well. This study aims to evaluate the effectiveness of the first biologic with or without conventional
synthetic DMARD (csDMARDs) in patients with moderate disease activity.
Methods:
Biologic naïve patients enrolled in the Ontario Best Practices Initiative (OBRI), with moderate disease activity score
(DAS28: >3.2-5.1), or high disease activity score (DAS28: >5.1) were included. Patients were also required to remain on
the biologic for 6 months and to have complete follow up data during this time period. Clinical response to their first
biologic was measured by the change in DAS28 and by the proportion of patients who reached low disease activity (LDA)
during the first 6 months of treatment. The change in DAS28 was assessed using linear regression modelling, adjusted for
potential confounders (age, gender, disease duration, and physician global assessment). Multivariate logistic regression was
used to compare the proportion of patients who reached LDA in each group at 6 months, adjusting for the same potential
confounders.
Results:
The analysis included 443 patients. At initiation of their first biologic, 238 patients had a moderate DAS28 and 205 had a
high DAS28. Patient demographics for the two groups are shown in Table 1. At initiation of their first bDMARD, the two
groups were similar with respect to age, gender, and disease duration. All of the DAS28 components, as well as the
physician global were significantly different between the two groups. A significant change in DAS28 was found in both the
moderate disease group [-0.89 (95% CI -1.12, -0.66)] and the high disease group [-1.86 (95% CI -2.10, -1.62)], with greater
improvement seen in the high disease activity group. A comparison of the change in DAS28 between the two groups was
also significant (0.97±0.16, p<0.0001). After 6 months of biologic treatment, a higher proportion of patients in the
moderate DAS28 group reached LDA, when compared to the high DAS28 group (OR: 1.65; 95%CI: 1.03-2.65, p=0.04).
Table 1. Patient Characteristics at initiation of first bDMARD, by DAS28 group

DAS28 group at Moderate DAS28 High DAS28 P-
bDMARDs start 3.2-5.1 >5.1 value
N 238 205
Age, years 55.3 (13.2) 57.1 (12.9) 0.14
Female n(%) 192 (80.7%) 169 (82.4%) 0.63
Disease duration, years 7.4 (8.8) 6.7 (7.6) 0.36
DAS28 4.18 (0.54) 5.98 (0.63) <0.0001
28 swollen joint count 5.4 (3.7) 9.1 (4.7) <0.0001
28 tender joint count 4.5 (3.5) 12.4 (5.8) <0.0001
ESR, mm/h 19.1 (16.5) 34.3 (22.7) <0.0001
CRP, mg/L 8.7 (15.4) 17.7 (24.6) <0.0001
Patient global 5.0 (2.5) 6.7 (2.2) <0.0001
assessment (0-10)
Physician global 4.6 (2.0) 6.3 (1.8) <0.0001
assessment (0-10)
Rheumatoid factor 160 (72.7%) 143 (75.7%) 0.50
positive n (%)
Previous CsDMARDs 213 (90%) 182 (89%) 0.81
use ≥2 n(%)
Receiving oral steroid, n 50 (21.0%) 37 (18.1%) 0.43
(%)
Values are given as mean (standard deviation) unless otherwise specified.
Conclusion:
Conclusions: Treatment with bDMARDs is effective in patients with moderate disease activity. While patients with high
disease activity showed greater improvement after 6 months of biologic treatment, patients with moderate disease activity
at initiation of a bDMARD were more likely to reach a LDA state.
Disclosure: X. Li, None; A. Cesta, None; M. Movahedi, None; C. Bombardier, Canada Research Chair in Knowledge
Transfer for Musculoskeletal Care Non-remunerativePfizer Research Chair in Rheumatology, 6.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/clinical-response-to-the-first-biologic-

in-rheumatoid-arthritis-patients-with-moderate-disease-in-a-real-world-clinical-cohort
Rheumatoid Arthritis Patients Resistant to Biologic Therapy, Are They

Different?
Adeeba Al-Herz1, Aqeel Ghanem2, Khulood Saleh3, Adel Al-Awadhi4, Waleed Al-Kandari3, Eman Hasan5, Mohammad
Hussain5, Ibrahim Nahar2, Fatemah Abutiban6, Ahmad Alenizi6, Yaser Ali2, Ali Aldei1, Hebah Alhajeri2, Sawsan Hayat2,
Ahmad Khadrawy3, Ammad Fazal3, Khaled Mokaddem1, Agaz Zaman2, Ghada Mazloum2, Youssef Bartella1, Sally
Hamed1, Ramia Alsouk6 and Ahmed Al-Saber7, 1Rheumatology, Al-Amiri Hospital, Kuwait city, Kuwait, 2Rheumatology,
Mubarak Al-Kabeer Hospital, Hawally, Kuwait, 3Rheumatology, Farwania Hospital, Farwania, Kuwait, 4Faculty of
Medicine, Kuwait, Kuwait, 5Al-Amiri Hospital, Kuwait city, Kuwait, 6Rheumatology, Jahra Hospital, Jahra, Kuwait,
7Department of Mathematics, Kuwait Technical College, Kuwait city, Kuwait

SESSION INFORMATION
Background/Purpose: Patients with rheumatoid arthritis (RA) may fail to respond to biologic therapy. We study patients
who are resistant to different classes of biologic agents and compare their clinical and serological features to patients who
are biologic respondents.
Methods: Patient from The Kuwait Registry for Rheumatic Diseases (KRRD) who satisfied the ACR classification criteria
for RA from four major hospitals were studied from February 2013 through May 2017. Patients were divided into two main
groups, biologic therapy resistant defined as patients previously switched from a biologic agent or who are currently not
responding to biologic therapy (DAS28 > 3.2). The second group are patients who are biologic therapy respondents defined
as patients who have been in remission or in low disease activity (DAS28 < 3.2) on biologics for at least three months with
no previous history of any biologic resistance.
Biologic agents were then divided into anti-TNF and non-anti-TNF agents.
In addition, patients who were resistant to >3 biologics were further studied.
Results: Among 1,280 patients with RA, 318(24%) have been prescribed at least one anti-TNF agent sometime during
their disease course. Among them, 194(61%) were resistant to one anti-TNF or more. 554(43%) were prescribed at least
one non-anti-TNF. Among them, 313(56%) were resistant to one non-anti-TNF or more. Of the total resistant patient,
29/507(5.7%) have failed 3 or more biologics.
Comparing the anti-TNF resistant group with the anti-TNF respondents, there was a tendency toward a thyroid disease
(15.5% vs 8.1%,p=0.051) and a lower serum uric acid (means=263 vs 283 µmol/L,p=0.06). Patients who were resistant to
non-anti-TNFs had more females than patients who responded to non-anti-TNFs (78% vs 68.5%, p=0.012) and a lower uric
acid (means=249 vs 267µmol/L, p=0.012). Comparing patients who were resistant to > 3 biologics with patients who are
biologic respondents, resistant patients had more females (93.1% vs 69.4%,p=0.007), more hyperlipidemia (24.1% vs
9.5,p=0.014), more hypertension (41.4% vs 21.4%,p=0.014) and more osteoporosis (24.1 vs 10.4%,p=0.026).
Other factors such as age, age at RA diagnosis, body mass index, rheumatoid factor, anti-cyclic citrullinated peptide
antibodies, ANA, extra-articular features, family history of a rheumatic disease and other co-morbidities including
cardiovascular diseases were comparable between the groups.
Conclusion: RA patients resistant to biologic therapy have some features that are different from patients who are
respondents. Further study of those patients may allow an early recognition aiming at a better planning of treatment and
improving their outcome.
Disclosure: A. Al-Herz, None; A. Ghanem, None; K. Saleh, None; A. Al-Awadhi, None; W. Al-Kandari, None; E.
Hasan, None; M. Hussain, None; I. Nahar, None; F. Abutiban, None; A. Alenizi, None; Y. Ali, None; A. Aldei, None;
H. Alhajeri, None; S. Hayat, None; A. Khadrawy, None; A. Fazal, None; K. Mokaddem, None; A. Zaman, None; G.
Mazloum, None; Y. Bartella, None; S. Hamed, None; R. Alsouk, None; A. Al-Saber, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rheumatoid-arthritis-patients-resistant-

to-biologic-therapy-are-they-different
Viral Hepatitis Influences Patient Reported Outcomes Measures in

Suraj Timilsina1, Harlan Sayles2, Bryant R. England3, James R. O'Dell4, Ted R. Mikuls5 and Kaleb Michaud2, 1Division
of Rheumatology & Immunology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE,
2University of Nebraska Medical Center, Omaha, NE, 3Division of Rheumatology & Immunology, Department of Internal
Medicine, Nebraska-Western IA VA Health Care System & University of Nebraska Medical Center, Omaha, NE,
4Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 5Internal Medicine, Division of
Rheumatology, University of Nebraska Medical Center, Omaha, NE
SESSION INFORMATION
Background/Purpose: Viral hepatitis may complicate the treatment of RA since select DMARD have the potential to
cause hepatotoxicity or reactivation of latent viral infections. Whether treatment patterns and RA outcomes are impacted by
this comorbid condition is not well studied. Similarly, little is known about RA factors and the risk the developing of
hepatitis. Thus, we assessed the associations of viral hepatitis with RA disease outcomes and DMARD use and determined
the RA factors predictive of incident hepatitis.
Methods: We studied participants with RA within the National Data Bank for Rheumatic Diseases (NDB) from 2004 to
2017. Sociodemographic, health behaviors, comorbidities, RA measures, and medications were collected every 6 months
via self-report. Additionally, participants were assessed for current or prior history of viral hepatitis. We used multivariable
linear and logistic regression models to assess associations of prior viral hepatitis with RA outcome measures and
treatments. We also assessed the associations of RA measures and DMARD with incident viral hepatitis using
multivariable Cox proportional hazard regression models.
Results: Among 22,942 participants with RA, current or prior hepatitis was self-reported present in 207 (Hepatitis A), 165
(Hepatitis B), and 317 (Hepatitis C). Adjusting for age, sex, employment, education level, comorbidity index, smoking,
alcohol and drug use, patients with prior hepatitis B and C had higher pain scores while patients with hepatitis C had higher
patient activity scale (PAS) scores. Hepatitis C was also marginally associated with higher patient global assessment scores.
MTX use was less frequent in those with hepatitis B and C while the use of NSAIDs and biologics did not differ between
groups (Table 1). Over 90,952 patient-years of follow-up, 132 patients developed incident viral hepatitis. After
multivariable adjustment, higher pain and PAS scores were independently associated with an increased risk of viral
hepatitis (Table 2). Biologics were not associated with incident viral hepatitis while MTX was associated with a lower risk
of incident hepatitis. To assess whether misclassification of prevalent hepatitis as incident hepatitis was occurring, we used
a 6-month lag for viral hepatitis diagnosis, finding similar results.
Conclusion: History of viral hepatitis infection is associated with worse RA patient reported outcomes measures and lower
use of MTX. Clinicians should be aware of the potential for viral hepatitis to influence patient reported outcomes measures
in RA. Reassuringly, biologic DMARD do not appear to increase the risk of incident viral hepatitis.
Table 1: Association of viral hepatitis with RA
outcomes and treatment
Outcome Hepatitis A Hepatitis B Hepatitis
C
Linear regression
HAQ 0.01 (-0.09, 0.02 (-0.84, 0.05 (-0.03,
0.11) 0.13) 0.12)
Pain scale -0.02 (-0.40, 0.59 (0.18, 0.48 (0.18,
0.36) 1.01)* 0.79)*
Patient global 0.01 (-0.31, 0.26 (-0.12, 0.28 (-0.05,
0.34) 0.63) 0.56)
Patient activity 0.01 (-0.28, 0.31 (-0.07, 0.30 (0.06,
score 0.29) 0.62) 0.55)*
SF-36 Physical -0.17 (-1.60, -1.23 -0.58
Summary 1.26) (-2.96, (-1.88,
0.49) 0.71)
SF-36 Mental -1.37 (-3.25, -0.92 -0.93
Summary 0.51) (-3.03, (-2.32,
1.20) 0.47)
Logistic regression
Methotrexate 0.83 (0.63, 0.42 (0.30, 0.60 (0.47,
1.10) 0.59)* 0.76)*
Leflunomide 0.83 (0.51, 0.64 (0.34, 0.87 (0.59,
1.35) 1.81) 1.29)
Biologic 1.02 (0.77, 0.90 (0.65, 0.95 (0.75,
1.34) 1.23) 1.19)
Any NSAID 0.93 (0.70, 0.84 (0.61, 0.99 (0.79,
1.23) 1.16) 1.25)
Prednisone 1.11 (0.82, 0.58 (0.40, 0.93 (0.72,
1.50) 0.84)* 1.20)
Values β or Odds ratio (95%CI)
* p <0.05
Parameters assessed in separate models, each adjusted

for age, sex, employment, education level, comorbidity
index, smoking, alcohol and drug use
Table 2: Association of RA measures and
treatments with incident viral hepatitis
Hazard
Variable 95%CI p-value
Ratio
RA disease 0.98,
1.00 0.578
duration (years) 1.01
0.88,
HAQ 1.12 0.356
1.41
1.00,
Pain scale (0-10) 1.06 0.039
1.13
Patient global 0.98,
1.05 0.115
(0-10) 1.12
Patient activity 1.00,
1.07 0.046
score (0-10) 1.15
SF-36 Physical 0.95,
0.98 0.022
summary 0.99
SF-36 Mental 0.96,
0.98 0.040
summary 0.99
0.40,
Methotrexate 0.58 0.003
0.83
0.61,
Leflunomide 1.05 0.728
1.79
0.66,
Biologic 0.93 0.693
1.31
0.89,
Any NSAID 1.25 0.193
1.77
0.93,
Prednisone 1.34 0.109
1.93
Parameters assessed in separate models,
each adjusted for age, sex, employment,
education level, comorbidity index,
smoking, alcohol and drug use
Disclosure: S. Timilsina, None; H. Sayles, None; B. R. England, None; J. R. O'Dell, Medac, 5,Coherus, 5; T. R. Mikuls,
BMS, 2,Ironwood Pharm, 2,Pfizer Inc, 5,NIH, VA, 2; K. Michaud, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/viral-hepatitis-influences-patient-

reported-outcomes-measures-in-rheumatoid-arthritis
Medication Utilization Patterns of Rheumatoid Arthritis Patients Receiving

Anti-TNF Infusion in Community Rheumatology Practices in the United
States: Will Differences in Dosing and Administration Efficiencies between
Intravenous Golimumab and Infliximab Have a Cost Impact for Payers?
Sergio Schwartzman1, Lorie A. Ellis2, Dennis Parenti3, Shawn Black3, Stephen Xu4, Wayne Langholff4 and Shelly
Kafka3, 1Weill Cornell Medical College, New York, NY, 2Janssen HECOR Immunology, Horsham, PA, 3Janssen Scientific
Affairs, LLC, Horsham, PA, 4Janssen Research & Development, LLC, Spring House, PA
SESSION INFORMATION
Background/Purpose: AWARE (Comparative and Pragmatic Study of Golimumab IV Versus Infliximab in Rheumatoid
Arthritis) is an ongoing Phase 4 comparator study designed to provide a real-world assessment of intravenous golimumab
(GLM) and infliximab (IFX) in patients (pts) with rheumatoid arthritis (RA). Although the primary objective of AWARE is
to compare the proportion of GLM and IFX pts with an infusion reaction, RA medication utilization patterns and biologic
infusion times are collected for purposes of conducting dosing and cost analyses. Although cost and managed care
coverage are frequently cited by practicing rheumatologists as variables involved in therapeutic choices, data is lacking in
the published literature. Here we report on GLM and IFX drug utilization patterns from an interim analysis (IA) of the
ongoing AWARE study.
Methods: AWARE is a prospective, noninterventional, observational, multicenter 3-year study conducted at 100 sites in the
US. RA pts (1,200 adults) will be enrolled at the time of initiating treatment with either GLM or IFX. All treatment
decisions including prescribed dose, administered drug amount and dosing interval are made at the discretion of the treating
rheumatologist. Infusion duration was reported by the site. Data shown are mean ± standard deviation.
Results: 421 GLM pts and 326 IFX pts were included in the IA. GLM pts were 61.0 ±12.97 years and IFX pts were 57.2
±13.02 years. Body weight of GLM pts was 85.3 ± 24.6 kg and body weight of IFX pts was 85.5 ± 23.3kg. BMI of GLM
pts was 32.2 ± 13.4 kg/m2 and BMI of IFX pts was 31.7 ± 9.5 kg/m2. Of GLM pts, 34.7% were bionaïve and 49.7% of IFX
pts were bionaïve. The % of GLM and IFX pts with prior exposure to 1 or 2 biologics was similar (data not shown),
however exposure to ≥3 biologics was 19.2% of GLM pts compared to 9.8% of IFX pts. GLM and IFX were infused at a
rheumatologist practice (95.0% and 96.3%, respectively). GLM pts received 1434 infusions at 2.00 ± 0.08 mg/kg, and IFX
pts received 1328 infusions at 3.71 ± 1.21 mg/kg. The duration of GLM infusions was 0.65 ± 0.23 hours and IFX infusions
was 2.0 ± 0.46 hours. There was a significant (p<0.0001) difference in the % of pts with a reported dose increase from
baseline between GLM and IFX (2.6% vs 32.2%, respectively).
Dose Range:
Prescribed Dose: mg/kg (n) Administered Dose (mg) (n)
mg/kg
Inf #* GLM IFX GLM IFX GLM IFX
2.0 ± 0.08 3.36 ± 0.74 1.0 – 172.1 ± 50.3 298.5 ± 96.7
1 2.0 – 7.0
(417) (323) 3.0 (421) (326)
2.0 ± 0.07 3.38 ± 0.73 1.0 – 173.0 ± 51.5 303.0± 99.9
2 2.0 – 7.0
(364) (304) 2.5 (366) (307)
2.0 ± 0.08 3.53 ± 0.92 1.0 – 174.3 ± 53.9 319.3 ± 117.5
3 3.0 – 8.0
(280) (265) 2.7 (282) (267)
2.0 ± 0.01 3.99 ± 1.32 2.0 – 182.2 ± 75.4 359.5 ± 158.3
4 3.0 -10.0
(187) (188) 2.1 (187) (189)
2.0 ± 0.00 4.38 ± 2.0 – 3.0 – 173.3 ± 48.3 393.3 ± 171.0
5
(117) 1.57(129) 2.0 10.0 (117) (130)
2.0 ± 0.00 4.65 ± 1.86 2.0 – 2.0 – 170.7 ± 46.3 421.2 ± 202.7
6
(47) (65) 2.0 10.0 (47) (65)
2.0 ± 0.0 0 5.06 ± 2.13 2.0 – 157.3 ± 46.0 445.6 ± 245.5
7 3.0 -10.0
(12) (29 ) 2.0 (12) (29)
* Inf # = Infusion number
Conclusion: This IA of the AWARE study, reported on drug and administration utilization characteristics of GLM and IFX.
While the dose of GLM was not reported to change over the course of the first 7 infusions, among pts with 7 infusions the
mean dose of IFX increased by approximately 152% between the first and seventh dose. IFX dose escalation was evident at
the third dose. These data provide evidence that in a real-world rheumatology practice setting, the dose of GLM remains
constant, whereas the dose of IFX is more variable and the mean infusion time of GLM was consistently shorter compared
to IFX. The AWARE study will utilize these data to assess the relative cost effectiveness of GLM relative to IFX.
Disclosure: S. Schwartzman, AbbVie, Antares, Genentech, Janssen, Lilly, Novartis, Pfizer, Regeneron, Sanofi, UCB,
5,AbbVie, Janssen, Genentech, Pfizer, UCB, Crescendo, Novartis, 8,Crescendo Biosciences, Discus Analytics, National
Psoriasis Foundation, 6; L. A. Ellis, Janssen, 3,Johnson & Johnson, LLC, 1; D. Parenti, Janssen, 3,Johnson & Johnson,
LLC, 1; S. Black, Janssen, 3,Johnson & Johnson, LLC, 1; S. Xu, Janssen, 3,Johnson & Johnson, LLC, 1; W. Langholff,
Janssen, 3,Johnson & Johnson, LLC, 1; S. Kafka, Janssen, 3,Johnson & Johnson, LLC, 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/medication-utilization-patterns-of-

rheumatoid-arthritis-patients-receiving-anti-tnf-infusion-in-community-rheumatology-practices-in-the-united-states-will-
differences-in-dosing-and-administration-eff
Comparison of Tofacitinib Efficacy in Patients with Moderate Vs Severe

Rheumatoid Arthritis: Pooled Analysis of Phase 3 Studies
Sergio Schwartzman1, Prashanth Sunkureddi2, Liza Takiya3, Mark Snyder3, Haiyun Fan4, Tatjana Lukic5, Jacqui
Roberts6 and William F C Rigby7, 1Hospital for Special Surgery, New York, NY, 2Clear Lake Rheumatology, Nassau Bay,
TX, 3Pfizer Inc, Collegeville, PA, 4Pfizer Inc, Groton, CT, 5Pfizer Inc, New York, NY, 6Pfizer Inc, Tadworth, United
Kingdom, 7Geisel School of Medicine at Dartmouth, Lebanon, NH
SESSION INFORMATION
Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We
evaluated tofacitinib 5 and 10 mg twice daily (BID) efficacy in patients (pts) with moderate vs severe RA.
Methods: Tofacitinib 5 and 10 mg BID efficacy data were from 6 randomized, double-blind Phase 3 studies of 6–24
months’ (Mos) duration. Pts received tofacitinib as monotherapy (NCT00814307 ORAL Solo; NCT01039688 ORAL Start)
or with csDMARDs, mainly MTX (NCT00960440 ORAL Step; NCT00847613 ORAL Scan; NCT00856544 ORAL Sync;
NCT00853385 ORAL Standard). Pts receiving MTX monotherapy (ORAL Start) or placebo (PBO) (±csDMARDs) were
combined as a single PBO group. Baseline (BL) disease severity was classified as moderate or severe using Disease
Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28: moderate 3.2–≤5.1; severe >5.1) and Clinical Disease
Activity Index (CDAI; moderate 10–≤22; severe >22). Mo 3 efficacy outcomes included: pts (%) achieving low disease
activity (LDA; DAS28≤3.2, CDAI ≤10), remission (REM; DAS28<2.6, CDAI ≤2.8), HAQ-DI <0.5 (normal physical
functioning), HAQ-DI improvement >0.22, and mean change from BL (Δ) in DAS28, CDAI, and HAQ-DI. This post-hoc
analysis had no multiplicity adjustments.
Results: More pts had severe disease at BL by DAS28 (91.8%) and CDAI (90.7%). Mo 3 efficacy outcomes for pts were
classified by BL DAS28 disease severity (Table). BL characteristics were balanced between treatment groups in each
disease severity category (Table). In general, Mo 3 efficacy was significantly greater for tofacitinib 5 and 10 mg BID vs
PBO, regardless of BL disease severity. Larger proportions of tofacitinib-treated pts with moderate vs severe BL RA
achieved LDA by either DAS28 (32.3–36.7% vs 13.8–19.1%) or CDAI (49.2–55.0% vs 26.0–31.7%). A higher proportion
of pts achieved REM in the moderate vs severe BL groups by DAS28 (20.0–22.8% vs 6.2–9.0%) or CDAI (11.5–12.1% vs
5.1–6.7%). A greater proportion of pts achieved HAQ‑DI <0.5 with moderate vs severe RA classified by BL DAS28 (45.0–
60.6% vs 24.5–30.0%) or BL CDAI (40.8–52.4% vs 24.7–30.4%). Pts with severe vs moderate RA had greater
improvements from BL in disease activity and HAQ-DI when classified by BL DAS28 (Table), and by BL CDAI
(tofacitinib 5/10 mg BID ΔCDAI: -21.1/-23.0 vs -8.1/-9.4; ΔHAQ‑DI: -0.5/-0.6 vs -0.3/-0.4).
Conclusion: Tofacitinib 5 and 10 mg BID demonstrated efficacy in treating pts with moderate and severe RA with >7
years’ mean disease duration. By Mo 3, pts with severe vs moderate BL disease activity had greater improvements in
disease activity and physical functioning; higher proportions of pts with moderate vs severe BL disease activity achieved
REM, LDA, or normal physical functioning. This post-hoc analysis may be limited by the smaller sample size of the
moderate disease group and the combining of mono- and combination-therapy results.
Disclosure: S. Schwartzman, AbbVie, Antares, Eli Lilly, Genentech, Janssen, Novartis, Pfizer Inc, Regeneron, Sanofi,
UCB, 5,Crescendo Bioscience, Discus Analytics, National Psoriasis Foundation, 6,AbbVie, Crescendo Bioscience,
Genentech, Janssen, Pfizer Inc, UCB, 8; P. Sunkureddi, Pfizer Inc, 5,Pfizer Inc, 8; L. Takiya, Pfizer Inc, 1,Pfizer Inc, 3;
M. Snyder, Pfizer Inc, 1,Pfizer Inc, 3; H. Fan, Pfizer Inc, 1,Pfizer Inc, 3; T. Lukic, Pfizer Inc, 1,Pfizer Inc, 3; J. Roberts,
Pfizer Inc, 1,Pfizer Inc, 3; W. F. C. Rigby, Amgen, Pfizer Inc, Roche, 2,Bristol-Myers Squibb, Eli Lilly, Pfizer Inc, Roche,
5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/comparison-of-tofacitinib-efficacy-in-

patients-with-moderate-vs-severe-rheumatoid-arthritis-pooled-analysis-of-phase-3-studies

Rheumatoid Arthritis Patient Characteristics Also Predict Response to
Therapy with Biologic Agents: Results from the Corrona Certain Study
Dimitrios A. Pappas1, James Murray2, Carol J. Etzel1, David R Nelson2, Bernice Gershenson3, Katherine C. Saunders1,
Sabrina Rebello1 and Joel Kremer4, 1Corrona, LLC, Southborough, MA, 2Eli Lilly and Company, Indianapolis, IN,
3University of Massachusetts Medical School, Worcester, MA, 4Albany Medical College and The Center for
Rheumatology, Albany, NY
SESSION INFORMATION
Background/Purpose: Response to biologic agents approved for RA may be associated with patient reported factors that
are not related to disease and usually not included in studies attempting to predict response to therapy. The objective was to
evaluate whether such factors can influence the probability of response to biologic agents and persistency of therapy.
Methods: Patients with RA initiating a biologic agent while in moderate or high disease activity (based on CDAI levels)
were eligible for participation in the Corrona-CERTAIN comparative effectiveness study and were included in the analysis.
ENSEMBLE Minimum Data Set (MDS), which is comprised of 10 patient (pt) reported scales not specific to RA, (such as
income levels, depression, perceived stress and depression, social support, education) was used to evaluate prediction of
response to biologic agents in combination with factors collected in the Corrona registry (“traditional factors”).
ENSEMBLE components were measured at time of initiation of biologic. Response to biologic therapy was evaluated at 6
months as achievement of low disease activity (LDA). Persistency was estimated using the Kaplan-Meier method.
Associations of response to therapy and persistency with baseline values of ENSEMBLE components were assessed based
on logistic and Cox regression, respectively. To determine whether ENSEMBLE components added value to “traditional”
disease related factors in predicting response, Akaike information criterion (AIC) and Bayesian information criterion (BIC)
were evaluated for the three models: mix of “traditional” and ENSEMBLE variables; traditional variables only; and
emphasis of ENSEMBLE over traditional variables. The resulting response and persistency models with lowest AIC and
BIC were identified and further evaluated for discriminatory power.
Results: Analysis included 2152 biologic initiations in moderate or high disease activity. At 6 months, 682 patients had
achieved LDA (responders) and 1470 had not (non-responders). Of the responders, 58% were treated with a TNF inhibitor
and 37% were biologic naïve prior to enrollment in CERTAIN, vs 49% and 30% of non-responders respectively. Of the
three response models, the best AIC and BIC values corresponded to the logistic model that emphasized ENSEMBLE over
traditional variables and the discriminatory power for this model was comparable (72.6%) to the other two models (72%
and 72.5%).%) in predicting response to therapy. For time to discontinuation of biologic, the emphasized ENSEMBLE
model was again the best in terms of lowest AIC and BIC and discriminatory power (C-statistic) was comparable (60.8% to
59.7% and 61.7%).
Conclusion: The generic, non-disease specific set of scales of ENSEMBLE added value to models predicting response to
therapy of RA with biologic agents. Such factors may allow a refined assessment of patient heterogeneity beyond
traditionally used disease specific measures and have a similar performance in predicting therapy response and persistency
with traditional factors.
Disclosure: D. A. Pappas, Corrona, LLC, 3,Novartis Pharmaceutical Corporation, 9; J. Murray, Eli Lilly and Company,
1,Eli Lilly and Company, 3; C. J. Etzel, Corrona, LLC, 3,Merck Human Health, 9; D. R. Nelson, Eli Lilly and Company,
1,Eli Lilly and Company, 3; B. Gershenson, None; K. C. Saunders, Corrona, LLC, 3; S. Rebello, Corrona, LLC, 3; J.
Kremer, Corrona, LLC, 1,Corrona, LLC, 3,AbbVie, Amgen, BMS, Genentech, Lilly, Regeneron, Sanofi, Pfizer, 5,AbbVie,
Genentech, Lilly, Novartis, Pfizer, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rheumatoid-arthritis-patient-
characteristics-also-predict-response-to-therapy-with-biologic-agents-results-from-the-corrona-certain-study
Novel Interaction between Anti-Citrulline Monoclonal Antibodies and

Apoptotic Cells Is Mediated through Citrullinated Nuclear Antigens
Katy A. Lloyd1, Peter Sahlström2, Johanna Steen1, Philip J. Titcombe3,4, Diana Zhou1, Christina Lundqvist5, Olov
Ekwall6,7, Jimmy Ytterberg1, Johan Rönnelid8, Daniel L. Mueller3, Lars Klareskog1, Vivianne Malmström1 and Caroline
Grönwall9, 1Dept. of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm,
Sweden, 2Dept. of Medicine, Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden, 3Dept. of Medicine,
University of Minnesota Medical School, Minneapolis, MN, 4Dept. of Medicine, Rheumatology Unit, Karolinska Institutet,
Karolinska University Hospital, Sweden, Sweden, 5Dept. of Rheumatology and Inflammation Research, Institute of
Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden, 6Dept. of Rheumatology and
Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg, Göteborg, Sweden, 7Dept
of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden,
8Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden, 9Dep. of Medicine,
Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
SESSION INFORMATION
Session Title: Rheumatoid Arthritis – Human Etiology and Pathogenesis Poster I
Background/Purpose:
Anti-citrullinated protein antibodies (ACPA) display broad cross-reactivities and target proteins including a-enolase,
filaggrin, vimentin, fibrinogen, and histones. However, every monoclonal ACPA has a distinct recognition pattern.
Citrullination occurs during physiological processes such as NETosis and apoptosis, yet the interaction of ACPA with
nuclear antigens in apoptotic cells has not been previously investigated. Apoptotic cells, and especially defects in clearance
of apoptotic and dead cells resulting in increased exposure to nuclear antigens, have been postulated to play a pivotal role
in the pathogenesis of autoimmune disease.
Methods:
We screened a total of 12 recombinant monoclonal human ACPA-IgG, derived from synovial plasma cells or circulating
memory B cells, and two control mAb for binding to full-length citrullinated histones by ELISA. Apoptotic cell binding
was determined by flow cytometry and Western blotting, followed by mass spectrometry to identify key antigen targets.
Fluorescent microscopy was performed to screen ACPA staining in anti-nuclear antibody (ANA)-Hep-2 tests and for
binding to human thymus tissue. A total of 210 seropositive and 50 seronegative RA patients and 157 population controls
from the EIRA case-control cohort, were screened for IgG reactivity against full-length native and citrullinated histone 2B
(Cit-H2B) by ELISA. Reactivity to citrullinated peptides was determined by antigen microarray multiplex assay.
Results:
A distinct subset of ACPA bound apoptotic cells of human and murine origin. We could also observe nuclear staining for
these ACPA in human thymus tissue, and ANA positivity with a nuclear dense fine speckled staining pattern. Mass
spectrometry revealed that H2B was the pre-dominant target within apoptotic cells. The ANA-positive ACPA had strong
recognition of citrullinated histones (H2B, H4). Among CCP2-positive RA patients, 26% were positive for elevated anti-
cit-H2B normalized for reactivity to native H2B, and the titer correlated the strongest with binding to citrullinated filaggrin
and fibrinogen peptides (R=0.4, p<0.0001). We also observed a weak correlation with disease activity in seropositive RA
(R=0.20, p=0.02). Interestingly, 32% seronegative RA patients had autoreactivity to native H2B compared to 4.5%
(p<0.0001) among controls, while there was no elevation in reactivity to cit-H2B normalized for native H2B (4% compared
to 4.5% in controls).
Conclusion:
Interactions between ACPA and citrullinated histones facilitate apoptotic cell binding. We hypothesize that this may be a
key functional feature in RA pathogenesis.
Disclosure: K. A. Lloyd, None; P. Sahlström, None; J. Steen, None; P. J. Titcombe, None; D. Zhou, None; C.
Lundqvist, None; O. Ekwall, None; J. Ytterberg, None; J. Rönnelid, None; D. L. Mueller, None; L. Klareskog, None;
V. Malmström, None; C. Grönwall, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/novel-interaction-between-anti-

citrulline-monoclonal-antibodies-and-apoptotic-cells-is-mediated-through-citrullinated-nuclear-antigens
Monoclonal ACPA-IgG Feature Extensive Fab Glycosylation

Katy A. Lloyd1, Johanna Steen1, Philip J. Titcombe2,3, Khaled Amara4, Diana Zhou1, Lena Israelsson5, Susanna L.
Lundström6, Daniel L. Mueller3, Lars Klareskog1, Vivianne Malmström1 and Caroline Grönwall7, 1Dept. of Medicine,
Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, 2Dept. of Medicine,
Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Sweden, Sweden, 3Dept. of Medicine,
University of Minnesota Medical School, Minneapolis, MN, 4Department of Medicine, Rheumatology Unit, Karolinska
Institutet, Stockholm, Sweden, 5Dept. of Medicine, Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden, 6Dept.
of Medical Biochemistry and Biophysics, Division of Physiological Chemistry, Karolinska Institutet, Stockholm, Sweden,
7Dep. of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
SESSION INFORMATION
Background/Purpose:
Fab-glycosylation is found in ~15-25% serum IgG and while its exact consequence remains unknown, it may alter IgG
functionality. Recent data revealed elevated Fab-glycosylation in polyclonal anti-citrullinated protein autoantibodies
(ACPA) from rheumatoid arthritis (RA) patients. Herein, we characterize the Fab-glycan profile of monoclonal ACPA.
Methods:
A total of 14 recombinant human ACPA, derived from RA synovial plasma cells or circulating memory, were evaluated for
predicted N-linked glycosylation sites using the NetNGlyc server. Fab-glycosylation was verified with enzymatic digestion,
Western blot, lectin-ELISA, and mass spectrometry. Antigen binding was investigated by CCP3 ELISA. VH-VL structure
models were generated using the PIGS tool and the GlyProt server. The frequency of predicted VH-VL sites was compared
to single-cell paired heavy and light chains from extensively mutated mAbs (>15 mutation in VH or VL): 51 expressed
non-ACPA synovial B cells from seropos. RA, and 27 from seroneg. RA, and 198 bone marrow (BM) plasma cells, and 27
clones from healthy control circulating memory. These were compared to 19 highly-mutated broadly-neutralizing (bn) HIV
mAbs and 103 plasmodium faciparium (PF) specific mAbs from the literature. Fisher’s exact test or Kruskal-Wallis test
was used in statistical analysis.
Results:
The majority of ACPA exhibited variable region N-linked motifs (85.7%), compared to 18.5% in control (p<0.0001),
21.2% in RA BM plasma cells (p<0.0001), 31.4% non-ACPA synovial RA mAbs (p=0.0005), 7.4% of clones from
seroneg. RA (p<0.0001), 25.2% in PF mAbs (p<0.0001), and 63.2% of HIV bnAbs (p=0.24), featured in both framework
and CDRs generated by somatic hypermutation (SHM). Indeed, ACPA displayed high level of SHM (average 30 VL and
52 VH), yet when adjusted for SHM, N-linked motifs were significantly elevated in ACPA compared to all groups
including bnAbs. IgG mAb characterization revealed that N-linked motifs were indeed glycosylated, although preliminary
data suggested that glycans had no striking effect on antigen-binding. Homology-based structures predicted glycans to be
primarily positioned outside of the potential antigen-binding site. Lectin analysis and mass spectrometry suggested that
ACPA mAb Fab-glycan composition was distinctly different from Fc-glycans, and could have high sialic acid content.
Conclusion:
The results support that Fab glycosylation is a key feature of ACPA. Significant increases in N-linked motifs in ACPA
compared to other highly-mutated antibodies signifies that this is not solely associated to mutation frequency. Future
studies are merited to further investigate the selection mechanisms and functional role of Fab-glycosylated autoantibodies
Disclosure: K. A. Lloyd, None; J. Steen, None; P. J. Titcombe, None; K. Amara, None; D. Zhou, None; L. Israelsson,
None; S. L. Lundström, None; D. L. Mueller, None; L. Klareskog, None; V. Malmström, None; C. Grönwall, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/monoclonal-acpa-igg-feature-extensive-

fab-glycosylation
Ectopic Lymphoid Tissue in the Lung Is Uniquely Associated with the ACPA
IgA Isotype Even in Absence of Classifiable RA
Lindsay B. Kelmenson1, M. Kristen Demoruelle1, Carlyne D. Cool2 and Kevin D. Deane1, 1Rheumatology Division,
University of Colorado Denver, Aurora, CO, 2Pathology, University of Colorado Denver, Aurora, CO
SESSION INFORMATION
Background/Purpose:
Antibodies to citrullinated protein antigens (ACPA) precede the development of rheumatoid arthritis (RA) and may be
generated in the lung of established and preclinical RA patients. An association has been demonstrated between serum
ACPA and ectopic lymphoid tissue (ELT) in the lung of RA and non-RA patients with lung disease, suggesting that ELT
may be a mechanism for ACPA generation in the lung (Rangel-Moreno 2016, Brown ACR 2015, Abstract #963). To further
explore the mucosal basis of ACPA, we examined ACPA isotypes and lung histopathology in patients with and without RA.
Methods:
Using materials from the NIH's Lung Tissue Resource Consortium (LTRC) we evaluated lung biopsies and serum samples
from 10 RA patients with interstitial lung disease (RA-ILD), 30 non-RA patients with ILD (Non-RA ILD) and 35 non-RA
patients with emphysema or airway disease (Non-ILD). Serum was tested for IgA and IgG ACPA isotypes using the CCP3
antigen plate (Inova, research only). Lung tissue was evaluated by a pathologist blinded to patientsÕ clinical status to
determine the presence of ELT defined as germinal centers (GCs) or lymphoid aggregates. Logistic regression was used to
determine associations of isotype levels with ELT.
Results:
Patients' characteristics are presented in the Table. There were significantly higher mean IgG ACPA levels in RA cases
compared to non-RA patients (Figure). Mean IgA ACPA levels were higher compared to IgG in non-RA ILD (83.2 vs.
26.6) and non-ILD patients (40.3 vs. 5.3), although in RA patients, there was no significant difference in isotype levels
(Figure). There was an association between serum IgA ACPA levels and ELT in all subjects (p=0.01), but not IgG.
Smoking, age, and gender were not significantly associated with ELT; however, RA was significantly associated with ELT
(p=0.03). To evaluate the relationship between serum ACPA isotypes and ELT in absence of RA, an analysis of only non-
RA subjects showed that IgA ACPA levels remained significantly associated with ELT (OR 1.14 for every 10-unit increase
in IgA; 95% CI 1.01-1.28; p=0.02).
Conclusion:
Our findings support a link between serum ACPA and lung ELT. Given the strongest association was seen between ELT
and IgA ACPA for non-RA subjects, it may be that IgA ACPA are related to ELT even in absence of articular disease. The
strong association of IgG ACPA with RA may indicate that this isotype is a marker for RA-specific articular processes.
Future studies should assess the mechanisms underlying these findings, and how differentiating IgA and IgG ACPA may
help in the management of RA and non-RA patients with lung disease.
Disclosure: L. B. Kelmenson, None; M. K. Demoruelle, None; C. D. Cool, None; K. D. Deane, Inova Diagnostics, Inc.,
5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/ectopic-lymphoid-tissue-in-the-lung-is-

uniquely-associated-with-the-acpa-iga-isotype-even-in-absence-of-classifiable-ra
Protein Carbamylation Is Induced By Activated Neutrophil: Ex Vivo

Analysis
Shuichiro Nakabo1, Koichiro Ohmura1, Shuji Akizuki1, Nobuo Kuramoto1, Kosaku Murakami2, Ran Nakashima2,
Motomu Hashimoto3, Hajime Yoshifuji1, Masao Tanaka3 and Tsuneyo Mimori1, 1Department of Rheumatology and
Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 2Clinical Immunology and
Rheumatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 3Department of Advanced Medicine for
Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan
SESSION INFORMATION
Protein carbamylation is induced by activated neutrophil: ex vivo analysis
Background/Purpose:
Anti-carbamylated protein (anti-CarP) antibodies were reported to be detected in 45% of rheumatoid arthritis (RA) patients
[1]. We previously reported that carbamylated albumin (CarALB) was one of the target antigens of anti-CarP antibodies,
and serum myeloperoxidase (MPO) level was elevated in rheumatoid arthritis patients with anti-CarALB antibody [2].
Protein carbamylation occurs by cyanate which MPO produces from thiocyanate (SCN-) and hydrogen peroxide (H2O2),
and MPO abundantly exists in neutrophil. Therefore, neutrophil is a strong candidate for the production of carbamylated
antigen. The purpose of this study is to demonstrate that activated neutrophil induces protein carbamylation.
Methods:
Human neutrophils were isolated from whole blood by ficoll-dextran methods. They were pre-treated for 30 min at 37ºC in
RPMI medium with or without 10ƒÊM diphenyleneiodonium (DPI), which inhibits NADPH-dependent reactive oxygen
species (ROS) production. Subsequently, they were incubated overnight at 37 ºC in RPMI medium containing 0.01mg/mL
ALB with or without 10ƒÊM DPI, 20nM phorbol 12-myristate 13-acetate (PMA) and 100ƒÊM potassium thiocyanate
(KSCN). Then proteins in the medium were collected by trichloroacetic acid/acetone precipitation. The carbamylation of
ALB was confirmed by Western blotting using anti-carbamyl-lysine (CBL) polyclonal antibody. MPO in the medium was
detected by Western blotting using anti-MPO polyclonal antibody.
Results:
ALB was carbamylated only when both neutrophil and KSCN were present (Figure 1, lanes 4 and 5). Although the
carbamylation occurred in the medium both with and without PMA, the level of the carbamylation was much higher in the
medium with PMA (lane 5) than without PMA (lane 4). Carbamylation was inhibited by the presence of DPI, which
diminishes ROS (lanes 7 and 8). MPO was released into the culture supernatant from the neutrophils (Figure 2, lane 2), and
its release was accelerated by PMA (lanes 3 and 5), but attenuated by DPI (lanes 7 and 8).
Conclusion:
ALB in the culture medium was carbamylated by neutrophil. Given that PMA induces ROS production of neutrophil, and
this reaction subsequently increases the MPO release, our data suggest that carbamylation is dependent on ROS and MPO
from neutrophil. Addition of KSCN was necessary. This is the first report that showed direct relationship between
neutrophil and protein carbamylation.
Reference:
[1] Shi J. Proc Natl Acad Sci U S A. 2011. [2] Nakabo S. Rheumatology (Oxford). 2017.
Figure 1: Western blotting of carbamylated albumin
Figure 2: Western blotting of MPO
Disclosure: S. Nakabo, None; K. Ohmura, None; S. Akizuki, None; N. Kuramoto, None; K. Murakami, None; R.
Nakashima, None; M. Hashimoto, None; H. Yoshifuji, None; M. Tanaka, None; T. Mimori, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/protein-carbamylation-is-induced-by-

activated-neutrophil-ex-vivo-analysis

ANTI-Carbamylated Protein Antibodies (CARP) in Palindromic
Rheumatism: Prevalence and Clinical Significance
Raul Castellanos-Moreira Sr.1, Virginia Ruiz-Esquide1, María José Gomara2, Sonia Cabrera-Villalba1, Sebastian C
Rodriguez-Garcia1, Georgina Salvador3, Andrea Cuervo1, Julio Ramírez1, M. Victoria Hernández1, Juan Cañete1, Isabel
Haro2 and Raimon Sanmartí1, 1Rheumatology Service, Hospital Clínic de Barcelona, Barcelona, Spain, 2Unit of Synthesis
and Biomedical Applications of Peptides, IQAC-CSIC, Barcelona, Spain, 3Hospital Universitario Mutua Terrassa,
Barcelona, Spain
SESSION INFORMATION
Background/Purpose: Autoantibodies (RF or ACPA) are found in sera from patients with palindromic rheumatism (PR)
but there are no studies analyzing the presence of Anti-carbamylated proteins antibodies (Anti-CarP) in patients with PR.
The aim of this study was to analyse the prevalence of Anti-CarP in patients with PR and to evaluate their clinical
significance and association with autoantibody status (RF and ACPA).
Methods: Patients with pure PR (not associated with any rheumatic disease at the time of serum measurement) with sera
collected between June 2012 and June 2013 were included (Cabrera-Villalba S et al J Rheumatol 2014;41:1650-5). Anti-
CarP were determined by a home-made ELISA test using a synthetic chimeric fibrin/filaggrin homocitrullinated peptide
(CFFHP) as antigen. IgG, IgA and IgM isotype were measured using the corresponding secondary antibodies. Cut-off
values were determined using ROC curves, with a specificity of 98% compared with a healthy population. ACPA, RF,
progression toward persistent arthritis fulfilling ACR/EULAR RA criteria, and remission (no joint attacks in the last 6
months) was analyzed during the follow-up (until May 2017). Patients were treated according to physician criteria. A
control group of established RA patients was also included.
Results: Anti-CarP antibodies were analyzed in 54 patients with pure PR and 53 patients with established RA controlled by
age, gender and disease evolution. ACPA (CCP2) was positive in 64.8% of PR and 66.0% of RA patients. Anti-CarP were
found in 9 out of 54 (16.7%) of PR patients. Patients with PR and Anti-CarP (+) were all ACPA positive and presented
higher ACPA titers than Anti-CarP (-) patients (Table 1). In PR patients, IgG was the predominant isotype (100%) and only
one patient presented IgA (11.1%) and none IgM. In the RA control group, the prevalence of Anti-CarP was 39.6% and the
percentages of IgG, IgA and IgM were 57.1%, 47.6% and 38.1% of Anti-CarP (+) patients respectively. DMARDs were
administered in 64.8% of patients (in all Anti-CarP (+) patients) at the last assessment, mainly antimalarials and
methotrexate. More Anti-CarP (+) patients developed RA (33.3% vs. 16.3%) during follow up although the difference was
not significant. Remission was more frequent in Anti-CarP negative patients (Table 1).
Conclusion:
Table 1. Clinical and serological characteristics of PR patients according to Anti-CarP status

RP with Anti- RP with Anti- p value
CarP (+) CarP (-)
n: 9 n: 45
Female 5 (55.6%) 29 (64.4%) NS
Smoking Hx 5 (55.6%) 19 (44.4%) NS
Age at onset 42.9±8.9 39.1 ±11.8 NS
(years)
Mean disease 11.3± 7.6 12± 10.9 NS
duration
(years)*
Follow-up 3.8±1.23 3.9±1.07 NS
(years)**
RF + (%) 7 (77.8%) 26 (57.8%) NS
RF titer (UI) 286.7± 134.5 207.8± 325.6 NS
Anti-CCP2 + 9 (100%) 26 (57.8%) 0.003
(%)
Anti-CCP2 titer 769.2± 638.4 381.1± 411.6 0.02
UI)
Progression to 3 (33%) 7 (15.5%) NS
RA
Remission at 2 (22.2%) 26 (60.5%) 0.03
last follow-up
DMARDs 9 (100%) 26 (57.8%) 0.003
Antimalarials 5 18 NS
Methotrexate 1 8 NS
* At the time of serum measurement
**: From sera measurement to last follow-up
Disclosure: R. Castellanos-Moreira Sr., None; V. Ruiz-Esquide, None; M. J. Gomara, None; S. Cabrera-Villalba,

None; S. C. Rodriguez-Garcia, None; G. Salvador, None; A. Cuervo, None; J. Ramírez, Gebro, 2; M. V. Hernández,
None; J. Cañete, None; I. Haro, None; R. Sanmartí, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/anti-carbamylated-protein-antibodies-

carp-in-palindromic-rheumatism-prevalence-and-clinical-significance
Immunocompetent Cells Expressing Citrullinated Proteins in Joint Synovium

of Osteoarthritis and Rheumatoid Arthritis
Kyoko Honne1, Masahiro Iwamoto2, Shunichiro Hanai1, Satoshi Machida3, Hitoshi Sekiya4, Reina Tsuda5, Tatsuhiko
Ozawa5, Tadayoshi Karasawa6, Atsushi Muraguchi5, Masafumi Takahashi6, Hiroyuki Kishi5 and Seiji Minota7, 1Division
of Rheumatology and Clinical Immunology, Jichi Medical University, Shimotsuke, Japan, 2Deivision of Rheumatology and
Clinical Immunology, Jichi Medical University, Shimotsuke, Japan, 3Department of Orthopaedic Surgery, Orthopedics
Clinic Medical Papas, Tochigi, Japan, 4Department of orthopedic surgery, Jichi Medical University, Shimotsuke, Japan,
5Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama,
Japan, 6Division of Inflammation Research Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Japan,
7Division of Rheumatology and Clinical Immunology, Jichi Medical University, Tochigi, Japan
SESSION INFORMATION
Background/Purpose: Human monoclonal ACPA (Human-ACPA) is reported to strongly bind to synovium in RA patients
[1]. The aims of our study were 1) To investigate whether Human-ACPA, which was generated from peripheral blood B
cells from an RA patient by us, binds to synovium from OA and RA, and 2) To identify cell-type expressing citrullinated
proteins in synovium from OA and RA patients.
Methods: Human-ACPA was produced by a method published earlier [2, 3]. Joint synovium from OA or RA patients (10
OA, 10 RA) were immunohistochemically stained with Human-ACPA. Double-label immunofluorescence staining with
Human-ACPA/CD3, Human-ACPA/CD20 or Human-ACPA/CD68 (3 OA, 3 RA), and confocal laser scanning microscope
(3 RA) were performed in the synovia for the images.
Results: Human-ACPA bound to all layers in synovium from RA patients. Human-ACPA positive cells were limited in the
surface layer in 7 of 10 OA patients, while no Human-ACPA positive cells were found in the remaining 3 OA synovia.
Human-ACPA positive cells in synovium of OA were not double-stained with CD3, CD20 or CD68 monoclonal antibody.
On the other hand, there were Human-ACPA/CD3, Human-ACPA/CD20 or Human-ACPA/CD68 double positive cells in
synovium of RA patients.
Most of the ACPA positive cells were stained with CD68. Human-ACPA/CD3 and Human-ACPA/CD20 double positive
cells also existed in deeper layers of synovium in RA patients.
Conclusion: All layers of synovium in RA patients were studded with cells which contained citrullinated proteins. Cells
positive for citrullinated protein in RA were mainly macrophage-lineage (CD68+). Citrullinated protein was also expressed
in T cells (CD3+) and B cells (CD20+) in RA. Citrullinated protein existed in the strip-shaped form only in the surface layer
of OA synovia and may have been induced by mechanical stresses. No macrophages, T cells or B cells were positive for
citrullinated protein in OA.
[1]Amara K et al. Monoclonal IgG antibodies generated from joint-derived B cells of RA patients have a strong bias toward
citrullinated autoantigen recognition. J Exp Med 2014; 210: 445-55.
[2] Jin A et al. A rapid and efficient single-cell manipulation method screening antigen-specific antibody-secreting cells
from human peripheral blood. Nat Med 2009; 15: 1088-92
[3]Tsuda et al. Monoclonal antibody citrullinated peptides obtained from rheumatoid arthritis patients reacts with numerous
citrullinated microbial and food proteins. Arthritis and Rheumatol 2015; 67: 2020-31
Disclosure: K. Honne, Takeda science fundation, 2; M. Iwamoto, None; S. Hanai, None; S. Machida, None; H. Sekiya,
None; R. Tsuda, None; T. Ozawa, None; T. Karasawa, None; A. Muraguchi, None; M. Takahashi, None; H. Kishi,
None; S. Minota, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/immunocompetent-cells-expressing-

citrullinated-proteins-in-joint-synovium-of-osteoarthritis-and-rheumatoid-arthritis

The Link between ACPA and Erosion Development: Is ACPA Sufficient? an
Association Study in Clinically Suspect Arthralgia
Robin M ten Brinck1, REM Toes2 and Annette H.M. van der Helm-van Mil1, 1Department of Rheumatology, Leiden
University Medical Center, Leiden, Netherlands, 2Rheumatology, Leiden University Medical Center, Leiden, Netherlands
SESSION INFORMATION
Background/Purpose:
Anti-citrullinated protein antibodies (ACPA) associate with more severe joint erosions in rheumatoid arthritis (RA), but the
underlying mechanism is unclear. Recent in vitro and murine studies indicate that ACPAs can directly activate osteoclasts
leading to bone erosion and pain. This study sought evidence for this hypothesis on the human level and evaluated in
arthralgia patients at risk for RA whether ACPA associated with erosions (detected by MRI) independent of inflammation,
and also independent of the presence of other autoantibodies (Rheumatoid Factor, RF).
Methods:
225 patients with Clinically Suspect Arthralgia underwent ACPA- and RF-determination and 1.5T contrast-enhanced MRI
of metacarpophalangeal, wrist and metatarsophalangeal joints at baseline. MRIs were scored for presence of local
inflammation and erosions.
Results:
ACPA-positive patients had higher erosion-scores than ACPA-negative patients (p=0.02; Figure Panel A). ACPA-positive
patients without subclinical inflammation did not have higher erosion-scores than ACPA-negative patients (p=0.45), in
contrast to ACPA-positive patients with local inflammation (p=0.001, Figure Panel B). Mediation analyses suggested that
local inflammation is in the causal path of ACPA leading to higher erosion-scores. Compared to autoantibody-negative
patients, ACPA-positive/RF-negative patients did not differ (p=0.41), but ACPA-positive/RF-positive patients had higher
erosion-scores (p=0.001 Figure Panel C).
Conclusion:
The effect of ACPA on erosions is mediated by inflammation and is not independent of RF.
Figure. Histograms showing median erosion-scores of patients with Clinically Suspect Arthralgia comparing ACPA-
positive and ACPA-negative patients (A), ACPA-positivity and -negativity in relation to the concomitant presence of MRI-
detected subclinical inflammation (B) or rheumatoid factor (C).
Legend:
Histograms showing median erosion-scores with standard deviations.
* indicates significance at p<0.05 level, ** indicates significance of p<0.01 level, NS indicates non-significance
Disclosure: R. M. ten Brinck, None; R. Toes, None; A. H. M. van der Helm-van Mil, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-link-between-acpa-and-erosion-

development-is-acpa-sufficient-an-association-study-in-clinically-suspect-arthralgia
Anti-Peptidylarginine Deiminase-4 Antibodies Are Present in the Sputum of

RA Patients and Can Activate Peptidylarginine Deiminase-4 Enzyme Activity
M. Kristen Demoruelle1, Hong Wang2, Ryan L. Davis2, A. Itzam Marin1, Jill M. Norris3, V. Michael Holers1, Kevin D.
Deane1 and Erika Darrah2, 1Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, 2Division
of Rheumatology, The Johns Hopkins University, Baltimore, MD, 3Department of Epidemiology, Colorado School of
Public Health, Aurora, CO
SESSION INFORMATION
Background/Purpose: Anti-peptidylarginine deiminase (PAD)-4 antibodies (Abs) are present in a portion of RA patients
and associate with more severe joint disease, suggesting that they play a role in pathogenesis. A subset of anti-PAD4 Abs
cross-react with PAD3, and these Abs are found to enhance PAD4 enzyme activity at physiologic calcium concentrations
which can lead to increased citrullination. Anti-PAD3/4 cross-reactive Abs have also been associated with more severe lung
disease in RA, suggesting they may have a direct effect in the lung. Because sputum anti-CCP Abs have been identified in
RA, we sought to explore the presence and activity of anti-PAD4 Abs in the sputum of RA patients.
Methods: We studied 48 serum anti-CCP+ RA patients and 24 healthy controls. Induced sputum was tested for CCP using
commercial ELISAs. Serum and sputum were tested for anti-PAD4 Abs using an established immunoprecipitation method.
All anti-PAD4+ samples underwent testing for the presence of PAD3 cross-reactivity. To determine the effect of anti-PAD
Abs on PAD4 enzymatic activity, Igs were purified from each anti-PAD+ sample and their effect on citrullination of the
histone H3 substrate by PAD4 at increasing calcium concentrations (i.e. 0.2 and 2 mM) was measured by an anti-
citrullinated histone H3 immunoblot.
Results: Serum anti-PAD4 Abs were detected in 6/48 (13%) of RA patients and 0/24 (0%) controls. Of the positive
patients, 2/6 (33%) were also serum anti-PAD3+. Sputum anti-PAD4 Abs were detected in 3/48 (6%) of RA patients, and of
those positive, 1/3 (33%) was also sputum anti-PAD3+. Serum anti-PAD4 Abs were more prevalent in RA patients with
sputum anti-CCP Abs, with all anti-PAD4+ RA patients demonstrating sputum anti-CCP positivity (Table). In serum, anti-
PAD4 Abs were predominately IgG, whereas in sputum, anti-PAD4 Abs were predominately IgA (Figure). Interestingly, all
three samples (serum and sputum) with measurable anti-PAD3/4 Abs were able to increase PAD4 activity at 0.2 mM
calcium (i.e. physiologic levels).
Conclusion: We identified serum anti-PAD4 Abs in a portion of RA patients, of which a subset was also anti-PAD3+. We
demonstrate for the first time that anti-PAD4 Abs are also present in the sputum in a portion of RA patients, and
predominately IgA. Importantly, we found that anti-PAD3/4 IgA present in the sputum was able to lower the calcium
threshold required for PAD4 enzymatic activity. These findings suggest that anti-PAD4 Abs may have pathogenic activity
directly in the lung, although larger studies are needed to understand the relationship between anti-PAD3/4 and underlying
lung disease.
Table. Characteristics associated with serum anti-PAD4 antibodies

Serum anti- Serum anti-
PAD4(+) PAD4(-)
(N=6) (N=42) p-value*

Age, median (IQR) 51 (29-64) 58 (45-62) 0.49
% Female 83 79 0.24
% Ever smoker 17 55 0.19
% Current smoker 17 19 1.0
% Shared epitope positive 80 66 1.0
% RA disease duration >1 year 33 62 0.22
% Any self-reported lung disease 33 38 1.0
% Sputum anti-CCP positivity** 100 50 0.03
*P-value compares median levels (Mann-Whitney U) or prevalence of positivity (Chi-
Square/Fishers) between groups as appropriate.
**Includes positivity for commercial assays CCP3 (IgG, Inova) and/or anti-
CCP3.1(IgG/IgA, Inova). The cut-off level used to determine sputum anti-CCP positivity
was established in a separate healthy control group.
Disclosure: M. K. Demoruelle, None; H. Wang, None; R. L. Davis, None; A. I. Marin, None; J. M. Norris, None; V. M.
Holers, None; K. D. Deane, Inova Diagnostics, Inc., 5; E. Darrah, patent, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/anti-peptidylarginine-deiminase-4-

antibodies-are-present-in-the-sputum-of-ra-patients-and-can-activate-peptidylarginine-deiminase-4-enzyme-activity
Sputum Neutrophils Demonstrate Increased Neutrophil Extracellular Trap

Formation in RA-Free Subjects at-Risk of Future RA
Yuko Okamoto1, Michael P. Mohning2, Stacey M. Thomas2, Ashley Visser1, Lindsay B. Kelmenson3, Jill M. Norris4,
Mariana J. Kaplan5, William J. Janssen2, V. Michael Holers1, Kevin D. Deane1 and M. Kristen Demoruelle1, 1Division of
Rheumatology, University of Colorado School of Medicine, Aurora, CO, 2Division of Pulmonary Disease and Critical Care
Medicine, National Jewish Health, Denver, CO, 3Division of Rheumatoloty, University of Colorado School of Medicine,
Aurora, CO, 4Department of Epidemiology, Colorado School of Public Health, Aurora, CO, 5Systemic Autoimmunity
Branch, NIAMS/NIH, Bethesda, MD
SESSION INFORMATION
Background/Purpose: Data support that ACPAs are generated in the lung in RA-free subjects At-Risk of future RA. Our
group previously demonstrated a significant positive correlation between sputum ACPA levels and remnants of neutrophil
extracellular traps (NETs) in At-Risk subjects (Demoruelle 2017). However, it is unknown if increased sputum NET levels
in these subjects is due to aberrant neutrophil function or ineffective macrophage function (e.g. decreased macrophage
efferocytosis that is a mechanism of apoptotic cell clearance). Herein, we sought to quantify ex vivo NET formation and
macrophage efferocytosis in association with ACPA in the sputum of At-Risk subjects.
Methods: We collected serum and induced sputum from 24 subjects At-Risk for RA based on familial RA or serum ACPA
positivity identified through community screenings [17 were serum ACPA- and 7 serum ACPA+ based on commercial
CCP3.1 (IgG/IgA, Inova)], 3 healthy Controls and 3 serum ACPA+ classified RA patients. Sputum was tested for ACPA
using CCP3.1 ELISA and the cut-off for positivity was determined in a separate healthy control group (N=70). Sputum
plugs were processed and incubated for 1 hour without stimulation for NET measurements and a subset (N=15) were also
incubated with apoptotic Jurkat cells for efferocytosis assays. The formation of NETs was assessed by fluorescence
microscopy with staining for Hoechst 33342, neutrophil elastase and citrullinated histone-H3. Microscopy-based methods
were used to quantify the percent of neutrophils demonstrating NET formation and the efferocytosis index for macrophages
ingesting apoptotic Jurkats.
Results: NET formation in sputum neutrophils was significantly higher in serum ACPA+ At-Risk subjects compared to
Controls (p=0.03) and serum ACPA- At-Risk subjects (p<0.01) (Figure Panel A), although a portion of serum ACPA- At-
Risk subjects had elevated rates of sputum NET formation. There was a trend toward a higher prevalence of sputum ACPA
positivity in At-Risk subjects with >60% NETosis [4/8 (50%) vs. 3/15 (20%), p=0.18]. There was no difference in NETosis
based on smoking history. The efferocytosis index was lower in serum ACPA+ At-Risk subjects compared to Controls
(p=0.03, Figure Panel B).
Conclusion: We found that sputum neutrophils in At-Risk subjects exhibit increased NET formation in serologically
ACPA+ At-Risk individuals. Furthermore, in these subjects, sputum macrophages exhibited decreased efferocytosis. These
findings suggest that enhanced neutrophil NET formation and ineffective macrophage efferocytosis in the lung may both
play a role in the development of systemic and potentially local mucosal ACPA generation in subjects At-Risk for RA.
Additional studies are needed to determine whether sputum NETs in At-Risk subjects contain unique citrullinated protein
cargo as well as whether these processes are aberrant at other mucosal sites.
Disclosure: Y. Okamoto, None; M. P. Mohning, None; S. M. Thomas, None; A. Visser, None; L. B. Kelmenson, None;
J. M. Norris, None; M. J. Kaplan, None; W. J. Janssen, None; V. M. Holers, None; K. D. Deane, Inova Diagnostics,
Inc., 5; M. K. Demoruelle, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/sputum-neutrophils-demonstrate-

increased-neutrophil-extracellular-trap-formation-in-ra-free-subjects-at-risk-of-future-ra
Different Citrullination Profiles in Spontaneous Versus Leukemia-Associated

Tal Gazitt1, Son Hong Nguyen2, Ari Salinger2, Christian Lood3, Xizhang Sun1, Lena M. Tanaka1, David Feith4, Jeffrey
Ledbetter5, Gordon Starkebaum6, Thomas Loughran Jr.7, Paul R. Thompson2 and Keith B. Elkon8, 1Division of
Rheumatology, University of Washington, Seattle, WA, 2Biochemistry and Molecular Pharmacology, University of
Massachusetts Medical School, Worcester, MA, 3Division of Rheumatology, Division of Rheumatology, Department of
Medicine, University of Washington, Seattle, WA, 4Hematology and Oncology, University of Virginia, Charlottesville, VA,
5University of Washington, Seattle, WA, 6Department of Medicine, Division of Rheumatology, University of Washington,
Seattle, WA, 7Hematology Oncology, University of Virginia, Charlottesville, VA, 8Division of Rheumatology, Department
of Medicine, University of Washington, Seattle, WA
SESSION INFORMATION
Background/Purpose:
Protein citrullination, the post-translational conversion of arginine to citrulline, mediated by peptidylarginine deiminase
(PAD) enzymes, is considered a likely mechanism for the stimulation of anti-citrullinated protein antibodies (ACPA) in
patients with rheumatoid arthritis (RA). Hypercitrullination, the citrullination of multiple intracellular proteins, is seen in
synovial fluid (SF) cells from RA patients. This unique form of citrullination is proposed to occur via immune-mediated,
pore-forming membranolytic pathways such as perforin-granzyme activation. Indeed, perforin and granzyme-producing
CD8+ T effector cells are found in the synovium of pre-clinical RA patients as well as in the peripheral blood (PB) and SF
of active RA patients, persisting into disease remission.
Insight into the existence of potential cytotoxic mechanisms occurring in RA comes from the co-occurrence of RA in up to
36% of cases of T-cell Large Granular Lymphocyte (T-LGL) Leukemia, a clonal condition characterized by neutropenia
attributed to the killing of neutrophils or their precursors by cytotoxic CD8+ T cells. We thus queried LGL leukemia as a
model for neutrophil (PMN)-directed cytotoxicity contributing to hypercitrullination and disease propagation in inflamed
joints of ACPA+ RA patients.
Methods:
The sera of 15 T-LGL leukemia patients (T-LGL), 19 T-LGL leukemia patients with co-existing RA (T-LGL/RA), and 4
healthy controls (HC) were analyzed for ACPA positivity by ELISA. ACPA titers of each group of patients were compared
using unpaired two-tailed T tests. Neutrophils (PMN) from each of these groups were isolated from blood cells by density
gradient centrifugation. Hypercitrullination of these cells (n=4/patient group) was compared with that of seropositive RA
patients by proteomic analysis using Rhodamine-PG labeling, protein precipitation followed by Streptavidin enrichment,
and sequent digestion. The resulting products were analyzed using LC-MS/MS on an LTQ-Orbitrap mass spectrometer. The
tandem MS data were searched using SEQUEST algorithm using a concatenated target/decoy variant of the human and
mouse International Protein Index database.
Results:
T-LGL/RA patients had significantly higher serum ACPA positivity than T-LGL patients or HC (Fig. 1A). Surprisingly,
however, the overall level of citrullinated proteins in PMN (Fig.1B) was not increased in T-LGL/RA compared to T-LGL
patients, and was highest in PMN obtained from RA patients (Fig. 1B).
Conclusion:
These results reveal an interesting dichotomy between RA that occurs spontaneously versus that occurring in patients with
LGL leukemia. Whereas both spontaneous and LGL-associated RA develop high titer ACPA, only RA patients show a high
degree of citrullination of neutrophil proteins. Whether this suggests a different source of immunogenic proteins or relates
to other biologic processes, remains to be determined.
Disclosure: T. Gazitt, None; S. H. Nguyen, None; A. Salinger, None; C. Lood, None; X. Sun, None; L. M. Tanaka,
None; D. Feith, None; J. Ledbetter, None; G. Starkebaum, None; T. Loughran Jr., None; P. R. Thompson, None; K.
B. Elkon, Celgene, 5,AstraZeneca, 5,Merck Human Health, 5,Resolve Therapeutic, 4,Amdax Therapeuti, 4.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/different-citrullination-profiles-in-

spontaneous-versus-leukemia-associated-rheumatoid-arthritis
Anti-Citrullinated Protein Antibody Reactivities in Treatment NaïVe Early

Maria K. Jonsson1,2, Aase Hensvold3, Monika Hansson4, Linda Mathsson-Alm5, Anna-Birgitte Aga2, Joseph Sexton2,
Bjørg-Tilde Fevang1,6, Siri Lillegraven2, Anca I. Catrina3 and Espen A. Haavardsholm2,7, 1Dept. of Rheumatology,
Haukeland University Hospital, Bergen, Norway, 2Dept. of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway,
3Karolinska Institute, Stockholm, Sweden, 4Rheumatology Unit, Department of Medicine, Karolinska Institute, Karolinska
University Hospital, Stockholm, Sweden, 5Thermo Fisher Scientific, Uppsala, Sweden, 6Dept. of Clinical Science,
University of Bergen, Bergen, Norway, 7University of Oslo, Oslo, Norway
SESSION INFORMATION
Background/Purpose: Anti-citrullinated protein antibody (ACPA) reactivities can precede RA onset, and may be involved
in the pathogenesis of the disease. We wanted to assess the prevalence of baseline ACPA reactivities in an inception cohort
of early RA patients, including subgroups based on anti-CCP/RF status, and to compare the findings to healthy controls.
Methods: 217 DMARD-naïve early RA patients from the ARCTIC trial (1) were analyzed. Radiographs were scored
according to van der Heijde Sharp (vdHS) score. Anti-CCP status was analyzed by FEIA (positive if ≥10 IU/mL) and RF
by ELISA (positive if ≥25 IU/mL). ACPA titres (AU/ml) were considered positive if above the 98-percentile of values in
619 non-RA subjects. Analysis of 13 ACPA reactivities targeting citrullinated peptides from fibrinogen, alpha-1 enolase,
vimentin, fillagrin and histone was performed at baseline in patients and 94 controls (blood donors matched for
age/gender/smoking), using a multiplex chip-based assay (2). Positivity and median number of ACPA reactivities in the
subgroups were compared using Chi-square test and Mann-Whitney U-test, respectively.
Results: Baseline characteristics are presented in the table. The median [IQR] number of antibody reactivities in all
patients was 7[3,10], compared to 0[0,0] in controls (p<0.001, figure). The corresponding numbers were 8[5,10] and 0[0,1]
for the anti-CCP+ vs. anti-CCP- patients (p<0.0001), 8[5,10] and 2[0,8] for the RF+ vs. RF- patients (p<0.001), and 8[6,10]
and 0[0,1] for the anti-CCP+/RF+ vs. the anti-CCP-/RF- (p<0.001) (table, figure). Positivity for ACPA reactivities was
seen mainly in the anti-CCP+, RF+ and anti-CCP+/RF+ patients, but also occurred more frequently in the anti-CCP-, RF-
and anti-CCP-/RF- patients than in controls (anti-CCP- vs controls p=0.002, RF- vs controls p<0.001, and anti-CCP-/RF-
vs. controls p=0.035) (table).
Table: Baseline characteristics

Anti- Anti- Anti- Anti-
CCP+ CCP- RF+ RF- CCP+/RF+ All RA Control
CCP-/RF-
n=178 n=39 n=154 n=63 n=147 n=32 n=217 n=94
Age, years 1 50.8(13.2)55.0(14.9)51.9(13.3)50.8(14.2) 51.7(13.6) 55.0(16.1) 51.5(13.6)52(9.4)
Female2 109(61) 22(56) 91(59) 40(63) 86(59) 17(53) 131(60) 63(59)
Ever- 122(69) 26(67) 109(71) 39(62) 103(70) 20(62) 148(68) 81(64)
smoker 2
DAS1 3.4(1.1) 4.0(1.3) 3.5(1.2) 3.5(1.2) 3.42(1.13) 3.9(1.2) 3.5(1.2) NA

vdHS 4[1.5,7.9] 4.5[2,10] 4.5[2,8] 3.5[1.5,9.8]4.5[2,8] 5.5[1.9,12.6]4 [1.5,8] NA
score3
Vim 60- 152(85) 7(18) 130(84) 29(46) 128(87) 5(16) 159(73) 5(5)
75cit4
H4 31- 142(80) 3(8) 119(77) 26(41) 118(80) 2(6) 145(67) 1(1)
50cit4
CEP14 137(77) 3(8) 117(76) 23(37) 115(78) 1(3) 140(65) 1(1)

Fil 307- 134(75) 2(5) 113(73) 23(37) 112(76) 1(3) 136(63) 0(0)
324cit 4
Fib 573cit4 121(68) 2(5) 99(64) 24(38) 99(67) 2(6) 123(57) 0(0)
Fib 36- 116(65) 1(3) 96(62) 21(33) 96(65) 1(3) 117(54) 2(2)
52cit4
H3 1-30cit4 106(60) 1(3) 93(60) 14(22) 92(63) 0(0) 107(49) 0(0)

H4 14- 103(58) 2(5) 90(58) 15(24) 88(60) 0(0) 105(48) 3(3)
34cit4
H3 21- 94(53) 2(5) 80(52) 16(25) 79(54) 1(3) 96(44) 1(1)
44cit4
Vim 2- 87(49) 1(3) 80(52) 8(13) 79(54) 0(0) 88(41) 0(0)
17cit4
Fib 591cit4 66(37) 3(8) 56(36) 13(21) 55(37) 2(6) 69(32) 1(1)
Fib 74cit 4 60(34) 6(15) 54(35) 12(19) 51(35) 3(9) 66(30) 3(3)
Fib 72cit4 24(13) 3(8) 21(14) 6(1) 20(14) 2(6) 27(12) 2(2)
Number of 8[5,10] 0[0,1] 8[5,10] 2[0,8] 8[6,10] 0[0,1] 7[3,10] 0[0,0]
ACPA
reactivities3
1Mean(SD), 2n(%), 3median[IQR], 4n positive(%)
Figure: Number of ACPA reactivities per patient

Conclusion: Prevalence of ACPA reactivities differed in subgroups of DMARD-naïve early RA patients according to anti-
CCP and RF status. In general, higher numbers of ACPA reactivities were seen in anti-CCP+ patients, but all RA
subgroups, including anti-CCP-, RF- and anti-CCP-/RF- patients, had higher prevalence of ACPA reactivities compared to
healthy controls.
References: 1) Haavardsholm et al BMJ 2016, 2) Hansson et al Arthr Res Ther 2012
Disclosure: M. K. Jonsson, None; A. Hensvold, None; M. Hansson, None; L. Mathsson-Alm, Thermo-Fisher Scientific,
3; A. B. Aga, None; J. Sexton, None; B. T. Fevang, Novartis Pharmaceutical Corporation, 2; S. Lillegraven, None; A. I.
Catrina, None; E. A. Haavardsholm, AbbVie, Pfizer, Roche, Eli Lilly, Celgene, UCB, 5,AbbVie, Pfizer, Roche, MSD,
UCB, 2,AbbVie, Pfizer, Roche, Eli Lilly, Celgene, UCB, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/anti-citrullinated-protein-antibody-

reactivities-in-treatment-naive-early-rheumatoid-arthritis

ARE ANTI-Citrullinated Protein Antibody Levels Associated with
Periodontal Disease in Rheumatoid Arthritis?
Jerián González Febles1, Fernando Sánchez-Alonso2, Jorge Luis Garnier Rodríguez3, Mariano Sanz Alonso1, Federico
Díaz-González4 and Beatriz Rodriguez Lozano5,6, 1Periodontology, Universidad Complutense de Madrid, Madrid, Spain,
2Unidad de Investigación, Spanish Society of Rheumatology, Madrid, Spain, 3Odontology, Dental Clinic Garnier, S/C
Tenerife, Spain, 4Servicio de Reumatología. Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain,
5Rheumatology, Rheumatology Department. Hospital Universitario de Canarias, S/C TENERIFE, Spain, 6Rheumatology,
Hospital de Canarias, S/C Tenerife, Spain
SESSION INFORMATION
Background/Purpose: Positivity of anti-citrullinated peptides antibodies (ACPA) indicates severity in Rheumatoid

Arthritis (RA). There is evidence for chronic periodontitis (PD) in RA autoimmune response by periodontopathogenic
bacteria, through protein citrullination. Thus, our objectives were: 1.To determine whether there is an association between
PD and its severity with ACPA(+).2.To assess relationship between PD and ACPA titres.3.To identify association between
certain periodontal parameters and ACPA titres and their possible cut-off points.
Methods: Cross-sectional study RA patients ≥18 yo with ≥4 teeth, no tooth cleaning, antibiotic intake 6 months before.
Comorbidities, demographics, DAS-28(ESR), DAS-28(CRP)and SDAI were taken. Serum ACPA detection: Ab IgG
against CCP2 (ELISA) Immunoscan CCPlus®test kit Euro Diagnostica: positive≥25 U/mL; ACPA titres stratification: Low
(25–75), moderate (76–300) and high (>300). Periodontal parameters: plaque index (PI), bleeding on probing (Bop),
probing pocket depth, clinical attachment level (CAL). CAL loss was categorized according to European Workshop 2005
(Tonetti):T level0 (absence), TL1 (mild), TL2 (severe). Statistical analysis: t-student, Kruskal Wallis, Chi- squared tests.
Results:
187 RA patients included (table 1), ACPA determined in 168 patients: 67.86% (+) with similar titres distribution: low 18%,
moderate 26%, high 23%. PD:182 patients (97.3%): TL1 52.4%, TL2 44.9%. Although prevalence of severe PD/ACPA(+)
was higher compared to PD/ACPA(-) (69.2% vs 30.7%), there was no association between PD and ACPA positivity/titres.
Regarding the association with periodontal parameters, there was tendency of association between ACPA(+) and number of
periodontal pockets ≥5mm, adjusted OR 1.02 (95% CI 0.9–1.04). However, there was a gradient effect, where number of
pockets ≥ 5mm increased as ACPA titles increased, which was significant for high ACPA titres (p≤0.05,OR 1.03 95% CI
1.0–1.05). Moreover, RA patients who have 15 pockets ≥ 5mm showed 1.789-fold risk of having high ACPA titres (95% CI
0.928-3.448, p 0.082). In the lineal regression analysis, a statistically significant increase of 6.946 U/mL (95% CI 2.271-
11.621) was found for each pocket ≥5mm in RA patients with moderate-high disease activity (p 0.004, adjusted by age,
gender and smoking). When ACPA(+) was related to %PI and BoP, a strong association was observed for PI, OR 10.32
(p<0,026), and only a tendency for BoP (p<0.062). A risk for ACPA(+) was detected with cut-off points of 8%(OR 2.19) PI
and 65% BoP (OR 2.45).
Conclusion: 1.Despite higher prevalence of severe PD in ACPA(+) patients, we found no association between the presence
of PD and ACPA positivity nor with serum titres. 2. On analysis of ACPA titres in relation to the severity of the periodontal
parameters, there was a “gradient” risk, where number of pockets ≥5mm increased as ACPA titres increased, which was
significant for high ACPA titres.3. There was a lineal correlation between ACPA titres and number of pockets ≥5mm.
Disclosure: J. González Febles, None; F. Sánchez-Alonso, None; J. L. Garnier Rodríguez, None; M. Sanz Alonso,
None; F. Díaz-González, None; B. Rodriguez Lozano, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/are-anti-citrullinated-protein-antibody-
levels-associated-with-periodontal-disease-in-rheumatoid-arthritis
Increased Expression of TNF-α and PAD-2 in Human Monocytes Following

Treatment with Protein Modified with Malondialdehyde-Acetaldehyde
(MAA) and Citrulline
Logan M. Duryee1, Michael J. Duryee2, Dahn L Clemens1, Evan M. Ryan1, Carlos D. Hunter2, Lynell W. Klassen3, James
R. O'Dell3, Daniel R. Anderson1, Ted R. Mikuls4 and Geoffrey M. Thiele1, 1University of Nebraska Medical Center,
Omaha, NE, 2Internal Medicine Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE,
3Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 4Internal Medicine, Division of
Rheumatology, University of Nebraska Medical Center, Omaha, NE
SESSION INFORMATION
Background/Purpose: We have previously shown that malondialdehyde-acetaldehyde (MAA) and citrullinated proteins
are present together in the synovial tissues of rheumatoid arthritis (RA) patients. Macrophage are a major source of not
only TNF-α, but also PAD enzymes and are both involved in the progression of RA. MAA adducts and citrullinated
proteins alone have the ability to increase TNF-α release in many different cell types. Therefore, the objective of this
study was to determine if proteins modified with both MAA and citrulline increase the expression and secretion of both
PAD and TNF-α in a human monocytic cell line.
Methods: THP-1 cells were grown and activated with PMA. Following serum starvation the cells were incubated with
either 50 µg/ml of human albumin (ALB), ALB-MAA, ALB-Citrulline (CIT) and ALB-MAA-CIT for 4 hours.
Supernatants were collected and assayed for TNF-α protein by a commercial ELISA kit. RNA was extracted from the
cells and subjected to RT-PCR for expression of PAD-2, PAD-4, and TNF-α.
Results: Human monocytic cells exposed to ALB-MAA significantly increased levels of TNF-α protein from 35.5 ± 0.75
pg/ml to 146.8 ± 33.55 pg/ml compared to ALB alone (P<0.01) (A). The addition of ALB-MAA-CIT significantly
increased the secretion 435.5 ± 17.88 pg/ml (P<0.001) when compared to ALB-MAA (A). Cells incubated with ALB-
MAA-CIT showed and increased expression of TNF-α mRNA by 6 fold (698.6 ± 96.62 RQ) compared to MAA-ALB
(20.09 ± 6.48 RQ) (P<0.001) (B). PAD-2 mRNA was increased following exposure to both ALB-MAA (1.79 ± 0.96 RQ)
and ALB-MAA-CIT (4.87 ± 1.71 RQ) (compared to each other (P<0.05), although only the latter achieved statistical
significance compared to ALB alone (P<0.02) (C). No increase in PAD-4 mRNA was detected in any of the groups.
Additionally, results from the stimulation by ALB-CIT were not different that ALB alone.
Conclusion: We and others have shown that MAA-modified proteins and citrullinated proteins alone can activate
macrophages to release TNF-α. Until now, no studies have reported on the effects of these modified protein moieties
commonly found in RA. The significantly increased expression of TNF-α and PAD-2 mRNA in human macrophages
following exposure to ALB-MAA-CIT, supported by the clinical observation that these protein(s) are found together in
synovial tissues strongly suggests a role in the pathogenesis of RA.
Disclosure: L. M. Duryee, None; M. J. Duryee, None; D. L. Clemens, None; E. M. Ryan, None; C. D. Hunter, None;
L. W. Klassen, None; J. R. O'Dell, Medac, 5,Coherus, 5; D. R. Anderson, None; T. R. Mikuls, BMS, 2,Ironwood Pharm,
2,Pfizer Inc, 5,NIH, VA, 2; G. M. Thiele, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/increased-expression-of-tnf-%ce%b1-

and-pad-2-in-human-monocytes-following-treatment-with-protein-modified-with-malondialdehyde-acetaldehyde-maa-and-
citrulline
Endotypic Clustering of Rheumatoid Arthritis Patients through the Use of

Tissue Specific Serum Biomarkers Identifies Structural Progressors
Joseph Patrick Michele Blair1, Cecilie Liv Bager1, Line Mærsk Staunstrup1, Henning Bay Nielsen1, Morten Karsdal2
and Anne-C. Bay-Jensen3, 1ProScion, Herlev, Denmark, 2Biomarkers and Reseacrh, Nordic Bioscience, Herlev, Denmark,
3Biomarkers and Reseach, Nordic Bioscience, Herlev, Denmark
SESSION INFORMATION
Background/Purpose:
Treatment of RA patients is guided by measures of disease activity such as DAS28, best practice recommendation, and less
often by a treat-to-target approach. This is due to a lack of diagnostic tools that can make an objective endotypic profile of
the patient allowing for better targeted treatment. Another challenge is that traditionally used biomarkers reflect the level of
systemic inflammation (e.g. cytokines) rather than the affected tissue. The aims were to test a novel combination of blood-
based biomarkers reflecting tissue turnover and inflammation to identify patients with different forms of RA. In addition,
we investigated whether such endotypes are associated with clinical disease activity and structural progression.
Methods:
Post-hoc analysis was conducted on a cohort of patients with active and moderate-severe RA from a biomarker sub-study
of LITHE, a phase III clinical trial (N=741). Only patients from the placebo arm were considered, who had serological
biomarkers measured at both baseline (BL) and week 4, as well as bone erosion (ERN) measured at BL and week 52
(n=69). Progression was defined as a positive absolute change in ERN from BL to week 52. The following biomarkers
reflecting tissue metabolite were measured in BL samples: PIINP and C2M (cartilage formation/degradation); CTX-I, OC
PINP and ICTP (bone resorption and formation); C1M and C3M (interstitial matrix degradation); C4M and C6M
(basement membrane degradation; and CRPM and VICM (inflammation).
All serum measurements were log transformed and normalized to have values between zero and one. Unsupervised
hierarchical clustering was then performed using serological biomarkers taken at BL and week 4. The significance of
change in ERN of each group was tested using a Mann-Whitney U test.
Results:
Hierarchical clustering revealed two main clusters. Cluster A (see figure) is defined by low levels of collagen biomarkers
and varying levels of other biomarkers. Cluster B displays high level of bone, connective tissue and basement membrane
markers, and low levels of the cartilage markers. Ten of the 12 biomarkers were significantly lower in cluster A than in
cluster B (p< 0.5). Cluster A can be divided into several subgroups characterised by high bone biomarkers and low bone
biomarkers respectively. Due to the small population size in this study, the significance of these clusters was not
investigated.
There is a trend showing that patients in cluster B have a higher DAS28 score at BL (p=0.08). The change in ERN was
significantly different between the clusters (p=0.04) indicating group B (55% progressors) progresses faster than group A
(29%).
Conclusion:
Using hierarchical clustering we were able to identify different endotypes of structural progression, including faster
progressors in most need of treatment. Other likely endotypes were also identified, which shall be investigated further.
Disclosure: J. P. M. Blair, ProScion, 3; C. L. Bager, ProScion, 3; L. M. Staunstrup, ProScion, 3; H. B. Nielsen,

ProScion, 3; M. Karsdal, Nordic Bioscience Diagnostic, 1; A. C. Bay-Jensen, Nordic Bioscience Diagnostic, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/endotypic-clustering-of-rheumatoid-

arthritis-patients-through-the-use-of-tissue-specific-serum-biomarkers-identifies-structural-progressors
Clinical and Biomarker Factors in the Prediction of Future Inflammatory

Arthritis in ACPA Positive Subjects without Inflammatory Arthritis at
Baseline
John P. Gerstenberger1, Colin I. O'Donnell2, Sarah L. Dill3, Randall Tagg4, Masoud Asadi-Zeydabadi4, M. Kristen
Demoruelle5, V. Michael Holers6 and Kevin D. Deane7, 1Department of Medicine, University of Colorado Denver School
of Medicine, Aurora, CO, 2University of Colorado Denver School of Medicine, Aurora, CO, 3Division of Rheumatology,
University of Colorado Denver School of Medicine, Aurora, CO, 4Department of Physics, University of Colorado Denver,
Denver, CO, 51775 Aurora Ct, 1775 Aurora Ct, Aurora, CO, 6Rheumatology Division, University of Colorado School of
Medicine, Aurora, CO, 7Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO
SESSION INFORMATION
Background/Purpose:
Antibodies to citrullinated protein antigens (ACPA) can identify individuals who may develop future inflammatory arthritis
(IA) and classifiable rheumatoid arthritis (RA). Indeed, there are clinical trials underway where ACPA(+) individuals are
treated to determine how IA/RA can be prevented or delayed. However, not all ACPA(+) subjects progress to IA/RA within
the 2-3 years that is often duration for a clinical prevention trial. As such, identifying ways to predict which ACPA(+)
subjects will most likely progress to IA/RA within defined time periods could improve selection of individuals for RA
prevention trials as well as help to improve understanding of the biology of IA/RA development.
Methods:
21 ACPA(+) (CCP3, Inova) individuals without historical or current IA were identified at a Colorado-based health-fair.
These individuals were followed prospectively for up to 24 months for incident IA/RA. Clinical and examination factors,
and biomarkers including the shared epitope, CCP3, RF-IgM (Inova), and high sensitivity C-reactive protein (hsCRP), were
evaluated to determine which factors predicted incident IA/RA. Specifically, optimal levels for association with IA/RA of
autoantibodies and hsCRP were determined with machine learning techniques, and these optimal levels were then evaluated
with other factors to identify the overall best models for discrimination of the development of IA/RA.
Results:
9 of 21 subjects (43%) developed IA/RA after a median of 11 months (Table 1). In univariate analyses of baseline factors,
only self-reported joint stiffness was significantly associated with the development of IA/RA. Results from AUC analyses
incorporating various variables are presented in Table 2. Overall, models using a combination of demographic and clinic
factors, and optimized biomarker levels, had the highest discrimination (AUC 1.0) for the development of future IA/RA.
Conclusion:
Individuals at high risk for progression to IA/RA can be identified through health-fair evaluations for ACPA. Furthermore,
clinically-obtainable factors including biomarkers that are optimized using machine learning techniques can be used to
determine with high discrimination which serum ACPA(+) individuals will develop IA/RA within 24 months. Caveats
include that this is a small sample set with potential overfitting of the models in regard to the optimized levels of
biomarkers; therefore, these findings need additional validation. Nevertheless, this approach appears useful to better
identify candidates for IA/RA preventive interventions.
Table 1. Descriptions and univariate analyses of
baseline variables of subjects identified with anti-CCP3
positivity in absence of IA
Incident No P-
IA/RA IA/RA value
N=9 N=12
Months to IA/RA or total follow- 11 (4-23) 10 (6- 1.00
up, median (range) 24)
Age, median (range) 55 (40- 48 (29- 0.31
73) 83)
Female, N (%) 4 (44%) 6 (50%) 1.00
Non-Hispanic White, N (%) 8 (89%) 9 (75%) 0.60
Ever Smoker, N (%) 6 (67%) 5 (42%) 0.39
Current Smoker, N (%) 0 (0%) 1 (8%) 1.00
Pack-Years, median (range) 4 (0-18) 0 (0-18) 0.35
Weekly alcohol intake >=1 unit, 8 (89%) 10 1.00
N (%) (83%)
Self-report FDR, N (%) 2 (22%) 1 (8%) 0.55
Shared Epitope Positive, N (%) 5 (56%) 3 (25%) 0.20
CCP3 Positive, N (%) (>=20 9 (100%) 12 1.00
units) (100%)
CCP3 Level, median (range) 78 (27- 55 (24- 0.60
262) 377)
RF-IgM Positive, N (%) (>=13.6 3 (33%) 3 (25%) 1.00
units)
RF-IgM Level, median (range) 7 (1-120) 2 (0-44) 0.55
hsCRP positive, N (%)(>10 0 (0%) 0 (0%) 1.00
mg/L)
hsCRP Level, median (range) 1.4 (0.2- 0.8 (0.3- 0.38
5.3) 5.1)
Self-Report Joint Pain (Any Joint 6 (67%) 3 (25%) 0.09
of 68), N (%)
Self-Report Morning Joint 6 (67%) 2 (17%) 0.03
Stiffness (Any duration, any
joint of 68)*
Subjects with >=1 tender joint on 3 (33%) 0 (0% 0.06
68 joint examination, N (%)
# of Tender Joints on 68 joint 0 (0-1) 0 (0-0) 1.00
examination, median (range)
Subjects with >=1 swollen joint 0 (0%) 0 (0%) 1.00
consistent with RA-like synovitis
on 66 joint examination
Meeting 2010 ACR/EULAR 7 (78%) 0 (0%) -
Criteria at time of development
of inflammatory arthritis, N (%)
*No subject reported a duration of morning joint stiffness
of >60 minutes; for all subjects, the overall median (range)
of duration of joint stiffness was 20 minutes (0-60).
Table 2. Discrimination of future
IA/RA
Variables in model AUC
Core variables* plus CCP3, 1.0
RF-IgM and hsCRP at
optimized cut-off levels***
Core variables* plus CCP3 0.90
and RF-IgM at standard cut-
off levels
Core variables* alone 0.76
*Core variables include age, gender,
race, history of smoking
(ever/never), presence of shared
epitope (present/absent), self-
reported joint pain (present/absent),
self-reported joint stiffness
(present/absent), and joint
tenderness on examination
(present/absent).
**Standard biomarker cut-off levels

for positivity are: CCP3 >=20 units;
RF-IgM >13.6 units; hsCRP >10
mg/L.
***Optimized biomarker levels are:

CCP3 >42.61 units; RF-IgM 0.69
units; hsCRP 0.85 mg/L.
Disclosure: J. P. Gerstenberger, None; C. I. O'Donnell, None; S. L. Dill, None; R. Tagg, None; M. Asadi-Zeydabadi,
None; M. K. Demoruelle, None; V. M. Holers, None; K. D. Deane, Inova Diagnostics, Inc., 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/clinical-and-biomarker-factors-in-the-

prediction-of-future-inflammatory-arthritis-in-acpa-positive-subjects-without-inflammatory-arthritis-at-baseline
Streptococcus Species Enriched in the Oral Cavity of RA Patients: A

Persistent Source of Peptidoglycan-Polysaccharide Polymers Which Drive
Disseminated Synovial Inflammation
Rabia Moentadj1, Linda Rehaume2, Paraic O Cuiv3, Kate Ormerod4, Muralidhara Maradana3, Vanessa Anne Lakis3,
Mark Morrison2, Philip Hugenholtz4, Helen Benham5, Kim-Anh Lê Cao6 and Ranjeny Thomas1, 1University of
Queensland Diamantina Institute, Brisbane, Australia, 2The University of Queensland Diamantina Institute, Translational
Research Institute, Brisbane, Australia, 3The University of Queensland Diamantina Institute, Brisbane, Australia,
4Australian Centre for Ecogenomics, The University of Queensland, Brisbane, Australia, 5The University of Queensland
Faculty of Medicine, Brisbane, Australia, 6School of Mathematics and Statistics, Centre for Systems Genomics, The
University of Melbourne, Melbourne, Australia
SESSION INFORMATION
Background/Purpose:
In Rheumatoid Arthritis (RA), genetic predisposition and environmental risk factors promote dysbiosis of oral and fecal
microbiota. We hypothesized that specific microbial taxa (operational taxonomic units, OTUs) from the oral microbiota
differentiate between RA and HC and that bacteria enriched in RA subjects directly promote inflammatory arthritis.
Methods:
We chacterized a prospective cohort of RA probands, FDR and HC. Probands met ACR 2010 criteria and/or had a
confirmed RA diagnosis. FDRs included parents, full siblings or offspring of an RA proband; HC were drawn from the
community. From all individuals, we obtained demographics, medical history, epidemiological questionnaires and tissue
collections. After DNA extraction from tongue swabs, we undertook targeted 16S rRNA gene sequencing of all samples
and next-generation sequencing of 18 samples. Statistical analysis used the mixOmics R package. Axenic Streptococcus
isolates (n=3 per group, 16 isolates) were produced.
Results:
116 RA patients, 63 FDR and 43 HC matched for age and gender were recruited. 56% of RA, 4% of FDR and 0% of HCs
were ACPA+. Oral microbiota were altered in RA relative to HC. The oral OTU profile of some FDRs segregated with the
RA patients and some segregated with HC. The oral community profile in RA was enriched in Streptococcus, Rothia,
Bifidobacteria, Actinomyces and Prevotella spp. Axenic Streptococcus isolates grown from oral swabs from 16 individuals
were characterised as Streptococcus Salivarius, Streptococcus Parasanguinis or Streptococcus Infantis using 16S rRNA
sequencing. The abundance of Streptococcal spp. was strongly associated with smoking history. Streptococcal cell walls
(SCW) were generated from reference Streptococcus pyogenes and each of the oral isolates. After one i.p. injection of
purified peptidoglycan-polysaccharide polymers (PG-PS 10S) from Streptococcus pyogenes to ZAP-70W163C-mutant
BALB/c (SKG) mice, significant acute and chronic swelling occurred in wrist and ankle joints.
Conclusion:
We demonstrate distinct oral community profiles in RA patients and FDR relative to HC, which are influenced by smoking.
Thus, compound genetic and environmental risks may create niches for opportunistic pathogens, such as Streptococcus,
before and after the development of RA. The chronicity of SCW-induced arthritis in SKG mice suggests inability of a
genetically predisposed host to effectively clear PG-PS 10S, which is resistant to degradation in vivo. Dissemination of
persistently activated macrophages loaded with inflammatory bacterial remnants from the oral mucosa to lymphoid organs
and peripheral joints may propagate the presentation of bacterial antigens and macrophage-driven inflammation in RA.
Disclosure: R. Moentadj, None; L. Rehaume, None; P. O Cuiv, None; K. Ormerod, None; M. Maradana, None; V. A.
Lakis, None; M. Morrison, None; P. Hugenholtz, None; H. Benham, AbbVie, 2,AbbVie, 8; K. A. Lê Cao, None; R.
Thomas, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/streptococcus-species-enriched-in-the-

oral-cavity-of-ra-patients-a-persistent-source-of-peptidoglycan-polysaccharide-polymers-which-drive-disseminated-
synovial-inflammation
Is Leukotoxin_A Produced By Aggregatibacter Actynomycetemcomitans

Important for Initiating Autoimmune Responses Underlying Rheumatoid
Arthritis?
Mikhail Volkov1, Jacqueline Dekkers1, Bruno G. Loos2, Sergio Bizzarro2, Tom W.J. Huizinga3, Helle A. Praetorius4, Rene
E.M. Toes5 and Diane van der Woude1, 1Department of Rheumatology, Leiden University Medical Center, Leiden,
Netherlands, 2Department of Periodontology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and
Vrije Universiteit, Amsterdam, Netherlands, 3Department of Rheumatology, LUMC, Leiden, Netherlands, Leiden,
Netherlands, 4Department of Biomedicine, Aarhus University, Aarhus, Denmark, 5Rheumatology, Leiden University
Medical Center, Leiden, Netherlands
SESSION INFORMATION
Background/Purpose: In a recent publication in Science Translational Medicine, Konig et al. (2016) describe a potential
explanation for the link between periodontal infection and RA. They identify a specific periodontitis-associated bacterium:
Aggregatibacter actinomycetemcomitans (Aa), which via its pore-forming toxin (leukotoxin A: LtxA) can dysregulate the
activity of citrullinating enzymes in neutrophils. Furthermore, the authors report that the risk conferred by the most
important genetic risk factor for RA: the HLA-DRB1 shared epitope (HLA SE) alleles, was limited to RA patients who had
been exposed to Aa as determined by seropositivity to LtxA. Aiming to replicate their findings, we focused on two main
questions: 1) is the increased exposure to Aa as measured by the presence of anti-LtxA-antibodies specific for RA, or also
present in other forms of inflammatory arthritis? 2) can we replicate the finding that the association between HLA SE
alleles and ACPA-positive RA is limited to the anti-LtxA-positive subset?
Methods: We established an ELISA against purified LtxA (acquired from the same source as in the original article) and
tested sera from 594 patients from the Leiden Early Arthritis Clinic with various diagnoses, including RA, OA, SpA, PsA,
sarcoidosis, and gout. Serial dilutions of a mix of 3 strongly positive RA patients were used as a standard, and the lowest
point of the linear part of the standard curve (2000 AU/ml) was defined as the cut-off.
Results: As shown in Figure 1, anti-LtxA antibodies could be found in a substantial proportion of RA patients, but also in
patients with other forms of arthritis. Within RA patients, there was no association with the presence of HLA SE alleles
and/or ACPA, in contrast to the previous findings.
Conclusion: Although microbial influences may well be important in the development of RA, our results do not support a
key role of exposure to LtxA originating from the periodontal pathogen Aa in linking the effect of the HLA SE alleles and
periodontal disease to anti-citrullinated protein autoimmunity in RA.
Figure 1.
Distribution of anti-LtxA antibodies in sera of 594 patients suffering from early arthritis. Levels of anti-LtxA antibodies in
the serum of each individual are shown.
LtxA Leukotxin A, RA Rheumatoid arthritis, Aa Aggregatibacter actinomycetemcomitans, OA Inflammatory osteoarthritis,

SpA Spondylarthritis with peripheral arthritis, PsA Psoriatic arthritis, Sarc Sarcoidosis, ACPA anti-citrullinated protein
antibodies, SE shared epitope. Red lines indicate the median level per group. The dashed line indicates the cut-off. The
number of patients per group and percentage of patients positive according to the cut-off are shown underneath.
Reference:
M. F. Konig, L. Abusleme, J. Reinholdt, R. et al, Aggregatibacter actinomycetemcomitans–induced hypercitrullination

links periodontal infection to autoimmunity in rheumatoid arthritis. Sci. Transl. Med. 8, 369ra176 (2016).
Disclosure: M. Volkov, None; J. Dekkers, None; B. G. Loos, None; S. Bizzarro, None; T. W. J. Huizinga, None; H. A.
Praetorius, None; R. E. M. Toes, None; D. van der Woude, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/is-leukotoxin_a-produced-by-

aggregatibacter-actynomycetemcomitans-important-for-initiating-autoimmune-responses-underlying-rheumatoid-arthritis
Methotrexate Is an Antibacterial Drug Metabolized By Human Gut Bacteria

Renuka R. Nayak1, Kye Stapleton-Gray2, Colleen O'Loughlin3, Michael Fischbach4 and Peter J. Turnbaugh5,
1Department of Medicine, Division of Rheumatology, Rosalind Russell / Ephraim P. Engleman Rheumatology Research
Center, San Francisco, CA, 2Carnegie Mellon University, Pittsburgh, PA, 3University of California, San Francisco, San
Francisco, CA, 4Department of Bioengineering and Therapeutic Sciences,, University of California, San Francisco, San
Francisco, CA, 5Microbiology and Immunology, University of California, San Francisco, San Francisco, CA
SESSION INFORMATION
Background/Purpose:
Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology causing inflammation and irreversible damage in
joints and other organs. Methotrexate (MTX) is first-line therapy used in the treatment of RA. However, not all patients
respond to MTX -- about 50-60% of patients require additional therapy. Because MTX is a folic acid analogue that may
affect evolutionarily conserved pathways found in bacteria, we hypothesized that the gut microbiome is altered by MTX
and that gut bacteria metabolize the drug. Since gut bacteria have been shown previously to metabolize many
pharmacologic drugs, we also sought to investigate the impact of the microbiome on inter-individual variations in MTX
response. Here, we focus on the response of bacteria to MTX and ask whether bacteria can metabolize MTX.
Methods:
We tested the in vitro growth of 40 gut bacterial isolates in response to MTX. The minimal inhibitory concentration (MIC),
or the concentration of MTX required to suppress bacterial growth > 90%, was identified for each isolate. We asked if these
in vitro findings were recapitulated in vivo by colonizing germ-free mice with human gut bacteria and treating with daily
oral MTX at high (50 mg/kg) and low (1 mg/kg) doses. Next, we asked if bacteria metabolized MTX by examining either
pure bacterial cultures in vitro or human stool sample ex vivo. Samples were incubated with MTX and metabolism was
measured using HPLC. In select cases, we also used UPLC-MS-MS to learn the identity of MTX metabolites.
Results:
MTX inhibited the growth of 33 of the 40 isolates examined. MICs ranged from 2 ug/ml to >900 ug/ml in vitro. At the
Phylum level, Bacteroidetes tended to be sensitive and Firmicutes tended to be resistant to the antimicrobial effects of
MTX (Wilcoxon rank sum, p=0.005). In vivo studies showed that high-dose MTX altered the humanized gut microbiome of
mice compared to those that were saline-treated (ANOSIM, p=0.001). The relative abundance of Bacteroidetes decreased
while Firmicutes increased, recapitulating what was seen in vitro. Low-dose MTX also produced changes to the
microbiome, but this effect was subtler. We next asked whether gut bacteria metabolize MTX, and found that 8 possessed
this ability in vitro. At least two species metabolized MTX into polyglutamated MTX, which is a novel finding that has not
been described previously in the literature. In ex vivo studies, human fecal slurries incubated with MTX produced known as
well as novel MTX metabolites.
Conclusion:
We conclude that MTX is an antibacterial drug. Furthermore, we find that gut bacteria metabolize MTX. One metabolite
found in our study was polyglutamated MTX, which prior studies have shown to be associated with patient response. Our
ongoing and future studies will examine the in vivo implications of these findings in mice and examine whether bacterial
metabolism of MTX is associated with clinical response in patients. Our findings support the hypothesis that a patient’s
response to MTX may be influenced by their gut microbiome. Thus, the microbiome may be an important factor in
predicting patient response to MTX and perhaps other rheumatologic medications as well.
Disclosure: R. R. Nayak, None; K. Stapleton-Gray, None; C. O'Loughlin, None; M. Fischbach, None; P. J.

Turnbaugh, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/methotrexate-is-an-antibacterial-drug-

metabolized-by-human-gut-bacteria-2
The Oral Microbiome Is Altered in Patients with Rheumatoid Arthritis

Sheila Arvikar1, Hatice Hasturk2, Klemen Strle3, Daniel Nguyen4, Marcy B. Bolster5, Deborah Collier6, Alpdogan
Kantarci2 and Allen Steere1, 1Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital,
BOSTON, MA, 2Department of Applied Oral Health Sciences, Forsyth, Cambridge, MA, 3Department of Immunology and
Inflammatory Diseases, Massachusetts General Hospital, BOSTON, MA, 4Forsyth, Cambridge, MA, 5Rheumatology,
Allergy and Immunology, Endocrine Associates, Massachusetts General Hospital, Boston, MA, 6Rheumatology,
Massachusetts General Hospital, Boston, MA
SESSION INFORMATION
Background/Purpose:
The mouth is the second most abundantly colonized mucosal surface in the human body. Periodontitis, a polymicrobial
infectious and inflammatory disease of tooth-supporting structures, is associated with rheumatoid arthritis (RA) and may be
caused by oral microbial dysbiosis, with shift toward pathogenic commensal species. Particular pathogens such as
Porphyromonas gingivalis (Pg), and Aggregatibacter actinomycetecomitans (Aa) have been implicated, but few studies
have analyzed oral microbiota composition in RA patients.
Methods: 73 subjects, 33 RA patients, the majority with new-onset RA, all meeting 2010 ACR/EULAR criteria, 20 age-
and gender-matched healthy subjects (HS) without periodontitis or RA, and 20 patients with chronic periodontitis who
lacked RA (non-RA CP) completed standardized periodontal examination. Subgingival plaque samples (2 per subject) were
evaluated for the presence of 40 bacterial taxa associated with periodontitis biofilms by checkerboard DNA-DNA
hybridization.
Results: Typical of RA cohorts, the 33 patients were mainly female (85%) with median age of 51; 23 had DMARD-naive
early disease, 58% had rheumatoid factor (RF) or anti-citrullinated protein antibody (ACPA). Only one currently smoked.
The majority (91%) received regular dental care with cleanings every 6 months.
Of the RA patients, 10 (30%) had periodontal health, 13 (39%) had gingivitis, and 10 (30%) had periodontitis. Pocket
depth, clinical attachment loss, and bleeding on probing were all increased in the 33 patients compared with HS (P<0.002).
The RA patients had a significantly higher total bacterial load in dental plaque (111.8 x 105) compared with HS (58.9 x 105,
P=0.01) and non-RA CP (70.5 x 105, P=0.03). RA patients with periodontal health had lower bacterial burden than those
with gingivitis and periodontitis (P=0.03). Seropositive RA patients also tended to have a higher oral bacterial load than
seronegative patients. By phylum, RA patients had particularly higher levels of Actinobacteria, Proteobacteria, and
Firmicutes compared to both HS and non-RA CP (P≤0.03), whereas Fusobacteria, Spirochaetes, and Bacteroidetes were
elevated compared to HS (P≤0.03) but similar to non-RA CP.
Accounting for multiple comparisons, 21 of 40 individual microbes had higher DNA probe counts (levels) in RA patients
versus HS (P ≤0.01), this included only 1 red-complex classic pathogen, Tannerella forsythia. Notably, levels of Pg,
detected in 5 RA patients, were not significantly different from HS. Aa was detected in only one RA patient who also had
periodontitis.
While none of the 40 organisms correlated directly with ACPA, 4 correlated with RF levels, particularly Eubacterium
saburreum (R=0.549, P≤0.001), and 9 organisms correlated with swollen joint counts, 6 of which were Actinobacteria
species.
Conclusion: Despite routine dental care and lack of smoking, new-onset RA patients had an abundance of oral bacteria,
with expansion of pathogenic species seen in non-RA CP. Thus dysbiosis is a feature of the oral, as well as gut microbiome,
in RA. Besides pathogens such as Pg and Aa, other oral microbes here were associated with RA autoantibodies and will
require further study.
Disclosure: S. Arvikar, None; H. Hasturk, None; K. Strle, None; D. Nguyen, None; M. B. Bolster, Johnson and
Johnson, 1,Eli Lilly and Company, 2,Rheumatology Research Foundation Amgen Fellow Award, 9; D. Collier, None; A.
Kantarci, None; A. Steere, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-oral-microbiome-is-altered-in-


Efficacy of Tofacitinib in Patients with Moderate to Severe Rheumatoid
Arthritis By Baseline C-Reactive Protein Levels and Erythrocyte
Sedimentation Rates
Sergio Schwartzman1, Ronald F van Vollenhoven2, Alan K Matsumoto3, Dana Orange4, Shweta Shah5, Ryan DeMasi5,
Haiyun Fan5, Palle Dahl6, Ann Wouters7 and Edward C. Keystone8, 1Hospital for Special Surgery, New York, NY,
2Karolinska Institute, Stockholm, Sweden, 3Arthritis & Rheumatism Associates, Wheaton, MD, 4Rockefeller University;
Hospital for Special Surgery; and New York Genome Center, New York, NY, 5Pfizer Inc, Collegeville, PA, 6Pfizer Inc,
Ballerup, Denmark, 7Pfizer Inc, New York, NY, 8University of Toronto, Toronto, ON, Canada
SESSION INFORMATION
Session Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy Poster I: Comorbidities and Adverse
Events; Efficacy and Safety of Small Molecules
Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. This post-hoc analysis
investigated the impact of inflammation severity at baseline (BL) – measured by BL CRP levels and ESR – on efficacy and
safety of tofacitinib.
Methods: Data were analyzed from studies of tofacitinib in RA patients (pts) with prior inadequate response (IR) to
conventional synthetic (cs) or biologic (b) DMARDs, who initiated tofacitinib 5 mg or 10 mg BID as monotherapy or in
combination with csDMARDs, mainly methotrexate. Data were pooled from 4 Phase 2 trials (NCT00413660;
NCT00550446; NCT00603512; NCT00687193) and 5 Phase 3 randomized, double-blind, placebo-controlled trials (ORAL
Scan [NCT00847613]; ORAL Solo [NCT00814307]; ORAL Sync [NCT00856544]; ORAL Standard [NCT00853385];
ORAL Step [NCT00960440]). Analyses were stratified by tertiles, by BL CRP and BL ESR levels, separately. Efficacy
variables analyzed at Month (M) 6 included ACR20/50/70 response rates, and changes from BL to M6 in Clinical Disease
Activity Index (CDAI), DAS28-4 (ESR), and Simple Disease Activity Index (SDAI). Summary/descriptive statistics were
provided. Adverse events (AEs) to M6 were summarized. The results were not adjusted for multiplicity.
Results: The pooled population included 2,161 pts in the csDMARD-IR group and 512 pts in the bDMARD-IR group. Pt
characteristics at BL (Table) were generally similar between groups and across CRP and ESR tertiles, except for RA
duration. In both dose groups, ACR20/50/70 response rates at M6 were generally numerically higher with higher BL CRP
for both csDMARD-IR and bDMARD-IR pts (Figure). Generally, a trend for greater improvement from BL in disease
activity at M6 was observed with higher BL CRP but not with higher BL ESR. Proportion of pts with AEs, serious AEs,
serious infections, and discontinuations due to AEs to M6 were generally similar regardless of BL CRP or ESR.
Conclusion: While efficacy outcomes in csDMARD-IR and bDMARD-IR RA pts were improved after 6 months’
administration of tofacitinib 5 and 10 mg BID across BL CRP/ESR tertiles, this post-hoc analysis suggests that ACR
response rates and disease activity improvements may be numerically greater with higher BL CRP, especially in
bDMARD-IR RA pts. Of interest, this was not noted with higher BL ESR. This disproportionate potential predictive value
needs further investigation. Analyses investigating the impact of inflammation severity at BL on tofacitinib efficacy in pts
with RA are warranted and will include data based on both CRP/ESR tertiles as well as Tender Joint Count (TJC) and
Swollen Joint Count (SJC) tertiles.
Disclosure: S. Schwartzman, AbbVie, Antares, Eli Lilly, Genentech, Janssen, Novartis, Pfizer Inc, Regeneron, Sanofi,
UCB, 5,Crescendo Bioscience, Discus Analytics, National Psoriasis Foundation, 6,AbbVie, Crescendo Bioscience,
Genentech, Janssen, Pfizer Inc, UCB, 8; R. F. van Vollenhoven, AbbVie, Amgen, Bristol-Myers Squibb, GSK, Pfizer Inc,
Roche, UCB, 2,AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo, Eli Lilly, GSK, Janssen, Merck,
Novartis, Pfizer Inc, Roche, UCB, Vertex, 5; A. K. Matsumoto, AbbVie, Amgen, Bristol-Myers Squibb, Pfizer Inc,
2,AbbVie, Amgen, Bristol-Myers Squibb, Pfizer Inc, 5; D. Orange, None; S. Shah, Pfizer Inc, 1,Pfizer Inc, 3; R. DeMasi,
Pfizer Inc, 1,Pfizer Inc, 3; H. Fan, Pfizer Inc, 1,Pfizer Inc, 3; P. Dahl, Pfizer Inc, 1,Pfizer Inc, 3; A. Wouters, Pfizer Inc,
1,Pfizer Inc, 3; E. C. Keystone, Pfizer Inc, 2,Pfizer Inc, 5,Pfizer Inc, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/efficacy-of-tofacitinib-in-patients-with-

moderate-to-severe-rheumatoid-arthritis-by-baseline-c-reactive-protein-levels-and-erythrocyte-sedimentation-rates
Repeated Rituximab Infusions for the Therapy of Rheumatoid Arthritis Is

Not Associated with Increased Rates of Serious Infections
Dimitrios A. Pappas1,2, George W. Reed1,3, Steve Zlotnick4, Jennie Best4, Robert Magner3, Gioia Persuitte1 and Jeffrey
D Greenberg1,5, 1Corrona, LLC, Southborough, MA, 2Department of Medicine, Division of Rheumatology, Columbia
University, College of Physicians and Surgeons, New York, NY, 3University of Massachusetts Medical School, Worcester,
MA, 4Genentech, Inc., South San Francisco, CA, 5NYU School of Medicine, New York, NY
SESSION INFORMATION
Background/Purpose: Extended observations in clinical trials have not demonstrated an increased risk of serious infection
events (SIE) in patients with rheumatoid arthritis (RA) treated with rituximab.1 However, continuous surveillance using
large-scale observational data is of importance. Therefore, the objective of this study was to evaluate the rate of SIEs
among patients with RA who received only an initial rituximab infusion vs those retreated with ≥ 1 rituximab infusion
during the first year of therapy, and also to describe characteristics of rituximab-treated patients who experienced an SIE vs
those who did not.
Methods: Patients with RA enrolled in the Corrona registry (NCT01402661) and treated with rituximab were followed
until their most recent Corrona registry visit, first SIE, switch to another biologic or targeted synthetic disease-modifying
antirheumatic drug, or 12 months after the most recent infusion with no further retreatment – whichever occurred first. The
rate of SIEs was estimated in the overall population as well as in patients retreated with ≥ 1 infusion every 12 months after
rituximab initiation and in those who did not receive a repeat infusion in the first 12 months. Patient characteristics were
compared between those who experienced an SIE and those who did not.
Results: A total of 1361 patients with 1821 patient-years (PY) of follow-up were included; there were 59 SIEs for a rate of
3.24 SIE/100 PYs. 637 patients (46.8%) received ≥ 1 rituximab retreatment during the first 12 months and 724 (53.2%)
received only the initial infusion. In the retreatment population there were 40 SIEs per 1312.8 PY for a rate (95% CI) of
3.05/100 PY (2.18-4.15), and in the no retreatment population there were 19 SIEs per 508.71 PY for a rate (95% CI) of
3.73/100 PY (2.25-5.83). The Kaplan-Meier curve depicting the occurrence of SIEs in the 2 cohorts during the first year of
follow-up is shown (Figure). In the 59 patients (4.3%) who experienced an SIE, the mean (SD) number of rituximab
infusions was 1.88 (1.18), compared with 2.07 (1.70) in the 1302 patients (95.7%) who did not experience an SIE. Patients
who experienced an SIE vs those who did not were older (mean age [SD]: 62.9 [9.9] vs 58.1 [12.55] years), had longer
disease duration (19.1 [13.1] vs 13.6 [10.4] years), were more frequently diabetic (16.9% vs 8.3%) and more frequently had
cardiovascular disease (25.4% vs 12.8%), prior history of SIEs (18.6% vs 5.8%) and pulmonary disease (10.2% vs 4.8%).
There were no differences in other clinical, demographic and medication history characteristics; steroid therapy was similar
between the groups.
Conclusion: Retreatment with rituximab infusions did not result in a higher rate of SIEs in this study. Patients who
experienced an SIE had a higher prevalence of risk factors for infections.
References:
1. van Vollenhoven RF, et al. J Rheumatol. 2015;42:1791-6.

Disclosure: D. A. Pappas, Corrona, LLC, 3,AbbVie, 2,AbbVie, 5; G. W. Reed, Corrona, LLC, 3,Corrona, LLC, 1; S.
Zlotnick, Genentech, Inc, 3; J. Best, Genentech, Inc, 3; R. Magner, None; G. Persuitte, Corrona, LLC, 3; J. D.
Greenberg, corrona, LLC, 1,Corrona, LLC, 3,Genentech, Janssen, Novartis, Pfizer, Eli Lilly, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/repeated-rituximab-infusions-for-the-

therapy-of-rheumatoid-arthritis-is-not-associated-with-increased-rates-of-serious-infections
The JAK1 Selective Inhibitor Filgotinib Regulates Both Enthesis and Colon
Inflammation in a Mouse Model of Psoriatic Arthritis
Catherine Robin-Jagerschmidt1, Stéphanie Lavazais1, Florence Marsais1, Maté Ongenaert2, Alain Monjardet1, Angélina
Cauvin1, Corinne Saccomani1, Isabelle Parent1, Didier Merciris1, Emilie Chanudet1, Roland Blanqué1, Monica
Borgonovi1, Liên Lepescheux1, Marielle Auberval1, Sonia Dupont1, Philippe Clément-Lacroix1 and René Galien1,
1Galapagos SASU, Romainville, France, 2Galapagos NV, Mechelen, Belgium
SESSION INFORMATION
Background/Purpose:
Because of their pleotropic role in cytokine signaling, Janus Kinases (JAKs) are key players in inflammatory diseases.
Among the 4 members of the JAK family (JAK1, JAK2, JAK3, TYK2), JAK1 has been demonstrated as a validated target
in inflammatory diseases with filgotinib (GLPG0634, GS-6034) displaying efficacy and safety in several phase 2 studies in
rheumatoid arthritis (RA) patients. Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease characterized
by the association of skeletal involvement and extra-skeletal symptoms such as psoriasis and Inflammatory Bowel Disease
(IBD) with common findings including enthesitis and dactylitis. Current treatments include anti-TNFa, anti-IL-17 and anti-
IL-12/IL-23 antibodies with varying success rates. The involvement of several pro-inflammatory cytokines suggests that
therapies targeting JAKs may be effective. To gain insight in the potential of a JAK1-selective inhibitor in PsA, we
evaluated filgotinib efficacy in a mouse model of PsA induced by the overexpression of IL-23.
Methods:
Overexpression of IL-23 was induced by hydrodynamic delivery of mIl23 enhanced Episomal Expression Vector (SBI) to
male B10.RIII mice1. Evolution of paw and finger inflammation was assessed by clinical scoring as well as by in vivo
molecular imaging (Bruker In-Vivo Xtreme imaging system). Enthesis, colon and fingers were collected for transcriptomic
analysis. Using immunohistochemistry, infiltration of immune inflammatory cells and pSTAT3 positive cells, were
analyzed in Achilles’ enthesis, subcutaneous area and skin. Colon was also collected for histology and gene expression
analysis.
Results:
High levels of IL-23 were maintained during the time-course of the study and were correlated with severity of finger and
paw swelling and asscociated with inflammation of enthesis and finger as observed in PsA patients. Only moderate
inflammation of the colon was observed. Filgotinib significantly improved clinical scoring and tended to prevent
neutrophil/granulocyte infiltration in paw (notably at earlier time points) while strongly decreasing immune cell infiltration
in the skin. Transcriptomic analysis of enthesis, fingers and colon showed that filgotinib reversed the effect of IL-23 for a
consistent number of genes. Notably, expression of some upregulated inflammatory genes in enthesis and/or fingers
(CCL20, CXCL1, IL‑22, MMP9 and TNFa) as well as the target-related gene Mx2 were reduced. Filgotinib also
significantly counteracted pSTAT3 induction in the subcutaneous area and in the epidermis (mainly concentrated in
proliferating keratinocytes) further demonstrating target engagement in the diseased tissue.
Conclusion:
In a mouse model of PsA, filgotinib improved global clinical score and decreased signs of inflammation in hindlimbs.
Target engagement both in hindlimbs and colon was also demonstrated. These data support the evaluation of filgotinib in
patients with PsA.
References:
1- Sherlock et al. 2012 Nature Med 7:1069–1076
Disclosure: C. Robin-Jagerschmidt, Galapagos SASU, 3; S. Lavazais, Galapagos SASU, 3; F. Marsais, Galapagos

SASU, 3; M. Ongenaert, Galapagos NV, 3; A. Monjardet, Galapagos SASU, 3; A. Cauvin, Galapagos SASU, 3; C.
Saccomani, Galapagos SASU, 3; I. Parent, Galapagos SASU, 3; D. Merciris, Galapagos SASU, 3; E. Chanudet,
Galapagos SASU, 3; R. Blanqué, Galapagos SASU, 3; M. Borgonovi, Galapagos SASU, 3; L. Lepescheux, Galapagos
SASU, 3; M. Auberval, Galapagos SASU, 3; S. Dupont, Galapagos SASU, 3; P. Clément-Lacroix, Galapagos SASU, 3;
R. Galien, Galapagos SASU, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-jak1-selective-inhibitor-filgotinib-

regulates-both-enthesis-and-colon-inflammation-in-a-mouse-model-of-psoriatic-arthritis

Response to Abatacept of Different Patterns of Interstitial Lung Disease in
Rheumatoid Arthritis. Multicenter Study of 63 Patients
Carlos Fernández-Díaz1, Santos Castañeda2, Clara Ojeda-Garcia3, Alejandro Olivé4, Patricia Carreira5, Trinidad Perez
Sandoval6, Miriam Retuerto Guerrero7, Evelin Cecilia Cervantes Pérez8, Samantha Rodriguez9, Bryan Josue Robles
Flores10, Blanca Hernández-Cruz11, Ana Urruticoechea-Arana12, Olga Maiz13, Desiree Palma14, Luis Arboleya15, Gema
Bonilla16, Manuel Rodríguez-Gómez17, Concepción Delgado18, Rosa Expósito19, Ana Ruibal Escribano20, Juan Blanco
Madrigal21, José Antonio Bernal22, Paloma Vela23, Belen Alvarez-Rodriguez24, María Concepción Fito Manteca25, Javier
Narváez26, Manuel Jose Moreno27, Mireia López-Corbeto28, Natalia Mena-Vazquez29, S. Romero-Yuste30, Clara
Aguilera-Cros31, Sergi Ordoñez32, Ignacio Villa-Blanco33, Nuria Vegas-Revenga1, Victor Mora-Cuesta34, Javier Loricera1,
Miguel Angel González-Gay1, José Luis Hernandez35 and Ricardo Blanco1, 1Rheumatology, Hospital Universitario
Marqués de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain, 2Hospital Universitario de
La Princesa, Madrid. Spain, Madrid, Spain, 3Rheumatology, Hospital Virgen de la Macarena, Sevilla, Spain,
4Rheumatology, Hospital Germans Trias i Pujol, Badalona, Spain, 5Department of Rheumatology, Hospital Universitario
12 de Octubre, Madrid, Spain, 6Rheumatology, Hospital de León, LEÓN, Spain, 7Rheumatology, Hospital de León, Leon,
Spain, 8Rheumatology, Hospital Santiago de Compostela, Santiago de Compostela, Spain, 9H. German Trias., Barcelona,
Spain, 10Rheumatology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain, 11Rheumatology, Hospital
Universitario Virgen Macarena, Sevilla, Spain, 12Rheumatology Department. Hospital Can Misses, IBIZA, Spain,
13Hospital Donostia. Spain, San Sebastian, Spain, 14Rheumatology, Rafael Mendez Hospital, Spain., Lorca (Murcia),
Spain, 15Rheumatology, Hospital Universitario Central de Asturias, Oviedo, Spain, 16Hospital Universitario La Paz,
Madrid, Spain, 17Complejo Hospitalario Universitario de Ourense, Ourense, Spain, 18H. Clínico Universitario Lozano
Blesa, Zaragoza, Spain, 19Rheumatology, Hospital Comarcal de Laredo. Spain, Laredo, Spain, 20Rheumatology, Hospital
Universitario de Araba, Vittoria, Spain, 21Rheumatology, Hospital de Basurto, BIlbao, Spain, 22Reumatología, Hospital
Universitario del Vinalopó, Elche, Spain, 23Reumatología, Hospital General Universitario de Alicante. Alicante. Spain,
Alicante, Spain, 24Hospital Txagorritxu, Vittoria, Spain, 25Reumatología, Hospital de Navarra, Pamplona, Spain,
26Rheumatology Department, Hospital de Bellvitge. Barcelona. Spain, L’Hospitalet de Llobregat, Spain, 27Rheumatology,
Hospital Virgen de la Arrixaca, MURCIA, Spain, 28Hospital Universitario Vall d´Hebron, Barcelona, Spain,
29Rheumatology, Hospital Universitario de Malaga, Malaga, Spain, 30H. Pontevedra, Pontevedra, Spain, 31Rheumatology,
Hospital Virgen del Rocio, Sevilla, Spain, 32Hospital Universitario Arnau de Vilanova, Vilanova, Spain, 33Hospital de
Sierrallana, Sierrallana, Spain, 34Neumology, Hospital Universitario Marqués de Valdecilla, IDIVAL,, Santander, Spain,
35Division of Internal Medicine., Hospital Universitario Marqués de Valdecilla, IDIVAL,, Santander, Spain
SESSION INFORMATION
Background/Purpose: Disease modifying antirheumatic drugs (DMARD) such as methotrexate (MTX), ) or antiTNFα
have been implicated in exacerbation of Interstitial lung disease (ILD)of rheumatoid arthritis (RA). Several radiological
patterns of ILD have been described: i) usual interstitial pneumonia (UIP), ii) nonspecific interstitial pneumonia (NSIP), iii)
obliterating bronchitis (OB), and iv) Organized pneumonia (OP)
Our aime was to assess the response to Abatacept (ABA) in these patterns of ILD
Methods: Retrospective multicenter study of RA-ILD treated with ABA. ILD was diagnosed by high-resolution CT scan
(HRCT) and classified in radiological patterns (Travis et al). We consider 3 subgroups: a) UIP, b) NSIP and c) "other" (OB,
OP or mixed). ABA was used at standard dose. We assessed: a) Dyspnea (Medical Research Council-modified scale;
significant variations≥1); B) Respiratory function tests; significant changes≥10% in forced vital capacity (FVC) and
DLCO≤10%, c) HRCT, d) DAS28. A comparative study was performed for the qualitative variables (Fisher test) between
the baseline and 3, 6 and 12 months
Results: We included 63 patients 29 UIP 17 NSIP 17 Others (27 women/36 men), mean age; 63.1±9.6 years. Patients with
RA was seropositive in 85.7%. The ILD was related to DMARDs: MTX (4), etanercept (3), adalimumab (3), certolizumab
(2), Infliximab (1). ABA was used in monotherapy (26) or combined with other DMARDs (37); LFN (15), Cyclosporin (1),
sulfasalazine (4), MTX (6), hydroxychloroquine (10), azathioprine (4), chloroquine (1). Figure shows the evolution in the
available cases. A significant improvement in dyspnea and HRCT. DLCO remained stable in most patients regardless of the
radiological pattern. The activity of RA (DAS28) also improved.
a)
b)
c)
Figure a), b) c): Evolution of different ILD patterns.
Conclusion: ABA appears to be effective in ILD associated-RA, including the pattern of poor prognosis (UIP).
Disclosure: C. Fernández-Díaz, None; S. Castañeda, None; C. Ojeda-Garcia, None; A. Olivé, None; P. Carreira,
None; T. Perez Sandoval, None; M. Retuerto Guerrero, None; E. C. Cervantes Pérez, None; S. Rodriguez, None; B. J.
Robles Flores, None; B. Hernández-Cruz, None; A. Urruticoechea-Arana, None; O. Maiz, None; D. Palma, None; L.
Arboleya, None; G. Bonilla, None; M. Rodríguez-Gómez, None; C. Delgado, None; R. Expósito, None; A. Ruibal
Escribano, None; J. Blanco Madrigal, None; J. A. Bernal, None; P. Vela, None; B. Alvarez-Rodriguez, None; M. C.
Fito Manteca, None; J. Narváez, None; M. J. Moreno, None; M. López-Corbeto, None; N. Mena-Vazquez, None; S.
Romero-Yuste, None; C. Aguilera-Cros, None; S. Ordoñez, None; I. Villa-Blanco, None; N. Vegas-Revenga, None; V.
Mora-Cuesta, None; J. Loricera, None; M. A. González-Gay, None; J. L. Hernandez, None; R. Blanco, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/response-to-abatacept-of-different-

patterns-of-interstitial-lung-disease-in-rheumatoid-arthritis-multicenter-study-of-63-patients
Assessment of Early Improvement in Pain and Other ACR Components As

Predictors for Achieving Low Disease Activity or Remission in Three Phase 3
Trials of RA Patients Treated with Baricitinib
Michael Weinblatt1, Mark C. Genovese2, Joel Kremer3, Luna Sun4, Himanshu Patel4, Alisa Koch4, David Muram4,
Jeffrey R. Curtis5, Cynthia J. Larmore4 and Baojin Zhu4, 1Brigham and Women’s Hospital, Boston, MA, 2Stanford
University Medical Center, Palo Alto, CA, 3The Center for Rheumatology, Albany Medical College, Albany, NY, 4Eli Lilly
and Company, Indianapolis, IN, 5University of Alabama at Birmingham, Birmingham, AL
SESSION INFORMATION
Background/Purpose:
The purpose of this analysis was to assess whether early improvement in ACR components could act as predictors of low
disease activity (LDA) or remission (REM) at Week 12 in Phase 3 trials of baricitinib (BARI). The patient’s assessment of
pain, a patient-reported outcome measured by a 0-100 mm visual analog scale (VAS), was a focus for this analysis.
Methods:
In RA-BEAM1, 487 patients with inadequate response (IR) to methotrexate (MTX) were randomized to BARI 4 mg once
daily. In RA-BEACON2, a trial of bDMARD-IR patients, 174 patients were randomized to BARI 2 mg and 177 to BARI 4
mg once daily. In RA-BUILD3, a trial with csDMARDs-IR patients, 229 patients were randomized to BARI 2 mg and 227
to BARI 4 mg once daily. LDA was defined as CDAI ≤10 or DAS28-ESR ≤3.2 and REM as CDAI ≤ 2.8 or DAS28-
ESR<2.6 at Week 12. Early improvement, changes from baseline to Week 4, for each of the ACR components (pain VAS,
patient global assessment of disease activity [PtGA], physician global assessment of disease activity [PGA], swollen joint
count, tender joint count [TJC], HAQ-DI, hsCRP, and ESR) was evaluated on their respective predictability for LDA or
REM at Week 12 using area under the curve (AUC) of receiver operating characteristic (ROC) curves. The optimum cutoff-
point in percent improvement at Week 4 was evaluated based the Youden index and the negative predictive value (NPV).
Results:
Early improvement in pain VAS, TJC, PtGA, and PGA had among the highest predictability, whereas hsCRP and ESR had
among the lowest, as measured by AUC of ROC (Figs. 1 and 2 for RA-BEAM data), for achieving both LDA and REM at
Week 12. A threshold of 30-50% improvement in pain from baseline to Week 4 had the optimum range for predicting LDA
and REM at Week 12 (Table). Consistent results were observed for csDMARD-IR and bDMARD-IR patients, and these
results were similar for both BARI 2 mg and BARI 4 mg doses.
Conclusion:
In these trials, patients with a lack of early response to BARI, as assessed by improvement in pain VAS at Week 4, tended
to be less likely to achieve LDA or REM at Week 12 vs. patients with an early response. A minimum of 30% improvement
in pain resulted in optimum NPV in this analysis.
References:
1. Taylor et al. N Engl J Med 2017; 376:652-662

2. Genovese et al. N Engl J Med 2016; 374:1243-1252
3. Dougados et al. Ann Rheum Dis. 2017;76:88-95
Disclosure: M. Weinblatt, Amgen, BMS, Crescendo Bioscience, UCB, Genzyme, 2,Amgen, Abbvie, BMS, Eli Lilly and
Company, Gilead, Merck, Pfizer, Novartis, Roche, UCB, Crescendo Bioscience, Genzyme, Samsung, 5; M. C. Genovese,
AbbVie, Eli Lilly and Company, Galapagos, Gilead, Pfizer, 5,AbbVie, Eli Lilly and Company, Galapagos, Gilead, Pfizer, 2;
J. Kremer, Abbvie, Amgen, BMS, Genentech, GSK, Eli Lilly and Company, Novartis,Pfizer, 5,Abbvie, Genentech, Eli
Lilly and Company, Novartis, Pfizer, 2,Corrona, 1,Corrona, 3; L. Sun, Eli Lilly and Company, 1,Eli Lilly and Company, 3;
H. Patel, Eli Lilly and Company, 1,Eli Lilly and Company, 3; A. Koch, Eli Lilly and Company, 1,Eli Lilly and Company,
3; D. Muram, Eli Lilly and Company, 1,Eli Lilly and Company, 3; J. R. Curtis, AbbVie, Amgen, BMS, Janssen, Pfizer,
Roche/Genentech, Corrona, UCB, 2,AbbVie, Amgen, BMS, Janssen, Pfizer, Roche/Genentech, Corrona, UCB,
5,University of Alabama at Birmingham, 3; C. J. Larmore, Eli Lilly and Company, 1,Eli Lilly and Company, 3; B. Zhu,
Eli Lilly and Company, 1,Eli Lilly and Company, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/assessment-of-early-improvement-in-

pain-and-other-acr-components-as-predictors-for-achieving-low-disease-activity-or-remission-in-three-phase-3-trials-of-ra-
patients-treated-with-baricitinib
Low Patient Global Assessment Scores in Rheumatoid Arthritis Are

Associated with Pain and Physical Function in Patients Treated with
Tofacitinib: A Post-Hoc Analysis of Phase 3 Trials
Vibeke Strand1, Rieke Alten2, Jeffrey Kaine3, Arif Soonasra4, Christopher W Murray4, Haiyun Fan4, Christopher F
Mojcik5 and Gene Wallenstein6, 1Stanford University, Palo Alto, CA, 2Schlosspark-Klinik, University Medicine Berlin,
Berlin, Germany, 3Sarasota Arthritis Research Center, Sarasota, FL, 4Pfizer Inc, Collegeville, PA, 5Pfizer Inc, New York,
NY, 6Pfizer Inc, Groton, CT
SESSION INFORMATION
Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We
examined associations of pain and physical function with Patient Global Assessment of disease activity (PtGA) in patients
(pts) receiving tofacitinib 5 mg twice daily (BID) or placebo (PBO) with background conventional synthetic disease-
modifying antirheumatic drugs (csDMARDs).
Methods: This was a post-hoc analysis of pooled data from three Phase 3 randomized controlled trials (ORAL Sync
[NCT00856544]; ORAL Standard [NCT00853385]; ORAL Scan [NCT00847613]) in pts with inadequate responses to
biologic or csDMARDs (ORAL Sync) or methotrexate (MTX) (ORAL Standard/Scan). Patient Assessment of Arthritis
Pain (Pain; visual analog scale [VAS] 0–100 mm), Health Assessment Questionnaire-Disability Index (HAQ-DI), and
PtGA (VAS 0–100 mm) scores were recorded at baseline (BL) and Month (M) 3. Associations between ‘low global
assessment of disease’ (PtGA ≤20) and mild Pain (VAS score ≤30) or HAQ-DI response (score ≤0.5 or change from
baseline ≥0.22) were independently evaluated. Relationships between PtGA and Pain or HAQ-DI were assessed using
Spearman rank correlation coefficients at BL and M3 without adjustments for multiplicity.
Results: At M3 216/695 (31.1%) pts receiving tofacitinib 5 mg BID and 62/366 (16.9%) pts receiving PBO reported PtGA
≤20; 346/695 (49.8%) and 109/366 (29.8%) had Pain scores ≤30; 514/694 (74.1%) and 197/365 (54.0%) were HAQ-DI
responders. Across treatment groups, of pts reporting PtGA ≤20 at M3, a larger proportion also reported Pain ≤30 vs Pain
>30 (Table 1); of pts with PtGA >20, a high proportion had Pain scores >30. Of pts reporting PtGA ≤20 at M3, a larger
proportion were HAQ-DI responders than HAQ-DI non-responders. Similar associations were noted between PtGA ≤20
and moderate or substantial improvements in Pain (data not shown). The proportions of pts reporting PtGA ≤20 and Pain
≤30 were numerically higher than those with PtGA ≤20 and HAQ-DI responses. Pain and HAQ-DI were significantly
correlated with PtGA at BL and M3 (p<0.0001); correlation coefficients appeared numerically higher between PtGA and
Pain than HAQ-DI (Table 2).
Conclusion: In this post-hoc analysis, reports of low PtGA scores were associated with low pain levels and improved
physical function across treatment groups. Attainment of low PtGA levels appears more associated with improvements in
pain than HAQ-DI responses.
Disclosure: V. Strand, AbbVie, Amgen, Bristol Myers Squibb, CORRONA, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB,
5; R. Alten, None; J. Kaine, Pfizer Inc, Bristol-Myers Squibb, 8; A. Soonasra, Pfizer Inc, 1,Pfizer Inc, 3; C. W. Murray,
Pfizer Inc, 1,Pfizer Inc, 3; H. Fan, Pfizer Inc, 1,Pfizer Inc, 3; C. F. Mojcik, Pfizer Inc, 1,Pfizer Inc, 3; G. Wallenstein,
Pfizer Inc, 1,Pfizer Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/low-patient-global-assessment-scores-

in-rheumatoid-arthritis-are-associated-with-pain-and-physical-function-in-patients-treated-with-tofacitinib-a-post-hoc-
analysis-of-phase-3-trials
Patient-Reported Outcomes of Long-Term Upadacitinib Use in Patients with

Rheumatoid Arthritis: Interim Analysis Results of a Phase 2, Open-Label
Extension Study
Vibeke Strand1, Namita Tundia2 and Alan Friedman2, 1Stanford University, Palo Alto, CA, 2AbbVie Inc., North Chicago,
IL
SESSION INFORMATION
Background/Purpose: Janus kinase (JAK) inhibitors are being evaluated for treatment of active rheumatoid arthritis (RA).
The efficacy of upadacitinib (UPA), a selective JAK inhibitor, in improving patient-reported outcomes (PROs) has been
demonstrated.1 These analyses evaluated the long-term benefits of UPA on PROs in patients with active RA.
Methods: M13-538 (NCT02049138) is an ongoing, Phase 2 open-label extension study designed to assess long-term
efficacy and safety of UPA in RA patients who completed BALANCE I and BALANCE II randomized controlled trials
(RCTs) where doses of 3, 6, 12 and 18 mg BID were evaluated. All eligible patients received UPA 6 mg bid within 30 days
of completing either RCT. At weeks 6 and 12, patients with <20% improvement from baseline in tender (TJC) and swollen
joint counts (SJC) received a dose increase to 12 mg bid UPA. After 6 weeks on 12 mg bid, patients failing to achieve
≥20% improvement in TJC and SJC discontinued treatment. After week 6, at the discretion of the investigator, the dose
could be titrated to 12 mg bid for patients who did not meet low disease activity as defined by the Clinical Disease Activity
Index. Continuing patients were divided into 3 cohorts: those who remained on 6 mg bid (never titrated); who increased to
and remained on 12 mg bid (titrated up); and who increased to 12 mg bid and subsequently reduced to 6 mg bid only for a
safety concern or intolerability (titrated up and down). PROs included: Patient’s Global Assessment of Disease Activity
(PtGA), Pain by Visual Analog Scale (Pain VAS), Health Assessment Questionnaire – Disability Index (HAQ-DI), FACIT
– Fatigue Scale (FACIT-F), Work Instability Score for Rheumatoid Arthritis (RA-WIS), and EuroQoL-5D (EQ-5D). For
this interim analysis, data collected on or before January 13, 2017 were analyzed. Mean changes from baseline and 95%
confidence intervals (CI) were calculated for each PRO at week 48.
Results: 493 patients received UPA. Across cohorts, mean age was 53–56 years, 78%–87% were female, and mean
duration of RA 8.6–9.5 years. The total patient population exposure to UPA was 725.1 patient-years; with 78% of patients
having exposure of ≥12 months and 72% having exposure of ≥18 months. At week 48, patients within all cohorts reported
improvements across all PROs (Table). The majority of patients who never titrated dose reported the largest improvements
from baseline across PROs at week 48, followed by those who titrated up or up and down.
Conclusion: Patients treated with UPA maintained clinically meaningful improvements in disease activity, pain, physical
functioning, fatigue, work functioning, and overall health status till week 48.
Reference
1. Strand V et al. Poster SAT0217. EULAR, Madrid, Spain, 2017.
Table. Mean change in PRO scores from baseline to week 48.

Never Titrateda Titrated Up and Not Titrated Up and
Down a Downa
N=328
N=150 N=15
PRO n Week Change n Week Change n Week Change
48 48 48
PtGA 250 23.4 −39.6 114 36.6 −31.2 14 42.5 −22.4
Pain 250 21.3 −42.7 114 35.5 −32.0 14 29.9 −35.6
VAS
HAQ-DI 249 0.7 −0.8 114 1.0 −0.6 14 0.7 −0.7
FACIT-F 249 40.6 10.8 114 36.3 10.5 14 40.5 11.1
RA- 60 5.2 −7.3 41 9.3 −4.2 4 13.3 −2.8
WISb
EQ-5D 249 77.4 26.5 114 70.5 19.8 14 74.7 21.1
aTitration status was determined based on dosing information up to the cutoff
date for the interim analysis.
bOnly included patients working at the time of questionnaire administration.
Disclosure: V. Strand, AbbVie, Amgen, AstraZeneca, BMS, Celgene, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer,
Regeneron, Sanofi, and UCB, 5,AbbVie, Amgen, AstraZeneca, BMS, Celgene, Genentech, GSK, Janssen, Lilly, Novartis,
Pfizer, Regeneron, Sanofi, and UCB, 9; N. Tundia, AbbVie, 3,AbbVie, 1; A. Friedman, AbbVie, 3,AbbVie, 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/patient-reported-outcomes-of-long-

term-upadacitinib-use-in-patients-with-rheumatoid-arthritis-interim-analysis-results-of-a-phase-2-open-label-extension-
study
Reduction in Disease Activity in Patients with RA and an Inadequate

Response to MTX: Baricitinib Compared to Adalimumab and Placebo
Peter Nash1, Janet E. Pope2, Anabela Cardoso3, Marta Casillas3, Douglas E. Schlichting3, Baojin Zhu3, Scott D. Beattie3
and Josef S. Smolen4, 1University of Queensland, Brisbane, Australia, 2St. Joseph's Health Care, London, ON, Canada,
3Eli Lilly and Company, Indianapolis, IN, 4Rheumatology, Medical University of Vienna, Vienna, Austria
SESSION INFORMATION
Background/Purpose: Baricitinib (BARI), is an oral Janus kinase (JAK)1/JAK2 selective inhibitor for treatment of
patients with moderately to severely active RA. RA-BEAM was a phase 3 study in patients with RA and an inadequate
response to MTX (MTX-IR) in which BARI demonstrated significant improvements in ACR20 response rates and DAS28-
CRP compared to placebo (PBO) and adalimumab (ADA). This abstract examines the effects of baricitinib on disease
activity scores and the improvement of disease activity compared to PBO and ADA utilizing CDAI, which does not include
acute phase reactants and only uses clinical measures (adding physician and patient global assessments, to tender and
swollen joint counts).
Methods: In RA-BEAM, 1305 patients were treated with PBO (N=488), ADA (N=330) or BARI 4 mg (N=487) and
continued to receive background MTX. CDAI for the three treatment groups was determined at baseline (mean [SD] of
37.6 [12.8], 38.1 [12.0], 37.9 [13.0] for PBO, BARI and ADA, respectively) and at each visit post baseline for up to 24
weeks, and for the BARI and ADA groups for up to 52 weeks. In this analysis, CDAI and the improvement from baseline
to Weeks 12 and 24 were compared between treatment groups using analysis of covariance (ANCOVA). The proportions of
patients reaching a disease activity threshold and improvement threshold at Weeks 12 and 24 were compared between
treatment groups using logistic models. Analyses were not adjusted for multiplicity. Missing values were imputed using
modified last observation carried forward.
Results: At baseline, across all treatment arms, 91% of patients had high disease activity and 9% had moderate disease
activity. Treatment with BARI resulted in significantly lower mean disease activity at Weeks 12 and 24 than PBO (p<0.001
at both Weeks 12 and 24) and ADA (p=0.008, Week 12; p=0.035, Week 24). Fewer patients treated with BARI (16.4%)
remained in high disease activity at Week 24 compared to PBO (47.6%, p<0.001) and ADA (22.9%, p=0.017). Patients
treated with BARI had significantly greater improvement in the mean disease activity compared to PBO (p<0.001) and
ADA (p=0.023) at 24 weeks. A larger proportion of patients receiving BARI (86.2%) were able to achieve at least a 12-
point reduction in CDAI, the minimal clinically important difference in disease activity improvement, by Week 24
compared to patients receiving PBO (52.4%, p<0.001) or ADA (77.5%, p=0.001) (Table and graphs).
Conclusion: In MTX-IR RA patients with moderate to severe disease activity, BARI significantly reduced the overall
disease activity compared to PBO and ADA.
CDAI: Disease Activity from Baseline to Weeks 12 and 24
Week 12 Week 24
Placebo BARI 4- ADA Placebo BARI 4- ADA
mg mg
(N=488) (N=330) (N=488) (N=330)
(N=487) (N=487)
CDAI
LS Mean (SE) 24.7 15.6 18.1 23.9 13.4 15.5
(0.7)*** ++ (0.8)*** +
(0.7)*** (0.8)***
(0.6) (0.7)
% Patients with HDA 49.9 21.1*** 26.2*** 47.6 16.4***+ 22.9***
(CDAI >22)
% Patients with MDA 32.8 37.5 39.6 31.3 31.3 28.4
(10< CDAI ≤22)
% Patients with LDA§ 15.5 32.9***+ 27.4*** 16.9 36.4*** 36.9***
(2.8< CDAI ≤10)
% Patients with 1.9 8.5*** 6.7*** 4.1 15.9*** 11.9***
remission (CDAI
≤2.8)
Improvement in CDAI
LS Mean Change -12.9 -22.0 -19.5 -13.6 -24.2 -22.1
from baseline (SE) (0.6)*** ++ (0.7)*** (0.6)*** + (0.7)***
(0.6) (0.6)
LS Mean % 33.1 (1.5) 58.3 51.9 35.1 (1.7) 64.1 58.9
Improvement (SE) (1.5)***++ (1.8)*** (1.7)***+ (2.0)***
% Patients with CDAI 71.1 91.8*** 88.6*** 71.5 92.9*** 90.1***
improvement ≥6
% Patients with CDAI 51.4 83.1***+++ 70.1*** 52.4 86.2***++ 77.5***
improvement ≥12
***p<0.001 vs. placebo; +p<0.05, ++p<0.01, +++p<0.001 vs. adalimumab using
ANCOVA after adjusting for baseline value, region, and joint erosion status for the
CDAI improvement outcome; adjusting for region and joint erosion status for the CDAI
actual score; and using logistic regression models after adjusting for region and joint
erosion status for the proportions of patients reaching a disease activity threshold and
improvement threshold. §p-values for between treatment comparisons were based on
CDAI ≤10.ANCOVA=Analysis of Covariance; ADA=adalimumab; BARI=baricitinib;
CDAI=Clinical Disease Activity Index; HDA=high disease activity; LDA=low disease
activity; LS=least squares; MDA=moderate disease activity; SE=standard error
Disclosure: P. Nash, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Hospira, Janssen, MSD,
Novartis, Pfizer, Roche, Sanofi, and UCB, 5,AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company,
Hospira, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, 8,AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli
Lilly and Company, Hospira, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, 2; J. E. Pope, AbbVie, Amgen,
Bayer, BMS, Celtrion, Eli Lilly and Company, Merck, Novartis, Pfizer, Roche, UCB, 5,Amgen, Bayer, BMS, GSK, Merck,
Novartis, Pfizer, Roche, UCB, 2; A. Cardoso, Eli Lilly and Company, 1,Eli Lilly and Company, 3; M. Casillas, Eli Lilly
and Company, 1,Eli Lilly and Company, 3; D. E. Schlichting, Eli Lilly and Company, 1,Eli Lilly and Company, 3; B. Zhu,
Eli Lilly and Company, 1,Eli Lilly and Company, 3; S. D. Beattie, Eli Lilly and Company, 1,Eli Lilly and Company, 3; J.
S. Smolen, AbbVie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, Glaxo, ILTOO, Janssen, Eli
Lilly and Company, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, UCB, 5,AbbVie,
Janssen, Eli Lilly and Company, MSD, Pfizer, Roche, 2,AbbVie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion,
Chugai, Gilead, Glaxo, ILTOO, Janssen, Eli Lilly and Company, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche,
Samsung, Sanofi-Aventis, UCB, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/reduction-in-disease-activity-in-

patients-with-ra-and-an-inadequate-response-to-mtx-baricitinib-compared-to-adalimumab-and-placebo

BMS-986195 Is a Highly Selective and Rapidly Acting Covalent Inhibitor of
Bruton’s Tyrosine Kinase with Robust Efficacy at Low Doses in Preclinical
Models of RA and Lupus Nephritis
JR Burke, KM Gillooly, MA Pattoli, L Cheng, S Skala, EM Heimrich, TL Taylor, C Pulicicchio, DW Kukral, T Petrone,
IM Catlett, N Zheng, W Li, SH Watterson and JA Tino, Bristol-Myers Squibb, Princeton, NJ
SESSION INFORMATION
Background/Purpose: BMS-986195 is a potent, covalent, irreversible inhibitor of Bruton’s tyrosine kinase (BTK), a
member of the Tec family of non-receptor tyrosine kinases essential in antigen-dependent B-cell signaling and function.
BTK also plays a critical signaling role downstream of low-affinity activating Fcγ receptors (FcγR) in monocytic cells,
high-affinity immunoglobulin E receptors (FcεRI) in granulocytes, and the RANK receptor on osteoclasts. Pharmacologic
inhibition of BTK, therefore, represents an intriguing approach for the treatment of autoimmune disorders such as RA and
lupus. The present report details the cellular and in vivo pharmacology of BMS-986195.
Methods: The potency and selectivity of BMS-986195 were evaluated against a panel of 245 kinases. Cellular assays
included antigen-dependent responses in B cells and immune complex-stimulated cytokine production in human peripheral
blood mononuclear cells. BTK inactivation was determined using active-site probe-based measures of unmodified active
sites, and these assays were used to determine the in vitro rate of inactivation in human whole blood, as well as the kinetics
and dose relationships of in vivo inactivation of BTK in mice and cynomolgus monkeys after oral administration. The
efficacy of BMS-986195 was evaluated in collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA)
models in mice, as well as against nephritis in NZB/W lupus-prone mice.
Results: BMS-986195 is a potent and highly selective inhibitor of BTK, which acts by covalently modifying an active-site
cysteine residue. The compound is more than 5000-fold selective for BTK over all kinases outside of the Tec family, and
selectivity ranges from 9- to 1010-fold within the Tec family. BMS-986195 inactivated BTK in human whole blood with a
rapid rate of inactivation (3.5x10-4 nM-1·min-1) and potently inhibited antigen-dependent interleukin-6 production, CD86
expression and proliferation in B cells (IC50 <1 nM) without effect on antigen-independent measures in the same cells. A
similar potency was measured against FcγR-dependent TNF-α production in human cells. In mice, a dose as low as 0.5
mg/kg, taken orally (PO) daily (QD), resulted in peak BTK inactivation of 98% after only the second dose. BTK was
inactivated to similar levels in whole blood, lymph nodes and spleen in a dose-dependent manner. BMS-986195
demonstrated robust efficacy in murine models of RA including CIA and CAIA, protecting against clinically evident
disease, histologic joint damage and bone mineral density loss. In both models, maximal efficacy was observed at doses
≤0.5 mg/kg PO QD, which achieved ≥95% inactivation of BTK in vivo. At similar doses, the compound was also highly
protective against nephritis in the NZB/W mouse model of lupus. To investigate the dynamics of BTK inactivation and
resynthesis of BTK, cynomolgus monkeys were given single or multiple doses of BMS-986195. 100% peak inactivation of
BTK was obtained with a single administration of BMS-986195 at 0.5 mg/kg PO.
Conclusion: The high selectivity, rapid rate of BTK inactivation and robust efficacy at low doses in preclinical models of
RA and lupus support investigation of BMS-986195 in human autoimmune disorders.
Disclosure: J. Burke, Bristol-Myers Squibb, 3; K. Gillooly, Bristol-Myers Squibb, 3; M. Pattoli, Bristol-Myers Squibb, 3;
L. Cheng, Bristol-Myers Squibb, 3; S. Skala, Bristol-Myers Squibb, 3; E. Heimrich, Bristol-Myers Squibb, 3; T. Taylor,
Bristol-Myers Squibb, 3; C. Pulicicchio, Bristol-Myers Squibb, 3; D. Kukral, Bristol-Myers Squibb, 3; T. Petrone,
Bristol-Myers Squibb, 3; I. Catlett, Bristol-Myers Squibb, 3; N. Zheng, Bristol-Myers Squibb, 3; W. Li, Bristol-Myers
Squibb, 3; S. Watterson, Bristol-Myers Squibb, 3; J. Tino, Bristol-Myers Squibb, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/bms-986195-is-a-highly-selective-and-
rapidly-acting-covalent-inhibitor-of-brutons-tyrosine-kinase-with-robust-efficacy-at-low-doses-in-preclinical-models-of-ra-
and-lupus-nephritis
Monotherapy with Filgotinib, a JAK1-Selective Inhibitor, Reduces Disease-

Related Biomarkers in Rheumatoid Arthritis Patients
Peter C. Taylor1, René Galien2, Annegret Van der Aa3, Corinne Jamoul3, Pille Harrison3, Chantal Tasset3, Yang Pan4,
Lovely Goyal4, Wanying Li4 and Jacqueline Tarrant4, 1Kennedy Institute of Rheumatology, London, United Kingdom,
2Galapagos SASU, Romainville, France, 3Galapagos NV, Mechelen, Belgium, 4Gilead Sciences, Foster City, CA
SESSION INFORMATION
Background/Purpose: The JAK1 selective inhibitor filgotinib (GLPG0634, GS-6034) has been evaluated in a 24-week
phase 2B study (DARWIN 2) as monotherapy in active rheumatoid arthritis (RA) patients who were methotrexate
inadequate responders and has shown a good safety and efficacy profile1. A broad range of serum biomarkers were
measured to characterize the mode of action of filgotinib.
Methods: Serum samples from RA patients who received either placebo (PBO), or filgotinib monotherapy at 100mg or
200mg once daily (QD) were collected at baseline, weeks 4 and 12 and analyzed for 35 biomarkers by validated single- or
multi-plex immunoassays. Median % changes from baseline for biomarkers are reported. Wilcoxon rank-sum test assessed
the significance of the difference between filgotinib treated groups and PBO.
Results: Filgotinib monotherapy was associated with significant reductions in a broad panel of immune- and tissue-related
biomarkers relevant to RA, compared to placebo (27/35 markers). The largest reductions were in the pro-inflammatory
markers IL-6, SAA, and CRP (58-68% median reduction from baseline to week 12, p<0.01). Other top-ranked biomarkers
by effect size were related to joint degradation (MMP1, 3, YKL-40), immune cell recruitment (CXCL10, CXCL13), and
TH17/reg cells (IL-23 and IL-10) (reductions of 28-31%, p<0.05 for all). These effects were present from week 4 and were
maintained at week 12. Other biomarker changes also support down-modulation of TH1 (IL-2, IFN-γ, IL-12), TH2 (IL-4,
IL-5, IL-13), B cell (CXCL13, IL-7, IL-21), and myeloid cells (GM-CSF, MIP-1α). Filgotinib monotherapy did not
increase leptin above PBO-levels.
Table: Median percent change from baseline of biomarkers at week 12

PBO FILGO 200mg QD PBO FILGO 200mg QD PBO FILGO 200mg QD
(N=61) (N=65) (N=61) (N=65) (N=61) (N=65)
BAFF -3 -1 NS IL-6 2 -58 ** MIP-1β 3 3 NS
CRP -27 -68 ** IL-7 0 -21 ** MMP1 5 -28 *
CXCL10 -4 -31 * IL-8 -7 -8 NS MMP3 6 -31 ***
CXCL13 -4 -30 ** IL-10 13 -26 *** RESISTIN 1 -16 **
EGF 11 21 NS IL-12 6 -23 *** SAA 0 -68 ***
GM-
6 -21 *** IL-13 13 -20 *** sgp130 -2 0 NS
CSF
ICAM-1 -4 -8 NS IL-17A 1 -16 ** TNFα 5 -14 **
IFN-γ 6 -23 *** IL-21 4 -23 *** TNF-RI 0 -18 ***
IL-1β 8 -16 *** IL-23 -4 -31 *** VCAM-1 0 -9 ***
IL-2 10 -21 *** LEPTIN 20 26 NS VEGF 0 -22 **
IL-4 21 -22 *** MCP-1 -5 -13 NS YKL-40 -4 -31 **
IL-5 3 -14 *** MIP-1α 3 -6 **
p-values comparing % changes between filgotinib and PBO groups: NS, p>0.05; *p<0.05; **p<0.01; ***p<0.001
Conclusion: Filgotinib reduces the systemic levels of pro-inflammatory and RA-associated tissue-derived biomarkers.
These effects on biomarkers in multiple disease processes and immune cell subsets provide insight into the efficacy shown
by filgotinib evaluated as monotherapy in the Phase 2B study1.
References: 1Kavanaugh A, et al. Ann Rheum Dis 2017; 76: 1009–1019.
Disclosure: P. C. Taylor, UCB, 2,GlaxoSmithKline, 2,Galapagos NV, 2,Eli Lilly and Company, 2,UCB, 5,Eli Lilly and
Company, 5,Pfizer Inc, 5,Galapagos NV, 5,Merck Pharmaceuticals, 5,GlaxoSmithKline, 5,Abbvie, 5,Bristol-Myers Squibb,
5,Janssen Pharmaceutica Product, L.P., 5,Novartis Pharmaceutical Corporation, 5,Sandoz, 5,Biogen Idec, 5; R. Galien,
Galapagos SASU, 3; A. Van der Aa, Galapagos NV, 1,Galapagos NV, 3; C. Jamoul, Galapagos NV, 3; P. Harrison,
Galapagos NV, 1,Galapagos NV, 3; C. Tasset, Galapagos NV, 1,Galapagos NV, 3; Y. Pan, Gilead Sciences, 3; L. Goyal,
Gilead Sciences, 3; W. Li, Gilead Science, 3; J. Tarrant, Gilead Sciences, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/monotherapy-with-filgotinib-a-jak1-

selective-inhibitor-reduces-disease-related-biomarkers-in-rheumatoid-arthritis-patients
Exposure-Response Analyses of the Effect of Upadacitinib on ACR

Responses in the Phase 2b Rheumatoid Arthritis Trials in Patients with
Inadequate Response to Methotrexate or to Anti-Tumor Necrosis Factor
Therapy
Ben Klünder1, Mohamed-Eslam F. Mohamed2, Heidi S. Camp2 and Ahmed A. Othman2, 1AbbVie Deutschland GmbH &
Co. KG, Ludwigshafen, Germany, 2AbbVie, North Chicago, IL
SESSION INFORMATION
Background/Purpose:
Upadacitinib, a selective JAK1 inhibitor, demonstrated favorable efficacy in two Phase 2 studies in subjects with moderate
to severe rheumatoid arthritis (RA) who had inadequate response to prior treatment with anti-tumor necrosis factor (anti-
TNF) therapy in BALANCE I or with methotrexate in BALANCE II. This work was done to characterize upadacitinib
exposure-response relationships for effects on ACR responses in RA patients which supported dose selection for the
ongoing Phase 3 RA trials.
Methods:
The Analyses included data from 276 and 298 subjects in BALANCE I and BALANCE II, respectively. Subjects were
randomized to receive 3, 6, 12, or 18 mg twice daily (BID) or matching placebo in BALANCE I and 3, 6, 12, 18 mg BID or
24 mg once daily or matching placebo in BALANCE II. Upadacitinib was administered in both studies as immediate-
release formulation. Efficacy assessments and sparse blood samples for pharmacokinetic analyses were collected from over
a 12-week period. ACR20, ACR50, and ACR70 responses as well as dropouts were collectively analyzed using a
continuous-time Markov model, where upadacitinib enhanced transition of the status of patients to higher levels of
response (e.g. no response to ACR20, ACR20 to ACR50, ACR50 to ACR70). The final model was used to predict the
efficacy of different upadacitinib doses in both patient populations assuming 300 subjects for each dose. A separate model
was utilized for simulation of placebo response in the anti-TNF inadequate responders population to better capture the
lower placebo response in that population.
Results:
In the Markov analysis, point estimate for upadacitinib plasma concentrations associated with 50% of maximal effect on
the transition rates to higher ACR responses was higher for anti-TNF inadequate responders compared with the
methotrexate inadequate responders, however with overlapping confidence intervals between the populations. The
predicted median (90% Prediction interval) ACR responses are shown in Table 1 compared to the observed ACR responses
from BALANCE 1 and BALANCE II based on non-responder imputation.
Table 1. Predicted median (90% Prediction interval) ACR responses compared to the observed ACR responses based on
non-responder imputation.
Methotrexate Inadequate Anti-TNF Inadequate
Responders Responders
Dose
ACR20 ACR50 ACR70 ACR20 ACR50 ACR70
Group
47 (38- 18 (13- 34 (26- 12 (5-
Model-Predicted 8 (4-13) 3 (1-7)
Placebo 57) 27) 43) 20)
Observed 46 18 6 34 16 4
67 (60- 40 (33- 22 (17- 53 (45- 30 (23- 16 (10-
Model-Predicted
3 mg BID 72) 47) 28) 62) 37) 21)
Observed 62 38 22 53 24 13
69 (63- 44 (36- 25 (19- 58 (51- 35 (28- 20 (13-
Model-Predicted
6 mg BID 74) 51) 31) 67) 43) 27)
Observed 68 46 28 58 36 26
71 (65- 46 (38- 28 (21- 62 (56- 40 (32- 24 (17-
12 mg Model-Predicted
76) 54) 33) 71) 49) 32)
BID
Observed 80 50 16 71 42 22
72 (65- 47 (39- 29 (22- 63 (56- 41 (35- 25 (18-
18 mg Model-Predicted
78) 55) 35) 73) 53) 35)
BID
Observed 64 40 26 67 38 22
69 (63- 44 (37- 26 (20-
Model-Predicted - - -
24 mg QD 75) 52) 32)
Observed 76 39 22 - - -
Simulated dropouts are imputed with non-response.
Conclusion:
The exposure-response models adequately described upadacitinib exposure-response relationships for ACR20, ACR50, and
ACR70 in the BLANACE I and II studies. Using the immediate-release formulation, upadacitinib exposures associated
with 6 mg BID dose are predicted to achieve near maximal efficacy in methotrexate inadequate-responders, while
exposures associated with 12 mg BID dose may provide additional efficacy benefit in anti-TNF inadequate responders.
Disclosure: B. Klünder, AbbVie Inc, 1,AbbVie Inc, 3; M. E. F. Mohamed, AbbVie, 1,AbbVie, 3; H. S. Camp, AbbVie,
1,AbbVie, 3; A. A. Othman, AbbVie, 1,AbbVie, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/exposure-response-analyses-of-the-

effect-of-upadacitinib-on-acr-responses-in-the-phase-2b-rheumatoid-arthritis-trials-in-patients-with-inadequate-response-
to-methotrexate-or-to-anti-tumor-necrosis-fac
The Selective JAK1 Inhibitor Upadacitinib Has No Effect on

Pharmacokinetics of the Hormonal Contraceptives Levonorgestrel and
Ethinylestradiol
Mohamed-Eslam F. Mohamed1, Sheryl Trueman1, Tian Feng2, Alan Friedman3 and Ahmed A. Othman2, 1Clinical
Pharmacology and Pharmacometrics, AbbVie, North Chicago, IL, 2AbbVie, North Chicago, IL, 3AbbVie Inc., North
Chicago, IL
SESSION INFORMATION
Background/Purpose:
Upadacitinib is a selective JAK1 inhibitor being developed for the treatment of several inflammatory diseases, including
rheumatoid arthritis (RA). Upadacitinib showed favorable efficacy and acceptable safety profiles in two Phase 2 studies in
subjects with RA. Currently, doses of 15 mg and 30 mg once daily (QD) are being evaluated in ongoing Phase 3 studies in
RA. Oral contraceptives are expected to be commonly used with upadacitinib in patients with inflammatory diseases. This
study evaluated the effect of multiple doses of upadacitinib on pharmacokinetics of ethinylestradiol and levonorgestrel.
Methods:
Healthy female subjects (N = 20) received single doses of a combined oral contraceptive tablet containing 30 μg
ethinylestradiol and 150 μg levonorgestrel alone (Study Period 1) and on Day 12 of a 14-day regimen of upadacitinib 30
mg QD (Study Period 2). Upadacitinib was administered in the study using the extended-release tablet formulation being
utilized in Phase 3 studies in RA. Blood samples for ethinylestradiol and levonorgestrel assays were collected by
venipuncture prior to and for 96 hours after the oral contraceptive administration in each Study Period. Pharmacokinetic
parameters for ethinylestradiol and levonorgestrel were calculated using non-compartmental analyses.
Results:
The ratios (90% confidence intervals) for Cmax and AUCinf following administration of the oral contraceptive with
upadacitinib compared with administration of the oral contraceptive alone were 0.96 (0.89 to 1.02) and 1.11 (1.03 to 1.19),
respectively, for ethinylestradiol and 0.96 (0.87 to 1.06) and 0.95 (0.85 to 1.07), respectively, for levonorgestrel.
Figure 1. Plasma Concentration versus Time Profiles for Ethinylestradiol and Levonorgestrel Following
Administration of the Combined Oral Contraceptive Alone and with Upadacitinib 30 mg QD
Conclusion:
Upadacitinib has no effect on pharmacokinetics of ethinylestradiol and levonorgestrel; the 90% confidence intervals for the
ratios of ethinylestradiol and levonorgestrel AUC and Cmax when administered with upadacitinib relative to when
administered alone were within the bioequivalence boundaries of 0.8 to 1.25. Therefore, oral contraceptives containing
ethinylestradiol or levonorgestrel can be concomitantly administered with upadacitinib.
Disclosure: M. E. F. Mohamed, AbbVie, 1,AbbVie, 3; S. Trueman, AbbVie, 1,AbbVie, 3; T. Feng, AbbVie, 1,AbbVie, 3;
A. Friedman, AbbVie, 3,AbbVie, 1; A. A. Othman, AbbVie, 1,AbbVie, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-selective-jak1-inhibitor-

upadacitinib-has-no-effect-on-pharmacokinetics-of-the-hormonal-contraceptives-levonorgestrel-and-ethinylestradiol
Tofacitinib Monotherapy Improves Left Ventricular Mass and Cardiac

Output in Patients with Rheumatoid Arthritis
Kensuke Kume1, Kanzo Amano2, Susumu Yamada1, Toshikatsu Kanazawa3 and Kazuhiko Hatta4, 1Rheumatology,
Hiroshima Clinic, Hiroshima, Japan, 2rheumatology., hiroshima clinic, Hiroshima, Japan, 3rheumatology, hiroshima clinic,
hiroshima, Japan, 4Rheumatology, Hatta Clinic, Kure, Japan
SESSION INFORMATION
Background/Purpose: Rheumatologists need to develop primary prevention strategies for cardiovascular disease (CVD) in
rheumatoid arthritis (RA) patients. We reported tofacitinib (Tofa) plus methotrexate improved left ventricular mass index
(LVMI) in patients with rheumatoid arthritis. How about tofacitinib monotherapy? To study the effect of Tofa monotherapy
(MTX) on LV morphology and function in conventional DMARDs resistant active RA patients, in a cohort study design.
Methods: RA patients were eligible if they had active disease despite treatment with conventional DMARDs.
Consecutive 21 patients with moderate to severe active RA patients (DAS28>3.2) despite conventional DMARDs were
received Tofa monotherapy. LV morphology and function was assessed with cardio-MRI at baseline and 24 weeks follow-
up. Cardiovascular risk factors and clinical data were collected at regular visits.
Results: 19 patients completed 24 weeks. Left ventricular mass index (LVMI) was attenuated significantly by Tofa (week
0-week24, −10.02±4.8 g/m2; p=0.02). Cardiac output (CO) was attenuated significantly by Tofa (week 0-week24,-0.65 ±
0.9l/min). DAS28 and CRP improved significantly by Tofa (week 0-week24; DAS28: -2.16±0.95; CRP: 15.1±5.7 mg/l)
(p<0.05). Surprisingly, the change of disease activity (DAS 28 and CRP) is no correlation with the change of LVMI or CO
in this study. Observationally, 2 cases significantly improved right ventricular mass as well as left ventricular mass (20 %
improved right ventricular mass index from baseline).
Conclusion: Tofa monotherapy improved LVMI and CO in active RA despite MTX. Tofa monotherapy improves LVMI
and CO independently of its effects on disease activity. Tofa might be improved right ventricular mass. JAK-STAT pathway
might be an important role of LV hypertrophy. Tofa, JAK-STAT pathway blocking, may prevent cardiovascular morbidity
and mortality in RA.
References: 1) Tofacitinib improves left ventricular mass and cardiac output in patients with rheumatoid arthritis Kume K,
et al. presentation at annual meeting of EULAR 2017
2) Etanercept normalises left ventricular mass in patients with rheumatoid arthritis. Claire Immediato Daïen et al. Annals of
the rheumatic diseases. 2013 Jun; 72(6); 881-7. doi: 10.1136/annrheumdis-2012-201489.
Disclosure: K. Kume, None; K. Amano, None; S. Yamada, None; T. Kanazawa, None; K. Hatta, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/tofacitinib-monotherapy-improves-left-

ventricular-mass-and-cardiac-output-in-patients-with-rheumatoid-arthritis
Improved Patient-Reported Outcomes in Patients with Rheumatoid Arthritis

Who Failed Adalimumab or Placebo Treatment and Were Rescued with
Baricitinib
Bruno Fautrel1, Peter C. Taylor2, Kaleb Michaud3, Himanshu Patel4, Baojin Zhu4, Carol L Gaich4, Jiaying Guo4,
Amanda Quebe4 and Yoshiya Tanaka5, 1Paris VI Pierre et Marie Curie University, Paris, France, 2Botnar Research Centre,
University of Oxford, Oxford, United Kingdom, 3Rheumatology, National Data Bank for Rheumatic Diseases & University
of Nebraska Medical Center, Omaha, NE, 4Eli Lilly and Company, Indianapolis, IN, 5The First Department of Internal
Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
SESSION INFORMATION
Background/Purpose:
In the Phase 3 RA-BEAM study, baricitinib (BARI) 4 mg once daily showed significant clinical improvements compared
with placebo (PBO) and adalimumab (ADA).1 Switching from ADA to BARI, prompted by rescue or study design, without
an ADA washout was associated with improved disease control during the initial 12 weeks after the switch.2 The objective
of this analysis was to evaluate changes in patient-reported outcomes (PROs) from before and after rescue with BARI.
Methods:
1305 patients were randomized 3:3:2 to and treated with PBO for 24 weeks, BARI 4 mg once daily for 52 weeks, or ADA
40 mg every 2 weeks for 52 weeks. All patients received background methotrexate (MTX). Patients whose tender and
swollen joint counts were reduced <20% from baseline at Week 16 were rescued to open-label BARI 4 mg once daily; after
Week 16, rescue was at physician discretion. In this post hoc analysis, patients who were rescued between Weeks 16 and 24
were followed for 12 weeks after rescue. The pain visual analog scale (VAS, 0-100 mm), Health Assessment
Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), SF-36
physical and mental component scores (PCS and MCS), and duration of morning joint stiffness (MJS) were assessed for
patients rescued to BARI. Within group changes before and after rescue were assessed with sign tests for each of the
evaluated PROs. The percentage of patients who met or exceeded clinically relevant thresholds at Week 12 after rescue,
relative to the point of rescue, was also assessed. These analyses were not adjusted for multiplicity.
Results:
More patients randomized to PBO (26%, N=128) were rescued, than ADA (12%, N=40) or BARI (7%, N=35). Of the 203
patients rescued, 102 patients were rescued per protocol (Week 16) and 101 were rescued at the physician’s discretion.
Patients who failed PBO or ADA and rescued to BARI showed significantly greater improvements in pain, HAQ-DI,
FACIT-F, SF-36 PCS, and duration of MJS at 4 weeks after rescue which were sustained through 12 weeks (Table). A
greater percentage of patients rescued from PBO to BARI, followed by ADA to BARI patients, tended to show clinically
relevant improvements in pain, HAQ-DI, FACIT-F, and PCS compared to patients rescued from BARI to BARI (Figure).
Conclusion:
Upon treatment failure with either PBO or ADA, rescue with BARI 4 mg resulted in early, sustained, and clinically relevant
improvements in PROs representing measures of quality of life and symptoms that are important to patients.
References:
1Taylor et al. New Engl J Med 2017;376:652-62.
2Taylor et al., Arthritis Rheumatol 2016; 68 (suppl 10)

Disclosure: B. Fautrel, AbbVIe, Biogen, BMS, Celgene, Hospira, Janssen, Eli Lilly and Company, Novartis, Pfizer,
Roche, SOBI Pharma, UCB, 5; P. C. Taylor, Celgene, Eli Lilly and Company, Galapagos, UCB, Abide Therapeutics,
2,AbbVie, Eli Lilly and Company, Galapagos, GlaxoSmithKline, Pfizer, UCB, Biogen, Sandoz, Novartis, and Janssen, 5;
K. Michaud, Pfizer Inc, 2; H. Patel, Eli Lilly and Company, 1,Eli Lilly and Company, 3; B. Zhu, Eli Lilly and Company,
1,Eli Lilly and Company, 3; C. L. Gaich, Eli Lilly and Company, 1,Eli Lilly and Company, 3; J. Guo, Eli Lilly and
Company, 1,Eli Lilly and Company, 3; A. Quebe, Eli Lilly and Company, 1,Eli Lilly and Company, 3; Y. Tanaka,
Mitsubishi-Tanabe, Takeda, Bristol-Myers, Chugai, Astellas, Abbvie, MSD, Daiichi-Sankyo, Pfizer, Kyowa- Kirin, Eisai,
Ono, 2,Daiichi-Sankyo, Astellas, Pfizer, Mitsubishi-Tanabe, Bristol-Myers, Chugai, YL Biologics, Eli Lilly, Sanofi,
Janssen, UCB, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/improved-patient-reported-outcomes-

in-patients-with-rheumatoid-arthritis-who-failed-adalimumab-or-placebo-treatment-and-were-rescued-with-baricitinib
Long-Term Safety and Efficacy of Upadacitinib (ABT-494), an Oral JAK-1

Inhibitor in Patients with Rheumatoid Arthritis in an Open Label Extension
Study
Mark C. Genovese1, Joel Kremer2, Sheng Zhong3 and Alan Friedman3, 1Stanford University Medical Center, Palo Alto,
CA, 2Albany Medical College, Albany, NY, 3AbbVie Inc., North Chicago, IL
SESSION INFORMATION
Background/Purpose: Upadacitinib (UPA, ABT-494) is a selective, oral JAK-1 inhibitor studied in two phase 2
randomized controlled trials (RCTs) in patients (pts) with rheumatoid arthritis (RA). We assessed UPA safety and efficacy
in BALANCE-EXTEND, an ongoing, combined open-label extension (OLE) of the phase 2 RCTs.
Methods: Pts completing the two 12-week RCTs (in TNF-IR and MTX-IR pts)1,2 could enter the OLE. Pts switched to 6
mg UPA from their RCT dose of UPA 3, 6, 12, 18 mg twice daily (BID), 24 mg once daily (QD) or Placebo. A dose
increase to 12 mg BID was required for pts with <20% improvement in both SJC and TJC on 6 mg BID (at wk 6 or 12),
and permitted for pts not meeting CDAI LDA. Pts without 20% improvement in SJC and TJC 6 wks after escalation, or at
any 2 consecutive visits, were discontinued. The dose was decreased to 6 mg BID only in pts with a safety concern or
intolerability. Pts are grouped as: Never-titrated (on 6 mg BID throughout); Titrated-up (from 6 to 12 mg BID); Titrated-up
and back down (to 6 mg BID). After Jan 2017, the 6 and 12 mg BID doses were replaced by 15 and 30 mg QD extended-
release equivalents currently being studied in phase 3. Data up to Jan 13 2017 are reported. Adverse events (AE) per 100
yrs of pt exposure (PY) are summarized starting from day 1 of OLE. Efficacy is assessed by ACR20/50/70 and LDA (by
DAS28-CRP and CDAI), and observed data are presented upto Wk 72 of OLE due to sample size consideration.
Results: Out of 516 pts who completed the 2 RCTs, 494 entered the OLE, 493 were dosed, 328 (66.5 %) were never-
titrated, 150 (30.4%) were titrated-up, and 15 (3%) were titrated-up and back down; 150 pts (30.4%) were discontinued [42
(8.5%) withdrew consent, 37 (7.5%) due to AE and 24 (4.9%) due to lack of efficacy]. Mean exposure to UPA was 525.4 ±
221.4 days (range 1-961 days), and cumulative exposure was 725.1 PY (Table 1). The E/100PY for any AE in the OLE
(170.5) was lower than for the RCTs in TNF-IR (697.9, 48 PY) and MTX-IR (408.4, 54.6 PY). The E/100PY was 2.3 for
serious infection, 3.7 for herpes zoster, 0.8 for malignancies excluding non-melanoma skin cancer, and 1.0 for adjudicated
cardiovascular events. There were 2 deaths. Changes from baseline in laboratory parameters were consistent with
observations from phase 2 RCTs. For those pts completing Wk 72, efficacy was maintained in pts on 6 mg BID UPA from
day 1 of OLE (never-titrated); 55% pts met ACR70 and 83% were in LDA by DAS28-CRP and CDAI based on as
observed data (Table 2).
Conclusion: No unexpected safety signals were observed during this OLE. Efficacy responses were maintained upto 72
wks in pts on 6 mg BID UPA in the OLE.
Table 1. Summary of Adverse Events in Patients who Entered the OLE
As of Jan 13 2017
N=493, PYs=725.1
Events (E/100PY)
Any AE 1236 (170.5)
Serious AE 68 (9.4)
AE leading to discontinuation 42 (5.8)
AE leading to death# 2 (0.3)
Infections 427 (58.9)
-Serious infections 17 (2.3)
-Opportunistic infectionsδ 3 (0.4)
Anemia 19 (2.6)
Neutropenia 10 (1.4)
Lymphopenia 17 (2.3)
GI perforation 0
NMSCγ 5 (0.7)
Malignancy other than NMSCϮ 6 (0.8)
Herpes Zoster 27 (3.7)
CPK elevationǂ 36 (5.0)
Hepatic disorders§ 37 (5.1)
Adjudicated cardiovascular events 7 (1.0)
PY, patient years; E/100 PY, events/100 PY; AE, adverse events; NMSC, non-
melanoma skin cancer; CPK, creatine phosphokinase
#1 sudden death, likely due to cardiac disease (undetermined or unknown cause
of death);1 death due to Hodgkin’s lymphoma (non-cardiovascular death).
δ1 pt with coccidiomycosis (from an endemic area); 2 pts with oral candidiasis
γ3 pts with basal cell carcinoma; 1 pt with 2 events of squamous cell carcinoma
of skin
Ϯ2 pts with breast cancer (1 pt had bilateral cancer); 2 pts with lymphoma; 1 pt
with prostate cancer
ǂNot symptomatic
§All isolated elevations of ALT/AST or bilirubin; no Hy’s Law cases.
Table 2. Efficacy Measures at Week 72 in Patients who Entered the OLE,
n/N (%)
Never-titrated Titrated-up Overall efficacy in
OLEδ
ACR20 208/231 (90) 78/99 (79) 297/342 (87)
ACR50 172/230 (75) 44/100 (44) 224/342 (65)
ACR70 127/232 (55) 22/101 (22) 153/345 (44)
DAS28-CRP LDA 194/233 (83) 46/104 (44) 250/349 (72)
CDAI LDA 191/230 (83) 42/104 (40) 242/346 (70)
Observed data presented for pts completing Week 72. Efficacy data reflect
attrition in the OLE.
δ Includes pts who were never-titrated, titrated-up, and titrated-up and back down.
ACR20/50/70: 20/50/70% improvement in American College of Rheumatology

criteria; DAS28-LDA, 28-joint count disease activity score using C-reactive
protein; CDAI, clinical disease activity index; LDA, low disease activity
Ref:
1. Kremer et al. 2016, Arth & Rheum;68:2867

2. Genovese et al. 2016, Arth & Rheum;68:2857
Disclosure: M. C. Genovese, AbbVie, Lilly, Astellas, Pfizer, Galapagos, Gilead, 5,AbbVie, Lilly, Astellas, Pfizer,
Galapagos, Gilead, 2; J. Kremer, Corrona, 1,Corrona, 3,AbbVie, 2,BMS, Genentech, Gilead, GSK, Eli Lilly and Pfizer, 5;
S. Zhong, AbbVie, 1,AbbVie, 3; A. Friedman, AbbVie, 3,AbbVie, 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/long-term-safety-and-efficacy-of-

upadacitinib-abt-494-an-oral-jak-1-inhibitor-in-patients-with-rheumatoid-arthritis-in-an-open-label-extension-study
Association between Clinical Response and Normalization of Patient-

Reported Outcome Measures in Rheumatoid Arthritis: Post-Hoc Analysis
from Two Phase 2b Filgotinib Studies
Mark C. Genovese1, Annegret Van der Aa2, Corinne Jamoul2, Chantal Tasset2, Pille Harrison2, René Westhovens3 and
Arthur Kavanaugh4, 1Stanford University Medical Center, Palo Alto, CA, 2Galapagos NV, Mechelen, Belgium, 3University
Hospitals Leuven on behalf of the CareRA Study Group, Leuven, Belgium, 4Medicine, University of California, San
Diego, La Jolla, CA
SESSION INFORMATION
Background/Purpose:
Filgotinib (GLPG0634, GS-6034) is an oral, selective JAK1 inhibitor that has demonstrated safety and efficacy data in two
24-week placebo-controlled phase 2B studies as add-on to methotrexate and as monotherapy in active rheumatoid arthritis
(RA) patients with inadequate response to MTX (MTX-IR)1,2.
The objective is to evaluate the association between normalization of patient-reported outcome measures (PRO) and
clinical response (ACR20) in MTX-IR RA patients treated with either filgotinib or placebo, as add-on to methotrexate
(DARWIN 1), or as monotherapy (DARWIN 2).
Methods:
Patients with active RA were randomized in a double-blind manner to placebo (PBO) or one of 3 daily doses of filgotinib
(FIL, 50mg, 100mg or 200mg) as once daily (DARWIN 1 and DARWIN 2) or twice daily regimen (DARWIN 1) for 24
weeks .This post-hoc analysis at week 12 (W12) included patients treated FIL 100mg and 200mg QD (selected Phase 3
doses), and PBO. PRO included SF-36 (mental and physical components: MCS and PCS respectively; cut-off 50), FACIT-F
(cut-off 40), and HAQ-DI (cut-off 0.5).
Results:
594 and 283 patients with active RA were randomized in DARWIN 1 and 2 respectively. In DARWIN 1, 44%, 64%, and
69% of patients on PBO, FIL 100mg QD and FIL 200mg QD respectively achieved ACR20 response at W12; in DARWIN
2 the respective response was 29%, 66%, and 72%. For all PRO parameters (SF-36 MCS, SF-36 PCS, FACIT-F and HAQ-
DI) and in both studies, a higher proportion of patients with normalized scores was achieved in ACR20 responders
compared to non-responders at W12 across treatment groups (Table 1). .
Conclusion:
This post-hoc analysis of two phase 2B studies in MTX-IR RA patients after 12 weeks of treatment suggests that
normalization of PRO is associated with the ACR20 response, regardless of treatment with filgotinib and background
MTX.
Table 1. Percentage of patients reaching normalized values for PRO at Week 12, by ACR20 response status.
% of patients Placebo 100mg QD 200mg QD
DARWIN 1 (MTX add-on), W12, ITT-LOCF
responders non- responders non- responders non-
responders responders responders
N=38 N=54 N=59
N=48 N=31 N=27
SF-36 MCS ≥50 52.6 27.1 59.3 35.5 59.3 33.3
SF-36 PCS ≥50 7.9 0 14.8 0 16.9 0
FACIT-F ≥40 39.5 10.4 57.4 25.8 50.8 25.9
HAQ-DI ≤0.5 23.7 0 31.5 19.4 40.7 7.4
DARWIN 2 (monotherapy), W12, ITT-LOCF
responders non- responders non- responders non-
responders responders responders
N=21 N=46 N=50
N=51 N=24 N=19
SF-36 MCS ≥50 42.9 23.5 54.3 33.3 52.0 47.4
SF-36 PCS ≥50 9.5 2.0 17.4 4.2 14.0 10.5
FACIT-F ≥40 38.1 7.8 52.2 8.3 42.0 36.8
HAQ-DI ≤0.5 19.0 0 32.6 4.2 30.0 21.1
References
1Westhovens R, et al. Ann Rheum Dis 2017;76:998-1008; 2Kavanaugh A, et al.Ann Rheum Dis 2017;76:1009-1019.
Disclosure: M. C. Genovese, Gilead, 5,Galapagos NV, 5,AbbVie, 5,Eli Lilly and Company, 5; A. Van der Aa, Galapagos
NV, 1,Galapagos NV, 3; C. Jamoul, Galapagos NV, 3; C. Tasset, Galapagos NV, 1,Galapagos NV, 3; P. Harrison,
Galapagos NV, 1,Galapagos NV, 3; R. Westhovens, Celltrion, 5,BMS Research Fund, 5,Roche Pharmaceuticals,
5,Galapagos NV, 5; A. Kavanaugh, Gilead Sciences, Inc, 5,Galapagos NV, 5,Pfizer Inc, 5,AbbVie, 5,Eli Lilly and
Company, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/association-between-clinical-response-

and-normalization-of-patient-reported-outcome-measures-in-rheumatoid-arthritis-post-hoc-analysis-from-two-phase-2b-
filgotinib-studies
Safety Profile of Baricitinib for the Treatment of Rheumatoid Arthritis up to

5.5 Years: An Updated Integrated Safety Analysis
Mark C. Genovese1, Josef S. Smolen2, Tsutomu Takeuchi3, David Hyslop4, William L. Macias4, Terence P. Rooney4, Lei
Chen4, Christina L. Dickson4, Jennifer Riddle Camp4, Tracy Cardillo4, Taeko Ishii5 and Kevin Winthrop6, 1Stanford
University Medical Center, Palo Alto, CA, 2Rheumatology, Medical University of Vienna, Vienna, Austria, 3Division of
Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, 4Eli Lilly and
Company, Indianapolis, IN, 5Eli Lilly and Company, Kobe, Japan, 6Oregon Health & Science University, Portland, OR
SESSION INFORMATION
Background/Purpose: Baricitinib (bari), an oral, selective inhibitor of Janus kinase (JAK) 1 and JAK 2, is approved in the
EU for the treatment of moderately to severely active RA in adults. We further describe the drug’s safety profile with
updated data from an on-going long-term extension (LTE) study.
Methods: Long-term safety of once-daily bari was evaluated in the “all-bari-RA” dataset, which includes all patients (pts)
with active RA exposed to any bari dose from 8 randomized trials (4 Ph3, 3 Ph2, 1 Ph1b) and 1 LTE study (data up to 01-
Sept-2016). Previous all-bari-RA analyses1 are provided for comparison (data up to 10-Aug-2015). Placebo (PBO)
comparisons were evaluated for up to Wk 24 in the “PBO-4mg” dataset from the 6 Ph2/3 trials in which pts were
randomized to bari 4mg, with censoring at rescue or treatment switch. Dose responses were evaluated based on the 4 Ph2/3
trials in which pts were randomized to 2 or 4mg and includes data from the LTE (the “2mg-4mg-extended” dataset). Data
were censored at rescue or dose change (as-treated analysis). Because of the latent period for malignancy, 2mg-4mg-
extended was also analyzed without censoring for rescue or dose change (as-randomized analysis). Incidence rates (IR) per
100 patient-years (PY) were calculated.
Results: In the current analysis, 3492 pts received bari for 6637 total PY of exposure (an increase of over 2400 PY from
previous analysis); maximum exposure was 5.5 yrs (Table 1). No differences were seen for bari 4mg vs PBO in adverse
events (AEs) leading to permanent study drug discontinuation, death, malignancy, serious infection, or major adverse
cardiovascular event (MACE) (Table 1). Herpes zoster IR was significantly higher for bari 4mg vs PBO (IR 1.0 vs 4.3;
PBO, 4mg, respectively). In 2mg-4mg-extended, no significant differences were observed comparing bari 2mg vs 4mg for
the above mentioned events. Malignancy (excluding non-melanoma skin cancer (NMSC)) IR were 0.5 and 1.3 for 2mg and
4mg, respectively, with as-treated analysis and 0.7 and 0.9 with as-randomized analysis. For the above events, the current
IRs in all-bari-RA are similar to those previously reported (Table 1). The following IRs were observed in the current all-
bari-RA: lymphoma (0.09), gastrointestinal (GI) perforation (0.05), and tuberculosis (TB) (0.15, all in endemic areas). The
IRs for these events are also similar to those previously reported (Table 1). Fewer than 1% of pts discontinued due to
abnormal lab results.
Conclusion: In this updated integrated analysis of patients with moderately to severely active RA, including patients
exposed for up to 5.5 years, baricitinib maintained a safety profile that was similar to that previously reported1 and
acceptable in the context of demonstrated efficacy.2,3
References:
1Smolen JS et al. Ann Rheum Dis 2016:75(Suppl 2):243-4.
2Taylor PC et al. NEJM 2017:376:652-62.
3Genovese Mc et al. NEJM 2016:374:1243-52.

Disclosure: M. C. Genovese, AbbVie, Eli Lilly and Company, Galapagos, Gilead, Pfizer, 5,AbbVie, Eli Lilly and
Company, Galapagos, Gilead, Pfizer, 2; J. S. Smolen, AbbVie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion,
Chugai, Gilead, Glaxo, ILTOO, Janssen, Eli Lilly and Company, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche,
Samsung, Sanofi-Aventis, UCB, 5,AbbVie, Janssen, Eli Lilly and Company, MSD, Pfizer, Roche, 2,AbbVie, Amgen,
Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, Glaxo, ILTOO, Janssen, Eli Lilly and Company,
Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, UCB, 8; T. Takeuchi, Pfizer Japan Inc,
Astra Zeneca KK, Eli Lilly and Company Japan KK, Novartis Pharma KK, Daiichi Sankyo Co Ltd, Nipponkayaku Co Ltd,
Janssen Pharmaceutical KK, Merck Serono Co Ltd, Takeda Pharmaceutical Co Ltd, Mitsubishi Tanabe Pharma Co, Astellas
Pharma I, 5,Celtrion, Nipponkayaku Co Ltd, Pfizer Japan Inc, UCB Japan, Daiichi Sankyo Co Ltd, Takeda Pharmaceutical
Co Ltd., Chugai Pharmaceutical Co Ltd, Abbvie GK, Bristol-Myers KK, Eisai Co Ltd, Mitsubishi Tanabe Pharma Co.,
Janssen Pharmaceutical KK, Astellas Ph, 8; D. Hyslop, Eli Lilly and Company, 1,Eli Lilly and Company, 3; W. L. Macias,
Eli Lilly and Company, 1,Eli Lilly and Company, 3; T. P. Rooney, Eli Lilly and Company, 1,Eli Lilly and Company, 3; L.
Chen, Eli Lilly and Company, 1,Eli Lilly and Company, 3; C. L. Dickson, Eli Lilly and Company, 1,Eli Lilly and
Company, 3; J. Riddle Camp, Eli Lilly and Company, 1,Eli Lilly and Company, 3; T. Cardillo, Eli Lilly and Company,
1,Eli Lilly and Company, 3; T. Ishii, Eli Lilly and Company, 3,Eli Lilly and Company, 1; K. Winthrop, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/safety-profile-of-baricitinib-for-the-

treatment-of-rheumatoid-arthritis-up-to-5-5-years-an-updated-integrated-safety-analysis
Efficacy Response to Baricitinib Based on Baseline Characteristics in

Patients Who Are Inadequate Responders to Conventional DMARD
Maxime Dougados1, Terence P. Rooney2, Li Xie2, Rena Klar3, Christina L. Dickson2, Ana Pinto Correia2, Yoshiya
Tanaka4, Michael Schiff5 and Edward C. Keystone6, 1Department of Rheumatology, Rene Descartes University, Hôpital
Cochin, Paris, France, 2Eli Lilly and Company, Indianapolis, IN, 3Quintiles IMS Holdings, Inc., Durham, NC, 4The First
Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan, 5University of
Colorado, Greenwood Village, CO, 6University of Toronto, Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose: Rheumatoid arthritis (RA) is a chronic disease and some patients (pts) have an inadequate response
(IR) to conventional DMARDs (csDMARDs). Baricitinib is an oral, selective inhibitor of Janus kinase (JAK) 1 and JAK 21
approved in the EU for the treatment of moderately to severely active RA in adults. We evaluated the effects of baseline
characteristics, including prior csDMARD use, on the efficacy of bari in csDMARD-IR pts.
Methods: Eligible pts had active RA, were csDMARD-IR and biologic DMARD (bDMARD)-naïve, and were randomized
to bari 4 mg or placebo in 5 global, randomized trials (2 Phase 3, 3 Phase 2). This analysis pooled data to evaluate efficacy
outcomes (ACR50, DAS28-CRP ≤3.2, change from baseline in HAQ-DI) at Week (Wk) 12 in bari 4 mg vs placebo for
potential subgroup interactions based on a variety of baseline characteristics including age, gender, weight, disease
duration, etc. A logistic regression model was used to detect significant interactions; p-value ≤0.1 was considered
significant, with significance in >1 measure given more weight.
Results: Overall samples were N=881 (4 mg) and N=803 (placebo). Pts were aged ~52 years, ~80% were female, and 44-
49% had a history of 1 prior csDMARD (Table 1). In the overall pooled population at Wk 12, responses for ACR50,
DAS28-CRP ≤3.2, and HAQ-DI change from baseline were significantly improved for bari 4 mg vs placebo (Tables 2, 3).
Across subgroups, odds ratios and least squares mean difference (LSMDs) predominately favored bari 4 mg over placebo at
Wk 12 (Tables 2, 3) and were generally similar to the overall pooled population. Significant quantitative interactions were
observed for bari 4 mg vs placebo for BMI in ACR50 and DAS28-CRP ≤3.2 (Table 2) and for race in ACR50 and DAS28-
CRP ≤3.2. No significant interactions were observed for the number of prior cDMARDs. No qualitative interactions were
observed.
Conclusion: Consistent with results in the overall pooled population of csDMARD-IR and bDMARD-naïve pts, at Wk 12
the point estimate for each endpoint favored baricitinib 4 mg vs placebo across subgroups. Thus, baricitinib demonstrated a
consistent, beneficial treatment effect in subgroups, irrespective of baseline characteristics.
1. Fridman JS et al. J Immunol 2010;184:5298-5307.

Disclosure: M. Dougados, AbbVie, Pfizer, Eli Lilly and Company, Novartis, UCB, Merck, Roche, BMS, UCB, 2,AbbVie,
Pfizer, Eli Lilly and Company, Novartis, UCB, Merck, Roche, BMS, UCB, 5; T. P. Rooney, Eli Lilly and Company, 1,Eli
Lilly and Company, 3; L. Xie, Eli Lilly and Company, 1,Eli Lilly and Company, 3; R. Klar, Quintiles IMS Holdings, 3; C.
L. Dickson, Eli Lilly and Company, 1,Eli Lilly and Company, 3; A. Pinto Correia, Eli Lilly and Company, 1,Eli Lilly and
Company, 3; Y. Tanaka, Mitsubishi-Tanabe, Takeda, Bristol-Myers, Chugai, Astellas, AbbVie, MSD, Daiichi-Sankyo,
Pfizer, Kyowa- Kirin, Eisai, Ono, 2,Daiichi-Sankyo, Astellas, Pfizer, Mitsubishi-Tanabe, Bristol-Myers, Chugai, YL
Biologics, Eli Lilly and Company, Sanofi, Janssen, UCB, 8; M. Schiff, AbbVie, Amgen, Antares, BMS, Eli Lilly and
Company, JJ, Novartis, Novo Nordisk, Pfizer, Roche, UCB, 5,Abbvie, BMS, 8; E. C. Keystone, Abbott Laboratories,
Amgen, AstraZeneca, BMS, Hoffmann-LaRoche, Janssen, Eli Lilly and Company, Novartis, Pfizer, Sanofi-Aventis, UCB,
2,Abbott, AstraZeneca, Biotest, BMS, Crescendo Bioscience, Hoffmann-LaRoche, Genentech, Janssen, Eli Lilly and
Company, Merck, Pfizer, UCB, 5,Abbott, Astra Zeneca, BMS Canada, Hoffmann-LaRoche, Janssen, Pfizer, UCB, Amgen,
8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/efficacy-response-to-baricitinib-based-

on-baseline-characteristics-in-patients-who-are-inadequate-responders-to-conventional-dmard

Time to Achieve Moderate/Low Disease Activity and Remission in RA
Patients on Baricitinib Compared to Adalimumab, Methotrexate, and
Placebo
Edward C. Keystone1, Maxime Dougados2, Eric M. Ruderman3, Baojin Zhu4, Pedro Lopez-Romero5, Hanne Lund6,
Anabela Cardoso4, Douglas E. Schlichting4, Pindaro Martinez Osuna4, Robert Ortmann4 and Tore K. Kvien7, 1University
of Toronto, Toronto, ON, Canada, 2Rene Descartes University, Cochin Hospital, Paris, France, 3Northwestern University
Feinberg School of Medicine, Chicago, IL, 4Eli Lilly and Company, Indianapolis, IN, 5Europe Research Center, Eli Lilly
and Company, Madrid, Spain, 6Eli Lilly Norge A.S., Oslo, Norway, 7Diakonhjemmet Hospital, Oslo, Norway
SESSION INFORMATION
Background/Purpose: Baricitinib (BARI), an oral, selective Janus kinase (JAK)1/2 inhibitor1, has shown efficacy in
DMARD naïve RA patients (pts)2 and in pts with inadequate response to methotrexate (MTX-IR).3 In the EU, BARI is
approved for treating moderate to severe active RA in adults. The objective of this analysis is to evaluate the time to
achieve moderate disease activity (MDA), low disease activity (LDA), and remission in pts treated with BARI 4-mg
compared to placebo (PBO) or active comparators, MTX and adalimumab (ADA) from the RA-BEGIN2 and RA-BEAM3
trials.
Methods: In RA-BEGIN, DMARD naïve pts were randomized to BARI 4-mg once daily (QD), MTX or BARI 4-
mg+MTX for 52 weeks (wks). In RA-BEAM, MTX-IR pts were randomized to PBO, BARI 4-mg QD or ADA 40-mg
biweekly for 52 wks (PBO switched to BARI 4-mg at 24 wks). This post hoc analysis estimated the time to achieve MDA
(Clinical Disease Activity Index, CDAI ≤22), LDA (CDAI ≤10), and remission (CDAI ≤2.8) in modified intent-to-treat
(mITT) pts and in the subset of pts with high baseline disease activity (HDA) defined as CDAI >22 from the two trials.
Cumulative incidence of MDA, LDA, and remission over 52 wks for RA-BEGIN and 24 wks for RA-BEAM were
estimated.4 Hazard ratios between treatments were obtained using Cox proportional hazards regression adjusting for region
and baseline joint erosions (1-2 or ≥3 erosions) without control for multiple comparisons.
Results: In DMARD naïve population, BARI 4-mg monotherapy pts were 1.6 times more likely to achieve MDA and LDA
and twice more likely to achieve remission compared to MTX (p<0.001) (Table). Median time to MDA and LDA with
BARI 4-mg treatment (2 and 12 wks, respectively) was 2 and 8 wks shorter than with MTX (4 and 20 wks, respectively)
(Figure). Bari 4-mg+MTX performed similar to BARI 4-mg monotherapy.
In MTX-IR population, BARI 4-mg treated pts were 1.7, 2.3, and 3.5 times more likely to achieve MDA, LDA, and
remission than PBO (p<0.001) and 1.0, 1.1, 1.4 times more likely to achieve MDA (p=0.557), LDA (p=0.295), and
remission (p=0.030) than ADA (Table). Median time to MDA was 5 wks shorter with BARI 4-mg treatment (2 wks) than
PBO (7 wks) but similar to ADA (2 wks). Median time to LDA with BARI 4-mg (12 wks) was 2 wks shorter than ADA
(14 wks) while PBO pts never reached the median time to LDA during the 24 wk study (Figure). Consistent results were
obtained in pts with HDA.
Conclusion: DMARD naïve and MTX-IR pts were more likely to achieve LDA and remission, and at a faster pace, with
BARI 4-mg than the comparator treatment groups.
References: 1. Fridman JS J Immunol 2010 2. Fleischmann R Arthritis Rheumatol 2017 3. Taylor PC N Engl J Med 2017 4.
Gooley TA Stat Med 1999
Disclosure: E. C. Keystone, Abbott, Amgen, AstraZeneca, BMS, Hoffmann-LaRoche, Janssen, Eli Lilly and Company,
Novartis, Pfizer, Sanofi-Aventis, UCB, 2,Abbott, AstraZeneca, Biotest, BMS, Crescendo Bioscience, Hoffmann-LaRoche,
Genentech, Janssen, Eli Lilly and Company, Merck, Pfizer, UCB, 5,Abbott, AstraZeneca, BMS Canada, Hoffmann-
LaRoche, Janssen, Pfizer, UCB, Amgen, 8; M. Dougados, Abbvie, Pfizer, Eli Lilly and Company, Novartis, UCB, Merck,
Roche, BMS UCB, 2,Abbvie, Pfizer, Eli Lilly and Company, Novartis, UCB, Merck, Roche, BMS, UCB, 5; E. M.
Ruderman, AbbVie, Amgen, BMS, GSK, Janssen, Eli Lilly and Company, Novartis, Pfizer, Roche/Genentech, 5; B. Zhu,
Eli Lilly and Company, 1,Eli Lilly and Company, 3; P. Lopez-Romero, Eli Lilly and Company, 1,Eli Lilly and Company,
3; H. Lund, Eli Lilly and Company, 1,Eli Lilly and Company, 3; A. Cardoso, Eli Lilly and Company, 1,Eli Lilly and
Company, 3; D. E. Schlichting, Eli Lilly and Company, 1,Eli Lilly and Company, 3; P. Martinez Osuna, Eli Lilly and
Company, 1,Eli Lilly and Company, 3; R. Ortmann, Eli Lilly and Company, 1,Eli Lilly and Company, 3; T. K. Kvien,
AbbVie, Biogen, BMS, Celltrion, Eli Lilly and Company, Janssen, Merck-Serono, MSD, Novartis, Oktal, Orion Pharma,
Hospira/Pfizer, Roche, Samsung, Sandoz, UCB, 5,AbbVie, Biogen, BMS, Celltrion, Eli Lilly and Company, Janssen,
Merck-Serono, MSD, Novartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Samsung, Sandoz, UCB, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/time-to-achieve-moderatelow-disease-

activity-and-remission-in-ra-patients-on-baricitinib-compared-to-adalimumab-methotrexate-and-placebo
BMS-986195, a Novel, Rapidly Acting, Covalent Inhibitor of Bruton’s

Tyrosine Kinase: Safety, Pharmacokinetic and Pharmacodynamic Profiles in
Healthy Participants
IM Catlett, L Wei, N Zheng, A Liu, B He, I Girgis and M Nowak, Bristol-Myers Squibb, Princeton, NJ
SESSION INFORMATION
Background/Purpose: Bruton’s tyrosine kinase (BTK) is an attractive, novel therapeutic target for autoimmune disease, as
it is required for signal transduction and activation via B-cell receptor, Fc receptor and RANKL pathways.1 Due to the
relatively slow turnover of BTK, a covalently bound inhibitor with a short pharmacokinetic (PK) half-life can lead to
prolonged pharmacodynamic (PD) effects. BMS-986195 is being developed for the treatment of autoimmune diseases. This
study assessed the safety, tolerability, PK and PD of BMS-986195 following oral administration in healthy participants.
Methods: Healthy participants (18–50 years) were randomized in a 3:1 ratio to receive a single dose (0.3–30 mg BMS-
986195 or placebo; n=30) or multiple doses (0.3–10 mg BMS-986195 or placebo once daily for 14 days; n=24). Safety and
tolerability were assessed by physical examinations, vital sign measurements, 12-lead electrocardiograms and clinical
laboratory evaluations. Plasma concentrations of BMS-986195 were measured using a validated liquid chromatography–
tandem mass spectrometry (LC-MS/MS) assay at various time points. BTK occupied by BMS-986195 was measured using
a novel LC-MS assay, as a PD and target engagement marker. Results: BMS-986195 was well tolerated in the single- and
multiple ascending dose study. No drug-related serious adverse events were observed. BMS-986195 was rapidly absorbed
with peak concentrations occurring in <1 hour and eliminated with a half-life of <2 hours across all dose levels tested.
Increases in the PK exposure (area under the curve and maximum serum concentration) were dose proportional. No time-
dependent changes in PK were observed following the multiple-dose administration of BMS-986195. BTK occupancy
increased in a dose-dependent manner following single-dose administration of BMS-986195. The mean (SD) peak BTK
occupancy following a single dose was 19% (3%) at 0.3 mg, and 100% (0%) at ≥10 mg. 100% BTK occupancy was
sustained for up to 24 hours. BTK occupancy returned towards baseline over the following 6 days (Figure). Total BTK
levels did not vary over time or by dose group. With multiple-dose administration, 100% BTK occupancy was reached at
≥3 mg once daily, and drug-occupied BTK exhibited similar kinetics to that observed following a single-dose
administration. Additional PD and safety results from the multiple ascending dose study will be presented. Conclusion:
BMS-986195 was well tolerated at the doses tested in healthy participants. It showed a favorable PK/PD profile with a
rapid elimination of the compound and sustained PD activity, due to the relatively slow turnover of BTK and covalent
binding of BMS-986195. 100% BTK occupancy over the entire daily dosing interval was observed. Overall results suggest
that BMS-986195 is an attractive candidate for further clinical development. 1. Whang JA, et al. Drug Discov Today
2014;19:1200–4.
Disclosure: I. Catlett, Bristol-Myers Squibb, 3; L. Wei, Bristol-Myers Squibb, 3; N. Zheng, Bristol-Myers Squibb, 3; A.
Liu, Bristol-Myers Squibb, 3; B. He, Bristol-Myers Squibb, 3; I. Girgis, Bristol-Myers Squibb, 3; M. Nowak, Bristol-
Myers Squibb, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/bms-986195-a-novel-rapidly-acting-

covalent-inhibitor-of-brutons-tyrosine-kinase-safety-pharmacokinetic-and-pharmacodynamic-profiles-in-healthy-
participants
Leukopenia and Tumor Necrosis Factor Alpha Inhibitor Therapy

Wenlu Xiong1, Rochella A. Ostrowski2, William Adams3 and Rodney Tehrani4, 1Rheumatology, Vanderbilt University
Medical Center, Nashville, TN, 2Rheumatology, Loyola University Medical Center, Maywood, IL, 3Clinical Research
Office, Loyola University Medical Center, Maywood, IL, 4Rheumatology & Immunology, Loyola University Medical
Center, Maywood, IL
SESSION INFORMATION
- Background/Purpose: Tumor necrosis factor (TNF) alpha, a key proinflammatory cytokine in rheumatoid arthritis
(RA) and inflammatory bowel disease (IBD), has been a major target in the treatment of these conditions. Although the
immunosuppressant side effects are well-known, recent studies suggest that TNF alpha inhibition is directly linked to the
development of leukopenia and that serial complete blood cell (CBC) counts should be monitored. However, most studies
investigating hematologic side effects of anti-TNF alpha therapy have been case studies. This study was designed to
identify the frequency of leukopenia in patients on anti-TNF alpha therapy at a tertiary care institution and whether certain
demographics, baseline white blood cell (WBC) counts, or other factors correlate with the development of leukopenia.
- Methods: The chart review was performed for adult patients who received anti-TNF alpha therapy (adalimumab,
etanercept, certolizumab, golimumab, or infliximab) at Loyola University Medical Center between 2007 and 2016 and who
had a baseline WBC count in the year prior to therapy. Subjects with baseline leukopenia (WBC <4 K/uL) were excluded.
Data analysis was performed using the chi-square test, analysis of variance, Student t-test, and a multivariable general
linear model.
- Results: Of 89 patients who met the study criteria, 17 patients (19%) developed leukopenia during anti-TNF alpha
therapy. Patients in the study were treated for RA, IBD, psoriasis, psoriatic arthritis, IBD with associated arthritis,
inflammatory arthritis not otherwise specified, or other diagnoses. Patients who developed leukopenia had significantly
lower mean WBC counts compared to those who did not develop leukopenia (p = 0.01) while all other factors including
sex, race, age, type of TNF inhibitor, diagnosis, duration of therapy, and concomitant methotrexate use were comparable
between the two groups (Table 1). After controlling for these variables, baseline WBC count was the only significant
predictor of lowest WBC count. For every one unit (K/uL) decrease in baseline WBC, the lowest WBC on therapy
decreased by 0.35 K/uL (p<0.001).
- Conclusion: In summary, leukopenia developed in a considerable proportion of patients on anti-TNF alpha therapy.
This observation was not associated with several variables studied, including type of TNF inhibitor used, diagnosis,
duration of therapy, and concomitant use of methotrexate. A lower baseline WBC count was the only significant predictor
for both the development of leukopenia and of the greatest degree of leukopenia. These findings suggest that leukopenia
should be screened periodically for all patients on TNF alpha inhibitor therapy regardless of baseline demographics and
that those who have lower baseline WBC counts may warrant closer monitoring.
Disclosure: W. Xiong, None; R. A. Ostrowski, None; W. Adams, None; R. Tehrani, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/leukopenia-and-tumor-necrosis-factor-

alpha-inhibitor-therapy

Efficacy of Adding Iguratimod Therapy in Rheumatoid Arthritis Patients
Who Had Inadequate Response to Biologic Dmards
Toshiaki Miyamoto, Rheumatology, SEIREI HAMAMATSU GENERAL HOSPITAL, Hamamatsu, Japan
SESSION INFORMATION
Background/Purpose: Iguratimod (IGU) was approved in June 2012 and recommended by JCR guideline 2014 in the
treatment of rheumatoid arthritis (RA). Although there have been efficacy of monotherapy and concomitant MTX in
clinical trials, however, there have been no reports of concomitant biologic DMARDs（Bio）.Therefore, we investigated
efficacy of concomitant IGU therapy in RA patients who had inadequate response to Bio at the author’s institution.
Methods: IGU were prescribed to 62 RA patients from August 2012 to June 2016, subjects were 57 patients adding IGU
who had inadequate response to Bio. Previous treatment Bio was ADA. And concomitant MTX (mean 12 mg/week) of 54
patients (94%). Baseline characteristics were Mean age 53 years, mean duration of illness 5.5 years, corticosteroid use 14%
(mean 2.9mg/day) . The course of DAS28, SDAI, CDAI and remission rates were analyzed.
Results: Mean DAS28-ESR, DAS28-CRP, SDAI, CDAI were significantly decreased from the initiation of IGU treatment
at 24 weeks (3.07→2.27, 2.55→1.63, 6.94→2.21, 6.23→1.95). Remission rates of DAS28-ESR, DAS28-CRP, SDAI,
CDAI were 67%、82%、72%、74% at 24 weeks. There were almost no side-effect after adding IGU.
Conclusion: IGU might be a new RA treatment option for aiming remission in patients who had inadequate response to
Bio.
Disclosure: T. Miyamoto, None;
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/efficacy-of-adding-iguratimod-therapy-

in-rheumatoid-arthritis%e3%80%80patients-who-had-inadequate-response-to-biologic-dmards
Evaluation of the Effectiveness of Injectable Methotrexate for the Treatment

of Rheumatoid Arthritis
Jenny Wan1, Michele Spence2, Fang Niu2, Rita Hui3, Stephen Cheng1, Logan Saito4 and Antony Lin5, 1Kaiser
Permanente Drug Information Services - California Regions, Downey, CA, 2Kaiser Permanente Pharmacy Outcomes
Research Group, Downey, CA, 3Kaiser Permanente Pharmacy Outcomes Research Group, Oakland, CA, 4Kaiser
Permanente Southern California Clinical Pharmacy Services, Downey, CA, 5Rheumatology, Kaiser Permanente Fontana
Medical Center, Fontana, CA
SESSION INFORMATION
Background/Purpose:
Systemic methotrexate (MTX) is the first-line disease-modifying antirheumatic drug (DMARD) for treating early and
established rheumatoid arthritis (RA). When compared to oral MTX, subcutaneous MTX enhances tolerability with a
significant reduction in gastrointestinal side effects. Subcutaneous MTX has further demonstrated better clinical efficacy
than oral MTX in patients who were both oral MTX-experienced and MTX-naïve. This study aimed to better quantify the
role of subcutaneous MTX in delaying initiation of biologic DMARD (bioDMARD).
Methods:
In this retrospective cohort analysis, new users of oral MTX were identified between January 1, 2008 and December 31,
2014 (N=42,413). Patients aged 18 years or older with continuous health plan membership, drug benefit, and RA diagnosis
(n=7,968) were included in this analysis. Patients who had at least one ≥2.5 mg increase in the weekly oral MTX dose
(n=3,970) were compared to those who switched from oral MTX to subcutaneous MTX (n=421). The primary outcome was
the likelihood of initiating a bioDMARD, which was analyzed using Cox proportional hazard model. Other outcomes
measured were the timing of changes in treatment, and doses of oral or subcutaneous MTX at the time of switches or at the
end of follow-up.
Results:
Comparing the two treatment strategies, the unadjusted and adjusted Cox regression analyses showed no significant
difference in the likelihood of initiating bioDMARD. Factors associated with a reduced likelihood of initiation of
bioDMARD included older age, African American, and the initiation of azathioprine. In contrast, the use of systemic
prednisone at baseline and higher erythrocyte sedimentation rate (ESR) during follow-up were associated with an increased
likelihood of initiation of bioDMARD. Among the patients who started bioDMARD, more than two-third of the patients
never received MTX at doses >20 mg/week prior to initiating bioDMARD. Compared to patients who had a dose increase
in oral MTX, patients who switched to subcutaneous MTX significantly delayed the use of bioDMARDs by 9 months
(p<0.001).
Conclusion:
There is no significant difference in the likelihood of initiating bioDMARD between the two treatment strategies.
Compared to oral MTX group, switching to subcutaneous MTX delayed the use of bioDMARD by 9 months. Given that
bioDMARDs are costly and require injections, switching from oral MTX to subcutaneous MTX before using bioDMARD
may be a reasonable alternative for patients who fail oral MTX.
Disclosure: J. Wan, None; M. Spence, None; F. Niu, None; R. Hui, None; S. Cheng, None; L. Saito, None; A. Lin,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/evaluation-of-the-effectiveness-of-

injectable-methotrexate-for-the-treatment-of-rheumatoid-arthritis
The Occurrence of Shingles and the Effect of Zoster Vaccination with the Use
of Methotrexate in Rheumatoid Arthritis Patients
Antony Lin1, Qiaowu Li2, Jiaxiao Shi2, Serena Lin3, Danielle Wang4, Jenny Wan5, Kevin Lee3, Hung-Fu Tseng2 and TC
Cheetham6, 1Southern California Permanente Medical Group, Pasadena, CA, 2Department of Research and Evaluation,
Kaiser Permanente, Pasadena, CA, 3Stanford University, Stanford, CA, 4UCI Medical Center, Irvine, CA, 5Kaiser
Permanente Drug Information Services - California Regions, Downey, CA, 6Western University of Health Sciences,
Pomona, CA
SESSION INFORMATION
Background/Purpose:
To investigate the efficacy and safety of zoster vaccines administered in rheumatoid arthritis(RA) patients taking
methotrexate(MTX).
Methods:
By reviewing data through the Kaiser Permanente electronic medical record (EMR) retrospectively, we identified 893 adult
RA patients who received zoster vaccination between January 1, 2007 and December 31, 2012 and had at least 2 RA
diagnoses documented within one year prior to the vaccination date. Patients treated with any biologic DMARDs within 6
months prior to the index dates were excluded. The cohort was followed until the occurrence of zoster infection,
disenrollment, death or the end of study, whichever came first. The primary outcome, vaccination safety, was measured by
time to occurrence of zoster infections within 42 days after zoster vaccines administered. The secondary outcome, vaccine
efficacy, measured by time to occurrence of zoster infections (after day 42) until the end of follow-up period, was studied
among those who maintain the treatment during follow-up period (n=762). Dosage effect was also analyzed among those
taking MTX (n=342) by comparing patients taking >=25mg/week and those taking 22.5mg/week or less. Cox proportional
model was used to analyze hazard ratios between groups.
Results:
Among 893 RA patients who were given zoster vaccines, 366 patients were taking MTX within 6 months prior to the zoster
vaccination and 527 patients were not taking MTX. At baseline, 707(79%) patients were female with a mean age of 70.1
(SD: .5) and disease duration of 6.6 (3.9) years. The analysis showed that the rate of zoster infection was 0.13 per 1000-
person day in the MTX group and the rate was 0.23 per 1000-person day in the non-MTX group. We found no significant
statistical difference in the rate of zoster infections within the first 42 days of vaccination with adjusted hazard ratio of
.50(95% CI 0.09-2.69, p-value=0.42). During the subsequent follow-up period, 742 patients continued their baseline
treatment. The rate of zoster infection was 15.9 per 1000-person year in the MTX group and the rate was 18.6 per 1000-
person year in the non-MTX group with the adjusted hazard ratio 0.79(95% CI 0.47-1.33, p-value=0.37). Among the 334
patients taking MTX, 292 patients were taking a dose of 22.5 mg or under while 42 were taking the dose of 25mg or more.
The final analysis from the model showed no significant difference in dosage effect, the adjusted hazard ratio was
0.34(95% CI 0.04-2.54, p-value=0.29).
Conclusion:
Zoster vaccination is safe to be given to RA patients taking MTX regardless of the dosage. The vaccination is equally
effective in RA patients taking MTX and not taking MTX.
Disclosure: A. Lin, None; Q. Li, None; J. Shi, None; S. Lin, None; D. Wang, None; J. Wan, None; K. Lee, None; H. F.
Tseng, None; T. Cheetham, Bristol-Myers Squibb, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-occurrence-of-shingles-and-the-

effect-of-zoster-vaccination-with-the-use-of-methotrexate-in-rheumatoid-arthritis-patients
Filgotinib, a Selective Janus Kinase 1 Inhibitor, Has No Effect on QT Interval

in Healthy Subjects
Kacey Anderson1, Hao Zheng2, Chohee Yun3, Ellen Kwan4, Ann Qin1, Florence Namour5, Brian P. Kearney1 and Yan
Xin1, 1Clinical Pharmacology, Gilead Sciences, Inc., Foster City, CA, 2Gilead Sciences, Inc., Foster City, CA, 3Clinical
Research, Gilead Sciences, Inc, Foster City, CA, 4Clinical Operations, Gilead Sciences, Inc, Foster City, CA, 5Galapagos
NV, Romainville, France
SESSION INFORMATION
Background/Purpose:
Filgotinib is a potent and selective Janus kinase 1 (JAK1) inhibitor being developed to treat inflammatory diseases. Safety
pharmacology studies and Phase 1 studies indicate that there is a low risk of QT prolongation by filgotinib treatment. This
dedicated Phase 1 study was conducted to evaluate the potential effect of filgotinib on the QT interval prolongation in
healthy subjects per the International Conference on Harmonization (ICH) E14 guidance.
Methods:
52 healthy adults were randomized to receive a single dose of moxifloxacin 400 mg (positive control) or once daily doses
of filgotinib 200 mg (top therapeutic dose), filgotinib 450 mg (supratherapeutic dose), or placebo for 7 days. There was a
washout period of 9 days between each dosing period. Digital ECGs were collected in triplicates within 5 minutes at
matched time points on the 1st day (predose) and 7th day (postdose) with 24 hours measurements for each treatment on the
7th day. QTc (QTcF and QTcI) were derived and average of triplicates provided time-matched QTc. Subjects with large
QTc or QTc change from baseline were summarized. Changes from baseline in time-matched QTc were fit to a mixed effect
model, and difference of QTc change between filgotinib treatments or moxifloxacin vs placebo were quantified. PK of
filgotinib was evaluated, and safety was monitored throughout study. The 90% confidence intervals (CIs) were constructed
for the ratios of geometric least squares means of filgotinib PK parameters (AUCtau, Cmax, and Ctau) for 450 mg vs. 200
mg daily dose. The association between QTc and plasma concentrations of filgotinib was explored.
Results:
46 (88.5%) subjects completed study drug treatments. The mean (range) age of subjects was 38 (20-55) years, 39 (75%)
subjects were female, 28 (53.8%) were white and 15 (28.8%) were hispanic or latino.
Lack of QTcF prolongation has been demonstrated at both doses of filgotinib. The upper limits of the 2-sided 90% CI for
mean difference in QTcF between 200 mg or 450 mg vs placebo were less than 10 msec (≤ 8.35 msec) at all time points.
Similar results were observed with QTcI. Assay sensitivity was demonstrated using moxifloxacin at 400 mg, with the lower
96.7% CI for mean difference in QTcF above 5 msec (≥ 8.32 msec) at 2, 3, and 4 hours post dose. Filgotinib 450 mg
provided 2.1-fold higher Cmax than 200 mg. There were no clinically relevant relationships between change from baseline
(placebo-corrected) in QTcF/QTcI and plasma concentrations of filgotinib.
Overall, 8 (15.7%), 15 (30.0%), 0 (0.0%), and 5 (10.0%) subjects experienced treatment-related AEs during filgotinib 200
mg, filgotinib 450 mg, placebo, and moxifloxacin treatment periods, respectively. No serious or severe (≥ Grade 3) AEs
occurred, and the majority of the AEs reported were Grade 1 (mild) in severity. No Grade 4 laboratory abnormalities
occurred. There were no clinically significant trends in vital signs, or safety ECG recordings.
Conclusion:
Filgotinib does not affect QTc interval by definition of a negative thorough QT study per ICH E14 guidance at 200 mg (top
therapeutic dose) and 450 mg (supratherapeutic dose; 2.1-fold higher Cmax than 200 mg).
Disclosure: K. Anderson, Gilead Sciences, Inc, 1,Gilead Sciences, Inc, 3; H. Zheng, Gilead Sciences, Inc, 1,Gilead
Sciences, Inc, 3; C. Yun, Gilead Sciences, Inc, 1,Gilead Sciences, Inc, 3; E. Kwan, Gilead Sciences, Inc, 1,Gilead
Sciences, Inc, 3; A. Qin, Gilead Sciences, Inc, 1,Gilead Sciences, Inc, 3; F. Namour, Galapagos NV, 1,Galapagos NV, 3;
B. P. Kearney, Gilead Sciences, Inc, 1,Gilead Sciences, Inc, 3; Y. Xin, Gilead Sciences, Inc, 1,Gilead Sciences, Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/filgotinib-a-selective-janus-kinase-1-

inhibitor-has-no-effect-on-qt-interval-in-healthy-subjects
Clinical and Structural Responses of Patients with Active Rheumatoid

Arthritis (RA) Using Step-up Dosing of Tofacitinib in a Treat to Target
Approach
Norman Gaylis1, Joanne Sagliani1 and Steven Needell2, 1Arthritis & Rheumatic Disease Specialties, Aventura, FL, 2Boca
Radiology, Boca Raton, FL
SESSION INFORMATION
Background/Purpose: Tofacitinib has been shown to reduce the clinical signs and symptoms of some RA patients at an
approved dose of 5 mg bid. Studies report that 10 mg bid is an effective dose. This is the first community practice trial to
measure the clinical and structural benefits of stepping up the initial dose of 5 mg bid in non-responders to 10 mg bid in
order to achieve a clinical response using a treat to target approach.
Ojective:This study evaluates the optimal dose of tofacitinib (5 mg bid VS 10 mg bid) needed to reach treatment target in a
cohort of patients with active RA while comparing the corresponding structural findings measured by low field MRI
Methods: 20 RA patients who were unresponsive to either methotrexate (10-25 mg weekly) or MTX plus up to 2 prior
biologics with synovitis, osteitis or erosions on Baseline MRI (Esaote 0.3T) were treated with 5 mg bid tofacitinib with a
treat to target goal of LDA or remission depending on the Clinical Activity Index (CDAI) score at Baseline. If the target
was not met and sustained for 3 months, the dose of tofacitinib was increased to 10 mg bid in an attempt to reach target.
MRIs of the hand/wrist were blindly read by a musculoskeletal radiologist using a RAMRIS score. A CDAI score of >10
was needed at study entry.
Results: Of the 20 enrolled patients, 6 remained at 5 mg bid and 14 were dose escalated to 10 mg bid most at the 12 week
period. Of the 5 mg bid group, 3 completed the trial at target and 3 early termed (ET) for lack of efficacy, relocation and
AE. Structurally, there was no change in erosions in all 3 patients; 2 showed regression of synovitis and 1 showed no
change: 2 showed regression in osteitis and 1 no change. Of the 14 patients escalated to 10 mg bid, 11 completed the trial
with 7 remissions, 2 at LDA, and 1 at MDA. 3 patients ET due to lack of efficacy. In the 10 mg bid group, 9 patients
showed no change in erosions, 1 regression and 1 progression. 5 patients showed no change in synovitis and 6 showed
regression, and 7 showed no change in osteitis, 3 showed regression and 1 showed progression. The CRP values correlated
with the improvement of the clinical and structural results, in particular, the levels improved after the dose was increased to
10 mg bid.
Conclusion: Our results suggest that a significant number of patients treated with the standard dose of 5 mg bid may
potentially have improved outcomes including LDA or remission when treated at a higher dose (10 mg bid). This is
evidenced by the results of 11 of the 14 patients having significant improved response most after 3 months of treatment
with 10 mg bid. Furthermore, the structural findings correlate in large part to the clinical findings showing stabilization or
improvement in most patients. An extension trial is currently ongoing to determine if the positive outcome of LDA or
remission at the higher dose (10 mg bid) can be sustained if the dose if reduced back down to 5 mg bid.
CDAI 12
Mnth CDAI 12
CDAI 3 Mnth Mnth Dose
Remain on Increased
CDAI All taking 5
Patient BSL mg bid 5 mg bid 10 mg bid
001 24.9 0.6 6
002 56.1 20.9 2.7
003 45.9 27.4 2.3
004 65.2 33.8 0
005 56.1 15.5 3.1
006 34.7 38.9 19.4
007 27.9 56 1.5
008 34.3 18.4 1.8
009 43.6 3.3 2.3
010 33.5 12.6 ET
011 32.7 5.1 ET
012 25.3 13 0
013 21.2 2.4 ET
014 21.6 9.9 2.9
015 21.6 5.2 ET
016 27.7 0.4 ET
018 31.8 16.9 2.1
019 27.3 0.9 5.2
020 14.5 5.2 ET
021 30.5 2.1 1.9
Disclosure: N. Gaylis, None; J. Sagliani, None; S. Needell, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/clinical-and-structural-responses-of-

patients-with-active-rheumatoid-arthritis-ra-using-step-up-dosing-of-tofacitinib-in-a-treat-to-target-approach
Update on the Clinical Phase 1 and Phase 2 Trials Investigating the Fully
Human Immunocytokine Dekavil (F8IL10) in Patients with Rheumatoid
Arthritis
Mauro Galeazzi1, Gian Domenico Sebastiani2, Jürgen Wollenhaupt3, Jean Dudler4, Christof Specker5, Reinhard Voll6,
Pascal Zufferey7, Piercarlo Sarzi Puttini8, Ombretta Viapiana9 and Franziska Bootz10, 1Rheumatology, University Hospital
of Siena, Siena, Italy, 2Rheumatology, San Camillo Forlanini Hospital, Roma, Italy, 3Division of Reheumatology, Schoen-
Klinik Hamburg-Eilbek Teaching Hospital of the University of Hamburg, Hamburg, Germany, 4Rheumatology, Cantonal
Hospital Fribourg, Fribourg, Switzerland, 5Rheumatology, St. Josef Krankenhaus, Universitätsklinikum Essen, Esssen,
Germany, 6Clinic for Rheumatology and Clinical Immunology, Medical Center University of Freiburg, Freiburg, Germany,
7Department of Rheumatology, University Hospital Lausanne, Lausanne, Switzerland, 8Rheumatology, Luigi Sacco
Hospital, Milan, Italy, 9University Hospital Verona, Verona, Italy, 10Clinical Department, Philochem AG (Philogen Group),
Otelfingen, Switzerland
SESSION INFORMATION
Background/Purpose:
The antibody-based targeted pharmacodelivery of cytokines by means of immunocytokines has the potential to enhance
therapeutic activity at the site of disease while sparing healthy tissues. Dekavil (F8IL10) is a fully human immunocytokine
consisting of the targeting antibody F8 (specific to EDA) fused to the anti-inflammatory payload interleukin-10. Dekavil is
currently in phase 2 clinical development for the treatment of rheumatoid arthritis (RA).
Methods:
Patients diagnosed with RA according to ACR/EULAR classification criteria, who have active disease despite MTX
therapy and who failed anti-TNF treatment are the target population.
In a recently completed phase 1b dose escalation study with the aim to explore safety, tolerability and the maximum
tolerated dose (MTD), cohorts of 3-6 patients were treated with escalating doses of Dekavil (6-600 μg/kg + MTX). Patients
received 4 weekly s.c. injections of Dekavil in combination with a fixed dose of MTX (10-15 mg). Patients willing to
continue the treatment had the opportunity to receive 4 additional weekly injections of Dekavil.
The ongoing multicenter, double-blind, placebo-controlled phase 2 trial assesses therapeutic activity by measuring the
mean change from baseline of DAS28-CRP. Patients are randomized into two treatment groups (Dekavil 30 or 160 μg/kg
plus MTX) and one placebo group (placebo plus MTX). Study participants receive 8 weekly s.c. injections of Dekavil in
combination with a fixed dose of MTX (10-15 mg).
Both studies further investigate the possible formation of anti-fusion protein antibodies as well as F8IL10 signature.
Results:
In the phase 1 study, Dekavil was shown to be well tolerated up to the highest investigated dose (600 μg/kg) and an MTD
was not reached. In 34 out of 35 patients treated in the phase 1 study, no DLTs, no SAEs and no SUSARs have been
reported. One study subject in cohort 9 (450 μg/kg) experienced a DLT (G2 purpura), which was accompanied by a SAE
(G2 dyspnea, not drug related). The patient fully recovered within one week after having received corticosteroid treatment.
The most frequently observed adverse event was mild injection site reaction and occurred in 60% of the patients.
Furthermore, two cases of drug related anemia (G3 and G2; 160 μg/kg and 450 μg/kg, respectively) were reported in this
study. All adverse reactions resolved completely. At the first efficacy assessment after 4 cycles of treatment, 36.4% of
patients (12/33) revealed ACR responses. The fraction of responding patients increased to 45.8% (11/24) after 8 cycles of
treatment. Two patients benefited from a long lasting ACR70 responses for more than 12 months after the last drug
administration.
As of May 2017, 23 out of 87 patients have been enrolled in the phase 2 clinical study. Neither SAE nor SUSARs nor
treatment-related deaths were recorded so far. An interim analysis performed after 45 patients will allow for a more
thorough understanding of the product.
Conclusion:
The currently available data suggest that the biologic agent Dekavil is a safe and well tolerated novel therapeutic approach
for the treatment of RA.
Disclosure: M. Galeazzi, None; G. D. Sebastiani, None; J. Wollenhaupt, Abbott, BMS, MSD, Pfizer, UCB, 2,Abbott,
BMS, MSD, Pfizer, UCB, 5; J. Dudler, None; C. Specker, None; R. Voll, None; P. Zufferey, None; P. Sarzi Puttini,
None; O. Viapiana, None; F. Bootz, Philchem AG (Philogen group), 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/update-on-the-clinical-phase-1-and-

phase-2-trials-investigating-the-fully-human-immunocytokine-dekavil-f8il10-in-patients-with-rheumatoid-arthritis
Tofacitinib, an Oral Janus Kinase Inhibitor, in the Treatment of Rheumatoid

Arthritis: Safety and Efficacy in Open-Label, Long-Term Extension Studies
over 9 Years
Jürgen Wollenhaupt1, Joel Silverfield2, Eun Bong Lee3, Ketti Terry4, Kenneth Kwok5, Sander Strengholt6, Ryan
DeMasi7 and Lisy Wang4, 1Schoen-Klinik Hamburg-Eilbek Teaching Hospital of the University of Hamburg, Hamburg,
Germany, 2Healthpoint Medical Group, Tampa, FL, 3Division of Rheumatology, Department of Internal Medicine, Seoul
National University College of Medicine, Seoul, Korea, Republic of (South), 4Pfizer Inc, Groton, CT, 5Pfizer Inc, New
York, NY, 6Pfizer Inc, Capelle aan den IJssel, Netherlands, 7Pfizer Inc, Collegeville, PA
SESSION INFORMATION
Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here, we
report tofacitinib safety and tolerability up to 114 months (Mos) and clinical efficacy up to 96 Mos in long-term extension
(LTE) studies.
Methods: Data were pooled from 2 open-label studies (NCT00413699 [ongoing; database not locked at March 2017 data
cut]; and NCT00661661) of patients (pts) with RA who had participated in Phase 1/2/3 studies of tofacitinib. Pts received
tofacitinib 5 or 10 mg twice daily (BID) as monotherapy or with background DMARDs. As pts in the LTE studies were
allowed to switch doses, they were assigned to the 5 mg BID group if the total daily dose was <15 mg/day, and to the 10
mg BID group if it was ≥15 mg/day. Primary endpoints were adverse events (AEs) and confirmed laboratory safety data.
Secondary endpoints included clinical efficacy measures (ACR20/50/70 response rates, DAS28-4[ESR], HAQ-DI, and
Clinical Disease Activity Index). Safety data were included up to Mo 114 and completer-analyzed efficacy data up to Mo
96 (n≤100 post-Mo 96).
Results: 4967 pts were treated (mean [max] duration: 3.5 [9.4] years). Total tofacitinib exposure was 17,738.5 pt-years
(py); 76.4% of pts maintained their initial dose. In total, 2518 pts (50.7%) discontinued (AEs: 1189 [23.9%]; insufficient
clinical response: 179 [3.6%]). Most common AE classes with highest AEs: infections and infestations (69.6%; exposure
adjusted event rate [EAER; events per 100 py], 19.71) and musculoskeletal/connective tissue disorders (40.3%; EAER,
11.40). Most common AEs: nasopharyngitis (19.1%; EAER, 5.41), upper respiratory tract infection (17.9%; EAER, 5.07),
bronchitis (12.6%; EAER, 3.58), and urinary tract infection (12.5%; EAER, 3.55). Serious AEs occurred in 29.4% of pts,
and serious infections (SIEs) in 8.9% of pts. Malignancies, excluding non-melanoma skin cancer, were reported in 3.0% of
pts. Incidence rates (IR; pts with events per 100 py) for AEs of interest, with 95% confidence intervals (CIs), are provided
in Table 1. IRs for SAEs, SIEs and malignancies through Mo 114 did not increase vs reported data through Mo 105.1
Confirmed laboratory data are provided in Table 1. No new safety risks were identified. Clinical responses were sustained
from Mo 1 to Mo 96 (Table 2).
Conclusion: In patients with RA who remained in the LTE studies, tofacitinib (5 or 10 mg BID), with or without
background DMARDs, was associated with consistent safety through Mo 114 and sustained clinical efficacy through Mo
96.
Reference:
1. Wollenhaupt J et al. Arthritis Rheumatol 2016; 68 (suppl 10): Abstract 1647.

Disclosure: J. Wollenhaupt, Pfizer Inc, 1,Pfizer Inc, 8; J. Silverfield, Pfizer Inc, 2,Pfizer Inc, 8; E. B. Lee, Pfizer Inc, 5;
K. Terry, Pfizer Inc, 1,Pfizer Inc, 3; K. Kwok, Pfizer Inc, 1,Pfizer Inc, 3; S. Strengholt, Pfizer Inc, 1,Pfizer Inc, 3; R.
DeMasi, Pfizer Inc, 1,Pfizer Inc, 3; L. Wang, Pfizer Inc, 1,Pfizer Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/tofacitinib-an-oral-janus-kinase-

inhibitor-in-the-treatment-of-rheumatoid-arthritis-safety-and-efficacy-in-open-label-long-term-extension-studies-over-9-
years
Prevalence of Occult Hepatitis B Carrier Status and Its Associated Risk

Factors in Patients with Rheumatic Diseases Undergoing Biological
Therapies
Chi Chiu Mok1, Ling Yin Ho2, Kar Li Chan1, Sau Mei Tse1 and Chi Hung To3, 1Medicine, Tuen Mun Hospital, Hong
Kong, Hong Kong, 2Dept of Medicine, Tuen Mun Hospital, Hong Kong SAR, Hong Kong, 3Medicine, Pok Oi Hospital,
Hong Kong, Hong Kong
SESSION INFORMATION
Background/Purpose:
To study the prevalence of occult hepatitis B carrier status and its associated factors in patients with rheumatic diseases
undergoing biological therapies
Methods:
Consecutive adult patients with various rheumatic diseases who were currently receiving biological therapies between
November 2016 and April 2017 were recruited in this cross-sectional study. Blood was taken for evidence of hepatitis B
infection (HBsAg, anti-HBs, anti-HBc-IgG). For patients tested positive for HBsAg or anti-HBc-IgG, assay of serum HBV-
DNA level was also performed. Occult hepatitis B carrier was defined as patients who were HBsAg negative but anti-HBc-
IgG positive. Logistic regression was performed to study factors independently associated with occult hepatitis B carrier
status in these patients.
Results:
310 Chinese patients were studied (60% women, age at biological therapy 44.0±13.0 years). The underlying rheumatic
diseases requiring biological therapies were rheumatoid arthritis (46%), spondyloarthritis (31%), psoriatic arthritis (12%)
and systemic lupus erythematosus (8.1%). The biologics being used were the TNF inhibitors (66%), tocilizumab (16%),
abatacept (2.9%), rituximab (7.7%), belimumab (5.8%) and tofactinib (1.3%). Hepatitis B carrier (HBsAg+) status was
detected in 11 (3.5%) patients and they were all put on preemptive anti-viral therapy (entecavir). A total of 105 patients
(34%) were occult hepatitis B carriers (HBsAg- but anti-HBc-IgG+). Anti-HBs was present in 83/105 (79%) of these
patients. Occult hepatitis B carriers were significantly older than the non-carriers (49.9±11.1 vs 40.9±13.3 years; p<0.001),
and were more frequently identified in rheumatoid arthritis than other rheumatic diseases (45% vs 25%; p<0.001).
However, there was no gender difference in the prevalence of the occult hepatitis B carrier status (37% in women vs 28% in
men; p=0.10). Logistic regression revealed that older age (RR 1.05[1.03-1.08] per year; p<0.001) was the only independent
factor significantly associated with occult hepatitis B infection. Rheumatoid arthritis was not significantly associated with
occult hepatitis B carrier status after adjustment for age and sex. Of the occult hepatitis B carriers, 9 (8.6%) had detectable
HBV-DNA levels but all were very low titers (<100IU/ml). Five (56%) patients with detectable HBV-DNA levels received
entecavir treatment during biological therapies, while 19 (20%) patients without detectable HBV-DNA were put on
preemptive entecavir treatment (including all patients who were receiving rituximab). None of the overt (HBsAg+) or
occult hepatitis B (HBsAg- anti-HBc-IgG+) carrier patients developed clinical reactivation of hepatitis B during a mean of
5.0±3.7 years of biological therapies.
Conclusion:
Occult hepatitis B carrier status was present in one-third of Hong Kong Chinese patients with various rheumatic diseases
undergoing biological therapies. Older age was the only independent factor associated with occult hepatitis B infection.
Despite the relatively low rate of preemptive anti-viral treatment in these patients, clinical reactivation of hepatitis B was
not reported over 5 years of biological therapies.
Disclosure: C. C. Mok, None; L. Y. Ho, None; K. L. Chan, None; S. M. Tse, None; C. H. To, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prevalence-of-occult-hepatitis-b-carrier-

status-and-its-associated-risk-factors-in-patients-with-rheumatic-diseases-undergoing-biological-therapies

Predictors of Mortality in RA Patients before Biologic Therapy
Debora Cordeiro Rosario1, Camila Nobre Bulhoes1, Rodrigo Peres Toledo1, Karina Bonfiglioli2, Ana C.M. Ribeiro3, Julio
C. B. Moraes2, Carla G.S. Saad2, Clovis A Silva4, Eloisa Bonfa5 and Nadia E Aikawa2, 1Rheumatology Division,
Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil, 2Rheumatology Division, Faculdade de Medicina
da Universidade de São Paulo, São Paulo, Brazil, 3Division of Rheumatology, Faculdade de Medicina da Universidade de
São Paulo, São Paulo, Brazil, 4Pediatric Rheumatology Unit, Faculdade de Medicina da Universidade de São Paulo, São
Paulo, Brazil, 5Rheumatology Divison, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
SESSION INFORMATION
Background/Purpose: Several studies have evaluated mortality risk factors in rheumatoid arthritis (RA) but that are no
data regarding baseline predictors of mortality in patients under biologic therapy. In fact, definition of these predictors is
difficult due to many confounding variables such as age, gender, biologic drug itself and its duration. Therefore, the aim of
this study was to identify clinical and laboratory baseline predictors of death in RA patients matched for all these
parameters under biologic treatment.
Methods: This was a retrospective observational study that included all deceased RA patients (ACR classification criteria)
regularly followed in the biologic therapy center of Rheumatology Division of a tertiary university hospital. All relevant
parameters were evaluated using an electronic chart database established from 2007 to 2016. All biologic drugs, including
subcutaneous and intravenous agents, are regularly administered in-hospital. A control group of RA patients under biologic
treatment matched for gender, age, biologic drug and its duration was included. Demographic data, comorbidities, clinical
and laboratorial findings and concomitant treatment were assessed at the baseline of last biologic drug and at the last visit
before death.
Results: During the study, 22/436 (5%) RA patients died after biologic therapy start. Causes of death included infections in
18 (82%), complications of pulmonary fibrosis in 2 (9%), subarachnoid hemorrhage in 1 (4.5%) and hemorrhagic stroke in
1 (4.5%). Deceased and survivors patients were comparable with regard to current age (57 vs. 57 years, p=0.34), male
gender (27% vs. 27%, p=1.0) and last biologic duration (12 vs. 10 months, p=0.51). Analysis of baseline therapeutic
parameters of the last biologic drug in the deceased group compared to survival groups revealed similar median number of
biologic agents (p=0.94), need of at least one switching to another biologic agent (68% vs. 63, P=0.79) and frequencies of
other drugs [prednisone (p=0.25), methotrexate (p=0.8), leflunomide (p=0.79) or sulfasalazine (p=0.11)]. Likewise, clinical
and laboratorial characteristics were alike in both groups [Disease Activity Score in 28 joints (DAS28) (4.75 vs 4.96,
p=0.75), HAQ (1.75 vs. 1.185, p=0.37), RF (68% vs. 84%, p=0.2) and anti-CCP (18% vs. 21%, p=1.0]. Concerning
associated comorbidities, deceased patients had a significantly higher frequency of chronic renal failure (18% vs. 2%,
p=0.041) and a trend for a higher frequency of osteoporosis (59% vs. 33%, p=0.062) compared to the control group.
Further analysis of all parameters at last visit before death demonstrated that deceased group had a higher DAS28 (3.84 vs.
3.06, p=0.05) and Health Assessment Questionnaire (HAQ) (1.563 vs. 1.0, p=0.0054).
Conclusion: The present study design with rigorous control for confounding factors identified solely chronic renal failure
and possibly osteoporosis (in non elderly population) as the most important baseline predictors of mortality in RA patients
starting biologic therapy in a real life setting. High RA activity and severity at the last visit before death are short-term
predictors of death in patients already under biologic therapy.
Disclosure: D. C. Rosario, None; C. N. Bulhoes, None; R. P. Toledo, None; K. Bonfiglioli, None; A. C. M. Ribeiro,
None; J. C. B. Moraes, None; C. G. S. Saad, None; C. A. Silva, Fundação de Amparo à Pesquisa do Estado de São Paulo
(FAPESP #2014/14806-0 and 2015/03756-4 to CAS), Conselho Nacional de Desenvolvimento Científico e Tecnológico
(CNPq 303422/2015-7 - 1A to CAS), 2; E. Bonfa, None, 2; N. E. Aikawa, Fundação de Amparo à Pesquisa do Estado de
São Paulo (FAPESP #2015/03756-4 to NEA), 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/predictors-of-mortality-in-ra-patients-

before-biologic-therapy
Efficacy, Tolerability and Reasons for Changing Dmards, Biologics and Small
Molecule Drugs in RA Patients without RA Lung Disease from a
United States Tertiary Referral Center
Richard Meehan1, Isabelle Amigues2, David Muram3, Eric Hoffman4, Jim Crooks5, Tho Truong6 and Pearlanne
Zelarney7, 1MEDICINE, National Jewish Health, Denver, CO, 2Division of Rheumatology, Columbia University, College
of Physicians & Surgeons, New York, NY, 3Eli Lilly and Company, Indianapolis, IN, 4Medicine/Rheumatology, National
Jewish Health, Denver, CO, 5Biostatistics, National Jewish Health, Denver, CO, 6Rheumatology, National Jewish Health,
Denver, CO, 7Bioinformatics, National Jewish Health, Denver, CO
SESSION INFORMATION
Background/Purpose: The goal of therapy of rheumatoid arthritis (RA) is to achieve a state of low disease activity (LDA)
or remission and reduce joint damage and disability. When treatment with one agent is unsuccessful, an alternative
DMARD, biologic or small molecule drug will be prescribed. This retrospective study reports the frequency and reasons
for drug changes in RA patients in a tertiary US academic practice.
Methods: Records of 1300 RA patients were reviewed by 3 rheumatologists to select patients who received at least one
biologic (b) DAMRD, had no other rheumatic disease, no interstitial lung disease or chronic infections, and were followed
for at least one year to be included in this report. The study cohort consists of 198 patients who fulfilled the inclusion
criteria. Patient demographics, drugs used, duration of use, and reasons for change of therapy were recorded.
Results: Of the 198 patients, 75% were females, average age was 51, 65% were ACPA positive, and 31% of patients had
erosions at first visit. Patient demographics are summarized in Table 1. These patients received an average of 2.5 drugs
before their first visit. They changed to a new drug an average of 2.4 times during their average follow up visits of 6.2
years. The longest average duration of continuous use for any of the DMARDs was 6-24 months (Table 2). The main
reasons for discontinuation of these medications were lack of efficacy and the occurrence of adverse events (AEs). The rate
of AEs among patients receiving bDMARDs was similar to that in patients receiving conventional DMARDS. The reasons
for discontinuation of specific medications are summarized in Table 3.
Conclusion: This retrospective review suggests that most patients with RA will require a change of therapy every 2-3
years, primarily due to perceived lack of efficacy or the occurrence of AEs. The frequent change of therapy in patients with
chronic disease like RA suggests that patients will use many different drugs in the course of their illness. In the absence of
an effective biomarker that predicts response to a specific medication, therapeutic agents selected may not be efficacious
and require early recognition of lack of efficacy and subsequent change of therapy.
Disclosure: R. Meehan, Eli Lilly and Company, 2; I. Amigues, None; D. Muram, Eli Lilly and Company, 1,Eli Lilly and
Company, 3; E. Hoffman, Eli Lilly and Company, 2; J. Crooks, Eli Lilly and Company, 2; T. Truong, None; P. Zelarney,
Eli Lilly and Company, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/efficacy-tolerability-and-reasons-for-

changing-dmards-biologics-and-small-molecule-drugs-in-ra-patients-without-ra-lung-disease-from-a-united-states-tertiary-
referral-center
Comparative Pulmonary Safety of Abatacept and Tumor Necrosis Factor

Inhibitors in Patients with RA and Chronic Pulmonary Condition
Eun Ha Kang1, Yinzhu Jin2, Sara Dejene3, Gregory Brill3, Rishi J. Desai2, Jeffrey A. Sparks4 and Seoyoung C. Kim5,
1Division of Rheumatology, Department of Internal Medicine, Division of Rheumatology, Department of Internal
Medicine, Seoul National University Bundang Hospital, Seongnam, Korea, Republic of (South), 2Division of
Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, Boston, MA, 3Brigham and Women's
Hospital, Boston, MA, 4Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical
School, Boston, MA, 5Rheumatology, Immunology and Allergy; Pharmacoepidemiologyand Pharmacoeconomics,
SESSION INFORMATION
Background/Purpose: Patients with rheumatoid arthritis (RA) can have various pulmonary comorbidities including
asthma, chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). Biologics can pose a potential
risk for acute exacerbations (AE) of these pulmonary comorbidities by immunosuppression, drug-induced lung injury, or
other mechanisms. We therefore compared the risk of pulmonary AE among RA patients initiating abatacept vs. TNF
inhibitors (TNFi) with chronic pulmonary comorbidities at baseline.
Methods: We conducted a cohort study using claims data from Medicare (2008-2013) or a commercial health plan
(MarketScan 2006-6/2015) in the US. Adults with RA and chronic pulmonary condition (i.e., asthma, COPD, or ILD) who
initiated abatacept or TNFi were identified based on a combination of diagnosis codes and use of disease-specific
medications. The cohort entry date was the 1st use of abatacept or TNFi after ≥12 month continuous enrollment. The
primary outcome was a composite endpoint defined as any of: 1) inpatient stays or 2) ED visits for asthma, COPD, or ILD,
or 3) outpatient visits for asthma, COPD or ILD plus dispensing of oral corticosteroids or antibiotics, or for respiratory
complications such as pneumonitis and bronchitis. Secondary outcomes were individual components of the primary
composite endpoint. Follow-up time started from the day after cohort entry to the earliest event of outcome occurrence,
drug discontinuation, nursing home admission, disenrollment, end of study period, or death. To control for >50 potential
confounders at baseline, abatacept initiators were matched to TNFi initiators on a propensity score (PS) with a 1:2 ratio in
each of the three pulmonary condition subgroups. We estimated incidence rates (IR) and hazard ratios (HR) of the
outcomes among abatacept initiators versus TNFi in the main cohort and the subgroups. PS-matched HRs from the two
databases were then pooled using inverse variance-weighted fixed-effect method.
Results: After PS matching, we included 1,517 abatacept and 3,034 TNFi initiators with RA and chronic pulmonary
condition from both databases. Mean (SD) age was 73.0 (6.1) years in Medicare and 61.2 (12.1) years in MarketScan. At
baseline, 44% in MarketScan and 57% in Medicare used methotrexate. IR of the composite outcome per 100 person-years
ranged from 47.6-49.6 in the abatacept group and from 51.8-53.5 in the TNFi group. For the primary composite outcome,
the HR comparing abatacept to TNFi was 1.00 (95%CI 0.92-1.09) in Medicare and 1.00 (95%CI 0.89-1.12) in MarketScan
with a pooled HR of 1.00 (95%CI 0.93-1.07). Secondary and subgroup analyses showed similar results (Figure).
Conclusion: Among patients with RA and chronic pulmonary condition, acute exacerbations of underlying asthma, COPD
or ILD occurred frequently but we found no difference in the exacerbation risk between abatacept and TNFi initiators.
Disclosure: E. H. Kang, None; Y. Jin, None; S. Dejene, None; G. Brill, None; R. J. Desai, None; J. A. Sparks, None; S.
C. Kim, BMS, 2,Roche Pharmaceuticals, 2,AstraZeneca, 2,Pfizer Inc, 2,Merck Pharmaceuticals, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/comparative-pulmonary-safety-of-

abatacept-and-tumor-necrosis-factor-inhibitors-in-patients-with-ra-and-chronic-pulmonary-condition
Cardiovascular Safety of Tocilizumab Versus Abatacept in Patients with

Rheumatoid Arthritis: A Multi-Database Study
Seoyoung C. Kim1, Daniel H. Solomon1, James R. Rogers2, Sara Gale3, Micki Klearman3, Khaled Sarsour3 and Sebastian
Schneeweiss2, 1Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA,
2Brigham and Women's Hospital, Boston, MA, 3Genentech, South San Francisco, CA
SESSION INFORMATION
Background/Purpose: While tocilizumab (TCZ) may increase serum lipid levels, recent studies do not suggest an
increased cardiovascular (CV) risk associated with TCZ use compared to TNF inhibitors in patients with RA. The current
study examined comparative CV safety of TCZ versus abatacept in RA patients.
Methods: We conducted a cohort study using data from 3 U.S. healthcare claims databases – Medicare Parts A/B/D (2010-
13), ‘IMS’ PharMetrics Plus (2011-2014) or Truven ‘MarketScan’ (2011-6/2015). Adults aged ≥18 years with RA who
newly started TCZ or abatacept entered the cohort on the day of their first use of TCZ or abatacept. All patients had ≥12
month continuous enrollment free of TCZ and abatacept use before cohort entry. The primary outcome was a composite
CV endpoint of hospitalization of any length for myocardial infarction (MI) and stroke based on claims-based algorithms
(PPV>94%). Secondary outcomes were hospitalization for MI, stroke, coronary revascularization, heart failure and all-
cause mortality. For the primary as-treated analysis, follow-up time started the day after cohort entry and ended on
treatment discontinuation, outcome occurrence, disenrollment, death, or the end of study period. We estimated a propensity
score (PS) to control for >60 potential confounders including demographics, prior DMARD use, comorbidities,
medications, and healthcare utilization. TCZ starters were PS-matched to abatacept starters with a variable ratio of 1:3
within each database. We estimated incidence rates (IR) of composite CV events in the TCZ group compared to the
abatacept group separately in each database. Hazard ratios (HR) from the 3 PS-matched cohorts were combined by an
inverse variance-weighted, fixed-effects model.
Results: We included a total of 6,237 TCZ starters PS-matched to 14,685 abatacept starters in all three databases. Mean age
(in years) was 72 in Medicare, 51 in IMS and 53 in MarketScan. At baseline, 73% (Medicare), 70% (IMS) and 62%
(MarketScan) of TCZ or abatacept patients used methotrexate. In the as-treated analysis, the median follow-up time varied
between 175 days (MarketScan) to 183 days (IMS) in the TCZ group and 193 days (MarketScan) to 209 days (Medicare) in
the abatacept group. A total of 32 CV events occurred in TCZ starters and 112 events in abatacept starters across the three
databases. The IR of the primary composite CV events per 100 person-years ranged from 0.37 (IMS) to 1.64 (Medicare) in
the TCZ group and from 0.59 (IMS) to 1.69 (Medicare) in the abatacept group. The risk of the primary composite CV
events was similar between the two groups across all three databases (Table), with a combined HR of 0.82 (95%CI 0.55-
1.22) in TCZ initiators versus abatacept initiators. Analyses on secondary outcomes showed similar results.
Conclusion: This large multi-database cohort study found no increase in the risk of CV events in patients with RA who
newly start TCZ versus abatacept.
Disclosure: S. C. Kim, AstraZeneca, Bristol-Meyers-Squibb, Genentech, Lilly, Pfizer, 2; D. H. Solomon, Amgen,

AstraZeneca, Corrona, LLC, Genentech, Lilly, Pfizer, 2,Pfizer, 9; J. R. Rogers, None; S. Gale, Genentech, Inc., 3; M.
Klearman, Genentech/Roche, 1,Genentech/Roche, 3; K. Sarsour, Genentech, Inc., 3; S. Schneeweiss, Boehringer
Ingelheim, Genentech, Inc., 2,Aetion, Inc., WHISCON, LLC, 5,Aetion, Inc., 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/cardiovascular-safety-of-tocilizumab-

versus-abatacept-in-patients-with-rheumatoid-arthritis-a-multi-database-study
Impact of Comorbidities on the Occurrence of Infections in Rheumatoid

Arthritis Treated By Biologic Agents
Christopher Banse1, Nicolas Chrin2, Pascal Rottenberg3, Sophie Pouplin4, thierry Lequerre5 and Olivier Vittecoq3,
1Rheumatology, Rouen University Hospital, Rouen, France, 2Department of Biostatistics, Rouen University Hospital,
76031 Rouen, France, ROUEN, France, 3INSERM U905 & Normandy University, Institute for Research and Innovation in
Biomedicine, Rouen, France, 4Rheumatology Department & Inserm 905, Department of Rheumatology, Rouen University
Hospital & Inserm 905, Institute for Biomedical Research, University of Rouen, Rouen, France, 5Rheumatology
Department, Rouen University Hospital, University of Rouen, 76031 Rouen, France., ROUEN, France
SESSION INFORMATION
Background/Purpose: to investigate the potential relationship between the number of comorbidities at initiation of
biotherapy and the occurrence of a severe infection or recurrent infections under biologic agent in rheumatoid arthritis
(RA).
Methods: This was a monocentric and retrospective study conducted from 2001 to 2011. Population characteristics,
number and nature of comorbidities and treatments were collected at baseline. The occurrence of severe infections leading
to hospitalization or life threatening, as well as that of recurrent infections (> 4 per year) was collected during a 2 years-
follow-up period after the introduction of an anti-TNF biologic agent or a non anti-TNF biotherapy in RA.
Results: 554 RA (70% women) were assessed during this 2 years follow up period. Mean age and RA duration were
respectively at 64.1 (+/-13.8) years and at 15.2 (+/-10.4) years. 78% of patients were a rheumatoid factor or anti-CCP
positive. The mean Disease Activity Score of C-Reactive protein (DAS 28 CRP) was 4.1. X-rays showed structural damage
in 65.5% of cases. The mean dose of prednisone was 6.66 mg/l. 75.4% of patients received methorexate (mean dose:
10.5mg/week). Biological agents were prescribed as follows: abatacept (3.8%), adalimumab (20.6%), anakinra (7.8%),
certolizumab (0.36%), etanercept (37.5%), infliximab (25.3%), rituximab (3.2%) and tocilizumab (1.6%). At 1 year, the
therapeutic maintenance was 91.3%. In this population, 31.5% had no comorbidity, 27.4% had 1 comorbidity, 19.35% had
2 comorbidities and 21.7% had more than 2 comorbidities. The occurrence of recurrent infections during the 24th months
was 5.6% whereas the occurrence of a severe infection was 3.8%. After adjustment (age, corticosteroid and DAS 28 CRP),
there was a significant correlation between the number of comorbidities (more than 2 comorbidities) and the occurrence of
severe infections. The number of comorbidities was not correlated with the occurrence of repeated infections. The Rabbit
score predicted the risk of developing a severe infection of the order of 3.5%. Certain types of comorbidities were linked to
the occurrence of severe or recurrent infections.
Conclusion: The presence of more than 2 comorbidities is significantly related to the occurrence of a severe infection
during the 24 months following the initiation of a biological agent.
Disclosure: C. Banse, None; N. Chrin, None; P. Rottenberg, None; S. Pouplin, None; T. Lequerre, None; O. Vittecoq,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/impact-of-comorbidities-on-the-

occurrence-of-infections-in-rheumatoid-arthritis-treated-by-biologic-agents

Pulmonary Involvement in Our Patients with Rheumatoid Arthritis Under
Biological Therapy: A Tertiary Hospital Experience
Edurne Guerrero Basterretxea1, Maria Luz Garcia Vivar1, Itziar Calvo Zorrilla1, Oihane Ibarguengoitia2, Eva Galíndez
Agirregoikoa2, Juan Maria Blanco Madrigal3, Esther Ruíz Lucea1, Ignacio Torre Salaberri1, Olaia Begoña Fernandez
Berrizbeitia2, Clara Eugenia Perez1, Ana Rosa Intxaurbe Pellejero2, Natalia Rivera-García4 and Iñigo Gorostiza
Hormaetxe5, 1RHEUMATOLOGY, Rheumatology Department; Basurto University Hospital, Bilbao, Spain,
2RHEUMATOLOGY, Rheumatology Department; Basurto University Hospital, BILBAO, Spain, 3Rheumatology
Department; Basurto University Hospital, Bilbao, Spain, 4RESEARCH, Rheumatology Department; Basurto University
Hospital, Bilbao, Spain, 5RESEARCH, Research Department. Basurto University Hospital, BILBAO, Spain
SESSION INFORMATION
Background/Purpose: Use of biological therapy (BT) has dramatically improved Rheumatoid Arthritis (RA) management
and outcomes for the last decade. Classic extraarticular manifestations are now uncommon, excepting for pulmonary
involvement, which may be due to different factors and may itself affect also treatment election and patient prognosis. The
aim of this study is to evaluate the presence of pulmonary complications in RA patients under BT in our hospital, assess its
severity and related changes in treatment.
Methods: Review of clinical records of 208 RA patients receiving BT in the last 5 years (January 2012 to December 2016).
23 cases of preexisting lung disease for other causes (asthma, smoking) have been excluded. We collected demographic
data, characteristics of RA, types of pulmonary involvement, followup and changes in treatment of 26 patients finally
included. Statistical analysis were performed using SPSS v22.
Results:
73.1% were women, mean aged 59 years (31-80); 53.8% were never smokers. They suffered from longstanding RA yet
(median 176.92 months, SD 199.34); only 2 patients were early arthritis (RA diagnose during the previous year). 85% were
RF positive with positive CCP antibodies in 69.2%, and structural damage with erosions was present in 70%. Other
extraarticular manifestations (3 patients with rheumatoid nodules, 4 with cardiac involvement) were present in 25% .
At the time of lung disease diagnosis, 1/2 patients were in remission or low activity (DAS 28), with a median CRP 0.52
mg/dL (SD 1.72). 90% had received methotrexate and almost half of them leflunomide; 30% had been previously treated
with BT (50% TNF alpha inhibitors). Interstitial lung disease (ILD) was the most frequent pulmonary involvement (57.7%)
and non-specific intersticial pheumonia (NSIP) the most prevalent pattern (> 60%). We also found obstructive pulmonary
disease (11.5%) and vascular involvement (7.7%). Gold standard image diagnostic technique was high resolution CT (40%
presented a normal X-ray)
Treatment was modified in 53.8% of the cases (synthetic DMARD was kept in 68% and BT in 64%).
The average followup of pulmonary involvement was 37.85 months (1-156). 80% of the patients kept stable or improved
from their arthritis and also from respiratory disease. Only one patient received a lung trasplant and another one died.
We haven´t found association between different types of pulmonary involvement and the different variables analyzed in the
study. We did´t show significant differences in prognosis related to pulmonary disease distinct patterns; up to 80% of
patients with ILD stabilize or improve
Conclusion: Prevalence of pulmonary disease in our experience in RA patients under BT is similar to prevalence in other
observational studies (10-20%), diagnosis here was made for a casual detection in a routine chest X-ray or for clinical
suspicion for respiratory symptoms (cough, dyspnea…). Pulmonary involvement evolution here has been good perhaps for
the high prevalence of NSIP, which is also thought to require less therapeutic intervention. Protocols for search and
management of lung disease in RA patients are an unmet need in clinical practice, and its pathogenesis and treatment are
important fields for translational and clinical research.
Disclosure: E. Guerrero Basterretxea, None; M. L. Garcia Vivar, None; I. Calvo Zorrilla, None; O. Ibarguengoitia,
None; E. Galíndez Agirregoikoa, None; J. M. Blanco Madrigal, None; E. Ruíz Lucea, None; I. Torre Salaberri, None;
O. B. Fernandez Berrizbeitia, None; C. E. Perez, None; A. R. Intxaurbe Pellejero, None; N. Rivera-García, None; I.
Gorostiza Hormaetxe, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/pulmonary-involvement-in-our-

patients-with-rheumatoid-arthritis-under-biological-therapy-a-tertiary-hospital-experience
Efficacy and Safety of Baricitinib in Patients with Rheumatoid Arthritis: A

Meta-Analysis of Randomized Controlled Trials
Sumit Kunwar1, Christopher E. Collins2 and Florina Constantinescu2, 1Rheumatology, MedStar Washington Hospital
Center, washington, DC, 2Rheumatology, MedStar Washington Hospital Center, Washington, DC
SESSION INFORMATION
Background/Purpose:
Janus kinases (JAKs) play an important role in intracellular signaling for multiple cytokines in the pathogenesis of RA.
Baricitinib is an oral, selective JAK 1 and 2 inhibitor which has been shown to be effective in the treatment of RA in
several clinical trials. This meta-analysis aims to aggregate currently available data to assess the overall efficacy and safety
of baricitinib in RA.
Methods:
We searched PubMed, EMBASE and Cochrane CENTRAL from inception through 05/25/17 without language restriction.
Our eligibility criteria included human placebo-controlled RCTs in adults (≥ 18 years of age) that evaluated efficacy and
safety outcomes of barcitinib in RA patients. We excluded meeting abstracts without full text publication. We used RevMan
5.3 to perform meta-analysis between groups on baricitinib 4mg per day and placebo using random effect model calculating
odds ratio (OR) as well as 95% confidence interval (CI). I2 statistic was used to identify heterogeneity between studies, and
values of more than 50 was used to indicate significant heterogeneity. We measured efficacy using ACR20/50/70 and
DAS28-CRP response criteria and safety with adverse events.
Results:
Five studies with a total of 2006 patients (967 on baricitinib and 1039 on placebo) were included for meta-analysis. The
maximum study duration was 24 weeks. Baricitinib demonstrated greater efficacy in achieving ACR20/50/70 responses
compared to placebo (66.7 vs 36.6%, OR 3.33, 95% CI 2.18-5.07, I2 75%, P<0.00001; 44.1 vs 17.8%, OR 3.56, 95% CI
2.77-4.58, I2 20%, P<0000.1 and 24.4 vs 6.5%, OR 4.62, 95% CI 2.96-7.19, I2 40%, P<0.00001 respectively). There was a
small increase in any adverse events in the baricitinib group (70.4 vs 61.5%, OR 1.35, 95% CI 1-1.81, I2 47%, P=0.05),
however, no increase in serious adverse events (5.5 vs 4.8%, OR 1.12, 95% CI 0.75-1.67, I2 0%, P=0.58) or serious
infections (1.5 vs 1.5%, OR 0.94, 95% CI 0.46-1.92, I2 0%, P=0.86) when compared to placebo.
Conclusion:
Baricitinib is effective in treatment of RA, and did not appear to have significant safety concerns during the first six months
of treatment. However, the long term safety profile of this drug should be evaluated by future clinical trials.
Disclosure: S. Kunwar, None; C. E. Collins, None; F. Constantinescu, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/efficacy-and-safety-of-baricitinib-in-

patients-with-rheumatoid-arthritis-a-meta-analysis-of-randomized-controlled-trials
Comparative Effectiveness of Tofacitinib Versus Baricitinib in Rheumatoid

Arthritis Using a Systematic Review and Network Meta-Analysis of
Randomized Trials
Natalia Zamora1,2,3, Maria A. Lopez-Olivo1, Jean Tayar1, Robin Christensen2 and Maria Suarez-Almazor1, 1Section of
Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD
Anderson Cancer Center, Houston, TX, USA, Houston, TX, 2Musculoskeletal Statistics Unit, The Parker Institute,
Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark, Copenhagen, Denmark, 3Reumatologia, Instituto de
Rehabilitación Psicofísica, Buenos Aires, Argentina, Buenos Aires, Argentina
SESSION INFORMATION
Background/Purpose: To explore the comparative effectiveness of tofacitinib or baricitinib in patients with rheumatoid
arthritis (RA) following a systematic review of randomized trials, by performing a network meta-analysis inferring from
both direct and indirect evidence.
Methods: We used the data of the Cochrane systematic reviews on tofacitinib and baricitinib for treating rheumatoid
arthritis. For both reviews, the searches were performed in seven electronic databases and two trial registries. Retrieved
records were screened independently by 2 investigators to include controlled trials comparing tofacitinib or baricitinib
alone or in combination with methotrexate versus placebo, methotrexate or other traditional or biologic DMARDs.
Published and unpublished trials were considered. Quality appraisal and data extraction from the included studies was done
independently by 2 investigators. For the network meta-analysis the primary outcome was American College of
Rheumatology (ACR) 50% improvement criteria (ACR50) and secondary outcomes included remission according to the
Disease Activity Score (DAS28), functional ability measured by the Health Assessment Questionnaire (HAQ), and serious
adverse events as defined by the individual trials.
Results: Out of 2,673 unique citations, 21 trials met the inclusion criteria (9,839 patients). Most patients were female (74 to
96%) with a mean age and disease duration ranging from 48-56 years and 2.7-13 years, respectively. For the tofacitinib
trials, 2 out 14 trials were at high risk of reporting bias. For the baricitinib trials, selection bias could not be evaluated in 6
out 7 trials and for selection and performance bias in 7 out of 7. The network plot for the ACR50 included 12 nodes (i.e.,
daily doses: tofacitinib monotherapy 5 and 10 mgs, combined with methotrexate 5 and 10 mg, baricitinib monotherapy 4
mg, baricitinib combined with methotrexate 2, 4, and 8 mgs, adalimumab monotherapy, adalimumab combined with
methotrexate, methotrexate and placebo). The relative effect achieving an ACR 50 at 12 weeks against placebo in
descending order were: Bari8+MTX (13.5; 5.8-31.3), Tofa10+MTX (11.3; 5.9- 21.4), Tofa5+MTX (10.5; 5.4-20.2),
Bari2+MTX (9.6; 4.5-19.4), Bari4+MTX (9.5; 5.0-17.9), Bari4 (6.79; 3.2-14.3), ADA+MTX (6.8; 3.5-13.3), Tofa10 (6.2;
3.8-9.9), Tofa5 (5.1; 3.3-8.1), MTX (2.4; 1.4-4.4), and ADA (1.9; 0.8-4.7). When comparing indirectly, the only differences
were observed in favor of baricitinib+MTX compared with tofacitinib alone. For DAS 28 there were 11 nodes and the order
was (from most to least effective): Tofa10+MTX, ADA+MTX, Bari8+MTX, Bari4+MTX, Tofa5+MTX, Bari2+MTX,
Tofa10, Bari4, Tofa5, and MTX. Serious adverse events were less likely to occur in the PBO, ADA, Tofa5+MTX,
Tofa10+MTX, MTX, Bari8+MTX, Tofa10, Tofa5, Bari4+MTX, Bari4, and Ada+MTX.
Conclusion: All drug combinations were effective compared with placebo in reducing at least 50% of symptoms or
achieving remission at 12 weeks. Tofacitinib 10 mg and baricitinib 8 mg combined with methotrexate were among the most
efficacious options. Serious adverse events were less likely with the tofacitinib groups, although the within-class
differences were small and may not be clinically meaningful.
Disclosure: N. Zamora, None; M. A. Lopez-Olivo, None; J. Tayar, None; R. Christensen, None; M. Suarez-Almazor,
Pfizer Inc, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/comparative-effectiveness-of-

tofacitinib-versus-baricitinib-in-rheumatoid-arthritis-using-a-systematic-review-and-network-meta-analysis-of-randomized-
trials
Genetic Predictors of Iguratimod Clinical Response and Toxicity in Patients

with Rheumatoid Arthritis
Wenjing Xiao, Department of Rheumatology and Immunology, People’s Hospital, , Peking University, Beijing, Beijing,
China
SESSION INFORMATION
Background/Purpose: Iguratimod (IGU) is a novel DMARD in rheumatoid arthritis (RA). The purpose of this study was
to identify genetic predictors of response and adverse drug events (AEs) to IGU therapy in patients with RA.
Methods: Seven single nucleotide polymorphisms(SNPs) of enzyme and transporter proteins related to IGU,
CYP1A2*1F(rs762551),CYP2C19*2 (rs4244285),
NAT2(rs1495741),ABCB1(rs1045642,rs2032582C),ABCG2(rs2231142) and SLCO1B1 (rs4149036), were determined by
a genotyping approach in 272 IGU treated RA patients. SNPs were evaluated using real-time polymerase chain reaction.
The efficacy of the IGU therapy was estimated using EULAR good response criteria based on the DAS-28. All AEs were
recorded.
Results: 21.69% patients (59/272) were good responders and 36.40% patients (99/272) had AEs. Unvariant analyses and
multivariate analyses demonstrated that the ABCG2 A allele was associates with good response to IGU (OR=2.084, 95%CI
1.147-3.786, P=0.015; OR=1.944, 95%CI 1.038-3.641, P=0.038). NAT2 G carrier was significantly associated with less
favorable response to IGU (OR=0.476, 95%CI 0.256-0.884, P=0.017; OR=0.498, 95% CI 0.256-0.967, P=0.029).
CYP2C19*2 A carriers had higher risk for IGU-induced toxicity than did the GG genotyping (OR=2.122, 95%CI 1.273-
3.537, P=0.004; OR=2. 368, 95%CI 1.395-4.019, P=0.001). No significant association was found between the genotypes of
CYP1A2*1F, ABCB1 and SLCO1B1 SNP and the IGU response or AEs.
Conclusion: Our study suggests that ABCG2 (rs2231142), NAT2 (rs1495741) and CYP2C19*2 (rs4244285) genotyping
may help to identify patients who will benefit from IGU treatment.
Disclosure: W. Xiao, None;
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/genetic-predictors-of-iguratimod-

clinical-response-and-toxicity-in-patients-with-rheumatoid-arthritis
Assessment of Radiographic Progression in Patients with Rheumatoid

Arthritis Treated with Tofacitinib: Data from an Open-Label Long-Term
Extension Study over 3 Years
Désirée van der Heijde1, Jürgen Wollenhaupt2, Stanley B Cohen3, Sander Strengholt4, Ketti Terry5, Ryan DeMasi6,
Kenneth Kwok7, Irina Lazariciu8 and Lisy Wang5, 1Leiden University Medical Center, Leiden, Netherlands, 2Schön-Klinik
Hamburg-Eilbek Teaching Hospital of the University of Hamburg, Hamburg, Germany, 3Metroplex Clinical Research
Center and University of Texas Southwestern Medical Center, Dallas, TX, 4Pfizer Inc, Capelle aan den IJssel, Netherlands,
5Pfizer Inc, Groton, CT, 6Pfizer Inc, Collegeville, PA, 7Pfizer Inc, New York, NY, 8QuintilesIMS, Saint-Laurent, QC,
Canada
SESSION INFORMATION
Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. The long-term safety and
clinical efficacy of tofacitinib 5 and 10 mg twice daily (BID) has been reported in patients (pts) with active RA up to 105
months.1-3 We evaluated the long-term effects of tofacitinib on progression of radiographic structural damage in pts with
RA from a long-term extension (LTE) study.
Methods: Data were analyzed from an open-label LTE (NCT00413699 [ongoing; database not locked at Mar 2017 data-
cut]) of pts with RA who participated in Phase 2 (NCT01164579, methotrexate [MTX] naïve, early RA) or Phase 3
(NCT00847613, MTX-IR; NCT01039688, MTX naïve) tofacitinib index studies. Baseline (BL) was defined as last visit in
the index study prior to LTE entry. In the index studies pts received tofacitinib 5 or 10 mg BID as monotherapy (mono) or
with conventional synthetic DMARDs (csDMARDs); at the physicians’ discretion pts could switch tofacitinib dose in the
LTE, and were assigned to 5 mg BID if average total daily dose was <15 mg/day or to 10 mg BID if ≥15 mg/day. Outcomes
to evaluate structural damage from BL to Month (M)36 included: mean and mean change (Δ) from BL in van der Heijde
modified Total Sharp Score (mTSS), Erosion Score (ES), and Joint Space Narrowing Score (JSN); % of pts with no
radiographic progression (ΔmTSS ≤0.5); and % of pts with no new erosions (ΔES≤0.5). Observed data were analyzed
descriptively.
Results: A total of 1156 pts from the index studies were pooled in the LTE radiographic analysis; x-rays available in 88%
(n=1019) of pts at M6; 497 pts received tofacitinib mono (5 mg BID, n=42; 10 mg BID, n=455) and 659 pts received
tofacitinib with csDMARDs (5 mg BID, n=53; 10 mg BID, n=606). N at M12 was 86.8%, at M24 76.0%, and at M36
35.8% of the BL value. From LTE entry, mean duration of tofacitinib treatment in the total population was 1113 days
(range 21–2396), and mean mTSS, ES, and JSN only slightly increased from BL to M36 (Figure). Mean (standard error
[SE]) ΔmTSS was 0.25 (0.05) at M12 and 1.17 (0.28) at M36. Mean (SE) ΔES and ΔJSN were 0.21 (0.03) and 0.24 (0.02)
at M12 and 0.68 (0.17) and 0.78 (0.13) at M36. The % (SE) of all tofacitinib-treated pts with radiographic non-progression
decreased from 91.2% (0.9) at M6 to 84.5% (1.1) at M12 and 72.2% (2.2) at M36, and the % of pts with no new erosions
decreased from 96.0% (0.6) at M6 to 92.3% (0.8) at M12 and 85.3% (1.7) at M36. Similar trends were observed for all
endpoints from BL to M36 in the tofacitinib mono and csDMARD groups (Figure); change from BL in mTSS, ES, and JSN
score was similar at most time points in the csDMARD and mono populations (data not shown).
Conclusion: Structural damage progression was limited during treatment with tofacitinib alone or with csDMARDs for up
to 3 years in pts with RA.
References
1. Wollenhaupt J et al. Arthritis Rheumatol 2015; 67 Suppl 10; A1645

2. Wollenhaupt J et al. Arthritis Rheumatol 2016; 68 Suppl 10; A1647
3. Wollenhaupt J et al. J Rheumatol 2014; 41: 837–852
Disclosure: D. van der Heijde, AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim,
Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Merck, Novartis, Pfizer Inc, Regeneron, Roche, Sanofi,
Takeda, UCB, 5,Director of Imaging Rheumatology bv., 9; J. Wollenhaupt, Pfizer Inc, 1,Pfizer Inc, 8; S. B. Cohen,
AbbVie, Amgen, Boehringer Ingelheim, Gilead, Merck, Pfizer Inc, 5,AbbVie, Amgen, Boehringer Ingelheim, Gilead,
Merck, Pfizer Inc, 9; S. Strengholt, Pfizer Inc, 1,Pfizer Inc, 3; K. Terry, Pfizer Inc, 1,Pfizer Inc, 3; R. DeMasi, Pfizer Inc,
1,Pfizer Inc, 3; K. Kwok, Pfizer Inc, 1,Pfizer Inc, 3; I. Lazariciu, Quintiles, 3,Pfizer Inc, 5; L. Wang, Pfizer Inc, 1,Pfizer
Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/assessment-of-radiographic-

progression-in-patients-with-rheumatoid-arthritis-treated-with-tofacitinib-data-from-an-open-label-long-term-extension-
study-over-3-years
Effect of Baseline MTX Dose on Clinical Efficacy and Safety in Rheumatoid

Arthritis Patients Treated with Filgotinib: Post-Hoc Analysis from a Phase
2B Study
René Westhovens1, Annegret Van der Aa2, Corinne Jamoul2, Chantal Tasset2 and Pille Harrison2, 1KU Leuven
Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, Leuven, Belgium,
2Galapagos NV, Mechelen, Belgium

SESSION INFORMATION
Background/Purpose:
(RA) patients with inadequate response to MTX (MTX-IR)1,2.The objective was to assess the effect of MTX dose on
clinical efficacy and safety in MTX-IR RA patients treated with filgotinib as add-on to background MTX for 24 weeks.
Methods:
Patients with active RA on stable dose of MTX were randomized in a double-blinded manner to receive either placebo
(PBO) or one of 3 daily doses of filgotinib (50mg, 100mg or 200mg) as once or twice daily regimen for 24 weeks1. This
post-hoc analysis includes patients treated with the selected Phase 3 filgotinib doses, 100mg and 200mg QD, and PBO for
the efficacy parameters, and all dose groups for the safety analysis. MTX dose was categorized as low (≤12.5mg/wk),
medium (>12.5 to <17.5 mg/wk) or high (≥17.5mg/wk).
Results:
Baseline disease activity was high and similar across the three MTX subgroups, with an overall mean DAS28(CRP) score
of 6.10, mean HAQ-DI of 1.73, mean CDAI score of 42.10 and mean SDAI score of 44.57. Across all MTX subgroups,
patients on filgotinib 100mg or 200mg QD for 24 weeks showed efficacy over PBO, as measured by change from baseline
in DAS28(CRP), CDAI, SDAI, HAQ-DI, and ACR20 response. No pattern was observed to suggest that the baseline MTX
dose had any effect on filgotinib efficacy. The incidences of TEAE and serious TEAE were comparable regardless of the
MTX dose (Table 2).
Conclusion:
Post-hoc analysis of a phase 2B study in MTX-IR RA patients suggests that filgotinib treatment at 100mg and 200mg QD
on the background of MTX is consistently associated with improved clinical outcomes compared to placebo, across all key
efficacy parameters, irrespective of MTX dose. The safety profile was overall favorable and consistent with previous
studies in RA with filgotinib, regardless of MTX dose.
Table 1. Mean (SE) change from baseline in key efficacy parameters at Week 24 by MTX subgroup.
filgotinib 100mg filgotinib 200mg
PBO
QD QD
Low MTX dose (≤12.5mg/wk)
N 14 9 8
DAS28(CRP) -0.94 (0.28) -1.96 (0.47) -2.49 (0.43)
CDAI -15.74 (4.67) -23.32 (6.36) -27.31 (5.27)
SDAI -15.31 (4.68) -24.87 (6.34) -29.63 (5.70)
HAQ-DI -0.30 (0.14) -0.61 (0.26) -0.73 (0.26)
Medium MTX dose (>12.5 to <17.5mg/wk)
N 43 48 44
DAS28(CRP) -1.05 (0.23) -2.77 (0.20) -2.73 (0.21)
CDAI -14.49 (2.81) -29.73 (2.14) -30.05 (2.04)
SDAI -14.35 (2.92) -31.49 (2.19) -31.30 (2.23)
HAQ-DI -0.36 (0.11) -0.71 (0.09) -0.79 (0.08)
High MTX dose (≥17.5mg/wk)
N 28 27 34
DAS28(CRP) -1.51 (0.32) -2.82 (0.30) -2.97 (0.21)
CDAI -18.67 (3.50) -28.47 (2.76) -29.18 (2.50)
SDAI -18.36 (3.53) -29.48 (2.86) -30.95 (2.67)
HAQ-DI -0.39 (0.10) -0.94 (0.15) -0.87 (0.13)
ACR20 by subgroup, n (%)
Low MTX dose
5 (36%) 4 (44%) 7 (88%)
(≤12.5mg/wk)
Medium MTX
dose (>12.5 to 18 (42%) 31 (65%) 32 (73%)
<17.5mg/wk)
High MTX dose
13 (46%) 17 (63%) 24 (71%)
(≥17.5mg/wk)
Table 2. Treatment-emergent adverse events (TEAE) and serious TEAEs at Week 24 by MTX subgroup.
% of patients PBO Filgotinib
Low MTX dose (≤12.5mg/wk)

TEAE 57 55
Serious TEAE 7 3
Medium MTX dose (>12.5 to <17.5mg/wk)
TEAE 47 46
Serious TEAE 2 2
High MTX dose (≥17.5mg/wk)
TEAE 57 57
Serious TEAE 7 2
References
Disclosure: R. Westhovens, Bristol-Myers Squibb, 2,Roche Pharmaceuticals, 2,CellTrion, 5,Galapagos NV, 5; A. Van der
Aa, Galapagos NV, 1,Galapagos NV, 3; C. Jamoul, Galapagos NV, 3; C. Tasset, Galapagos NV, 1,Galapagos NV, 3; P.
Harrison, Galapagos NV, 1,Galapagos NV, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effect-of-baseline-mtx-dose-on-clinical-

efficacy-and-safety-in-rheumatoid-arthritis-patients-treated-with-filgotinib-post-hoc-analysis-from-a-phase-2b-study
Effect of a Step-up or Step-Down in Tofacitinib Dose on Efficacy and Safety

in Long-Term Extension Studies
Ruediger Mueller1, Hendrik Schulze-Koops2, Daniel E Furst3, Stanley B Cohen4, Kenneth Kwok5, Anna Maniccia5, Lisy
Wang6, Ermeg Akylbekova7 and Johannes von Kempis1, 1Kantonsspital St. Gallen, St. Gallen, Switzerland, 2Klinikum der
Universität München, Munich, Germany, 3UCLA, Los Angeles, CA, 4Metroplex Clinical Research Center and University
of Texas Southwestern Medical Center, Dallas, TX, 5Pfizer Inc, New York, NY, 6Pfizer Inc, Groton, CT, 7QuintilesIMS,
Durham, NC
SESSION INFORMATION
Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. Efficacy and safety of
tofacitinib 5 and 10 mg BID have been shown in long-term extension (LTE) studies up to 105 months. We assessed the
impact of tofacitinib dose changes on efficacy and safety in patients (pts) who increased dose (step-up), and pts who
decreased dose (step-down), vs pts who remained on the same dose when entering LTE studies.
Methods: In this exploratory, post-hoc analysis, data were pooled from 2 open-label LTE studies (NCT00413699 [ongoing;
database not locked at January 2016 data-cut]; NCT00661661) of RA pts who had participated in Phase (P) 1/2/3
tofacitinib index studies and had ≥81 days of tofacitinib exposure (to allow ≥2 assessments) in each period (P1/2/3 index,
LTE). Dose changes from index study dose were either mandated by protocol (upon LTE entry) or at the investigator’s
discretion (during LTE). This analysis only included pts who remained on their initial/changed dose once in the LTE. Pts
were analyzed in 4 groups: 5 mg BID [index]→10 mg BID [LTE] (Step-up; N=833); 5 mg BID [index]→5 mg BID [LTE]
(Remain 5; N=248); 10 mg BID [index]→10 mg BID [LTE] (Remain 10; N=951); 10 mg BID [index]→5 mg BID [LTE]
(Step‑down; N=234). To determine whether initial efficacy (last index study assessment) may affect response following
dose change on LTE entry, sub-groups for the Step-up and Remain 5 groups were defined based on initial ACR20 response,
and sub-groups for the Step-down and Remain 10 groups were defined based on initial ACR50 response. Efficacy was
assessed up to Month 12 in the LTE based on ΔDAS28-4(ESR). Exposure-adjusted event rates (pts with event/100 pt-yrs)
are presented for the most common AEs for the entire LTE study exposure.
Results: No statistically significant differences in ΔDAS28‑4(ESR) were observed between the Step-up and Remain 5
groups (Figure), whether or not they had an initial ACR20 response. In general, no significant differences in
ΔDAS28‑4(ESR) were observed between the Step‑down and Remain 10 groups (Figure), whether or not they had an initial
ACR50 response. The rates and types of adverse events (AEs) were similar across all groups (Table).
Conclusion: In RA pts, the safety profile was similar regardless of dose change. Step-up from tofacitinib 5 to 10 mg BID,
or step-down from 10 to 5 mg BID did not affect efficacy over 12 months vs remaining on the same dose, and was not
influenced by initial response. Conclusions are limited by small pt numbers in some groups, the open-label design, and
inclusion of pts in the LTE who show tolerability for tofacitinib and drug retention.
Disclosure: R. Mueller, None; H. Schulze-Koops, None; D. E. Furst, Pfizer Inc, 5; S. B. Cohen,
AbbVie,Amgen,Boehringer Ingelheim,Gilead,Merck,Pfizer Inc, 5,Abbvie,Amgen,Boehringer
Ingelheim,Gilead,Merck,Pfizer Inc, 9; K. Kwok, Pfizer Inc, 1,Pfizer Inc, 3; A. Maniccia, Pfizer Inc, 1,Pfizer Inc, 3; L.
Wang, Pfizer Inc, 1,Pfizer Inc, 3; E. Akylbekova, QuintilesIMS, 3,Pfizer Inc, 5; J. von Kempis, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effect-of-a-step-up-or-step-down-in-

tofacitinib-dose-on-efficacy-and-safety-in-long-term-extension-studies
Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis:

A Retrospective Analysis of Real-World Data from the St. Gallen Cohort
Ruediger Mueller1, Frederik Mattow2, Florian Popp3 and Johannes von Kempis4, 1Division of Rheumatology, Cantonal
Hospital, St. Gallen, Switzerland, 2Kantonsspital St. Gallen, St. Gallen, Switzerland, 3Rorschacherstrasse 95, Kantonsspital
St. Gallen, St. Gallen, Switzerland, 4Rheumatology, Kantonsspital St. Gallen, St. Gallen, Switzerland
SESSION INFORMATION
Background/Purpose:
Tofacitinib is an oral JAK inhibitor for the treatment of RA. Efficacy and safety of tofacitinib have been shown in several
clinical studies. The study presented here aimed to assess the clinical effectiveness and tolerability of tofacitinib among
patients with RA in real life.
Methods:
Consecutive patients between June 2013 and April 2017 with RA who fulfilled the American College of
Rheumatology/EULAR 2010 criteria were analyzed in a prospectively designed analysis of retrospective data. Patients
were initiated on tofacitinib 5mg bid. The primary objective was to analyze safety of tofacitinib in a real life cohort. Safety
was assessed by the reasons to stop tofacitinib during follow up and changes of liver enzymes, hemoglobin, and creatinine.
The secondary outcome was to analyze the frequency and time to achieve low disease activity (LDA) and remission as
defined by DAS28.
Results:
Overall, 58 patients were treated with tofacitinib. 86% of the patients were pre-exposed to at least one biological agent. The
average DAS 28 at initiation of tofacitinib was 4.5. 65% were rheumatoid factor and 52% ACPA positive. The mean follow
up was 1.74 years after initiation of tofacitinib treatment. 32 (57%) patients remained on tofacitinib during follow up. The
average time to stop tofacitinib was 112 days. Reasons to stop tofacitinib were: gastrointestinal (n=12), insufficient
response (n=5), flare (n=3), pneumonia (n=2), blue toe syndrome (n=1), thoracic pain (n=1), and myalgia (n=1).
Increased of ALAT and ASAT were detected in 4 and 8 patients (>2x ULN: n=1 and n=2). These elevated transaminase
levels were transient in 2 and 5 patients, respectively. The average hemoglobin level decreased by 2.6%. A decrease of
more than 10% of the hemoglobin level was found in 7 patients during follow up. The average lymphocyte count increased
by 6.6%. A decrease below 1000 Lymphocytes/mcl was detected in four patients. Three of them were transient. The mean
creatinine level increased by 3.4%. An increase of more than 10% was detected in seven patients (n=1 with pathological
creatinine level).
37 (63.8%) and 31(53.4%) of the patients achieved LDA or remission after 62.0 and 65.3 days respectively.
Conclusion:
Tofacitinib is a safe and effective treatment option for patients with RA. Tofacitinib may induce high rates of LDA and
remission in patients with active disease, even after use of one or more biologics, over prolonged periods of time.
Tofacitinib may be a valuable option in a treat to target approach because the time to determine its efficacy or adverse
reaction leading to discontinuation is short, based on the data of our cohort
Disclosure: R. Mueller, None; F. Mattow, None; F. Popp, None; J. von Kempis, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effectiveness-tolerability-and-safety-of-

tofacitinib-in-rheumatoid-arthritis-a-retrospective-analysis-of-real-world-data-from-the-st-gallen-cohort
No Effect of Baseline Serum CRP Levels on Clinical Efficacy Parameters in

Rheumatoid Arthritis Patients Treated with Filgotinib: Post Hoc Analysis
from Two Phase 2B Studies
Arthur Kavanaugh1, Annegret Van der Aa2, Corinne Jamoul2, Chantal Tasset2, Pille Harrison2 and René Westhovens3,
1Medicine, University of California, San Diego, La Jolla, CA, 2Galapagos NV, Mechelen, Belgium, 3Department of
Rheumatology, University Hospitals Leuven, Leuven, Belgium
SESSION INFORMATION
Background/Purpose:
(RA) patients with inadequate response to MTX (MTX-IR)1,2.
The objective was to evaluate the effect of baseline serum CRP levels on clinical efficacy after 12 weeks of treatment, as
assessed by the ACR and DAS28(CRP) subcomponents in MTX-IR RA patients treated with filgotinib.
Methods:
Patients were randomized in a double-blind manner to placebo (PBO) or one of 3 daily doses of filgotinib (50mg, 100mg or
200mg) for 24 weeks. In the DARWIN 1 study, filgotinib on MTX background was evaluated as once (QD) or twice daily
treatment. In the DARWIN 2 study once-daily filgotinib was assessed as monotherapy. The inclusion criterion for CRP was
amended during the studies and was decreased from 13.5 mg/L to 6.3 mg/L. This post-hoc analysis included patients
treated with the selected Phase 3 filgotinib doses, 100mg and 200mg QD, and PBO. Efficacy outcomes were analyzed by
baseline CRP level (low: ≤9 mg/L and high: >9 mg/L, with 9mg/L as ULN).
Results:
Baseline disease activity was high and balanced across the different treatment groups. Comparable baseline values were
shown between both CRP subgroups, except for the mean CRP levels (Table 1).
In both low and high CRP subgroups, patients on filgotinib at 100mg or 200mg QD for 12 weeks showed efficacy over
PBO, as measured by change from baseline in different subcomponents of the ACR/DAS28(CRP) composite score (TJC68,
SJC66, Pt pain, Pt GDA, Inv GDA, HAQ-DI and CRP) (Table 1). In both studies, there was no clear pattern suggesting that
baseline CRP level had a consistent effect on filgotinib efficacy.
Conclusion:
This post-hoc analysis of two Phase 2B studies in MTX-IR RA patients suggests that filgotinib treatment once daily at
100mg and 200mg both on the background of MTX and as monotherapy was consistently associated with improved clinical
outcomes compared to placebo at Week 12, regardless of baseline CRP levels, as measured by ACR and DAS28(CRP)
subcomponents.
Table 1. Mean baseline and change from baseline (SE) values in key efficacy parameters at Week 12 by CRP subgroup
DARWIN 1 DARWIN 2
PBO filgotinib filgotinib PBO filgotinib filgotinib
100mg QD 200mg QD 200mg QD
100mg QD
Low CRP subgroup (≤9 mg/L)
N 33 25 15 11 20 20
TJC68 26.60 23.70
23.45 21.94 21.64 27.13
-14.87 -16.63
-9.42 (2.68) -12.17 (2.04) -3.55 (3.59) -14.68 (2.90)
(2.82) (2.71)
SJC66 17.00
15.52 14.30 14.18 19.50 13.21
-12.07
-8.82 (1.62) -10.09 (1.57) -5.09 (3.11) -10.75 (2.04) -9.51 (1.30)
(2.53)
Pt pain 64.94 69.67 72.64 66.05
61.24 73.15
-19.24 -27.27 -11.27 -32.30
-30.12 (5.77) -36.05 (6.76)
(6.41) (6.25) (7.63) (8.50)
Pt GDA 62.88 72.60 74.09 67.80
66.96 71.85
-17.82 -35.33 -13.36 -30.25
-36.16 (5.74) -38.20 (5.74)
(5.92) (7.88) (7.68) (7.35)
Inv GDA 65.27 67.00 76.18 68.55
65.84 74.25
-29.24 -41.40 -33.36 -49.75
-38.88 (4.85) -50.50 (4.73)
(5.84) (5.53) (9.51) (4.86)
HAQ-DI 1.47 1.91 1.93 1.72
1.51 1.75
-0.21 -0.64 -0.12 -0.74
-0.76 (0.133) -0.74 (0.172)
(0.121) (0.100) (0.163) (0.158)
CRP 4.29
5.57 5.57 4.44 5.20 4.41
+0.04
+5.97 (2.53) +0.14 (1.96) +1.56 (1.49) -0.09 (0.99) +0.89 (1.31)
(1.69)
High CRP subgroup (>9 mg/L)
N 53 60 71 61 50 49
TJC68 29.32 27.28
25.94 26.73 25.87 27.22
-18.22 -17.73
-8.98 (1.44) -14.86 (1.68) -6.21 (1.62) -15.29 (1.82)
(1.49) (1.79)
SJC66 17.43 16.77
16.51 17.15 16.30 18.31
-10.80 -10.87
-6.87 (1.03) -9.67 (1.22) -3.89 (1.34) -11.65 (1.48)
(1.03) (1.27)
Pt pain 66.11 66.42 71.38 69.00
67.14 72.42
-15.49 -32.24 -13.70 -30.86
-26.19 (3.72) -29.66 (4.02)
(3.53) (3.29) (3.41) (3.82)
Pt GDA 65.00 67.87 70.59 69.33
67.83 71.30
-15.98 -33.94 -11.21 -27.43
-26.18 (3.84) -26.78 (4.03)
(3.39) (3.46) (3.19) (3.57)
Inv GDA 67.25 65.54 69.33 67.33
66.65 71.14
-25.77 -37.25 -21.87 -38.38
-31.33 (3.10) -39.02 (3.15)
(3.65) (2.62) (3.29) (3.30)
HAQ-DI 1.83 1.78 1.73 1.77 1.82 1.82
-0.61 (0.087) -0.65 (0.081)

-0.49 -0.78 -0.25 -0.74
(0.080) (0.076) (0.074) (0.086)
CRP 31.91 40.82 30.82
22.89 32.44 33.70
-20.90 -10.56 -21.27
+0.61 (3.22) -19.28 (3.60) -17.12 (6.19)
(3.88) (5.01) (3.33)
References
Disclosure: A. Kavanaugh, AbbVie, 5,Amgen, 5,Celgene, 5,Novartis Pharmaceutical Corporation, 5,Janssen

Pharmaceutica Product, L.P., 5,Eli Lilly and Company, 5,Pfizer Inc, 5,UCB, 5,Galapagos NV, 5; A. Van der Aa, Galapagos
NV, 1,Galapagos NV, 3; C. Jamoul, Galapagos NV, 3; C. Tasset, Galapagos NV, 1,Galapagos NV, 3; P. Harrison,
Galapagos NV, 1,Galapagos NV, 3; R. Westhovens, Bristol-Myers Squibb, 2,Roche Pharmaceuticals, 2,CellTrion,
5,Galapagos NV, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/no-effect-of-baseline-serum-crp-levels-

on-clinical-efficacy-parameters-in-rheumatoid-arthritis-patients-treated-with-filgotinib-post-hoc-analysis-from-two-phase-
2b-studies
Severe Adverse Drug Reactions Due to Disease Modifying Drugs in Patients

with Incident Rheumatoid Arthritis
Lydia A Alcazar1, Judit Font Urgelles2, Cynthia Milagros León Cárdenas2, Cristina Vadillo Font2, Dalifer Freites Núñez1,
Leticia Leon1, Juan A Jover Jover2 and Zulema Rosales Rosado1,2, 1Instituto de Investigación Sanitaria San Carlos
(IdISSC), Madrid, Spain, 2Rheumatology, Hospital Clínico San Carlos, Madrid, Spain
SESSION INFORMATION
Background/Purpose: There is a well-known risk of developing adverse drug reactions (ADR) in rheumatology due,
mainly, to the Disease Modifying Drugs (DMARD) used. It is mandatory to increase our knowledge of ADR; especially
those that put the patient live at risk. The purpose of our study was to describe the incidence and characteristics of severe
ADR to DMARD in patients with incident RA as well as the factors associated to their development.
Methods: An observational longitudinal study was conducted. Patients: all recent onset RA patients diagnosed between
April 15th 2007 and 31st June 2011 followed in outpatient clinic at Hospital Clinico San Carlos until December 31st 2016,
which used any DMARD treatment (synthetic and biologic). Primary outcome: development of a severe ADR
(discontinuation and hospitalization or death as a result of the ADR) due to DMARD treatment. Incidence rates of
discontinuation (IR) per 100 patient-years were estimated using survival techniques with their respective 95% confidence
interval [CI]. Comparisons between associated factors were run by Cox bivariate and multivariate regression models.
Results were expressed by hazard ratio (HR) and [CI].
Results: We included 1054 courses of DMARD treatment in 405 patients (2277.9 patient-years). Of these, 78.27% were
women with a mean age at diagnosis of 57 ± 15 years. The median time to the start of the first DMARD was 0.3 [± 0.6]
days and the median value of ESR at diagnose was 40 [± 27] mm/h. 16.3% of patients were taking biological DMARD,
73.3% were using monotherapy and 89% were taking corticoids. There were 369 ADRs in 212 patients, 41 of them (11.1%)
severe (IR: 1.8 [1.3-2.4]). Infection was the most frequent cause of severe ADR (n=26, 63.4%), followed by cancer (n=3,
7.3%); 6 patients died during follow up. Incidence rates are shown in table 1. In the multivariate analysis after adjusting by
age: female sex (HR: 2.7 [1.2-5.9]), the use of biological DMARD compared to synthetic DMARD (HR: 3.6 [1.03-12.6]),
higher ERS at the beginning of the DMARD (HR: 1.01 [1-1.02]) and the presence at baseline of congestive heart failure
(HR: 4.3 [2-9.2]), periphery arteriopathy (HR: 3.1 [1.02-9.2]) and cancer (HR: 3.2 [1.6-6.5]) achieved statistically
significant association with the development of a severe ADR. Whereas number of concomitant DMARD dropped from the
model (HR: 1.23 [0.5-2.6]).
Conclusion: This study describes the incidence of severe ADR occurred in RA patients taking DMARD in real life
conditions. The IR of severe ADR in our cohort was 1.8% patient-years, increasing to 3.6% in the population over 70 years
old. Infection was the main cause of severe ADR followed by cancer. Caution might be taken regarding severe ADR in
patients of female sex, those using biological DMARD, with higher ERS at the beginning of treatment or with certain
comorbidities.
TABLE 1 patients-years n IR 95%CI
Global 2277.9 41 1.8 1.3-2.4
Women 1835.4 24 1.3 0.9-2
Men 442.5 17 3.8 2.4-6.2

By age category
1065.5 11 1 0.6-1.9
18-50 years
716.9 12 1.7 0.9-2.9
51-70 years
495.5 18 3.6 2.3-5.8
> 70 years
By therapy regimen
1609.5 25 1.6 1.1-2.3
Monotherapy
568.9 12 2.1 1.2-3.7
Double therapy
99.4 4 4 1.5-10.7
Triple therapy
By type of DMARD
2048.3 31 1.5 1.1-2.2
Synthetic
229.5 10 4.4 2.3-8.1
Biological
By corticoids use
1997.2 39 1.9 1.4-2.7
Yes
278.3 2 0.7 0.2-2.9
No
By drug
8.3 2 24.2 6.1-96.8
Abatacept
81.5 1 1.2 0.2-8.7
Adalimumab
749.7 6 0.8 0.4-1.8
Antimalarials
16 1 6.2 0.9-44.1
Certolizumab
65.2 2 3.1 0.8-12.3
Etanercept
9.1 1 11 1.5-78
Golimumab
18.4 3 16.3 5.3-50.6
Infliximab
340.4 7 2.1 0.9-4.3
Leflunomide
1463.5 24 1.6 1.1-2.4
Methotrexate
83.6 7 8.4 4-17.6
Gold
154 6 3.9 1.8-8.7
Sulfasalazine
Disclosure: L. A. Alcazar, None; J. Font Urgelles, None; C. M. León Cárdenas, None; C. Vadillo Font, None; D.
Freites Núñez, None; L. Leon, None; J. A. Jover Jover, None; Z. Rosales Rosado, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/severe-adverse-drug-reactions-due-to-

disease-modifying-drugs-in-patients-with-incident-rheumatoid-arthritis
Comparison of Oral Versus Parenteral Methotrexate in Rheumatoid

Arthritis: A Meta-Analysis
Sahar Janjua1, Andreea Bujor1, Michael P. LaValley2, Josefina Duran3, Jürgen Braun4 and David T. Felson5, 1Department
of Rheumatology, Boston Medical Center, Boston, MA, 2Boston University School of Public Health, Boston, MA,
3Pontificia Universidad Católica de Chile, Santiago, Chile, 4Institut für angewandte Statistik Dr. Jörg Schnitker GmbH,
Bielefeld, Germany, 5Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston,
MA
SESSION INFORMATION
Background/Purpose: Methotrexate (MTX) is the mainstay first-line therapy for rheumatoid arthritis (RA), and it can be
given orally or parenterally. Bioavailability of oral MTX may decrease at high doses, and parenteral administration could
bypass this limitation. Practice guidelines recommend changing to biologics if response to MTX is suboptimal but these
guidelines are based on studies comparing biologics to oral MTX. There is some evidence that parenteral MTX may be
more efficacious than the oral form at equivalent doses. Also, studies suggest that the side effect profile of parenteral MTX
may be better than oral MTX. We carried out a meta-analysis to compare the efficacy of oral versus parenteral MTX in
RA.
Methods:
PubMed, Web of Science and Embase were systematically searched from inception to June 8th 2017 and reviewed
following PRISMA 2009 guidelines. We also examined bibliographies of reviews and other articles. To be included, trials
had to study adults with RA randomized to the same dose of either oral or parenteral MTX. Studies were selected and data
extracted by two independent reviewers and at each stage the reviewers met to adjudicate discrepancies. The primary
endpoint was ACR20 at 6 months. Other endpoints included ACR50, ACR70, SDAI, and DAS28 remission. One large trial
allowed switching for poor response at 16 weeks and included only 24 week data, and trial authors reanalyzed data at 16
weeks. For another trial, data were reanalyzed to provide ACR20/50/70 rates. Intention-to-treat analyses were used when
possible. Data from direct comparisons between oral and parenteral methotrexate were pooled and quantitatively analyzed
using maximum likelihood random effects meta-analysis. Relative treatment effects were generated as odds ratio [OR]
(OR>1 indicated a benefit for parenteral therapy). We also examined the mean difference in ACR20 rates between
parenteral and oral MTX.
Results:
The search yielded 357 papers or abstracts. After review of titles or abstracts, we excluded 314. We then examined 43 full-
text papers or abstracts and found 4 that met inclusion criteria with 703 patients randomized. Dose of MTX started at
15mg/week and increased to as high as 22.5mg/week. In each trial, ACR20 rates were higher for those randomized to
parenteral than to oral MTX. The summary OR for achieving ACR20 using parenteral vs. oral MTX was 2.84 (95% CI
1.35, 5.98) (see figure). Those on parenteral had an 18.5% (95% CI 3.3%, 33.6%) greater absolute risk of attaining ACR20
than those on oral MTX. Similar results were seen for ACR50 and 70 and for SDAI and DAS.
Conclusion:
In this meta-analysis, parenteral MTX therapy had a significantly higher odds than oral MTX of achieving reduction in
disease activity. We propose that parenteral MTX is more effective than oral MTX with a better safety profile; its
widespread use may lead to better control of disease and a decrease in demand for biologic agents.
Disclosure: S. Janjua, None; A. Bujor, None; M. P. LaValley, None; J. Duran, None; J. Braun, Abbvie (Abbot),
Amgen, Biogen, BMS, Boehringer, Celgene, Celltrion, centocor, Chugai, EBEWE Pharma, Epirus, Hikma, Hospira,
Janssen, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB,
5,Abbvie (Abbot), Amgen, Biogen, BMS, Boehringer, Celgene, Celltrion, centocor, Chugai, EBEWE Pharma, Epirus,
Hikma, Hospira, Janssen, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis
and UCB, 2,Abbvie (Abbot), Amgen, Biogen, BMS, Boehringer, Celgene, Celltrion, centocor, Chugai, EBEWE Pharma,
Epirus, Hikma, Hospira, Janssen, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-
Aventis and UCB, 6; D. T. Felson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/comparison-of-oral-versus-parenteral-

methotrexate-in-rheumatoid-arthritis-a-meta-analysis
Being Elderly Is Not a Predictive Factor of Discontinuation of Abatacept Due

to Adverse Events in Rheumatoid Arthritis Patients with Concomitant
Methotrexate: A Retrospective Observational Study Based on Data from a
Japanese Multicenter Registry Study
Nobunori Takahashi, Toshihisa Kojima, Shuji Asai, Tatsuo Watanabe, Takuya Matsumoto, Nobuyuki Asai, Yasumori
Sobue and Naoki Ishiguro, Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
SESSION INFORMATION
Background/Purpose:
Abatacept is a new class of biologic agent for the treatment of rheumatoid arthritis (RA) that inhibits T cell activation by
binding to CD80/86. Some evidences demonstrating that the abatacept may offer advantage on safety over the TNF
inhibitors have been accumulated. Therefore, we sometimes tend to use abatacept in the elderly patients easily. We studied
the clinical response and safety profile of abatacept in the real-world patients using the Japanese multicenter registry data.
Methods:
Participants were the consecutive 508 RA patients treated with abatacept who were registered in the Tsurumai Biologics
Communication Registry (TBCR). We divided the patients into three groups according to the tertile value of age. As the
efficacy endpoints, we compared mean and categorical distribution of DAS28-CRP score and EULAR response rate
between the young (<62 years), middle (62-72 years), and elderly (>72 years) group at baseline, 4, 12, 24, and 52 weeks.
As the safety endpoints, we studied the incidence rate (Kaplan-Meier method) and the predictive factors (multivariate Cox
regression analysis) of the discontinuation of abatacept due to adverse events for up to 4 years. We studied the safety
endpoints separately in the patients with and without concomitant methotrexate (MTX) treatment, since the MTX usually
affects the safety profile.
Results:
There was significant difference between the young, middle, and elderly groups in age (52.7, 67.7, and 78.1 years;
p<0.001), eGFR value (108.5, 91.1, and 79.6 ml/min/1.73m2; p<0.001), and MTX usage rate (57.7, 44.9, and 32.2 %;
p<0.001). There was no significant difference between three groups in all of the clinical efficacy endpoints (data not
shown). For the safety analysis, we divided the patients into two groups according to the cut-off value (69.5 years) from the
ROC curve for age in the MTX (-) patients (Fig. A). The elderly group (>69.5 years) demonstrated higher incidence rate of
discontinuation due to adverse events (1.0 vs 4.9% at 24 weeks, p=0.005) in the MTX (-) patients (Fig. B). The age of
>69.5 years was identified as an independent predictor of incidence of discontinuation due to adverse events in the MTX (-)
patients (Fig. C). However, there was no such difference in the incidence rate (Fig. B) and the being elderly (>69.5 years)
was not a predictor in the MTX (+) patients (Fig. C).
Conclusion:
It was remarkable that abatacept therapy demonstrated the comparative efficacy in the elderly patients. Similar to a case of
other biologics, we should pay attention to the incidence of severe adverse events in the elderly patients without
concomitant MTX. However, especially in the patients being treated with MTX concomitantly, abatacept would be a good
treatment option in the elderly from the view point of both efficacy and safety.
Disclosure: N. Takahashi, None; T. Kojima, None; S. Asai, None; T. Watanabe, None; T. Matsumoto, None; N. Asai,
None; Y. Sobue, None; N. Ishiguro, Abbott, Astellas Pharma, Bristol-Myers, Chugai Pharmaceutical, DaiichiSankyo,
Eisai, Hisamitsu, Janssen Pharmaceutical, Kaken Pharmaceutical, Mitsubishi Tanabe Pharma, Otsuka Pharmaceutical,
Pfizer, Takeda Pharmaceutical, Taisho Toyama Pharmaceutical, UCB, 2,Abbott, Astellas Pharma, Bristol-Myers, Chugai
Pharmaceutical, DaiichiSankyo, Eisai, Hisamitsu, Janssen Pharmaceutical, Mitsubishi Tanabe Pharma, Otsuka
Pharmaceutical, Pfizer, Takeda Pharmaceutical, Taisho Toyama Pharmaceutical, UCB, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/being-elderly-is-not-a-predictive-factor-

of-discontinuation-of-abatacept-due-to-adverse-events-in-rheumatoid-arthritis-patients-with-concomitant-methotrexate-a-
retrospective-observational-study-based
Decreasing Trend of Serious Infections Incidence Rate Along Years in

Rheumatoid Arthritis Patients Exposed to Biologics. Data from Two Latin
America Registries
Roberto Ranza1, Ieda Maria Magalhães Laurindo2, Georges Christopoulos2, Gimena Gomez3, Enrique R Soriano4,
Miguel Angel Descalzo5 and Maria de la Vega6, 1on behalf of the BiobadaBrasil study group, Sociedade Brasileira de
Reumatologia, Uberlandia, Brazil, 2on behalf of the BiobadaBrasil study group, Sociedade Brasileira de Reumatologia, São
Paulo, Brazil, 3on behalf of BiobadaSar study group, Sociedad Argentina de Reumatologia, Buenos Aires, Argentina,
4Argentina, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina, 5Research Unit, Fundacion piel sana AEDV,
Madrid, Spain, Madrid, Spain, 6on behalf of BiobadaSar study group, Sociedad Argentina de Reumatologia, Buenos aires,
Argentina
SESSION INFORMATION
Background/Purpose: Infections are the most frequent and concerning serious adverse events related to rheumatoid
arthritis (RA) treatment with biologic drugs (bDMARDs). Their safety profile might have substantial regional differences.
Since January 2009, BiobadaAmerica, a common platform registry project open to all Latin America countries, was started
with the goal of focusing on safety monitoring of bDMARDs. This study aims to to present data on the serious infections
(SI) incidence rate trend along years in patients with RA exposed to bDMARDs in two no- compulsory Latin America
registries.
Methods: Data from Brazil (BiobadaBrasil) and Argentina ( BiobadaSar) registries were downloaded on December 31,
2016 and merged. The same constant monitoring process granted data quality. Patients with rheumatic diseases were
included prospectively when started on the first bDMARD. Time of exposure was set from starting of treatment to the date
of last administration or censorship. SI incidence rate was calculated per 1000 patient/years with 95%CI
Results: Data from 2591 RA patients on bDMARDs were analyzed, for a total of 9300 p/y. There were 3784 treatment
courses, 64% with aTNF (Adalimumab, Certolizumab, Etanercept, Golimumab, Infliximab), 36% non-aTNF (Abatacept,
Rituximab, Tocilizumab) including Tofacitinib. Females 85%, mean age at baseline 53 yrs (SD 12.8) , mean disease
duration 10 yrs (8.5), mean follow-up 2.7 yrs (2). The overall incidence rate of SI (2010 – 2016) was 30.54 (CI 27.18-
34.30), The trend along the years is reported in the following table.
2010 2011 2012 2013 2014 2015 2016
26.57 26.03 36.59 35.85 18.3 16.18 7.27
(14.71-47.98) 18.09-36.46 28.41-47.12 28.55-45.03 13.62-24.59 12.04-21.75 4.79-11.05
Remarkable, the trend was the same in both registries when data were analyzed separately and reflected the general
tendency seen for all serious side effects.
Conclusion: A decreasing trend of serious infections incidence rate has been observed along the years in patients with RA
exposed to bDMARDs, in accordance with published data from other registries
Disclosure: R. Ranza, None; I. M. M. Laurindo, None; G. Christopoulos, None; G. Gomez, None; E. R. Soriano,
AbbVie, Janssen, Novartis, Pfizer Inc, UCB, 2,AbbVie, Janssen, Novartis, Pfizer Inc, UCB, 5,AbbVie, Bristol-Myers
Squibb, Janssen, Novartis, Pfizer Inc, Roche, UCB, 8; M. A. Descalzo, None; M. de la Vega, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/decreasing-trend-of-serious-infections-

incidence-rate-along-years-in-rheumatoid-arthritis-patients-exposed-to-biologics-data-from-two-latin-america-registries

Is There Any Difference in RA Patients for Methotrexate Use Vs.
Leflunomide Use As a Concomitant Treatment with Biological and Targeted
Synthetic Dmards in Turkbio Registry?
Nevsun Inanc1, Gulsen Ozen2, Yasemin Yalçınkaya1, Ediz Dalkilic3, Suleyman Serdar Koca4, Gerçek Can5, Ahmet
Karatas6, Yavuz Pehlivan7, Ayten Yazici8, Ayse Cefle9, Abdurrahman Tufan10, Servet Akar11, Soner Senel12, Burak Oz13,
Nurullah Akkoc14 and Fatos Onen15, 1Departement of İnternal Medicine, Division of Rheumatology, Marmara University,
Istanbul, Turkey, 2Rheumatology, Marmara University, School of Medicine, Rheumatology, Istanbul, Turkey, 3Department
of Internal Medicine, Division of Rheumatology, Uludag University, School of Medicine, Rheumatology, Bursa, Turkey,
4Department of Rheumatology, Firat University School of Medicine, Elazig, Turkey, 5Rheumatology, Dokuz Eylul
University Faculty of Medicine, İzmir, Turkey, 6Department of Rheumatology, Firat University, School of Medicine,
Rheumatology, Elazig, Turkey, 7Department of Rheumatology, Uludag University, Bursa, Turkey, 8Rheumatology, Kocaeli
University, Kocaeli, Turkey, 9Rheumatology, Kocaeli University, School of Medicine, Rheumatology, Kocaeli, Turkey,
10Internal Medicine-Rheumatology, Gazi University Medical School, Rheumatology, Ankara, Turkey, 11Rheumatology,
Izmir Katip Celebi University, School of Medicine, Rheumatology, Izmir, Turkey, 12Rheumatology, Kayseri Erciyes
University, School of Medicine, Rheumatology, Kayseri, Turkey, 13Rheumatology, Firat University, School of Medicine,
Rheumatology, Elazig, Turkey, 14Rheumatology, Private Practice, Rheumatology, İzmir, Turkey, 15Rheumatology, Dokuz
Eylul University Faculty of Medicine, Izmir, Turkey
SESSION INFORMATION
Background/Purpose: TURKBIO registry is the Turkish version of Danish DANBIO rheumatologic database which has
been established in 2011. Demographic and clinical data including age, sex, disease type, disease duration, and previous or
current treatment with conventional (csDMARD) and targeted synthetic (tsDMARD), and biological DMARDs
(bDMARDs) were collected. In this study, we aimed to investigate the efficacy and safety status of methotrexate (MTX) vs.
leflunomide (LEF) use as a concomitant treatment with bDMARDs and tsDMARD in this registry.
Methods: Frequencies of achievement of remission or remission+low disease activity (LDA) at the 6th month of bDMARD
or tsDMARD treatment were compared between patients who were on these medications with MTX vs. LEF as a
concomitant treatment. Similarly, patients who were on TNF inhibitors (TNFi), abatacept (ABA), rituximab (RTX),
tocilizumab (TCZ), and tofacitinib (TOFA) with MTX vs. LEF were also assessed separately for the achievement of
remission and remission+LDA. Drug survival and switch rates of bDMARDs and tsDMARD treatments either with MTX
or LEF were compared. The adverse effects with MTX and LEF concomitant use were evaluated as well.
Results:
The study included 725 bDMARD or tsDMARD receiving RA patients from 8 participating centers of the TURKBIO
registry. Of these patients, 462 (63.7%) were receiving concomitant MTX and 263 (36.3%) LEF. Demographic findings are
given in the Table. Achievement of remission and remission+LDA at the 6th month of bDMARD or tsDMARD initiation
was similar in concomitant MTX vs LEF groups (51.4% vs. 53%, P=0.683). When each bDMARD and tsDMARD was
evaluated separately, achievement of remission were again similar in MTX and LEF concomitant users (TNFi: 53% vs.
54%; ABA: 50% vs. 59%; RTX: 53% vs. 61%; TCZ: 42% vs. 35%; P>0.05 for all). For TOFA, although remission+LDA
rate was numerically higher in MTX concomitant group than LEF group (42% vs. 21%), the difference was not statistically
significant due to the smaller sample size of TOFA (N=33). The results were similar for all DMARD groups when
remission was evaluated alone. Drug survival (17±12 vs. 16±11 months, p>0.05 ) and drug discontinuation (42,2 vs 38,
p>0.05 ) rates of bDMARDs or tsDMARD were also not different in MTX vs. LEF concomitant users. Adverse effects rate
(19.5% vs 20.5%, p>0.05) were similar between MTX vs. LEF concomitant users as well.
Conclusion: Achievement of remission or remission+LDA was not different with the concomitant use of MTX vs. LEF
with any bDMARD or tsDMARD treatment in RA patients with a similar safety profile. LEF might be an alternative as a
concomitant DMARD in MTX-intolerant RA patients initiating bDMARDs or tsDMARD.
Table. Demographic findings of patients.
Sex, n (%) Female 596 (82,2)

Male 129 (17,8)
Age, Median (Q1-Q3) 55 (45-62)
Age, Mean±SD 54±13
Disease duration, Ortanca (Q1-Q3) 12 (8-17)
Disease duration, Ort±SD 13±8
Biological and targeted synthetic drugs, n (%) TNFi* 354 (48,8)
RITUXIMAB 144 (19,9)
ABATACEPT 127 (17,5)
TOCILIZUMAB 61 (8,4)
TOFACITINIB 36 (5,0)
ANAKINRA 3 (0,4)
Biological+MTX, n (%) 462 (63,7)
Biological+LEF, n (%) 263 (36,3)
*TNFi: ETANERCEPT, ADALIMUMAB, CERTOLIZUMAB, GOLIMUMAB, INFLIXIMAB, REMSIMA.
Disclosure: N. Inanc, None; G. Ozen, None; Y. Yalçınkaya, None; E. Dalkilic, AbbVie, 2,AbbVie, MSD, Roche, UCB
and Pfizer, 9; S. S. Koca, None; G. Can, None; A. Karatas, None; Y. Pehlivan, None; A. Yazici, None; A. Cefle, None;
A. Tufan, None; S. Akar, None; S. Senel, None; B. Oz, None; N. Akkoc, None; F. Onen, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/is-there-any-difference-in-ra-patients-

for-methotrexate-use-vs-leflunomide-use-as-a-concomitant-treatment-with-biological-and-targeted-synthetic-dmards-in-
turkbio-registry
Adverse Events in Rheumatoid Arthritis Patients Treated with Disease

Modifying Biological Drugs at Hospital Docente Padre Billini in Santo
Domingo
I Mercedes-Núñez, E Tejada-Reyes, Y Cruz-Rojas, E Rodríguez-Bautista, R Munoz-Louis, V Rosario, R Peña-Blanco, T
Valdez-Lorie and R Alba-Fériz, Rheumatology, Hospital Docente Padre Billini (HDPB), Santo Domingo, Dominican
Republic
SESSION INFORMATION
Background/Purpose: Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune chronic disease with disability
and deforms joints. After the introduction of biological therapies the prognosis of patients has improved. Approximately
one-third of patients do not respond to treatment with conventional disease modifying drugs (sDMARDs). There are
registers about adverse events (AE) of biological drugs disease modifying (bDMARDs), BIOBADASAR registry in
Argentina with a frequency of adverse events with the use of biologicals of 26%, with respiratory tract infections being the
most frequent. According to the BIOBADASER record loss of efficacy is the most frequent cause with more than 42% of
cases, infections 21%. Since we do not have reports of this type, our objective is to describe the AE in patients with RA
treated with bDMARDs anti TNF and non anti TNF. The bDMARDs used were adalimumab (ADA), golimumab (GLM),
Etanercept (ETN) as anti TNF, anti IL6 Tocilizumab (TCZ) and anti CD20 Rituximab (RTX).
Methods: A descriptive, ambispective cross-sectional study. Data were collected from the rheumatology service of
Hospital Docente Padre Billini, which is a national reference hospital. Statistical analyses were performed using SPSS
(V.23). We included all patients diagnosed with RA according to 2010 ACR/EULAR classification criteria treated with
bDMARDs during the period January 2013 - April 2017. Patients who did not have continuous follow-up by rheumatology
of at least 3 consecutive consultations in one year were excluded.
Results: We have 863 patients diagnosed with RA, 398 patients treated with bDMARDs, 220 patients met inclusion
criteria. 93% were women, mean age 57.2 years old, time of disease 9.9 years. The bDMARDs distributions was 51.4%
TCZ, 19.9% ADA, 12.3% ETN, 9.1% GLM, 7.7% RTX. 46.8% had AE: 37.2% treated with ADA, 48.1% ETN, 30%
GLM, 23.5% RTX, 56.6% TCZ. In the follow-up we found a 5% therapeutic failure of which 45.5% were by ADA, 18.2%
ETN, 18.2 TCZ%, 9.1% RTX, 9.1% GLM. 14.1% presented infections of which 16% were serious. 0.9% adverse event
were due to pulmonary tuberculosis (TB). 8.6% dyslipidemia of these 73.7% were TCZ, 6.4% hypertransaminemia of these
71.4% TCZ. 6.4% (13) neutropenia. 1.4% was diagnosed with neoplasm.
Conclusion: We found 46.8% of AE of these only 4.8 were serious unlike other records that report a 13.1%. Patients had a
good therapeutic response, in spite of the economic limitations of the population and the shortage of drugs occasionally.
The majority of patients used in our cohort TCZ. Even though a tropical country with high TB prevalence of we only found
two patients.
Disclosure: I. Mercedes-Núñez, None; E. Tejada-Reyes, None; Y. Cruz-Rojas, None; E. Rodríguez-Bautista, None; R.

Munoz-Louis, None; V. Rosario, None; R. Peña-Blanco, None; T. Valdez-Lorie, None; R. Alba-Fériz, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/adverse-events-in-rheumatoid-arthritis-

patients-treated-with-disease-modifying-biological-drugs-at-hospital-docente-padre-billini-in-santo-domingo
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PF-

06650833, a Novel, Potentially First-in-Class Inhibitor of Interleukin-1
Receptor Associated Kinase-4 (IRAK-4) in Healthy Subjects
Spencer Danto1, Negin Shojaee1, Cheryl Li1, Steven A. Gilbert2, Ravi Shankar Singh1, Zorayr Manukyan1 and Iain
Kilty1, 1Worldwide Research and Development, Pfizer, Inc., Cambridge, MA, 2Pfizer, Inc., Cambridge, MA
SESSION INFORMATION
Background/Purpose: IRAK‑4 is a key node in innate immune signaling and is activated by the interleukin (IL)‑1 family
receptors (IL‑1R, IL‑18R, and IL‑33R), in addition to the Toll‑like receptors (TLRs). Inhibition of IRAK‑4 blocks the
production of inflammatory cytokines such as type I interferons, IL‑6, tumor necrosis factor (TNF), IL‑1, and IL‑12 that are
key drivers of autoimmune and inflammatory diseases. Therefore, IRAK‑4, would be an attractive therapeutic target for
autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). PF-06650833 is a
recently described, small molecule, reversible, highly potent and specific inhibitor of IRAK-4. Nonclinical studies of PF-
06650833 have been conducted in rats and dogs that support studies up to 3 months in duration. The current abstract
describes the results from the single and multiple ascending dose (SAD, MAD) studies of PF-06650833 in healthy subjects.
Methods: The SAD and MAD studies of PF-06650833 were conducted in male and female (of nonchildbearing potential)
healthy subjects. The first-in-human study was a 5-way crossover SAD study that explored extemporaneously (extemp)
prepared immediate (IR)- and modified release (MR) formulations of PF-06650833 from 1 – 6000 mg. The MAD study
was a 14 day sequential ascending dose study of extemp IR and MR tablet formulations administered after a standard meal.
Doses from 25 mg BID to 1000 mg QID of the IR formulation and 300 mg MR tablets were explored. Standard clinical,
ECG, and laboratory safety monitoring were performed as well as exploratory biomarkers.
Results: PF-06650833 was generally safe and well tolerated after both SD and MD up to the maximal planned doses, with
dose limiting toxicity. Safety profile in both the SAD and MAD studies were similar, with the most common adverse events
(AEs) being headache, and gastrointestinal symptoms (mainly nausea and abdominal pain). There were no clinically
significant changes in vital signs, ECGs, or any laboratory parameter (including LFTs). PK analyses showed a moderate
absorption rate with median Tmax from ~2 h for IR doses and ~4 h for MR tablets after a standard meal at steady state.
Exposures increased proportionally up to about 100 mg and somewhat less than proportionally > 100 mg. In the MAD
study, T½ ranged from ~25 – ~31 h across the top IR and MR doses after a standard meal.
Conclusion: PF-06650833, a highly selective and potent inhibitor of IRAK-4, is shown to be generally safe and well
tolerated up to 6000 mg SD and 1000 mg QID in healthy subjects, with an MR PK profile sufficient to support QD dosing
in patient populations. To the authors’ knowledge, PF-06650833 is the first IRAK-4 inhibitor to advance to Phase 2 clinical
studies.
Disclosure: S. Danto, Pfizer, Inc., 3; N. Shojaee, Pfizer Inc, 3; C. Li, Pfizer Inc, 3; S. A. Gilbert, Pfizer Inc, 3; R. S.
Singh, Pfizer Inc, 3; Z. Manukyan, Pfizer Inc, 3; I. Kilty, Pfizer Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/safety-tolerability-pharmacokinetics-

and-pharmacodynamics-of-pf-06650833-a-novel-potentially-first-in-class-inhibitor-of-interleukin-1-receptor-associated-
kinase-4-irak-4-in-healthy-subjects
Incidence of Infusion Reactions to Intravenous Golimumab: Results from a

Prospective, Real-World Community Registry
Rafat Faraawi1, Andrew Chow2, Majed M M Khraishi3, Derek Haaland4, Milton F. Baker5, Cathy Tkaczyk6, Allen J
Lehman7, Francois Nantel6 and Brendan Osborne6, 1McMaster University, Hamilton, ON, Canada, 2Credit Valley
Rheumatology, Mississauga, ON, Canada, 3Faculty of Medicine, Memorial University of Newfoundland, St John's, NF,
Canada, 4Rheumatology, Clinical Immunology & Allergy, McMaster University, Barrie, ON, Canada, 5VIHA, Victoria,
BC, Canada, 6Medical Affairs, Janssen Inc., Toronto, ON, Canada, 7Janssen Inc., Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose: Golimumab (GLM) is a monoclonal antibody targeting TNF-alpha, indicated for the treatment of
adults with rheumatoid arthritis in combination with methotrexate (MTX). GLM-IV is recommended to be administered at
a dose of 2 mg/kg given as a 30-minute intravenous (IV) infusion at weeks 0, 4 and every 8 weeks thereafter. In two
separate trials, GO-LIVE and GO-FURTHER, infusion reactions (IRs) were observed in a relatively small group of GLM-
treated patients with 2.2% and 3.3% of patients having documented IRs, respectively. The GO-IV registry was initiated to
evaluate the incidence and management of IRs with GLM-IV in a real-world Canadian practice setting.
Methods: GO-IV was a prospective, observational, non-interventional, multicenter study conducted at 11 Canadian sites
from 2014-2016. GLM infusions were followed to document IRs and their management, pre-medication uses and adverse
events (AE). An IR was defined as any AE occurring during the infusion or within 1 hour post-infusion. Patients had to be
at least 18 years of age or older, a confirmed diagnosis of rheumatoid arthritis, provide written consent for data collection,
be naïve to GLM (both subcutaneous and intravenous formulations) and be seen by a Canadian rheumatologist.
Results: The study was terminated early due to lack of public listing for the drug. At that time, a total of 79 patients were
enrolled and 62 of them were still ongoing. Reasons for premature discontinuation included AEs (7), lack of response (4),
geographic issues (3), mis-diagnosis, switch to subcutaneous GLM or withdrawal of consent (one each). A total of 77
patients were included in the primary analysis and 78 in the safety analysis. Only 4 patients (5.1%) documented an IR over
483 infusion visits (0.8%), none of which classified as serious or leading to discontinuation. Three of those IRs occurred at
the first infusion and on at infusion number three. Infusion-related AEs included palpitations, nausea, fatigue, infusion site
pain, dizziness and headache (one each). The impact of pre-medication could not be established since only four infusions
were pre-medicated with diphenhydramine and one with steroids.
A total of 164 AEs were reported in 45 patients (57.7%); 2 patients (2.6%) reported a serious adverse event (acute
myocardial infarction; multiple fractures, pneumothorax, concussion, traumatic haematoma and pneumothorax resulting
from a fall). There was one incidence of a lipoma and no death. There were 30 infectious AEs reported in 24 patients.
Conclusion: The GO-IV registry shows that, in community-based infusion clinics, IRs to GLM are uncommon and
predominantly mild in nature.
Primary Analysis
(n=77)
Age (years), mean (SD) 55.5 (11.58)
Female Gender, n(%) 61 (79.2%)
Weight (Kg), mean (SD) 77.2 (19.55)
Any co-morbidity, n (%) 19 (24.6%)
Concomitant Medication
Any DMARD, n (%) 70 (90.9%)
Corticosteroids, n (%) 32 (41.6%)
MTX, n(%) 58 (75.3%)
Number of infusions
Mean per subject (SD) 6.1 (2.69)
Median per subject 6.0
Mean IV Administration 36.03
(minutes)
Safety Analysis (n=78)
No. subjects with at least 1 4 (5.1%)
infusion reaction, n (%)
Subject with ≥1 AE, n (%) 45 (57.7%)
Subject with ≥1 SAE, n 2 (2.6%)
(%)
Disclosure: R. Faraawi, None; A. Chow, None; M. M. M. Khraishi, None; D. Haaland, None; M. F. Baker, None; C.
Tkaczyk, Janssen Inc, 3; A. J. Lehman, Janssen Inc., 3; F. Nantel, Janssen Inc., 3; B. Osborne, Janssen Inc., 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/incidence-of-infusion-reactions-to-

intravenous-golimumab-results-from-a-prospective-real-world-community-registry
Concomitant Hydroxychloroquine Impact on Anti-TNF Persistence in

Patients with Rheumatoid Arthritis
Ming Zhao1, Harlan Sayles2, James R. O'Dell1 and Kaleb Michaud2,3, 1Rheumatology, University of Nebraska Medical
Center, Omaha, NE, 2University of Nebraska Medical Center, Omaha, NE, 3National Data Bank for Rheumatic Diseases,
Wichita, KS
SESSION INFORMATION
Background/Purpose: Tumor necrosis factor-α inhibitors (TNFi) have been widely used in patients who failed
conventional DMARDs in the treatment of rheumatoid arthritis (RA). While most patients respond well to TNFi, some
patients experience loss of efficacy over time possibly due to forming TNFi antibodies. Studies have shown that
concomitant use of methotrexate (MTX) with TNFi is associated with increased drug survival compared with TNFi
monotherapy. However, whether hydroxychloroquine (HCQ) may also prolong TNFi persistence is unknown and was the
purpose of this study.
Methods: We analyzed patients with RA and ≥1 year participation in the National Data Bank for Rheumatic Diseases
(NDB), an ongoing US-wide longitudinal observational study with biannual questionnaires since 1998. Patients initiating 3
TNFi’s, infliximab, adalimumab, or etanercept, were categorized according to concomitant DMARD use: none
(monotherapy), HCQ +/- other DMARDs but no MTX, MTX +/- other DMARDs but no HCQ, and HCQ and MTX +/-
other DMARDs. Patients who have previously taken other biologics were also enrolled into our study. Patients were
considered as continuing the TNFi if it was on hold for less than 12 months due to infection or surgery and the same TNFi
was resumed after that. Baseline characteristics (including all prior therapies) were collected via self-report at enrollment
while therapy continuation was collected on each follow-up questionnaire. We followed patients until TNFi
discontinuation, censoring, or death. We compared the discontinuation rate and mean drug survival time between subgroups
using Pearson chi-square tests and Kruskal-Wallis tests with Dunn’s tests.
Results: A total of 8611 patients were included with mean (SD) age of 59 (13) years, 81% female and RA duration 14 (11)
years. Patients who received concomitant HCQ with TNFi initiation had similar therapy discontinuation rates compared to
TNFi monotherapy. Concomitant HCQ use was associated with a longer drug survival compared to etanercept (p=0.007) or
infliximab (p<0.001) monotherapy. Concomitant MTX use has the largest impact in infliximab comparing to monotherapy,
associated with both lower discontinuation rate (p<0.001) and longer drug survival time (p<0.001). Concomitant MTX use
is also associated with longer drug survival in adalimumab (p<0.001), while such association was not found with
concomitant HCQ use (p=0.183). Otherwise, concomitant HCQ use has similar effect in prolonging TNFi survival
comparing to concomitant MTX use.
Table 1. Discontinuation and mean drug survival of TNFi by concomitant HCQ and MTX use (+) and nonuse (–)
A B C D
P values
Monotherapy +HCQ – +MTX – +HCQ ≤0.05
MTX HCQ +MTX
Etanercept N=815 N=251 N=1251 N=344
Discontinued, % 53.7 58.6 53.2 59.3 C vs. D
Drug survival, months 32 (37) 41 (45) 36 (41) 39 (44) A vs. B, C,
(SD) &D
Infliximab N=1864 N=145 N=1487 N=303

Discontinued, % 61.2 56.6 52.0 55.8 A vs. C
Drug survival, months 17 (21) 32 (38) 41 (42) 38 (42) A vs. B, C,
(SD) &D
B vs. C &
D
Adalimumab N=640 N=184 N=1106 N=221

Discontinued, % 58.1 62.0 56.5 56.6 None
Drug survival, months 25 (29) 28 (33) 30 (32) 30 (31) A vs. C &
(SD) D
Conclusion: Concomitant use of HCQ with TNFi’s is associated with increased TNFi persistence. Our initial findings
show promise for increased TNFi effectiveness with either HCQ or MTX, and followup studies examining TNFi-antibody
levels may help explain this association.
Disclosure: M. Zhao, None; H. Sayles, None; J. R. O'Dell, Medac, 5,Coherus, 5; K. Michaud, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/concomitant-hydroxychloroquine-

impact-on-anti-tnf-persistence-in-patients-with-rheumatoid-arthritis

Long-Term Risk of Serious Infections in Patients with Rheumatoid Arthritis
Treated with Rituximab: 5 Year Data from the British Society for
Rheumatology Biologics Register for Rheumatoid Arthritis
Diederik De Cock1, Lianne Kearsley-Fleet1, Lucía Silva Fernández2, Mark Lunt1, Kath Watson1, Deborah P.M.
Symmons1,3 and Kimme L. Hyrich1,3, 1Arthritis Research UK Centre for Epidemiology, University of Manchester,
Manchester Academic Health Science Centre, Manchester, United Kingdom, 2Arthritis Research UK Centre for
Epidemiology, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University of
Manchester, Manchester, United Kingdom, 3National Institute of Health Research Manchester Musculoskeletal Biomedical
Research Centre, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester,
United Kingdom
SESSION INFORMATION
Background/Purpose: In the United Kingdom (UK), rituximab (RTX) or a second tumour necrosis factor inhibitor (TNFi)
are both permitted treatment options for patients with rheumatoid arthritis (RA) who have failed a first TNFi. The risk of
serious infection (SI) is similar between these 2 treatments during the first year. However, long-term data on risk of SI for
RTX are scarce but required, in light of reports of reduction in IgG following repeated dosing. We compared the risk of SI
over 5 years of treatment in patients with RA who had failed a first TNFI and then received either RTX or TNFi .
Methods: This study used patients with RA registered with the British Society for Rheumatology Biologics Register
(BSRBR-RA) a large national prospective study established primarily to assess the long-term safety of exposure to biologic
therapies in patients with RA. This analysis included patients treated with either a second TNFi or RTX after failing a first
TNFi. Patients were followed until first SI, 90 days (TNFi) or 9 months (RTX) following last dose when treatment was
discontinued, last recorded follow-up or the end of the 5th year after the switch, which ever came first. SI was defined as
infection requiring intravenous antibiotics, hospitalisation or resulting in death. The risk of first SI was compared between
TNFi and RTX using (i) unadjusted, (ii) adjusted for sex and age, and (iii) propensity score adjusted Cox proportional
hazard models. A Nelson-Aalen (NA) plot was constructed to show the cumulative incidence of SI over 5 years.
Results: This analysis included 3419 TNFi-treated patients contributing 9527 person-years (pyrs), median (IQR) exposure
time per person 2.0 (0.8-3.3) years; and 1396 RTX patients contributing 3570 pyrs , median (IQR) exposure time 2.9 (1.7-
3.9) years. A total of 362 and 135 first SI were reported in TNFi and RTX patients respectively, giving a crude incidence
rate (95% CI) of 38 (34-42) SI/1000 pyrs (TNFi) and 38 (32-45) SI/1000 pyrs (RTX). The unadjusted, adjusted for sex and
age, and propensity score adjusted hazard ratios (95%CI) for SI were 0.9 (0.8-1.1), 0.9 (0.7-1.0) and 0.9 (0.7-1.1)
respectively. The NA plot showed a similar cumulative incidence risk of SI between the two groups over 5 years of
treatment (figure).
Conclusion: The risk of serious infections was comparable over 5 years of treatment between TNFi and RTX treatment in
patients who had failed a single prior TNFi.
Disclosure: D. De Cock, None; L. Kearsley-Fleet, None; L. Silva Fernández, None; M. Lunt, None; K. Watson, None;
D. P. M. Symmons, None; K. L. Hyrich, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/long-term-risk-of-serious-infections-in-

patients-with-rheumatoid-arthritis-treated-with-rituximab-5-year-data-from-the-british-society-for-rheumatology-biologics-
register-for-rheumatoid-arthritis
LDL and HDL Changes with Sirukumab Treatment Are Anti-Atherogenic:

Results from Two Phase 3 Trials in Patients with Rheumatoid Arthritis
Matthew Loza1, Androniki Bili2, Shruti Daga3, Kurt Brown4, Jennifer Gilbride5, Bidisha Dasgupta2, Benjamin Hsu2 and
Iain B. McInnes6, 1Janssen Research & Development, LLC, Springhouse, PA, 2Janssen Research & Development, LLC,
Spring House, PA, 3GlaxoSmithKline, Uxbridge, United Kingdom, 4GlaxoSmithKline, Collegeville, PA, 5Sum of Squares
Ltd, Hertfordshire, United Kingdom, 6University of Glasgow, Glasgow, United Kingdom
SESSION INFORMATION
Background/Purpose: Sirukumab (SIR), a human monoclonal antibody that selectively binds to the IL-6 cytokine with
high affinity, has demonstrated efficacy in RA in the phase 3 SIRROUND studies. Lipid elevations have been observed
with SIR, consistent with IL-6 pathway inhibition (Lancet 2017. 389:1206). A post hoc analysis evaluated the impact of
SIR treatment on plasma lipids and lipid particle subtypes.
Methods: Lipids were analyzed in plasma samples obtained from RA patients in SIRROUND-H (active comparator
monotherapy study; n=160, 159, and 162 for adalimumab (ADA) 40mg q2w, SIR 50mg q4w, and SIR 100mg q2w
treatment groups) and SIRROUND-D (placebo(PBO)-controlled DMARD-inadequate responder (IR) study; n=293, 470,
and 437 patients for PBO (excluding early escape patients), SIR 50mg q4w, and SIR 100mg q2w treatment groups). Plasma
fasting levels of HDL, LDL, IDL, VLDL and their respective particle subtypes (LipoProfile® test), triglycerides,
Apolipoproteins (Apo) A1 and B, and total cholesterol were measured centrally. LDL-receptor (LDL-R) levels on blood
leukocytes were measured by flow cytometry in 15 (ADA 40mg q2w), 23 (SIR 50mg q4w), and 20 (SIR 100mg q2w)
patients in SIRROUND-H. Significance of differences between baseline and week (Wk)24 sample data was tested using
Wilcoxon signed-rank and Mann-Whitney tests (p<0.05 considered significant).
Results: Elevations in total cholesterol, LDL, HDL, IDL, VLDL and triglycerides from baseline to Wk24 were observed
with SIR compared to PBO or ADA (p<0.05; Table 1 for the SIRROUND-H study). However, atherogenic indices
increased slightly (total cholesterol:HDL) or remained unchanged (ApoB/ApoA1) with SIR. Increases in LDL levels with
SIR were mainly due to increases in anti-atherogenic large particles, with decreases in smaller pro-atherogenic particle
sizes. Increases in HDL were mainly due to increases in small anti-atherogenic particles, with decreases in medium
particles. Increases in VLDL with SIR were associated with increases in all particle sizes. Results were similar for both SIR
doses and both studies, with similar changes observed by Wk4 (SIRROUND-H). ADA was associated with smaller but
significant decreases in very small, small, and medium LDL particles (Table 1). LDL-R levels were decreased (p=0.044)
only in the SIR 100mg q2w group, but changes in LDL-R levels did not correlate to changes in lipids or lipid particles
(p>0.05).
Conclusion: SIR treatment was associated with increased plasma lipid levels compared to placebo and ADA. However,
atherogenic indices, which are considered more reliable lipid markers in RA (Mediators Inflamm 2012. 2012: 785946),
remained unchanged or changed minimally with SIR. Changes in LDL and HDL levels with SIR were mainly due to a
shift towards a more anti-atherogenic lipid profile. Despite the small sample size, modulation of LDL-R levels did not
appear to be involved in the observed lipid changes.
Disclosure: M. Loza, Johnson & Johnson, 1,Johnson & Johnson, 3; A. Bili, Johnson & Johnson, 1,Johnson & Johnson, 3;
S. Daga, GlaxoSmithKline, 3,GlaxoSmithKline, 1; K. Brown, GlaxoSmithKline, 3,GlaxoSmithKline, 1; J. Gilbride, Sum
of Squares Ltd., 3,GlaxoSmithKline, 9; B. Dasgupta, Johnson & Johnson, 3; B. Hsu, Johnson & Johnson, 1,Johnson &
Johnson, 3; I. B. McInnes, Janssen, Novartis, UCB, Pfizer, Abbvie, Lilly, and BMS, 9,Roche, UCB, BMS, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/ldl-and-hdl-changes-with-sirukumab-
treatment-are-anti-atherogenic-results-from-two-phase-3-trials-in-patients-with-rheumatoid-arthritis
Increases in Lipid Levels Following Sirukumab Treatment Are Associated

with Suppression of Inflammation in Rheumatoid Arthritis: Results from
Two Phase 3 Trials
Bidisha Dasgupta1, Matthew Loza1, Androniki Bili1, Shruti Daga2, Kurt Brown3, Jennifer Gilbride4, Benjamin Hsu1 and
Iain B. McInnes5, 1Janssen Research & Development, LLC, Spring House, PA, 2GlaxoSmithKline, Uxbridge, United
Kingdom, 3GlaxoSmithKline, Collegeville, PA, 4Sum of Squares Ltd, Hertfordshire, United Kingdom, 5University of
Glasgow, Glasgow, United Kingdom
SESSION INFORMATION
Background/Purpose: Understanding interactions of inflammatory cytokines and lipid metabolism in RA is of

considerable interest. Blocking IL-6 receptor elevates lipid levels in RA while lowering inflammatory disease activity1.
Sirukumab (SIR), a human monoclonal antibody that selectively binds to the IL-6 cytokine with high affinity, demonstrated
efficacy in RA in the phase 3 SIRROUND studies. This study evaluated the relationships between lipid levels and the
suppression of inflammation and disease activity by SIR compared to adalimumab (ADA) in patients with moderate to
severe RA.
Methods: Plasma from the SIRROUND-H (monotherapy) study was evaluated: 99 patients in SIR 50mg q4w group, 95
patients in SIR 100mg q2w group, and 140 patients in ADA 40mg q2w group (subcutaneous). Fasting HDL, LDL, IDL,
VLDL levels and concentrations of specific particles (large, medium, small, and, for LDL, very small) plus triglycerides
were measured using NMR. Apolipoproteins (Apo) A1 and B, total cholesterol, and cholesterol/HDL ratio were measured
at Covance, LLC. CRP and SAA were measured using ELISA. Disease activity was measured using CDAI and DAS(CRP).
Analyses were performed at baseline (BL), Wk 4, Wk 8 and Wk 24 timepoints. We compared changes from BL using non-
parametric Wilcoxon signed-rank and Mann-Whitney tests (comparisons between treatment groups).
Results: SIR treatment significantly increased cholesterol, triglycerides, ApoA1, ApoB, HDL, IDL, LDL, and VLDL
levels (p<0.0001 both SIR groups Wk 24 vs BL) while minimal changes were observed with ADA treatment. Increases in
lipid biomarkers by SIR were observed by Wk 4 and sustained through Wk 24. Total cholesterol, LDL and large LDL
particles were inversely correlated with CRP, and large and medium HDL and medium and small VLDL particles were
inversely correlated with both CRP and SAA levels at BL (p<0.0001, -0.42<r<-0.30). Post-treatment increases in lipids
were associated with reduced inflammation with SIR treatment: increases in HDL correlated with decreased SAA while
increased ApoA1, cholesterol, LDL, and large LDL particles correlated with strong suppression of CRP and SAA at Wk 4
(p<0.0001 and -0.43<r<-0.31). In contrast, these trends were not observed with ADA as lipid levels post treatment
remained similar to BL. BL values and changes from BL in lipid parameters did not correlate with disease activity. Results
were similar for both doses of SIR. These results were confirmed in the placebo-controlled SIRROUND-D study.
Conclusion: Patients with higher BL inflammation have lower starting lipid levels. IL-6 inhibition by SIR results in
significant increases in lipid levels that correlate to suppression of acute phase reactants. These findings were not observed
with ADA where lipid levels were generally unchanged. The results suggest that the increase in lipid levels with SIR may
be at least in part associated with improvement of underlying inflammation in RA.
Reference:
1. Robertson J, et al. Nat Rev Rheumatol. 2013;9(9):513-23.
Disclosure: B. Dasgupta, Johnson & Johnson, 3; M. Loza, Johnson & Johnson, 1,Johnson & Johnson, 3; A. Bili, Johnson
& Johnson, 1,Johnson & Johnson, 3; S. Daga, GlaxoSmithKline, 3,GlaxoSmithKline, 1; K. Brown, GlaxoSmithKline,
3,GlaxoSmithKline, 1; J. Gilbride, Sum of Squares Ltd, 3,GlaxoSmithKline, 9; B. Hsu, Johnson & Johnson, 1,Johnson &
Johnson, 3; I. B. McInnes, Janssen, Novartis, UCB, Pfizer, Abbvie, Lilly, and BMS, 9,Roche, UCB, BMS, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/increases-in-lipid-levels-following-

sirukumab-treatment-are-associated-with-suppression-of-inflammation-in-rheumatoid-arthritis-results-from-two-phase-3-
trials
Long-Term Safety of Tocilizumab from Large Clinical Trial and

Postmarketing Populations
Shalini Mohan1, Margaret Michalska2, Jeffrey Yourish2, Jinglan Pei2, Sara Gale1, Christine Birchwood2 and Erhan
Berber2, 1Genentech, South San Francisco, CA, 2Genentech, Inc., South San Francisco, CA
SESSION INFORMATION
Background/Purpose: Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody targeted against the
interleukin-6 receptor that was approved to treat rheumatoid arthritis (RA) in the EU in 2009 and in the US in 2010, and
has now completed long-term extension (LTE) follow-ups in a number of intravenous and subcutaneous RA trials. The
objective of this study was to provide an updated report on the incidence of safety events during TCZ treatment in patients
with RA using data from multiple completed clinical trials and their LTEs, as well as an update from the global TCZ
postmarketing safety database.
Methods: To provide an updated report on the incidence of safety events during TCZ treatment in patients with RA using
data from multiple completed clinical trials and their LTEs, as well as an update from the global TCZ postmarketing safety
database.
Results: The clinical trial all-exposure population consisted of 7647 TCZ-treated patients with RA (81.6% female; mean
[SD] age, 52 [12.6] years), constituting 22,394 PY (mean follow-up: 2.93 years) of exposure. The overall rate (95% CI) of
serious adverse events (SAE) in the clinical trial population was 14.16 (13.67-14.66) per 100 PY. Overall incidence rates
for individual events for the clinical trial population are reported in the Table and were consistent in each 6-month period
over the 5-year duration. The global postmarketing population included 606,937 patients. The overall spontaneous
reporting rate (range) of adverse events of special interest in the postmarketing population was 9.37 (7.35-10.56) cases per
100 patients. Reporting rates of individual safety events of interest in the global postmarketing population are shown in the
Table and were consistent in each 6-month period over the 7-year duration.
Conclusion: The safety profile of TCZ in the current analysis, which includes information about safety events from 12
clinical trials and their LTEs and across 7 years of real-world postmarketing reports encompassing ~ 600,000 patients, was
consistent with previous safety reports. These findings are consistent with the previously reported profile of TCZ and
indicate that there is no evidence of increased safety risk with increasing exposure to TCZ.
Table. Adverse Events Across 12 RA Clinical Trials and the Global
Postmarketing Safety Database in Patients Who Received TCZ
Global Postmarketing
RA Clinical Trial All- Safety Database
Exposure Population Population*
(N = 7,647; 22,394 PY) (N = 606,937 Pts)

Reporting Rate
Patients With Incidence Rate
Adverse event of No. of (Range),
(95% CI),
special interest Cases
≥ 1 AE (%) Events/100 PY
Cases/100 Pts
4.29 2.86
Serious
730 (9.5) 17,350
infections
(4.02-4.57) (2.11-3.62)
1.18 0.26
Malignancies† 242 (3.2) 1560
(1.05-1.33) (0.18-0.51)
6.51
Injection site
444 (5.8) N/A N/A
reactions
(6.18-6.85)
Strokes / 0.67 0.34
cerebrovascular 130 (1.7) 2069
disorders (0.56-0.78) (0.22-0.94)
Serious bleeding 0.43 0.40‡
89 (1.2) 2440‡
events
(0.35-0.52) (0.28-0.76)
Myocardial 0.33 0.32
72 (0.9) 1946
infarction
(0.26-0.42) (0.21-0.88)
Gastrointestinal 0.20† 0.10
39† (0.5) 632
perforations
(0.15-0.27) (0.06-0.30)
Serious 0.26
hypersensitivity 56 (0.7) N/A N/A
reactions§ (0.20-0.33)
0.09 0.20
Anaphylaxisǁ 21 (0.3) 1222
(0.06-0.14) (0.09-0.38)
Serious hepatic
0.04 0. 59‡
9 (0.1) 3567‡
events (0.02-0.08) (0.34-1.21)
0.04 0.01
Demyelination 8 (0.1) 66
(0.02-0.07) (0.00-0.02)
AE, adverse event; N/A, not available; PY, patient year; RA, rheumatoid
arthritis; TCZ, tocilizumab.
* Data are for multiple indications and from several sources (spontaneous
reports, non-interventional programs, literature cases) reported following
market authorization.
†Events of gastrointestinal perforations (Clinical Trial data set) and
malignancies were medically confirmed.
‡ Includes both serious and non-serious cases.
§ Serious hypersensitivity was defined as a serious adverse event occurring
during or within 24 hours of the injection or infusion, excluding injection site
reactions, and not judged ‘unrelated’ to study treatment by the investigator.
ǁ Events of anaphylactic reactions meeting Sampson criteria (MedDRA SMQ
(algorithmic) Anaphylactic reaction)).
Disclosure: S. Mohan, Genentech, Inc., 3; M. Michalska, Genetech, Inc., 3; J. Yourish, Genentech, Inc, 3; J. Pei,
Genentech, Inc., 3; S. Gale, Genentech, Inc., 3; C. Birchwood, Genentech, Inc., 3; E. Berber, Genentech, Inc., 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/long-term-safety-of-tocilizumab-from-

large-clinical-trial-and-postmarketing-populations
Comparison of Drug Tolerability and Discontinuation Reasons between 7

Biologics in Patients with Rheumatoid Arthritis -Results from Kansai
Consortium for Well-Being of Rheumatic Disease Patients (ANSWER
cohort)-
Kosuke Ebina1, Makoto Hirao2, Motomu Hashimoto3, Moritoshi Furu4, Wataru Yamamoto5, Ryota Hara6, Takanori
Fujimura6, Toru Hirano7, Shuzo Yoshida8, Koji Nagai8, Hideki Amuro9, Yonsu Son9, Akira Onishi10, Kengo Akashi11,
Masaki Katayama12, Keiichi Yamamoto13 and Hideki Yoshikawa14, 1Orthopaedic Surgery, Osaka University Graduate
School of Medicine, Osaka, Japan, 2Orthopaedic Surgery, Osaka University, Graduate School of Medicine, Suita, Japan,
3Department of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto,
Japan, 4Graduate School of Medicine, Kyoto University, Kyoto, Japan, 5Kurashiki Sweet Hospital, Okayama, Japan, 6The
Center for Rheumatic Diseases, Nara Medical University, Kashihara, Japan, 7Respiratory Medicine, Allergy and Rheumatic
Diseases, Osaka University Graduate School of Medicine, Suita, Japan, 8Osaka Medical College, Osaka, Japan, 9Kansai
Medical University, Osaka, Japan, 10Kobe University Graduate School of Medicine, Kobe, Japan, 11Department of
Rheumatology and Clinical Immnology, Kobe University Graduate School of Medicine, Kobe, Japan, 12Osaka Red Cross
Hospital, Osaka, Japan, 13Osaka City University, Osaka, Japan, 14Department of Orthopedics, Osaka University Graduate
School of Medicine, Suita Osaka, Japan
SESSION INFORMATION
Background/Purpose: More than 4 years have passed since 7 biologics became available for patients with rheumatoid
arthritis (RA) in Japan, still lack reliable evidence in their differences of tolerability and discontinuation reasons.
Methods: A total of 1,037 biologics treatment courses of RA from 2009 to 2016 [female 81.8%, baseline age 59.6 y,
disease duration 7.8y, bio continued duration 17.1 months, RF positivity 81.5%, ACPA positivity 86.7%, DAS28-ESR 4.4,
CDAI 16.8, HAQ 1.1, Bio naïve 57.1% and switched 42.9%, methotrexate (MTX) 5.9 mg/week (limited to 16mg/week in
Japan) (68.6%), prednisolone (PSL) 2.5 mg/day (43.5%), abatacept (ABT) 21.3%, tocilizumab (TCZ) 20.7%, golimumab
(GLM) 16.9%, etanercept (ETN) 13.6%, adalimumab (ADA) 11.1%, infliximab (IFX) 8.5%, certolizumab pegol (CZP)
7.9%] were included in this 7-center, retrospective study. The drug tolerability and discontinuation reasons at 36 months
were estimated using Kaplan-Meier method, and adjusted by potent confounders [Sex / Age / Bio started date / Disease
duration / ACPA positivity / RF positivity / bio naive or switched / combined csDMARDs (MTX, tacrolimus, bucillamine,
salazosulfapyridine, iguratimod) and PSL / baseline DAS28-ESR / HAQ] which may affect biologics retention rates using a
Cox proportional hazards model.
Results: There were no significant differences in the baseline disease activity (DAS28-ESR and CDAI). The major
causes of 7 biologics treatment discontinuation were as follows. Drug inefficacy (47.7%), other nontoxic reasons (12.3%),
remission (8.6%), infection (7.5%), patients’ preference (7.5%), other adverse events such as malignant, cardiovascular,
pulmonary, renal, hematologic complications (6.2%), skin or systemic reaction (5.3%), and changing hospital (5.1%).
Adjusted discontinuation reasons and ratio at 36 months in each drug were as follows. Drug inefficacy (TCZ 16.1%, ABT
23.7%, ETN 28.4%, CZP 32.9%, IFX 33.3%, ADA 42.3%, and GLM 46.1%; P=0.14), remission (IFX 11.4%, ADA 2.6%,
ETN 1.4%, ABT 0.5%, TCZ 0.5%, GLM 0.0%, and CZP 0.0%; P<0.001), infection (ABT 1.4%, TCZ 1.5%, GLM 2.0%,
ETN 2.3%, ADA 2.5%, IFX 4.0%, and CZP 5.5%; P=0.77), other adverse events (ABT 1.2%, ETN 2.0%, CZP 4.9%, GLM
5.6%, ADA 7.2%, TCZ 8.5%, and IFX 11.7%; P=0.03), and skin or systemic reaction (ABT 0.0%, TCZ 0.5%, GLM 1.1%,
ADA 1.7%, ETN 2.1%, CZP 3.7%, and IFX 4.5%; P=0.02), respectively. Adjusted total retention rates at 36 months were
as follows. TCZ 58.9%, ABT 55.1%, CZP 51.4%, ETN 50.2%, GLM 37.6%, ADA 32.7%, and IFX 21.7% (P=0.006).
Conclusion: When adjusted by potent confounders, TCZ showed lowest inefficacy and highest retention rate, ABT
showed lowest infection, skin or systemic reaction, or other toxic adverse events rate, and IFX showed highest remission
discontinuation rate at 36 months compared to other biologics in RA.
Disclosure: K. Ebina, Chugai Pharmaceutical, Eisai, Ono Pharmaceutical, Mitsubishi Tanabe Pharma, UCB Japan, 8; M.
Hirao, None; M. Hashimoto, Astellas Pharma, 2,Tanabe-Mitsubishi, Chugai, Ayumi, UCB, Bristol-Meyers, 5; M. Furu,
None; W. Yamamoto, None; R. Hara, None; T. Fujimura, None; T. Hirano, Mitsubishi Tanabe Pharma Corporation
Chugai Pharmaceutical Co., Ltd. AbbVie, Ono Pharmaceutical, Astellas Pharma Inc., 5; S. Yoshida, None; K. Nagai,
None; H. Amuro, None; Y. Son, None; A. Onishi, None; K. Akashi, None; M. Katayama, None; K. Yamamoto, None;
H. Yoshikawa, Chugai Pharmaceutical, Eisai, Ono Pharmaceutical, Mitsubishi Tanabe Pharma, Phizer, Astellas Pharma, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/comparison-of-drug-tolerability-and-

discontinuation-reasons-between-7-biologics-in-patients-with-rheumatoid-arthritis-results-from-kansai-consortium-for-
well-being-of-rheumatic-disease-patients-answ
Mast Cells Are Involved in the Pathogenesis of Sjögren Syndrome By

Inducing Tissue Fibrosis
Shinjiro Kaieda1, Kyoko Fujimoto2, Masaki Okamoto3, Masaki Tominaga2, Tomoaki Hoshino4 and Hiroaki Ida5,
1Department of Medicine, *Division of Respirology, Neurology and Rheumatology, Kurume University School of
Medicine, kurume, Japan, 2Kurume University School of Medicine, Kurume, Japan, 3Medicine, Kurume University School
of Medicine, Kurume, Japan, 4Department of Medicine, Division of Respirology, Neurology and Rheumatology, Kurume
University School of Medicine, Kurume, Japan, 5Respiorogy, Neurology and Rheumatology, Kurume University School of
Medicine, Kurume, Japan
SESSION INFORMATION
Session Title: Sjögren's Syndrome Poster I: Translational Research
Background/Purpose:
Mast cells have been implicated in many immune-inflammatory disorders. They mediate a variety of inflammatory and
fibrotic conditions, but their role in sialadenitis and interstitial lung disease in patients with primary Sjögren syndrome is
unclear. We examined whether mast cells play a critical role in the pathogenesis of Sjögren syndrome.
Methods:
Labial salivary glands and lung tissue were examined using histological and immunohistochemistry methods. Labial
salivary gland samples were collected from 15 individuals with primary Sjögren syndrome and 7 with sicca syndrome
(controls). Saliva production was evaluated by Saxon test.
Affected lung tissue from four patients with Sjögren syndrome-associated interstitial lung disease was obtained via biopsy.
As control samples, we used 10 noncancerous lung sections from patients who had undergone surgery for lung cancer. We
used immunohistochemistry to identify and quantify tryptase-positive mast cells and vimentin-positive fibroblasts. Fibrous
tissue was identified by using EVG stain. Human mast cell line 1 (HMC-1) cells were co-cultured with pulmonary
fibroblasts for 7 days using a transwell system, and IL-6, TGF-β, and VEGF expression in these cells was evaluated by RT-
qPCR.
Results:
We found that the number of mast cells in labial salivary glands and lung tissues of patients with Sjögren syndrome was
significantly increased compared to that in control subjects (p<0.001 and p<0.01, respectively). There was a significant
negative correlation between the Saxon test results and the number of mast cells (r=0.81, P<0.01), suggesting the
involvement of mast cells in decreased salivary secretion. The mast cells were usually present in close proximity to EVG-
stained fibrous tissue in the labial salivary glands and lung tissues. Immunohistochemical analysis revealed that the mast
cells were proximal to vimentin-positive fibroblasts. We hypothesized that mast cells were involved in the development of
tissue fibrosis via modulation of fibroblast immune function, and conducted in vitro co-culture of HMC-1 cells and
pulmonary fibroblasts. In these co-cultures, IL-6, TGF-ß, and VEGF expression was significantly increased compared to in
mast cell or fibroblast monoculture. These observations suggest that an amplification loop is generated between mast cells
and fibroblasts, enhancing production of IL-6, TGF-ß and VEGF.
Conclusion:
These results suggest a novel role for mast cells in the development of sialadenitis and interstitial lung disease in patients
with Sjögren syndrome via induction of tissue fibrosis. An amplification loop between mast cells and fibroblasts enhances
production of the pro-fibrotic factor, TGF-β, and angiogenic factor, VEGF, which may contribute to tissue fibrosis in
sialadenitis and interstitial lung disease.
Disclosure: S. Kaieda, None; K. Fujimoto, None; M. Okamoto, None; M. Tominaga, None; T. Hoshino, None; H. Ida,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/mast-cells-are-involved-in-the-

pathogenesis-of-sjogren-syndrome-by-inducing-tissue-fibrosis
Decreased Circulating CXCR3+CCR9+ Th Cells Coincides with Elevated

Levels of Their Ligands CXCL10 and CCL25 in the Salivary Gland of
Sjögren’s Syndrome Patients Which Synergistically Facilitate Th Cell
Migration
Sofie L.M. Blokland1,2, Maarten R. Hillen3,4, Stephan Meller5, Bernhard Homey5, Glennda Smithson6, Aike A. Kruize2,
Timothy R.D.J. Radstake2,7 and Joel A.G. van Roon2,3, 1Rheumatology & Clinical Immunology/ Laboratory of
Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands, 2Department of Rheumatology &
Clinical Immunology, University Medical Center Utrecht, Utrecht, Netherlands, 3Laboratory of Translational Immunology,
UMC Utrecht, Utrecht, Netherlands, 4Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht,
Netherlands, 5Department of Dermatology, University of Düsseldorf, Düsseldorf, Germany, 6Takeda Global Research &
Development Center, Inc, Chicago, IL, 7Rheumatology and Clinical Immunology, Laboratory of Translational
Immunology, University Medical Center Utrecht, Utrecht, Netherlands
SESSION INFORMATION
Background/Purpose:
Primary Sjögren’s syndrome (pSS) is characterized by dryness and lymphocytic infiltration in the salivary glands. CXCR3+
T cells and ligands CXCL9/10/11 are known to be abundantly present in the salivary glands of pSS patients. In addition,
both CXCR5+ T follicular helper (Tfh) cells and CCR9+ Tfh-like cells and their specific chemotactic ligands CXCL13 and
CCL25 are present at increased levels in the salivary glands of pSS patients. Recently, we and others found that CCR9+ Th
cells are elevated in pSS peripheral blood and co-express CXCR3 and other chemokine receptors, known to be
differentially expressed by Th cell subsets. CCR9+ Th cells play an important role in mucosal immunity and have been
shown to produce high levels of IFN-γ, like CXCR3+ Th1 cells. Since CXCL9/10/11 and CXCR3 are abundantly expressed
in the salivary glands of pSS and CCR9+ Th cells have Th1 characteristics, the potential role in lymphocytic infiltration of
the combination of the CXCL10-CXCR3 and CCL25-CCR9 interactions was studied in comparison with other chemokine
receptors.
Methods:
CXCL10, CCL25, CXCL13, CCL17 and CCL20 mRNA and protein expression in the salivary gland of pSS and non-
Sjögren’s sicca (nSS) patients was assessed (mRNA: n=9 vs n=9 and protein: n=24 vs n=33, respectively). Frequencies of
CXCR3, CCR9, CXCR5, CCR4 and CCR6 expressing Th cells in blood of pSS patients and healthy controls were assessed
by flow cytometry (n=11 vs n=11). Chemotaxis assays (n=6 HC, n=10 pSS) were performed to study migration induced by
CXCL10 and CCL25.
Results:
CCL25, CXCL10 and CXCL13 expression were increased in pSS compared to nSS patients, both at mRNA and protein
level in salivary gland supernatants (all p<0.05). CCL17 and CCL20 expression were low and detectable in only few
patients. Protein levels of CXCL10 and CXCL13 correlated with lymphocytic focus scores and all 3 chemokines correlated
with serum IgG levels in pSS (all p<0.05). CCL25 protein levels correlated with CXCL10 (p=0.01) but not with CXCL13.
A relative decrease of CXCR3+ cells was found in the CCR9+ Th subset in the peripheral blood of pSS patients (p=0.04),
which was most pronounced in the effector and effector memory subsets (64% vs 26%, p=0.03 and 51% vs 27% p=0.01,
respectively). CCR4 or CCR6-expressing CCR9+ Th cells and CXCR3 or CCR6-expressing CXCR5+ Th cells were not
decreased. To test the hypothesis that CXCR3 ligands and CCL25 facilitate migration, co-migration of lymphocytes in
response to CXCL10 and CCL25 was studied. CXCL10 and CCL25 induced synergistic Th cell chemotaxis in vitro (both
p<0.01 as compared to CCL25 or CXCL10 only).
Conclusion:
The decreased frequency of CXCR3+CCR9+ Th cells in blood of pSS patients may be facilitated by a concerted action of
overexpressed ligands at the site of inflammation. Elevated expression of ligands CXCL10 and CCL25 in the salivary gland
and the synergistic effect on chemotaxis in vitro indicate a potential role for these chemokines in formation of lymphocytic
infiltrates in exocrine glands of pSS patients.
Disclosure: S. L. M. Blokland, None; M. R. Hillen, None; S. Meller, None; B. Homey, None; G. Smithson, Takeda, 3;
A. A. Kruize, None; T. R. D. J. Radstake, Takeda, 5; J. A. G. van Roon, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/decreased-circulating-cxcr3ccr9-th-
cells-coincides-with-elevated-levels-of-their-ligands-cxcl10-and-ccl25-in-the-salivary-gland-of-sjogrens-syndrome-
patients-which-synergistically-faci
Prognostic Significance of Double Positive Anti Ro/SS-a and La/SS-B

Antibodies in Patients with Primary Sjogren’s Syndrome: Prospective
Salivary Gland Ultrasound Study
Sang Heon Lee1, Kyung-Ann Lee2 and Hae-Rim Kim3, 1Division of Rheumatology, Department of Internal Medicine,
Konkuk University School of Medicine, Seoul, Korea, Republic of (South), 2Department of Nuclear medicine, Konkuk
University Medical center, seoul, Korea, Republic of (South), 3Division of Rheumatology, Department of Internal
Medicine, Konkuk University Medical Center, Seoul, Korea, Republic of (South)
SESSION INFORMATION
Background/Purpose: The aim of the study was to assess the diagnostic value of salivary gland ultrasonography (SGUS)
as a single test for the detection of primary sjogren’s syndrome (pSS) and to examine the prognostic factors for severe
structural changes of major salivary glands based on SGUS scoring system.
Methods: Patients with pSS (n = 80) and idiopathic sicca syndrome (n = 42) were evaluated using a SGUS scoring system
(0-48 scale) consisted of five SGUS parameters: parenchymal echogenicity, parenchymal homogeneity, number of
hypoechoic areas, hyperechogenic reflections, and clearness of salivary gland posterior borders of both parotid and
submandibular glands. The volumes and parenchymal power Doppler signal were also assessed. A multivariate regression
was performed to determine factors associated with higher SCUS score.
Results: Patients with pSS revealed a significant higher SGUS score in comparison with controls (median (IQR): 25.0
(13.75) vs 6.5 (3.5), P < 0.001). The SGUS cut-off ≥ 12 showed a sensitivity of 82.5%, a specificity of 92.9%, a positive
predictive value of 95.7%, and a negative predictive value of 73.6% for pSS diagnosis. There was no significant difference
in the volumes between pSS and controls. Double positivity of anti Ro/SS-A and La/SS-B was independently associated
with higher SGUS score (β = 5.45, p = 0.009). The SGUS score was also associated with unstimulated salivary flow test
(USFR), rheumatoid factor, and IgG.
Conclusion: A new imaging modality, SGUS could be used as a highly specific diagnostic tool in pSS. Our study
demonstrates double positivity of anti Ro/SS-A and La/SS-B could independently predict the severe structural damage of
major salivary glands in pSS.
Disclosure: S. H. Lee, None; K. A. Lee, None; H. R. Kim, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prognostic-significance-of-double-

positive-anti-ross-a-and-lass-b-antibodies-in-patients-with-primary-sjogrens-syndrome-prospective-salivary-gland-
ultrasound-study

The Corrected QT(QTc) Interval Is Associated with Myocardial Fibrosis in
Primary Sjögren Syndrome, Assessed By a Cardiac Magnetic Resonance
Approach: A Prospective Pilot Study at a Single Center
Atsuma Nishiwaki1, Hitomi Kobayashi1, Isamu Yokoe2, Yosuke Nagasawa3, Kaita Sugiyama3, Natsumi Ikumi4,
Takamasa Nozaki3, Noboru Kitamura5 and Masami Takei5, 1Hematology and Rheumatology, Nihon University School of
Medicine, Tokyo, Japan, 2Rheumatology, Kyoundo Hospital, Sasaki Institute, Tokyo, Japan, 3Nihon University School of
Medicine, Tokyo, Japan, 4St. Vincent's University Hospital, Department of Rheumatology, Dublin, Ireland, 5Division of
Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan
SESSION INFORMATION
Background/Purpose:
Congenital heart block in the fetus and neonate, which can cause acquired QT prolongation, may be associated with
maternal anti-SS-A/anti-SS-B autoantibodies. However, there are increasing reports that primary Sjögren syndrome (pSS)
is associated with an increased risk of cardiovascular disease and that disease-related clinical and immunological markers
may promote cardiovascular disease. We hypothesized that myocardial abnormalities were associated with the corrected
QT (QTc) interval in pSS. We used cardiac magnetic resonance imaging (CMR) to assess cardiac involvement and
determine its association with the QTc interval in pSS patients without cardiac symptoms.
Methods:
Consecutive pSS patients, classified according to the 2012 ACR criteria with no history or clinical findings of
hypertension, cardiovascular disease, diabetes, or dyslipidemia underwent contrast-enhanced CMR. Late gadolinium
enhancement (LGE) was used to assess myocardial fibrosis. Myocardial inflammation was assessed using a black-blood
T2-weighted image (T2-WI). The Sjögren syndrome disease activity index (ESSDAI) was determined. Eighty-six percent
patients had documentation of a minor salivary gland biopsy. Salivary gland biopsy data were classiﬁed by focus score
(FS). A QTc interval of 440 ms was considered as prolonged.
Results:
Fifty-five pSS patients were enrolled (mean age: 53.2±9.6 years). The mean ESSDAI was 2.5±2.7. Myocardial edema was
seen in 3 patients (5%) on T2-WI. LGE was found in 9 (16%), 2 of whom demonstrated edema on T2-WI. Raynaud’s
phenomenon was significantly associated with LGE-positive patients (p=0.0064). The greatest relative difference between
LGE-positive and -negative patients was observed in FS ≥4, with an adjusted odds ratio of 4.0, although the FS was not
associated with the QTc interval.
PSS patients had a longer mean QTc interval than did controls (432.5±24.9 vs. 420.5±14.4; p=0.003). Furthermore, there
was significant difference in the QTc interval between the LGE-positive and LGE-negative group (447.7±15.7 vs
429.5±25.4; p=0.012). Other pSS characteristics, such as disease duration, anti-SS-A/anti-SS-B autoantibodies, ESSDAI,
and cardiovascular risk factors, were not significantly associated with myocardial abnormalities and QTc interval.
A receiver operating characteristic analysis showed that the QTc interval reliably detected myocardial abnormalities (area
under the curve, 0.77).
Conclusion:
Subclinical myocardial involvement, as detected by CMR, was frequent in pSS patients without cardiac symptoms.
Abnormal CMR findings were associated with a QTc interval. To our knowledge, this was the first study to show that
myocardial abnormalities in pSS were associated with the QTc interval.
Disclosure: A. Nishiwaki, None; H. Kobayashi, None; I. Yokoe, None; Y. Nagasawa, None; K. Sugiyama, None; N.
Ikumi, None; T. Nozaki, None; N. Kitamura, None; M. Takei, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-corrected-qtqtc-interval-is-

associated-with-myocardial-fibrosis-in-primary-sjogren-syndrome-assessed-by-a-cardiac-magnetic-resonance-approach-a-
prospective-pilot-study-at-a-single-center
Identification and Validation of S100 Salivary Proteins As Putative

Biomarkers for Different Subsets of Primary Sjögren’s Syndrome Patients
Chiara Baldini1, Francesco Ferro2, Nadia Ucciferri3, Enza Polizzi2, Silvia Rocchiccioli3, Marta Mosca2 and Antonella
Cecchettini3, 1Internal Medicine, Rheumatology Unit, University of Pisa, Pisa, Italy, 2Rheumatology Unit, University of
Pisa, Pisa, Italy, 3IFC, CNR, Pisa, Italy
SESSION INFORMATION
Background/Purpose: S100 A proteins are multifunctional proteins expressed predominantly by myeloid cells, with a
regulatory role in a variety of cellular processes including inflammation. Recently, serum and salivary S100A proteins have
been described as increased in patients with primary Sjögren’s syndrome (pSS) with respect to healthy volunteers. In this
study, we aimed at investigating whether salivary expression of S100 proteins may reflect different pSS disease phenotypes
stratified on the basis of the complexity of minor salivary gland biopsies (MSGB) and on the impairment of unstimulated
salivary flow rate (USFR).
Methods: Patients with pSS (AECG 2002) were included in this study at the diagnosis of the disease. Demographic and
clinical data were collected prospectively as well as their USFR and MSGBs. A focus score (FS) ≥3 was considered as high
and an USFR<2.5 ml/15’ was considered as low. Saliva samples were collected on ice, centrifuged and stored at -80°C.
After removal of Albumin and IgG, a nano-HPLC system coupled with a Triple TOFTM 5600 mass spectrometer was used
for the analysis of saliva proteomes of pSS patients. For the validation phase of the study, S100A7/psoriasin levels were
determined by CircuLex S100A7/psoriasin ELISA kit (MBL International Corporation), according to manufacturer’s
instructions.
Results: Fifteen pSS women were enrolled for the proteomic analysis: 5 with high FS and normal USFR, 5 with high FS
and reduced USFR and 5 with low FS and reduced USFR. Among differentially expressed proteins, we found that S100
A2, 7, 8,9, 11 and 12 were significantly over-expressed in pSS with respect to controls. In details, S100 A7 levels were
significantly increased in patients with higher FS and lower USFR with respect to the other two groups of patients; S100
A8 and A9 were increased in patients with higher FS and lower USFR only with respect to patients with high FS and
normal USFR and S100 A 12 in patients with low FS and reduced USFR with respect to patients with high FS and normal
USFR. We validated salivary expression of S100 A7 in 19 additional pSS patients and 8 controls confirming that S100A7
expression was significantly higher in patients with high FS and reduced USFR (305.6± 174 ng/ml vs 11±14 ng/ml vs
75.7±21.6 ng/ml, p=0.000).
Conclusion: Salivary S100 A proteins appeared as interesting novel potential biomarkers for the non-invasive stratification
of homogenous subgroups of patients with pSS. ELISA results excellently mirrored proteomics and open the possibility to
be clinically translated into routine diagnostic.
Disclosure: C. Baldini, None; F. Ferro, None; N. Ucciferri, None; E. Polizzi, None; S. Rocchiccioli, None; M. Mosca,
None; A. Cecchettini, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/identification-and-validation-of-s100-

salivary-proteins-as-putative-biomarkers-for-different-subsets-of-primary-sjogrens-syndrome-patients
Enhanced Expression of NLRP3 Inflammasome-Related Inflammation in

Peripheral Blood Mononuclear Cells in Sjögren’s Syndrome
Seong-Kyu Kim1, Jung-Yoon Choe2, Sung-Hoon Park3 and Hwajeong Lee2, 1Rheumatology, Catholic University of
Daegu School of Medicine, Daegu, Korea, Republic of (South), 2Catholic University of Daegu School of Medicine, Daegu,
Korea, Republic of (South), 3Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea, Republic
of (South)
SESSION INFORMATION
Background/Purpose: Sjögren's syndrome is a systemic autoimmune disease characterized by lymphocyte infiltration and
subsequent dysfunction of exocrine glands, finally leading to dryness in the exocrine glands and dysfunction in the affected
organs and tissues. The precise mechanism of Sjögren's syndrome remains unclear. Recently, novel insight into the
NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome that is responsible for innate immunity, has
implicated it as a crucial regulator that plays a role in the pathogenesis of Sjögren's syndrome. The aim of this study was to
identify the association of NLRP3 inflammasome-induced inflammation with disease activity and damage in Sjögren's
syndrome.
Methods: A total of 33 female patients with Sjögren's syndrome and 34 sex- and age-matched, healthy controls were
consecutively enrolled. The mRNA expression levels of NLRP3, ASC, caspase-1, interleukin-1b (IL-1b), and IL-18 in
peripheral blood mononuclear cells (PBMCs) were measured, as well as serum IL-1b and IL-18 protein expression levels.
The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and Sjögren's Syndrome Disease Damage Index
(SSDDI) were also evaluated.
Results: Patients with Sjögren's syndrome group showed higher expression of mRNA IL-1b and IL-1b at the protein level
than controls (p < 0.001 of both). The mRNA levels of caspase-1 and ASC were significantly increased in patients with
Sjögren's syndrome compared to controls (p = 0.001 and p = 0.002, respectively). Based on the SSDDI scores, patients with
damage (SSDDI ≥ 1) had higher IL-1b mRNA expression compared to patients without damage (SSDDI = 0) (p = 0.034).
SSDDI scores were closely related with IL-18 protein levels (r = 0.357, p = 0.041). The levels of IL-1b mRNA and IL-1b
protein were correlated with the mRNA level of NLRP3 (r = 0.597, p < 0.001 and r = 0.502, p = 0.003, respectively). IL-1b
mRNA expression was responsible for the presence of damage for Sjögren's syndrome (p = 0.034).
Conclusion: This study confirmed that NLRP3 inflammasome-mediated inflammation might be implicated in the
pathogenesis of Sjögren's syndrome.
Disclosure: S. K. Kim, None; J. Y. Choe, None; S. H. Park, None; H. Lee, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/enhanced-expression-of-nlrp3-

inflammasome-related-inflammation-in-peripheral-blood-mononuclear-cells-in-sjogrens-syndrome
Salivary Syndecan-1 Levels Are Associated with Salivary Gland Dysfunction

and Immune Dysregulation in Patients with Sjögren’s Syndrome
Eon Jeong Nam1, Jong Wan Kang1, Jung Su Eun1, Na Ri Kim1, Sang Jin Lee1, Keum Hee Sa2, Gi Bum Bae3 and Young
Mo Kang4, 1Division of Rheumatology, Department of Internal Medicine, Kyungpook National University School of
Medicine, Daegu, Korea, Republic of (South), 2Division of Rheumatology, Department of Internal Medicine, Kyungpook
National University, Daegu, Korea, Republic of (South), 3Division of Rheumatology, Department of Internal Medicine,
Daegu, Korea, Republic of (South), 4Division of Rheumatology, Department of Internal Medicine, Kyungpook National
University School of Medicine, Daegu, Republic of Korea, Daegu, Korea, Republic of (South)
SESSION INFORMATION
Background/Purpose: Sjögren’s syndrome (SJS) is a chronic autoimmune disorder with lymphocytic infiltration of
exocrine and non-exocrine epithelia, in which epithelial cells play a critical role in the initiation and amplification of
inflammatory processes. Syndecan-1 (sdc-1), a transmembrane heparan sulfate proteoglycan, is predominantly expressed
on epithelial cells and functions primarily as coreceptors through the binding of heparan sulfate chain to a wide range of
ligands, such as extracellular matrix components, cytokines, and chemokines. Although ectodomain of sdc-1 is
constitutively shed, ectodomain shedding is accelerated in response to diverse pathophysiological conditions and may be
related with pathogenesis of SJS. In this study, we investigated the association of sdc-1 levels in plasma and saliva with
functional parameters of salivary glands in SJS patients.
Methods: Unstimulated and stimulated salivary flow rates and sdc-1 levels of saliva and plasma were measured in 37 SJS
patients and 34 normal controls (NC). We assessed the disease activity indexes, including ESSDAI and ESSPRI, and
performed salivary gland scan and serologic markers in SJS patients.
Results: ESSDAI and ESSPRI scores of SJS patients were 3.78 ± 3.33 and 3.95 ± 1.50, respectively. Salivary flow rates in
SJS patients and NC were 0.02 ± 0.04 and 0.31 ± 0.20, respectively (p<0.001). While unstimulated salivary flow rates were
correlated with ejection fraction (EF) of submandibular glands (r=0.423, p=0.025) in salivary gland scan, stimulated
salivary flow rates were associated with EF of parotid glands (r=0.531, p=0.04). Salivary flow rates were inversely
associated with ESSPRI scores (r=-0.390, p=0.036) and dryness domain of ESSPRI (r=-0.622 p<0.001) in SJS patients.
Plasma and salivary sdc-1 levels were significantly higher in SJS patients than NC (both p<0.001), and inversely correlated
with salivary flow rate (plasma, r=-0.515, p<0.001; saliva, r=-0.472, p=0.003). Plasma sdc-1 levels were positively
correlated with salivary sdc-1 levels in SJS patients (r=0.632, p<0.001) but not in NC (r=0.217, p=NS). Plasma and salivary
sdc-1 levels were related with submandibular gland dysfunction in salivary gland scan. While plasma sdc-1 levels showed
an inverse correlation with EF (r=-0.426, p=0.038), salivary sdc-1 levels were inversely correlated with both uptake ratio at
20 minutes (r=-0.526, p=0.017) and EF (r=-0.446, p=0.019). Furthermore, salivary sdc-1 levels were correlated with serum
levels of anti-Ro (r=0.397, p=0.030) and -La antibodies (r=0.441, p=0.015) and IgG, although serum level of IgG showed a
marginal statistical significance (r=0.331, p=0.074).
Conclusion: Plasma and salivary sdc-1 levels are increased in SJS patients, which is associated with salivary gland
dysfunction. In addition, salivary sdc-1 levels may be related with immune dysregulation in pathogenesis of SJS.
Disclosure: E. J. Nam, None; J. W. Kang, None; J. S. Eun, None; N. R. Kim, None; S. J. Lee, None; K. H. Sa, None; G.
B. Bae, None; Y. M. Kang, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/salivary-syndecan-1-levels-are-

associated-with-salivary-gland-dysfunction-and-immune-dysregulation-in-patients-with-sjogrens-syndrome
Performance of Multiple Platforms for Autoantibody Testing in Sjogren’s

Syndrome
Astrid Rasmussen1, Kiely Grundahl2, Lida Radfar3, C. Erick Kaufman4, David M. Lewis5, Barbara M. Segal6, Nelson L.
Rhodus7, Harini Bagavant1, Umesh Deshmukh8, Christopher J Lessard8, R. Hal Scofield1 and Kathy L. Sivils1, 1Arthritis
and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 2Arthritis and Clinical
Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma CIty, OK, 3Department of Oral
Diagnosis and Radiology, University of Oklahoma College of Dentistry, Oklahoma City, OK, 4College of Medicine,
University of Oklahoma Health Sciences Center, Oklahoma City, OK, 5Department of Oral Pathology, University of
Oklahoma College of Dentistry, Oklahoma City, OK, 6Rheumatology, Hennepin County Medical Center, Minneapolis,
MN, 7Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Minneapolis, MN,
8Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK
SESSION INFORMATION
Background/Purpose: The research classification and clinical diagnosis of SjšgrenÕs syndrome (SS) relies heavily on the
detection of autoantibodies against Ro/SSA and La/SSB, particularly in the absence of salivary gland biopsy or when the
histopathology of the minor salivary gland is normal. However, there is little consensus on the method or combination of
methods that yield the best balance of sensitivity and specificity for SS.
Methods: We analyzed the results of multiple serology assessment platforms in 1530 subjects with SS or non-SS sicca
evaluated at the OMRF SjšgrenÕs Research clinic. Our standard tests include ANA by indirect immunofluorescence on
HEp-2 cells, Chrithidia luciliae for dsDNA, and double immunodiffusion (DID) for ENA. Anti-Ro/SSA and anti-La/SSB
were determined by DID, a line assay (InnoLia ANA Update) and a bead-based assay (Bio-Rad BioPlex 2200) for anti-
Ro52, Ro60 and La; and ELISA (Immunovision) for anti-Ro60. A subset of cases were also evaluated for anti-
Ro52/TRIM21 by immunoprecipitation with human antigen and anti-La(+)/Ro(-) cases were confirmed by DID on HEp-
2000 cells and RT-PCR.
Results: We observed significant differences in the performance of the tests in the same individuals. The concordance rate
(kappa statistic) is detailed in Fig. 1. The most significant discrepancies were between DID and Bioplex and InnoLia; in
almost all discordant cases, DID results were negative while they were positive for at least one of the other tests (anti-Ro
353/1318, 26.8%; anti-La 145/1253, 11.5%). InnoLia and Bioplex were highly concordant or Ro52 and are likely
interchangeable; anti-Ro60 also showed high concordance across the three platforms tested but the minor discrepancies
would result in the loss of 1.1% of positive subjects. Another clinically relevant finding was that in 1% of Ro52(+)/Ro60(+)
cases total anti-Ro was negative, an artifact that has previously been reported. All tests and analytes showed excellent
specificity for classification as primary SS, albeit at the expense of low sensitivity (Table 1).
Conclusion: The very low sensitivity of anti-Ro and anti-La DID in SS patients may result in misclassification of up to
25% of cases. Algorithms for a tiered approach for additional testing are necessary in the clinical setting to optimize
diagnosis at a reasonable cost. For research, in particular clinical trials that require high specificity, all the tested platforms
perform very well.
Disclosure: A. Rasmussen, None; K. Grundahl, None; L. Radfar, None; C. E. Kaufman, None; D. M. Lewis, None; B.
M. Segal, None; N. L. Rhodus, None; H. Bagavant, None; U. Deshmukh, None; C. J. Lessard, None; R. H. Scofield,
None; K. L. Sivils, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/performance-of-multiple-platforms-for-

autoantibody-testing-in-sjogrens-syndrome
Clinical Relevance of Serum Free Light Chain Level As Biomarker in

Primary Sjögren′s Syndrome
Gwenny M. Verstappen1, Johan Bijzet1, Jolien F. van Nimwegen1, Martha S. van Ginkel1, Arjan Vissink2, Hendrika
Bootsma1 and Frans G.M. Kroese1, 1Rheumatology and Clinical Immunology, University of Groningen, University
Medical Center Groningen, Groningen, Netherlands, 2Oral and Maxillofacial Surgery, University of Groningen, University
Medical Center Groningen, Groningen, Netherlands
SESSION INFORMATION
Background/Purpose:
During immunoglobulin synthesis in B-cells, kappa and lambda light chains are produced in excess compared to heavy
chains, and the surplus of light chains are secreted into serum as free light chains (FLC). Compared to healthy individuals,
elevated serum levels of polyclonal FLCs are seen in autoimmune diseases associated with increased B-cell activation,
including primary Sjögren’s syndrome (pSS). In pSS, serum FLC levels correlate with IgG, rheumatoid factor and systemic
disease activity.1 However, the clinical relevance of serum FLC levels as biomarker in pSS remains unclear. The objective
of this study is to assess if I) FLCs are already elevated at the time of diagnosis, II) FLC levels can discriminate non-SS
sicca from pSS patients, and III) FLCs can be used to monitor treatment response.
Methods:
Serum samples of 102 consecutive patients referred to our expertise center for suspicion of pSS were included. Patients
were classified by a panel of 3 clinical experts as non-SS sicca, incomplete pSS or pSS and fulfillment of ACR-EULAR
criteria for pSS was assessed. Longitudinal serum samples of pSS patients treated with rituximab (n=20) or abatacept
(n=15) were also included. Kappa (κ) and lambda (λ) FLCs were measured in serum by the Freelite assay (Binding Site,
UK). Area under the ROC curve (AUC) was used to assess the ability of serum FLC levels to predict a pSS diagnosis.
Generalized estimating equations were used to measure changes during treatment.
Results:
At the time of diagnosis, FLCκ and FLCλ serum levels were significantly higher in pSS patients compared to non-SS sicca
patients (FLCκ: median (IQR)=29 (17-39) vs. 15 (11-17) mg/L, p<0.001; FLCλ: 27 (18-34) vs. 15 (13-18) mg/L, p<0.001).
The κ/λ ratio was slightly increased in pSS compared to non-SS sicca patients (p=0.045). FLCκ and FLCλ both showed
good accuracy to discriminate pSS from non-SS (FLCκ: AUC=0.806, 95% CI=0.708-0.904; FLCλ: AUC=0.802, 95%
CI=0.705-0.899). However, the accuracy of serum IgG was higher (AUC=0.885, 95% CI=0.811-0.959). Interestingly,
FLCκ was also elevated (>20 mg/L) in 4/9 incomplete pSS patients. In two of them, also FLCλ was elevated (>32 mg/L).
In patients fulfilling ACR-EULAR criteria, FLCκ and FLCλ levels correlated with systemic disease activity, assessed by
EULAR Sjögren’s syndrome disease activity index (FLCκ: Spearman’s ρ=0.282, p=0.004; FLCλ: ρ=0.321, p=0.001).
Treatment with rituximab significantly lowered FLCκ and FLCλ levels (p<0.001 for both). Treatment with abatacept also
reduced FLCκ and FLCλ levels, although to a smaller extent (p=0.006 and p=0.087, respectively).
Conclusion:
Serum FLCs are elevated in pSS patients at the time of diagnosis and can discriminate non-SS sicca from pSS. FLCκ is
already elevated in a large part of the incomplete SS patients and may serve as an early diagnostic biomarker. Furthermore,
serum FLC levels can be used to monitor the effect of treatment on B-cell activity and may be more sensitive to change
than serum IgG, because of a shorter half-life.
1. Gottenberg et al., Ann Rheum Dis 2007;66:23-7.
Disclosure: G. M. Verstappen, None; J. Bijzet, None; J. F. van Nimwegen, None; M. S. van Ginkel, None; A. Vissink,
None; H. Bootsma, None; F. G. M. Kroese, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/clinical-relevance-of-serum-free-light-

chain-level-as-biomarker-in-primary-sjogren%e2%80%b2s-syndrome
Comprehensive Immuno-Phenotyping of Follicular Helper T Cell and B Cell

Subpopulations in Primary Sjögren’s Syndrome
Nida Meednu1, Cécile Seifert2, Jennifer Barnard3, Madhu Ramaswamy4, Jeffrey Riggs5, Alex Rosenberg6, Jamie Biear7,
Gianluca Carlesso4, Ralf G. Thiele8, Andreea Coca9, Fanny Monneaux2, Helene Dumortier2, Jacques-Eric Gottenberg2 and
Jennifer H. Anolik1, 1Medicine- Allergy, Immunology and Rheumatology, University of Rochester Medical Center,
Rochester, NY, 2CNRS, Immunopathologie et Chimie Thérapeutique/Laboratory of Excellence Medalis, Institut de
Biologie Moléculaire et Cellulaire, Strasbourg, France, 3Medicine-Allergy, Immunology and Rheumatology, University of
Rochester Medical Center, Rochester, NY, 4MedImmune LLC, Gaithersburg, MD, 5Respiratory, Inflammation and
Autoimmunity (RIA), MedImmune LLC, Gaithersburg, MD, 6Department of Microbiology and Informatics Institute,
University of Alabama at Birmingham, Birmingham, AL, 7Rheumatology, University of Rochester Medical Center,
Rochester, NY, 8Medicine, University of Rochester Medical Center, Rochester, NY, 9University of Rochester Medical
Center, Rochester, NY
SESSION INFORMATION
Background/Purpose: Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by immune cell
infiltration in the salivary glands resulting in ocular and oral dryness. Abnormalities in B cell activation and skewing of T
cell polarization toward Th2 and T follicular helper (TFH) associated with ectopic germinal center formation in the salivary
gland are observed in pSS. However, the interplay between B and T cell subsets, and other immune abnormalities, as well
as relationship to disease status, has yet to be fully elucidated. In this study, we evaluated changes in peripheral blood B and
T cell populations in pSS compared to SLE and RA diseases and healthy controls.
Methods: Two cohorts of patients with pSS according to European-American Consensus and ACR criteria and age-
matched healthy controls (HC) were recruited (Rochester, USA and Strasbourg, France) and disease activity assessed by
ESSDAI and ESSPRI. The Rochester cohort also included RA (n=20) and SLE (n=15) classified based on ACR criteria.
PBMCs were isolated by Ficoll-Hypaque and the frequencies of B and T subpopulations measured by multi-parameter flow
cytometry. Data are reported as median [25th-75th quartile]. Correlation analysis was done by Pearson method, p < 0.05
was considered significant.
Results: We examined the expression of ICOS and PD-1, two important co-regulatory molecules of the B7-family, on
memory T cells (CD4+CD45RA-) in pSS compare to HC, SLE and RA. pSS and SLE had higher frequency of memory T
cells expressing both ICOS and PD-1 than HC while RA had higher frequency of PD-1+/hi T cells. Accordingly, T
follicular helper cells (TFH: CXCR5+ICOS+PD-1+) were found at higher frequency in pSS and SLE compared to HC (pSS
(n=40): 5.96 [3.75-8.71]%; HC (n=58): 4.18 [2.51-4.91]%, p=0.0005; SLE (n=15): 4.61 [3.51-9.84]%, p=0.002). Further
evaluation of TFH subsets (based on CXCR3 and CCR6), revealed higher frequency of TFH1 and lower TFH17 subset in
pSS compare to HC and RA, also confirmed in the Strasbourg cohort. Characterization of B cells in pSS patients from
Rochester cohort revealed significant contractions of switched memory (SM) and un-switched memory (USM) B cell
compared to HC (pSS SM (n=39): 3.52 [1.65-7.28]%; HC SM (n=38): 7.57 [5.49-10.86]%, p=0.005; pSS USM (n=39):
10.07 [5.47-15.62]%; HC USM (n=38): 21.44 [15.16-31.27]%, p<0.0001). Furthermore, frequencies of ICOSL expressing
SM and USM were lower in pSS than HC. There was a significant inverse correlation between ICOSL+ USM B cells and
TFH1 in pSS patients (ρ= -0.55, p=0.0255). There were two distinct clusters of pSS based on T and B cell subsets, with one
group distinct from HC and associated with higher disease activity and autoantibodies. In a subset of pSS (n=10), T and B
cell frequencies were evaluated longitudinally at 6 months. Significant changes in frequency of ICOSL+ B cells were
observed and negatively correlated with changes in CXCR5+ICOS+ T cells (ρ= -0.634, p=0.049).
Conclusion: Our data highlight the significant abnormalities in the peripheral TFH and B cell compartment in pSS and
further suggest the critical role of TFH- B cell interactions. The decrease in ICOSL+ memory B cells suggests interaction
with ICOS+ T cells in germinal center-like structures in salivary glands.
Disclosure: N. Meednu, None; C. Seifert, None; J. Barnard, None; M. Ramaswamy, MedImmune LLC, 3; J. Riggs,
MedImmune, LLC, 3,AstraZeneca, 1; A. Rosenberg, None; J. Biear, None; G. Carlesso, MedImmune LLC, 3; R. G.
Thiele, Amgen, 8,AbbVie, 8,BioClinica, 5,Fujifilm SonoSite, 9; A. Coca, None; F. Monneaux, None; H. Dumortier,
None; J. E. Gottenberg, BMS, Gilead, Medimune,Pfzer SanofiAventis, Ucb, 2; J. H. Anolik, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/comprehensive-immuno-phenotyping-

of-follicular-helper-t-cell-and-b-cell-subpopulations-in-primary-sjogrens-syndrome
Anti-Muscarinic Receptor 3 Antibodies – a Cross Reactive Result of Ro60

Immunization
Syed M.S. Quadri1, Biji T Kurien2, Kristi A. Koelsch3 and R. Hal Scofield4, 1Medicine, University of Oklahoma Health
Sciences Center, Oklahoma City, OK, 2Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation,
Oklahoma City, OK, 3Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Okalahoma
City, OK, 4Oklahoma Medical Research Foundation, Oklahoma City, OK
SESSION INFORMATION
Background/Purpose: Sjogren’s syndrome (SS) is a chronic autoimmune inflammatory disease characterized by impaired
function of salivary and lacrimal glands leading to dry mouth and dry eyes. The hallmark of SS is the presence of
autoantibodies against Ro and La antigens. High titers of anti-Ro60 autoantibodies have shown to correlate with severity of
the disease. It is yet unclear how these antiRo60 antibodies correlate with severity. Autoantibodies against M3R are also
prevalent in SS. Muscarinic receptor 3 abbr. as M3R is an end organ parasympathetic GPCR mainly present in lacrimal and
salivary glands. The stimulation of M3R is well studied and is known to induce secretion in lacrimal and salivary glands
and so an effect to M3R could possibly lead to a reduction in secretion.We immunized rabbits with Ro60 and found that
immunization not only resulted in the formation of antibodies against Ro60 but also to 2nd and 3rd extracellular domains of
the M3 receptor. The reactivity to Ro60 and M3R 2nd and 3rd extracellular domains has also shown a high correlation.
Methods:
Immunization of rabbits: NZW rabbits were immunized with 500µg of either unmodified Ro60, Smith or RNP antigen)
emulsified in 0.5 ml of complete Freund’s adjuvant given I/P with subsequent boosters at days 26, 53 and 99 with a final
I/V boost on day 152. The sera were collected weekly in pre and post-immunized rabbits. Ro60 and M3R experiments:
Reactivity of sera towards Ro60, MAPS of M3R 2nd or 3rd extracellular domains were tested using ELISA. Seral dilution
ELISA was done using dilution 1:100 to 1: 100,000 and competition ELISA by preincubating sera with either Ro60 and
MAPS of 2nd ECL was done to see the specificity of antibody binding.
Results: Rabbits immunized with Ro60 developed antibodies against Ro60, M3R 2nd and 3rd ECLs in a progressive way.
A positive correlation was found between both Ro60 and M3R 2nd ECL (R2 =0.66, p = <0.0001) and between Ro60 and
M3R 3rd ECL(R2 =0.789, p = <0.0001) . A positive correlation was also found between M3R 2nd and 3rd ECL ELISA (R2
=0.56, p = 0.0001). Rabbits immunized with Smith and RNP antigen did not develop antibodies to any of the extracellular
domains of M3R to significant levels. Seral dilution ELISA showed a sequential decline in reactivity for both the 2nd and
the 3rd ECL of M3R. Competition ELISA for 2nd ECL of M3R using sera preincubated with M3R 2nd ECL showed an
inhibition of 48.2% to 58.99%, sera preincubated with Ro60 showed an inhibition of 54.5 to 89.03% verifying the specific
binding.
Conclusion: Previously our studies found high reactivity for M3R and Ro60 antigen in fully human recombinant
monoclonal antibodies produced from plasmablasts isolated from salivary glands of SS patients and was found to be
inhibitory. The subsequent step, immunization of rabbits with Ro60 also supported the same hypothesis. The rabbits
immunized with Ro60 developed antibodies to M3R extracellular domains supporting the concept of cross-reactivity. Our
next step is to see whether the immunization of rabbits with M3R develops anti-Ro60 antibodies. Our future studies are
also aimed at passive transfer of IgGs (from Ro60 immunized rabbit sera as well as human recombinant IgGs positive for
M3R and Ro) to mice to see the invivo functional consequences of this cross-reactivity.
Disclosure: S. M. S. Quadri, None; B. T. Kurien, None; K. A. Koelsch, None; R. H. Scofield, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/anti-muscarinic-receptor-3-antibodies-

a-cross-reactive-result-of-ro60-immunization
The Effect of Non-Invasive Vagus Nerve Stimulation on Fatigue and Immune

Responses in Patients with Primary Sjögren’s Syndrome
Jessica Tarn1, Sarah Legg2, Sheryl Mitchell2, Bruce Simon3 and Wan-Fai Ng4, 1Institute of Cellular Medicine,
Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-Upon-Tyne, UK,
Newcastle-Upon-Tyne, United Kingdom, 2Freeman Hospital, Newcastle upon Tyne, United Kingdom, 3electroCore
Medical LLC, Basking Ridge, NJ, 4Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United
Kingdom
SESSION INFORMATION
Background/Purpose: Primary Sjšgren's syndrome (pSS) sufferers have rated chronic fatigue as the most important
symptom needing improvement and the main contributing factor to the loss of work productivity. Emerging data suggest
cross-talk exists between the autonomic nervous system and the immune system via the vagus nerve in particular. The
gammaCore device (electroCore), was developed to deliver stimulation of the cervical vagus nerve non-invasively, and has
been CE marked for the treatment of epilepsy and migraine and has recently been FDA approved for the acute treatment of
episodic cluster headache. In this study, we use the gammaCore device to dissect the relationship between the vagus nerve,
fatigue and immune responses in pSS.
Methods: Fifteen female pSS subjects fulfilling the American European Consensus Group Classification criteria (2002)
were included. At baseline, blood was drawn before and after non-invasive vagus nerve stimulation (nVNS). The subjects
were then instructed to use the gammaCore device twice daily (2 min. over each carotid artery). The participants were
followed up at day 7 and Day 28. At each visit, blood was drawn and patient reported outcome measures (PROMs) were
collected including EULAR SjogrenÕs syndrome Patient Reported Index (ESSPRI), Profile of fatigue (PRO-F), visual
analogue scale (0-100 cm) of abnormal fatigue and Epworth Sleepiness Scale (daytime sleepiness). Whole blood samples
were stimulated with 2ng/mL Lipopolysaccharides (LPS) or RPMI-1640 as control. After 24 hours, the levels of IFNγ ,
IL12-p70, TNFα , MIP1a, IFNa, IL-10, IL-1β, IL-6 and IP10 were measured in the supernatants by cytometric bead array
(BD). In addition, whole blood cell subset proportions were profiled using flow cytometry.
Results: PRO-F, and Daytime sleepiness were significantly reduced across three visits. Trends of improvement were also
observed in Abnormal fatigue VAS, ESSPRI-Dryness and ESSPRI-Physical fatigue subscales. Participants who appeared to
have a sustained reduction in fatigue related PROMs over the study period concurrently had a significantly higher
proportion of T-cells at most time points. Cytokine production, particularly TNFα by whole blood cells upon LPS
stimulation was reduced over the period of device use. Additionally, TNFα and IL-1β levels were significantly reduced
after the first device use compared with pre-VNS.
Conclusion: To our knowledge this is the first study into the effects of nVNS in pSS. These preliminary observations
suggest that in some individuals, nVNS may reduce clinical symptoms of fatigue, which could be underpinned by
biological changes detectable in the whole blood.
Disclosure: J. Tarn, None; S. Legg, None; S. Mitchell, None; B. Simon, electroCore, 3; W. F. Ng, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-effect-of-non-invasive-vagus-nerve-

stimulation-on-fatigue-and-immune-responses-in-patients-with-primary-sjogrens-syndrome
Molecular Identification of a Ro-Specific Salivary IgA Repertoire with

Unique Clonal Signatures in Primary Sjogren’s Syndrome
Jing Jing Wang1, Alexander Colella1, Tim Chataway2, R. Hal Scofield3 and Tom Gordon1,4, 1Immunology, Flinders
University, Adelaide, Australia, 2Proteomic Facility, Flinders University, Adelaide, Australia, 3Arthritis and Clinical
Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 4Immunology, SA Pathology,
Adelaide, Australia
SESSION INFORMATION
Background/Purpose: Autoantibodies against 60-kD Ro (Ro60)/SSA have been detected in the saliva and serum of
patients with primary Sjögren's syndrome (SS) by routine methods that are unable to resolve molecular characteristics of
interacting antibodies. Accordingly, it is unknown whether the parallel glandular and systemic anti-Ro60 responses derive
from related or independent antibody repertoires. In the present study, we have identified a Ro60-specific salivary IgA
repertoire by analysing immunoglobulin variable region (IGV) subfamily composition and mutational profiles of matched
salivary and serum proteomes.
Methods: Anti-Ro60 autoantibodies were purified and sequenced from Ro-specific precipitins prepared by
electrophoresing native Ro60 protein against whole saliva or serum collected from 9 patients with seropositive primary SS.
Microgram amounts of precipitating anti-Ro60 Igs were separated by SDS-PAGE, and in-gel chymotrypsin digests
performed on heavy (H) and light (L) chain bands. VH/VL and constant-region peptides were subjected to nano-high
performance liquid chromatography-mass spectrometry (nHPLC-MS/MS) followed by combined de novo amino acid
sequencing and database matching using Peaks 8.0 software utilising ImMunoGeneTics (IMGT) and Uniprot databases.
Results: High-resolution MS sequencing of purified salivary anti-Ro60 H- and L-chains revealed a common (9/9 patients)
oligoclonal IgA Ro60 repertoire dominated by IGHV3-23 and IGKV3-20 subfamily expression. Paired serum anti-Ro60
proteomes expressed a more diversified IgG1 repertoire with expression of additional IGHV1 and IGHV3 families in the
systemic compartment. IGHV3-23-encoded H-chains were present in matched saliva and serum samples but were distinct
in terms of their patterns of somatic mutations, suggesting independent pathways of affinity maturation. Three of 9 patients
showed a less abundant IgG1 salivary anti-Ro60 proteome that was similar to the paired serum proteome.
Conclusion: Proteomic profiling of salivary and serum anti-Ro60 autoantibodies in primary SS reveals a unique salivary
IgA repertoire with specific V-region peptide profiles, consistent with a parallel yet distinct salivary gland pathway of
somatically selected anti-Ro60 autoantibodies. The novel proteomic workflow reported herein will allow analysis of clonal
turnover of mucosal and systemic autoantibody repertoires in early versus established disease and provide molecular
biomarkers to assess responses to therapy in the glandular and peripheral compartments.
Disclosure: J. J. Wang, None; A. Colella, None; T. Chataway, None; R. H. Scofield, None; T. Gordon, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/molecular-identification-of-a-ro-

specific-salivary-iga-repertoire-with-unique-clonal-signatures-in-primary-sjogrens-syndrome
Fatigue in Primary Sjögren’s Syndrome (pSS) Is Associated with Lower

Levels of Proinflammatory Cytokines: A Validation Study
Kristen Davies1, Kamran Mirza1, Jessica Tarn2, Nadia Howard Tripp3, Robert J. Moots4, Nagui Gendi5, Michele
Bombardieri6, Costantino Pitzalis6, Nurhan Sutcliffe6, Simon Bowman7, Neil J. McHugh8, John McLaren9, Devesh
Mewar10, David Coady11, Kirsten MacKay12, Susan Knight13, Monica Gupta14, Marian Regan15, Cathy Lawson16,
Jacqueline Andrews17, Peter Lanyon18, Mohammed Akil19, Elizabeth Price20, Annie Cooper21, Frances Hall22, Theodoros
Dimitroulas23, Gavin Clunie24, Saravanan Vadivelu25, Ian Giles26, Bhaskar Dasgupta27, Steve Young-Min28, Dennis
Lendrem29,30 and Wan-Fai Ng2,31, 1Institute of Cellular Medicine, Musculoskeletal Research Group, Institute of Cellular
Medicine, Newcastle University, Newcastle-Upon-Tyne, UK, Newcastle-Upon-Tyne, United Kingdom, 2Musculoskeletal
Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-Upon-Tyne, UK, Newcastle-Upon-Tyne,
United Kingdom, 3Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK, Newcastle-upon-
Tyne, United Kingdom, 4University of Liverpool, Liverpool, UK, Liverpool, United Kingdom, 5Basildon and Thurrock
University Hospital, Basildon, UK, Basildon, United Kingdom, 6Barts Health NHS Trust & Barts and the London School
of Medicine & Dentistry, London, UK, London, United Kingdom, 7Department of Rheumatology, University Hospitals
Birmingham NHS Foundation Trust, Birmingham, UK, Birmingham, United Kingdom, 8Royal National Hospital for
Rheumatic Diseases, Bath, UK, Bath, United Kingdom, 9NHS Fife, Kirkcaldy, UK, Kirkcaldy, United Kingdom, 10Royal
Liverpool University Hospital, Liverpool, UK, Liverpool, United Kingdom, 11Sunderland Royal Hospital, Sunderland, UK,
Sunderland, United Kingdom, 12Torbay Hospital, Torquay, UK, Torquay, United Kingdom, 13Macclesfield General
Hospital, Macclesfield, UK, macclesfield, United Kingdom, 14Gartnavel General Hospital, Glasgow, UK, Glasgow, United
Kingdom, 15Royal Derby Hospital, Derby, UK, Derby, United Kingdom, 16Harrogate District Hospital, Harrogate, UK,
Harrogate, United Kingdom, 17Leeds Teaching Hospitals NHS Trust, Leeds, UK, Leeds, United Kingdom, 18Nottingham
University Hospitals NHS Trust, Nottingham, UK, Nottingham, United Kingdom, 19Royal Hallamshire Hospital, Sheffield,
UK, Sheffield, United Kingdom, 20Great Western Hospital, Swindon, UK, Swindon, United Kingdom, 21Royal Hampshire
County Hospital, Winchester, UK, Winchester, United Kingdom, 22Addenbrooke’s Hospital, Cambridge, UK, Cambridge,
United Kingdom, 23Dudley Group of Hospitals NHS Foundation Trust, Dudley, UK, Dudley, United Kingdom, 24Ipswich
Hospital NHS Trust, Ipswich, UK, Ipswich, United Kingdom, 25Queen Elizabeth Hospital, Gateshead, UK, Gateshead,
United Kingdom, 26Centre for Rheumatology, University College London, Centre for Rheumatology, University College
London, UK, London, United Kingdom, 27Rheumatology, Southend University Hospital NHS Foundation Trust, Southend,
UK, Westcliff-on-Sea, United Kingdom, 28Queen Alexander Hospital, Portsmouth, UK, Portsmouth, United Kingdom,
29Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK, Newcastle, United Kingdom,
30Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-Upon-Tyne, UK,
Newcastle-upon-Tyne, United Kingdom, 31Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne,

UK, Newcastle-Upon-Tyne, United Kingdom
SESSION INFORMATION
Background/Purpose: Primary Sjögren’s syndrome (pSS) is a chronic autoimmune rheumatic disease causing various
symptoms including dryness, fatigue and pain. Previous work by our group has suggested that certain pro-inflammatory
cytokines are inversely related to patient-reported levels of fatigue. This model in that study using pro-inflammatory
cytokine levels, disease-specific and clinical parameters was able to predict fatigue with 67% accuracy. To date, these
findings have not been validated. This study aims to validate this observation.
Methods: Blood levels of seven cytokines were measured in 120 patients with pSS from the United Kingdom Primary
Sjögren’s Syndrome Registry and 30 age-matched healthy non-fatigued controls. Patient-reported scores for fatigue were
classified according to severity and compared to cytokine levels using analysis of variance. The differences between
cytokines in cases and controls were evaluated using Wilcoxon test. A logistic regression model was used to determine the
most important predictors of fatigue.
Results: Three cytokines, interferon-γ-induced protein-10 (IP-10), tumour necrosis factor-α (TNFα) and interferon-α
(IFNα) were significantly higher in patients with pSS (n=120) compared to non-fatigued controls (n=30). Levels of two
pro-inflammatory cytokines, TNF-α (p=0.021) and lymphotoxin-α (p=0.043), were inversely related to patient-reported
levels of fatigue. Based on the model previous used a regression model was created to predict fatigue in pSS. Cytokine
levels, disease-specific and clinical parameters as well as pain, anxiety and depression were used as predictors in this
validation model. The model correctly predicts fatigue levels with 85% accuracy.
Conclusion: Depression, pain and proinflammatory cytokines appear to be the most powerful predictors of fatigue in pSS,
which is consistent with the original study. This data further challenges the notion that proinflammatory cytokines directly
mediate fatigue in chronic immunological conditions. Validation in an independent international cohort would be necessary
to further confirm these results.
Figure 1: Box plot showing median cytokine levels and IQR for a) IP-10, b) TNF-α, c) LT-α and d) IFN-γ in controls and
pSS fatigue groups.
Figure 2: (A) Full ordinal logistic regression model with all parameters. All of these variables predict fatigue correct in
85% of cases. (B) shows that IFN-γ, IP-10, depression and pain alone predicted fatigue level with 80% accuracy.
Disclosure: K. Davies, None; K. Mirza, None; J. Tarn, None; N. Howard Tripp, None; R. J. Moots, None; N. Gendi,
None; M. Bombardieri, GSK, Amgen/MedImmune and UCB, 5; C. Pitzalis, None; N. Sutcliffe, None; S. Bowman, I
have consulted in the field of Sjogren's for: AstraZeneca/Meddimmune, BMS, Celgene, Eli Lilly, Glenmark, GSK,
MTPharma, Novartis, Ono, Takeda, UCB, xtlbio). Roche provided Rituximab for the TRACTISS Study, 5; N. J. McHugh,
None; J. McLaren, None; D. Mewar, None; D. Coady, None; K. MacKay, None; S. Knight, None; M. Gupta, None; M.
Regan, None; C. Lawson, None; J. Andrews, None; P. Lanyon, None; M. Akil, None; E. Price, None; A. Cooper, None;
F. Hall, None; T. Dimitroulas, None; G. Clunie, None; S. Vadivelu, None; I. Giles, None; B. Dasgupta, None; S. Young-
Min, None; D. Lendrem, None; W. F. Ng, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/fatigue-in-primary-sjogrens-syndrome-

pss-is-associated-with-lower-levels-of-proinflammatory-cytokines-a-validation-study
Immune Response to Seasonal Flu Vaccination in Patients with Primary

Sjogren’s Syndrome
Albin Björk1, Marika Kvarnström2, Gudny Ella Thorlacius2 and Marie Wahren-Herlenius2, 1Department of Medicine,
Unit of Experimental Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital,
Stockholm, Sweden, Stockholm, Sweden, 2Unit of Experimental Rheumatology, Department of Medicine, Karolinska
Institutet, Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden
SESSION INFORMATION
Background/Purpose: Vaccination of rheumatic patients has been reported to induce lower antibody titers than in healthy
individuals. However, studies have primarily included patients treated with immunomodulatory drugs. Previous data from
our group revealed that untreated patients with primary Sjögren’s syndrome (pSS) respond with higher vaccine specific
antibody titers than healthy controls (HC) following vaccination with a squalene adjuvanted H1N1 vaccine. Whether non-
adjuvanted vaccines would also induce higher specific antibody responses in non-treated patients is not known. In the
present study, we therefore monitored the vaccination response to the adjuvant-free vaccine for seasonal flu (Fluarix) in HC
and untreated patients as well as that in patients receiving hydroxychloroquine (HCQ).
Methods: The study included 17 pSS patients without treatment, 8 pSS patients receiving HCQ, and 16 HC. All
participants were women and all pSS patients were positive for SSA autoantibodies at the time of diagnosis. All individuals
were vaccinated with the Fluarix 2015/2016 vaccine as part of the standard vaccination program. Clinical parameters were
recorded using a questionnaire based on ESSPRI. Antibody titers were analysed by ELISA. RNA expression analysis was
performed in CD14+ monocytes and CD19+ B cells using the Human Immunology v2 CodeSet (Nanostring).
Results: Untreated patients with pSS responded with significantly higher vaccine specific IgG titers than HC after
immunization. Further, levels of anti-Ro52 autoantibodies increased in untreated patients, but not in HCQ-treated patients
after vaccination. Nanostring RNA expression data confirmed the presence of an interferon (IFN)-signature in monocytes
and in B cells from pSS patients and an IFN score calculated from B cell expression data could discriminate between high
and low vaccine antibody response at day 29. No significant changes in self-reported clinical parameters were registered.
Conclusion: Untreated pSS patients display an increased serological responsiveness to the non-adjuvanted seasonal flu
vaccine when compared to healthy controls. The increased response is however not mirrored by any clinical aggravation of
the patients’ rheumatic disease.
Disclosure: A. Björk, None; M. Kvarnström, None; G. E. Thorlacius, None; M. Wahren-Herlenius, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/immune-response-to-seasonal-flu-

vaccination-in-patients-with-primary-sjogrens-syndrome
Minor Salivary Gland Histopathology, Major Salivary Gland

Ultrasonography, and Secretory Function in Smoking Patients with Primary
Sjögren’s Syndrome
Daniel S. Hammenfors1, Haris Causevic2, Johan G. Brun3, Roland Jonsson1 and Malin V. Jonsson4, 1Department of
Rheumatology, Haukeland University Hospital, University of Bergen, Bergen, Norway, 2Broegelmann Research
Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway, 3Department of Rheumatology,
Haukeland University Hospital, Bergen, Bergen, Norway, 4Department of Clinical Dentistry, Section for Oral and
Maxillofacial Radiology, University of Bergen, Bergen, Norway
SESSION INFORMATION
Background/Purpose:
Several studies have reported a protective effect of smoking with regard to risk for primary Sjögren’s syndrome (pSS) and
minor salivary gland inflammation. To our knowledge, there are no studies investigating major salivary gland
ultrasonography (SGUS) findings in smokers with pSS. The aim of this study was to investigate the frequency of smokers
in a cohort of pSS, and to determine the possible impact of smoking on minor salivary gland histopathology, major salivary
gland ultrasonography, and secretory function of the salivary and lacrimal glands.
Methods:
Patients with pSS (n=98) were recruited from the Department of Rheumatology, Haukeland University Hospital, Bergen,
Norway. All patients had undergone clinical examination and SGUS using a simplified scoring system for glandular
homogeneity and hypoechogenic areas. The parotid and submandibular salivary gland scans were graded 0-3; grades 0-1
considered corresponding to normal/non-specific changes and grades 2-3 to SS-like pathological changes. In addition,
routine clinical and serological parameters, information regarding focus score, sicca symptoms, secretory function, fatigue,
and smoking habits were available for retrospective analysis. All patients fulfilled the 2002 AECG criteria for pSS.
Results:
The majority of patients in this pSS cohort (n=59) were non-smokers, the remaining consisted of former smokers (n=27)
and current smokers (n=12). Pathological SGUS findings were found in 38/59 (64 %) of the non-smokers, 13/27 (48 %) of
the former smokers, and in 7/12 (58 %) of the current smokers.
Data on focus score (FS) was available in 83 patients, and correlated with SGUS score (p=0.010, r=0.283). Interestingly,
49/54 (91 %) non-smokers, 17/21 (81 %) former smokers and 3/8 (38 %) current smokers had FS≥1 (p<0.010, r=0.283).
Mean focus score was 2.0 for non-smokers, 2.1 for former smokers, and 0.6 for current smokers; the difference between
current and former smokers was significant (p=0.023).
Oral sicca symptoms correlated with SGUS score (p<0.001, r=0.378). Unstimulated salivary secretion was ≤1.5 ml/15 min
in 42/57 (74 %) non-smokers, 18/26 (69 %) former smokers, and 7/12 (58 %) current smokers. Stimulated saliva was ≤3.5
ml/5 min in 27/57 (47 %) non-smokers, 12/26 (46 %) former smokers, and 4/12 (33 %) current smokers. Schirmer’s I-test
levels (right and left eye, respectively) for current smokers were 9.3 and 11.3 mm, former smokers 4.9 and 3.8 mm, and
non-smokers 7.7 and 7.9 mm. Differences were significant for the left eye when comparing current smokers and former
smokers (p=0.021), and non-smokers and former smokers (p=0.048).
Interestingly, anti-Ro/SSA titers were elevated in 9/12 (75 %) current smokers and 20/27 (74 %) former smokers, compared
to 35/58 (60 %) non-smokers. A similar trend was observed for anti-La/SSB titers in 6/12 (50 %) current smokers, 12/27
(44 %) former smokers, and 19/58 (33 %) non-smokers.
Conclusion:
In this cohort, smokers with pSS had a lower degree of minor salivary gland inflammation and pathological imaging
findings in the major salivary glands. The sub-group also presented with better secretory function compared to non-
smokers and former smokers.
Disclosure: D. S. Hammenfors, None; H. Causevic, None; J. G. Brun, None; R. Jonsson, None; M. V. Jonsson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/minor-salivary-gland-histopathology-

major-salivary-gland-ultrasonography-and-secretory-function-in-smoking-patients-with-primary-sjogrens-syndrome
Complement Consumption As a Predictor of Pulmonary Manifestation in

Patients with Primary Sjögren’s Syndrome: Results from a Unicentric
Observational Study
Alisson Pugliesi1, RACHEL ZERBINI MARIANO2, Raquel Baldini Campos3, Simone Appenzeller4, Manoel Bertolo5
and ZORAIDA SACHETTO1, 1INTERNAL MEDICINE, DISCIPLINE OF RHEUMATOLOGY, Faculty of Medical
Sciences, State University of Campinas (UNICAMP), CAMPINAS, Brazil, 2Radiology and Diagnostic Imaging, Faculty of
Medical Sciences, State University of Campinas (UNICAMP), CAMPINAS, Brazil, 3Internal Medicine, Faculty of
Medical Sciences, State University of Campinas (UNICAMP), CAMPINAS, Brazil, 4Pediatric Rheumatology Unit, State
University of Campinas, Campinas, Brazil, 5INTERNAL MEDICINE, DISCIPLINE OF RHEUMATOLOGY, Faculty of
Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil
SESSION INFORMATION
Complement Consumption as a Predictor of Pulmonary Manifestation in Patients with Primary Sjögren’s Syndrome:
Results from a Unicentric Observational Study
Background/Purpose: Primary Sjögren’s syndrome (pSS) may present with respiratory manifestations ranging from
proximal and distal airways impairment to various forms of interstitial lung disease (pSS-ILD), which can affect up to 16%
of patients1. Studies on factors associated with pulmonary manifestations of pSS are few and of heterogeneous results2,3,4.
Our main objective was to identify clinical and laboratory elements related to pSS that may be predictors of lung disease.
Methods: Retrospective study of pSS patients in follow-up at a university hospital. Patients older than 18 years who met
pSS classificatory criteria according to the American-European Consensus of 2002 were included. Patients with other CTD
were excluded. Epidemiological, clinical, and laboratory data were extracted from medical records. Chest CT scans were
reviewed by a radiologist without knowledge of the patients’ clinical data. Data from patients with pSS with and without
pulmonary manifestations were compared and Fischer’s test was applied for statistical evaluation.
Results: Seventy patients with pSS were selected (68% female and mean age 45.8 ± 9.5). Fifteen (21.4%) had some form
of pulmonary manifestation, 14 (20%) of ILD and 1 of bronchiolitis (1.4%). Among the analyzed variables, a statistically
significant association was found between complement consumption (C3 or C4) and presence of pulmonary manifestation
(38.4% versus 10.2%; p: 0.02). No association was found between autoantibodies such as ANA, RF, Ro/SSA and La/SSB
or other forms of extraglandular manifestation (Table 1). No variables were correlated with the presence of pulmonary cysts
or pSS-ILD. The radiological findings of patients with pulmonary manifestations are summarized in Table 2.
Conclusion: In our series of patients with pSS, we found a high frequency of individuals with pSS and pulmonary
impairment. Complement consumption was a predictor of this form of manifestation, an association never seen before.
Disclosure: A. Pugliesi, None; R. Z. MARIANO, None; R. Baldini Campos, None; S. Appenzeller, None; M. Bertolo,
None; Z. SACHETTO, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/complement-consumption-as-a-

predictor-of-pulmonary-manifestation-in-patients-with-primary-sjogrens-syndrome-results-from-a-unicentric-
observational-study
Is the Oral Microbiome Involved in the Pathogenesis of Sjogren’s Syndrome?

Taco A van der Meulen1, Frans G.M. Kroese2, S.C. Liefers2, Arnau Vich Vila3, Hermie J.M. Harmsen4, Hendrika
Bootsma2, Fred K.L. Spijkervet1 and Arjan Vissink5, 1Oral and Maxillofacial Surgery, University of Groningen, University
Medical Center Groningen, Groningen, Netherlands, 2Rheumatology and Clinical Immunology, University of Groningen,
University Medical Center Groningen, Groningen, Netherlands, 3Gastroenterology, University of Groningen, University
Medical Center Groningen, Groningen, Netherlands, 4Medical Microbiology, University of Groningen, University Medical
Center Groningen, Groningen, Netherlands, 5Department of Oral and Maxillofacial Surgery, University of Groningen,
University Medical Center Groningen, Groningen, Netherlands
SESSION INFORMATION
Background/Purpose: Environmental factors involved in the pathogenesis of primary Sjögren’s syndrome (pSS) are still
largely unknown. The oral cavity is the microbial habitat closest to the salivary glands – the most affected tissue in pSS.
Hypofunction of the salivary glands is the major cause underlying symptoms of a dry mouth (xerostomia), occurring in
over 90% of the patients with pSS. The aim of our study was to explore whether the oral microbiome, in particular the
bacterial composition and/or the presence of bacterial species, is specific for the oral microbiome of patients with pSS.
Methods: To assess whether changes in the oral microbiome of pSS patients are a cause of pSS or an effect of oral dryness,
we included two control groups: patients with oral dryness not diagnosed as pSS (non-SS sicca patients) and population
based controls. We collected a swab from the buccal mucosa of 82 patients with oral dryness referred to our outpatient
clinic for a complete diagnostic work-up for pSS. After completing the diagnostic workup, 32 patients could be classified
as pSS according to the 2002 AECG classification criteria and 50 patients as non-SS sicca. The bacterial composition of the
buccal mucosa samples was determined with 16S rRNA sequencing. Buccal mucosa swab samples from a population based
cohort study were used as population controls (n=118).
Results: Mean unstimulated whole salivary flow rates in pSS and non-SS sicca patients were 0.09 and 0.17 mL/min
respectively. Significantly less 16S rRNA reads per sample were obtained from the buccal swab samples of patients with
oral dryness (pSS and non-SS sicca together) compared to population controls (p<0.0001). Also the diversity of the
bacterial composition from the buccal mucosa was significantly lower in pSS and non-SS sicca patients than in population
controls (p=0.01 and p<0.001 respectively), but no difference was observed between pSS and non-SS sicca patients.
Principal coordinate analysis showed no evident separation of the individual samples between the three different study
groups, but the buccal mucosa bacterial communities from pSS patients were significantly more dissimilar to those from
population controls than non-SS sicca patients from population controls (p=0.028). Multivariate analysis showed highly
significant associations between oral dryness and the genera Olsenella, Cryptobacterium and Fretibacterium – all which
have been associated with periodontal disease – since these genera were only detected in samples from the buccal mucosa
of patients with oral dryness and not in population controls (p-value <0.005). However, no oral bacterial taxa were
specifically associated with pSS.
Conclusion: Patients with pSS have a dysbiosis of the oral microbiome, viz. a reduced diversity and increase of pathogenic
bacteria. We presume that dysbiosis in the oral microbiome of patients with pSS is largely an effect of oral dryness and not
a causal factor in the pathogenesis of pSS. On top of this dysbiosis as a consequence of oral dryness, there might be a
specific effect of pSS on the diversity of the oral microbiome.
Disclosure: T. A. van der Meulen, None; F. G. M. Kroese, None; S. C. Liefers, None; A. Vich Vila, None; H. J. M.
Harmsen, None; H. Bootsma, None; F. K. L. Spijkervet, None; A. Vissink, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/is-the-oral-microbiome-involved-in-

the-pathogenesis-of-sjogrens-syndrome
Signalling Pathways Identified in Salivary Glands from Primary Sjögren’s

Syndrome Patients Reveal Enhanced Adipose Tissue Development, As
Demonstrated By Microarray Analysis, Real-Time PCR and
Immunohistochemistry
Lara A Aqrawi1, Janicke C Liaaen Jensen1, Gunnvor Øijordsbakken2, Ann-Kristin Ruus3, Ståle Nygård4,5, Marit Holden6,
Roland Jonsson7,8, Hilde Kanli Galtung9 and Kathrine Skarstein10,11, 1Department of Oral Surgery and Oral Medicine,
University of Oslo, Oslo, Norway, 2Department of Clinical Medicine, University of Bergen, Gade Laboratory for
Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway, 3Department of Oral Biology,
University of Oslo, Oslo, Norway, 4Department of Informatics, University of Oslo, Oslo, Norway, 5Bioinformatics core
facility, Institute for Cancer research, Oslo University Hospital, Oslo, Norway, 6Norwegian Computing Center, Oslo, Oslo,
Norway, 7Broegelmann Research laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway,
8Department of Rheumatology, Haukeland University Hospital, Bergen, Bergen, Norway, 9Department of Oral Biology,
University of Oslo, Oslo, Pakistan, 10Gade Laboratory for Pathology, Department of Clinical Medicine, University of
Bergen, Bergen, Norway, 11Department of Pathology, Haukeland University Hospital, Bergen, Bergen, Norway
SESSION INFORMATION
Background/Purpose: : A characteristic feature of Sjögren’s syndrome (SS) is the destruction of salivary and lacrimal
glands mediated by mononuclear cell infiltration. Adipocytes can also occupy a large portion of the salivary gland (SG)
tissue area, although little is known about their significance in SS. We have previously investigated adipose tissue
infiltration in SG biopsies from SS patients and non-SS sicca controls. Our findings indicated distinct incidence of adipose
tissue replacement in SS patients, where adipocytes were detected in IL6 rich regions. We now aimed to examine the
development of adipocytes in the SG microenvironment, and delineate their possible involvement in immune reactions.
Methods: A microarray analysis was performed on SG from 6 SS patients and 6 non-SS controls, where the expression
levels of genes involved in adipose tissue development were assessed. Real-time PCR was carried out on SG from 14 SS
patients and 15 non-SS controls to account for interleukin (IL)-6, IL10 and IL17 mRNA levels. Immunohistochemical
staining of frozen SG tissue using IL17 was also conducted.
Results: Upregulated signalling pathways identified in SG of SS patients show prominent adipose tissue development and
mitochondrial fatty acid beta-oxidation, including the genes ARID5B, OXCT1, BDH1, SOX8, HMGCS2, FTO, ECHS1,
PCCA, ACADL and ACADVL. Genes involved in interferon production and signalling were also detected (IRF1, IRF9,
IRF7), in addition to IL6, IL10, and IL17 (Figure 1, Table 1). Higher mRNA levels of IL6, IL17 and IL10 were also
observed in the SG of SS patients compared to controls. Moreover, IL17+ cells were observed mostly interstitially in the
SG and around adipocytes, also within the focal infiltrates.
Conclusion: Adipocyte development seems to be more prominent in the SG of SS patients at the site of inflammation,
where adipose tissue replacement is also evident. Detection of IL17 positive adipocytes in the target organ suggests their
involvement in immune reactions.
Disclosure: L. A. Aqrawi, None; J. C. Liaaen Jensen, None; G. Øijordsbakken, None; A. K. Ruus, None; S. Nygård,
None; M. Holden, None; R. Jonsson, None; H. K. Galtung, None; K. Skarstein, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/signalling-pathways-identified-in-

salivary-glands-from-primary-sjogrens-syndrome-patients-reveal-enhanced-adipose-tissue-development-as-demonstrated-
by-microarray-analysis-real-time-pcr-and
Anti-Modified Protein Antibody Response Pattern in Primary Sjögren’s

Syndrome: Clinical and Prognostic Implications
Alessia Alunno1, Francesco Carubbi2,3, Holger Bang4, Onelia Bistoni1, Paul Studenic5, Günter Steiner5, Elena Bartoloni6,
Josef S. Smolen5,7 and Roberto Gerli1, 1Department of Medicine, Rheumatology Unit, University of Perugia, Perugia,
Italy, 2ASL1 Avezzano L'Aquila Sulmona, L'Aquila, Italy, 3Rheumatology Unit, University of L'Aquila, L'Aquila, Italy,
4Orgentec Diagnostika GmbH, Mainz, Germany, 5Division of Rheumatology, Department of Internal Medicine III, Medical
University of Vienna, Vienna, Austria, 6Rheumatology Unit, University of Perugia, Perugia, Italy, 7Hietzing Hospital,
Department of Internal Medicine, Vienna, Austria
SESSION INFORMATION
Background/Purpose: Over the last decades, several post translationally modified proteins have been identified as auto-
antigens in rheumatoid arthritis (RA). No data regarding Abs against acetylated proteins (AAPA) and very few on Abs
against carbamylated proteins (anti-CarP) are currently available in primary Sjögren’s syndrome (pSS). Acetylation of
lysine/ornithin results from the addition of an acetyl group by the N-acetyltranferase enzyme, while carbamylation is the
conversion of lysine residues into homocitrulline. In RA, carbamylation can be induced by cigarette smoke. The aim of our
study was to investigate the prevalence and significance of AAPA and anti-CarP Abs in pSS.
Methods:
Eighty-seven pSS patients according to the 2002 American-European Consensus Criteria where enrolled. AAPA and anti-
CarP were assessed by ELISA using mutated vimentin acetylated or carbamylated in position 7 as antigen. Acetylation
could target either a lysin or an ornithin residue. To assess the possible effect of nearby antigens, acetylation and
carbamylation were also alternatively included in position 2 (inverse peptide). Acetylated histone and non histone peptides
were also employed as antigens. Clinical and serological records, including glandular and extraglandular manifestations,
cardiovascular (CV) risk factors and CV events were retrospectively collected.
Results:
AAPA were identified in 20 pSS patients (23%). Seven patients displayed only one AAPA specificity while 13 displayed 2
or more AAPA specificities. Anti-CarP Abs have been identified in 4 pSS patients (5%) and in all cases the antigen was
mutated vimentin carbamylated at position 7 but not the inverse peptide. AAPA+ patients did not display extra-glandular
involvement including renal, pulmonary, gastrointestinal, central/peripheral nervous system manifestations or myositis.
Conversely, binary logistic regression revealed that AAPA positivity was associated with cardiac (namely pericarditis) and
cardiovascular (CV) events (heart failure, pulmonary arterial hypertension, pulmonary embolism) (odds ratio=11;
p<0.0001) but not with smoking or systemic arterial hypertension. pSS patients with anti-CarP Abs displayed more
frequently leukopenia (p=0.01) and parotid gland swelling (p=0.03) but surprisingly none of the anti-CarP+ patients
displayed articular involvement and none of them was a current or former smoker.
Conclusion:
Our study demonstrated for the first time that AAPA are detectable in pSS. Although preliminary, our results support the
evidence of a possible association of AAPA and cardiac/CV manifestations. Likewise, specific anti-CarP Abs against
mutated carbamylated vimentin are present in a small proportion of pSS patients and seem to be associated with leukopenia
and parotid gland swelling but not with articular involvement and smoking. These results are of particular importance in
light of the increased CV risk in pSS and will be assessed in a larger cohort of patients fopr validation purposes.
Furthermore, it might be speculated that carbamylation in pSS may be induced by mechanisms other than cigarette
smoking.
Disclosure: A. Alunno, None; F. Carubbi, None; H. Bang, None; O. Bistoni, None; P. Studenic, None; G. Steiner,
None; E. Bartoloni, None; J. S. Smolen, None; R. Gerli, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/anti-modified-protein-antibody-

response-pattern-in-primary-sjogrens-syndrome-clinical-and-prognostic-implications
Biopsy Accuracy in Sjögren’s Syndrome: Analysis of 803 Patients Presenting

with Sicca Syndrome Referred to Labial Salivary Gland Biopsy
Diego Baenas1, Soledad Retamozo2, Juan Pablo Pirola3, Nadia Benzaquén4, María Flavia Ceballos5, Soledad Fiorentino3,
Maria Jezabel Haye Salinas4, Nadia Riscanevo6, Janet Flores7, Ana C. Alvarez4, Verónica Saurit8, Alejandro Alvarellos8
and Francisco Caeiro9, 1Reumatologia, Hospital Privado Universitario de Córdoba, Córdoba, Argentina, 2Rheumatology
Unit, Hospital Privado Universitario de Córdoba, Institute University of Biomedical Sciences University of Córdoba
(IUCBC), Cordoba, Argentina, 3Rheumatology, Rheumatology Unit, Hospital Privado Universitario de Córdoba., Cordoba,
Argentina, 4Rheumatology, Rheumatology Unit, Hospital Privado Universitario de Córdoba, Córdoba, Argentina,
5Rheumatology, Rheumatology Unit, Hospital privado Universitario de Córdoba., Cordoba, Argentina, 6Rheumatology,
Rheumatology Unit, Hospital privado Universitario de Córdoba, Cordoba, Argentina, 7Rheumatology Unit, Hospital
privado Universitario de Córdoba, Cordoba, Argentina, 8Rheumatology, Rheumatology Unit, Hospital Privado
Universitario de Córdoba, Cordoba, Argentina, 9Rheumatology, Hospital Privado Centro Médico de Córdoba, Córdoba,
Argentina
SESSION INFORMATION
Background/Purpose:
Labial salivary gland biopsy (LSGB) is a minimally invasive procedure used in the diagnostic of Sjögren's Syndrome (SS).
Objectives: to describe demographic, clinical and histological features of patients submitted to LSGB; to analyze the
usefulness of LSGB in diagnosis of primmary SS (pSS) and secondary SS (sSS); to assess the association between
histological findings and autoantibodies; to compare the sensitivity (Sn) and specificity (Sp) of the American-European
2002 (AE02) and ACR 2012 criteria.
Methods:
An observational, analytical, cross-sectional study was performed. A total of 803 patients were included between June 1996
and May 2016. A sub analysis of 674 patients was performed, excluding those with SSs and others without antibodies.
Grades III and IV biopsy of the Chisholm and Mason´s (CM) classification were considered positive. Data was analyzed
using STATA 17 software.
Results:
803 patients were included, 90% females. The mean age was 53 years (range 14-86). PSS was diagnosed in 238 (29.6%),
and SS in 45 (5.6%), with female predominance in both groups (30.1% and 5.8%, respectively). Table 1 shows the clinical
characteristics and complementary studies in patients with nonspecific dryness syndrome (NoSS) and SSP and SS.
Table 1.
Parameters n (%) NoSS PSS SSS P value

n(%) n(%) n(%)
Xerostomía 399 200 39 0.019
(76.6) (84) (88.6)
Xerophthalmia 447 220 36 0.018
(85.8) (92.4) (81.8)
Abnormal ophtalmic test 209 175 28 <0.01
(67.4) (96.2) (96.6)
Abnormal parotid 31 (52.5) 24 (75) - 0.036
sialography
Ro/SS-A 11 (2.4) 73 13 <0.01
(32.7) (32.5)
La/SS-B - <0.01
31 (14) 3 (7.5)
ANA 61 (12.4) <0.01
116 20
RF 81 (16.4) (49.6) (48.8) <0.01
96 31
(41.6) (73.8)
LSGB G III-IV 8 (1.5) 217 26 <0.01
(91.2) (59.1)
Pilocarpine 21 (4.04) 57 2 (4.6) <0.01
(24.1)
Hydroxychloroquine 43 (8.3) 26 (59) <0.01
206
Prednisone <20mg 68 (65) (86.9) 30 (5.5) <0.01
Prednisone >20 mg 6 (1.5) 68 6 (13.6) <0.01

(29.5)
Rituximab 2 (0.4) 1 (2.3) 0.27
3 (1.5)
Other immunosuppressive 64 (15.7) 38 <0.01
drug 2 (0.9) (86.4)
171
(72.8)
In the subanalysis of 674 patients, 33.1% were pSS, of which 204 (91.5%) were female. The mean age was 54 years (range
14-86). LSGB was 0, I or II grades in 8.5% patients with PSS, versus 91.5% patients with III-IV grades (p <0.01); Sn
91.5%, Sp 98.5%, positive predictive value (PPV) 96.7, negative predictive value (NPV) 95.9. Table 2 compares the
serological characteristics of patients using LSGB as a "gold standard".
Table 2.
Parameters LSGB LSGB p Sensitivity Specificity PPV NPV LR

(+) (-)
Ro/SS-A 58 26 (31) <0.01 27.5 94.4 69.1 74.1 4.9
(27.5)
La/SS-B 24 7 (1.5) <0.01 11.4 98.5 77.4 70.9 7.5
(11.4)
ANA 97 71 <0.01 46.4 84.6 57.7 77.6 3
(46.4) (15.4)
RF 84 78 <0.01 40.8 83 51.9 75.7 2.4
(40.8) (48.2)
In multivariate analysis the significance for anti-Ro (OR: 2.0), ANA (OR: 2.9) and RF (OR: 2.5) was maintained.
The AE02 criteria had a Sn of 32.3%, Sp 97.3%, PPV 85.7% and NPV 74.4%.
The ACR 2012 had a Sn of 83.4%, Sp 98.5%, PPV 96.4% and NPV 92.3%.
Conclusion:
LSGB is a simple, safe, and useful tool for the diagnosis of Sjögren's syndrome. It exhibits an adequate balance between
Sn, Sp, PPV and NPV..
Antibodies showed a significant association with a positive LSGB with low Sn for pSS screening but high Sp.The LSGB
had a great value in "seronegatives patients".
Disclosure: D. Baenas, None; S. Retamozo, None; J. P. Pirola, None; N. Benzaquén, None; M. F. Ceballos, None; S.
Fiorentino, None; M. J. Haye Salinas, None; N. Riscanevo, None; J. Flores, None; A. C. Alvarez, None; V. Saurit,
None; A. Alvarellos, None; F. Caeiro, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/biopsy-accuracy-in-sjogrens-syndrome-

analysis-of-803-patients-presenting-with-sicca-syndrome-referred-to-labial-salivary-gland-biopsy
Subepithelial Infiltrate of the Vagina in Primary Sjogren’s Syndrome: The

Cause of Vaginal Dryness?
Jolien F. van Nimwegen1, Karin van der Tuuk2, Ellen R. Klinkert2, Erlin A. Haacke3, Frans G.M. Kroese1, Harry
Hollema3, Marian J. Mourits2 and Hendrika Bootsma1, 1Rheumatology and Clinical Immunology, University of
Groningen, University Medical Center Groningen, Groningen, Netherlands, 2Obstetrics and Gynaecology, University of
Groningen, University Medical Center Groningen, Groningen, Netherlands, 3Pathology and Medical Biology, University of
Groningen, University Medical Center Groningen, Groningen, Netherlands
SESSION INFORMATION
Background/Purpose: Women with primary Sjögren’s syndrome (pSS) often experience vaginal dryness. The cause of this
symptom is unknown. This study compared the vaginal and cervical health of women with pSS and controls, using clinical
and histopathological parameters.
Methods: Consecutive premenopausal women with pSS according to the AECG and ACR-EULAR criteria, with
symptoms of vaginal dryness, and age-matched controls planned for a risk-reducing salpingo-oophorectomy underwent a
vaginal examination. Excluded were women with an inflammatory or infectious gynaecological disease, intra-uterine
contraceptive device, or use of hormone therapy or DMARDs. Participants were screened for chlamydia, gonorrhea, and
vaginal bacterial and fungal infections. The vaginal health index was recorded, which consists of 5 domains (elasticity,
fluid secretion, pH, epithelial mucosa, moisture). Each domain was scored on a scale of 1-5, resulting in a score of 5-25.
Low scores correspond to low vaginal health. In pSS patients, vaginal and endocervical biopsies were taken under local
anesthesia. In controls, the investigation was performed under general anesthesia, prior to surgery. Formalin fixed and
paraffin embedded tissue sections were stained for HE and CD45 (leucocytes) and examined by a dedicated
gynaecopathologist. The percentage of area stained for CD45 was calculated with Aperio ImageScope v12.0. Groups were
compared using Mann-Whitney U test.
Results: A total of 9 pSS patients and 5 controls were included so far. One pSS patient was excluded from the analysis due
to presence of Chlamydia trachomatis. Median age was 35 years (IQR 30-46) in pSS patients and 37 years (IQR 36-42) in
controls (p=0.62). Median vaginal health index was lower in pSS patients (18.5, range 14-23) compared to controls (23.0,
range 20-23, p=0.019). In the HE staining of the vaginal tissue, a mild (n=6) or moderate (n=2) infiltrate was seen in all
pSS patients. In controls, no infiltrate (n=3) or a mild infiltrate (n=2) was seen in the vaginal tissue. Infiltrates were mainly
located in the subepithelial layer, with aggregates in dermal papillae (figure 1). The median percentage of area stained for
CD45 in the vagina was higher in pSS patients (2.0%, range 1.0-5.0%) compared to controls (1.4%, range 0.4-1.4%,
p=0.03). Endocervical tissue was obtained in 5 pSS patients and in 3 controls. In the HE staining of the endocervical tissue,
moderate or severe infiltrates were seen in 3 pSS patients, and a moderate infiltrate in 1 control. The median percentage of
area stained for CD45 in the endocervix did not differ between groups (patients 4.4%, range 1.1-28.3%; controls 3.2%,
range 2.0-13.0%, p=1.00).
Conclusion: In this preliminary analysis, pSS patients show a lower vaginal health index and a higher percentage of
subepithelial infiltrate in the vagina compared to controls, while endocervical histopathology did not differ. Detailed
phenotypic evaluation of the infiltrate will follow.
Disclosure: J. F. van Nimwegen, None; K. van der Tuuk, None; E. R. Klinkert, None; E. A. Haacke, None; F. G. M.
Kroese, None; H. Hollema, None; M. J. Mourits, None; H. Bootsma, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/subepithelial-infiltrate-of-the-vagina-in-

primary-sjogrens-syndrome-the-cause-of-vaginal-dryness
Is Elastography a New Tool to Differentiate Sjögren Syndrome to Sicca

Syndrome?: Results of the Elsa (elastography of salivary glands) Study
Sandrine Jousse-Joulin1, luc Bressollette2, thibault depinoy3, guillermo carvajal Alegria3, Divi Cornec4, Thierry
Marhadour5, Dewi Guellec6, Valérie Devauchelle-Pensec7 and Alain Saraux8, 1Rheumatology, CHu La cavle Blanche,
Brest, France, 2Doppler unit, Cavale Blanche hospital, brest, France, 3rheumatology department, cavale blanche hospital,
brest, France, 4CHU Brest, Brest, France, 5Rheumatology, CHU La Cavale Blanche, Brest, France, 6Rheumatology, CHU
Brest, Brest, France, 7Rheumatology, Brest university medical school, EA 2216, Lab Ex, INSERM, IGO,UBO and CHU de
la Cavale Blanche,, Brest, France, 8Rheumatology, Brest University Medical School Hospital, Brest, France
SESSION INFORMATION
Background/Purpose:
Ultrasonography (US) has been developed in salivary glands (SG) and particularly in primary Sjögren syndrome (pSS) for
10 years. However, the training curve is long and the reliability is not completely achieved (1). A new tool procedure has
been developed to study the elasticity of the tissue parenchyma using elastography and could be implemented in the
evaluation of SGUS pSS patients. The objective was to evaluate SGUS using grey scale (GS) and the elasticity salivary
glands parenchyma using elastography to differentiate pSS from sicca syndrome (SS) patients in a longitudinal consultation
of sicca syndrome in Doppler Unit of Brest (France).
Methods: 63 patients complaining of sicca syndrome were enrolled in the ELSA study. At inclusion, all patients underwent
a standardized workup including a clinical evaluation, laboratory tests, SG histology, SGUS and elastography.
Immunological testing included: anti-nuclear antibodies, anti-SSA (recognizing both Ro 52 and 60 kDa), anti SSB, native
anti-DNA, ANCA, rheumatoid factors and anti-CCP. A Toshiba Applio machine was used to evaluate in GS SGUS
parenchyma and elastography -elastometry. The 6 main SG were examined in US according to previous scoring (2)
elastography (with color map) and elastometry (in cm/sec) and :left parotid gland (USLPG), left submandibular gland
(USLSMG), left sublingual gland (USLSLG), right parotid gland, (USRPG) right submandibular gland (USRSMG), right
sublingual gland (USRSLG).
Results: 15 patients fulfilled the AECG criteria. The clinical characteristics of the patients in terms of ocular dryness and
shirmer test were not significant between pSS and Sicca patients. There was a significant difference (p= 0.04) concerning
oral dryness (p=0.04), immunological datas: Antinuclear antibodies and anti SSA and minor salivary glands biopsy
(p=0.007). We found significant differences between the 2 groups in GS for the USLPG (p=0.021) and USLSMG (p=0.05).
Evaluation of sublingual glands using US in grey scale and elastometry of the 6 SG showed no significant differences
between the two groups.
Conclusion: Grey scale SGUS seems to be more sensitive to differentiate pSS to Sicca patients compared to elastometry.
US of sublingual glands showed no involvement in the echostructural damage in pSS patients and suggest not examining
these glands in the USpSS evaluation. Elastometry has been described to be a new tool and might be added as a new
imaging technique to ultrasonography in pSS patients (3). However, ELSA study results showed no differences between
pSS and Sicca patients. We need to follow the evolution of the Sicca population with US in GS and elastometry to detect
potential echostrural parenchymal damage which might not yet be present at inclusion.
Disclosure: S. Jousse-Joulin, None; L. Bressollette, None; T. depinoy, None; G. carvajal Alegria, None; D. Cornec,
None; T. Marhadour, None; D. Guellec, None; V. Devauchelle-Pensec, None; A. Saraux, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/is-elastography-a-new-tool-to-

differentiate-sjogren-syndrome-to-sicca-syndrome-results-of-the-elsa-elastography-of-salivary-glands-study
Distinct Clinical and Immunological Features of Anti-Centromere Antibody

Positive Primary Sjögren’s Syndrome: A Single Center Cross-Sectional
Cohort Study
Masako Tsukamoto1,2, Katsuya Suzuki1, Noriyuki Seta2 and Tsutomu Takeuchi1, 1Division of Rheumatology,
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, 2Department of Internal Medicine,
Tokyo Dental College Ichikawa General Hospital, Ichikawa, Japan
SESSION INFORMATION
Background/Purpose: Anti-centromere antibody (ACA) positive Sjögren’s syndrome (SS) is considered as a subtype in
SS. Recent international collaborative large scale cohort study highlighted several clinical features such as Raynaud’s
phenomenon、 sclerodactyly and extra glandular dysfunction (Arthritis Care Res. 2016). Assessment of ACA is potentially
valuable for definitive diagnosis of this subtype and medical management in a certain number of patients uncovered by
current 2015 ACR/EULAR classification criteria. However, enough information of clinical and immunological features of
ACA positive SS has not been accumulated and clinical significance of ACA in SS may not be fully established. The aim
of this study is to clarify clinical and immunological features of ACA positive SS.
Methods: All patients with primary SS (pSS) who visited to our Division of Rheumatology at Keio University Hospital in
Tokyo between May 1995 and December 2016 were enrolled. Clinical information and immunological tests including
immunoglobulin (Ig) and serum autoantibodies were collected and statistically analyzed.
Results: Five hundred and ninety nine patients were clinically classified as pSS (female: 93%, mean age: 55 ± 15). They
were divided into 4 groups by serum ACA and anti-SS-A antibody status. Only discrete-speckled pattern in anti-nuclear
antibody (ANA) test and/or anti-centromere antibody positive (ACA alone) were detected in 39 patients (6.5%), while only
anti-SS-A antibody with no ACA (SS-A alone) were detected in 449 patients (75.0%). Number of patients with both ACA
and SS-A (Double positive) was 40 (6.7%), while 67 patients had neither ANA nor SS-A (Seronegative). Then we
statistically compared these 4 groups. The proportions of Raynaud’s phenomenon or sclerodactyly were higher in ACA
alone and Double positive groups (p<0.01 or p<0.01). The proportion of dryness was no difference among 4 groups. The
proportions of increase of serum IgG or IgA were 15% or 7% in ACA alone group, 61% or 20% in SS-A alone group, 50%
or 28% in Double positive group and 22% or 4% in Seronegative group (p<0.01 or p<0.01). Existence of anti-SS-A
antibody, not ACA associated to high concentration of IgG or IgA, while there was no difference between 4 groups as IgM
(p=0.40). Regarding C3, C4 or CH50, there were no differences among 4 groups. Remarkably, the proportion of
leukocytopenia in ACA alone group was significantly higher than the others (p=0.02). As compared with pulmonary,
cardiac or articular involvements, no differences were found among 4 groups. Importantly the proportion of patients who
had facial erythema was significantly lower in ACA positive SS (p<0.01).
Conclusion: Our large-scale study identified distinct characteristics of ACA-positive SS patients different from anti-SS-
A/Ro antibody positive or seronegative SS patients in Japanese population.
Disclosure: M. Tsukamoto, None; K. Suzuki, None; N. Seta, None; T. Takeuchi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/distinct-clinical-and-immunological-

features-of-anti-centromere-antibody-positive-primary-sjogrens-syndrome-a-single-center-cross-sectional-cohort-study
Immunosignature-Based Diagnosis and Prediction of Therapeutic Response

Enables Retrospective Patient Stratification in a Phase IIa Clinical Trial for
VAY736 in Primary Sjögren’s Syndrome
Robert Gerwien1, Theodore M. Tarasow2, Jonathan Melnick2, Anna Lei3, Arvind Kinhikar4, Julie Doucet5, Remi
Kazma5, Paul Maguire4, Irina Koroleva6, Giulio Macchiarella4, Alexandre Avrameas5, Marie-Anne Valentin5, Stephen
Oliver5 and Alessandra Vitaliti5, 1HealthTell, Inc, san ramon, CA, 2HealthTell, Inc., San Ramon, CA, 3Health Tell, San
Ramon, CA, 4Novartis, Cambridge, MA, 5Translational Medicine, Novartis Institutes for Biomedical Research, Basel,
Switzerland, 6Novartis Institutes for BioMedical Research, Novartis Pharma AG, Cambridge, MA
SESSION INFORMATION
Background/Purpose: Although patient stratification can improve the success rate of clinical trials, efforts to apply this
strategy to autoimmune studies such as Sjögren’s syndrome are hindered by the nature of this disease area, intra-disease
patient diversity, difficulties around diagnostic criteria and response metrics, as well as the lack of clear biological
mechanisms to explain drug efficacy. In some of the diseases, the nexus of these variables is B-cell biology.
Methods: The ImmunoSignature Technology — the semi-quantitative profile of antibody binding specificity — is
designed to enable patient stratification in autoimmune disease trials. HealthTell’s unique approach to peptide microarray
fabrication, combining silicon wafer-based photolithographic synthesis with optimized peptide coupling chemistry and
MALDI-based quality control, permits high-throughput ImmunoSignaturing with exceptional scalability, reproducibility
and accuracy, making it broadly-applicable to diagnostic, clinical and discovery applications. In this study, HealthTell’s
ImmunoSignature platform was applied to key steps in a clinical trial (NCT02149420) with VAY736, an anti-B cell
activating factor (BAFF) receptor monoclonal antibody, in patients with primary Sjögren’s Syndrome.
Results: The ImmunoSignature distinguished Sjögren’s patients from healthy volunteers with an AUC of 0.84, with
individual peptides showing a correlation to the EULAR Sjögren’s syndrome disease activity index (ESSDAI) of up to 0.74
(Pearson’s r). Using serum collected prior to treatment, the ImmunoSignature predicted which patients will respond to
study drug with a drop in ESSDAI of ≥3, yielding an AUC of 0.75 from a small study (18 treated patients with 9 placebo).
Response to therapy performance was also measured using sera drawn 12 weeks post treatment and resulted in an AUC of
0.84. Using the 12-week sample, principle component analysis correctly segregated drug-treated responders from drug-
treated non-responders, placebo non-responders and the single placebo-responsive patient. Alignment of the peptides that
comprise these contrasts to the human proteome yields not only known Sjögren’s autoantigens but also potential novel
biomarkers.
Conclusion: The Immunosignature identified in this study is important for disease diagnosis and explanation of study drug
response.
Disclosure: R. Gerwien, HealthTell, 3; T. M. Tarasow, HealthTell, 3,HealthTell, 1; J. Melnick, HealthTell, 3,HealthTell,

1; A. Lei, HealthTell, 3; A. Kinhikar, Novartis Pharmaceutical Corporation, 3; J. Doucet, Novartis Pharma AG, 3; R.
Kazma, Novartis Pharma AG, 3; P. Maguire, Novartis Pharmaceutical Corporation, 3; I. Koroleva, Novartis
Pharmaceutical Corporation, 3; G. Macchiarella, Novartis Pharmaceutical Corporation, 3; A. Avrameas, Novartis Pharma
AG, 3; M. A. Valentin, Novartis Pharma AG, 3; S. Oliver, Novartis Pharma AG, 3; A. Vitaliti, Novartis Pharma AG, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/immunosignature-based-diagnosis-and-

prediction-of-therapeutic-response-enables-retrospective-patient-stratification-in-a-phase-iia-clinical-trial-for-vay736-in-
primary-sjogrens-syndrome
The Value of C-Reactive Protein As a Predictor of Radiographic Spinal

Progression Is Strongly Dependent on β-Fibrinogen and Factor XIII a-
Subunit Genotypes in Patients with Axial Spondyloarthritis
Denis Poddubnyy1,2, Christian Schwedler2, Hildrun Haibel2, Martin Rudwaleit2,3, Joachim Sieper2 and Berthold Hoppe4,
1German Rheumatism Research Centre, Berlin, Germany, 2Charité Universitätsmedizin Berlin, Berlin, Germany,
3Klinikum Bielefeld Rosenhöhe, Bielefeld, Germany, 4Unfallkrankenhaus Berlin, Berlin, Germany
SESSION INFORMATION
Session Title: Spondyloarthropathies and Psoriatic Arthritis – Clinical Aspects and Treatment Poster I
Background/Purpose:
It has been shown in the past that inflammatory activity (i.e., elevated C-reactive protein) predicts radiographic spinal
progression in patients with axial spondyloarthritis (axSpA). Fibrinogen and factor 13 genotypes have been recently
identified as factors modifying inflammatory response due to differences in the properties of the fibrin network related to
particular genotype constellations [1].
The objective of the current study was to investigate the association between α-fibrinogen (FGA), β-fibrinogen (FGB) and
factor XIII A-subunit (F13A) genotypes with the level of CRP and radiographic spinal progression over 2 years in patients
with early (up to 10 years symptom duration) axial SpA.
Methods:
Altogether 207 patients with early axial SpA from the German Spondyloarthritis Inception Cohort (GESPIC) were
included. Clinical data and CRP level were collected at baseline and every 6 months thereafter. A time-averaged CRP level
over 2 years (up to 5 time-points) was calculated. Structural damage in the spine was assessed on spinal radiographs at
baseline and after two years according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Significant
radiographic spinal progression was defined as the worsening of the mSASSS by ≥2 points over two years. FGB −455G>A
(rs1800790), FGA T312A (rs6050) and F13A V34L (rs5985) genotypes were determined with available samples using
allele-specific primer pairs.
Results:
No clear association between studied genotypes and the time-averaged CRP or radiographic spinal progression could be
found. However, the effect of CRP in the predictive model for radiographic spinal progression was strongly dependent on
FGB genotype (table): the odds ratio (OR) for the elevated time-averaged CRP as a predictor of the mSASSS worsening by
≥2 points over two years was 5.47 (95%CI 1.51-19.79) in FGB −455GG (wild-type) carriers, while there was no such
effect of CRP in carriers of the alternative (A) allele, OR=0.99 (95%CI 0.20-4.92). Interestingly, this effect modification
was dependent also on F13A genotype: in carriers of the wild-type genotypes of both FGB (−455GG) and F13A (34VV),
n=65, the OR for the elevated CRP as a predictor of radiographic spinal progression was 10.8 (95%CI 1.07-108.0), while
alternative allele carriers (F13A 34L) showed a weak and non-significant association of CRP with radiographic spinal
progression even in the presence of the wild-type FGB genotype (n=59): OR=2.01 (95%CI 0.34-12.04). F13A itself as well
as FGA genotypes showed no effect-modifying effects on CRP.
Conclusion:
The predictive value of CRP regarding radiographic spinal progression seems to be dependent on FGB and F13A
genotypes. This might also suggest that CRP is not a good indicator of inflammation in individuals with a specific genetic
background.
References:
1. Hoppe B, et al. Ann Rheum Dis. 2012 Jul; 71(7):1163-1169.

Disclosure: D. Poddubnyy, None; C. Schwedler, None; H. Haibel, None; M. Rudwaleit, None; J. Sieper, None; B.
Hoppe, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-value-of-c-reactive-protein-as-a-

predictor-of-radiographic-spinal-progression-is-strongly-dependent-on-%ce%b2-fibrinogen-and-factor-xiii-a-subunit-
genotypes-in-patients-with-axial-spondyloarthriti
Added Value of Biomarkers Compared to Routine Clinical Parameters for

the Prediction of Radiographic Spinal Progression in Axial Spondyloarthritis
Lorraine Tietz1, Lien Le2, Agnes Hartl1, Martin Rudwaleit1,3, Joachim Sieper1, Ulrich Mansmann2 and Denis
Poddubnyy1,4, 1Charité Universitätsmedizin Berlin, Berlin, Germany, 2Ludwig-Maximilian University, Munich, Germany,
3Klinikum Bielefeld Rosenhöhe, Bielefeld, Germany, 4German Rheumatism Research Centre, Berlin, Germany
SESSION INFORMATION
Background/Purpose:
Structural damage in the spine is an important determinant of the functional status and spinal mobility in axial
spondyloarthritis (axSpA). Already present syndesmophytes, elevated C-reactive protein, cigarette smoking, and to a lesser
extent male sex are routine clinical parameters predicting radiographic spinal progression in axSpA. In the last years,
several biomarkers with a predictive value for radiographic spinal progression were identified. It is, however, not known, if
biomarkers have a meaningful added value over clinical parameters in prediction of radiographic spinal progression in
axSpA.
The objective of the study was to examine whether adding biomarkers to the routine clinical parameters would improve
prediction of radiographic spinal progression in axSpA.
Methods:
Altogether 120 patients with radiographic axSpA who completed a 2-year clinical and radiographic follow-up in the
ENRADAS trial were included. Structural damage in the spine was assessed on spinal radiographs at baseline and year 2
according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Radiographic spinal progression was
defined as a worsening of the mSASSS by ≥2 points after 2 years. Clinical predictors of radiographic spinal progression at
baseline included syndesmophytes, elevated (>5mg/L) CRP, cigarette smoking, and sex. Serum biomarkers measured at
baseline included: matrix metalloproteinase-3, vascular endothelial growth factor (VEGF), calprotectin, leptin, high
molecular weight adiponectin (HMW-APN), ostoprotegerin, sclerostin, N-terminal telopeptide, procollagen type II N-
terminal propeptide, and serum amyloid A (SAA).
Results: Repeated cross-validation analysis revealed two biomarker combinations: (1) Leptin + HWM-APN + VEGF +
Sclerostin and (2) Leptin + HWM-APN + VEGF+ SAA with added predictive value compared to the clinical model
(syndesmophytes, smoking, elevated CRP, and sex). Adding these biomarker combinations to the clinical model resulted in
improvement of the predictive value reflected by the Area Under the Curve (AUC): AUCClinical+Biomarkers(1)=0.765
(95%CI 0.664-0.867) and AUCClinical+Biomarkers(2)=0.775 (95%CI 0.674-0.876) vs. AUCClinical=0.656 (95%CI 0.546-
0.766) – figure. The average prediction error (APE) of the Clinical+Biomarker(1) and Clinical + Biomarker(2) models
were 0.227 and 0.229, respectively as compared to the APE for the pure clinical model (0.248). These findings were
supported by the results of stability analyses.
Conclusion:
Biomarkers are able to improve prediction of radiographic spinal progression in axSpA if used in addition to the clinical
parameters, but the added value seems to be rather small.
Disclosure: L. Tietz, None; L. Le, None; A. Hartl, None; M. Rudwaleit, None; J. Sieper, None; U. Mansmann, None;
D. Poddubnyy, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/added-value-of-biomarkers-compared-

to-routine-clinical-parameters-for-the-prediction-of-radiographic-spinal-progression-in-axial-spondyloarthritis
Circulating MiR-145 As a Marker of Therapeutic Response to Anti-TNF

Therapy in Patients with Ankylosing Spondylitis
Klára Prajzlerová1, Veronika Hruskova1, Martin Komarc2, Šárka Forejtová1, Karel Pavelka3, Jiri Vencovsky3, Ladislav
Senolt3 and Maria Filkova1, 1Institute of Rheumatology and Department of Rheumatology, 1st Faculty of Medicine,
Charles University, Prague, Czech Republic, Prague, Czech Republic, 2Department of Anthropometrics and Methodology,
Faculty of Physical Education and Sport, Charles University, Prague, Czech Republic, Prague, Czech Republic, 3Institute
of Rheumatology, Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic,
Prague, Czech Republic
SESSION INFORMATION
Background/Purpose: The altered expression of miRNAs contributes to the pathophysiology of inflammatory conditions.
In addition, circulating miRNAs may serve as promising therapeutic and prognostic biomarkers. Our aim was to investigate
the effect of anti-TNF therapy on the levels of circulating miRNAs in patients with ankylosing spondylitis (AS).
Methods: Our study included 19 AS patients. Disease activity scores (ASDAS-CRP, BASDAI) and laboratory parameters
of disease activity were obtained at baseline (M0), month 3 (M3) and 12 (M12) after initiation of anti-TNF therapy. Total
RNA was isolated from plasma using miRNeasy Serum/Plasma Kit (Qiagen). A comprehensive analysis of miRNAs was
performed using TaqMan Low Density Array (TLDA) in 3 patients at M0, M3 and M12. dCt method was used for relative
quantification: dCt=Ct(miRNA)–Ct(array average). Seventeen miRNAs with >1.5-fold change in the expression prior and
after the therapy initiation in all 3 samples were selected for next validation using single assays. The levels of miRNAs in
validation measurements were normalized to an average of 3 spike-in controls of C. elegans origin: dCt=Ct(spike-in
average)-Ct(miRNA). Data were analyzed using ANOVA with Bonferroni corrections and Spearman’s correlation
coefficient.
Results:
All AS patients had high disease activity (BASDAI 6.3±1.5, ASDAS 4.1±0.7, CRP 32.5±28.9mg/l, ESR 40.1±19.6mm/h)
prior commencing anti-TNF therapy with a good therapeutic response at M3 (BASDAI 2.8±1.2, ASDAS 2.15±0.65, CRP
9.8±13.6mg/l, ESR 15.2±21.3mm/h, p<0.001 for all comparisons) and M12 (BASDAI 2.3±1.7, ASDAS 1.9±0.9, CRP
7.4±9.6mg/l, ESR 13.7±12.2mm/h, p<0.001 for all comparisons).
Out of all 380 miRNAs analyzed by TLDA, 125 miRNAs were detected in all samples, 148 miRNAs were detected at M0,
154 at M3 and 151 at M12. Validation of 17 selected miRNAs confirmed significant downregulation of miR-145 at M3
(TLDA 1.59-change; single assays 1.62-change, p=0.024), but the downregulation did not reach statistical significance at
M12 (TLDA 1.46-change; single assays 1.11-change, p>0.05)
At baseline, miR-145 positively correlated with VAS (r=0.450, p=0.048). In addition, the decrease in miR-145 expression
from M0 to M3 significantly correlated with disease activity improvement over time from M3 to M12 as per BASDAI
(ΔBASDAI M3/12=-0.50±1.93, r=0.670, p=0.002) and ASDAS scores (ΔASDAS M3/12=-0.28±0.70, r=0.614, p=0.005)
and VAS at M12 (r=0.528, p=0.020). In line with this observation, high levels of miR-145 at M3 significantly correlated
with disease activity worsening based on an increase in ASDAS from M3 to M12 (r=0.595, p=0.007) and higher ASDAS
(r=0.535, p=0.018) and VAS (r=0.564, p=0.012) at M12.
Conclusion:
We propose that an early change in miR-145 levels may be a predictor of future outcome of AS patients as it’s early
decrease after anti-TNF initiation correlated with further disease activity improvement. These data, similarly to previous
studies showing correlation of miR-145 with CRP and pro-inflammatory IL-6 (Cell Biochem Funct. 2015;33(5)), suggest
potential use of circulating miRNAs as biomarkers of treatment response in AS.
Acknowledgement: Grant projects 17-33127A and SVV 260373.

Disclosure: K. Prajzlerová, None; V. Hruskova, None; M. Komarc, None; Š. Forejtová, None; K. Pavelka, None; J.
Vencovsky, None; L. Senolt, None; M. Filkova, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/circulating-mir-145-as-a-marker-of-

therapeutic-response-to-anti-tnf-therapy-in-patients-with-ankylosing-spondylitis
Tenascin-C, a TLR 4 Endogenous Ligand Levels Are Increased in Ankylosing

Spondylitis
Latika Gupta, Shruti Bhattacharya and Amita Aggarwal, Clinical Immunology, Sanjay Gandhi Postgraduate Institute of
Medical Sciences, Lucknow, India
SESSION INFORMATION
Background/Purpose:
Monocytes of patients with Ankylosing Spondylitis (AS) over-express Toll-like receptor (TLR) 4 on their monocytes.
Tenascin-C (TNC) is an extracellular-matrix-glycoprotein and acts as an endogenous TLR4 ligand. Thus we studied the
serum and synovial fluid levels of TNC in adults with AS.
Methods:
TNC was measured in serum of 36 AS patients (ASAS 2009 criteria) and 10 healthy controls by ELISA. 22 patients were
followed-up after 3 months of standard of care treatment. Five paired serum-synovial fluid samples were also analyzed.
Disease activity was assessed by BASDAI, ASDAS, tender and swollen joint count; enthesitis score, ESR and CRP. All
values are in median (IQR).
Results:
Median age was 30 (20-35) years and disease duration 5.5(1.3-10) years. 31 were male and 5 female. 25 cases had
peripheral arthritis (69.5%). Median BASDAI was 5.3(3.3-6.7). HLA B27 was positive in 34 (94.5%) cases.
Median serum Tenascin C levels were higher in AS [554.6ng/ml] as compared to healthy controls [32.88 ng/ml,
p<0.00001]. Serum TNC levels correlated with ASDAS ESR [r=0.367, p=0.028] and ESR [r=0.39, p=0.035]; but not with
other disease activity measures. In patients with disease duration less than 5 years (early disease) serum levels had better
correlation with ESR [r=0.59, p=0.009] and CRP [r=0.479, p=0.044]. On ROC analysis for active (PhGA≥6) vs. inactive
(PhGA≤4) disease, TNC (AUC=0.60) performed as well as CRP (AUC=0.65) and ESR (AUC=0.73). The synovial fluid
levels [11.61(5.99-176.9) ng/ml] were lower than in the serum [627.4 (488.5-779.1) ng/ml, p=0.008].
TNC levels fell with treatment [630.8 ng/ml to 376.4 ng/ml p=0.0006] in treatment responders (n=11) but not in non-
responders (n=11) [562.3 to 445.6,p=0.33].
Conclusion:
Serum TNC levels are significantly raised in AS and can serve as marker of inflammation in early disease. Treatment
reduces the TNC levels, probably due to control of disease activity.
Disclosure: L. Gupta, none, 2; S. Bhattacharya, None; A. Aggarwal, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/tenascin-c-a-tlr-4-endogenous-ligand-

levels-are-increased-in-ankylosing-spondylitis
Diagnostic Value of Anti-CD74 Antibodies in Early Axial Spondyloarthritis:

Data from the Spondyloarthritis Caught Early (SPACE) Cohort
Janneke de Winter1, Marleen van de Sande1, Niklas Thomas Baerlecken2, Inger Berg3, Roberta Ramonda4, Désirée van
der Heijde5, Floris van Gaalen6, Torsten Witte7 and Dominique Baeten1,8, 1Clinical Immunology and Rheumatology,
Amsterdam Rheumatology and immunology Center, Academic Medical Center/University of Amsterdam, Amsterdam,
Netherlands, 2Rheumatology, Private Practice, Cologne, Germany, 3Rheumatology, Diakonhjemmet Hospital, Oslo,
Norway, 4Rheumatology Unit, Department of Medicine DIMED, University of Padova, Padova, Italy, 5Rheumatology,
Leiden University Medical Center, Leiden, Netherlands, 6Leiden University Medical Center, Leiden, Netherlands, 7Clinical
Immunology and Rheumatology, Medical University Hannover, Hanover, Germany, 8UCB Pharma, Slough, United
Kingdom
SESSION INFORMATION
Background/Purpose:
Anti-CD74 IgG antibodies are reported to be elevated in serum of patients with axial spondyloarthritis (axSpA). This study
aimed to assess the diagnostic value of anti-CD74 antibodies to discriminate between early axSpA and non-SpA in early
back pain patients.
Methods:
Using ELISA, we first confirmed the elevation of anti-CD74 IgG and IgA serum antibodies in patients with radiographic
axSpA (ankylosing spondyloarthritis, (AS)) (n=138) when compared to healthy controls (n=57). Next, we tested their
diagnostic value in patients with early axSpA (n=274) and non-SpA back pain controls (n=319) from the SPondyloArthritis
Caught Early (SPACE) cohort.
Results:
Median anti-CD74 IgG antibodies (OD) were higher in AS patients than in healthy controls (0.70 vs. 0.51, p<.0001) and
present in 79.7% of AS patients vs. 43.9% of healthy controls (p<0.0001). Anti-CD74 IgG antibody levels (OD) did not
differ between axSpA patients and non-SpA back pain controls (0.50 vs. 0.52, p=0.152) and were present in 46.4% of the
axSpA patients vs. 47.9% of the non-SpA back pain controls (p=0.713). Median anti-CD74 IgA antibodies (OD) were
higher in AS patients than in healthy controls (0.31 vs. 0.20, p<0.0001) and present in 28.5% of AS patients vs. 5.3% of
healthy controls (p<0.0001). In the SPACE cohort, anti-CD74 IgA antibodies (U/mL) were higher in axSpA patients than in
non-SpA back pain controls (19.92 vs. 14.02, p<0.0001) and present in in 54.7% vs. 37.0% of the axSpA patients vs. non-
SpA back pain controls (p<0.0001), respectively. This resulted in a PPV of 58.8% and a NPV of 59.1%. In a multivariate
logistic regression model including anti-CD74 IgA and total serum IgA, total serum IgA was associated with a diagnosis of
axSpA (Exp(B) 1.19, p<0.0001) whereas anti-CD74 IgA was not (Exp(B) 1.01, p=0.332).
Conclusion:
Anti-CD74 IgG and anti-CD74 IgA were elevated in AS versus healthy controls. Only anti-CD74 IgA is elevated in
patients with early axSpA versus chronic back pain controls of the SPACE cohort. In the SPACE cohort, these differences
disappear in a multivariate analysis with total IgA levels and have limited diagnostic value in these early back pain patients.
Other biomarker or biological features of anti-CD74 IgA, including prediction/contribution to radiographic progression,
should be investigated.
Disclosure: J. de Winter, None; M. van de Sande, Takeda, Tillots, MSD, Abbvie,novartis, boeringer ingelheim, 8,Takeda,
Tillots, MSD, Abbvie,novartis, boeringer ingelheim, 2,Takeda, Tillots, MSD, Abbvie,novartis, boeringer ingelheim, 5; N.
T. Baerlecken, None; I. Berg, None; R. Ramonda, None; D. van der Heijde, None; F. van Gaalen, None; T. Witte,
None; D. Baeten, UCB, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/diagnostic-value-of-anti-cd74-

antibodies-in-early-axial-spondyloarthritis-data-from-the-spondyloarthritis-caught-early-space-cohort
Low Dose Computed Tomography Detects More Progression of Bone

Formation in Comparison to Conventional Radiography in Patients with
Ankylosing Spondylitis
Anoek de Koning1, Freek de Bruin2, Rosaline van den Berg3, Sofia Ramiro4, Xenofon Baraliakos5, Jürgen Braun5, Floris
van Gaalen3, M. Reijnierse6 and Désirée van der Heijde7, 1Rheumatology, Leiden University Medical Center, Leiden,
Netherlands, 2LUMC, Leiden, Netherlands, 3Rheumatology, LUMC, Leiden, Netherlands, 4Rheumatology, Department of
Rheumatology, LUMC, Leiden, Netherlands, Leiden, Netherlands, 5Rheumazentrum Ruhrgebiet, Herne, Germany,
6Department of Radiology, Leiden University Medical Center, Leiden, Netherlands, 7Leiden University Medical Center,
Leiden, Netherlands
SESSION INFORMATION
Background/Purpose : A newly developed scoring method for low dose CT (ldCT) of the whole spine, CT
Syndesmophyte Score (CTSS), has shown good inter-reader reliability and sensitivity to detect changes in bone formation
over 2 years in Ankylosing Spondylitis (AS) patients1. Next step in validation is the comparison of assessment of bone
formation on ldCT with conventional radiographs (CR).
Methods : Patients from the Sensitive Imaging in Ankylosing Spondylitis cohort were analysed. Inclusion criteria: mNY-
criteria+, ³1 syndesmophyte on cervical/lumbar spine CR and _1 inflammatory lesions on MRI-spine. Patients had baseline
and two-year CR of the lateral cervical and lumbar spine and whole spine ldCT (approximately 4mSV). Two readers
independently assessed CR and ldCT in separate sessions. Images were paired per patient, blinded to time order, patient
information, and results of the other imaging technique. CR was assessed using mSASSS. On ldCT, syndesmophytes were
scored in coronal and sagittal planes, assessing eight ÔquadrantsÕ per vertebral unit (VU). Scores for syndesmophytes
according to the CTSS were: absent=0, <50% of intervertebral disc height (IVDH)=1, _50% of IVDH=2 or IVDH
bridging=3. Formation of new syndesmophytes (CR score 0/1¨2/3, CTSS 0¨1/2/3) and growth of existing syndesmophytes
(CR score 2¨3, CTSS 1¨2/3, or 2ˆ3) and the combination of new or growing syndesmophytes was calculated per
corner/quadrant. Consensus about each outcome was defined by agreement of readers on the same corner/quadrant. The
number of syndesmophytes on CR and CT was compared by level. Level 1: upper four quadrants of a VU on ldCT and
upper corner on CR. Level 2: lower four quadrants on ldCT and lower corner on CR. Data of CR and ldCT was compared
per reader and for the consensus score.
Results : Fifty patients (mean age 50 years; 84% male; 86% HLA-B27+) were included in the analysis. In all comparisons,
ldCT detected more patients with progression (table 1). This is especially apparent in case of growth and for cut-offs of a
higher number of syndesmophytes per patient. E.g. using the consensus score, 30% of the patients showed bony
proliferation (new or growing syndesmophytes) at ³3 sites on ldCT compared with only 6% on CR. ldCT detected more
syndesmophytes in all sections of the spine, with most syndesmophytes occurring in the thoracic spine (figure 1).
Conclusion : Whole spine ldCT is more sensitive in assessing the formation and growth of syndesmophytes than CR,
which is limited to cervical and lumbar spine and is a promising method of assessment for clinical research of AS.
1. de Bruin F et al. A&R 2016; 68 (suppl 10).
Table 1. Comparison of CR and ldCT per reader

and consensus* for the formation or growth of
syndesmophytes in 50 patients with ankylosing
spondylitis.
Reader 1 Reader 2 Consensus
CR ldCT CR ldCT CR ldCT
n(%) n(%) n(%) n(%) n(%) n(%)
New syndesmophytes
³1 27 (54) 43 (86) 30 (60) 44 (88) 19 (38) 21 (42)
³2 14 (28) 38 (76) 14 (28) 41 (82) 7 (14) 15 (30)
³3 6 (12) 32 (64) 8 (16) 30 (60) 2 (4) 10 (20)
Growth of syndesmophytes
³1 10 (20) 35 (70) 7 (14) 32 (64) 3 (6) 16 (32)
³2 8 (16) 36 (52) 6 (12) 27 (54) 3 (6) 11 (22)
³3 2 23 (46) 4 18 (36) 1 (2) 6 (12)
(4) (8)
New syndesmophytes or growth of syndesmophytes
³1 28 (56) 45 (90) 33 (66) 48 (96) 21 (42) 25 (50)
³2 18 (36) 42 (82) 19 (38) 44 (88) 9 (18) 20 (40)
³3 12 (24) 36 (72) 12 (24) 38 (76) 3 (6) 15 (30)
Results are presented as the number (%) of patients
with ³1, ³2 and ³3 newly formed syndesmophytes and
syndesmophytes that grew, as well as for the
combination of new formation or growth. *Both
readers agree about the formation or growth of a
syndesmophyte at the same vertebral corner. CR:
conventional radiography, ldCT: low-dose computed
tomography.
Disclosure: A. de Koning, None; F. de Bruin, None; R. van den Berg, None; S. Ramiro, None; X. Baraliakos, None; J.
Braun, None; F. van Gaalen, None; M. Reijnierse, None; D. van der Heijde, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/low-dose-computed-tomography-

detects-more-progression-of-bone-formation-in-comparison-to-conventional-radiography-in-patients-with-ankylosing-
spondylitis
Associations of Changes of Radiographic Disease and Spinal Mobility

Measures in Ankylosing Spondylitis
Mark Hwang1,2,3, Michael Weisman4, MinJae Lee5, Lianne S. Gensler6, Matt Brown7, Amirali Tahanan5, Laura A.
Diekman8, Thomas Learch9, Seth Eisen10, Mohammad H. Rahbar5, Michael Ward11 and John D. Reveille12, 1Medicine,
University of Texas-McGovern Medical School, Houston, TX, 2Internal Medicine-Rheumatology, University of Texas-
McGovern Medical School, Saint Louis, MO, 3Washington University at Saint Louis School of Medicine, Saint Louis,
MO, 4Cedars-Sinai Medical Center Division of Rheumatology, Los Angeles, CA, 5Biostatistics/Epidemiology/Research
Design (BERD) Core | Center for Clinical and Translational Sciences, University of Texas-McGovern Medical School,
Houston, TX, 6Medicine/Rheumatology, UCSF, San Francisco, CA, 7Translational Genomics Group, Institute of Health
and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Brisbane, Australia,
Brisbane, Australia, 8Rheumatology, University of Texas-McGovern Medical School, Houston, TX, 9Radiology, Cedars
Sinai Medical Center, Los Angeles, CA, 10Division of Rheumatology, Washington University at Saint Louis School of
Medicine, St Louis, MO, 11NIH/NIAMS, Bethesda, MD, 12University of Texas McGovern Medical School, Houston, TX
SESSION INFORMATION
Background/Purpose:
Metrology indices aimed as assessing spinal mobility in ankylosing spondylitis (AS) patients are used in clinical trials and
clinical practice to assess disease severity and progression. The purpose of this study was to examine the association
between changes in spinal mobility and radiographic disease in AS patients enrolled in a longitudinal outcome study.
Methods:
AS patients meeting modified New York Criteria with at least 2 sets of radiographs for assessment of modified Stoke
Ankylosing Spondylitis Spine Score (mSASSS) spaced at least two years apart were included. Spinal mobility
measurements conducted over the same interval as the sets of radiographs included occiput-to-wall distance, cervical
rotation, cervical lateral bending, Schober's and lateral lumbar bending (mean number of sets of mobility measurements per
patient, 2.7±0.9). Because some patients had cervical spine films not visualizing the lower segments, the cervical and
lumbar spine assessments were analyzed separately. Visits were categorized into 3 groups based on changes of their
metrology between visits: improving, worsening or no change in spinal mobility. Longitudinal multivariable negative
binomial regression analyses using generalized estimating equation accounting for the correlation of repeated measures
over time were conducted to assess associations between each of the respective spinal mobility indices and mSASSS
progression. We adjusted each analysis for baseline mSASSS, study sites and clinical/demographic variables (gender,
education, disease duration, current smoking status, longitudinal Bath Ankylosing Spondylitis Disease Activity scores,
baseline CRP levels, and Patient Global Assessment).
Results:
523 patients met these criteria for the cervical spine analyses and 548 for the lumber spine analyses. The median patient
follow up time was 4.08 years (IQR= [2.17, 6.58]) for the cervical spinal and 4.17 years (IQR= [2.17, 6.67]) for the lumbar
spinal measurements. Data summarized in Based on multivariable models, increases in occiput to wall distance were
significantly associated with increased cervical mSASSS scores compared to no change (adjusted rate ratio (RR) =1.95;
p=0.02) and no change in occiput to wall distance was negatively associated with increasing mSASSS compared to
decreased occiput to wall distance (adjusted RR= 0.49; p<0.01). Despite a weak trend, no significant differences were
noted when comparing positive vs. negative change in lateral cervical bending, cervical rotation, Schober or lateral lumbar
bending assessments and changes in the mSASSS.
Conclusion:
Significant associations were observed between longitudinal changes in occiput to wall and mSASSS scores but not
between cervical (lateral cervical bending, cervical rotation measures) or lumbar spinal mobility measures (Schober's,
lateral lumbar bending). The occiput-to-wall analysis suggested any change of this measure, positive or negative, was
associated with radiographic progression. This suggests that concomitant cervical and lumbar metrology and radiographic
disease changes may be measuring different structural phenomena.
Disclosure: M. Hwang, None; M. Weisman, None; M. Lee, None; L. S. Gensler, Janssen Pharmaceutica Product, L.P.,
5,Novartis Pharmaceutical Corporation, 5,Amgen, 2,UCB, 2,AbbVie, 2; M. Brown, None; A. Tahanan, None; L. A.
Diekman, None; T. Learch, None; S. Eisen, None; M. H. Rahbar, None; M. Ward, None; J. D. Reveille, Janssen,
Novartis, 5,UCB, Eli Lilly, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/associations-of-changes-of-
radiographic-disease-and-spinal-mobility-measures-in-ankylosing-spondylitis
Factors Associated with the “Bamboo Spine” Phenotype – Data from the
Comospa Study
Koei Oh1, Anna Molto2, Corinne Miceli-Richard3, Soksay Singvongsa4, Adrien Etcheto4 and Maxime Dougados4,
1Departmen of Rheumatology, Paris Descartes University, Hôpital Cochin, Paris, France, 2Hôpital Cochin, Department of
Rheumatology, Paris Descartes University, Paris, France, 3Department of Rheumatolgy, Paris Descartes University, Hôpital
Cochin, Paris, France, 4Department of Rheumatology, Paris Descartes University, Hôpital Cochin, Paris, France
SESSION INFORMATION
Background/Purpose: The factors associated with “Bamboo spine” occurrence, i.e. the most severe axial phenotype of
SpA patients, have been poorly assessed to date. The aim of this study was to clarify the factors associated with the severe
type of AS “Bamboo spine” by investigating associations with various demographics, clinical and functional outcomes.
Methods: 275 patients with Bamboo spine enrolled by ASAS-COMOSPA study (Cross-sectional international study
involving 22 countries and including 3984 SpA patients fulfilling the ASAS SpA criteria) were included in the analysis.
Demographic, Clinical, and biological characteristics were compared between Bamboo-spine and non-Bamboo spine
patients. Variables with significant difference in univariate analyses were used as dependent variables in multivariable and
logistic regression. A logistic regression was used for the analysis to clarify the parameters associated with the Bamboo
spine phenotype. Independent variables with a p value less than 0.2 in univariate linear/logistic regression analysis were
tested in multivariate regression models. Odds ratio (ORs) with 95% CIs were calculated.
Results: Results of the univariate analysis are provided in the table. Multivariate analysis showed that Bamboo spine
phenotype was independently associated with NSAIDs intake from first symptom (OR 4.29; 95% CI 1.45-12.71 P<0.02),
male gender (OR 4.09; 95% CI 2.37-7.05; P<0.02), HLA-B27 positivity (OR 2.26; 95% CI 1.34-3.83; P<0.02), increased
CRP (OR 1.76; 95% CI 1.20-2.60; P<0.02), osteoporosis (OR 1.52; 95% CI 0.99-2.34; P=0.05), with only a trend for
smoking (OR 1.38, 95% CI 0.97-1.98; P=0.07).
Conclusion: The results of this study confirm parameters that have been previously associated with axial structural severity
(longer disease duration, uveitis, smoking, HLA-B27 and male gender). NSAIDs have been reported to have a potential
protective effect on the structural progression of the disease. Nevertheless, in this cross sectional study, NSAIDs intake
from the first symptoms was associated with the Bamboo spine phenotype, suggesting that severe axial involvement leads
to a sustained NSAIDs intake for pain relief. This also suggest that patients evolving to a bamboo spine phenotype have not
been under-exposed to NSAIDs treatment and/or that NSAIDs sustained exposure is not sufficient to protect from Bamboo
spine phenotype.
Disclosure: K. Oh, None; A. Molto, None; C. Miceli-Richard, None; S. Singvongsa, None; A. Etcheto, None; M.
Dougados, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/factors-associated-with-the-bamboo-

spine-phenotype-data-from-the-comospa-study
Frequencies of Ligament Ossification in Patients with Ankylosing Spondylitis

According to Several Ligaments Around Spine By Whole Spine CT Scan
Ran Song1, Ji-Young Choi2, Yeon-Ah Lee2, Seung-Jae Hong2, Hyung-In Yang3 and Sang-Hoon Lee1, 1Rheumatology,
Kyung Hee University Hospital at Gang dong, Seoul, Korea, Republic of (South), 2Rheumatology, Kyung Hee University
Hospital, Seoul, Korea, Republic of (South), 3Kyung Hee University Hospital at Gang dong, Seoul, Korea, Republic of
(South)
SESSION INFORMATION
Background/Purpose:
Ankylosing spondylitis is chronic inflammatory arthritis with ligament ossification in spine such as ant. longitudinal
ligaments, post. longitudinal ligaments, or other several ligaments around spine joints. We generally use mSASSS to
evaluate progression of ossification which method only calculate amount of ossification in ant. longitudinal ligament. But
there has not been known which ligaments are ossified most commonly.
We performed whole spine CT scan in patients with ankylosing spondylitis to analyze the frequency of ligaments
ossification according to the sites of spine.
Methods:
This is a retrospective chart review study. We enrolled the patients who were diagnosed as ankylosing spondylitis by
modified NY criteria in our hospital. Among these patients, we analyzed the male patients who had been performed by
whole spine CT scans in ages between 40 and 45. Total 119 patients were enrolled. We analyzed the frequency of
ossification in ant. longtudinal ligaments, post. longitudinal ligaments, ligamentum flavum, ligaments around facet joints,
interspinous ligaments, supraspinus ligaments and annulus fibrosus according to C, T and L spine.
Results:
The most frequent ossification site was lateral side of annulus fibrosus in T spine (68.9%). Even regardless of C, T, L spine,
ossification of lateral side in annulus fibrosus was also the most frequent site (157 sites). Second common ligaments
ossified were ant. longitudinal ligaments (142 sites) and third common ligaments were ligaments around facet joints (109
sites). According to spine, the ligaments of T spine were the most common ligaments ossified (252). The ligaments in L
spine were second common ligaments ossified (177). Interestingly ossification in the ligaments around L spine did not
developed, but developed in T spine in 27 patients (22.7%). This is very important finding because ossification in the
ligaments around T spine is not included in mSASSS method which method is used to evaluate disease progression in
ankylosing spondylitis at present. Ossification in ant. longitudinal ligaments was strongly statistically correlated with
ossification in ligaments around facet joints in L spine strongly (p=0.00. r=0.547).
Conclusion:
Ligaments around T spine were most commonly ossified in ankylosing spondylitis and we need to find new method to
evaluate of ossification in T spine.
Disclosure: R. Song, None; J. Y. Choi, None; Y. A. Lee, None; S. J. Hong, None; H. I. Yang, None; S. H. Lee, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/frequencies-of-ligament-ossification-in-
patients-with-ankylosing-spondylitis-according-to-several-ligaments-around-spine-by-whole-spine-ct-scan
Validation of Online Calibration Modules for the Spondyloarthritis Research

Consortium of Canada MRI Scores Based on Real-Time Experiential
Learning
Matthew Maksymowych1, Hanne Boutrup2, Jonathan Cheah3, Riccardo Guglielmi4, Eric Heffernan5, Jacob Jaremko1,
Mats-Peter Johansson6, Simon Krabbe7, Georg Kroeber8, Fardina Malik9, Susanne Juhl Pedersen7, Sander Shafer6, Ulrich
Weber10, Pam Weiss11, Brian Trinh12, Joel Paschke13 and Robert G. Lambert14, 1Radiology, University of Alberta,
Edmonton, AB, Canada, 2University of Copenhagen, Copenhagen, Denmark, 3Medicine, Hospital for Special Surgery,
New York, NY, 4Radiology, Ente Ospedaliero Cantonale, Lugano, Switzerland, 5Radiology, St. Vincent's University
Hospital, Dublin, Ireland, 6Rheumatology, Gentofte Hospital, Copenhagen, Denmark, 7Center for Rheumatology and Spine
Diseases, Copenhagen Center for Arthritis Research, Rigshospitalet, Copenhagen, Denmark, 8University of Southern
Denmark, Odense, Denmark, 9Medicine- Rheumatology, Weill Cornell Medical College, New York, NY, 10Department of
Research, King Christian 10th Hospital for Rheumatic Diseases, Graasten, Denmark, 11Pediatrics, Children's Hospital
Philadelphia, Philadelphia, PA, 12CARE Arthritis, EDMONTON, AB, Canada, 13CARE Arthritis, Edmonton, AB, Canada,
14University of Alberta, Edmonton, AB, Canada
SESSION INFORMATION
Background/Purpose: The appropriate use of imaging-based scoring instruments is usually an ad hoc process based on
passive learning from published manuscripts. Moreover, most instruments lack knowledge transfer tools that would
facilitate attainment of pre-specified performance targets for reader reliability prior to use in clinical trials and research. We
aimed to develop and validate online calibration modules for the SPARCC MRI Scores based on consensus scores from
these instrument developers, experiential game psychology, and real-time iterative feedback built into a scoring schematic
directly on the DICOM image.
Methods: The SPARCC BME inflammation calibration module is comprised of 50 DICOM cases, each with scans from
baseline and 12 weeks after the start of tumor necrosis factor inhibitor therapy. The SPARCC structural score is comprised
of 40 cases, each with scans from baseline and after 2 years follow-up. Scans are scored in pairs for status and change
scores blinded-to-time-point. Continuous visual real-time feedback regarding concordance/discordance of scoring per SIJ
quadrant with expert readers is provided by a color-coding scheme. Reliability is additionally assessed by real-time intra-
class correlation coefficient with the first ICC data being provided after 20 cases per SIJ coronal slice (calibration-per-
slice), and further ICC data after the entire case has been scored (calibration-per-case). Accreditation for SPARCC BME is
achieved with a status score ICC of > 0.8 and a change score ICC of > 0.7, and for SPARCC structural, status score ICC of
>0.7 is required for fat and ankylosis, >0.5 for erosion and backfill, and >0.5 for change score in all domains. 14 readers
scored the SPARCC BME module and 11 the SPARCC structural module, only 2 having prior experience with these scores,
and 9 being rheumatology fellows.
Results: For the SPARCC BME score and the calibration-per-slice method, all 14 readers completed the scoring and
attained the required level of proficiency. For the SPARCC structural scores and the calibration-per-slice method, all 11
readers completed scoring, proficiency for status was attained by 10 for each lesion domain, and proficiency for change
was attained by 11, 5, 6, 8 for fat, erosion, backfill, ankylosis, respectively. All readers rated the modules as easy and
intuitive with average time for reading each case for SPARCC BME and Structural being 9 min and 12 min, respectively.
Conclusion: Experiential online learning is an effective and feasible calibration tool in the scoring of MRI scans.
SPARCC Calibration per SIJ Slice Calibration per Case

score Baseline 12 weeks Change Baseline 12 weeks Change
SPARCC 0.97(0.96- 0.94(0.91- 0.94(0.92- 0.77(0.71- 0.86(0.81- 0.69(0.59-
BME 0.97) 0.96) 0.95) 0.84) 0.91) 0.78)
SPARCC Fat 0.84(0.73- 0.89(0.83- 0.81(0.74- 0.85(0.78- 0.86(0.79- 0.90(0.87-
0.94) 0.96) 0.88) 0.93) 0.92) 0.94)
SPARCC 0.83(0.74- 0.81(0.73- 0.46(0.28- 0.59(0.43- 0.46(0.26- 0.39(0.25-
Erosion 0.91) 0.89) 0.63) 0.75) 0.65) 0.53)
SPARCC 0.58(0.38- 0.79(0.70- 0.49(0.31- 0.67(0.49- 0.61(0.43- 0.56(0.38-
Backfill 0.78) 0.88) 0.67) 0.86) 0.78) 0.74)
SPARCC 0.92(0.88- 0.96(0.92- 0.71(0.56- 0.95(0.87- 0.92(0.85- 0.54(0.31-
Ankylosis 0.96) 1.00) 0.86) 1.00) 0.98) 0.77)
Disclosure: M. Maksymowych, None; H. Boutrup, None; J. Cheah, None; R. Guglielmi, None; E. Heffernan, None; J.
Jaremko, None; M. P. Johansson, None; S. Krabbe, None; G. Kroeber, None; F. Malik, None; S. J. Pedersen, None; S.
Shafer, None; U. Weber, None; P. Weiss, None; B. Trinh, None; J. Paschke, None; R. G. Lambert, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/validation-of-online-calibration-

modules-for-the-spondyloarthritis-research-consortium-of-canada-mri-scores-based-on-real-time-experiential-learning
Detection of Structural Lesions on T1 Weighted MRI Versus Radiography of

the Sacroiliac Joints in Early Axial Spa: 2-Year Data
Walter P. Maksymowych1, Pascal Claudepierre2, Manouk de Hooge3, Robert G. Lambert4, Robert B.M. Landewé5, Anna
Molto6, Désirée van der Heijde3, Jack F Bukowski7, Heather Jones8, Isabelle Logeart9, Lisa Marshall8, Ronald Pedersen10,
Annette Szumski11, Bonnie Vlahos12 and Maxime Dougados13, 1Radiology & Diagnostic Imaging, University of Alberta,
Edmonton, AB, Canada, 2Universite Paris Est Creteil, Paris, France, 3Leiden University Medical Center, Leiden,
Netherlands, 4University of Alberta, Edmonton, AB, Canada, 5Amsterdam Rheumatology & Immunology Center,
Amsterdam, Netherlands, 6Hôpital Cochin, Department of Rheumatology, Paris Descartes University, Paris, France,
7Clinical Affairs, Pfizer, Collegeville, PA, 8Inflammation & Immunology Global Medical Affairs, Pfizer, Collegeville, PA,
9Medical Affairs, Pfizer, France, Paris, France, 10Department of Biostatistics, Pfizer, Collegeville, PA, 11inVentiv Health,
Princeton, NJ, 12Clinical Sciences, Pfizer, Collegeville, PA, 13Hopital Cochin, Paris Descartes University, Paris, France
SESSION INFORMATION
Background/Purpose: At the SI joint (SIJ) level, several methods exist for evaluating structural damage, e.g., MRI, CT
scan, radiographs. In EMBARK (NCT01258738) and DESIR (NCT01648907), MRI and radiographs were available at
baseline and Week 104. We evaluated: (1) the association between presence/absence of erosion on MRI and
presence/absence of erosion or sacroiliitis on radiographs at the SIJ at baseline and Week 104, and (2) the association
between decrease/increase in erosion on MRI and decrease/increase in erosion or sacroiliitis on radiographs at the SIJ
between baseline and Week 104.
Methods: Patients in both studies had early axial SpA (axSpA). EMBARK included a 12-week double-blind placebo-
controlled period, then open-label etanercept for 92 weeks. DESIR patients had no history of biologic therapy and did not
receive biologics for 2 years. MRI and radiographs of the SIJ from DESIR and EMBARK were combined and anonymized;
readers were unaware of film chronology and original patient cohort. Three experienced readers evaluated T1 weighted
MRI images using the SpondyloArthritis Research Consortium of Canada (SPARCC) SIJ Structural Score (SSS), graded
radiographic sacroiliitis using the modified New York grading system, and recorded the presence/absence of individual
radiographic lesions (erosion, sclerosis, ankylosis) for each SIJ. Presence/absence of lesions at each time point and
decrease/increase in lesions was identified for each patient based on agreement of 2 out of 3 readers. Statistical analyses
included kappa coefficient of agreement and McNemar’s test for asymmetry.
Results: 224 patients had MRI and radiographs available. At baseline, concordance for presence or absence of erosion was
observed in 162/224 (72.3%) (κ=0.42) (Table). In cases of discordance, erosion was more frequent on MRI (21.4%) than
radiographs (6.3%; P<0.0001). Week 104 data were similar to baseline. Decrease in erosion from baseline to 104 weeks
was more frequent than increase only when assessed by MRI, and was significantly more frequent on MRI than
radiographs. Similarly, decrease in erosion on MRI was significantly more frequent than decrease in sacroiliitis grade.
Conclusion: In patients with early axSpA, erosion was present more often on MRI than on radiographs at baseline and
Week 104. Decrease in erosion at Week 104 was noted more frequently on MRI than radiographs.
Table. Concordance between MRI and radiographs; baseline, Week 104, and change between baseline and Week 104
N Present / Absent Absent / Present Kappa P-value for
Present / Present / (95% CI) discordance
Absent Absent asymmetry*
Erosion on MRI /
50 112 14 48 0.42 (0.30,
Erosion on x-ray at 224 <0.0001
(22.3%) (50.0%) (6.3%) (21.4%) 0.53)
BL
Erosion on MRI /
44 119 15 44 0.41 (0.29,
Erosion on x-ray at 222 0.0002
(19.8%) (53.6%) (6.8%) (19.8%) 0.53)
Week 104
Erosion on MRI /
60 97 29 38 0.39 (0.26,
sacroiliitis on x-ray 224 0.27
(26.8%) (43.3%) (12.9%) (17.0%) 0.51)
at BL
Erosion on MRI /
56 99 35 32 0.37 (0.25,
sacroiliitis on x-ray 222 0.71
(25.2%) (44.6%) (15.8%) (14.4%) 0.50)
at Week 104
Erosion decrease on
162 6 49 0.06 (-0.05,
MRI / Erosion 221 4 (1.8%) <0.0001
(73.3%) (2.7%) (22.2%) 0.16)
decrease on x-ray
Erosion increase on
187 17 15 0.03 (-0.12,
MRI / Erosion 221 2 (0.9%) 0.72
(84.6%) (7.7%) (6.8%) 0.18)
increase on x-ray
Erosion decrease on
MRI / sacroiliitis 154 14 45 0.08 (-0.05,
221 8 (3.6%) <0.0001
grade decrease on (69.7%) (6.3%) (20.4%) 0.21)
x-ray
Erosion increase on
MRI / sacroiliitis 180 24 13 0.09 (-0.07,
221 4 (1.8%) 0.07
grade increase on x- (81.4%) (10.9%) (5.9%) 0.25)
ray
*McNemar’s test.
BL, baseline.
Disclosure: W. P. Maksymowych, Abbvie, Pfizer, 2,Abbvie, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, 5; P.
Claudepierre, None; M. de Hooge, MdH Research, 3; R. G. Lambert, BioClinica, 5,AbbVie, 8; R. B. M. Landewé,
Abbott/AbbVie, Ablynx, Amgen, Astra-Zeneca, Bristol Myers Squibb, Celgene, Janssen (formerly Centocor), Galapagos,
GlaxoSmithKline, Novartis, Novo-Nordisk, Merck, Pfizer, Roche, Schering-Plough, TiGenix, UCB, and Wyeth, 5,Abbott,
Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB, and Wyeth, 2,Abbott/AbbVie, Amgen, Bristol Myers
Squibb, Janssen (formerly Centocor), Merck, Pfizer, Roche, Schering-Plough, UCB, and Wyeth, 8; A. Molto, None; D. van
der Heijde, AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos,
Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCBAbbVie, Amgen,
Astellas, AstraZeneca, BMS, Boehringe, 5,Director: Imaging Rheumatology bv, 9; J. F. Bukowski, Pfizer Inc, 1,Pfizer Inc,
3; H. Jones, Pfizer Inc, 1,Pfizer Inc, 3; I. Logeart, Pfizer Inc, 1,Pfizer Inc, 3; L. Marshall, Pfizer Inc, 1,Pfizer Inc, 3; R.
Pedersen, Pfizer Inc, 1,Pfizer Inc, 3; A. Szumski, inVentiv Health, 3; B. Vlahos, Pfizer Inc, 1,Pfizer Inc, 3; M. Dougados,
Pfizer, AbbVie, UCB, Merck and Lily, 2,Pfizer, AbbVie, UCB, Merck and Lily, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/detection-of-structural-lesions-on-t1-

weighted-mri-versus-radiography-of-the-sacroiliac-joints-in-early-axial-spa-2-year-data
Inflammatory Lesions of the Sacroiliac Joints, but Not of the Spine, Are of
High Utility for Recent Onset Axial Spondyloarthritis Recognition
Anna Molto1, Laure Gossec2, Violaine Foltz2, Romain Beaufort3, Jean Denis Laredo4, Pascal Richette5, Philippe Dieude6,
Philippe Goupille7, Antoine Feydy8 and Maxime Dougados9, 1Hôpital Cochin, Department of Rheumatology, Paris
Descartes University, Paris, France, 2UPMC University Paris 06, Pitié-Salpétrière Hospital, Paris, France, 3Private
Practice,, Paris, France, 4Radiology Department, Lariboisière Hospital, Paris, France, 5Rheumatology Department,
Université Paris Diderot, Paris, France, 6Université Paris-Diderot, Paris, France, 7Université François-Rabelais, Tours,
France, 8Univ. Paris Descartes, PRES Sorbonne Paris Cité, Service de radiologie B, Hôpital Cochin, Assistance Publique -
Hôpitaux de Paris, Paris, France, Paris, France, 9Department of Rheumatology, Paris Descartes University, Hôpital Cochin,
Paris, France
SESSION INFORMATION
Background/Purpose: only scarce data are available regarding the prevalence of MRI inflammatory lesions of the
sacroiliac joints (SIJ) or the spine suggestive of axial Spondyloarthritis (axSpA) in patients with recent onset mechanical
chronic back pain (CBP).The aim of this study was to evaluate the prevalence of MRI (SIJ,Spine) inflammatory lesions
suggestive of axSpA in a non-axSpA CBP population and to compare its prevalence to an recent onset axSpA cohort.
Methods:
Patients: a) Recent onset axSpA patients: first, a sample of 100 patients representative in terms of imaging abnormalities of
the global DESIR (1) recent onset axSpA cohort (> 3 months but <3 years), based on the results of the previously published
central reading of baseline films of DESIR(2) were selected (e.g. 35% of patients fulfilling the ASAS definition of MRI
sacroiliitis). b) Recent onset CBP patients: consecutive in- and outpatients consulting for recent (>3months but <5years)
mechanical CBP, initiating before the age of 45y and with a maximum age of 50y, in four tertiary care Hospitals were
included in the study. Imaging: MRI scans (T2-STIR and T1 sequences) of the SIJ and full spine were performed in both
groups with identical protocol. Central reading: an experienced reader (AM) centrally read all MRI scans, blinded for
clinical diagnosis. Statistical analysis: prevalence of MRI inflammatory lesions suggestive of axSpA were compared in
both groups. Sensitivity, specificity and positive likelihood ratio of each lesion were calculated.
Results:
A total of 98 patients with recent onset CBP were included, and compared to 100 recent onset axSpA patients. Age and
gender were comparable (mean(SD) 36.2(9.9) vs. 32.2(8.7)y, and 41.8% and 45% males, in the CBP vs. axSpA groups,
respectively). MRI inflammatory lesions of the SIJ were quite frequent in the CBP group (25% patients with at least one
inflammatory lesion) but were significantly more frequently observed in the axSpA group (Table), with a mean SIJ -
SPARCC score of 4.9 (8.8) vs. 0.6 (1.3), p<0.001. The ASAS definition of MRI sacroiliitis presented a high specificity and
a good positive likelihood ratio. Conversely, prevalence of inflammatory lesions of the spine was very frequent in the CBP
group and not significantly lower compared to the axSpA group (SPARCC spine 5.6 (13.5) vs. 3.3(5.8), in the axSpA vs.
CBP groups, respectively). Regardless the definition of a positive MRI for the spine applied, performances were not good,
with positive likelihoods ratios below 2.
CBP SpA
p Sensitivity Specificity LR+
N=98 N=100
At least one 24
40 1.6
inflammatory 0.4 (0.3, 0.8 (0.7,
(25.3%) 0.028 (1.0,
lesion of the (40.0%) 0.5) 0.8)
2.4)
SIJ n=95
SIJ-MRI
ASAS 8
35 4.2
definition of 0.4 (0.3, 0.9 (0.8,
(8.4%) <0.001 (2.0,
positive MRI (35.0%) 0.5) 0.9)
8.5)
sacroiliitis n=95
At least one 52
44 1.2
inflammatory 0.5 (0.4, 0.6 (0.5,
(52.5%) NS (0.9,
lesions of the 0.6) 0.7)
(44.9%) 1.6)
spine n=99
ASAS
definition of 44
1.4
positive MRI 33 0.4 (0.3, 0.7 (0.6,
(44.4%) NS (0.9,
Spine-MRI spine ≥3 (33.7%) 0.6) 0.8)
1.9)
inflammatory n=99
lesions)
SPACE (3)
30
definition of 1.2
positive MRI 25 0.3 (0.2, 0.7 (0.7,
(30.3%) NS (0.8,
spine ≥5 (25.5%) 0.4) 0.8)
1.9)
inflammatory n=99
lesions)
Conclusion:
ASAS definition of a positive MRI-sacroiliitis performed very well for axSpA recognition; however, definitions proposed
for a positive MRI-spine suggestive of axSpA did not seem to perform adequately in this recent disease stage. This supports
the idea of not including a positive MRI of the spine in the ASAS classification criteria.
Ref:1.- Dougados M, et al.Joint Bone Spine.2015. 2. van den Berg R et al.Ann Rheum Dis.2015.- de Hooge M et al.Ann
Rheum Dis.2016
Disclosure: A. Molto, None; L. Gossec, None; V. Foltz, None; R. Beaufort, None; J. D. Laredo, None; P. Richette,
None; P. Dieude, None; P. Goupille, None; A. Feydy, None; M. Dougados, Abbvie, Pfizer, Eli Lilly and Company,
Novartis, UCB, Merck, Roche, BMS UCB, 2,Abbvie, Pfizer, Eli Lilly and Company, Novartis, UCB, Merck, Roche, BMS,
UCB, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/inflammatory-lesions-of-the-sacroiliac-

joints-but-not-of-the-spine-are-of-high-utility-for-recent-onset-axial-spondyloarthritis-recognition
Erosions at the Sacroiliac Joints and Fatty Lesions at the Spine Are the Most
Discriminant Lesions for Recent Onset Axial Spondyloarthritis Recognition
Université Paris Diderot, Paris, France, 6Université Paris-Diderot, Paris, France, 7Department of Rheumatology, CHRU de
Tours; and Université François-Rabelais de Tours, Tours, France, 8Univ. Paris Descartes, PRES Sorbonne Paris Cité,
Service de radiologie B, Hôpital Cochin, Assistance Publique - Hôpitaux de Paris, Paris, France, Paris, France, 9Paris,
Paris, France
SESSION INFORMATION
Background/Purpose: only scarce data are available regarding the prevalence of MRI structural lesions of the sacroiliac
joints (SIJ) or the spine suggestive of axial Spondyloarthritis (axSpA) in patients with recent onset mechanical chronic back
pain (CBP). The aim was to evaluate the prevalence of MRI (SIJ and Spine) structural lesions suggestive of axSpA in a
non-axSpA CBP population and to compare its prevalence to an recent onset axSpA cohort.
Methods:
Study design: Observational cross-sectional national multicentre study. Patients: a) Recent onset axSpA patients: first, a
sample of 100 patients representative in terms of imaging abnormalities of the global DESIR (1) recent onset axSpA cohort
(> 3 months but <3 years), based on the results of the previously published central reading of baseline films of DESIR(2)
were selected (e.g. 21% of patients fulfilling the modified NY criteria (mNY)). b) Recent onset CBP patients: consecutive
in- and outpatients consulting for recent (>3months but <5years) mechanical CBP, initiating before the age of 45y and with
a maximum age of 50y, in four tertiary care Hospitals were included in the study. Imaging: MRI scans (T2-STIR and T1
sequences) of the SIJ and cervico-thoracic and thoraco-lumbar spine were performed in both groups with identical protocol.
Central reading: an experienced reader (AM) centrally read all MRI scans, blinded for clinical diagnosis. Statistical
analysis: prevalence of lesions and lesions combinations previously proposed(3) to be suggestive of axSpA was compared
in both groups. Sensitivity, specificity and positive likelihood ratio (LR+) of each lesion were calculated.
Results:
Results: A total of 98 patients with recent onset CBP were included, and compared to 100 recent onset axSpA patients.
Age and gender were comparable (mean (SD) 36.2 (9.9) vs. 32.2 (8.7)y, and 41.8% and 45% males, in the CBP vs. axSpA
groups, respectively).Prevalence of chronic lesions of the SIJ was significantly greater in the axSpA group but up to 17%
patients with CBP presented at least one chronic lesion of the SIJ (Table). The presence of at least 3 subchondral bone
erosions at the SIJ performed the best for axSpA discrimination. Prevalence of chronic lesions of the spine was comparable
in the two groups, with high prevalence of fatty lesions across groups; erosions were rare in both groups. The presence of at
least 5 fatty lesions was the most discriminant, with a high specificity. Performances of all other structural lesions of the
spine were poor.
CBP SpA p Se Spe LR+
N=98 N=100
MRI
SIJ
N(%) patients 16/95 24 NS 0.2 (0.2, 0.8 (0.7,0.0) 1.4 (0.8,
with at least 0.3) 2.5)
one structural (16.8%) (24%)
lesion
N(%) patients 10 /95 32 (32%) <0.001 0.32 0.9 (0.8, 1.0) 3.0 (1.6,
with ≥3 (0.2, 5.8)
subchondral (10.5%) 0.4)
bone erosions
N(%) patients 11/95 29 (29%) 0.004 0.29 0.88 (0.8, 0.9) 2.5 (1.3,
with ≥3 (0.2, 4.7)
bone fatty
lesions
N(%) patients 13/95 33 (33%) 0.002 0.33 0.9 (0.8, 0.9) 2.4 (1.4,
with ≥5 (0.2, 4.3)
bone erosions
or fatty
lesions)
MRI
spine
N(%) patients 49 42/99 NS 0.4 (0.3, 0.5 (0.4, 0.6) 0.8 (0.6,
with at least (50.0%) 0.5) 1.2)
one structural (42.4%)
lesion
N(%) patients 6 (6.1%) 7/99 (7.1%) NS 0.1 (0.0, 0.9 (0.9, 1.0) 1.2 (0.4,
with ≥3 0.1) 3.3)
subchondral
bone erosions
N(%) patients 21(21.4%) 15/99(15.2%) NS 0.2 (0.1, 0.8 (0.7, 0.9) 0.7 (0.4,
with ≥3 0.2) 1.23
subchondral
bone fatty
lesions
N(%) patients 8 (8.2%) 21/99 0.02 0.2 0.9 (0.8, 0.9) 2.5 (1.2,
with ≥5 (21.2%) (0.1,0.3) 5.4)
subchondral
bone fatty
lesions
N(%) patients 19 11 /99 NS 0.1 (0.1, 0.8 (0.7, 0.9) 0.6 (0.3,
with ≥5 (19.4%) (11.1%) 0.2) 1.1)
subchondral
bone erosions
OR fatty
lesions
Conclusion: Presence of at least 3 erosions at the MRI-SIJ and at least 5 fatty lesions at the MRI-spine seemed to
performed well for axSpA recognition. This suggests that these definitions might be considered (in the future) to be
integrated in axSpA classification criteria
UCB, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/erosions-at-the-sacroiliac-joints-and-

fatty-lesions-at-the-spine-are-the-most-discriminant-lesions-for-recent-onset-axial-spondyloarthritis-recognition
X-Ray Spine Lesions Are Rare and Not Discriminant for Axial
Spondyloarthritis Recognition in Patients with Recent Onset Chronic Back
Pain
Université Paris Diderot, Paris, France, 6Université Paris-Diderot, Paris, France, 7Université François-Rabelais, Tours,
France, 8Univ. Paris Descartes, PRES Sorbonne Paris Cité, Service de radiologie B, Hôpital Cochin, Assistance Publique -
Hôpitaux de Paris, Paris, France, Paris, France, 9Department of Rheumatology, Paris Descartes University, Hôpital Cochin,
Paris, France
SESSION INFORMATION
Background/Purpose: only very scarce data is available regarding the prevalence of spine Xrays abnormalities suggestive
of axial Spondyloarthritis (axSpA) in patients with recent onset mechanical chronic back pain (CBP).
Objective: To evaluate the frequency of spine X-ray abnormalities suggestive of axSpA in a non-axSpA CBP population
and to compare its prevalence to an recent onset axSpA cohort.
Methods:
Methods : Study design: Observational cross-sectional national multicentre study. Patients: a) Recent onset axSpA
patients: first, a sample of 100 patients representative in terms of imaging abnormalities of the global DESIR (1) recent
onset axSpA cohort (> 3 months but <3 years), based on the results of the previously published central reading of baseline
films of DESIR(2) were selected (e.g. 21% of patients fulfilling the modified NY criteria (mNY)). b) Recent onset CBP
patients: consecutive in- and outpatients consulting for recent (>3months but <5years) mechanical CBP, initiating before
the age of 45y and with a maximum age of 50y, in four tertiary care Hospitals were included in the study. Imaging: Full
spine Xrays were performed in both groups with an identical protocol. Central reading: an experienced reader (AM)
centrally read X-ray films, blinded for clinical diagnosis. Statistical analysis: Number of lesions suggestive of axSpA were
compared in both groups.
Results: A total of 98 patients with recent onset CBP were included, and compared to 100 recent onset axSpA patients.
Age and gender were comparable (mean (SD) 36.2 (9.9) vs. 32.2 (8.7)y, and 41.8% and 45% males, in the CBP vs. axSpA
groups, respectively). Prevalence of spine lesions was globally very low, and only squaring was significantly more frequent
in the axSpA group.
CBP SpA p
(N=95) (N=100)
Number of erosions 0.4 (0.8) 0.3 (0.5) NS
Number of sclerosis lesions 0.4 (1.6) 0.5 (1.4) NS
Number of squarring lesions 0.01 0.2 (0.8) 0.037
(0.1)
mSASSS* 2.0 2.2 NS
(14.5) (15.1)
n=89 n=91
Number of patients with at 2 (2.1%) 5 (5.0%) NS
least one full bone bridge
*exclusion of patients with more than 75% missing corners per section (cervical and lumbar)
Conclusion: Lesions suggestive of axSpA in spine Xrays of patients with CBP are rare; however, even in this recent onset
disease patients, squaring lesions were significantly more frequent in the recent onset axSpA patients.
Funding = ASAS grant
Ref: (1) Dougados M, et al. Joint Bone Spine. 2015; (2) van den Berg R et al. Arthritis Rheumatol. 2014
UCB, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/x-ray-spine-lesions-are-rare-and-not-

discriminant-for-axial-spondyloarthritis-recognition-in-patients-with-recent-onset-chronic-back-pain
Inflammation on MRI of Spine and Sacroiliac Joints Is Highly Predictive of

Structural Damage in Axial Spondyloarthritis: The 5 Years Data of the
DESIR Cohort
Alexandre Sepriano1, Sofia Ramiro2, Robert B.M. Landewé3, Maxime Dougados4 and Désirée van der Heijde1, 1Leiden
University Medical Center, Leiden, Netherlands, 2Rheumatology, Department of Rheumatology, LUMC, Leiden,
Netherlands, Leiden, Netherlands, 3University of Amsterdam and Atrium Medical Center, Amsterdam, Netherlands, 4Paris-
Descartes University,, Paris, France
SESSION INFORMATION
Background/Purpose: The effect of local inflammation on structural damage in patients (pts) with axial spondyloarthritis
is not well known. We aimed to test the possible effect of inflammation on structural damage both assessed by MRI and at
the level of the spine and SIJ.
Methods: Pts with recent onset (≤3 years) axSpA (according to the treating rheumatologist) from the DESIR cohort were
included. MRI of the SIJ (MRI-SIJ) and spine (MRI-spine) were obtained at baseline (BL), 2 and 5 years and scored by 3
trained central readers. Bone Marrow Edema (BME) at MRI-SIJ was assessed according to ASAS definition and at the
MRI-spine by the presence of ≥ 3 lesions. Structural damage in the SIJ (MRI-SIJ-STR) and in the spine (MRI-spine-STR)
was defined by ≥ 3 fatty lesions. The % of structural net progression (number of ‘progressors’ minus the number of
‘regressors’ divided by total number of pts) was assessed according to CRP and BME status at BL. The effect of BME on
MRI-SIJ on MRI-SIJ-STR and of BME on MRI-spine on MRI-spine-STR was evaluated using two types of binomial
generalized estimating equations (GEE) models: i. effect at BL on 5 years incorporating measurements from all readers
(GEE adjusted for reader); ii. effect of BME over 5 years (longitudinal time-lagged models with auto-regression). The final
models were adjusted for variables proved to confound the association of interest (variables tested: age, gender, HLA-B27,
smoking status, CRP, BASDAI, ASDAS, treatment with NSAIDs and TNFi).
Results: In total, 151 and 145 pts had complete 5-year MRI-SIJ and MRI-spine data available from 3 readers, respectively.
Of the 151 pts with complete MRI-SIJ data, the net % pts who switched from MRI-SIJ-STR negative to positive ranged
from 3.8% to 24% according to the presence of objective signs of inflammation at BL (figure). Low number of pts did not
allow for similar analysis in the spine. In the multivariable analysis, both the presence of BME at MRI-SIJ (OR=4.2 [95%
CI: 2.4-7.3]), and BME at MRI-spine (OR=8.9 [95% CI: 2.1-38.7]) at baseline were highly predictive of MRI-SIJ and
MRI-spine structural progression respectively 5 years later, adjusting for CRP (only factor found to confound the
association of interest). Similar positive associations were found in the longitudinal models testing the effect of BME on
MRI-SIJ-STR and MRI-spine-STR over 5 years (table).
Conclusion: Our results show that local inflammation is strongly associated with the development of structural damage
over 5 years both in the SIJ and spine in early axSpA and that this effect is independent of systemic inflammation.
Disclosure: A. Sepriano, None; S. Ramiro, None; R. B. M. Landewé, None; M. Dougados, None; D. van der Heijde,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/inflammation-on-mri-of-spine-and-

sacroiliac-joints-is-highly-predictive-of-structural-damage-in-axial-spondyloarthritis-the-5-years-data-of-the-desir-cohort
Which Imaging Outcomes for AxSpA Are Most Sensitive to Change? a 5-

Year Analysis of the DESIR Cohort
Alexandre Sepriano1, Sofia Ramiro2, Désirée van der Heijde1, Maxime Dougados3, Pascal Claudepierre4, Antoine
Feydy5, M. Reijnierse6, Damien Loeuille7 and Robert B.M. Landewé8, 1Leiden University Medical Center, Leiden,
Netherlands, 2Rheumatology, Department of Rheumatology, LUMC, Leiden, Netherlands, Leiden, Netherlands, 3Paris-
Descartes University,, Paris, France, 4Hôpital Henri Mondor, Créteil, France, 5Univ. Paris Descartes, PRES Sorbonne Paris
Cité, Service de radiologie B, Hôpital Cochin, Assistance Publique - Hôpitaux de Paris, Paris, France, Paris, France,
6Department of Radiology, Leiden University Medical Center, Leiden, Netherlands, 7Rheumatology, CHRU Nancy,
Vandoeuvre les Nancy, France, 8University of Amsterdam and Atrium Medical Center, Amsterdam, Netherlands
SESSION INFORMATION
Background/Purpose: Several imaging outcomes have become available to assess inflammation and structural damage
over time in patients with axial spondyloarthris (axSpA). However, no formal comparison of their sensitivity to change has
been made in the early phases of the disease. We aimed to compare the sensitivity to change of different MRI and
radiographic scoring methods in patients with early axSpA.
Methods: Patients from the DESIR cohort fulfilling the ASAS axSpA criteria were included. Radiographs and MRI of the
sacroiliac joints and spine were obtained at baseline, 1 year, 2 years and 5 years. Each film was scored by 2 or 3 readers in
3 ‘reading-waves’ (wave 1: baseline; wave 2: baseline, 1 year, 2 years; wave 3: baseline, 2 years, 5 years). Outcomes
measuring inflammation and structural damage both on MRI and radiographs in the spine and SIJ were assessed (Table).
The analysis of change captured over time was performed using generalized estimating equations (GEE) longitudinal
models separately for each outcome, taking into account data from all readers and waves (‘integrated analysis’). To allow
comparisons across outcomes, these were standardized (difference between the individual score and the mean of all scores
divided by the standard deviation, per reader, wave and time-point) before running the models. The higher the standardized
coefficient the more change in inflammation/damage is captured.
Results: In total, 345 patients were included (mean (SD) symptom duration: 1.6 (0.9) years; 53% males; 89% HLA-B27
positive). Inflammation on MRI-SIJ (according to both the ASAS definition of sacroiliitis and the continuous SPARCC
score) was more sensitive to change as compared to inflammation on the spine that remained essentially unchanged
regardless of the outcome (table). Structural damage on the SIJ was found to increase over time, but with a higher
standardized yearly rate of change on MRI-SIJ (range: 0.015-0.274) as compared to X-SIJ (range: 0.043-0.126). Notably,
≥3 Fatty lesions on MRI-SIJ was the structural outcome in the SIJ with highest sensitive to change (0.274), while ≥3
erosions was the least sensitive (0.015). Spine structural damage slowly progressed over time but, in contrast to SIJ,
radiographic outcomes (i.e. ≥ 1 syndesmophytes and mSASSS) were more sensitive to change than MRI structural
outcomes.
Conclusion: Our data adds to the body of evidence showing that structural damage assessed in pelvic radiographs only has
low sensitivity to change. MRI-SIJ is a promising alternative (especially fatty lesions) capturing more structural changes. In
contrast, in detecting structural change in early axSpA radiographic outcomes outperform MRI outcomes.
Disclosure: A. Sepriano, None; S. Ramiro, None; D. van der Heijde, None; M. Dougados, None; P. Claudepierre,
None; A. Feydy, None; M. Reijnierse, None; D. Loeuille, None; R. B. M. Landewé, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/which-imaging-outcomes-for-axspa-

are-most-sensitive-to-change-a-5-year-analysis-of-the-desir-cohort
Progression of Structural Damage on MRI in Patients with Axial

Spondyloarthritis Is Limited: The 5 –Year Results in the DESIR Cohort
Alexandre Sepriano1, Sofia Ramiro2, Robert B.M. Landewé3, Maxime Dougados4 and Désirée van der Heijde1, 1Leiden
University Medical Center, Leiden, Netherlands, 2Rheumatology, Department of Rheumatology, LUMC, Leiden,
Netherlands, Leiden, Netherlands, 3University of Amsterdam and Atrium Medical Center, Amsterdam, Netherlands, 4Paris-
Descartes University,, Paris, France
SESSION INFORMATION
Background/Purpose: Reliably detecting radiographic structural change in patients with axial spondyloarthritis (axSpA),
especially in the sacroiliac joints (SIJ), is notoriously difficult. Magnetic resonance imaging (MRI) is an alternative for
radiographs to assess structural damage. However, so far the utility of MRI in capturing change in structural damage over
time has been poorly studied. We aimed to evaluate the change over time of structural lesions on MRI of the SIJ and spine
in patients with axSpA.
Methods: Patients with recent onset (≤3 years) axSpA (according to the treating rheumatologist) from the DESIR cohort
were included. MRI of the SIJ (MRI-SIJ) and spine (MRI-spine) were obtained at baseline and 5 years and scored by 3
trained central readers unaware of their chronology. Structural damage in the SIJ (MRI-SIJ-STR) and in the spine (MRI-
spine-STR) was defined according to 3 binary rules (A1: ≥ 5 fatty lesions and / or erosions; B1: ≥ 3 erosions; and C1: ≥ 3
fatty lesions) and 3 continuous scores (A2: number of fatty lesions /erosions; B2: number of erosions; and C2: number of
fatty lesions). For binary outcomes, structural damage was defined by the agreement of at least 2 out of 3 readers and the %
of net progression by subtracting the number of patients that ‘improved’ from those that ‘worsened’ divided by the total
number of patients with complete baseline and 5-year data. For continuous outcomes, the mean of the 3 readers was used
and the difference between year 5 and baseline was calculated.
Results: In total, 151 and 145 patients had complete MRI-SIJ and MRI-spine data available from 3 readers, respectively.
The percentages of net progression at SIJ level are summarized in the figure. These were 6.6%, 0.7% and 7.9% for the
binary outcomes A1, B1 and C1 respectively. Notably, the percentage of ‘improvement’ (4.6%) was almost as high as the
percentage of ‘worsening’ (5.3%) for definition B1 (≥3 erosions); while no ‘improvements’ were seen by the 3 readers for
definition C1 (≥3 fatty lesions). Similar differences were seen for the mean (standard deviation) change of the 3 MRI-SIJ-
STR continuous outcomes (A2: 1.02 (2.60); B2: 0.20 (1.39); and C2: 0.83 (2.20); p<0.01 for all). MRI-spine-STR net
change over time was almost absent (A1: -0.7%; B1: 0.0%; C1: 0.7%) considering the binary outcomes, and small (though
statistically significant) considering definition A2 (0.18 (0.52); p<0.01) and C2 (0.14 (0.48); p<0.01) but absent for
definition B2 (0.03 (0.24); p=0.109).
Conclusion: These results suggest that patients with early axSpA only show modest structural progression in the MRI of
the SIJ and that fatty lesions are more sensitive to change compared to erosions. In this early axSpA population, MRI-
detected structural progression in the spine is very limited/absent.
Disclosure: A. Sepriano, None; S. Ramiro, None; R. B. M. Landewé, None; M. Dougados, None; D. van der Heijde,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/progression-of-structural-damage-on-
mri-in-patients-with-axial-spondyloarthritis-is-limited-the-5-year-results-in-the-desir-cohort
Imaging Biomarkers in Crohn’s Associated Axial Spondyloarthritis

Fardina Malik1, John A. Carrino2, Madeline Epsten3, Ellen Scherl4, Stephanie Wichuk5, Ulrich Weber6, Susanne J
Pedersen7, Joel Paschke8, Jackie Szymonifka3, Georg Kroeber9, Randy Longman4, Walter P. Maksymowych5 and Lisa A.
Mandl3, 1Rheumatology, Hospital For Special Surgery, New York, NY, 2Radiology, Hospital for Special Surgery, New
York, NY, 3Rheumatology, Hospital for Special Surgery, New York, NY, 4Gastroenterology, Weill Cornell Medical College,
New York, NY, 5Medicine, University of Alberta, Edmonton, AB, Canada, 6Institute of Regional Health Research,
University of Southern Denmark, Odense, Denmark, 7Copenhagen Center for Arthritis Research, Glostrup Hospital,
University of Copenhagen, Copenhagen, Denmark, 8CARE Arthritis, Edmonton, AB, Canada, 9University of Southern
Denmark, Odense, Denmark
SESSION INFORMATION
Background/Purpose: Axial SpA has been reported in 4-16% of patients with Crohn's disease (CD). However, some plain
radiograph or magnetic resonance imaging (MRI) studies in Crohn's population suggest presence of sacroiliitis in up to
40% patients. Whether axial SpA is underdiagnosed and hence undertreated is unclear, especially since it does not correlate
with CD activity. This study utilizes standardized MRI SI joint (SIJ) imaging to determine prevalence of axial SpA in a
cohort of CD patients and investigate its relationship with other clinical and serologic measures. In addition, we compare
MRIs from our cohort of CD patients with separate cohorts of patients with known axial SpA with and without
inflammatory bowel disease (IBD).
Methods: Adult consecutive patients meeting pathological, radiological and/or endoscopic criteria of CD and not currently
on any biologic except vedolizumab, were prospectively enrolled from an IBD Clinic. Data collected included length of
CD, history of joint/back pain, HLA-B27 status, BASMI, BASDAI, Harvey-Bradshaw Index (HBI) scores- a measure of
CD activity, Ankylosing Spondylitis Disease Activity Score-C reactive protein (ASDAS-CRP). All patients underwent T1
and short tau inversion recovery (STIR) sequence MRI of SIJ. 3 expert readers, blinded to clinical history reviewed MRIs
for presence of active and/or structural lesions globally indicative of SpA, for ASAS MRI positivity, detailed lesion scores
using the SpA Research Consortium of Canada (SPARCC) SIJ inflammatory and structural scoring methods after
calibration using validated modules. These images were compared to MRIs from age and sex-matched AS patients with and
without IBD.
Results: 32 CD patients were enrolled: 76% females, 80% white, median age 36.4 years (IQR 27.2 – 49) with moderate
CD activity (mean HBI 8.8 ± SD 4.5). 56% had peripheral SpA and only 1 was HLA-B27 positive. 20 reported back pain
and 14 (70%) met ASAS inflammatory back pain (IBP) criteria. Mean BASDAI, ASDAS-CRP and BASMI were higher
than patients without back pain (p <0.05). Total of 9 SIJ MRIs (35% of all patients with back pain and 16% of those
without) showed global evidence of SpA (bone marrow edema BME ≥ 2 and/or structural lesions) and 6 out of those were
ASAS positive (presence of active inflammation/BME), including 2 asymptomatic patients. Older age (OR 1.4, 95% CI
1.04 - 1.90) and higher BASMI (OR 3.2 95% CI 1.1-9.6) were associated with MRI SpA findings. But presence of IBP,
peripheral SpA, CD duration, BASDAI, ASDAS-CRP or HBI did not show association. Compared to historic cohort of AS
patients with (n=23) and without (n=24) IBD, CD patients with IBP had similar BASDAI and ASDAS-CRP scores (p
<0.05) but they had lower BME and structural lesions (p 0.02 and <0.001) compared to IBD with and without SpA.
Conclusion: MRI evidence of axial SpA was 35% and 16% in our cohort of CD patients with and without back pain
respectively. MRI is a valuable tool to diagnose axial SpA in CD patients with back pain, especially those who are older
and has evidence of restricted spinal mobility on exam. Presence of IBP did not show association, as previously suggested,
although these patients experience similar morbidity as our comparator cohort with known AS with or without IBD.
Disclosure: F. Malik, None; J. A. Carrino, None; M. Epsten, None; E. Scherl, None; S. Wichuk, None; U. Weber,
None; S. J. Pedersen, None; J. Paschke, None; J. Szymonifka, None; G. Kroeber, None; R. Longman, None; W. P.
Maksymowych, None; L. A. Mandl, Boehringer Ingelheim, 2,American College of Physicians, 3,Up To Date, 7.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/imaging-biomarkers-in-crohns-

associated-axial-spondyloarthritis
Improved Patient-Reported Outcomes in Psoriatic Arthritis Patients Treated

with Abatacept: Results from a Phase III Trial
Vibeke Strand1, E Alemao2, T Lehman2, A Johnsen2, S Banerjee2, HA Ahmad2 and Philip J Mease3, 1Stanford
University, Palo Alto, CA, 2Bristol-Myers Squibb, Princeton, NJ, 3Swedish Medical Center and University of Washington,
Seattle, WA
SESSION INFORMATION
Background/Purpose: In the Phase III ASTRAEA study (NCT01860976), abatacept (ABA) significantly increased
ACR20 responses, alleviating musculoskeletal symptoms in patients (pts) with active psoriatic arthritis (PsA).1 Here we
explore the effect of ABA on pt-reported outcomes (PROs) in ASTRAEA. Methods: Pts were randomized (1:1) to SC
ABA 125 mg weekly or placebo (PBO) for 24 weeks (W). At W16, pts without ≥20% improvement in joint counts escaped
to open-label ABA. Adjusted mean changes from baseline to W16 (all pts) and W24 (non-escape responder analysis) in
Short Form-36 (SF-36; physical and mental component summary [PCS, MCS] and individual domain scores using
spydergrams), HAQ-DI, Dermatology QoL Index (DLQI), and Functional Assessment of Chronic Illness Therapy-Fatigue
(FACIT-F) scores were evaluated in total population (prespecified intent-to-treat analysis) and subgroups (post hoc)
stratified by baseline CRP and prior TNF inhibitor (TNFi) use. Proportions of pts reporting improvements from baseline
≥minimal clinically important difference (MCID) in SF-36 summary (≥2.5) and domains (≥5.0), FACIT-F (≤−4.0), and
HAQ-DI (≤–0.35), and scores ≥normative values in SF-36 summary (≥50) and individual domains, FACIT-F (<40), and
HAQ-DI (<0.5) at W16 were analyzed in the total population. Results: In the total population, numerical improvements in
most PROs were reported with ABA (n=213) vs PBO (n=211) at both time points (significant for SF-36 PCS at W16,
HAQ-DI at W24, and DLQI at both time points; Table). At W16 before escape, improvements in all SF-36 domains were
numerically greater with ABA (significant for physical function, bodily pain, and vitality). A higher proportion of pts
receiving ABA vs PBO reported improvements ≥MCID in SF-36 PCS, SF-36 MCS, SF-36 domains, FACIT-F, HAQ-DI
(Figure), and DLQI (not shown) at W16. Proportion of pts reporting scores ≥normative values at W16 was higher with
ABA vs PBO for SF-36 PCS, SF-36 MCS, FACIT-F, and HAQ-DI. At W24, improvements in most SF-36 domain scores
accrued in responders in both groups; numerical differences favored ABA. Improvements were observed in all PROs in the
ABA vs PBO group for TNFi-naïve and -exposed subpopulations at W16. Improvements in all PROs were reported with
ABA in baseline CRP >upper limit of normal (ULN) vs CRP ≤ULN subpopulation at W16 (Table). Subgroup data at W24
were difficult to interpret due to lower number of pts assessed vs W16.
Conclusion: Abatacept treatment improved many PROs in pts with active PsA, with larger benefits in the elevated CRP
subpopulation and regardless of prior TNFi exposure. 1. Mease PJ, et al. Ann Rheum Dis 2017 [Epub ahead of print]
Disclosure: V. Strand, AbbVie, Amgen Corporation, AstraZeneca, Biogen, BMS, Boehringer Ingelheim, Celgene,
Celltrion, Corrona, Crescendo / Myriad Genetic, EMD Serono, Genentech / Roche, GlaxoSmithKline, Janssen, Lilly,
Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sano, 5; E. Alemao, Bristol-Myers Squibb, 1,Bristol-Myers
Squibb, 3; T. Lehman, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1, 9; A. Johnsen, Bristol-Myers Squibb, 1,Bristol-
Myers Squibb, 3; S. Banerjee, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1, 9; H. Ahmad, Bristol-Myers Squibb,
3,Bristol-Myers Squibb, 1, 9; P. J. Mease, AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, UCB,
2,AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Corrona, Demira, Janssen, Lilly, Novartis, Pfizer, Sun, UCB,
Zynerba, Speaker Bureau: AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Novartis, Pfizer,
UCB, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/improved-patient-reported-outcomes-

in-psoriatic-arthritis-patients-treated-with-abatacept-results-from-a-phase-iii-trial

Effect of Tofacitinib on Patient-Reported Outcomes in Patients with Active
Psoriatic Arthritis: Results from 2 Phase 3 Studies
Vibeke Strand1, Kurt de Vlam2, Jose A Covarrubias-Cobos3, Philip J Mease4, Dafna D Gladman5, Thijs Hendrikx6,
Elizabeth Kudlacz7, Daniela Graham7, Joseph Wu7, Joseph C Cappelleri7 and Ming-Ann Hsu7, 1Stanford University, Palo
Alto, CA, 2UZ Leuven, Leuven, Belgium, 3Unidad Reumatologica Las Americas S.C.P, Yucatán, Mexico, 4Swedish
Medical Center and University of Washington, Seattle, WA, 5Department of Medicine, University of Toronto, Toronto
Western Hospital, Toronto, ON, Canada, 6Pfizer Inc, Collegeville, PA, 7Pfizer Inc, Groton, CT
SESSION INFORMATION
Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor under investigation for the treatment of psoriatic
arthritis (PsA). Safety and efficacy were investigated in 2 Phase 3 randomized controlled trials (RCTs: OPAL Broaden [12
months; NCT01877668]; OPAL Beyond [6 months; NCT01882439]). This analysis evaluated patient-reported outcomes
(PROs) in patients with active PsA in OPAL Broaden (N=422), with inadequate responses (IR) to ≥1 conventional
synthetic DMARD, naïve to tumor necrosis factor inhibitors (TNFi); and in OPAL Beyond (N=394), IR to ≥1 TNFi.
Methods: Patients were randomized to tofacitinib 5 or 10 mg twice daily (BID) or placebo (PBO) advanced to either
tofacitinib 5 or 10 mg BID at Month 3, and, in OPAL Broaden, to adalimumab 40 mg subcutaneously every 2 weeks. Based
on a longitudinal model, least squares mean (LSM) changes from baseline were reported for the following: Patient Global
Assessment of Disease Activity Visual Analog Scale (PtGA VAS), Pain VAS, Short Form-36 Health Survey Version 2 (SF-
36v2), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Dermatology Life Quality Index (DLQI),
and Ankylosing Spondylitis Quality of Life (ASQOL). Findings were reported using nominal p values without adjustments
for multiple comparisons.
Results: Improvements in PtGA and Pain were observed as early as Week 2 (first assessment), and exceeded PBO at
Month 3 with both tofacitinib doses in both RCTs (p≤0.05 vs PBO) (Table). At Month 3, SF-36v2 Physical Component
Summary (PCS), physical functioning (PF), bodily pain (BP), and vitality (VT) domains, and FACIT-F scores, exceeded
PBO with both doses (p≤0.05) in both trials; improvements in PCS, PF, BP, and FACIT-F exceeded minimum clinically
important differences (MCID). DLQI and ASQOL scores at Month 3 exceeded PBO with both doses in both RCTs
(p≤0.05), and social functioning (SF) domain with both doses in OPAL Beyond and 5 mg BID in OPAL Broaden (p≤0.05).
PRO improvements reported in OPAL Broaden with tofacitinib were similar to adalimumab. The percentages of patients
receiving both tofacitinib doses reporting changes ≥MCID at Month 3 in SF-36v2 PCS, PF, and BP domains were
statistically significant in both RCTs, as were general health (GH) and mental health (MH) domains with 10 mg BID and
FACIT-F with both doses in OPAL Broaden, and SF domains with both doses in OPAL Beyond and role physical (RP) with
10 mg BID.
Conclusion: Patients with active PsA receiving tofacitinib reported statistically greater and clinically meaningful
improvements in PROs compared with PBO at Month 3 in both RCTs.
Disclosure: V. Strand, AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, 5;
K. de Vlam, Eli Lilly, Pfizer Inc, 5,Galapagos, 9; J. A. Covarrubias-Cobos, Bristol-Myers Squibb, Eli Lilly, Janssen,
Pfizer Inc, 2; P. J. Mease, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, Sun
Pharmaceutical, UCB, 2,AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, Sun
Pharmaceutical, UCB, 5,AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer Inc, UCB,
8; D. D. Gladman, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB,
2,AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, 5; T. Hendrikx, Pfizer
Inc, 1,Pfizer Inc, 3; E. Kudlacz, Pfizer Inc, 1,Pfizer Inc, 3; D. Graham, Pfizer Inc, 1,Pfizer Inc, 3; J. Wu, Pfizer Inc,
1,Pfizer Inc, 3; J. C. Cappelleri, Pfizer Inc, 1,Pfizer Inc, 3; M. A. Hsu, Pfizer Inc, 1,Pfizer Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effect-of-tofacitinib-on-patient-

reported-outcomes-in-patients-with-active-psoriatic-arthritis-results-from-2-phase-3-studies
Ixekizumab Improves Patient-Reported Outcomes through 52 Weeks in

Patients with Active Psoriatic Arthritis and Previous Inadequate Response to
Tumor Necrosis Factor-Inhibitors
Arthur Kavanaugh1, Helena Marzo-Ortega2, Ronald Vender3, Julie Birt4, David Adams4, Olivier Benichou4, Chen-Yen
Lin4 and Peter Nash5, 1Medicine, University of California, San Diego, La Jolla, CA, 2Department of Rheumatology,
Chapel Allerton Hospital, Leeds, United Kingdom, 3Dermatrials Research, Inc., Hamilton, ON, Canada, 4Eli Lilly and
Company, Indianapolis, IN, 5University of Queensland, Brisbane, Australia
SESSION INFORMATION
Background/Purpose: Ixekizumab (IXE) is a high affinity monoclonal antibody that selectively targets interleukin-17A.
Up to 24 weeks, IXE was superior to placebo (PBO) in improving health related quality of life of patients with active
psoriatic arthritis (PsA) and previous inadequate response to TNF inhibitors (TNFi) in a phase 3 trial (SPIRIT-P2;
NCT02349295).1 Herein, we report the Week 52 interim patient-reported outcome (PROs) findings of IXE treatment
during the Extension Period (EP) of SPIRIT-P2.
Methods: All 363 patients entering SPIRIT-P2 had an inadequate response to or were intolerant to TNFi. During the
Double-Blind Treatment Period (DBTP; Weeks 0-24), patients were randomly assigned 1:1:1 to subcutaneous
administration of either 80 mg IXE every 4 weeks (Q4W; N=122) or 2 weeks (Q2W; N=123) following a 160 mg starting
dose at Week 0 or PBO (N=118). Of these, 310 patients completed the DBTP and entered the EP (Weeks 24-156). Patients
randomized to IXE at Week 0 continued the same dose regimen in the EP. PBO patients were re-randomized (1:1) to IXE
Q4W or Q2W at Week 16 (inadequate responders) or Week 24 and received a 160 mg starting dose. At baseline and Week
52, the following PROs were assessed: Short Form-36 Health Survey (SF-36) Physical Component Summary (PCS) and
Mental Component Summary (MCS), European Quality of Life 5 Dimensions Visual Analog Scale (EQ-5D VAS; 0-100
scale), Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP; absenteeism, presenteeism, work
productivity, and activity impairment), fatigue Numeric Rating Scale (NRS; 0 [no fatigue]-10 [as bad as you can imagine]
scale), and the itch NRS (0 [no itch]-10 [worst itch imaginable] scale). The fatigue NRS has not been validated. Itch NRS
was assessed in patients with baseline psoriatic lesion involving ≥3% body surface area (BSA; N=175). All analyses were
performed on the EP population. Change in PRO measures from baseline at Week 52 were summarized using descriptive
statistics. Missing values were imputed by modified baseline observation carried forward.
Results: Mean baseline (Week 0) scores of PROs indicated that the EP population had impaired physical and mental
function, quality of life, and work productivity (Table). Patients receiving IXE up to 52 weeks reported improvements in
SF-36 (PCS and MCS), EQ-5D VAS, WPAI-SHP (presenteeism, work productivity, and activity impairment), and fatigue
NRS (Table). For PsA patients with ≥3% BSA baseline psoriasis, improvements in itch NRS were observed for patients
receiving IXE up to 52 weeks.
Conclusion: In patients with active PsA and previous inadequate response to TNF-i, IXE provided sustained improvement
up to 52 weeks in all measured PROs, including physical and mental function, quality of life, work productivity, fatigue,
and itch (≥3% BSA psoriasis).
1. Kavanaugh et al. EULAR. 2017 June 17; Madrid, Spain; [abstract SAT0446]
Disclosure: A. Kavanaugh, Eli Lilly and Company, 5; H. Marzo-Ortega, Janssen Pharmaceutica Product, L.P., 2,Abbvie,
Celgene, Janssen, Eli Lilly and Company, MSD, Novartis, Pfizer, UCB, 5; R. Vender, AbbVie, Actelion, Amgen, Celgene,
Cipher, Eli Lilly and Company, Galderma, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Palladin, Pfizer, and Valeant,
5,AbbVie, Amgen, Centocor, Dermira, Eli Lilly and Company, Galderma, GlaxoSmithKline,Leo Pharma, Merck, Novartis,
Pfizer, Regeneron, and Takeda, 2,AbbVie, Actelion, Amgen, Celgene, Cipher, Eli Lilly and Company, Galderma,
GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Palladin, Pfizer, and Valeant, 8; J. Birt, Eli Lilly and Company, 3,Eli
Lilly and Company, 1; D. Adams, Eli Lilly and Company, 1,Eli Lilly and Company, 3; O. Benichou, Eli Lilly and
Company, 3,Eli Lilly and Company, 1; C. Y. Lin, Eli Lilly and Company, 1,Eli Lilly and Company, 3; P. Nash, AbbVie,
Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Hospira, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi,
and UCB, 5,AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Hospira, Janssen, MSD, Novartis,
Pfizer, Roche, Sanofi, and UCB, 8,AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Hospira,
Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/ixekizumab-improves-patient-reported-

outcomes-through-52-weeks-in-patients-with-active-psoriatic-arthritis-and-previous-inadequate-response-to-tumor-
necrosis-factor-inhibitors
Efficacy of Ustekinumab in Psoriatic Arthritis Patients By Prior Treatment

Exposure and Disease Duration
Arthur Kavanaugh1, Soumya D. Chakravarty2,3, G. James Morgan4, M. Isabel Apaolaza5, Shelly Kafka2, Elizabeth C.
Hsia6,7, Michael Song7, Yin You7 and Iain B. McInnes8, 1Medicine, University of California, San Diego, La Jolla, CA,
2Janssen Scientific Affairs, LLC, Horsham, PA, 3Drexel University College of Medicine, Philadelphia, PA, 4Janssen
Scientific Affairs, LLC, Spring House, PA, 5Janssen Biologics BV, Leiden, Netherlands, 6University of Pennsylvania
School of Medicine, Philadelphia, PA, 7Janssen Research & Development, LLC, Spring House, PA, 8University of
Glasgow, Glasgow, United Kingdom
SESSION INFORMATION
Background/Purpose: To evaluate the efficacy of ustekinumab (UST) by prior treatment exposure and disease duration in
adult PsA patients (pts) in the Phase 3 trials PSUMMIT 1 and PSUMMIT 2.
Methods: Pts had active PsA (≥5 swollen, ≥5 tender joints, CRP ≥ 3.0mg/L,) for ≥6 mos despite treatment with
csDMARDs and/or NSAIDs (PSUMMIT 1) or csDMARDs, NSAIDs, and/or anti-tumor necrosis factor (TNF) agents
(PSUMMIT 2). In both studies, pts were randomized to SC injections of placebo (PBO) or UST 45mg or 90mg at wks 0, 4
and every 12 wks. PBO pts crossed over to UST 45mg at wk 24. At wk 16, early escape (PBOàUST45mg;
UST45mgàUST90mg; UST90mgàUST90mg) was possible. Stable doses of MTX were allowed. Pooled data from both
PSUMMIT 1 and 2 were analyzed. Efficacy assessments included ACR response, DAS28-CRP response, DAS28-CRP
remission (score <2.6), changes in enthesitis (modified MASES index) and dactylitis scores, and total van der Heijde-Sharp
(vdH-S) score for radiographic progression. Pts who were anti-TNF-naïve, MTX- and anti-TNF-naïve, all csDMARD- and
anti-TNF-naïve were evaluated. ACR response at wks 4 and 16 to assess for early efficacy was also evaluated for anti-
TNF-naïve pts with PsA duration <1 year, ≥1 to <3 years, and ≥ 3 years.
Results: In the pooled data, 747 pts were anti-TNF-naïve (53.8% were male; mean age=47 years); 179 pts were MTX- and
anti-TNF-naïve (63.7% were male; mean age =47 years); 146 pts were all csDMARD- and anti-TNF-naïve (61.0% male;
mean age=46 years). In all three prior treatment populations, significantly greater proportions of pts in the combined UST
group vs PBO achieved an ACR20, ACR50, or ACR70 at wk 24. (Table). Similarly, greater proportions of pts in the
combined UST group had DAS28-CRP response or remission vs PBO across all three prior treatment populations. In anti-
TNF-naïve pts, improvements in enthesitis and dactylitis were significantly greater in the combined UST group vs PBO,
and mean change in total vdH-S score was significantly greater for pts in the PBO group than the combined UST group;
comparable trends were observed for the MTX- and anti-TNF-naïve pts and all csDMARD- and anti-TNF-naïve pts, but
did not reach statistical significance due to the smaller sample sizes in both subgroups. Among anti-TNF-naïve pts treated
with UST, ACR20/50/70 response rates were similar across different PsA disease duration groups at early time-points
(either wk 4 or wk 16).
Conclusion: UST-treated patients had greater improvements in signs and symptoms of PsA regardless of prior treatment
exposure and disease duration.
Table. Efficacy at week 24 in PSUMMIT 1 and PSUMMIT 2 combined.
Anti-TNF-naive MTX- and anti-TNF- All csDMARD- and
naive anti-TNF-naive
Placebo Combined Placebo Combined Placebo Combined
UST UST UST
(45mg/90mg) (45mg/90mg) (45mg/90mg)
Randomized 248 499 56 123 45 101
pts, n
ACR20 59 (23.8%) 237 (47.5%) 10 66 (53.7%) 9 (20.0%) 57 (56.4%)
(17.9%)
p<0.001 p<0.001 p<0.001
ACR50 21 (8.5%) 132 (26.5%) 7 (12.5%) 43 (35.0%) 7 (15.6%) 38 (37.6%)
p<0.001 p=0.002 p=0.007

ACR70 7 (2.8%) 64 (12.8%) 2 (3.6%) 24 (19.5%) 2 (4.4%) 20 (19.8%)
p<0.001 p=0.006 p=0.017

DAS28-CRP 90 (36.3%) 327 (65.5%) 17 87 (70.7%) 16 (35.6%) 71 (70.3%)
response (30.4%)
p <0.001 p<0.001 p<0.001
DAS28-CRP 19 (7.7%) 99 (19.8%) 6 (10.7%) 34 (27.6%) 6 (13.3%) 29 (28.7%)
remission
p <0.001 p=0.012 p=0.043
Enthesitis
(modified
MASES
index)
Pts with 351 39 89 29
enthesitis at
baseline, n 176 75
Percent of 19.9 36.2 18.9 34.8 (31/89) 21.4 (6/28) 38.7 (29/75)
patients with (33/166) (123/340) (7/37)
resolution of p=0.077 p=0.096
enthesitis at p<0.001
week 24
Dactylitis (0-
3)
Pts with 233
dactylitis at
baseline, n 113 23 56 16 46
Percent of 42.9 (97/226) 22.7 42.9 (24/56) 20.0 (3/15) 47.8 (22/46)
patients with (5/22)
resolution of p=0.003 p=0.121 p=0.118
dactylitis at 25.5
week 24 (27/106)
Change from
baseline in 1.1 ± 4.2 0.3 ± 1.7 0.8 ± 2.6 0.2 ± 1.4 1.0 ± 2.8 0.2 ± 1.4
total vdH-S
score p<0.001 p=0.197 p=0.105
Data presented as n (%) or mean ± SD unless otherwise noted.
ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology

criteria; DAS28-CRP, 28-joint count disease activity score; MASES, Maastricht
Ankylosing Spondylitis Enthesitis Score ;UST, ustekinumab
Disclosure: A. Kavanaugh, Pfizer, AbbVie, Amgen, Janssen, UCB, Novartis, Eli Lilly, 5,AbbVie, Amgen, Janssen, UCB,
Eli Lilly, Novartis, Pfizer, 2; S. D. Chakravarty, Janssen Scientific Affairs, LLC, 3,Johnson & Johnson, 1; G. J. Morgan,
Janssen Scientific Affairs, LLC, 9,Johnson & Johnson, 1; M. I. Apaolaza, Janssen Biologics BV, 3,Johnson & Johnson, 1;
S. Kafka, Janssen Pharmaceuticals, 3,Johnson & Johnson, 1; E. C. Hsia, Janssen Research & Development, LLC,
3,Johnson & Johnson, LLC, 1; M. Song, Janssen Research & Development, LLC, 3,Johnson & Johnson, 1; Y. You, Janssen
Research & Development, 3,Johnson & Johnson, 1; I. B. McInnes, Janssen Research and Development, LLC, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/efficacy-of-ustekinumab-in-psoriatic-

arthritis-patients-by-prior-treatment-exposure-and-disease-duration
Intravenous Golimumab in Adult Patients with Active Psoriatic Arthritis:

Efficacy and Safety through Week 24
Arthur Kavanaugh1, M. Elaine Husni2, Diane D. Harrison3, Lilianne Kim3, Kim Hung Lo3 and Elizabeth C. Hsia4,
1Medicine, University of California, San Diego, La Jolla, CA, 2Rheumatology, Cleveland Clinic, Cleveland, OH, 3Janssen
Research & Development, LLC, Spring House, PA, 4Janssen Research & Development, LLC/University of Pennsylvania,
Spring House/Philadelphia, PA
SESSION INFORMATION
Background/Purpose: The GO-VIBRANT study was designed to evaluate the safety and efficacy of intravenous (IV)
golimumab (GLM) in adult patients (pts) with active PsA (biologic-naïve).
Methods: GO-VIBRANT is a Phase 3, multicenter, randomized, double-blind, placebo (PBO)-controlled trial. Biologic-
naïve active PsA pts were randomized (1:1) to IV GLM 2mg/kg at weeks (wk) 0, 4, and every 8 wks thereafter or PBO at
wks 0, 4, 12, and 20 with crossover to GLM at wk24. The primary endpoint was ACR20 response at wk14. Multiplicity-
controlled endpoints included ACR50, ACR70, PASI 75, change from baseline in HAQ-DI, enthesitis, dactylitis; and
ACR50 and change from baseline in total modified vdH-S (structural damage) score at wk24. Efficacy analyses were based
on randomized treatment. Adverse events (AE) through wk24 are reported here.
Results: 480 pts were randomized (PBO: 239; GLM: 241). The study met its primary and all controlled secondary
endpoints. At wk14, significantly greater proportions of GLM pts vs PBO achieved ACR20 (75.1% vs. 21.8%). Also, GLM
treatment resulted in significant change from baseline HAQ-DI score (-0.60 vs. -0.12), ACR50 (43.6% vs. 6.3%), PASI 75
(59.2% vs. 13.6%), ACR70 (24.5% vs. 2.1%), and change from baseline in enthesitis and dactylitis scores (-1.8 vs. -0.8 and
-7.8 vs. -2.8, respectively) (all p<0.001) at wk14. At wk24, significantly greater proportions of GLM pts vs. PBO pts
achieved ACR 50 (53.5% vs. 6.3%, p<0.001). At wk24, there was significantly less progression of structural damage for
GLM pts vs PBO as measured by change from baseline in total modified vdH-S score (-0.36 vs. 1.95; p<0.001). ACR20
was significantly higher with GLM than PBO as early as wk2 (45.6% vs. 7.5%; p<0.001). 27.0% of GLM pts (vs. 4.2%
PBO) achieved Minimal Disease Activity by wk14. In a post-hoc analysis, the number needed to treat for ACR20 at wk14
was 1.9 (Table). Through wk24, 46.3% of GLM pts and 40.6% of PBO pts had ≥1 AE; 2.9% vs. 3.3% of pts, respectively,
had ≥1 serious AE. Two deaths and 2 malignancies, all in PBO pts and 1 demyelinating event in a GLM pt were reported.
The most common type of AE was infection (20.0% of GLM pts vs. 13.8% of PBO pts). No opportunistic infection or
tuberculosis was reported through wk24. The rate of infusion reactions in GLM-treated pts was low at <2%; none was
serious or severe.
Conclusion: In pts with active PsA, IV GLM demonstrated significant and clinically meaningful improvements of disease
activity and physical function, skin psoriasis clearance, HRQoL, dactylitis and enthesitis, and inhibition of structural
damage progression. GLM was well-tolerated through wk24; the safety profile was consistent with other anti-TNF
therapies, including SC GLM.
Table. Clinical Response
Placebo Golimumab 2 P-
mg/kg values
Patients randomized, n 239 241
Clinical efficacy at wk14
ACR20, n (%) 52 (21.8%) 181 (75.1%)) p<0.001
ACR50, n (%) 15 (6.3%) 105 (43.6%) p<0.001
ACR70, n (%) 5 (2.1%) 59 (24.5%) p<0.001
PASI 75, n (%)* 27/198 (13.6%) 116/196 (59.2%) p<0.001
Change from baseline in HAQ-
DI (n) 222 233
Mean (SD) -0.12 (0.47) -0.60 (0.53) p<0.001
enthesitis** (n) 173 182
Mean (SD) -0.8 (1.98) -1.87 (1.75) p<0.001
dactylitis** (n) 115 130
Mean (SD) -2.8 (7.03) -7.8 (8.57) p<0.001
Minimal Disease Activity
MDA n/N (%) 10/239 (4.2%) 65/241 (27.0%) p<0.001
Number Needed to Treat (ACR
20)
NNT (95% CI) 1.9 (1.64, 2.18)
Clinical efficacy at Week 24
ACR50, n (%) 15 (6.3%) 129 (53.5%) p<0.001
Imaging data at Week 24
Change from baseline in vdH-S 237 237
score (N)
Mean (SE) 1.95 (0.264) -0.36 (0.144) p<0.001
*Among pts with ≥3% BSA involvement at baseline

**Among pts with finding at baseline
ACR, American College of Rheumatology Criteria; PASI, Psoriasis Area

Severity Index; HAQ-DI, Health assessment questionnaire disability index; CI,
confidence interval; SD, standard deviation; SE, standard error; vdH-S, total
modified van der Heijde-Sharp
Disclosure: A. Kavanaugh, Pfizer, AbbVie, Amgen, Janssen, UCB, Novartis, Eli Lilly, 5,AbbVie, Amgen, Janssen, UCB,
Eli Lilly, Novartis, Pfizer, 2; M. E. Husni, AbbVie, Janssen, BMS, Novartis, Eli Lilly, 5; D. D. Harrison, Janssen
Research & Development, LLC, 3,Johnson & Johnson, LLC, 1; L. Kim, Janssen Research & Development, LLC,
3,Johnson & Johnson, LLC, 1; K. H. Lo, Janssen Research & Development, LLC, 3,Johnson & Johnson, LLC, 1; E. C.
Hsia, Janssen Research & Development, LLC, 3,Johnson & Johnson, LLC, 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/intravenous-golimumab-in-adult-
patients-with-active-psoriatic-arthritis-efficacy-and-safety-through-week-24
Low Rates of Major Adverse Cardiac Events, Malignancies, and Serious

Infections in Subjects with Psoriasis and Psoriatic Arthritis Treated with
Apremilast for ≥156 Weeks: Pooled Analysis from the Esteem and Palace 1-3
Phase 3 Trials
Arthur Kavanaugh1, Matthias Augustin2, Eric Lespessailles3, Kim A. Papp4, Maria Paris5, Rongdean Chen5, Dafna D
Gladman6, David M. Pariser7 and Ketty Peris8, 1University of California, San Diego, School of Medicine, La Jolla, CA,
2Institute for Health Care Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf,
Hamburg, Germany, 3University of Orleans, Orleans, France, 4Probity Medical Research, Waterloo, ON, Canada, 5Celgene
Corporation, Summit, NJ, 6Toronto Western Hospital, Toronto, ON, Canada, 7Eastern Virginia Medical School and Virginia
Clinical Research, Inc., Norfolk, VA, 8Catholic University of Rome, Rome, Italy
SESSION INFORMATION
Background/Purpose: Apremilast (APR), an oral PDE4 inhibitor, was effective in phase 3, randomized, placebo (PBO)-
controlled trials assessing treatment of moderate to severe plaque psoriasis (ESTEEM 1 and 2) and psoriatic arthritis (PsA;
PALACE 1-3). We report MACE, malignancies, and serious infections (SIs; opportunistic and non-opportunistic)
incidences in subjects receiving APR 30 mg BID (APR30) for ≥156 wks in a pooled analysis of these studies.
Methods: Incidence rates and exposure-adjusted incidence rates (EAIR)/100 subject-yrs of MACE, malignancies, SIs, and
serious opportunistic infections (SOIs) are reported for 0 to 16 wks, 0 to ≤52 wks, and the APR-exposure period (0 to ≥156
wks) for subjects receiving APR30 any time during the studies, through February 2015; ~30% (n=575) of sbjs received >3
yrs (>156 wks) of APR exposure.
Results: 2,242 subjects were included in the safety analysis for 0 to 16 wks (PBO n=913, subject-yrs exposure [sy]=260.2;
APR30 n=1,329, sy=377.8); 1,905 subjects received APR30 during the APR-exposure period, representing 3,527.5 sy.
Exposure during 0 to ≤52 wks was 1,524.5 sy. At baseline, 64.2% of APR30 subjects with PsA (PALACE 1-3) were
receiving concomitant DMARDs (including methotrexate). Incidence of MACE with APR30 was low and comparable to
PBO during 0 to 16 wks. During 0 to ≤52 wks and the APR-exposure period, incidence of MACE (EAIR/100 subject-yrs)
remained low (Table). Incidence rates (EAIR/100 subject-yrs) of hematologic malignancies, nonmelanoma skin cancers,
and solid tumors were similar with PBO (0.0, 1.2, 0.4) and APR30 (0.0, 1.3, 0.3) during 0 to 16 wks; incidence rates
remained low during 0 to ≤52 wks and the APR-exposure period (Table). During 0 to 16 wks, the overall rate of SIs and
non-SIs was low and comparable between subjects receiving PBO (20.6%) and APR30 (24.8%). The overall rate of SIs and
non-SIs was 42.2% during 0 to ≤52 wks and comparable to rates during the PBO-controlled period (0 to 16 wks); the
majority of reported infections (upper respiratory tract infection, nasopharyngitis, sinusitis) were not serious. During the
PBO-controlled period (0 to 16 wks), rates of SIs with APR30 were low and comparable to PBO; no SOIs were reported.
During 0 to ≤52 wks, the overall rate of SIs was low (0.6%; EAIR/100 subject-yrs: 0.7). The rate of SIs remained low
(1.8%; EAIR/100 subject-yrs: 1.0) during the long-term cumulative APR-exposure period (0 to ≥156 wks) (Table). No
clustering of any particular event was noted with respect to SIs; most events occurred in only 1 subject. No clinical
reactivation of tuberculosis was reported with long-term APR30 exposure (0 to ≥156 wks). The rate of marked hematologic
abnormalities remained low with long-term APR exposure.
Conclusion: Incidence of MACE, malignancies, and SIs was low in subjects with psoriasis and PsA receiving APR30 for
≥156 wks. No new safety signals or SOIs were observed over time with APR30.
Disclosure: A. Kavanaugh, Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche,
UCB, 2; M. Augustin, AbboVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene Corporation, Centocor, Eli
Lilly, GSK, Janssen-Cilag, LEO Pharma, Medac, Merck, MSD, Novartis, Pfizer, UCB, XenoPort, 5,AbboVie, Almirall,
Amgen, Biogen, Boehringer Ingelheim, Celgene Corporation, Centocor, Eli Lilly, GSK, Janssen-Cilag, LEO Pharma,
Medac, Merck, MSD, Novartis, Pfizer, UCB, XenoPort, 8; E. Lespessailles, Amgen, Eli Lilly, Novartis, Servier, 2,Amgen,
Eli Lilly, Novartis, Servier, 8; K. A. Papp, AbbVie, Akros, Amgen, Astellas, AstraZeneca, Baxalta, Baxter, Boehringer
Ingelheim, Bristol-Meyers Squibb, Can-Fite, Celgene, Dermira, Devonian, Dow Pharma, Eli Lilly, Galderma, Genentech,
Janssen, Kyowa Hakko Kirin, Leo Pharma, Meiji Seika Pharma, 5,Merck MSD, Merck-Serono, Mitsubishi Pharma, Mylan,
Novartis, Pfizer Inc, Regeneron, Roche, Sanofi-Aventis/Genzyme, Takeda, UCB, Valeant, 5,AbbVie, Amgen, Astellas,
Celgene, Devonian, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin, Leo Pharma, Merck MSD, Novartis, Pfizer Inc,
Valeant, 8,Abbvie, Akros, Allergen, Amgen, Anacor, Astellas, Baxalta, Boehringer Ingelheim, Bristol-Meyers Squibb,
Celgene, Dermira, Dow Pharma, Eli Lilly, Galderma, Genentech, GSK, Janssen, Kyowa Hakko Kirin, Leo Pharma,
MedImmune, Merck MSD, Merck-Serono, Mylan, 2,Novartis, Pfizer Inc, Regeneron, Roche, Sanofi-Aventis/Genzyme,
Stiefel, Takeda, UCB, Valeant, 2,AbbVie, Akros, Amgen, Baxter, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma,
Janssen, Kyowa Hakko Kirin, Merck MSD, Merck-Serono, Mitsubishi Pharma, Novartis, Pfizer Inc, Takeda, UCB,
Valeant, 9,Akros, Anacor, Kyowa Hakko Kirin, 9,AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen,
Kyowa Hakko Kirin, Merck MSD, Merck-Serono, Novartis, Pfizer Inc, Regeneron, Sanofi-Aventis/Genzyme, Valeant,
9,AbbVie, Amgen, Astellas, Baxter, Boehringer Ingelheim, Bristol-Meyers Squibb, Celgene, Dow Pharma, Eli Lilly,
Galderma, Janssen, Merck MSD, Novartis, Pfizer Inc, Regeneron, Sanofi-Aventis/Genzyme, UCB, Valeant, 9; M. Paris,
Celgene Corporation, 3; R. Chen, Celgene Corporation, 3; D. D. Gladman, Abbvie, 2,Amgen, 2,Celgene, 2,BMS,
2,Janssen Pharmaceutica Product, L.P., 2,Eli Lilly and Company, 5,Novartis Pharmaceutical Corporation, 2,Pfizer Inc,
2,UCB, 2; D. M. Pariser, Abbott Laboratories, Amgen, Astellas Pharma US, Asubio Pharmaceuticals, Basilea
Pharmaceutical, Celgene Corporation, Dow Pharmaceutical Sciences, Eli Lilly, Galderma Laboratories, Graceway
Pharmaceuticals, Intendis, Johnson and Johnson, Novartis Pharmaceu, 2,LEO Pharma US and Pfizer, 9; K. Peris, Eli Lilly,
LEO Pharma, MEDA, Roche, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/low-rates-of-major-adverse-cardiac-

events-malignancies-and-serious-infections-in-subjects-with-psoriasis-and-psoriatic-arthritis-treated-with-apremilast-for-
%e2%89%a5156-weeks-pooled-analysis-from
Long-Term (4-Year) Efficacy and Safety of Apremilast Monotherapy in

DMARD-Naive Subjects with Active Psoriatic Arthritis
Alvin F. Wells1, Christopher J. Edwards2, Alan J. Kivitz3, Paul Bird4, Dianne Nguyen5, Maria Paris5, Lichen Teng5 and
Jacob A. Aelion6, 1Rheumatology and Immunotherapy Center, Franklin, WI, 2University Hospital Southampton,
Southampton, United Kingdom, 3Altoona Center for Clinical Research, Duncansville, PA, 4University Of New South
Wales, Sydney, Australia, 5Celgene Corporation, Summit, NJ, 6West Tennessee Research Institute, Jackson, TN
SESSION INFORMATION
Background/Purpose: Apremilast (APR) is an oral phosphodiesterase 4 inhibitor that helps regulate the immune responses
that cause joint inflammation and other manifestations of psoriatic arthritis (PsA), including skin disease. The primary
findings from the PALACE 4 study (NCT01307423) demonstrated greater efficacy with APR vs. placebo in disease-
modifying anti-rheumatic drug (DMARD)-naïve subjects with active PsA.1 We describe the long-term efficacy and safety
of APR monotherapy in DMARD-naïve subjects in PALACE 4 for up to 208 weeks.
Methods: Subjects were randomized (1:1:1) to placebo, APR 30 mg BID (APR30), or APR 20 mg BID (APR20). At Week
16, subjects were eligible for early escape. At Week 24, all subjects remaining on placebo were switched to APR. Double-
blind treatment continued to Week 52, with open-label APR treatment for up to 4 additional years; subjects randomized to
APR30 or APR20 continued with their assigned dose during open-label treatment.
Results: A total of 527 subjects were randomized and received ≥1 dose of placebo (n=176), APR30 (n=176), or APR20
(n=175). Of the subjects entering the fourth year of treatment, 92.6% (250/270) completed the Week 208 visit. At Week 52,
58.0% (119/205) of subjects receiving APR30 achieved a ≥20% improvement in modified American College of
Rheumatology (ACR20) response. At Week 208, rates of improvement in PsA signs and symptoms and physical function
were sustained (Table). Of the subjects still receiving study drug, 68.2%, 43.4%, and 23.1% achieved a modified ACR20,
ACR50, and ACR70 response, respectively; 40.5% and 67.6% achieved ≥75% and ≥50% reduction from baseline Psoriasis
Area and Severity Index (PASI-75 and PASI-50) responses, respectively (Table). During Weeks >156 to ≤208, the most
common adverse events (AEs) among APR30-exposed subjects were upper respiratory tract infection (4.3%) and
nasopharyngitis (6.5%); serious AEs occurred in 5.8% of APR30 subjects; serious infection was reported by 1 APR30
subject and no opportunistic infections were reported during Week >156 to ≤208. In general, no change in the types of AEs
and no increase in the incidence and severity of AEs were seen with longer-term exposure. The APR20 safety profile was
similar to that of APR30.
Conclusion: Over 208 weeks, APR monotherapy demonstrated sustained response and improvements in PsA signs and
symptoms, including swollen and tender joint counts, enthesitis, dactylitis, physical function, and psoriasis. APR continued
to demonstrate an acceptable safety profile and was generally well tolerated.
Reference: 1. Wells et al. Arthritis Rheum. 2014;66(10 Suppl):S264-5. Abstract 602.

Disclosure: A. F. Wells, Celgene Corporation, 2; C. J. Edwards, Celgene Corporation, Pfizer, Roche, Samsung, 2,Celgene
Corporation, Pfizer, Roche, Samsung, 5,Abbott, GSK, Pfizer, Roche, 8; A. J. Kivitz, Cytori Therapeutics, 2; P. Bird,
Celgene Corporation, 2; D. Nguyen, Celgene Corporation, 3; M. Paris, Celgene Corporation, 3; L. Teng, Celgene
Corporation, 3; J. A. Aelion, AbbVie, Ardea Biosciences, AstraZeneca, BMS, Celgene Corporation, Centocor, Eli Lilly,
Galápagos, Genenech, GSK, Human Genome Sciences, Janssen, Merck, Mesoblast, Novartis, Novo Nordisk, Pfizer,
Roche, Sanofi-Aventis, Takeda, UCB, Vertex, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/long-term-4-year-efficacy-and-safety-

of-apremilast-monotherapy-in-dmard-naive-subjects-with-active-psoriatic-arthritis
Improvements in Work Productivity with up to 104 Weeks of Apremilast

Monotherapy: Results from a Phase 3b, Randomized, Controlled Study in
Biologic-NaïVe Subjects with Active Psoriatic Arthritis
Philip J Mease1, Dafna D Gladman2, Eric K Davenport3, Xiaolei Zhou3, Benoit Guerette4, Lichen Teng4, Satyin Kaura4
and Peter Nash5, 1Swedish Medical Center and University of Washington School of Medicine, Seattle, WA, 2Krembil
Research Institute, Toronto Western Hospital, Toronto, ON, Canada, 3RTI Health Solutions, Research Triangle Park, NC,
4Celgene Corporation, Summit, NJ, 5University of Queensland, Brisbane, Australia
SESSION INFORMATION
Background/Purpose: Patients with active psoriatic arthritis (PsA) may experience disease manifestations across multiple
domains, as well as impaired functioning in daily activities at home and at work. ACTIVE, a phase 3b study, is evaluating
the efficacy of apremilast (APR) monotherapy in biologic-naïve subjects with PsA who may have had exposure to 1 prior
conventional disease-modifying anti-rheumatic drug. The ACTIVE work productivity findings through Week 104 are
reported.
Methods: Subjects were randomized (1:1) to receive APR 30 mg BID or placebo. Subjects who did not improve at least
10% in both swollen and tender joint counts at Week 16 were eligible for early escape. At Week 24, all remaining placebo
subjects were switched to APR. Work productivity and activity impairment were assessed at baseline and Week 16 using
the 6-item, self-administered Work Productivity and Activity Impairment Questionnaire: Psoriatic Arthritis (WPAI:PsA).
The WPAI:PsA includes 4 subscale scores: Absenteeism, Presenteeism, Work Productivity Loss, and Activity Impairment;
subscale scores each range from 0% to 100%, with higher scores indicating greater impairment. Work-related subscales
were evaluated only among employed subjects, while activity impairment was evaluated among all subjects, regardless of
employment. Correlations were examined at Week 16 between WPAI:PsA subscale scores and selected 36-item Short-Form
Health Survey version 2 (SF-36v2) domain scores (i.e., Physical Functioning [PF], Bodily Pain [Pain], and Vitality [VIT]).
Improvement in work productivity was assessed through Week 104.
Results: Baseline characteristics were similar between the APR and placebo subjects with WPAI:PsA scores included in
the current analysis. At Week 16, APR significantly improved work productivity and the ability to carry out daily activities
compared with placebo, with significantly greater mean improvements observed in the overall Work Productivity Loss
score (P=0.001) and Activity Impairment score (P<0.001) (Table). Estimated mean change in the Absenteeism score was
similar with APR vs. placebo (P=0.679). By contrast, the Presenteeism score showed significant improvement with APR
vs. worsening with placebo (−10.8% vs. 4.1%; P=0.002). At Week 16, statistically significant correlations were observed
between WPAI:PsA subscale scores (except Absenteeism) and SF-36v2 domain scores (i.e., PF, Pain, and VIT). Among
subjects randomized to receive APR at baseline, Week 16 WPAI:PsA subscale score improvements were generally
maintained through Week 104.
Conclusion: In biologic-naïve subjects with active PsA, APR monotherapy contributed to an overall improvement in work
productivity at Week 16, which correlated with SF-36v2 PF, Pain, and VIT scores; improvements in WPAI:PsA subscale
scores were generally maintained to Week 104.
Disclosure: P. J. Mease, Celgene, Novartis, AbbVie, Amgen, BMS, Lilly, Pfizer and UCB, 2,Celgene, Corrona, Novartis,
AbbVie, Amgen, BMS, Crescendo, Genentech, Janssen, Lilly, Merck, Pfizer and UCB, 5,AbbVie, Amgen, BMS,
Crescendo, Celgene, Genentech, Janssen, Pfizer and UCB, 8; D. D. Gladman, Abbvie, 2,Amgen, 2,Celgene, 2,BMS,
2,UCB, 2; E. K. Davenport, None; X. Zhou, None; B. Guerette, Celgene Corporation, 3; L. Teng, Celgene Corporation,
3; S. Kaura, Celgene Corporation, 3; P. Nash, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company,
Lilly and Company, Hospira, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, 8,AbbVie, Amgen, Bristol-Myers
Squibb, Celgene, Eli Lilly and Company, Hospira, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/improvements-in-work-productivity-
with-up-to-104-weeks-of-apremilast-monotherapy-results-from-a-phase-3b-randomized-controlled-study-in-biologic-naive-
subjects-with-active-psoriatic-arthritis
Characterization of Clinical Benefits in Subjects Classified As ACR20 Non-

Responders at Week 104 of Apremilast Treatment: Subanalysis of 3 Long-
Term, Phase III Trials
Philip J Mease1, Dafna D Gladman2, Arthur Kavanaugh3, Priscila Nakasato4, Benoit Guerette4, Lichen Teng4 and Peter
Nash5, 1Swedish Medical Center and University of Washington School of Medicine, Seattle, WA, 2Krembil Research
Institute, Toronto Western Hospital, Toronto, ON, Canada, 3University of California, San Diego, School of Medicine, La
Jolla, CA, 4Celgene Corporation, Summit, NJ, 5University of Queensland, Brisbane, Australia
SESSION INFORMATION
Background/Purpose: The PALACE 1, 2, and 3 trials evaluated the efficacy and safety of apremilast (APR) in subjects
with active psoriatic arthritis (PsA) despite prior conventional disease-modifying anti-rheumatic drugs and/or biologics.
The objective of this analysis is to further characterize the clinical benefits associated with long-term APR exposure in
subjects who failed to achieve an ACR20 response at Week 104.
Methods: Subjects were randomized (1:1:1) at baseline to receive placebo (PBO), APR 30 mg BID (APR30), or APR 20
mg BID. Subjects who were randomized to APR30 at baseline and classified as ACR20 non-responders (ACR20NRs) at
Week 104 were considered for this analysis. At Weeks 24, 52, and 104, ACR core components were examined as well as
the proportions of subjects achieving a low disease activity (LDA) state (Clinical Disease Activity in Psoriatic Arthritis
[cDAPSA] score ≤13), PASI-75/PASI-50 response among those with psoriasis involvement >3% of the body surface area at
baseline, and dactylitis count and Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) of 0 among those with
dactylitis or enthesitis at baseline. Safety is described for the overall PALACE 1-3 population.
Results: A total of 109 subjects randomized to APR30 treatment at baseline were ACR20NRs at Week 104. Lack of
improvement in Patient's Global Assessment of Disease Activity, patient’s assessment of pain, HAQ-DI, and C-reactive
protein outcomes most commonly had an impact on patients’ inability to achieve an ACR20 response. Baseline ACR core
components were similar for ACR20NRs and ACR20 responders at Week 104. Among these ACR20NRs, several core
components of ACR response, including swollen/tender joint counts and static Physician’s Global Assessment of Disease
Activity (visual analog scale) scores, showed sustained improvements from baseline through Week 104 (Table).
Importantly, of the 109 ACR20NRs at Week 104, 27.5% achieved cDAPSA LDA state and 50.0% achieved a PASI-50
response after continued treatment with APR30 through Week 104 (Table). Among ACR20NRs with baseline dactylitis
(n=44) or enthesitis (n=74), 68.2% achieved a dactylitis count of 0 and 33.8% achieved a MASES of 0 at Week 104. In the
overall subject population, no new safety concerns were identified through 104 weeks.
Conclusion: ACR20NRs receiving APR30 demonstrated significant improvements in core PsA domains. The data may
explain why subjects who failed to achieve an ACR20 response remained on long-term APR treatment. These findings
suggest that some subjects with PsA may experience meaningful clinical improvement that is not completely captured by
the assessment of ACR20 response criteria. Outcome measures specifically designed for PsA patients may be more suitable
for evaluating treatment response in PsA patients.
Disclosure: P. J. Mease, Celgene, Novartis, AbbVie, Amgen, BMS, Lilly, Pfizer and UCB, 2,Celgene, Corrona, Novartis,
AbbVie, Amgen, BMS, Crescendo, Genentech, Janssen, Lilly, Merck, Pfizer and UCB, 5,AbbVie, Amgen, BMS,
Crescendo, Celgene, Genentech, Janssen, Pfizer and UCB, 8; D. D. Gladman, Abbvie, 2,Amgen, 2,Celgene, 2,BMS,
2,UCB, 2; A. Kavanaugh, Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche,
UCB, 2; P. Nakasato, Celgene Corporation, 3; B. Guerette, Celgene Corporation, 3; L. Teng, Celgene Corporation, 3; P.
Nash, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/characterization-of-clinical-benefits-in-

subjects-classified-as-acr20-non-responders-at-week-104-of-apremilast-treatment-subanalysis-of-3-long-term-phase-iii-
trials
Consistent Safety Profile with up to 4 Years of Apremilast Treatment:

Analysis of Data from 1,493 Subjects with Psoriatic Arthritis in 3 Large,
Phase III, Long-Term Studies
Philip J Mease1, Dafna D Gladman2, Juan J. Gomez-Reino3, Stephen Hall4, Arthur Kavanaugh5, Eric Lespessailles6,
Georg Schett7, Maria Paris8, Lichen Teng8 and Jürgen Wollenhaupt9, 1Swedish Medical Center and University of
Washington School of Medicine, Seattle, WA, 2Toronto Western Research Institute, Toronto, ON, Canada, 3Hospital
Clínico Universitario de Santiago, Santiago de Compostela, Spain, 4Monash University, CabriniHealth, Melbourne,
Australia, 5University of California, San Diego, School of Medicine, La Jolla, CA, 6University of Orleans, Orleans, France,
7Friedrich Alexander University Erlangen-Nurnberg, Erlangen, Germany, 8Celgene Corporation, Summit, NJ, 9Schön
Klinik Hamburg-Eilbek, Klinik fur Rheumatologie, Hamburg, Germany
SESSION INFORMATION
Background/Purpose: Apremilast (APR), an oral phosphodiesterase 4 inhibitor, regulates immune activity in psoriatic
arthritis (PsA) patients. We evaluated the long-term safety of APR treatment for up to 4 years in subjects with active PsA
despite prior conventional disease-modifying anti-rheumatic drugs (DMARDs) and/or biologics. Safety data were pooled
from the phase 3 PALACE 1, 2, and 3 studies.
Methods: Subjects were randomized at baseline (1:1:1) to receive placebo (PBO), APR 30 mg BID (APR30), or APR 20
mg BID (APR20). PBO subjects were re-randomized to APR30 or APR20 at Week 16 (early escape) or Week 24. Double-
blind APR treatment continued to Week 52; subjects could continue APR during an open-label, long-term treatment phase
for up to 5 years treatment. Visits in years 2, 3, and 4 were scheduled at 13-week intervals. Safety was assessed at each visit
throughout the study, and results are summarized here by exposure.
Results: A total of 1,493 subjects were randomized and received ≥1 dose of study medication (PBO: n=495; APR30:
n=497; APR20: n=501). At the 4-year data cut, the numbers of subjects receiving APR30 and APR20 in each exposure
period were 1,441 in Weeks 0 to ≤52, 1,028 in Weeks >52 to ≤104, 865 in Weeks >104 to ≤156, and 767 in Weeks >156 to
≤208. During the 0- to ≤52-week APR-exposure period, adverse events (AEs) occurring in ≥5% of APR30-exposed
subjects were diarrhea, nausea, headache, upper respiratory tract infection, and nasopharyngitis (Table). Most diarrhea and
nausea AEs were reported within the first 2 weeks of treatment and usually resolved within 4 weeks; the frequency of
gastrointestinal AEs decreased with longer APR30 exposure, and the frequency of other common AEs either decreased or
remained stable with prolonged exposure (Table). Most AEs were mild or moderate in severity. During Weeks >156 to
≤208 of APR exposure, the discontinuation rate due to AEs was 1.7% with APR30, and the rate of serious AEs (SAEs) was
7.0%, consistent with earlier periods; most SAEs occurred in 1 subject each. Rates were very low for major cardiac events,
malignant neoplasms, and serious opportunistic infections, comparable to the first year of treatment. Rates of depression
remained very low in Weeks >156 to ≤208. Marked laboratory abnormalities were infrequent, and most returned to baseline
values with continued treatment.
Conclusion: APR30 demonstrated a favorable and consistent safety profile and was well tolerated for up to 208 weeks,
marked by the lack of an increase in infection rates or a need for specific laboratory monitoring. The incidence of AEs
remained stable or decreased with long-term exposure to APR30.
Disclosure: P. J. Mease, Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Genentech, Janssen,
Novartis, Pfizer, Roche, UCB, 2,Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Genentech, Janssen,
Novartis, Pfizer, Roche, UCB, 5,Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB, 8; D. D.
Gladman, Abbvie, 2,Amgen, 2,Celgene, 2,BMS, 2,Janssen Pharmaceutica Product, L.P., 2,Eli Lilly and Company,
5,Novartis Pharmaceutical Corporation, 2,Pfizer Inc, 2,UCB, 2; J. J. Gomez-Reino, Roche, Schering-Plough, 2,BMS,
Pfizer, Roche, Schering-Plough, UCB, 5; S. Hall, Boehringer Ingelheim, MSD, Roche, Schering-Plough, Servier, Wyeth,
5,Amgen, AstraZeneca, Boehringer Ingelheim, Centocor, GSK, MSD, Pfizer, Sanofi Aventis, Sanofi Pasteur, Schering-
Plough, Serono, Wyeth, 9,Boehringer Ingelheim, GSK, MSD, Pfizer, Roche, Sanofi Aventis, Schering-Plough, Wyeth, 8;
A. Kavanaugh, Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB, 2; E.
Lespessailles, Amgen, Eli Lilly, Novartis, Servier, 2,Amgen, Eli Lilly, Novartis, Servier, 8; G. Schett, Abbott, Celgene
Corporation, Roche, UCB, 2,Abbott, Celgene Corporation, Roche, UCB, 5; M. Paris, Celgene Corporation, 3; L. Teng,
Celgene Corporation, 3; J. Wollenhaupt, Abbott, BMS, MSD, Pfizer, UCB, 2,Abbott, BMS, MSD, Pfizer, UCB, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/consistent-safety-profile-with-up-to-4-

years-of-apremilast-treatment-analysis-of-data-from-1493-subjects-with-psoriatic-arthritis-in-3-large-phase-iii-long-term-
studies
Ixekizumab Exhibits a Favorable Safety Profile during 24 Weeks of

Treatment in Subjects with Active Psoriatic Arthritis: Integrated Safety
Analysis of Two Randomized, Placebo Controlled, Phase III Clinical Trials
Philip J Mease1, Gerd R. Burmester2, Susan Moriarty3, Olivier Benichou3, Wen Xu3 and Peter Nash4, 1Swedish Medical
Center and University of Washington, Seattle, WA, 2Department of Rheumatology and Clinical Immunology, Charité -
University Medicine Berlin, Free University and Humboldt University Berlin, Berlin, Germany, 3Eli Lilly and Company,
Indianapolis, IN, 4University of Queensland, Brisbane, Australia
SESSION INFORMATION
Background/Purpose: Ixekizumab (IXE) is a high affinity monoclonal antibody that selectively targets IL-17A. The
objective of this analysis is to report the integrated safety of IXE in 2 pivotal trials in patients with active PsA.
Methods: The SPIRIT phase 3 trials consist of patients with active PsA who were bDMARD-naive (SPIRIT-P1,
NCT01695239) or were inadequate responders to TNF-inhibitors (SPIRIT-P2; NCT02349295). Patients were randomized
to 80 mg IXE every 4 weeks (Q4W, N=229) or 2 weeks (Q2W, N=225) after a 160 mg starting dose or PBO (N=224).
Integrated safety data are presented from the PBO-controlled treatment periods (Weeks 0-24). Safety was assessed for
patients who received at least 1 dose of study drug. At Week 16, patients deemed Inadequate Responders received rescue
therapy and were included in this dataset only up to Week 16. Data was analyzed using a Cochran-Mantel-Haenszel test
stratified by trial.
Results: The percentage of patients with ≥1 treatment emergent adverse event (TEAE) was significantly greater in the IXE
compared to PBO treatment groups (Table 1). No clear difference was seen between groups for the percentage of patients
with ≥1 serious adverse event (SAE) or discontinued early from study drug. Infection-related SAEs were reported in a
significantly higher percentage of IXE Q2W than PBO patients. Treatment-emergent infections were numerically more
frequent with IXE treatment compared to PBO (Table 2); upper respiratory tract infections, nasopharyngitis, and sinusitis
were the most common infections. One PBO, 4 IXE Q4W, and 8 IXE Q2W-treated patients had ≥1 Candida infection.
Injection site reactions were reported in a significantly higher percentage of patients in the IXE than the PBO treatment
groups; most were of mild or moderate severity. Allergic reactions/hypersensitivity events were reported in a significantly
higher percentage of IXE Q2W than PBO patients; no case of anaphylaxis was reported. Two cases of malignancy were
reported (both IXE Q4W patients): prostate cancer and basal cell carcinoma. There were no major adverse cardiac events
(MACE). While there were no reports of Crohn’s disease or ulcerative colitis, 1 IXE Q2W patient had SAEs of anal abscess
and anal fistula, considered to represent inflammatory bowel disease; this patient continued study drug. There were no
deaths or reports of suicide or suicidal ideation.
Conclusion: The safety profile of IXE during the placebo-controlled treatment period was consistent with published
findings in patients receiving ixekizumab for moderate-to-severe plaque psoriasis1.
1Strober, B et al. JAAD. 2017 76(3):432
Disclosure: P. J. Mease, None; G. R. Burmester, AbbVie, 5,AbbVie, 9,Celgene, 5,Celgene, 9,Gilead, 5,Gilead, 9,Eli Lilly
and Company, 5,Eli Lilly and Company, 9,Pfizer Inc, 5,Pfizer Inc, 9; S. Moriarty, Eli Lilly and Company, 1,Eli Lilly and
Company, 3; O. Benichou, Eli Lilly and Company, 3,Eli Lilly and Company, 1; W. Xu, Eli Lilly and Company, 1,Eli Lilly
and Comany, 3; P. Nash, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Hospira, Janssen, MSD,
Novartis, Pfizer, Roche, Sanofi, and UCB, 5,AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company,
Lilly and Company, Hospira, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/ixekizumab-exhibits-a-favorable-safety-

profile-during-24-weeks-of-treatment-in-subjects-with-active-psoriatic-arthritis-integrated-safety-analysis-of-two-
randomized-placebo-controlled-phase-iii-cli
Secukinumab Demonstrates Consistent Safety over Long-Term Exposure in

Patients with Psoriatic Arthritis and Moderate to Severe Plaque Psoriasis:
Updated Pooled Safety Analyses
Philip J Mease1, Iain B. McInnes2, Kristian Reich3, Peter Nash4, Mats Andersson5, Ken Abrams6, Luminita Pricop6 and
Todd Fox5, 1Swedish Medical Center and University of Washington, Seattle, WA, 2University of Glasgow, Glasgow,
United Kingdom, 3Dermatologikum Hamburg, Hamburg, Germany, 4University of Queensland, Brisbane, Australia,
5Novartis Pharma AG, Basel, Switzerland, 6Novartis Pharmaceuticals Corporation, East Hanover, NJ
SESSION INFORMATION
Background/Purpose: Pooled safety data from secukinumab psoriasis (PSO) and psoriatic arthritis (PsA) clinical trial
programs after ~1 year of exposure have been reported previously.1, 2 Here, we report updated longer-term safety data of
secukinumab exposure from PSO and PsA studies.
Methods: The PSO data pool consisted of 9 Phase III studies in moderate-to-severe plaque PSO and PsA pool consisted of
3 Phase III studies in active PsA. Secukinumab doses differed in the studies and included intravenous (up to 10 mg/kg) or
subcutaneous (s.c.; 75–300 mg) loading, followed by s.c. maintenance dosing (300, 150 or 75 mg). Placebo patients were
re-randomized to secukinumab at 12–24 weeks depending on study design. Exposure adjusted incident rates (EAIR) were
used to adjust for differences in treatment exposure and analyses included all patients who received ≥1 dose of
secukinumab.
Results: A total of 3893 and 1380 patients from PSO and PsA studies representing an exposure of 7769.0 and 2841.3
patient years, respectively, were included in this pooled safety analysis. In both PsO and PsA, the most frequently reported
adverse events (AEs) with secukinumab were nasopharyngitis, headache, non-serious infections of the upper respiratory
tract and arthralgia (Table). The EAIRs of AEs of special interest with secukinumab including serious infections, Candida
infections, inflammatory bowel disease, and major adverse cardiac events (Table) were similar in both PSO and PsA
indications, and comparable to those reported previously.1,2 No cases of tuberculosis were reported.
Conclusion: Secukinumab demonstrated a favorable safety profile during long term treatment (up to 7769 patient-years of
exposure) in patients with moderate-to-severe plaque PSO or PsA consistent with previous reports. Safety was comparable
across psoriasis and PsA patients supporting long-term use in these chronic conditions.
References: 1. Van de Kerkhof PC, et al. J Am Acad Dermatol. 2016;75:83–98; 2. Mease PJ, et al. Arthritis Rheumatol.
201567:A2886.
Table: Summary of Secukinumab Safety across PSO and PsA studies: Entire Safety Period
PSO PsA
Any Any
secukinumab secukinumab
N = 3893 N = 1380
Total exposure, patient-years 7769.0 2841.3
Min–max exposure (days) 1–1526 8–1464
Exposure (days), mean (SD) 728.9 (421.9) 752.0 (379.8)
Death, n (%) 7 (0.2) 7 (0.5)
EAIR per 100 Patient-years (95% Cl)
Any AE 196.9 (190.3, 203.6) 162.0 (152.9,171.5)
Any serious AE 7.2 (6.6, 7.8) 7.9 (6.8, 9.0)
Frequent AEs ^
Nasopharyngitis 18.2 (17.1, 19.3) 12.8 (11.4, 14.3)
Headache 6.3 (5.7, 6.9) 4.5 (3.7, 5.3)
Upper respiratory tract infection 6.2 (5.6, 6.8) 11.0 (9.7, 12.4)
Arthralgia 5.1 (4.6, 5.6) 3.9 (3.2, 4.7)
AEs of special interest
Serious infections 1.4 (1.2, 1.7) 1.7 (1.2, 2.2)
Candida infections 2.1 (1.8, 2.4) 1.7 (1.3, 2.3)
Inflammatory Bowel Disease 0.3 (0.2, 0.4) 0.4 (0.2, 0.7)
Crohn's disease 0.1 (0.0, 0.1) 0.1 (0.0, 0.3)
Ulcerative colitis 0.2 (0.1, 0.3) 0.1 (0.0, 0.3)
MACE 0.3 (0.2, 0.5) 0.4 (0.2, 0.7)
^Adverse events in the secukinumab group that occurred with an EAIR of ≥5 during the entire safety period in either of the
pooled groups. AE, adverse event; EAIR, exposure adjusted incidence rate per 100 patient-years; MACE, major adverse
cardiac event; N, number of patients in the analysis; SD, standard deviation
Disclosure: P. J. Mease, AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, SUN, and UCB,
2,AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, SUN, and
UCB, 5,AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB, 8; I. B. McInnes,
Novartis, Amgen, Janssen, BMS, Pfizer, UCB, AbbVie, Celgene, Lilly, 5; K. Reich, AbbVie, Amgen, Biogen, Boehringer
Ingelheim Pharma, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cliag, Leo, Lilly, Medac,
Merck Sharp and Dohme Corp., Novartis, Ocean Pharma, Pfizer, Regeneron, Takeda, UCB Pharma, Xenoport, 2,AbbVie,
Amgen, Biogen, Boehringer Ingelheim Pharma, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-
Cliag, Leo, Lilly, Medac, Merck Sharp and Dohme Corp., Novartis, Ocean Pharma, Pfizer, Regeneron, Takeda, UCB
Pharma, Xenoport, 8; P. Nash, Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, and Celgene, 2,Novartis, Abbvie, Roche,
Pfizer, BMS, Janssen, and Celgene, 5,Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, and Celgene, 8; M. Andersson,
Novartis Pharma AG, 3; K. Abrams, Novartis Pharmaceutical Corporation, 3,Novartis Pharmaceutical Corporation, 1; L.
Pricop, Novartis Pharmaceutical Corporation, 1,Novartis Pharmaceutical Corporation, 3; T. Fox, Novartis Pharma AG,
1,Novartis Pharma AG, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/secukinumab-demonstrates-consistent-

safety-over-long-term-exposure-in-patients-with-psoriatic-arthritis-and-moderate-to-severe-plaque-psoriasis-updated-
pooled-safety-analyses
Secukinumab Treatment of Psoriatic Arthritis and Moderate to Severe

Psoriasis Relieves Anxiety/Depression up to 52 Weeks: An Overview from
Secukinumab Phase 3 Clinical Trials
Philip J Mease1, Mark Lebwohl2, Isabelle Gilloteau3, Todd Fox3, Jaime Oliver3, Steffen Jugl3 and Alice B Gottlieb4,
1University of Washington School of Medicine and Swedish Medical Center, Seattle, WA, 2Icahn School of Medicine at
Mount Sinai, New York, NY, 3Novartis Pharma AG, Basel, Switzerland, 4Department of Dermatology, New York Medical
College, Vallhalla, NY
SESSION INFORMATION
Background/Purpose: Secukinumab (SEC), a fully human monoclonal antibody selectively neutralizing interleukin-17A,
exhibits significant efficacy, with a favorable safety profile, in the treatment of psoriatic arthritis (PsA) and moderate to
severe psoriasis. SEC has a rapid onset of action and demonstrates sustained responses. PsA and psoriasis patients are at
greater risk for psychological distress, including depression and suicidality. Previous analysis, using pooled data from phase
3 studies FIXTURE and ERASURE, reported high and sustained relief from anxiety/depression in psoriasis patients treated
with SEC 300 mg up to Week (Wk) 52 (~80% of patients reported not being anxious/depressed) from the EuroQol 5-
dimensional (Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression) and 3-level questionnaire
(EQ-5D-3L). Here, we aim to confirm these results in additional phase 3 SEC trials in patients with PsA and psoriasis.
Methods: Results of the ‘Anxiety/Depression’ dimension ("not anxious/depressed", "moderately anxious/depressed", or

"extremely anxious/depressed) of EQ-5D-3L were derived from three phase 3 studies using an approved SEC dose:
FUTURE 1 and FUTURE 2, two randomized, double-blind clinical trials, comparing SEC 150 mg to placebo in active
PsA; and CLEAR, a multicenter, double-blind, parallel-group study comparing SEC 300 mg to ustekinumab in moderate to
severe psoriasis. The proportions of patients reporting as not being anxious/depressed are described as observed for each
individual study up to Wk 52.
Results: In FUTURE 1, 76/200 (38.0%) of PsA patients treated with SEC 150 mg reported being not anxious/depressed at
baseline, increasing to 99/192 (51.6%) at Wk 4 and 109/184 (59.2%) at Wk 52 (Fig. 1). Similarly, in FUTURE 2, 32/100
(32.0%) and 41/99 (41.4%) of PsA patients treated with SEC 150 mg or 300 mg, respectively reported being not
anxious/depressed at baseline, increasing to 51/99 (51.5%) and 52/95 ( 54.7%) at Wk 4 and 49/89 (55.1%) and 55/95
(57.9%) at Wk 52 (Fig. 1). In the CLEAR study, 154/326 (47.2%) psoriasis patients treated SEC 300 mg reported being not
anxious/depressed at baseline, and this increased to 238/322 (73.9%) at Wk 4, 263/326 (80.7%) at Wk 16, and was
sustained up to Wk 52 (237/292, 81.2%) (Fig. 1).
Conclusion: This analysis of the patient-reported EQ-5D-3L anxiety/depression measure from three phase 3 SEC trials
showed consistently higher anxiety/depression burden among patients with PsA than among those with moderate to severe
psoriasis; however, it also indicates that SEC treatment improves and provides sustained relief from anxiety/depression
among all treated patients, regardless of their disease, up to 1 year.
Figure 1. Percentages of patients with psoriatic arthritis or psoriasis reporting not being anxious/depressed on EQ-5D
following treatment with secukinumab in three phase 3 clinical trials (as observed).
Disclosure: P. J. Mease, AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, SUN, and UCB,
2,AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, SUN, and
UCB, 5,AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB, 8; M. Lebwohl,
Mount Sinai Medical Center, 3,AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Research &
Development, LLC, Kadmon, LEO Pharma, Novartis, Pfizer and ViDac, 2; I. Gilloteau, Novartis Pharma AG, 3; T. Fox,
Novartis Pharma AG, 1,Novartis Pharma AG, 3; J. Oliver, Novartis Pharma AG, 3; S. Jugl, Novartis Pharma AG,
1,Novartis Pharma AG, 3; A. B. Gottlieb, Amgen Inc, Astellas, Akros, Centocot Janssen), Inc; Celgene Corp, Bristol
Myers Squibb Co, Beiersdorf Inc, Abbott Labs Abbvie), TEVA, Actelion, UCB, Novo Nordisk, Novartis, Dempipsor Ltd.,
Incyle, Pfizer, Canfite, Eli Lilly and Company, Coronado, Vertex,, 5,Janssen Incyte, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/secukinumab-treatment-of-psoriatic-

arthritis-and-moderate-to-severe-psoriasis-relieves-anxietydepression-up-to-52-weeks-an-overview-from-secukinumab-
phase-3-clinical-trials
Presence of Poor Prognostic Factors May Predict Response to Abatacept in

Patients with Active Psoriatic Arthritis: Results from a Post Hoc Analysis
from a Phase III Study
Philip J Mease1, Iain B. McInnes2, Vibeke Strand3, O FitzGerald4, H Ahmad5, A Johnsen5, J Ye5 and S Banerjee5,
1Swedish Medical Center and University of Washington, Seattle, WA, 2University of Glasgow, Glasgow, Great Britain,
3Stanford University, Palo Alto, CA, 4Department of Rheumatology, St Vincent’s University Hospital and University
College Dublin, Dublin, Ireland, 5Bristol-Myers Squibb, Princeton, NJ

SESSION INFORMATION
Background/Purpose: Abatacept, a selective T-cell co-stimulation modulator, significantly increased ACR20 response and
had an overall beneficial effect on musculoskeletal symptoms in patients with active psoriatic arthritis (PsA) in the Phase
III Active pSoriaTic athRitis rAndomizEd triAl (ASTRAEA, NCT01860976).1 Factors that may predict responses to
abatacept were explored in this post hoc analysis. The aim of this study was to evaluate the relationship between baseline
characteristics and abatacept response in a post hoc analysis of ASTRAEA. Methods: Patients were randomized (1:1) to
SC abatacept 125 mg weekly or placebo for 24 weeks in this trial. Patients without >20% improvement in joint counts at
Week 16 were switched to open-label abatacept (early escape). ACR20 response rate in patients stratified by baseline
variables was investigated in a multivariate analysis and odds ratios (ORs) generated to identify differences in response.
Using a cut-off of OR 1.2, indicating patient subgroups in whom abatacept appeared to have a meaningful treatment
benefit, baseline variables were further investigated in a univariate analysis and estimated differences calculated.
Results: Of 424 patients enrolled, 213 received abatacept and 211 placebo. In abatacept-treated patients, the multivariate
model showed a difference in ACR20 response (OR >1.2) for baseline CRP (>upper limit of normal [ULN] vs ≤ULN; OR
1.346 [95% CI 0.668, 2.712]), DAS28 (CRP) (>5.1 vs ≤5.1; 1.489 [0.782, 2.836]), dactylitis (>0 vs 0; 1.372 [0.708,
2.659]), and median baseline erosions (≥3 vs <3; 1.924 [1.032, 3.587]). In placebo-treated patients, the OR was >1.2 for
dactylitis only (1.406 [0.619, 3.193]). These factors, which have been identified previously as indicating poor prognosis in
PsA, were balanced between treatment arms at baseline. In the univariate model by poor prognostic factors, the differences
in ACR20 response rates with abatacept treatment vs placebo in distinct subgroups were numerically greater in patients
who were positive for these prognostic factors at baseline than in those who were not (Figure).
Conclusion: These findings identified subgroups of patients with PsA with certain baseline characteristics in whom
abatacept is most likely to be effective. The predictive factors identified are aligned with poor prognostic factors in the
EULAR and Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) guidelines,2,3 and may
indicate patients with the highest unmet medical need.
1. Mease P, et al. Arthritis Rheumatol 2016;68(Suppl 10):Abstract 1041.
2. Gossec L, et al. Ann Rheum Dis 2016;75:499–510. 3. Coates LC, et al. Arthritis Rheumatol 2016;68:1060–71.
Original abstract © EULAR/BMJ. First presented at EULAR 2017 and published in Ann Rheum Dis 2017;76 (Suppl
2):SAT0468. Any reprints, promotional options, education material etc have to be done through the original source
(ARD/BMJ).
Disclosure: P. J. Mease, AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, UCB, 2,AbbVie, Amgen,
BMS, Celgene, Crescendo Bioscience, Corrona, Demira, Janssen, Lilly, Novartis, Pfizer, Sun, UCB, Zynerba, 5,AbbVie,
Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Novartis, Pfizer, UCB, 8; I. B. McInnes, BMS,
Celgene, Janssen, UCB, Roche, 2,BMS, Celgene, Janssen, Novartis, Pfizer, AbbVie, UCB, Lilly, 5; V. Strand, AbbVie,
Amgen Corporation, AstraZeneca, Biogen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Corrona, Crescendo / Myriad
Genetics, EMD Serono, Genentech / Roche, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron,
Samsung, Sandoz, Sanof, 5; O. FitzGerald, AbbVie, Pfizer, BMS, 2,AbbVie, Pfizer, BMS, Celgene, Janssen, Novartis,
UCB, Lilly, 5,AbbVie, BMS, Lilly, Novartis, Celgene, Janssen, 8; H. Ahmad, Bristol-Myers Squibb, 3,Bristol-Myers
Squibb, 1, 9; A. Johnsen, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; J. Ye, Bristol-Myers Squibb, 1,Bristol-Myers
Squibb, 3; S. Banerjee, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/presence-of-poor-prognostic-factors-

may-predict-response-to-abatacept-in-patients-with-active-psoriatic-arthritis-results-from-a-post-hoc-analysis-from-a-
phase-iii-study
Body Mass Index Does Not Influence the Efficacy of Subcutaneous Abatacept
in Patients with Psa: Results from a Phase III Trial
Iain B. McInnes1, Gianfranco Ferraccioli2, MA D'Agostino3, M Le Bars4, S Banerjee5, H Ahmad5, Y Elbez6, J Ye5 and
Philip J Mease7, 1University of Glasgow, Glasgow, Great Britain, 2Division of Rheumatology - Institute of Rheumatology
and Affine Sciences, Catholic University of the Sacred Heart, Rome, Italy, 3Hôpital Ambroise Paré, Boulogne-Billancourt,
France, 4Bristol-Myers Squibb, Rueil-Malmaison, France, 5Bristol-Myers Squibb, Princeton, NJ, 6Excelya, Boulogne-
Billancourt, France, 7Swedish Medical Center and University of Washington, Seattle, WA
SESSION INFORMATION
Background/Purpose: Obesity is a risk factor for the development and severity of psoriatic arthritis (PsA).1,2 Patients (pts)
with increased BMI (overweight/obese) are less likely to achieve sustained minimal disease activity (MDA) vs those with
normal BMI, independent of biologic and non-biologic DMARD use.3 Moreover, obese pts with PsA respond less
favourably to TNFα inhibitors vs normal BMI pts.4,5 In the Phase III ASTRAEA study (NCT01860976),6 abatacept (ABA)
significantly improved disease activity and was well tolerated; the primary endpoint of ACR20 at 24 weeks (W) was met.6
We evaluated the relationship beween BMI and ABA response in a post hoc analysis of ASTRAEA. Methods: Pts were
randomized (1:1) to weekly SC ABA 125 mg or placebo (PBO) for 24W. Pts without ≥20% improvement in joint counts at
W16 were switched to open-label ABA (early escape; EE). Pts designated as EE or with missing data were imputed as non-
responders. ACR20/50/70 responses and % of pts with DAS28 (CRP) ≤3.2 or <2.6, MDA, HAQ-DI response (change from
baseline [CFB] ≥0.35) and radiographic non-progression (PsA-modified total Sharp/van der Heijde score, CFB ≤0) at W24
were compared for ABA vs PBO between three BMI subgroups (underweight/normal: <25 kg/m²; overweight: 25–30
kg/m²; obese: >30 kg/m²) using univariate and multivariate analyses. BMI <25 kg/m² subgroup was the reference and key
potential confounding factors for treatment efficacy were included in the multivariate model. Odds ratios (ORs), 95% CIs
and p values were calculated for each BMI subgroup comparison.
Results: Overall, 212 ABA- and 210 PBO-treated pts had available baseline BMI status. For ABA vs PBO, respectively, 31
(14.6%) vs 39 (18.6%) were underweight/normal, 77 (36.3%) vs 57 (27.1%) were overweight and 104 (49.1%) vs 114
(54.3%) were obese. In the ABA and PBO groups, neither overweight nor obese pts had a significantly lower ACR20
response vs underweight/normal pts in the univariate model. This was confirmed in the multivariate models in overweight
and obese pts, respectively, vs underweight/normal pts: ABA: OR (95% CI) 1.215 (0.437, 3.378), p=0.7087 and 0.446
(0.162, 1.228), p=0.1181; PBO: OR (95% CI) 0.554 (0.189, 1.621), p=0.2811 and 0.460 (0.166, 1.271), p=0.1343. Similar
results were observed for all other outcomes tested (Figure). Conclusion: As in RA, BMI does not appear to affect the
efficacy of abatacept in PsA; this is consistent across both objective and pt-reported outcome measures. Given that 1 in 3
pts with PsA are overweight/obese, these data strongly suggest an advantage of abatacept therapy in this debilitating
disease.
1. Kumar S, et al. J Eur Acad Dermatol Venereol 2013;27:1293–8.
2. Armstrong AW, et al. Nutr Diabetes 2012;2:e54.
3. Eder L, et al. Ann Rheum Dis 2015;74:813–7.
4. di Minno MN, et al. Arthritis Care Res (Hoboken) 2013;65:141–7.
5. Gremese E, et al. Front Immunol 2014;5:576.
6. Mease P, et al. Arthritis Rheumatol 2016;68(Suppl 10):[Abstract 1041].
Disclosure: I. B. McInnes, BMS, Celgene, Janssen, UCB, Roche, 2,BMS, Celgene, Janssen, Novartis, Pfizer, AbbVie,
UCB, Lilly, 5; G. Ferraccioli, Roche, BMS, Pfizer, 2,MSD, UCB, Pfizer, AbbVie, Lilly, Cellgene, Novartis, Roche, 8; M.
D'Agostino, BMS, AbbVie, Novartis, 8; M. Le Bars, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1, 9; S. Banerjee,
Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; H. Ahmad, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1, 9; Y.
Elbez, None; J. Ye, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; P. J. Mease, AbbVie, Amgen, BMS, Celgene,
Janssen, Lilly, Novartis, Pfizer, Sun, UCB, 2,AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Corrona, Demira,
Janssen, Lilly, Novartis, Pfizer, Sun, UCB, Zynerba, 5,AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech,
Janssen, Novartis, Pfizer, UCB, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/body-mass-index-does-not-influence-
the-efficacy-of-subcutaneous-abatacept-in-patients-with-psa-results-from-a-phase-iii-trial
Baseline Structural Damage Predicts Response to Abatacept in Patients with

Psoriatic Arthritis: A Post Hoc Analysis from a Phase III Study
Georg Schett1, T Lehman2, HA Ahmad2, A Johnsen2, S Banerjee2 and Philip J Mease3, 1University of Erlangen-
Nuremberg, Erlangen, Germany, 2Bristol-Myers Squibb, Princeton, NJ, 3Swedish Medical Center and University of
Washington, Seattle, WA
SESSION INFORMATION
Background/Purpose: Psoriatic arthritis (PsA) is a heterogeneous disease in which treatment selection and patient
stratification based on clinical domains have recently been proposed.1 The efficacy and safety of the co-stimulation
modulator abatacept in patients with PsA was investigated in the Phase III ASTRAEA study (NCT01860976).2 The aim of
this analysis was to identify baseline factors that predict response to abatacept treatment in patients with PsA in
ASTRAEA. Methods: Baseline disease and demographic characteristics of patients treated with abatacept (n=213) or
placebo (n=211) in the Phase III ASTRAEA study achieving high-level response (ACR50: abatacept n=41, placebo n=26;
ACR70: abatacept n=22, placebo n=14) at Day 169 (Week 24) were compared with those of patients not achieving an
ACR20 response (abatacept n=129, placebo n=164). Due to the inclusion of an early escape (EE) at Day 114 (Week 16),
patients who entered the EE were imputed as non-responders at Day 169 and included in the ACR20 non-responders group.
Results: For both the abatacept and placebo groups, most baseline demographic and disease characteristics, including age,
BMI, disease duration and disease activity at baseline, were similar among ACR50 and ACR70 responders and ACR20
non-responders (Table, abatacept group). Joint-space narrowing, erosion, total PsA-modified Sharp/van der Heijde scores,
and the swollen joint count, however, were higher in abatacept ACR50 and ACR70 responders than in ACR20 non-
responders. Conversely, placebo ACR 20 non-responders show a higher degree of baseline structural damage than ACR50
and ACR70 responders. Baseline CRP was higher in both abatacept and placebo ACR50 and ACR70 responders than in
ACR20 non-responders.
Conclusion: These data show that a higher degree of baseline structural joint damage and higher swollen joint count is
associated with a greater response to abatacept therapy in PsA. These observations suggest that PsA patients with signs of
synovitis-driven osteoclast formation and disease activity including swollen joints and structural damage may be good
candidates for abatacept treatment. These results are in accordance with recent data showing that CTLA-4 controls
osteoclast differentiation and bone resorption3 and the known mechanism of abatacept on T-cell co-stimulation mediated
inflammation2. 1. Coates L, et al. Arthritis Rheumatol 2016;68:1060–71. 2. Mease P, et al. Ann Rheum Dis 2017 May 4;
Epub ahead of print. 3. Bozec A, et al. Sci Transl Med 2014;6:235ra60.
Table. Baseline Disease Characteristics in ACR20 Non-responders,
ACR50 Responders and ACR70 Responders to Abatacept
ACR20 ACR50 ACR70
non-responders responders responders
(n=129) (n=41) (n=22)
Age (years) 51.5 (10.3) 50.2 (11.7) 49.1 (10.9)
BMI (kg/m2) 31.7 (7.1) 28.4 (4.0) 29 (4.4)
Duration of PsA (years) 8.7 (8.8) 7.6 (6.9) 7.0 (6.2)
Tender joints 20.1 (12.8) 20.1 (12.8) 22.5 (12.7)
Swollen joints 10.8 (7.0) 14.1 (8.5) 15.5 (8.0)
DAS28 (CRP) 4.9 (1.0) 5.0 (1.1) 5.3 (0.8)
Joint-space narrowing
6.7 (16.4) 16.6 (36.3) 10.5 (34.9)
score
Erosion score 9.5 (20.7) 21.8 (48.1) 14.3 (41.1)
Total SHS score 16.2 (36.6) 38.4 (84.0) 24.8 (75.8)
Baseline CRP (mg/L) 13 (21.8) 15.5 (18.0) 14.7 (18.5)
Data are expressed as mean (SD)
PsA=psoriatic arthritis; SHS=Sharp/van der Heijde score
Disclosure: G. Schett, None; T. Lehman, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1, 9; H. Ahmad, Bristol-Myers
Squibb, 3,Bristol-Myers Squibb, 1, 9; A. Johnsen, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; S. Banerjee, Bristol-
Myers Squibb, 1,Bristol-Myers Squibb, 3; P. J. Mease, AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer,
Sun, UCB, 2,AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Corrona, Demira, Janssen, Lilly, Novartis, Pfizer,
Sun, UCB, Zynerba, 5,Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Novartis, Pfizer, UCB, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/baseline-structural-damage-predicts-

response-to-abatacept-in-patients-with-psoriatic-arthritis-a-post-hoc-analysis-from-a-phase-iii-study
Effectiveness of Early Adalimumab Therapy in Psoriatic Arthritis Patients

from Reuma.Pt
Helena Santos1, Mónica Eusébio2, Joana Borges3, Diana Gonçalves4, Pedro Ávila-Ribeiro5, Daniela Santos Faria6, Carina
Lopes7, João Rovisco8, Ana Águeda9, Patrícia Nero10, Paula Valente11, Ana Rita Cravo12 and Maria José Santos13,
1Instituto Português de Reumatologia, Lisbon, Portugal, 2Sociedade Portuguesa de Reumatologia, LIsboa, Portugal,
3Instituto Português de Reumatologia, Lisboa, Portugal, 4Centro Hospitalar de São João, Coimbra, Portugal, 5Centro
Hospitalar Lisboa Norte, Lisbon, Portugal, 6ULSAM, Ponte de Lima, Portugal, 7Hospital de Egas Moniz-CHLO, Lisbon,
Portugal, 8Centro Hospitalar e Universitário de Coimbra, Lisbon, Portugal, 9Centro Hospitalar do Baixo Vouga, Aveiro,
Portugal, 10Hospital CUF Descobertas, Lisbon, Portugal, 11Centro Hospitalar Entre o Douro e Vouga, Lisbon, Portugal,
12Medical, AbbVie, Lisbon, Portugal, 13Reuma.pt, Almada, Portugal, Almada, Portugal
SESSION INFORMATION
Background/Purpose: There is a lack of evidence on the effect of biologics in early treatment of psoriatic arthritis (PsA)
patients (Pts). Benefit of concomitant use of DMARDs remains controversial in this indication.
Methods: To compare clinical outcomes in patients with PsA starting adalimumab (ADA), with short and long disease
duration and evaluate the potential effect of concomitant use of DMARDs or corticosteroids (CS), both on PsARC response
and persistence on ADA.The analyses included adult PsA Pts who have been registered on Reuma.pt between June 2008 -
June 2016 and have received ADA therapy for at least 3 months. PsARC, DAS28, tender and swollen joint count, ESR,
CRP, PtGA, PhGA evaluated on a 10 cm VAS, and HAQ were compared between Pts <5 years of disease (early PsA) and
those with ≥5 years of disease duration (late PsA) when starting ADA. Time to achieve PsARC response was estimated
using Kaplan-Meier method, adjusted with Cox Regression with Efron method for ties with robust estimates of variance for
baseline characteristics. Same analyses were repeated to compare patients with and without concomitant use of DMARDs
or CS.
Results: We included 135 PsA patients who started ADA, 41 of them with early PsA. Pts with early PsA were younger,
more frequently males, smokers, had significantly more hypertension. Overall, PsARC response was achieved by 72.9% of
the Pts (88% early PsA vs 62.2% late PsA; p=0.022) at 3 months, by 85.4% of Pts at 24 months (100% early PsA vs 75.9%
late PsA; p=0.044) after starting ADA. Patients with early PsA, achieved significantly less painful joints (2.7 vs 6.7;
p=0.006), lower mean CRP (0.5 mg/dl vs 1.3 mg/dl, p=0.011) and PhGA (18.3 vs 28.1; p=0.020) at 3 months. In the long
term, early PsA Pts showed less swollen joints (0.3 vs 1.7; p=0.030), lower PhGA (6.3 vs 21.9; p<0.001), CRP (0.4 mg/dl
vs 1.0 mg/dl; p=0.026) and disease activity evaluated by DAS28 (2.2 vs 3.2; p=0.030). Early PsA Pts obtained PsARC
response more rapidly than those with late PsA (3.8 and 7.4 months, respectively; p=0.008). Concomitant DMARDs, in the
long term, showed clinical benefit (PsARC response at 2 years 88.3% vs 60.0%; p=0.044). Concomitant CS had no
noticeable effect on PsARC response, over 2 years of follow-up. Survival on treatment with ADA was similar in the 2
groups and was not influenced by DMARD or CS therapy.
Conclusion: Patients with early PsA had greater chance of improvement after starting ADA, better functional outcome and
achieved PsARC response more rapidly than patients with longer disease duration. Our results suggest that comedication
with DMARDs may improve PsARC response in the long term.
Disclosure: H. Santos, None; M. Eusébio, None; J. Borges, None; D. Gonçalves, None; P. Ávila-Ribeiro, None; D.
Santos Faria, None; C. Lopes, None; J. Rovisco, None; A. Águeda, None; P. Nero, None; P. Valente, None; A. R.
Cravo, AbbVie, 3,AbbVie, 1; M. J. Santos, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effectiveness-of-early-adalimumab-

therapy-in-psoriatic-arthritis-patients-from-reuma-pt
Safety and Effectiveness of Ustekinumab for the Treatment of Psoriatic

Arthritis over a 6 Month Period
Regan Arendse1, Anna Jaroszynska2, Derek Haaland3, Pauline Boulos4, Isabelle Fortin5, Raheem Kherani6, Ariel
Masetto7, Jonathan Chan8, Eliofotisti Psaradellis9, Melissa Stutz9, Brendan Osborne10, Francois Nantel10 and Allen J
Lehman11, 1University of Saskatchewan, Saskatoon, SK, Canada, 2Private practice, Burlington, ON, Canada,
3Rheumatology, Clinical Immunology & Allergy, McMaster University, Barrie, ON, Canada, 4Rheumatology, McMaster
University, Hamilton, ON, Canada, 5Centre de Rhumatologie De l’Est du Quebec, Rimouski, QC, Canada, 6University of
British Columbia, Richmond, BC, Canada, 7Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada,
8Rheumatology, University of British Columbia, Vancouver, BC, Canada, 9JSS Medical Research, Montreal, QC, Canada,
10Medical Affairs, Janssen Inc., Toronto, ON, Canada, 11Janssen Inc., Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose: Ustekinumab (UST) is a fully human immunoglobin monoclonal antibody against interleukin-12
(IL-12) and interleukin-23 (IL-23) that has been proven safe and efficacious for the treatment of PsA in randomized clinical
trials. The aim of the current analysis was to assess the safety and effectiveness of UST among PsA patients treated under
Canadian routine clinical care.
Methods: BioTRAC is an ongoing, prospective registry of patients initiating treatment with infliximab or golimumab for
rheumatoid arthritis, ankylosing spondylitis, or PsA, or with UST for PsA. Eligible participants for this analysis included
UST-treated PsA patients enrolled between 2014-2016. Clinical outcomes assessed at Baseline and the Month 6 visit were:
SJC, TJC, pain (100mm visual analogue scale; VAS), PtGA and MDGA (100mm VAS), PASI, HAQ-DI, DAS-28, and joint
counts for dactylitis and enthesitis. Safety was ascertained by the incidence of adverse events (AEs), reported per 100
patient years (PY) of follow-up. Descriptive statistics were produced for all variables, and between-visit changes in
outcomes were assessed for statistical significance with the paired-samples t-test.
Results: A total of 63 UST-treated PsA patients were identified. Mean (SD) age and disease duration at Baseline was 52.8
(11.2) and 5.5 (8.1) years, respectively. A majority of patients were female (63.5 %), and 100.0% were biologic naïve.
Changes from Baseline to Month 6 were statistically significant for all clinical outcomes (p < 0.05), except for the PtGA
(Table 1). With respect to enthesitis and dactylitis, missing data did not permit assessment of improvement from baseline to
Month 6. At baseline, 50.9% of patients had some dactylitis and 34.9% had some enthesitis.
Overall, 36 AEs were reported by 21 patients from Baseline to the Month 6 visit. The majority were mild in nature
(n=26/36; 72.2%); “probable” and “very likely” relation to the study drug was determined for 11.1% (n=4/36) and 8.3%
(n=3/36) of AEs, respectively. The most common AEs included General Disorders and Administration Site Conditions
(n=7/21; 33.3%) and Infections and Infestations (n=8/21; 38.1%). No serious AEs were reported.
Table 1. Clinical outcome parameters over time, and changes from Baseline to Month 6
Baseline Month 6 Change† p-value§
Parameter, mean (SD)
SJC-28 3.8 (3.8) 1.6 (2.1) -2.7 (6.0) 0.014
TJC-28 6.5 (5.6) 3.4 (5.7) -2.6 (3.6) <0.001
Pain, mm* 55.1 (22.2) 44.6 (27.7) -11.3 (22.5) 0.008
PtGA, mm* 58.2 (22.4) 49.1 (28.3) -9.7 (33.0) 0.101
MDGA, mm* 51.8 (22.9) 23.4 (19.7) -28.3 (25.5) <0.001
PASI 4.4 (7.2) 0.7 (1.1) -3.5 (4.7) <0.001
HAQ-DI 1.1 (0.6) 0.8 (0.6) -0.3 (0.7) 0.019
DAS-28 4.0 (1.2) 3.5 (1.2) -0.5 (0.9) 0.026
†
* 100 mm VAS; Based on patients with available Baseline and Month
6 data; § P-value derived from the paired samples t-test
Conclusion: The results of this analysis demonstrate that UST, administered to PsA patients in a routine clinical care
setting, is safe and effective in improving clinical outcomes over 6 months of treatment.
Disclosure: R. Arendse, None; A. Jaroszynska, None; D. Haaland, None; P. Boulos, None; I. Fortin, None; R.
Kherani, None; A. Masetto, None; J. Chan, None; E. Psaradellis, Janssen Inc., 9; M. Stutz, None; B. Osborne, Janssen
Inc., 3; F. Nantel, Janssen Inc., 3; A. J. Lehman, Janssen Inc., 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/safety-and-effectiveness-of-

ustekinumab-for-the-treatment-of-psoriatic-arthritis-over-a-6-month-period
Effect of Tofacitinib on Efficacy and Patient-Reported Outcomes in Psoriasis

Patients with Baseline Psoriatic Arthritis: A Pooled Analysis of 2 Phase 3
Studies
Hervé Bachelez1, Christopher EM Griffiths2, Kim Papp3, Stephen Hall4, Joseph F Merola5, Steven R Feldman6, Majed
Khraishi7, Anna Tallman8, Huaming Tan9 and Ming-Ann Hsu9, 1Sorbonne Paris Cité Université Paris Diderot, AP-HP
Hôpital St. Louis, Paris, France, 2Dermatology Centre, University of Manchester, Manchester, United Kingdom, 3Probity
Medical Research and K. Papp Clinical Research Inc, Waterloo, ON, Canada, 4Emeritus Research, Melbourne, Australia,
5Harvard Medical School, Boston, MA, 6School of Medicine, Wake Forest University, Winston-Salem, NC, 7Memorial
University of Newfoundland, St. John's, NF, Canada, 8Pfizer Inc, New York, NY, 9Pfizer Inc, Groton, CT
SESSION INFORMATION
arthritis (PsA). Up to 42% of patients (pts) with psoriasis also have PsA. We examined tofacitinib efficacy and patient-
reported outcomes (PROs) in pts with psoriasis and concomitant PsA.
Methods: Data were pooled from identical 52-week, randomized, controlled studies: OPT Pivotal 1 (NCT01276639) and
OPT Pivotal 2 (NCT01309737). Both studies enrolled pts with moderate to severe psoriasis. This analysis included only
those with a medical history of PsA at baseline (prior diagnosis by a rheumatologist). Pts were randomized 2:2:1 to receive
tofacitinib 5 or 10 mg twice daily (BID), or placebo (PBO). Pts receiving PBO advanced to tofacitinib at Week 16. The co-
primary efficacy endpoints at Week 16 were the proportion of pts achieving a 75% improvement in the Psoriasis Area and
Severity Index score (PASI75) and the proportion of pts achieving Physician’s Global Assessment (PGA) of “clear” or
“almost clear”. Secondary endpoints included the proportion of pts achieving Patient’s Global Assessment (PtGA) of
“clear” or “almost clear” and changes from baseline in Joint Pain Assessment (ΔJPA), Nail Psoriasis Severity Index
(ΔNAPSI), and Short Form-36 Health Survey (ΔSF-36) physical component summary (PCS) score, mental component
summary (MCS) score, and 8 domain scores.
Results: The analysis included 430 psoriasis pts with PsA at baseline; 172, 168, and 90 pts received tofacitinib 5 mg BID,
tofacitinib 10 mg BID, and PBO, respectively. At Week 16 a greater proportion of pts achieved PASI75, PGA, and PtGA
responses with tofacitinib 5 and 10 mg BID vs PBO (all p<0.0001 vs PBO; Table). Improvements were observed with
tofacitinib 5 and 10 mg BID vs PBO in ΔJPA and ΔNAPSI (all p<0.0001 vs PBO; Table). Tofacitinib 5 mg BID
significantly improved SF-36 PCS (p≤0.05) and 5 of 8 domain scores (physical functioning, role limitations: physical,
bodily pain, vitality, social functioning [all p≤0.05]). Tofacitinib 10 mg BID significantly improved SF-36 PCS (p<0.001),
MCS (p<0.001), and all 8 domain scores (all p≤0.05). A dose-response was observed across all endpoints following
tofacitinib treatment (Table).
Conclusion: Tofacitinib significantly improved clinical endpoints and PROs vs PBO at Week 16 in pts who had
concomitant psoriasis and PsA. Details of safety endpoints in pts with psoriasis and PsA in the OPT Pivotal studies will be
included in the final presentation.
Disclosure: H. Bachelez, Pfizer Inc, 2,AbbVie, Amgen, Boehringer Ingelheim, Baxalta, Celgene, Eli Lilly, Janssen, Leo
Pharma, Novartis, Pfizer Inc, Sun Pharmaceuticals, UCB, 5,AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen,
Leo Pharma, Novartis, Pfizer Inc, Sun Pharmaceuticals, 8; C. E. Griffiths, AbbVie, Celgene, Eli Lilly, GSK, Janssen, Leo
Pharma, Pfizer Inc, Novartis, Sandoz, 2,AbbVie, Almirall, Celgene, Eli Lilly, GSK, Janssen, Leo Pharma, Novartis, Pfizer
Inc, Sun Pharmaceuticals, UCB, 5,AbbVie, Almirall, Celgene, Eli Lilly, GSK, Janssen, Leo Pharma, Novartis, Pfizer Inc,
Sun Pharmaceuticals, UCB, 8; K. Papp, AbbVie, Akros, Allergen, Amgen, Anacor, Astellas, Baxalta, Boehringer
Ingelheim, Bristol-Myers Squibb, Celgene, Dermira, Dow Pharma, Eli Lilly, Galderma, Genentech, GSK, Janssen, Kyowa
Hakko Kirin, Leo Pharma, MedImmune, Merck MSD, Merck-Serono, Mylan, 2,Novartis, Pfizer Inc, Regeneron, Roche,
Sanofi-Aventis/Genzyme, Stiefel, Takeda, UCB, Valeant, 2,AbbVie, Akros, Amgen, Astellas, AstraZeneca, Baxalta, Baxter,
Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite, Celgene, Dermira, Devonian, Dow Pharma, Eli Lilly, Galderma,
Genentech, Janssen, Kyowa Hakko Kirin, Leo Pharma, Meiji Seika Pharma, 5,Merck MSD, Merck-Serono, Mitsubishi
Pharma, Mylan, Novartis, Pfizer Inc, Regeneron, Roche, Sanofi-Aventis/Genzyme, Takeda, UCB, Valeant, 5,AbbVie,
Amgen, Astellas, Celgene, Devonian, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin, Leo Pharma, Merck MSD,
Novartis, Pfizer Inc, Valeant, 8,Akros, Anacor, Kyowa Hakko Kirin, 9,AbbVie, Amgen, Boehringer Ingelheim, Celgene,
Eli Lilly, Janssen, Kyowa Hakko Kirin, Merck MSD, Merck-Serono, Novartis, Pfizer Inc, Regeneron, Sanofi-
Aventis/Genzyme, Valeant, 9,AbbVie, Amgen, Astellas, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene,
Dow Pharma, Eli Lilly, Galderma, Janssen, Merck MSD, Novartis, Pfizer Inc, Regeneron, Sanofi-Aventis/Genzyme, UCB,
Valeant, 9; S. Hall, AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, UCB, 5; J. F. Merola, AbbVie,
Amgen, Biogen Idec, Eli Lilly, Janssen, Kiniksa, Momenta, Mallinckrodt, Novartis, Pfizer Inc, Sumumed, UCB, 5,AbbVie,
8,Biogen Idec, Novartis, Pfizer Inc, 9; S. R. Feldman, Eli Lilly, Janssen, Novartis, Pfizer Inc, 2,AbbVie, Celgene, Eli Lilly,
Janssen, Novartis, Leo Pharma, Pfizer Inc, 5,AbbVie, Eli Lilly, Celgene, Janssen, Novartis, 8; M. Khraishi, Pfizer Inc, 5;
A. Tallman, Pfizer Inc, 1,Pfizer Inc, 3; H. Tan, Pfizer Inc, 1,Pfizer Inc, 3; M. A. Hsu, Pfizer Inc, 1,Pfizer Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effect-of-tofacitinib-on-efficacy-and-

patient-reported-outcomes-in-psoriasis-patients-with-baseline-psoriatic-arthritis-a-pooled-analysis-of-2-phase-3-studies
Effect of Tofacitinib on Reducing Pain in Patients with Rheumatoid Arthritis,

Psoriatic Arthritis and Ankylosing Spondylitis
Alexis Ogdie1, Kurt de Vlam2, Iain B. McInnes3, Philip J Mease4, Philip Baer5, Tatjana Lukic6, Kenneth Kwok6, Cunshan
Wang7, Ming-Ann Hsu7 and Anna Maniccia6, 1Division of Rheumatology, Department of Medicine, Perelman School of
Medicine at the University of Pennsylvania, Philadelphia, PA, 2UZ Leuven, Leuven, Belgium, 3Glasgow Biomedical
Research Centre, University of Glasgow, Glasgow, United Kingdom, 4Swedish Medical Center and University of
Washington, Seattle, WA, 5Baer Weinberg MPC, Scarborough, ON, Canada, 6Pfizer Inc, New York, NY, 7Pfizer Inc,
Groton, CT
SESSION INFORMATION
Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), which
has also been evaluated in other inflammatory rheumatic diseases (IRD) including psoriatic arthritis (PsA) and ankylosing
spondylitis (AS). Pain contributes substantial morbidity in patients (pts) with IRD and directly impacts treatment
adherence, assessment of disease improvement, and health-related quality of life. We evaluated the effectiveness of
tofacitinib in reducing pain in randomized controlled clinical trials in pts with RA, PsA, and AS.
Methods: Five pt populations treated with tofacitinib 5 mg twice daily (BID), 10 mg BID, or placebo (PBO) were
evaluated: [1] conventional synthetic disease-modifying antirheumatic drug (csDMARD)-inadequate response (IR) RA pts
pooled from ORAL Scan (NCT00847613), ORAL Sync (NCT00856544), and ORAL Standard (NCT00853385), [2] tumor
necrosis factor inhibitor (TNFi)-IR RA pts from ORAL Step (NCT00960440), [3] csDMARD-IR PsA pts from OPAL
Broaden (NCT01877668), [4] TNFi-IR PsA pts from OPAL Beyond (NCT01882439), and [5] AS pts from a Phase 2 study
(NCT01786668). Pain outcomes evaluated from baseline to Month (M)6 (Week [W]12 in the AS population) included Pt’s
Assessment of Arthritis Pain (PAAP) (RA and PsA populations only), Short-Form Health Survey (SF)-36v2 Q7 (bodily
pain in the past week), SF-36v2 Bodily Pain Domain (BP), EuroQol Five Dimensions Questionnaire Pain/Discomfort
Domain (EQ-5D PD; all populations), and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Q2 (level of AS
neck, back, or hip pain) and Q3 (other pain) score (PsA and AS populations only; PsA pts had presence of spondylitis at
screening and baseline BASDAI total score >0 in the full analysis set [FAS]). Data were analyzed descriptively.
Results: The csDMARD-IR RA, TNFi-IR RA, csDMARD-IR PsA, TNFi-IR PsA, and AS populations comprised a total of
2066, 399, 316, 394, and 155 pts in the FAS, respectively. In each RA or PsA csDMARD-IR and TNFi-IR population
treated with tofacitinib, mean PAAP at baseline (5 mg BID, range 55.7–65.7 mm; 10 mg BID, 54.4–60.1 mm) decreased as
early as W2 (1st post-baseline assessment; 45.8–49.8 mm; 38.9–44.8 mm) and continued to decrease through M6 (30.9–
34.4 mm; 28.2–36.7 mm); decreases were numerically greater vs PBO and the magnitude of change in RA and PsA
populations was similar (Table). Improvements in SF-36v2 Q7 (Table), SF-36v2 BP (Table), and EQ-5D PD were observed
in all 4 RA and PsA csDMARD-IR and TNFi-IR populations, and in BASDAI Q2 and Q3 in the csDMARD-IR PsA and
TNFi-IR PsA populations. In the AS population, improvements from baseline in mean SF-36v2 Q7 (Table), SF-36v2 BP
(Table), EQ-5D PD, and BASDAI Q2 and Q3 were reported at W12 and were numerically greater vs PBO.
Conclusion: Treatment with tofacitinib is associated with a rapid improvement and sustained reduction of pain in pts with
RA and PsA who are csDMARD-IR or TNFi-IR, and in pts with AS.
Disclosure: A. Ogdie, Novartis, University of Pennsylvania, 2,Novartis, Pfizer Inc, Takeda, 5; K. de Vlam, Eli Lilly,
Pfizer Inc, 5,Galapagos, 9; I. B. McInnes, Celgene, Janssen, Novartis, Pfizer Inc, Roche, UCB, 2,AbbVie, Celgene,
Janssen, Novartis, UCB, 5; P. J. Mease, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis,
Pfizer Inc, Sun Pharmaceutical, UCB, 2,AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis,
Pfizer Inc, Sun Pharmaceutical, UCB, 5,AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis,
Pfizer Inc, UCB, 8; P. Baer, AbbVie, Amgen, Eli Lilly, Johnson and Johnson, Novartis, Paladin, Sanofi-Genzyme, Takeda,
5,Amgen, Janssen, Lifelabs, Pfizer Inc, 8; T. Lukic, Pfizer Inc, 1,Pfizer Inc, 3; K. Kwok, Pfizer Inc, 1,Pfizer Inc, 3; C.
Wang, Pfizer Inc, 1,Pfizer Inc, 3; M. A. Hsu, Pfizer Inc, 1,Pfizer Inc, 3; A. Maniccia, Pfizer Inc, 1,Pfizer Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effect-of-tofacitinib-on-reducing-pain-

in-patients-with-rheumatoid-arthritis-psoriatic-arthritis-and-ankylosing-spondylitis
Efficacy of Tofacitinib By Background Methotrexate Dose in Patients with

Psoriatic Arthritis: A Post Hoc Analysis of Pooled Data from 2 Phase 3 Trials
Alan J. Kivitz1, Oliver FitzGerald2, Peter Nash3, Shirley Pang4, Valderilio F Azevedo5, Elizabeth Kudlacz6, Cunshan
Wang6, Daniela Graham6 and Liza Takiya7, 1Department of Rheumatology, Altoona Center for Clinical Research,
Duncansville, PA, 2Department of Rheumatology, St Vincent's University Hospital, Dublin, Ireland, 3Department of
Medicine, University of Queensland, St Lucia, Brisbane, Australia, 4St. Jude Medical Center, Fullerton, CA, 5Universidade
Federal do Paraná, Curitiba, Brazil, 6Pfizer Inc, Groton, CT, 7Pfizer Inc, Collegeville, PA
SESSION INFORMATION
Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor under investigation for psoriatic arthritis (PsA). The
efficacy of tofacitinib has been evaluated in 2 Phase 3 studies in patients (pts) with PsA. In this analysis, we describe the
efficacy of tofacitinib by background methotrexate (MTX) dose in pts with PsA.
Methods: This post hoc analysis utilized efficacy data pooled from 2 Phase 3, randomized, double-blind, placebo-
controlled studies (OPAL Broaden [12 months; NCT01877668] and OPAL Beyond [6 months; NCT01882439]) in pts with
a diagnosis (≥6 months) of active PsA (≥3 swollen and ≥3 tender joints). Pts in OPAL Broaden were tumor necrosis factor
inhibitor (TNFi)-naïve and had an inadequate response (IR) to ≥1 conventional synthetic disease-modifying antirheumatic
drug (csDMARD). Pts in OPAL Beyond had an IR to ≥1 TNFi. Pts were randomized to tofacitinib 5 or 10 mg twice daily
(BID), placebo, or adalimumab 40 mg subcutaneous every 2 weeks (OPAL Broaden; adalimumab data not shown). All pts
received a stable dose of 1 csDMARD (eg MTX, leflunomide, or sulfasalazine) as background therapy. The maximum dose
of MTX allowed per protocol was 20 mg/week. Efficacy outcomes for tofacitinib at Month 3 were evaluated by
background MTX dose (≤15 vs >15 mg/week) and included: ACR20/50/70 response rates (≥20/50/70% improvement from
baseline, respectively), Health Assessment Questionnaire-Disability Index (HAQ-DI) response rate (reduction from
baseline ≥0.35 points), and mean change from baseline in HAQ-DI score. Analyses were based on the full analysis set for
pts receiving MTX on Day 1; pts with missing data were considered as having a non-response for binary endpoints. No
statistical testing was performed.
Results: In total, data from 556 pts who received tofacitinib plus MTX only or placebo plus MTX only (tofacitinib 5 mg
BID, n=186; tofacitinib 10 mg BID, n=178; placebo, n=192) were included in this analysis. Most pts were treated with
background MTX at doses ≤15 mg/week (n=371, 66.7%; mean [SD] dose, 12.6 [3.1] mg/week) vs >15 mg/week (n=185,
33.3%; mean [SD] dose, 19.8 [0.8] mg/week). Baseline demographics and disease characteristics were generally similar
between arms in MTX dose groups (Table). At Month 3, tofacitinib 5 and 10 mg BID were generally associated with
numerically greater ACR and HAQ-DI response rates and greater changes from baseline in HAQ-DI score compared with
placebo. The magnitude of tofacitinib effects on efficacy outcomes appeared broadly similar between background MTX
dose groups (Table).
Conclusion: The results of this pooled analysis suggest that the efficacy of tofacitinib in pts with PsA was greater than
placebo and does not differ when evaluated by background MTX dose (≤15 vs >15 mg/week), although small pt numbers
in some groups may limit the conclusions that can be made. These results are consistent with findings from similar analyses
of tofacitinib in pts with rheumatoid arthritis.
Disclosure: A. J. Kivitz, AbbVie, Genentech, Genzyme, Janssen, Novartis, Pfizer Inc, Sanofi, UCB, 5,Celgene,
Genentech, Genzyme, Novartis, Pfizer Inc, Sanofi, 8; O. FitzGerald, AbbVie, Bristol-Myers Squibb, Novartis, Pfizer Inc,
2,Amgen, Celgene, Eli Lilly, Janssen, 5; P. Nash, None; S. Pang, None; V. F. Azevedo, AbbVie, Eli Lilly, Genentech,
GSK, Pfizer Inc, UCB, 2,AbbVie, Merck-Serono, Novartis, Pfizer Inc, 5,AbbVie, Janssen, Merck-Serono, Novartis, Pfizer
Inc, Sanofi, 8; E. Kudlacz, Pfizer Inc, 1,Pfizer Inc, 3; C. Wang, Pfizer Inc, 1,Pfizer Inc, 3; D. Graham, Pfizer Inc, 1,Pfizer
Inc, 3; L. Takiya, Pfizer Inc, 1,Pfizer Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/efficacy-of-tofacitinib-by-background-

methotrexate-dose-in-patients-with-psoriatic-arthritis-a-post-hoc-analysis-of-pooled-data-from-2-phase-3-trials
Integrated Safety Summary of Tofacitinib in Psoriatic Arthritis Clinical

Studies
Gerd R. Burmester1, Oliver FitzGerald2, Kevin Winthrop3, Valderilio F Azevedo4, William F C Rigby5, Keith S Kanik6,
Cunshan Wang6, Pinaki Biswas7, Thomas Jones8, Sujatha Menon6, Niki Palmetto7 and Ricardo Rojo6, 1Charité -
University Medicine Berlin, Berlin, Germany, 2Department of Rheumatology, St Vincent's University Hospital, Dublin,
Ireland, 3Oregon Health & Science University, Portland, OR, 4Universidade Federal do Paraná, Curitiba, Brazil, 5Geisel
School of Medicine at Dartmouth, Lebanon, NH, 6Pfizer Inc, Groton, CT, 7Pfizer Inc, New York, NY, 8Pfizer Inc,
Collegeville, PA
SESSION INFORMATION
Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor under investigation for psoriatic arthritis (PsA). We
describe the safety profile of tofacitinib from integrated Phase (P)3 and long-term extension (LTE) studies.
Methods: Data were analyzed for patients (pts) who received ≥1 dose of tofacitinib 5 or 10 mg twice daily (BID) or
placebo (PBO), integrated across 2 P3 studies (OPAL Broaden [12 months; NCT01877668]; OPAL Beyond [6 months;
NCT01882439]) and 1 LTE study (OPAL Balance [ongoing, database not locked; NCT01976364]). Common adverse
events (AEs; occurring in ≥2% of tofacitinib pts in any group) were analyzed in the PBO-controlled portion (Months 0–3)
of the P3 studies (Cohort 1 [C1]). Serious AEs (SAEs) and discontinuations due to AEs were analyzed over 12 months in
pts randomized to tofacitinib 5 or 10 mg BID in P3 studies (Cohort 2a [C2a]); pts randomized to PBO were excluded from
this analysis. Deaths and AEs of special interest (serious infections [SI], herpes zoster [HZ], opportunistic infections [OI]
including HZ, major adverse cardiovascular events [MACE], malignancies, non-melanoma skin cancer [NMSC]) were
evaluated in all tofacitinib-treated pts in the P3 and LTE studies (Cohort 3 [C3]). Incidence rates (IR; pts with events/100
pt‑years [PY] and 95% confidence intervals) are reported. Laboratory results will be reported in future publications.
Results: C1 included 474 tofacitinib- and 236 PBO-treated pts; C2a included 474 tofacitinib-treated pts; and C3 included
783 tofacitinib-treated pts (exposure: 776 PY). Nasopharyngitis (5.9%) and headache (8.5%) were the most commonly
reported AEs at Month 3 in pts receiving tofacitinib 5 and 10 mg BID, respectively (Table). In pts randomized to tofacitinib
5 or 10 mg BID, over 12 months (C2a), the IRs for SAEs were 7.92 (4.09, 13.84) and 8.11 (4.19, 14.17), respectively.
Discontinuation due to AEs occurred in 11 (4.6%) and 11 (4.7%) pts randomized to tofacitinib 5 and 10 mg BID,
respectively, with IRs of 7.16 (3.58, 12.82) and 7.31 (3.65, 13.08), respectively, over 12 months (C2a). Across all
tofacitinib-treated pts in the P3 and LTE studies (C3), SIs occurred in 11 pts (1.4%; IR 1.40 [0.70, 2.50]). HZ was reported
in 16 pts (2.0%; IR 2.05 [1.17, 3.33]) receiving tofacitinib. All 3 cases of multidermatomal HZ were adjudicated as OIs;
these were the only OIs (0.4%; IR 0.38 [0.08, 1.11]). In C3, 2 deaths occurred (0.3%; IR 0.25 [0.03, 0.91]); all were
considered unrelated to the study drug. MACE were reported in 3 pts (0.4%; IR 0.38 [0.08, 1.11]), malignancies (excluding
NMSC) in 5 pts (0.6%; IR 0.63 [0.21, 1.48]), and NMSC in 4 pts (0.5%; IR 0.51 [0.14, 1.30]) in C3.
Conclusion: Tofacitinib in active PsA demonstrated a safety profile consistent to that seen with tofacitinib in RA; no new
risks were identified. Longer-term follow-up and larger pt populations will provide further information on the safety profile
of tofacitinib in pts with PsA.
Disclosure: G. R. Burmester, Pfizer Inc, 2,Pfizer Inc, 5; O. FitzGerald, AbbVie, Bristol-Myers Squibb, Novartis, Pfizer
Inc, 2,Amgen, Celgene, Eli Lilly, Janssen, 5; K. Winthrop, Bristol-Myers Squibb, 2,AbbVie, Bristol-Myers Squibb, Eli
Lilly, Galapagos, Pfizer Inc, UCB, 5; V. F. Azevedo, AbbVie, Eli Lilly, Genentech, GSK, Pfizer Inc, UCB, 2,AbbVie,
Merck-Serono, Novartis, Pfizer Inc, 5,AbbVie, Janssen, Merck-Serono, Novartis, Pfizer Inc, Sanofi, 8; W. F. C. Rigby,
Roche, 5; K. S. Kanik, Pfizer Inc, 1,Pfizer Inc, 3; C. Wang, Pfizer Inc, 1,Pfizer Inc, 3; P. Biswas, Pfizer Inc, 1,Pfizer Inc,
3; T. Jones, Pfizer Inc, 1,Pfizer Inc, 3; S. Menon, Pfizer Inc, 1,Pfizer Inc, 3; N. Palmetto, Pfizer Inc, 1,Pfizer Inc, 3; R.
Rojo, Pfizer Inc, 1,Pfizer Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/integrated-safety-summary-of-

tofacitinib-in-psoriatic-arthritis-clinical-studies
Comparing Tofacitinib Safety Profile in Patients with Psoriatic Arthritis in

Clinical Studies with Real-World Data
Jeffrey R. Curtis1, Huifeng Yun1, Oliver FitzGerald2, Kevin Winthrop3, Valderilio F Azevedo4, Gerd R. Burmester5,
William F C Rigby6, Keith S Kanik7, Ricardo Rojo7, Sujatha Menon7, Cunshan Wang7, Pinaki Biswas8, Thijs Hendrikx9
and Niki Palmetto8, 1University of Alabama at Birmingham, Birmingham, AL, 2Department of Rheumatology, St Vincent's
University Hospital, Dublin, Ireland, 3Oregon Health & Science University, Portland, OR, 4Universidade Federal do
Paraná, Curitiba, Brazil, 5Rheumatology and Clinical Immunology, Charité - University Medicine Berlin, Free University
and Humboldt University Berlin, Berlin, Germany, 6Geisel School of Medicine at Dartmouth, Lebanon, NH, 7Pfizer Inc,
Groton, CT, 8Pfizer Inc, New York, NY, 9Pfizer Inc, Collegeville, PA
SESSION INFORMATION
arthritis (PsA). Two Phase 3 studies have been completed (NCT01877668; NCT01882439) and a long-term extension
(LTE) study is ongoing (database not locked; NCT01976364). This analysis compares incidence rates (IR) for adverse
events (AEs) of special interest in a tofacitinib cohort from the Phase 3 PsA trials with real-world experience in a
comparison cohort from the US Truven MarketScan database.
Methods: The tofacitinib cohort included adult patients (pts) from 2 Phase 3 studies with ≥6 months’ PsA diagnosis who
met CASPAR criteria, had active plaque psoriasis, and active arthritis (≥3 swollen and ≥3 tender/painful joints). Pts were
grouped by those who received tofacitinib 5 (N=238) or 10 mg (N=236) twice daily (BID) in the Phase 3 studies, and all
pts who received ≥1 dose of tofacitinib in the Phase 3 studies or the LTE (tofacitinib all doses, N=783). The comparison
cohort (N=5,799) comprised pts with moderate to severe PsA, defined by ≥1 inpatient or ≥2 outpatient 696.0 diagnosis
codes on 2 unique calendar days (≥1 by a rheumatologist) between Oct 2010 and Sep 2015, or initiated therapy with a
systemic agent for PsA. Key Phase 3 study exclusion criteria were applied to the comparison cohort. IRs for serious
infection events (SIEs), herpes zoster (HZ), malignancies (excluding non-melanoma skin cancer [NMSC]), NMSC, and
major adverse cardiovascular events (MACE) were compared.
Results: Mean age, gender, and diabetes history were generally similar between the tofacitinib and comparison cohorts
(48.7–49.5 years, 42.4–49.2% male, 12.2–15.7% history of diabetes). Overall, more tofacitinib-treated pts had prior
experience with corticosteroids (15.7–28.2%), csDMARDs (100%), and tumor necrosis factor inhibitors (48.1–55.9%) vs
the comparison cohort (11.9%, 46.6%, and 36.6%, respectively). IRs per 100 PY (95% CI) for SIEs requiring parenteral
antibiotics in an outpatient/emergency setting, or resulting in hospitalization were 1.30 (0.16, 4.69) and 2.00 (0.41, 5.83) in
the tofacitinib 5 and 10 mg BID groups, respectively (Table). IRs were generally similar between the tofacitinib and
comparison cohorts for SIEs resulting in hospitalization only, and for SIEs requiring parenteral antibiotics in emergency
settings or resulting in hospitalization (data not shown). In general, the tofacitinib cohort had a higher rate of HZ vs the
comparison cohort, and similar IRs for malignancies and MACE between cohorts (Table).
Conclusion: IRs of AEs of special interest reported in tofacitinib PsA Phase 3 studies were generally comparable to those
in a general PsA population comprising pts receiving a range of biologic agents, except HZ, which was higher for
tofacitinib-treated pts but similar to the incidence observed with tofacitinib treatment in other indications.
Disclosure: J. R. Curtis, Amgen, Corona, Crescendo Bio, Pfizer Inc, 2,AbbVie, Amgen, Bristol-Myers Squibb, Corona,
Eli Lilly, Janssen, Myriad, Pfizer Inc, Roche/Genentech, UCB, 5; H. Yun, Bristol-Myers Squibb, 2; O. FitzGerald,
AbbVie, Bristol-Myers Squibb, Novartis, Pfizer Inc, 2,Amgen, Celgene, Eli Lilly, Janssen, 5; K. Winthrop, Bristol-Myers
Squibb, 2,AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Pfizer Inc, UCB, 5; V. F. Azevedo, AbbVie, Eli Lilly,
Genentech, GSK, Pfizer Inc, UCB, 2,AbbVie, Merck-Serono, Novartis, Pfizer Inc, 5,AbbVie, Janssen, Merck-Serono,
Novartis, Pfizer Inc, Sanofi, 8; G. R. Burmester, Pfizer Inc, 2,Pfizer Inc, 5; W. F. C. Rigby, Roche, 5; K. S. Kanik, Pfizer
Inc, 1,Pfizer Inc, 3; R. Rojo, Pfizer Inc, 1,Pfizer Inc, 3; S. Menon, Pfizer Inc, 1,Pfizer Inc, 3; C. Wang, Pfizer Inc, 1,Pfizer
Inc, 3; P. Biswas, Pfizer Inc, 1,Pfizer Inc, 3; T. Hendrikx, Pfizer Inc, 1,Pfizer Inc, 3; N. Palmetto, Pfizer Inc, 1,Pfizer Inc,
3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/comparing-tofacitinib-safety-profile-in-

patients-with-psoriatic-arthritis-in-clinical-studies-with-real-world-data
Secukinumab Sustains Individual Clinical Responses over Time in Patients

with Psoriatic Arthritis: 2-Year Results from a Phase 3 Trial
Paul Emery1, Iain B. McInnes2, Philip J Mease3, Michael Schiff4, Luminita Pricop5, Steven Shen5, Zailong Wang5 and
Corine Gaillez6, 1NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, United
Kingdom, 2University of Glasgow, Glasgow, United Kingdom, 3Swedish Medical Center and University of Washington,
Seattle, WA, 4University of Colorado, Denver, CO, 5Novartis Pharmaceuticals Corporation, East Hanover, NJ, 6Novartis
Pharma AG, Basel, Switzerland
SESSION INFORMATION
Background/Purpose: Achieving, sustaining, and improving clinical responses to biologics in PsA are important parts of
EULAR and GRAPPA recommendations aimed to optimize treatment goals.1,2 Here we present patient (pt)-level
secukinumab data and report the likelihood of improving, sustaining, or worsening an ACR response and disease status
(28-joint disease activity score using CRP [DAS28-CRP]) from Week (Wk) 24 to 104 in pts with active PsA from the
FUTURE 2 trial.3,4
Methods: Data from FUTURE 2 trial through Wk 104 have been previously reported.4 This post-hoc shift analysis was
performed on ACR responses (ACR non-responders [NR], ACR20, 50, or 70) between Wks 24 and 104 for subgroups of
secukinumab-treated pts categorized by their highest ACR response criteria at the earlier time point, by evaluating whether
this response was improved, sustained or worsened at the later time point, using mutually exclusive ACR response
categories and as observed analyses. Similar shift analyses on DAS28-CRP derived criteria were performed in 4 exclusive
categories: high, moderate, and low disease activity (HDA, MDA, and LDA), and remission (REM) only.5
Results: In total, 86/100 (86%) and 76/100 (76%) pts in the secukinumab 300 and 150 mg groups, respectively, completed
the 104-wk treatment. Of which, 73/70 and 81/75 pts in secukinumab 300/150 mg were eligible for ACR and DAS28-CRP
shift analysis, respectively, from Wk 24 to 104. Baseline demographics and clinical characteristics were balanced across
treatment groups.3,4 Most secukinumab-treated pts who achieved at least an ACR20, 50, or 70 response at Wk 24,
improved or sustained their response at Wk 104 (Figure). Similarly, a majority of pts who were in the MDA, LDA, or REM
status at Wk 24 sustained or improved their disease status related to DAS28-CRP score at Wk 104 (Figure). In
secukinumab 300 mg group, 53% of pts with LDA improved to REM and a majority (76%) of pts with REM maintained
their status from Wk 24 to 104, whereas, in 150 mg group, a majority of pts (75% and 72% with LDA and REM,
respectively) improved or maintained their status by Wk 104.
Conclusion: In this post-hoc analysis, a majority of secukinumab-treated pts who achieved at least ACR20 response or at
least MDA at Wk 24 sustained or improved their ACR response or disease status at Wk 104. Numerically higher sustained
ACR response and LDA or REM rate was observed for secukinumab 300 mg, thereby extending the sustainability of ACR
response and lowering the disease activity that has been previously reported at group level.2,3
References: 1. Gossec L, et al. Ann Rheum Dis 2016;75:499–510; 2. Coates LC, et al. J Rheumatol 2014;41:1237–9; 3.
McInnes IB, et al. Lancet 2015;386:1137–46; 4. McInnes IB, et al. Arthritis Rheumatol 2016;68;abstract: 2757; 5. Wells G,
et al. Ann Rheum Dis 2009;68:954–60.
Disclosure: P. Emery, AbbVie, BMS, Merck, Novartis, Pfizer, Roche, UCB, 5; I. B. McInnes, Novartis, Amgen, Janssen,
BMS, Pfizer, UCB, AbbVie, Celgene, Lilly, 5; P. J. Mease, AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Merck,
Novartis, Pfizer, SUN, and UCB, 2,: AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly,
Merck, Novartis, Pfizer, SUN, and UCB, 5,AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Merck, Novartis,
Pfizer and UCB, 8; M. Schiff, AbbVie, BMS, Lilly, J&J, 5,AbbVie, 8; L. Pricop, Novartis Pharmaceutical Corporation,
1,Novartis Pharmaceutical Corporation, 3; S. Shen, Novartis Pharmaceutical Corporation, 3; Z. Wang, Novartis
Pharmaceutical Corporation, 3; C. Gaillez, Novartis Pharma AG, BMS, 1,Novartis Pharma AG, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/secukinumab-sustains-individual-

clinical-responses-over-time-in-patients-with-psoriatic-arthritis-2-year-results-from-a-phase-3-trial
Integrated Efficacy Analysis of Tofacitinib, an Oral Janus Kinase Inhibitor,

in Patients with Active Psoriatic Arthritis
Peter Nash1, Laura C Coates2, Roy Fleischmann3, Kim Papp4, Juan J. Gomez-Reino5, Keith S Kanik6, Cunshan Wang6,
Joseph Wu6, Thijs Hendrikx7 and William C Ports6, 1Department of Medicine, University of Queensland, St Lucia,
Brisbane, Australia, 2Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United
Kingdom, 3Metroplex Clinical Research Center and University of Texas Southwestern Medical Center, Dallas, TX,
4Probity Medical Research and K. Papp Clinical Research Inc, Waterloo, ON, Canada, 5Fundacion Ramon Dominguez,
Hospital Clinico Universitario, Santiago de Compostela, Spain, 6Pfizer Inc, Groton, CT, 7Pfizer Inc, Collegeville, PA
SESSION INFORMATION
Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor under investigation for treatment of psoriatic arthritis
(PsA). We examined tofacitinib efficacy in patients (pts) with active PsA.
Methods: Data were pooled from 2 placebo (PBO)-controlled, double-blind, multicenter, global Phase 3 studies (OPAL
Broaden [N=422; 12 months; NCT01877668]; OPAL Beyond [N=394; 6 months; NCT01882439]). Pts had active PsA and
either inadequate response (IR) to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD) and were
tumor necrosis factor inhibitor (TNFi)-naïve (OPAL Broaden), or had IR to ≥1 TNFi (OPAL Beyond). Pts were randomized
to tofacitinib 5 mg twice daily (BID), 10 mg BID, adalimumab 40 mg subcutaneous injection once every 2 weeks (OPAL
Broaden only), or PBO, and a single, stable csDMARD. PBO pts moved to tofacitinib 5 mg or 10 mg BID at Month (M)3.
Endpoints included ACR20/50/70 response rates (≥20%/≥50%/≥70% improvement), change from baseline (D) in Health
Assessment Questionnaire-Disability Index (HAQ-DI), HAQ-DI response (decrease from baseline [BL] of ≥0.35), ≥75%
improvement from BL in Psoriasis Area and Severity Index (PASI75), D Leeds Enthesitis Index (LEI) and enthesitis
absence, D Dactylitis Severity Score (DSS) and dactylitis absence, and Δ Dermatology Life Quality Index (DLQI).
Tofacitinib 5 mg and 10 mg BID data (to M6) and PBO data (to M3), were pooled. Significance was declared at p≤0.05
without correction for multiplicity.
Results: In total, 238, 236 and 236 pts received tofacitinib 5 mg BID, 10 mg BID, or placebo, respectively. Pts were white
(94.2%) and female (55.4%) with ≥5 peripheral swollen or tender joints (98.0%), enthesitis (LEI>0; 67.5%), dactylitis
(DSS>0; 52.5%), psoriatic body surface area ≥3% (67.7%), and C-reactive protein levels >2.87 mg/L (62.5%) at BL. Mean
age was 49.1 years; mean PsA duration was 8.0 years. Significant improvements vs PBO at M3 were seen for peripheral
arthritis and physical function endpoints for tofacitinib 5 mg and 10 mg BID: ACR20, ACR50, ACR70, DHAQ-DI, and
HAQ-DI response (Table 1). Significant improvements in psoriasis, enthesitis, and dactylitis endpoints vs PBO were seen
for tofacitinib 5 mg and 10 mg BID at M3: PASI75, DLEI, enthesitis absence (using LEI), DDSS, dactylitis absence (using
DSS), and ΔDLQI (Table 1). Efficacy was maintained or further improved at M6.
Conclusion: In a pooled analysis of csDMARD-IR/TNFi-naïve and TNFi-IR pts, tofacitinib 5 mg and 10 mg BID
improved peripheral arthritis and physical function, psoriasis, enthesitis, and dactylitis vs PBO at M3.
Disclosure: P. Nash, None; L. C. Coates, AbbVie, Janssen, 2,AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, MSD,
Novartis, Pfizer Inc, Sun Pharma, UCB, 5; R. Fleischmann, AbbVie, Pfizer Inc, UCB, 2,AbbVie, Pfizer Inc, UCB, 5; K.
Papp, AbbVie, Akros, Allergen, Amgen, Anacor, Astellas, Baxalta, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene,
Dermira, Dow Pharma, Eli Lilly, Galderma, Genentech, GSK, Janssen, Kyowa Hakko Kirin, Leo Pharma, MedImmune,
Merck MSD, Merck-Serono, Mylan, 2,Novartis, Pfizer Inc, Regeneron, Roche, Sanofi-Aventis/Genzyme, Stiefel, Takeda,
UCB, Valeant, 2,AbbVie, Akros, Amgen, Astellas, AstraZeneca, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers
Squibb, Can-Fite, Celgene, Dermira, Devonian, Dow Pharma, Eli Lilly, Galderma, Genentech, Janssen, Kyowa Hakko
Kirin, Leo Pharma, Meiji Seika Pharma, 5,Merck MSD, Merck-Serono, Mitsubishi Pharma, Mylan, Novartis, Pfizer Inc,
Regeneron, Roche, Sanofi-Aventis/Genzyme, Takeda, UCB, Valeant, 5,AbbVie, Amgen, Astellas, Celgene, Devonian, Eli
Lilly, Galderma, Janssen, Kyowa Hakko Kirin, Leo Pharma, Merck MSD, Novartis, Pfizer Inc, Valeant, 8,Akros, Anacor,
Kyowa Hakko Kirin, 9,AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Kyowa Hakko Kirin, Merck
MSD, Merck-Serono, Novartis, Pfizer Inc, Regeneron, Sanofi-Aventis/Genzyme, Valeant, 9,AbbVie, Amgen, Astellas,
Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dow Pharma, Eli Lilly, Galderma, Janssen, Merck MSD,
Novartis, Pfizer Inc, Regeneron, Sanofi-Aventis/Genzyme, UCB, Valeant, 9; J. J. Gomez-Reino, AbbVie, MSD, Pfizer
Inc, Roche, 2,Pfizer Inc, 5,AbbVie, Biogen, Bristol-Myers Squibb, Janssen, MSD, Pfizer Inc, Roche, 8; K. S. Kanik, Pfizer
Inc, 1,Pfizer Inc, 3; C. Wang, Pfizer Inc, 1,Pfizer Inc, 3; J. Wu, Pfizer Inc, 1,Pfizer Inc, 3; T. Hendrikx, Pfizer Inc,
1,Pfizer Inc, 3; W. C. Ports, Pfizer Inc, 1,Pfizer Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/integrated-efficacy-analysis-of-

tofacitinib-an-oral-janus-kinase-inhibitor-in-patients-with-active-psoriatic-arthritis
Safety and Efficacy of Tofacitinib, an Oral Janus Kinase Inhibitor, up to 36

Months in Patients with Active Psoriatic Arthritis: Data from the Second
Interim Analysis of OPAL Balance, an Open‑Label, Long-Term Extension
Study
Peter Nash1, Laura C Coates2, Alan J. Kivitz3, Philip J Mease4, Dafna D Gladman5, Jose A Covarrubias-Cobos6, Dona
Fleishaker7, Cunshan Wang7, Elizabeth Kudlacz7, Sujatha Menon7, Thijs Hendrikx8 and Keith S Kanik7, 1Department of
Medicine, University of Queensland, St Lucia, Brisbane, Australia, 2Leeds Institute of Rheumatic and Musculoskeletal
Medicine, University of Leeds, Leeds, United Kingdom, 3Department of Rheumatology, Altoona Center for Clinical
Research, Duncansville, PA, 4Swedish Medical Center and University of Washington, Seattle, WA, 5Department of
Medicine, University of Toronto, Toronto Western Hospital, Toronto, ON, Canada, 6Unidad Reumatologica Las Americas
S.C.P, Yucatán, Mexico, 7Pfizer Inc, Groton, CT, 8Pfizer Inc, Collegeville, PA
SESSION INFORMATION
Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor under investigation for psoriatic arthritis (PsA). Interim
data up to January 2017 (database not locked) report the safety, tolerability and efficacy of tofacitinib for patients (pts) with
active PsA from ≤36 months’ participation in an ongoing open-label, long-term extension study (LTE; NCT01976364
OPAL Balance).
Methods: Eligible pts from 2 pivotal Phase (P)3 tofacitinib PsA studies (NCT01877668 OPAL Broaden, NCT01882439
OPAL Beyond) could enter a 3-year LTE ≤3 months after completing the qualifying study or discontinuing for reasons
unrelated to the study drug. Pts received tofacitinib 5 mg twice daily (BID) for 1 month, after which an increase to 10 mg
BID for efficacy reasons or a reduction back to 5 mg BID for safety reasons was permitted. All pts entered on a background
of a csDMARD, as was mandated by the qualifying studies. Primary endpoints were incidence and severity of adverse
events (AEs) and change from baseline in laboratory values. Efficacy was a secondary endpoint.
Results: 686 pts were enrolled and treated in OPAL Balance and 530 pts (77.3%) remained at data cut-off. Mean (range)
duration of tofacitinib exposure in the LTE was 448 (1–1,015) days. On Day 1, 676 (98.5%) pts received a csDMARD, of
which 56 (8.3%) later discontinued. To Month 36, 1,685 AEs were reported in 502 (73.2%) pts, 72 (10.5%) pts had serious
AEs, and 52 (7.6%) discontinued due to AEs. AEs of special interest included 11 serious infections (1.6%), 19 herpes
zoster events (2.8%) including 1 serious event of facial herpes zoster, 2 major adverse cardiovascular events (0.3%), and 13
(1.9%) malignancies. No AEs of gastrointestinal perforation or inflammatory bowel disease were reported. One AE of
uveitis was reported. There were 4 deaths (not attributed to treatment, as assessed by the investigator) due to metastatic
pancreatic carcinoma, acute cardiac failure/hypertensive heart disease, chronic obstructive pulmonary disease, and
pulmonary embolism. Four AEs of latent tuberculosis were reported in pts whose previously negative QuantiFERON
response became positive. Few pts experienced elevated liver enzyme levels; ALT was elevated ≥3 x ULN in 20 (2.9%)
pts, AST ≥3 x ULN in 11 (1.6%) pts. Four (0.6%) pts met discontinuation criteria for laboratory values due to 2 sequential
hemoglobin values <8.0 g/dL or decreases >30% from baseline value, 2 sequential platelet counts <75 x109/L, 2 sequential
AST or ALT elevations ≥5 x ULN regardless of total bilirubin or accompanying signs or symptoms, and 2 sequential
increases in serum creatinine >50% and an increase >0.5 mg/dL over average of screening and baseline. Efficacy was
maintained in the LTE (Table).
Conclusion: Over 36 months in the LTE, the safety profile of tofacitinib in pts with active PsA was generally similar to
that of the pivotal P3 studies. No new safety signals were identified. Efficacy across various PsA disease domains was
maintained over time.
Disclosure: P. Nash, None; L. C. Coates, AbbVie, Janssen, 2,AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen,
Lilly, MSD, Novartis, Pfizer Inc, Sun Pharma, UCB, 5; A. J. Kivitz, AbbVie, Genentech, Genzyme, Janssen, Novartis,
Pfizer Inc, Sanofi, UCB, 5,Celgene, Genentech, Genzyme, Novartis, Pfizer Inc, Sanofi, 8; P. J. Mease, AbbVie, Amgen,
Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, Sun Pharmaceutical, UCB, 2,AbbVie, Amgen,
Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer Inc, Sun Pharmaceutical, UCB, 5,AbbVie, Amgen,
Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer Inc, UCB, 8; D. D. Gladman, AbbVie, Amgen,
BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, 2,AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen,
Novartis, Pfizer Inc, UCB, 5; J. A. Covarrubias-Cobos, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer Inc, 2; D.
Fleishaker, Pfizer Inc, 1,Pfizer Inc, 3; C. Wang, Pfizer Inc, 1,Pfizer Inc, 3; E. Kudlacz, Pfizer Inc, 1,Pfizer Inc, 3; S.
Menon, Pfizer Inc, 1,Pfizer Inc, 3; T. Hendrikx, Pfizer Inc, 1,Pfizer Inc, 3; K. S. Kanik, Pfizer Inc, 1,Pfizer Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/safety-and-efficacy-of-tofacitinib-an-

oral-janus-kinase-inhibitor-up-to-36-months-in-patients-with-active-psoriatic-arthritis-data-from-the-second-interim-
analysis-of-opal-balance-an-open%e2%80%91
Secukinumab Provides Sustained Improvement in Major and Moderate

Response of Disease Activity Index for Psoriatic Arthritis (DAPSA): 2-Year
Results from a Phase 3 Study
Josef S. Smolen1, Philip J Mease2, Christopher T. Ritchlin3, Tore K Kvien4, Luminita Pricop5, Todd Fox6, Lawrence
Rasouliyan7, Steffen Jugl6 and Corine Gaillez6, 1Medical University of Vienna, Vienna, Austria, 2Swedish Medical Center
and University of Washington, Seattle, WA, 3Division of Allergy, Immunology and Rheumatology, School of Medicine and
Dentistry, Division of Allergy, Immunology and Rheumatology, School of Medicine and Dentistry, University of Rochester,
Rochester, New York, USA, Rochester, NY, 4Diakonhjemmet Hospital, Oslo, Norway, 5Novartis Pharmaceuticals
Corporation, East Hanover, NJ, 6Novartis Pharma AG, Basel, Switzerland, 7RTI Health Solutions, Barcelona, Spain
SESSION INFORMATION
Background/Purpose: DAPSA score is a validated tool to measure disease activity states and response criteria, focusing
on peripheral joint involvement in patients (pts) with PsA.1 Secukinumab, a fully human anti–IL-17A mAb, significantly
improved signs and symptoms vs placebo (PBO) at Week (Wk) 24, with sustained ACR responses through Wk 104 from
the FUTURE 2 study2,3. This post-hoc analysis assessed DAPSA responses through Wk 104 from FUTURE 2 study.
Methods: FUTURE 2 study design has been previously reported.3 DAPSA score was derived as the sum of five variables:
tender and swollen joint counts (TJC 68 and SJC 66), pt global and pt pain assessed on a 10 cm visual analog scale, and
CRP level (mg/dL). DAPSA responses are presented for secukinumab 300 and 150 mg (approved doses) in overall
population and in pts stratified by prior anti-TNF therapy use (anti–TNF-naïve vs inadequate response/intolerance to these
agents [anti–TNF-IR]) and time since first PsA diagnosis (≤2 vs >2 years) using observed data.
Results: Baseline demographics and clinical characteristics were similar across treatment groups.3 A total of 96,100, and
87 pts treated with secukinumab 300, 150 mg, and PBO, respectively, were available for the evaluation of DAPSA response
at Wk 16. DAPSA response in overall population showed moderate/major response in 16%/14% and 22%/12% vs 2%/5%;
minor response in 28% and 23% vs 15%; no response in 43% and 43% vs 78% in secukinumab 300 and 150 mg vs PBO,
respectively. DAPSA response rates were higher and sustained at Wk 104 in secukinumab-treated pts. A higher proportion
(35% and 23%) of pts showed major response, with moderate response observed in 12% and 14% of pts treated with
secukinumab 300 and 150 mg, respectively, at Wk 104. The proportion of pts achieving DAPSA response at Wks 16 and
104 by anti-TNF use and time since first PsA diagnosis is shown in the figure. The proportion of pts in overall population
meeting DAPSA core components thresholds and other components of PsA among pts with DAPSA moderate/major
response at Wks 16 and 104 is shown in the table.
Conclusion: In the overall population, around 30% of secukinumab-treated pts at Wk 16 achieved DAPSA moderate/major
response vs <5% in PBO group, with numerical increase in the major response at Wk 104. Moderate/major response at Wk
16 was observed in pts regardless of prior anti-TNF use or time since first PsA diagnosis. Majority of the pts who achieved
major response met all core components criteria, in contrast to the pts with moderate response.
References: 1. Smolen JS, et al. Clin Exp Rheumatol. 2015; 33: S48–50; 2. McInnes IB, et al. Arthritis Rheumatol.
2016;68 (suppl 10); 3. McInnes IB, et al. Lancet 2015;386:1137–46.
Table: Proportion of Patients Meeting the Selected Variable Thresholds
DAPSA moderate response DAPSA major response
Criterion, Week Secukinumab Secukinumab Placebo Secukinumab Secukinumab Placebo
300 mg 150 mg 300 mg 150 mg
n/M (%)
PtGA <1 16 3/15 (20.0) 5/22 (22.7) 2/2 (100.0) 7/13 (53.8) 7/12 (58.3) 1/4 (25.0)
cm
104 1/10 (10.0) 1/11 (9.1) - 16/29 (55.2) 7/18 (38.9) -
CRP 16 15/15 (100.0) 22/22 (100.0) 2/2 (100.0) 13/13 (100.0) 12/12 (100.0) 4/4 (100.0)
<5 mg/dL 104 10/10 (100.0) 11/11 (100.0) - 29/29 (100.0) 18/18 (100.0) -
SJC 66 ≤1 16 7/15 (46.7) 14/22 (63.6) 2/2 (100.0) 11/13 (84.6) 11/12 (91.7) 4/4 (100.0)
104 8/10 (80.0) 7/11 (63.6) - 28/29 (96.6) 18/18 (100.0) -
TJC 68 ≤1 16 5/15 (33.3) 13/22 (59.1) 0 13/13 (100.0) 11/12 (91.7) 4/4 (100.0)
104 7/10 (70.0) 4/11 (36.4) - 27/29 (93.1) 15/18 (83.3) -
HAQ-DI 16 13/15 (86.7) 12/22 (54.5) 2/2 (100.0) 10/13 (76.9) 8/12 (66.7) 3/4 (75.0)
≤0.5 104 8/10 (80.0) 6/11 (54.5) - 26/29 (89.7) 15/18 (83.3) -
Enthesitis 16 13/15 (86.7) 21/22 (95.5) 2/2 (100.0) 13/13 (100.0) 11/12 (91.7) 4/4 (100.0)
resolution 104 9/10 (90.0) 9/11 (81.8) - 27/29 (93.1) 15/18 (83.3) -
Dactylitic 16 12/15 (80.0) 20/22 (90.9) 2/2 (100.0) 12/13 (92.3) 10/12 (83.3) 3/4 (75.0)
resolution 104 9/10 (90.0) 11/11 (100.0) - 25/29 (86.2) 17/18 (94.4) -
PASI 16 14/15 (93.3) 14/22 (63.6) 1/2 (50.0) 12/13 (92.3) 8/12 (66.7) 4/4 (100.0)
Score ≤1 104 8/10 (80.0) 7/11 (63.6) - 26/29 (89.7) 11/18 (61.1) -
CRP, C-reactive protein; DAPSA, Disease Activity Index for PSoriatic Arthritis; HAQ-DI, Health
Assessment Questionnaire - Disability Index; M, the number of evaluable patients; n, number of
patients who met the threshold criterion; PASI, Psoriasis Area and Severity Index; PtGA, Patient
Global Assessment; SJC, swollen joint count; TJC, tender joint count
Disclosure: J. S. Smolen, AbbVie, Janssen, Eli Lilly, MSD, Pfizer, Roche, Amgen, AstraZeneca, Astro, Celgene, Celltrion,
GSK, ILTOO, Medimmune, Novartis-Sandoz, Pfizer, Samsung, Sanofi and UCB, 2,AbbVie, Janssen, Eli Lilly, MSD,
Pfizer, Roche, Amgen, AstraZeneca, Astro, Celgene, Celltrion, GSK, ILTOO, Medimmune, Novartis-Sandoz, Pfizer,
Samsung, Sanofi and UCB, 5; P. J. Mease, AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, SUN,
and UCB, 2,: AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer,
SUN, and UCB, 5,AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer and UCB, 8; C. T.
Ritchlin, Amgen, UCB, Abbvie, Novartis, and Janssen, Amgen, UCB, Abbvie, Novartis, and Janssen, 2,Amgen, UCB,
Abbvie, Novartis, and Janssen, Amgen, UCB, Abbvie, Novartis, and Janssen, 5,Amgen, UCB, Abbvie, Novartis, and
Janssen, Amgen, UCB, Abbvie, Novartis, and Janssen, 8; T. K. Kvien, AbbVie, Biogen, BMS, Boehringer Ingelheim,
Roche, Sandoz, UCB, 5,AbbVie, Biogen, BMS, Boehringer Ingelheim, Celltrion, Eli Lilly, Epirus, Janssen, Merck-Serono,
MSD, Mundipharma, Novartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Sandoz, UCB, 8; L. Pricop, Novartis
Pharmaceutical Corporation, 1,Novartis Pharmaceutical Corporation, 3; T. Fox, Novartis Pharma AG, 1,Novartis Pharma
AG, 3; L. Rasouliyan, Novartis Pharmaceutical Corporation, 5,RTI Health Solutions, 3; S. Jugl, Novartis Pharma AG,
1,Novartis Pharma AG, 3; C. Gaillez, Novartis Pharma AG, BMS, 1,Novartis Pharma AG, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/secukinumab-provides-sustained-

improvement-in-major-and-moderate-response-of-disease-activity-index-for-psoriatic-arthritis-dapsa-2-year-results-from-a-
phase-3-study
Secukinumab Provides Sustained Minimal Disease Activity (MDA) and

Remission Related to Disease Activity Index for Psoriatic Arthritis (DAPSA):
2-Year Results from a Phase 3 Study
Laura C Coates1, Peter Nash2, Tore Kvien3, Laure Gossec4, Philip J Mease5, Lawrence Rasouliyan6, Luminita Pricop7,
Steffen Jugl8, Kunal Gandhi7, Corine Gaillez8 and Josef S. Smolen9, 1University of Oxford, Leeds, Great Britain,
2University of Queensland, Brisbane, Australia, 3Diakonhjemmet Hospital, Oslo, Norway, 4UPMC, University Paris 06,
Pitié-Salpétrière Hospital, Paris, France, 5Swedish Medical Center and University of Washington, Seattle, WA, 6RTI Health
Solutions, Barcelona, Spain, 7Novartis Pharmaceuticals Corporation, East Hanover, NJ, 8Novartis Pharma AG, Basel,
Switzerland, 9Medical University Vienna, Division of Rheumatology, Department of Internal Medicine III, Vienna, Austria
SESSION INFORMATION
Background/Purpose: Very low disease activity (VLDA) or remission (REM) and alternatively, minimal disease activity
(MDA) or low disease activity (LDA) are optimal targets to be achieved by psoriatic arthritis (PsA) patients (pts).1,2
DAPSA and MDA are validated composite indices used in PsA to measure disease activity states.3 This exploratory
analysis assessed the proportion of pts treated with secukinumab reaching DAPSA REM or LDA and those who reached
either MDA or VLDA at Weeks (wks) 16 and 104 in the FUTURE 2 study.
Methods: Data through 2 years for the FUTURE 2 study have been reported.4 DAPSA cut-offs included: REM (≤4) and
LDA (>4 and ≤14).5 MDA and VLDA are defined as having achieved at least 5 (≥5/7) or all (7/7) of the 7 pre-specified
criteria, respectively.6 DAPSA-REM, DAPSA-REM/LDA, MDA, and VLDA and their core components were assessed in
the overall population and in pts stratified by prior anti-tumor necrosis factor use and time since first PsA diagnosis using
as observed data. Only data for secukinumab 300 and 150 mg (approved doses) and placebo are reported.
Results: Baseline characteristics were similar across treatment groups.4 At Wk 16, in the overall population, the proportion
of pts treated with secukinumab 300/150 mg achieving remission was 14%/10% (DAPSA-REM) and 8%/6% (VLDA) and
achieving low disease activity was 42%/44% (DAPSA-REM/LDA) and 28%/23% (MDA). DAPSA and MDA responses
by prior TNF-inhibitor status and time since diagnosis are presented in figure. DAPSA and MDA responses with
secukinumab were sustained through Wk 104. Secukinumab treated pts who achieved either DAPSA-REM or VLDA at
Wk 16 had complete resolution of TJC, SJC, enthesitis and PtGA. Numerically somewhat higher proportion of pts achieved
skin clearance, HAQ-DI and PGA with VLDA than DAPSA-REM at Wk 16 and sustained to Wk 104 (Table).
Conclusion: In the overall population, a higher proportion of secukinumab treated pts at Wk 16 achieved DAPSA-REM,
VLDA, DAPSA-REM/LDA, and MDA than those treated with placebo with a greater number of pts achieving DAPSA-
REM or LDA than VLDA or MDA, respectively. These responses were sustained through Wk 104. At Wk 16, a higher
proportion of anti–TNF-naïve pts and pts with early diagnosis (≤2 years) treated with secukinumab achieved and sustained
DAPSA-REM, MDA and VLDA than in the overall population.
References: 1. Coates LC, et al. Arthritis Rheumatol 2016;68:1060–71 ; 2. Gossec L, et al. Ann Rheum Dis 2016;75:499–
510 ; 3. Coates LC, Helliwell PS. Ann Rheum Dis 2016;75:640-43; 4. McInnes IB, et al. Rheumatol. In press; 5. Schoels
MM, et al. Ann Rheum Dis 2016;75:811–8 ; 6. Coates LC, Helliwell PS. Arthritis Care Res (Hoboken). 2010; 62(7):965-
969.
Disclosure: L. C. Coates, Abbvie, BMS, Celgene, Pfizer, UCB, MSD, Boehringer Ingelheim, Novartis, Lilly, Janssen,
5,Abbvie, Janssen, 2; P. Nash, Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, and Celgene, 2,Novartis, Abbvie, Roche,
Pfizer, BMS, Janssen, and Celgene, 5,Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, and Celgene, 8; T. Kvien, AbbVie,
Biogen, BMS, Boehringer Ingelheim, Celltrion, Eli Lilly, Epirus, Janssen, Merck-Serono, MSD, Mundipharma, Novartis,
Oktal, Orion Pharma, Hospira/Pfizer, Roche, Sandoz, and UCB., 5,AbbVie, Biogen, BMS, Boehringer Ingelheim,
Roche, Sandoz, and UCB, 8; L. Gossec, UCB, Eli Lilly, and Pfizer, 2,AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis,
Pfizer, Roche, and UCB, 5; P. J. Mease, AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, SUN,
and UCB, 2,AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer,
SUN, and UCB, 5,AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB, 8; L.
Rasouliyan, Novartis, 5,RTI Health Solutions, 3; L. Pricop, Novartis Pharmaceutical Corporation, 1,Novartis
Pharmaceutical Corporation, 3; S. Jugl, Novartis Pharma AG, 1,Novartis Pharma AG, 3; K. Gandhi, Novartis
Pharmaceutical Corporation, 1,Novartis Pharmaceutical Corporation, 3; C. Gaillez, Novartis Pharma AG, BMS, 1,Novartis
Pharma AG, 3; J. S. Smolen, AbbVie, Janssen, Eli Lilly, MSD, Pfizer, Roche, Amgen, AstraZeneca, Astro, Celgene,
Celltrion, GSK, ILTOO, Medimmune, Novartis-Sandoz, Pfizer, Samsung, Sanofi and UCB, 2,AbbVie, Janssen, Eli Lilly,
MSD, Pfizer, Roche, Amgen, AstraZeneca, Astro, Celgene, Celltrion, GSK, ILTOO, Medimmune, Novartis-Sandoz, Pfizer,
Samsung, Sanofi and UCB, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/secukinumab-provides-sustained-
minimal-disease-activity-mda-and-remission-related-to-disease-activity-index-for-psoriatic-arthritis-dapsa-2-year-results-
from-a-phase-3-study
Tofacitinib Improves Composite Endpoint Measures of Disease in Patients

with Psoriatic Arthritis
Philip S. Helliwell1, Laura C Coates1, Oliver FitzGerald2, Peter Nash3, Enrique R Soriano4, M. Elaine Husni5, Ming-Ann
Hsu6, Keith S Kanik6, Thijs Hendrikx7, Joseph Wu6 and Elizabeth Kudlacz6, 1Leeds Institute of Rheumatic and
Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom, 2ASRI, Dublin, Ireland, Dublin, Ireland,
3Department of Medicine, University of Queensland, St Lucia, Brisbane, Australia, 4Hospital Italiano de Buenos Aires,
Buenos Aires, Argentina, 5Cleveland Clinic Lerner Research Institute, Cleveland, OH, 6Pfizer Inc, Groton, CT, 7Pfizer Inc,
Collegeville, PA
SESSION INFORMATION
arthritis (PsA). PsA is a heterogeneous disease and composite endpoints allow assessment of multiple clinical outcomes in
one instrument. We examined the effects of tofacitinib treatment on several composite endpoints in patients (pts) with PsA.
Methods: In 2 placebo (PBO)-controlled, double-blind, multicenter, global Phase 3 studies, pts had active PsA and either
had an inadequate response (IR) to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD) and were
tumor necrosis factor inhibitor (TNFi)-naïve (OPAL Broaden [N=422; 12 months; NCT01877668]), or had an IR to ≥1
TNFi (OPAL Beyond [N=394; 6 months; NCT01882439]). Pts were randomized to receive tofacitinib 5 mg BID,
tofacitinib 10 mg BID, adalimumab 40 mg subcutaneous injection once every 2 weeks (OPAL Broaden only), or PBO
(advancing to tofacitinib 5 or 10 mg BID at Month 3, OPAL Broaden and OPAL Beyond), in addition to continuing on a
single, stable csDMARD. Composite endpoints assessed: Psoriatic Arthritis Disease Activity Score (PASDAS), Disease
Activity Score using 28 joints with C‑reactive protein, Disease Activity Index for Reactive Arthritis/Psoriatic Arthritis
(DAREA/DAPSA), and Composite Psoriatic Disease Activity Index score.
Results: Demographics and baseline disease characteristics were generally similar between treatment groups within the 2
studies, except for duration of PsA disease (longer in OPAL Beyond) and geographic distribution (OPAL Broaden having
more Eastern EU pts). Baseline values for composite endpoints were generally similar across treatment groups and studies
(Table). Both doses of tofacitinib showed improvements in composite endpoints vs PBO at Month 3 in both studies (Table).
In OPAL Broaden, the effects of adalimumab were similar to both doses of tofacitinib across composite endpoints. Effect
size for the composite endpoints (using a subpopulation of pts who had all available data for all endpoints) was highest for
PASDAS and typically lowest for DAREA/DAPSA; this rank order of effect size was similar across treatment arms and
studies. At Month 3, effect sizes in pts receiving active treatment ranged from 0.90 (DAREA/DAPSA for tofacitinib 5 mg
BID) to 2.40 (PASDAS for tofacitinib 10 mg BID) in OPAL Broaden, and 0.81 (DAREA/DAPSA for tofacitinib 5 mg BID)
to 1.84 (PASDAS for tofacitinib 10 mg BID) in OPAL Beyond (Table). Standardized response means generally followed
the same pattern as effect size across studies with both doses of tofacitinib (Table).
Conclusion: In 2 Phase 3 studies, tofacitinib 5 mg and 10 mg BID improved composite endpoint scores vs PBO over 3
months in pts with PsA. The largest effect size and standardized response means were observed for PASDAS. Effect sizes
and standardized response means varied across endpoints but were consistent across studies.
Disclosure: P. S. Helliwell, AbbVie, Janssen, Pfizer Inc, 2,AbbVie, Amgen, Janssen, Pfizer Inc, UCB, 8,AbbVie, Janssen,
UCB, 9; L. C. Coates, AbbVie, Janssen, 2,AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer Inc,
Sun Pharma, UCB, 5; O. FitzGerald, AbbVie, Bristol-Myers Squibb, Novartis, Pfizer Inc, 2,Amgen, Celgene, Eli Lilly,
Janssen, 5; P. Nash, None; E. R. Soriano, AbbVie, Janssen, Novartis, Pfizer Inc, UCB, 2,AbbVie, Janssen, Novartis, Pfizer
Inc, UCB, 5,AbbVie, Bristol-Myers Squibb, Janssen, Novartis, Pfizer Inc, Roche, UCB, 8; M. E. Husni, AbbVie, Amgen,
Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Regeneron, UCB, 5,Pfizer Inc, 6,PASE Questionnaire, 7; M. A. Hsu,
Pfizer Inc, 1,Pfizer Inc, 3; K. S. Kanik, Pfizer Inc, 1,Pfizer Inc, 3; T. Hendrikx, Pfizer Inc, 1,Pfizer Inc, 3; J. Wu, Pfizer
Inc, 1,Pfizer Inc, 3; E. Kudlacz, Pfizer Inc, 1,Pfizer Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/tofacitinib-improves-composite-

endpoint-measures-of-disease-in-patients-with-psoriatic-arthritis

Ixekizumab Provides Sustained Improvement in Signs and Symptoms in
Patients with Active Psoriatic Arthritis: Two Year Results from a Phase 3
Trial
Philip S. Helliwell1, Eric Lespessailles2, Catherine Shuler3, Lotus Mallbris3, Janelle Erickson3 and Roy Fleischmann4, 1St.
Luke's Hospital and University of Leeds, Bradford, United Kingdom, 2University Orleans, Orleans, France, 3Eli Lilly and
Company, Indianapolis, IN, 4Metroplex Clinical Research Center, Dallas, TX
SESSION INFORMATION
Background/Purpose: Ixekizumab (IXE) is a high affinity monoclonal antibody that selectively targets IL-17A. In the
SPIRIT-P1 phase 3 study (NCT01695239), IXE was superior to placebo (PBO) in achieving ACR20 response at Week 24
in biologic DMARD (bDMARD)-naïve patients with active psoriatic arthritis (PsA). Here, the efficacy and safety of IXE
over 2 years in SPIRIT-P1 is evaluated.
Methods: During the SPIRIT-P1 double-blind treatment period (DBTP; Weeks 0-24), 417 bDMARD-naïve patients with
active PsA were randomized 1:1:1:1 to 80 mg subcutaneous IXE (160 mg starting dose at Week 0) every 4 weeks (Q4W),
every 2 weeks (Q2W), 40 mg adalimumab every 2 weeks (ADA, active reference arm), or PBO. Of these, 381 patients
entered the extension period (Weeks 24-52), followed by the long-term extension period (Weeks 52-156). Data presented
here are for the combined extension periods (CEP; Weeks 24-108) in patients who completed the initial 24 weeks of
treatment and received ≥1 dose of study drug during the CEP (CEP population). IXE-randomized patients continued on
IXE throughout the CEP. PBO and ADA patients were re-randomized (1:1) to IXE Q4W or Q2W at Week 16 (inadequate
responders) or Week 24; ADA patients had an 8-week washout period before receiving IXE. Patients failing to demonstrate
≥20% improvement in both tender joint count and swollen joint count at Week 32, or any subsequent visit, were
discontinued from the study. Efficacy measures included ACR20/50/70 responses, HAQ-Disability Index (DI) Score, DAS
28 based on C-reactive protein (DAS 28-CRP), 75%, 90%, and 100% improvement in the Psoriasis Area and Severity
Index (PASI 75/90/100), Leeds Enthesitis Index (LEI), and Leeds Dactylitis Index-Basic (LDI-B). Missing values were
imputed by nonresponder imputation for categorical data and modified baseline observation carried forward for continuous
data.
Results: Efficacy and safety results for the CEP population are summarized in Table 1. Improvements in ACR and PASI
responses, resolution in enthesitis and dactylitis, and improvements from baseline in HAQ-DI, DAS 28-CRP, enthesitis,
and dactylitis were observed at Week 108. Frequency of treatment-emergent adverse events (AEs) were similar across
treatment arms and the majority were mild or moderate in severity; serious AEs occurred in 46 patients. One death occurred
in the CEP population: an ADA/IXE Q4W patient with a history of dyslipidemia, diabetes mellitus, hypertension, and a
previous transient ischemic attack, suffered a cerebrovascular accident at Week 108.
Conclusion: For patients naïve to biologic treatment, IXE demonstrated clinically significant improvement in the signs and
symptoms of PsA across treatment groups up to 2 years of treatment. The safety profile of IXE observed during the CEP
was similar to that observed in the DBTP of SPIRIT-P1 and SPIRIT-P2, as well as other phase 3 studies of IXE in patients
with plaque psoriasis.
Disclosure: P. S. Helliwell, AbbVie, Janssen, Pfizer, 2,Abbvie, Jansen, Amgen, Pfizer, UCB, 9,Eli Lilly and Company, 5;
E. Lespessailles, Amgen, Eli Lilly, Novartis, Servier, 2,Amgen, Eli Lilly, Novartis, Servier, 8; C. Shuler, Eli Lilly and
Company, 1,Eli Lilly and Company, 3; L. Mallbris, Eli Lilly and Company, 1,Eli Lilly and Company, 3; J. Erickson, Eli
Lilly and Company, 1,Eli Lilly and Company, 3; R. Fleischmann, AbbVie, Amgen, Ardea Biosciences, Bristol-Myers
Squibb, Celgene, GlaxoSmithKline, Eli Lilly, Pfizer, Roche, Sanofi, and UCB, 2,AbbVie, Akros Pharma, Amgen,
AstraZeneca, Bristol-Myers Squibb, Janssen, Eli Lilly, Pfizer, Roche, Sanofi, and UCB, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/ixekizumab-provides-sustained-

improvement-in-signs-and-symptoms-in-patients-with-active-psoriatic-arthritis-two-year-results-from-a-phase-3-trial
Rapid Onset of Efficacy in Patients with Active Psoriatic Arthritis Treated

with Ixekizumab: A Pooled Analysis of Data from Two Phase III Clinical
Trials
Atul A. Deodhar1, Kim A. Papp2, Catherine Shuler3, So Young Park3 and Tore K. Kvien4, 1Oregon Health & Science
University, Portland, OR, 2K Papp Clinical Research and Probity Medical Research Inc, Waterloo, ON, Canada, 3Eli Lilly
and Company, Indianapolis, IN, 4Diakonhjemmet Hospital, Oslo, Norway
SESSION INFORMATION
Background/Purpose: Rapid onset of clinical improvement is an important attribute of treatment success for patients with
PsA. These analyses evaluate the speed of onset of clinical improvement in patients with active PsA treated with the IL-
17A selective monoclonal antibody ixekizumab (IXE) compared with placebo (PBO) and include populations naïve to
biologic treatment or with a previous inadequate response to TNF inhibitors.
Methods: Data were integrated from two Phase III, multicenter, double-blind, PBO- controlled trials. Patients with active
PsA either naïve to biologic disease modifying anti-rheumatic drugs (SPIRIT-P1) or with prior lack of efficacy or
intolerance to TNF-inhibitor(s) (SPIRIT-P2) were randomized to placebo (PBO, N=224), 80 mg IXE every 4 weeks (IXE
Q4W, N=229) or every 2 weeks (IXE Q2W, N=226), after a 160 mg starting dose. Continuous data were analyzed using
mixed-effects model for repeated measures; categorical data, using a logistic regression model with missing values imputed
by nonresponder imputation.
Results: ACR20 response rates were significantly greater for both IXE doses (p<.001) at week 1 (Fig 1). ACR50 response
rates were significantly greater by week 2 for IXEQ4W (p=.013) and week 1 for IXEQ2W (p=.030). ACR70 response rates
were significantly greater by week 4 (IXE Q4W, p=.039) or week 2 (IXE Q2W, p=.002). With the exception of the
IXEQ2W ACR70 response rate at week 4 (p=.176), response rates for ACR20, ACR50, and ACR70 remained statistically
significant compared to PBO through the 24-week, double-blind study period. In patients with plaque psoriasis (≥3% body
surface area) at baseline, both IXE dosing regimens achieved significant improvements in psoriasis area and severity index
total score compared to PBO by week 1 (Fig 2). Patients with HAQ-DI ≥ 0.35 at baseline demonstrated significantly
improved physical function by week 1, as measured by HAQ-DI minimal clinically important difference (≥0.35) response
rates (p<.001) for both doses of IXE (Fig 3).
Conclusion: Patients achieved significantly greater improvements in PsA, skin conditions, and physical function with both
IXE dose regimens compared to PBO. Statistically significant improvements in multiple clinical measures occurred as early
as week 1 and remained statistically significant through 24-weeks.
Disclosure: A. A. Deodhar, Eli Lilly and Company, GSK, Janssen, Novartis, Sun Pharma, UCB, 2,Abbvie, Eli LIlly and
Company, Janssen, Novartis, UCB, 5; K. A. Papp, Amgen, Anacor, AbbVie, Akros, Allergan, Astellas, Astra-Zenica,
Baxalta, Baxter, BMS, Boehringer-Ingelheim, Can-Fite, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly and Company,
Forward Pharma, Galderma, Genentech, GSK, Janssen, Kyowa Hakko Kirin, Leo P, 9; C. Shuler, Eli Lilly and Company,
3; S. Y. Park, Eli Lilly and Company, 1,Eli Lilly and Company, 3; T. K. Kvien, AbbVie, Biogen, BMS, Celltrion, Eli Lilly,
Janssen, Merck-Serono, MSD, Novartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Samsung, Sandoz and UCB,
5,AbbVie, Biogen, BMS, Celltrion, Eli Lilly, Janssen, Merck-Serono, MSD, Novartis, Oktal, Orion Pharma, Hospira/Pfizer,
Roche, Samsung, Sandoz and UCB, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rapid-onset-of-efficacy-in-patients-

with-active-psoriatic-arthritis-treated-with-ixekizumab-a-pooled-analysis-of-data-from-two-phase-iii-clinical-trials
Radiographic Progression of Structural Joint Damage in Patients with Active

Psoriatic Arthritis Treated with Ixekizumab over 52 Weeks
Désirée van der Heijde1, Masato Okada2, Chin H. Lee3, Catherine Shuler3, Suchitrita Rathmann3, Chen-Yen Lin3 and
Philip J Mease4, 1Leiden University Medical Center, Leiden, Netherlands, 2Immuno-Rheumatology Center, St. Luke's
International Hospital, Tokyo, Japan, 3Eli Lilly and Company, Indianapolis, IN, 4Swedish Medical Center and University
of Washington, Seattle, WA
SESSION INFORMATION
Background/Purpose: Ixekizumab (IXE), an anti-interleukin-17A monoclonal antibody, was shown to be superior to

placebo (PBO) in clinical responses and inhibiting the progression of structural joint damage in patients with PsA treated
for 24 weeks (wks).1 The objective was to assess the progression of structural joint damage in PsA pts with IXE for up to
52 wks.
Methods: Biologic DMARD-naïve pts with active PsA (N=417) entered into SPIRIT-P1 (NCT01695239), a double-blind
phase 3 trial. Pts must have had ≥1 joint erosion on the hand and foot x-rays confirmed by central reading or had a C-
reactive protein level >6 mg/L at screening. 417 pts were randomized to IXE 80 mg every 2 wks (Q2W; N=103) or 4 wks
(Q4W; N=107) following a 160 mg initial dose, PBO (N=106), or adalimumab 40 mg every 2 wks (ADA; active reference
arm; N=101) for 24 wks. In the Extension period (EXT: Wks 24-52), PBO and ADA pts were re-randomized (1:1) to
IXEQ2W or IXEQ4W at Wk 16 (inadequate responders) or Wk 24; ADA pts underwent a washout prior to IXE treatment.
All pts were assessed for structural joint damage using the van der Heijde-modified PsA Total Sharp Score (mTSS, 0-528
scale). X-rays at Wks 0, 24, and 52 were scored independently by 2 readers blinded to time point and clinical data (average
of readers). mTSS was excluded from the pre-specified analysis if the radiograph was taken after the scheduled visit date.
In a post hoc analysis, mTSS from a radiograph taken after the scheduled visit date was interpolated and considered as
observed data. Any missing data at Wk 52, in either presentation, were imputed using a linear extrapolation if they had at
least 1 post-baseline value.
Results: Pts had active PsA at Wk 0 (Table). 381 pts (91.3%) entered the EXT, with 374 (98.2%) having radiographs
collected during the EXT. Wk 52 mean (SD) mTSS change from baseline were 0.54 (2.11) and 0.09 (1.0) for pts
randomized to IXEQ4W and IXEQ2W at baseline, respectively. Similar changes at Wk 52 were obtained with the post hoc
analysis (Table). The majority of IXEQ2W or IXEQ4W pts exhibited no structural progression through 1 year of IXE
treatment (Figure). In pts who switched from PBO or ADA to IXE, Wk 52 mean change from baseline mTSS values scores
ranged from -0.03 to 0.41 (Table).
Conclusion: Over a 52-wk period, minimal changes in mTSS were observed in PsA pts entering the EXT and treated with
IXEQ2W or IXEQ4W.
1. Mease P et al. 2017 ARD 76(1):79

Disclosure: D. van der Heijde, AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi,
Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda,
UCB, 5,Leiden University Medical Centre, 3; M. Okada, St. Luke's International University, 3; C. H. Lee, Eli Lilly and
Company, 3; C. Shuler, Eli Lilly and Company, 3; S. Rathmann, Eli Lilly and Company, 3; C. Y. Lin, Eli Lilly and
Company, 1,Eli Lilly and Company, 3; P. J. Mease, Abbvie, Amgen, Bristol Myers Aquibb, Celgene, Genentech, Janssen,
Novartis, Pfizer, UCB, 8,Abbvie, Amgen, Bristol Myers Aquibb, Celgene, Lilly, Janssen, Novartis, Pfizer, UCB,
Sunpharma, 9,Abbvie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer, UCB, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/radiographic-progression-of-structural-

joint-damage-in-patients-with-active-psoriatic-arthritis-treated-with-ixekizumab-over-52-weeks
Efficacy and Safety of Apremilast through 104 Weeks in Subjects with

Moderate to Severe Psoriasis Randomized to Placebo, Apremilast, or
Etanercept Who Continued on or Switched to Apremilast after Week 16 in a
Phase 3b Study
Kristian Reich1, Mark Goodfield2, Lawrence Green3, Kristine Nograles4, Rongdean Chen4, Eugenia Levi4 and Richard
G.B. Langley5, 1Dermatologikum Hamburg, Hamburg, Germany, 2Leeds General Infirmary, Leeds, United Kingdom,
3George Washington University School of Medicine, Washington, DC, WA, 4Celgene Corporation, Summit, NJ,
5Dalhousie University, Halifax, NS, Canada
SESSION INFORMATION
Background/Purpose: Many subjects (sbj) with chronic plaque psoriasis exhibit nail and scalp involvement that can
markedly affect quality of life and be difficult to treat. The phase 3b LIBERATE study evaluated efficacy and safety of
apremilast or etanercept vs. placebo in biologic-naive sbj with moderate to severe plaque psoriasis. Efficacy assessments
included effects on preexisting nail and scalp disease and skin lesions.
Methods: In this double-blind, double-dummy study, sbj were randomized (1:1:1) to placebo (PBO), apremilast 30 mg
BID (APR), or etanercept 50 mg QW (ETN) through Wk 16; thereafter, all sbj switched to or continued APR (PBO/APR,
ETN/APR, APR/APR) through Wk 104. The primary endpoint was achievement of a PASI-75 response at Wk 16 with
APR vs. PBO; the secondary endpoint was PASI-75 achievement at Wk 16 with ETN vs. PBO. Physician assessments were
conducted for overall psoriatic activity (static Physician’s Global Assessment [sPGA]); scalp disease activity (Scalp
Physician Global Assessment [ScPGA], limited to sbj with score ≥3 at baseline [BL], indicating moderate to very severe
scalp disease); and nail disease (Nail Psoriasis Severity Index [NAPSI], limited to sbj with active disease [NAPSI ≥1] in the
target nail at BL). Responses were assessed through Wk 104 using last-observation-carried-forward methodology.
Results: The APR extension phase (Wks 16 to 104) included 226 sbj (PBO/APR n=73; APR/APR n=74; ETN/APR n=79).
At Wk 16, PASI-75 response vs. PBO was significant for both APR and ETN; long-term treatment with APR maintained
both PASI-75 and sPGA 0 or 1 response levels (Table). Improvements were seen in nail and scalp disease at Wk 16, and
the proportion of responders continued to increase with APR treatment over 104 wks and in sbj who switched from ETN to
APR (Table). ScPGA 0 or 1 was achieved by 50.0% to 59.2% of sbjsacross treatment arms, and mean percent improvement
from BL NAPSI score ranged from −48.1% to −51.1% (Table); the proportion of sbj achieving NAPSI-50 response ranged
from 48.6% to 65.2%. Adverse events (AEs) occurring in ≥5% of sbj during Wks 0 to 16 were diarrhea, nausea,
nasopharyngitis, upper respiratory tract infection, headache, and tension headache; long-term assessment by exposure-
adjusted incidence rates (EAIR)/100 sbj-yrs showed no increase with longer-term APR exposure. No increase in EAIR/100
sbj-yrs of serious AEs occurred during the APR extension phase (4.01 to 5.49, across groups) vs. Wks 0 to 16 (PBO 0.0;
APR 12.57; ETN 7.91). Changes in laboratory parameters were infrequent and transient; EAIR/100 sbj-yrs remained low
across groups through 104 wks.
Conclusion: APR demonstrated efficacy through Wk 104 in sbj who continued APR and sbj who switched from PBO or
ETN to APR at Wk 16. The AE profile remained consistent with prolonged APR exposure; no new safety or tolerability
issues were observed through Wk 104 in sbj with moderate to severe plaque psoriasis.
Disclosure: K. Reich, AbbVie, Amgen, Biogen, Boehringer Ingelheim, Celgene Corporation, Centocor, Covagen, Eli Lilly,
Forward Pharma, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Medac, Merck Sharp and Dohme, Novartis, Ocean
Pharma, Pfizer Wyeth, Regeneron, Takeda, UCB Pharma,, 5,AbbVie, Amgen, Biogen, Boehringer Ingelheim, Celgene
Corporation, Centocor, Covagen, Eli Lilly, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Medac,
Merck Sharp and Dohme, Novartis, Ocean Pharma, Pfizer Wyeth, Regeneron, Takeda, UCB Pharma,, 5; M. Goodfield,
None; L. Green, AbbVie, Amgen, Celgene Corporation, LEO Pharma, Novartis, Pfizer, and Valeant, 5,AbbVie, Amgen,
Celgene Corporation, LEO Pharma, Novartis, Pfizer, Valeant, 8; K. Nograles, Celgene Corporation, 3; R. Chen, Celgene
Corporation, 3; E. Levi, Celgene Corporation, 3; R. G. B. Langley, AbbVie, Amgen, Celgene Corporation, Eli Lilly, LEO
Pharma, Merck, Novartis, Pfizer, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/efficacy-and-safety-of-apremilast-

through-104-weeks-in-subjects-with-moderate-to-severe-psoriasis-randomized-to-placebo-apremilast-or-etanercept-who-
continued-on-or-switched-to-apremilast-after-week
Integrated Efficacy Results from Two Phase 3 Trials of Ixekizumab for the
Treatment of Psoriatic Arthritis
Bernard Combe1, Peter Nash2, David Adams3, Lisa Kerr3 and Olivier Benichou3, 1Rheumatology, CHU Lapeyronie and
Montpellier University, Montpellier, France, 2University of Queensland, Brisbane, Australia, 3Eli Lilly and Company,
Indianapolis, IN
SESSION INFORMATION
Background/Purpose: Ixekizumab (IXE) is a high-affinity monoclonal antibody that selectively targets interleukin-17A.
Here, we present integrated efficacy data at Week 24 from two phase 3 trials of IXE for the treatment of psoriatic arthritis
(PsA).
Methods: Patients with active PsA (SPIRIT-P1) and with prior lack of efficacy or intolerance to TNF-inhibitor(s) (SPIRIT-
P2) were randomized to placebo (PBO, N=224), 80 mg IXE every 4 weeks (IXEQ4W, N=229) or every 2 weeks (IXEQ2W,
N=226), after a 160 mg starting dose. All patients considered as inadequate responders at Week 16 received rescue therapy
(changes in background therapy), while inadequate responders to PBO were also re-randomized to IXEQ4W or IXEQ2W.
Continuous data were analyzed using mixed-effects model for repeated measures; categorical data, using a logistic
regression model with missing values imputed by non-responder imputation.
Results: At Week 24, significantly more patients treated with either dose of IXE (p<.001) compared to PBO achieved the
primary endpoint of ACR 20, as well as ACR 50, ACR 70, and HAQ-DI change from baseline. Treatment with either dose
of IXE resulted in significantly more patients achieving resolution of enthesitis (LEI; p<.05) and dactylitis (LDI-B; p<.001)
compared to PBO. LDI-B improvements from baseline were also significantly greater (p<.05) for IXE-treated patients
versus PBO. Finally, greater skin clearance (via PASI improvement) was significantly higher for IXE-treated patients
(p<.001).
Conclusion: Patients treated with either dose regimen of IXE achieved significantly greater improvements in arthritis,
physical function, and skin lesions compared to PBO at Week 24.
Disclosure: B. Combe, Pfizer, UCB, 2,BMS, Janssen, Lilly, MSD,Pfizer, Roche-Chugai, UCB, 8,Abbvie, BMS,Janssen,
Lilly, MSD,Novartis, Pfizer, Roche-Chugai, UCB, 5; P. Nash, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly
and Company, Hospira, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, 5,AbbVie, Amgen, Bristol-Myers
Squibb, Celgene, Eli Lilly and Company, Hospira, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, 8,AbbVie,
Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Hospira, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi,
and UCB, 2; D. Adams, Eli Lilly and Company, 1,Eli Lilly and Company, 3; L. Kerr, Eli Lilly and Company, 1,Eli Lilly
and Company, 3; O. Benichou, Eli Lilly and Company, 3,Eli Lilly and Company, 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/integrated-efficacy-results-from-two-

phase-3-trials-of-ixekizumab-for-the-treatment-of-psoriatic-arthritis
Is Earlier Golimumab Treatment Initiation in Psa and As Patients Associated

with Improved Outcomes?
Suneil Kapur1, Proton Rahman2, Michelle Teo3, Jodie Reis4, Rajwinder Dhillon5, Pauline Boulos6, Raman Rai7, Regan
Arendse8, Julie Vaillancourt9, Emmanouil Rampakakis9, Allen J Lehman10, Francois Nantel11 and Brendan Osborne11,
1University of Ottawa, 139 Greenbank Rd, Suite 203, ON, Canada, 2Rheumatology, St Claires Mercy Hospital, St Johns,
NF, Canada, 3Balfour Medical Clinic, Penticton, BC, Canada, 4University of Saskatchewan, Saskatoon, SK, Canada,
5Private Practice, Niagara Falls, ON, Canada, 6Private Practice, Dundas, ON, Canada, 7Private Practice, Hamilton, ON,
Canada, 8University of Saskatchewan, Saskatoon, ON, Canada, 9JSS Medical Research, Montreal, QC, Canada, 10Janssen
Inc., Toronto, ON, Canada, 11Medical Affairs, Janssen Inc., Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose: Previous studies have suggested that treating patients earlier with biologics could improve disease
outcomes. The aim of this analysis was to assess the impact of disease duration on clinical and patient-reported outcomes in
patients with psoriatic arthritis (PsA) or ankylosing spondylitis (AS) treated with subcutaneous golimumab (GLM) in
Canadian routine practice.
Methods: BioTRAC is an ongoing, prospective registry of patients initiating treatment with infliximab or GLM for
rheumatoid arthritis, AS, or PsA, or with ustekinumab for PsA. Eligible patients for this analysis included PsA and AS
patients initiating GLM treatment since 2010. Disease duration at entry in the registry was categorized by tertiles as early
(PsA: <2 years; AS: <1 year), mid (PsA: 2-5 years; AS: 1-2 years) and long-term (PsA: ≥6 years; AS: ≥3 years) duration.
Standard outcomes were assessed; key outcomes of interest were low disease activity (LDA), remission (based on DAS28-
ESR <2.6 and CDAI≤2.8), and minimal disease activity (MDA) achievement for PsA patients, and inactive disease
(ASDAS <1.3) for AS patients. In order to determine the impact of disease duration on disease activity at 12 and 24
months, multivariate logistic regression and general linear models adjusted for age, gender, prior biologic treatment, and
baseline disease parameters were utilized.
Results: A total of 253 PsA patients (54.4% female) and 376 AS patients (58.6% male) were included with a mean (SD)
age of 52.7 (13.2) and 44.7 (13.3) years, respectively. Most patients were biologic naïve (PsA: 95.3%; AS: 95.5%). The
mean (SD) duration of PsA and AS at baseline was 5.7 (7.7) and of 5.4 (9.8) years, respectively.
In the PsA patient group, significantly greater improvements in MD global assessment (MDGA) and pain from baseline to
month 24 were observed amongst patients treated at early term (Table 1). Based on multivariate logistic regression
analyses, patients treated at later stage disease were significantly less likely than patients treated early to achieve MDA
(OR: 0.10; p=0.025) and CDAI LDAS (OR: 0.06; p=0.002) at 24-month. There was no association between PsA duration
and LDA, remission and MDA achievement at 12 months.
Among AS patients treated at early term, significantly greater improvements in BASFI from baseline to month 24 were
observed (Table 1). Based on multivariate logistic regression analyses, AS patients treated at mid- and long-term were
significantly less likely than patients treated at early term to achieve inactive disease based on ASDAS at 12 months, with
odds ratios of 0.21 (p=0.028) and 0.12 (p=0.003), respectively. Disease duration was not associated with AS inactivity at
24-month.
Conclusion: The results of this analysis demonstrate that earlier treatment of PsA and AS with GLM in real-world is
associated with improved outcomes, particularly in selected patient-reported outcomes at 12 and 24 months.
Table 1. Adjusted changes in clinical and patient-reported outcomes from
baseline to 24 months by disease duration among PsA and AS patients
PsA Patients
Early Term Mid Term Long Term
Outcomes, LSM
p-value
(95% CI) (N=103) (N=62) (N=88)
ΔSJC -4.5 (-5.4; -3.6) -4.7 (-5.6; -3.7) -3.5 (-4.3; -2.8) 0.054
ΔTJC -6.5 (-7.8; -5.1) -6.5 (-7.9; -5.0) -5.0 (-6.2; -3.9) 0.089
ΔMDGA -4.0 (-4.9; -3.1) -3.1 (-4.1; -2.1) -2.5 (-3.3; -1.7) 0.009
ΔPtGA -33.0 (-47.2; -16.7 (-32.2; -21.0 (-33.3; 0.101
-18.9) -1.2) -8.7)
ΔPain -32.5 (-45.0; -10.9 (-24.1; -19.3 (-30.0; 0.012
-19.9) 2.3) -8.5)
ΔHAQ -0.3 (-0.6; -0.1) 0.0 (-0.2; 0.3) -0.2 (-0.4; 0.0) 0.071
ΔDAS28-ESR -2.1 (-2.9; -1.4) -2.4 (-3.2; -1.5) -1.4 (-2.0; -0.8) 0.115
ΔSDAI -19.2 (-23.0; -17.3 (-21.7; -13.5 (-16.9; 0.055
-15.4) -13.0) -10.0)
ΔCDAI -17.6 (-20.6; -16.1 (-19.2; -13.7 (-16.3; 0.063
-14.7) -12.9) -11.1)
ΔPASI -2.5 (-3.7; -1.3) -1.7 (-3.1; -0.3) -1.9 (-3.0; -0.9) 0.371
AS Patients
Outcomes, LSM Early Term Mid Term Long Term
p-value
(95% CI) (N=126) (N=117) (N=133)
ΔMDGA -3.0 (-4.1; -1.9) -2.5 (-3.4; -1.7) -2.6 (-3.6; -1.7) 0.685
ΔPtGA -24.6 (-51.7; -37.5 (-58.3; -21.1 (-52.5; 0.445
2.4) -16.7) 10.2)
ΔPain (ASAS pain) -2.7 (-3.9; -1.5) -2.4 (-3.3; -1.4) -1.7 (-2.8; -0.6) 0.293
ΔHAQ -0.4 (-0.7; -0.1) -0.3 (-0.5; -0.0) -0.2 (-0.4; 0.1) 0.401
ΔBASDAI -2.6 (-3.7; -1.5) -2.3 (-3.2; -1.5) -1.7 (-2.6; -0.7) 0.239
ΔBASFI -2.9 (-4.0; -1.8) -2.1 (-2.9; -1.2) -1.4 (-2.3; -0.4) 0.030
ΔASDAS -2.2 (-3.3; -1.1) -1.2 (-2.1; -0.2) -1.2 (-2.2; -0.3) 0.098
LSM: Least Square Mean
p-value reflects the comparison of early vs. mid vs. long term.
Disclosure: S. Kapur, None; P. Rahman, None; M. Teo, None; J. Reis, None; R. Dhillon, None; P. Boulos, None; R.
Rai, None; R. Arendse, None; J. Vaillancourt, Janssen Inc., 9; E. Rampakakis, Janssen Inc., 9; A. J. Lehman, Janssen
Inc., 3; F. Nantel, Janssen Inc., 3; B. Osborne, Janssen Inc., 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/is-earlier-golimumab-treatment-

initiation-in-psa-and-as-patients-associated-with-improved-outcomes
Effects of Intravenous Golimumab, an Anti-Tnfα Monoclonal Antibody, on

Mental and Physical Functioning and Health-Related Quality of Life in
Active Psoriatic Arthritis: 24-Week Results of a Phase 3 Trial
M. Elaine Husni1, Arthur Kavanaugh2, Eric K. H. Chan3, Nan Li4, Steven Peterson4, Elizabeth C. Hsia5, Lilianne Kim4,
Kim Hung Lo4 and Diane D. Harrison4, 1Rheumatology, Cleveland Clinic, Cleveland, OH, 2Medicine, University of
California, San Diego, La Jolla, CA, 3Janssen Global Services, LLC, Raritan, NJ, 4Janssen Research & Development, LLC,
Spring House, PA, 5Janssen Research & Development, LLC/University of Pennsylvania, Spring House/Philadelphia, PA
SESSION INFORMATION
Background/Purpose: To evaluate physical and mental health functioning, health state, and health-related quality of life
(HRQoL) in patients with active psoriatic arthritis (PsA) treated with intravenously administered (IV) golimumab (GLM),
an anti-TNFα monoclonal antibody.
Methods: In this Phase 3, multicenter, randomized, double-blind, placebo-controlled trial, adult patients (N=480) with
active PsA naïve to anti-TNFa therapy (mean age=46 yr) received IV GLM 2 mg/kg (N=241) at Weeks 0 and 4 and every 8
weeks thereafter or placebo (N=239) at Weeks 0, 4, 12, and 20 with crossover to IV GLM at Week 24. Three self-report
instruments were included: 1) Short Form Health Survey (SF-36), a generic instrument of physical and mental health
functioning: scores for its Physical (PCS) and Mental Component Summary (MCS) and 8 subscales (physical functioning,
role-physical, body pain, general health, vitality, social functioning, role-emotional, and mental health) each range from 0
to 100 with higher scores indicating better function; 2) EuroQol visual analog scale (EQ-VAS), a generic measure of
current health state (0=worst health you can imagine to 100=best health you can imagine); 3) Dermatology Life Quality
Index (DLQI), a disease-specific HRQoL instrument measuring impact of skin disorders on daily living (scores range from
0-30 with lower scores indicating lesser impact). SF-36 PCS and MCS at Week 14 were controlled secondary endpoints.
Least square mean differences between the treatment groups were estimated using analysis of covariance controlling for
methotrexate use and baseline score.
Results: Mean improvements from baseline with IV GLM vs placebo occurred as early as Week 8 in SF-36 PCS (8.0 vs
1.7) and MCS (5.0 vs 1.2) scores (Table 1). Greater mean improvements from baseline in PCS (p<0.001) and MCS
(p<0.001) scores were seen with IV GLM vs placebo at Weeks 14 and 24. Greater mean improvements in all 8 SF-36
subscales at Weeks 14 and 24 were also observed with IV GLM vs placebo (p<0.001 for all). The percentages of patients
achieving clinically meaningful change (5 points or greater) in PCS and MCS scores were higher in IV GLM vs placebo at
Weeks 14 and 24 (PCS: 67.6% vs 29.7%, 69.7% vs 29.3%; MCS: 51.5% vs 26.4%, 46.9% vs 29.3%; p<0.001 for all).
Mean EQ-VAS improvements were observed as early as Week 8 with IV GLM vs placebo (17.2 vs 3.7) and remained
greater with IV GLM vs placebo at Weeks 14 and 24 (both p<0.001; Table 1). Mean changes in DLQI were observed with
IV GLM as early as Week 8 (-7.2 vs -1.7; Table 1). Higher percentages of patients in the IV GLM cohort achieved DLQI
scores of 0 or 1 at Weeks 14 (35.3% vs 9.8%; p<0.001) and 24 (40.7% vs 9.8%; p<0.001) vs placebo.
Conclusion: Adult patients with active PsA treated with IV GLM showed marked improvements from baseline vs. placebo
in physical and mental health function, health state, and HRQoL as early as Week 8; improvements were maintained
through Weeks 14 and 24.
Table 1: Summary of mean (standard
deviation) changes in SF-36, EQ-VAS, and
DLQI
Golimumab Placebo
2 mg/kg
Patient self-report N=241 N=239
instruments
Mean (SD) Week 8 8.0 (7.30) 1.7 (5.40)
change from
baseline in SF-36 (n=237) (n=236)
PCS:
Week 8.6 (7.59) 2.6 (5.84)
14
(n=237) (n=236)
p<0.001
Week 9.4 (8.07) 2.4 (6.07)
24
(n=237) (n=236)
p<0.001*
Mean (SD) Week 8 5.0 (9.85) 1.2 (7.60)
change from
baseline in SF-36 (n=237) (n=236)
MCS:
Week 5.3 (9.88) 0.9 (7.58)
14
(n=237) (n=236)
p<0.001
Week 5.3 (10.20) 0.8 (7.45)
24
(n=237) (n=236)
p<0.001*
Mean (SD) Week 8 17.2 3.7
change from (22.70) (21.81)
baseline in EQ-
VAS: (n=232) (n=225)
Week 18.7 5.3
14 (24.29) (21.02)
(n=233) (n=222)
p<0.001*
Week 20.2 5.5
24 (24.23) (23.09)
(n=231) (n=221)
p<0.001*
Mean (SD) Week 8 -7.2 (7.24) -1.7 (4.91)
change from
baseline in DLQI: (n=194) (n=195)
Week -7.7 (7.18) -1.8 (5.70)
14
(n=194) (n=195)
p<0.001*
Week -8.1 (7.72) -1.9 (5.90)
24
(n=194) (n=195)
p<0.001*
*presented p values are nominal
Disclosure: M. E. Husni, AbbVie, Amgen, Janssen Research and Development, LLC, BMS, Novartis, Eli Lilly, 5; A.
Kavanaugh, Janssen Research Development, LLC, 2,Janssen Research Development, LLC, 5; E. K. H. Chan, Janssen
Global Services, LLC, 3,Johnson & Johnson, 1; N. Li, Janssen Research & Development, LLC, 3,Johnson & Johnson,
LLC, 1; S. Peterson, Janssen Research & Development, LLC, 3,Johnson & Johnson, LLC, 1; E. C. Hsia, Janssen Research
& Development, LLC, 3,Johnson & Johnson, LLC, 1; L. Kim, Janssen Research & Development, LLC, 3,Johnson &
Johnson, LLC, 1; K. H. Lo, Janssen Research & Development, LLC, 3,Johnson & Johnson, LLC, 1; D. D. Harrison,
Janssen Research & Development, LLC, 3,Johnson & Johnson, LLC, 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effects-of-intravenous-golimumab-an-

anti-tnf%ce%b1-monoclonal-antibody-on-mental-and-physical-functioning-and-health-related-quality-of-life-in-active-
psoriatic-arthritis-24-week-results-of-a
Predictors of Long-Term Retention of Methotrexate and Other Dmards with

Golimumab in Rheumatoid Arthritis and Psoriatic Arthritis: An Analysis
from a Prospective, Observational Registry
Derek Haaland1, Anna Jaroszynska2, B Haraoui3, Suneil Kapur4, Jacqueline Stewart5, Wojciech Olsynzynski6, Keltie
Anderson7, Raman Rai8, Michael Starr9, Alexander Tsoukas10, Eliofotisti Psaradellis11, Emmanouil Rampakakis11, Cathy
Tkaczyk12, Allen J Lehman13, Francois Nantel12 and Brendan Osborne12, 1Rheumatology, Clinical Immunology &
Allergy, McMaster University, Barrie, ON, Canada, 2Private practice, Burlington, ON, Canada, 3Institut de Recherche en
Rhumatologie de Montréal (IRRM), Montreal, QC, Canada, 4University of Ottawa, 139 Greenbank Rd, Suite 203, ON,
Canada, 5Penticton Regional Hospital, Penticton, BC, Canada, 6University of Saskatchewan, Saskatoon, ON, Canada,
7University of Saskatchewan, Saskatoon, SK, Canada, 8Private Practice, Hamilton, ON, Canada, 9Rheumatology, McGill
University, Pointe-Claire,, QC, Canada, 10McGill University, Montreal, QC, Canada, 11JSS Medical Research, Montreal,
QC, Canada, 12Medical Affairs, Janssen Inc., Toronto, ON, Canada, 13Janssen Inc., Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose: Previous studies have suggested that concomitant methotrexate therapy may increase the efficacy
of biologic treatments. A scarcity of data exists on the benefits of combination therapy with golimumab (GLM) and MTX
as well as other DMARDs (oDMARDs). The aim of this analysis was to compare the long-term retention of GLM
monotherapy vs. combination therapy with MTX and/or oDMARDs and to explore independent predictors of retention in
patients with rheumatoid arthritis (RA) and psoriatic arthritis followed in Canadian routine practice.
Methods: BioTRAC is an ongoing, prospective registry of patients initiating treatment with infliximab or GLM for RA,
ankylosing spondylitis, or PsA, or with ustekinumab for PsA. Eligible participants for this analysis included RA and PsA
patients treated with GLM. Patients were excluded if they had follow-up <24 months and were not discontinued. Treatment
durability was assessed with the Kaplan Meier (KM) estimator of the survival function and Cox regression.
Results: A total of 336 RA patients were included; baseline characteristics and disease parameters are summarized by
treatment group in Table 1. There were 195 (58.0%) patients who discontinued with a KM-based mean (SE) time to
discontinuation of 36.2 (1.7) months. Between group differences were observed with higher treatment durability for
MTX+GLM+oDMARDs [39.8 (2.3)] months, followed by MTX+GLM [37.4 (3.4)], GLM+oDMARDs [27.2 (4.8)] and
GLM monotherapy with [25.2 (3.0)] (p=0.025). Upon adjusting for potential confounders, higher durability was observed
for the MTX+GLM+oDMARDs group vs. GLM monotherapy [hazard ratio -HR- (95% CI): 0.59 (0.36-0.96), p=0.032].
Moreover, increased baseline DAS28 [HR (95% CI): 1.17 (1.03-1.32), p=0.014] and previous use of MTX [HR (95% CI):
1.73 (1.00-3.00), p=0.052], were independently associated with premature treatment termination.
A total of 167 PsA patients were included; baseline characteristics and disease parameters are described by treatment group
in Table 1. There were 96 (57.5%) patients who discontinued with a KM-based mean (SE) time to discontinuation of 34.7
(2.3) months. No between group differences were observed for treatment durability. However, upon adjusting for potential
confounders, increased baseline MDGA [HR (95% CI): 1.12 (1.01-1.25), p=0.038], previous use of MTX [HR (95% CI):
3.54 (1.09-11.45), p=0.035], and female gender [HR (95% CI): 1.96 (1.19-3.21), p=0.008] were independently associated
with premature treatment termination.
Conclusion: The results of this analysis have shown that combination therapy with GLM, MTX and other DMARDs is
significantly associated with higher treatment durability compared to GLM monotherapy among RA patients. Although
gender and MDGA were identified as significant independent predictors of long-term retention among PsA patients,
treatment durability was not affected by concomitant MTX and DMARD use.
GLM+
GLM
MTX+GLM MTX+GLM+oDMARDS p-
Cohort Baseline Parameter Monotherapy oDMARDs
(n=89) (n=175) value€
(n=41) (n=31)
RA Age, years 58.5 (16.2) 57.5 (13.1) 57.4 (13.1) 54.8 (11.9) 0.477
Disease Duration, 0.773
8.4 (9.5) 8.2 (9.0) 7.4 (7.8) 10.2 (11.5)
years
Females, n(%) 29 (70.7) 68 (76.4) 109 (62.3) 25 (80.6) 0.071
Bio-naïve, n(%) 39 (95.1) 84 (94.4) 166 (94.9) 26 (83.9) 0.126
MTX dose, mg/week NA 20.5 (12.9) 19.9 (4.5) NA NA
Sulfasalazine¥, n(%) NA NA 31 (17.7) 0 (0.0) NA
Hydroxychloroquine¥, NA NA
119 (68.0) 13 (41.9)
NA
n(%)
Leflunomide¥, n(%) NA NA 81 (46.3) 18 (58.1) NA
Cyclosporine¥, n(%) NA NA 1 (0.6) 0 (0.0) NA
Previous DMARD 38 (92.7) 87 (97.8) 169 (96.6) 30 (96.8) 0.543
use, n(%)
Previous MTX use, 34 (82.9) 79 (88.8) 154 (88.0) 23 (74.2) 0.163
n(%)
SJC 7.5 (5.0) 7.7 (5.9) 8.5 (6.0) 7.7 (5.4) 0.630
TJC 9.7 (6.7) 9.8 (7.4) 9.0 (6.8) 8.6 (6.7) 0.763
Pain, mm* 49.0 (25.5) 55.7 (27.5) 54.6 (25.9) 50.3 (27.7) 0.498
PtGA, mm* 53.2 (26.4) 56.8 (26.8) 56.7 (26.1) 48.2 (28.4) 0.536
MDGA, mm* 58.8 (18.9) 56.6 (24.7) 57.4 (21.3) 56.8 (24.8) 0.983
Morning stiffness, 0.240
42.0 (41.9) 36.3 (41.8) 46.6 (45.3) 36.5 (41.3)
min
DAS28 5.5 (1.3) 5.0 (1.7) 5.1 (1.5)
5.0 (1.3) 0.540
GLM GLM+
MTX+GLM MTX+GLM+oDMARDS p-
Cohort Baseline Parameter Monotherapy oDMARDs
(n=70) (n=44) value€
(n=30)
(n=23)
PsA Age, years 50.9 (12.8) 51.6 (13.4) 51.3 (13.0) 56.0 (12.0) 0.575
Disease Duration, 0.586
5.6 (9.0) 4.8 (5.6) 4.4 (6.3) 5.4 (6.3)
years
Females, n(%) 14 (46.7) 36 (51.4) 21 (47.7) 10 (43.5) 0.853
Bio-naïve, n(%) 27 (90.0) 64 (91.4) 43 (97.7) 21 (91.3) 0.526
MTX dose, mg/week NA 19.8 (5.8) 20.1 (4.9) NA NA
¥
Sulfasalazine , n(%) NA NA 23 (52.3) 5 (21.7) NA
Hydroxychloroquine¥, NA NA
17 (38.6) 2 (8.7)
NA
n(%)
Leflunomide¥, n(%) NA NA 11 (25.0) 16 (69.6) NA
Previous DMARD 26 (86.7) 68 (97.1) 41 (93.2) 23 (100.0) 0.108
use, n(%)
Previous MTX use, 24 (80.0) 66 (94.3) 39 (88.6) 18 (78.3) 0.088
n(%)
SJC 5.4 (4.0) 4.5 (4.0) 5.5 (4.1) 5.2 (5.2) 0.552
TJC 6.0 (5.7) 6.7 (6.8) 7.8 (6.8) 7.4 (7.4) 0.697
Pain, mm* 47.4 (23.2) 49.3 (25.5) 58.1 (23.8) 47.3 (27.3) 0.213
PtGA, mm* 44.5 (25.6) 50.1 (26.6) 58.9 (22.9) 53.8 (25.2) 0.179
MDGA, mm* 51.8 (17.9) 47.4 (23.5) 55.1 (18.8) 53.3 (21.1) 0.412
Morning stiffness, 0.253
44.1 (47.9) 31.0 (35.0) 47.5 (44.5) 45.7 (43.8)
min
DAS28 4.2 (1.5) 4.2 (1.4) 4.4 (1.5) 4.5 (1.9) 0.930
*100 mm VAS; mean (SD) is reported for age, disease duration, and disease parameters.
¥Concomitant DMARD use
€P-value derived from non-parametric Kruskal Wallis test for continuous variables and from Pearson Chi-
Square for categorical variables. No statistically significant between group differences were observed
among RA and PsA patients. NA=not applicable
Disclosure: D. Haaland, None; A. Jaroszynska, Janssen Pharmaceutica Product, L.P., 9; B. Haraoui, None; S. Kapur,
None; J. Stewart, None; W. Olsynzynski, None; K. Anderson, None; R. Rai, None; M. Starr, None; A. Tsoukas, None;
E. Psaradellis, Janssen Inc., 9; E. Rampakakis, Janssen Inc., 9; C. Tkaczyk, Janssen Inc, 3; A. J. Lehman, Janssen Inc.,
3; F. Nantel, Janssen Inc., 3; B. Osborne, Janssen Inc., 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/predictors-of-long-term-retention-of-

methotrexate-and-other-dmards-with-golimumab-in-rheumatoid-arthritis-and-psoriatic-arthritis-an-analysis-from-a-
prospective-observational-registry
Long-Term Golimumab Retention Rate in Patients with Psoriatic Arthritis.

Is Concomitant DMARD Important?
Belen Serrano1, Carlos M Gonzalez2, Roberto González3, Juan Gabriel Ovalles-Bonilla4, Juan Carlos Nieto2, Julia
Martínez-Barrio5, Iustina Janta2, Larissa Valor3, Indalecio Monteagudo2 and Francisco Javier López Longo6,
1Rheumatology, Hospital General Universitario Gregorio Marañón, Genoa, Italy, 2Rheumatology, Hospital General
Universitario Gregorio Marañón, Madrid, Spain, 3Rheumatology, Hospital general Universitario Gregorio Marañón,
Madrid, Spain, 4Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain, 5Servicio de Reumatologia,
Hospital General Universitario Gregorio Marañón, Madrid, Spain, 6Facultad de Medicina, Universidad Complutense de
Madrid, Madrid, Spain
SESSION INFORMATION
Background/Purpose: The efficacy of Golimumab (GLM) treatment in psoriatic arthritis (PsA) patients has been widely
documented. The aim of this study was to analyze the long-term retention of GLM and to identify independent predictors of
drug retention in patients with PsA including concomitant DMARD.
Methods: Prospective monocentric cohort of PsA patients treated with GLM according to clinical practice. Study was
approved by local Ethics Committee. Demographic and clinical variables were analyzed with Cox proportional hazard
regression model.
Results: 48 patients were included, 20/48 (41.7%) oligoarticular, 19/48 (39.6%) polyarticular and 9/48 (18.7%) with
peripheral and axial PsA. The baseline characteristics of the patients are shown in Table 1. Mean follow-up time was 22.3
months (SD 19.0). Mean survival time was 40.3 months (95% CI: 32.0-48.5). Age, mean evolution time and previous
biological use were significant in the univariate analysis. Concomitant DMARD had no influence on GLM retention rate
(HR: 1.3; 95% CI: 0.5-3.2; p: 0.6). Figure 1. Patients with PsA treated with GLM as first or second biological tended to
have a better retention rate of the drug, but did not reach statistical significance. Fig 2. 18/48 (37.5%) withdraw GLM
treatment. 13/18 (72.2%) due to lack of efficacy, 1/18 (0.6%) due to adverse events and 4/18 (22.2%) due to other reasons.
Table 1. Baseline demographic and clinical characteristics of the patients.

Age -mean (SD)-years 48.3 (11.1)
Female gender % 52.1%
Mean evolution time (SD)
8.4 (7.9)
years
TJC 4.1 (4.1)
SJC 2.9 (2.7)
CRP mg/dl Mean (SD) 0.6 (0.7)
DAS28-CRP 3.7 (1.5)
Concomitant DMARD % 50%
Biological Therapy naïve
52.1%
%
Conclusion: Real-world Golimumab retention rate in patients with PsA was good and did not depend on concomitant
treatment with DMARD. When used as first or second biologic, Golimumab retention rate tend to be better.
Disclosure: B. Serrano, None; C. M. Gonzalez, MSD, Celgene, Novartis, Abbvie, Janssen, 5,MSD, Celgene, Novartis,
Janssen, UCB Pharma, 8; R. González, None; J. G. Ovalles-Bonilla, Pfizer, Roche, BMS, Asacpharma, Nordic Pharma,
8,Sanofi-Aventis Pharmaceutical, 5; J. C. Nieto, Roche Pharmaceuticals, MSD, Abbvie, Novartis, Celgene, BMS, 8; J.
Martínez-Barrio, None; I. Janta, None; L. Valor, Roche, Novartis, Celgene, Janssen; Sanofi, 8; I. Monteagudo, None; F.
J. López Longo, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/long-term-golimumab-retention-rate-in-

patients-with-psoriatic-arthritis-is-concomitant-dmard-important
Improvement of Joint Inflammation As Assessed By MRI and

Power Doppler Ultrasound (PDUS) in an Open Label Study in Patients with
Active Psoriatic Arthritis Treated with Secukinumab.
Eleni Kampylafka1, Isabelle Oliveira1, Christina Linz2, Veronika Lerchen1, Matthias Englbrecht1, Michael Sticherling3,
Arnd Kleyer1, Juergen Rech1, Georg Schett1 and Axel J. Hueber1, 1Department of Internal Medicine 3 – Rheumatology
and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany, 2Department of Internal
Medicine 3 – Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg, e, Germany,
3Department of Dermatology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
SESSION INFORMATION
Background/Purpose:
Secukinumab, an anti-interleukin 17A monoclonal antibody, showed significant improvement of signs and symptoms of
psoriatic arthritis (PsA) in phase 3 studies. Available studies used conventional radiography, not allowing a deeper imaging
analysis of the inflammatory changes during application. The aim of this study was to assess short term efficacy of
secukinumab on inflammation and structural damage according to change in OMERACT-EULAR ultrasound score, the
MRI PsAMRIS score, and HRpQCT scans of the MCP and PIP joints in PsA patients.
Methods:
PsA patients with active disease (TJC and SJC ≥ 3), were included in the 24 week open label prospective PSARTROS
study and treated with subcutaneous secukinumab 300 mg once weekly over 4 weeks, then once every 4 weeks. Baseline
1,5T MRI hand scans, HRpQCT scans of the MCP and PIP joints, and ultrasound imaging of 28 joints were performed at
baseline and after 24 weeks of treatment. MRI was scored according to PsAMRIS. HRpQCT scans were evaluated for
erosions and osteo-proliferation. Ultrasound was assessed for synovial hypertrophy and Doppler activity according to
OMERACT scores. Statistical significance was set at p≤0.05.
Results: 20 patients, mean age 52 ± 9.9 years, 60% female, mean disease duration 6.7 ± 5.9 years, 50% naive for biological
therapy, were included in the study. Three patients were early discontinued (recurrent pharyngitis, lack of efficacy,
withdrawal of consent), and were not included into the longitudinal analysis. Baseline DAS28 was 5.03±0.96, baseline
DAPSA was 32.2±12. 1. On baseline MRI, all patients had at least one inflammatory sign (synovitis: 90%, osteitis: 20%,
periarticular inflammation: 25%, flexor tenosynovitis: 35%, bone proliferation: 30%, erosions: 60%). Baseline composite
PsAMRIS score was 11.6±12.8 and baseline PsAMRIS synovitis score was 3.7±3.3. Baseline ultrasound synovial
hypertrophy and Doppler activity were 6.2±4.5 and 3.5±4.0, respectively. Specific MRI and ultrasound scores were
significantly correlated with DAS28 and DAPSA at baseline. Clinical disease activity parameters significantly improved at
follow up (DAS28: 2.94±0.95, p<0.001; DAPSA: 8.8±5.8, p<0.001). PsAMRIS synovitis score (2.5±2.4) as well as
composite PsAMRIS score (8.8±10.0) decreased longitudinally with secukinumab treatment (p=0.034 and p=0.039,
respectively). There was no progression in erosion or proliferation scores between baseline and follow-up through MRI and
HRpQCT imaging. Synovial hypertrophy and Doppler activity in ultrasound also significantly improved with secukinumab
treatment (2.3±3.5; p=0.009 and 1.8±2.7; p=0.003, respectively). A significant percentage of patients reaching minimal
disease activity showed residual signs of synovitis in the MRI and US (66% and 50%, respectively).
Conclusion:
Secukinumab significantly improves MRI and ultrasound signs of joint inflammation in patients with PsA. No progression
in articular damage or osteo-proliferation was observed.
Disclosure: E. Kampylafka, None; I. Oliveira, None; C. Linz, None; V. Lerchen, None; M. Englbrecht, None; M.
Sticherling, None; A. Kleyer, None; J. Rech, None; G. Schett, None; A. J. Hueber, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/improvement-of-joint-inflammation-as-

assessed-by-mri-and-power-doppler-ultrasound-pdus-in-an-open-label-study-in-patients-with-active-psoriatic-arthritis
International League of Associations for Rheumatology. Systematic Review

of the Literature to Inform Treatment Recommendations for Psoriatic
Arthritis in Resource-Poor Countries
Musaab Elmamoun1, Maria Eraso2, Laura C Coates3, Ajesh Maharaj4, Vinod Chandran5, Ahmed Abogamal6, Valderilio
F Azevedo7, Wilson Bautista-Molano8, Alex G. Ortega9, Jorge Medina-Rosas10,11, Fabian Hernandez12,13, Adma Lima14,
Uyi Ima-Edomwonyi15, Adeola Ajibade16, Tarun Narang17, Olusola Ayanlowo18, Claudia Goldenstein-Schainberg19,
Roberto Ranza20,21,22,23,24,25, Girish M Mody26, Sueli Carneiro27,28, Aman Sharma29, Oscar Vega-Hinojosa30, Luis E.
Vega31, Adewale O Adebajo32 and Sergio Toloza33, 1Rheumatology, University of Toronto, Toronto Western Hospital,
Toronto, ON, Canada, 2University of Toronto, Toronto Western Hospital, Tornoto, ON, Canada, 3Nuffield Department of
Orthopaedics, Rheumatology and Musculoskeletal Sciences,, Oxford, United Kingdom, 4Nelson R. Mandela School of
Medicine, University of KwaZulu Natal, Durban, South Africa, 5Medicine, Krembil Research Institute, Toronto Western
Hospital, University of Toronto, Toronto, ON, Canada, 6Al-Azhar University, Cairo, Egypt, 7Adjunct Professor of
Rheumatology, Federal University of Paraná; Brazil, Curitiba, Brazil, 8School of Medicine, Universidad Militar Nueva
Granada and Rheumatology Department Hospital Militar. Colombia, Bogotá, Colombia, 9Virginia Commonwealth
University, Richmond, VA, 10Rheumatology, Universidad de la Sabana, Bogota, Colombia, 11Universidad del Valle, Cali,
Colombia, 12Universidad del Cauca, Popayan, Colombia, 13Universidad de Caldas, Pereira, Colombia, 14Federação
Universidade Regional de Blumenau, Blumenau, Brazil, 15Internal Medicine, Lagos University Teaching Hospital,
Surulere, Nigeria, 16Obafemi Awolowo University Teaching Hospitals Complex Osun state, Nigeria., Osogbo, Nigeria,
17Postgraduate Institute of Medical Education and Research, Chandigarh, India, 18Lagos University Teaching Hospital,
Lagos, Nigeria, 19Universidade de São Paulo, São Paulo, Brazil, 20on behalf of the BiobadaBrasil study group, Sociedade
Brasileira de Reumatologia, Uberlandia, Brazil, 21Rua Otavio Rodrigues DaCunha, Uberlandia MG, Brazil, 22Servicio de
Reumatología, Universidade Federal de Uberlandia, Uberlandia, Brazil, 23Reumatologia, Reumatologia, Universidade
Federal de Uberlandia, Uberlandia, Brazil, 24Matematica, Matematica, Universidade Federal de Uberlandia, Uberlandia,
Brazil, 25Universidade Federal de Uberlandia, Uberlandia MG, Brazil, 26Dept of Rheumatology, University of Kwa Zulu-
Natal, Durban, South Africa, 27Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 28University of São Paulo,
Sao Paulo, Brazil, 29Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India,
30Clínica Reumacenter,, Juliaca, Peru, 31Hospita Central Fuerza Aerea Perú, Lima, Peru, 32University of Sheffield,
Sheffield, United Kingdom, 33Rheumatology, Hospital San Juan Batista, Catamarca, Argentina, Catamarca, Argentina
SESSION INFORMATION
Background/Purpose:
Psoriatic Arthritis (PsA) is a heterogeneous disease which makes management of PsA a challenge. European League
Against Rheumatism (EULAR) and the Group for Research and Assessment of Psoriasis and PsA (GRAPPA) updated their
respective recommendations for the management of PsA in 2015. However, these recommendations are primarily based on
studies conducted in resource replete countries of Europe and North America; they may not necessarily be applicable to
PsA patients in countries in Central and South America, Africa and the Asia-Pacific region. Therefore there is a need to
adapt the EULAR and GRAPPA recommendations for each of these regions under the auspices of ILAR.
Methods:
1) The ADAPTE process for guideline adaptation was used to assess and adapt the EULAR and GRAPPA treatment
recommendations for PsA. Guideline quality was assessed using the 23 criteria of the Appraisal of Guidelines for Research
and Evaluation (AGREE) instrument.
2) A literature search included three databases Medline, Embase, LILACS to identify studies that addressed additional
treatment issues in Central and South America, Africa and the Asia-Pacific region.
Results:
The setup phase of the ADAPTE process was completed. Key health professionals in Pan-American League of
Associations for Rheumatology (PANLAR) and The African League of Associations in Rheumatology (AFLAR) as well as
patient research-partners identified key health issues faced. The adaptation phase of the ADAPTE process was carried out
with both EULAR and GRAPPA recommendations assessed for quality and relevance to ILAR regions. Three different
categories were assessed in the two guidelines; a) efficacy and safety of pharmacotherapy, b) recommendation for
physicians with limited access to other specialists, c) screening and management of tuberculosis (TB), hepatitis B/C, human
immunodeficiency virus (HIV), Chagas’ disease, leishmaniasis, and leprosy. The consensus (> 75% of votes) was to adapt
the GRAPPA guidelines in terms of recommendations regarding efficacy and safety of pharmacotherapy, however,
recommendations for combination therapy with conventional synthetic disease-modifying anti-rheumatic drugs
(csDMARDs) and biologic (b)DMARDs was not stated and evidence needed to be synthesized from literature review.
Similarly, recommendation for biosimilars, biomimics; physicians with limited access to specialists; screening and
management of TB, HB/C, HIV, Chagas’ disease, leishmaniasis, was lacking and referred to literature review.
The literature search retrieved a total of 634 articles; following exclusion of duplicates and off-topic items and after title
and abstract review 26 articles were included for full text review. Results from the literature review suggests lack of
recommendation/evidence around use of biosimilas/biomimics, skin treatment in the absence of dermatologist, and issues
around screening and management of certain diseases relevant to resource-poor countries.
Conclusion:
New ILAR recommendations have been devised using adaptation from the GRAPPA recommendations where appropriate
and additional SLR data to answer specific issues for resource poor settings and devise a research agenda for these regions.
Disclosure: M. Elmamoun, None; M. Eraso, None; L. C. Coates, None; A. Maharaj, None; V. Chandran, None; A.
Abogamal, None; V. F. Azevedo, None; W. Bautista-Molano, None; A. G. Ortega, None; J. Medina-Rosas, None; F.
Hernandez, None; A. Lima, None; U. Ima-Edomwonyi, None; A. Ajibade, None; T. Narang, None; O. Ayanlowo,
None; C. Goldenstein-Schainberg, None; R. Ranza, None; G. M. Mody, None; S. Carneiro, None; A. Sharma, None;
O. Vega-Hinojosa, None; L. E. Vega, None; A. O. Adebajo, None; S. Toloza, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/international-league-of-associations-

for-rheumatology-systematic-review-of-the-literature-to-inform-treatment-recommendations-for-psoriatic-arthritis-in-
resource-poor-countries
Short-Term Efficacy and Safety of New Biological Agents Targeting the IL-6,
IL-12/23 and IL-17 Pathways for Active Psoriatic Arthritis: A Network
Meta-Analysis of Randomised Controlled Trials
Dongze Wu, Jiang Yue and Lai-Shan Tam, Department of Medicine & Therapeutics, The Prince of Wales Hospital, The
Chinese University of Hong Kong, Hong Kong, Hong Kong
SESSION INFORMATION
Background/Purpose:
According to EULAR recommendations, in patients with peripheral arthritis and an inadequate response to at least one
conventional synthetic DMARD, biologic DMARDs targeting IL-12/23, IL-17 pathways may be used in patients for whom
TNF inhibitors are inappropriate. The objective of this study was to investigate comparative efficacy, safety and tolerability
of IL-6, IL-12/23 or IL-17 inhibitors for patients with active psoriatic arthritis (PsA).
Methods:
Randomized controlled trials (RCTs) evaluating the efficacy, safety and tolerability of IL-6, IL-12/23 or IL-17 inhibitors
were identified by a comprehensive systematic literature review. Pair-wise meta-analyses and Bayesian network meta-
analyses using the random-effects model were performed to estimate pooled odds ratios (ORs) and 95% credible interval
(CrI) of attaining a 20% improvement according to American College of Rheumatology criteria (ACR20) and ACR 50
response across trials.
Results:
Six trials were identified which included 2,411 participants and 11 treatments. Pair-wise meta-analysis showed that
secukinumab, ustekinumab and ixekizumab demonstrated superior efficacy over placebo in achieving ACR 20 and ACR50
response. However, Ixekizumab has a higher incidence of adverse events (AE) than placebo. In contrast, ustekinumab has a
higher tolerability (less likely to be discontinued due to AE) than placebo. Network meta-analysis showed that
secukinumab (300mg monthly) had the highest efficacy in achieving ACR20 and ACR50; whereas clazakizumab (200mg
monthly), ustekinumab (45mg 12 weekly), secukinumab (150mg monthly) had the lowest probability of having AE, serious
AE, and intolerability respectively. Considering overall risk-benefit profile, secukinumab (150mg monthly) may offer an
optimal balance for active PsA patients.
Conclusion:
From available evidence, secukinumab was found to be the safest and most efficacious short-term treatments for active
PsA amongst all the new biologics targeting the IL-6, IL-12/23 and IL-17 pathways.
Disclosures: This study has partly presented at EULAR2017.
Disclosure: D. Wu, None; J. Yue, None; L. S. Tam, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/short-term-efficacy-and-safety-of-new-

biological-agents-targeting-the-il-6-il-1223-and-il-17-pathways-for-active-psoriatic-arthritis-a-network-meta-analysis-of-
randomised-controlled-trials
Effect of Adding MTX to TNF Inhibitors on Joint Severity Indices and Skin
Scores in Psoriatic Arthritis: A Post-Hoc Meta-Analysis of Randomized,
Controlled Trials
Rochelle Castillo1, Khushboo Sheth2 and Santhanam Lakshminarayanan3, 1University of Connecticut, Farmington, CT,
2Rheumatology, Stanford University, Palo Alto, CA, 3Division of Rheumatology, University of Connecticut Health Center,
Farmington, CT
SESSION INFORMATION
Background/Purpose:
Co-medication of MTX with TNF inhibitors (TNFi) has proven superior to TNFi monotherapy in improving clinical
outcomes in patients with RA. Whether this holds true in psoriatic arthritis (PsA) remains unclear. We undertook this study
to summarize the post-hoc data from randomized, controlled trials (RCTs) on PsA to determine the effect of adding MTX
to TNFi on joint severity indices and skin scores.
Methods:
We performed a systematic search of PubMed, Medline, Scopus, and the reference lists of relevant articles for studies
published up to April 2017. RCTs containing data on the effect of combination MTX and TNFi versus TNFi monotherapy
were included. A random effects model was used to pool extracted data. Heterogeneity was evaluated with I2; p-values <
0.05 were considered significant. Relative benefit, the equivalent of relative risk in studies that aim to improve outcomes,
was used to measure the effect size of dichotomous variables.
Results:
Eight clinical trials consisting of 1,055 subjects were included. Responses were grouped into categories based on duration
of treatment (12±4 weeks, 24±4 weeks, 48±4 weeks) and outcome measured. Meta-analysis was performed when at least
two studies provided data for the same outcome during the same time frame. In studies measuring ACR 20/50/70 at Week
12, there was no statistically significant difference between combining TNFi with MTX vs. TNFi alone (Figure 1). The
same trend of no added benefit to combination therapy was observed in ACR 20/50/70 at Week 24 and ACR 20 at Week
48. In studies that measured PASI 75, there was a non-significant trend toward increased response at Weeks 24 and 48 with
combination therapy compared to TNFi monotherapy (Figure 2).
Conclusion:
In contrast to RA, the post-hoc data gleaned from PsA trials has not suggested a benefit to adding MTX to TNFi in
improving joint severity indices. This may be attributed to the fact that MTX monotherapy is generally considered less
effective in PsA than in RA. However, the non-significant trend toward increase in PASI 75 suggests that combination
therapy may be beneficial in the subset of PsA patients with significant skin involvement. An inherent limitation of the
included studies is that subjects in the MTX+TNFi group were already on stable MTX doses prior to initiating TNFi
therapy. Thus, studies directly comparing TNFi monotherapy with combination therapy with MTX in MTX-naive patients
are needed to arrive at definitive conclusions.
Figure 1. ACR 20/50/70 at Week 12 with adalimumab (ADA) and infliximab (IFX)
Figure 2. PASI 75 at Weeks 24/48 with ADA, etanercept (ETN), and IFX.
Disclosure: R. Castillo, None; K. Sheth, None; S. Lakshminarayanan, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effect-of-adding-mtx-to-tnf-inhibitors-

on-joint-severity-indices-and-skin-scores-in-psoriatic-arthritis-a-post-hoc-meta-analysis-of-randomized-controlled-trials
The Effect of Biologic Therapies on the Gut Microbial Composition in

Psoriatic Arthritis
Julia Manasson1, Carles Ubeda2, Lu Yang3, Melania Fanok4, Gary E. Solomon1, Soumya M. Reddy5, Sergei Koralov6,
Jose C. Clemente7 and Jose U. Scher1,4, 1Department of Medicine, Division of Rheumatology, New York University
School of Medicine, New York, NY, 2Institute for Research in Public Health, Valencia, Spain, 3New York University
School of Medicine, New York, NY, 4New York University School of Medicine, New York, NY, 5Department of Medicine,
Division of Rheumatology *contributed equally, New York University School of Medicine, New York, NY, 6Pathology,
New York University School of Medicine, New York, NY, 7Department of Genetics and Genomic Sciences, Icahn Institute
for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY
SESSION INFORMATION
Background/Purpose: Psoriatic arthritis (PsA) is a heterogeneous inflammatory arthritis affecting multiple clinical
domains. If left untreated, it has the potential for significant morbidity and disability. Prior to the introduction of TNF-alpha
inhibitors (TNFi), therapeutic options were limited. Agents that block the IL-17 pathway (IL-17i) were recently FDA-
approved, showing remarkable improvement in psoriasis, as well as similar efficacy to TNFi in PsA. Surprisingly, IL-17i
are not effective for all autoimmune conditions, and appear to exacerbate Crohn’s disease, even leading to de novo
intestinal inflammation. Because IL-17 plays a physiologic role in maintaining gut epithelial health and fighting
extracellular bacteria and fungi, we propose that intestinal inflammation occurs as a result of microbial dysbiosis. The goal
of this study was to better understand the interaction between IL-17i and the microbiome in humans and mice.
Methods: Fecal samples were collected from subjects with PsA pre- and post-treatment with secukinumab (n=9), an anti-
IL-17A monoclonal antibody, and adalimumab (n=10), a TNFi, which served as the control. In parallel, fecal pellets were
collected from wild type mice pre- and post-exposure to anti-IL-17 or MOPC isotype control antibodies. Samples
underwent DNA extraction, amplification, and 16S rRNA gene sequencing with Illumina MiSeq. Analysis was performed
with Quantitative Insights into Microbial Ecology (QIIME) and R. Additionally, short and medium chain fatty acids
(SCFA/MCFA) were measured utilizing liquid chromatography coupled with mass spectrometry (LC-MS/MS).
Results: PsA subjects treated with IL-17i did not show differences in overall microbial alpha or beta diversity pre- and
post-treatment. However, there was a significant shift in the Firmicutes to Bacteroidetes ratio after just five weeks of
therapy. Subjects clustered into two well-defined groups based on expansion or contraction of the Clostridiales taxa.
Relative abundance of Clostridiales correlated with levels of the SCFA acetate (r=0.4, p=0.09) and the MCFA hexanoate
(r=0.4, p=0.09). These differences were absent in TNFi-treated controls. Similarly, mice exposed to anti-IL-17 antibody
showed parallel perturbations in microbiota composition as demonstrated by alpha (p<0.05) and beta diversity (p<0.05),
with expansion of Clostridia and related taxa (p<0.05).
Conclusion: We characterized the effects of biologic therapies on gut microbiota composition and metabolites in human
PsA and in mice. Treatment with IL-17i leads to a gut microbial dysbiosis not seen with TNFi. Further studies to
understand the downstream effects of these perturbations may allow for the development of precision medicine approaches
to PsA.
Disclosure: J. Manasson, None; C. Ubeda, None; L. Yang, None; M. Fanok, None; G. E. Solomon, Abvie, 9; S. M.
Reddy, None; S. Koralov, None; J. C. Clemente, None; J. U. Scher, NIAMS-NIH, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-effect-of-biologic-therapies-on-the-

gut-microbial-composition-in-psoriatic-arthritis
Are There Clinical Demographic or Subclinical Ultrasonographic Data That

Can Predict Flare in Psoriatic Arthritis Patients during a Phase of Minimal
Disease Activity after Spacing of Anti-TNF Blockers Injections?
Pierluigi Macchioni1, Giovanni Ciancio2, Gilda Sandri3, Alen Zabotti4, Luca Montaguti5, Gentiana Vukatana6, Fabio
Mascella7, Donatella Chessa8, Elisa Verduci9, Marcello Govoni10, Amelia Spinella3, Francesca Zuliani11, Marco Bruschi5,
Nazzarena Malavolta12 and Mariacristina Focherini7, 1Rheumatology Unit, Arcispedale S Maria Nuova, IRCCS, Reggio
Emilia, Italy, 2Rheumatology Unit, Department of Medical Sciences, University of Ferrara and Azienda Ospedaliera-
Universitaria Sant’Anna - Ferrara (Italy), ferrara, Italy, 3Rheumatology Unit, University fo Modena & Reggio, Modena,
Italy, 4Rheumatology Clinic, Department of Medical and Biological Sciences, Santa Maria della Misericordia" University
Hospital, Udine, Italy, 5Dipartimento Internistico SS di Reumatologia, AUSL Romagna Ospedale Bufalini, Cesena, Italy,
6Rheumatology Unit, Department CardioThoracic Vascular, S.Orsola- Malpighi Hospital, Alma Mater Studiorum, Bologna,
Bologna, Italy, 7Internal Medicine and Rheumatology, Ospedale Infermi Rimini, Rimini, Italy, 8Internal Medicine,
Ospedale Paolo Dettori, Tempio Pausania, Italy, 9Rheumatology Unit, Arcispedale S. Maria Nuova, Reggio Emilia, Italy,
10Rheumatology Clinic, Department of Medical and Biological Sciences, University of Ferrara and Azienda Ospedaliera-
Universitaria Sant’Anna - Ferrara (Italy), ferrara, Italy, 11Rheumatology Unit, Department of Medical Sciences, Santa
Maria della Misericordia" University Hospital, Udine, Italy, 12Policlinico S.Orsola-Malpighi, Azienda Ospedaliero-
Universitaria of Bologna, Bologna, Italy
SESSION INFORMATION
Background/Purpose:
Tumour necrosis factor (TNF)-blocker tapering has been proposed for patients with psoriatic arthritis (PA) in clinical
remission. To evaluate if there are clinical, demographic and ultrasound (US) data predictive of disease recurrence after
spacing of anti-TNF therapy in PA patient during a phase of minimal disease activity (MDA)
Methods:
Patients treated with anti-TNF for at least 12 months and with at least 6 months duration of MDA were consecutively
recruited at 6 Italian centers.
In every center, the local rheumatologists provided PA pts to be examined by US. Personal history, demographic and
clinical data were recorded. Each patient underwent the following US examinations : metacarpophalangeal (MCP), knee
and tibio-tarsal (TT) joint, flexor and extensor tendon of hand digit, flexor and extensor tendon at carpal area, flexor and
extensor tendon of foot, and enthesis of common extensor tendon insertion on the lateral epicondyle of the humerus,
quadriceps tendon, patellar tendon, Achilles tendon and plantar fascia insertions on the calcaneus.. Each examination were
performed by rheumatologists expert in US, to assess synovitis (joint effusion, synovial proliferation, and power Doppler
(PD) signal), and bone erosions, flexor tendon tensynovitis, ext tendon tenonitis, and enthesel involvement using an Esaote
MyLabClass with a 5-13 or 6-18 MHz linear probe. US examinators were blind of clinical data of the pts. After the clinical
and US examination patients increased the interval between the anti-TNF administration according to a common protocol.
The patients were clinically evaluated at three month interval for the maintenance of a state of MDA. Baseline clinical and
US data were compared between the group of patients still in MDA at the end of a minimum follow-up period of 6 month
vs the group of patient with disease recurrence.
Results:
Sixty-three pts were recruited (mean age 53+13y, mean PA duration 13+8y, mean. MDA duration 21+11m). At the end of
follow-up period 5 patient were lost, 47 (81%) maintained a state of MDA and 11 (19%) had recurrence. At baseline US
examination 66.7 % of pts had at least one peripheral joint involved (17.5 % had peripheral active synovitis), 47.6% had
acute enthesitis and 95.2% chronic enthesopathy. US bursitis was present in 22.2% of pts, 3.7% had hand extensor finger
tendon involvement. No significant difference in any US and demographic data were present between the group in
persistent MDA vs the recurred group. Patients with baseline Maastricht enthesis index (MEI) > 0 had higher risk of
recurrences as compared with the group with MEI = 0 (36% vs 10%, p = 0.034).
Conclusion:
The presence of joint, entheseal and tendon abnormalities at US examination are not predictive of disease recurrence after
anti-TNF spacing in PA patients in MDA. Only a value of MEI > 0 is significanly correlated to recurrence.
/span>
Disclosure: P. Macchioni, None; G. Ciancio, None; G. Sandri, None; A. Zabotti, None; L. Montaguti, None; G.
Vukatana, None; F. Mascella, None; D. Chessa, None; E. Verduci, None; M. Govoni, None; A. Spinella, None; F.
Zuliani, None; M. Bruschi, None; N. Malavolta, None; M. Focherini, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/are-there-clinical-demographic-or-

subclinical-ultrasonographic-data-that-can-predict-flare-in-psoriatic-arthritis-patients-during-a-phase-of-minimal-disease-
activity-after-spacing-of-anti-tnf-blockers
Clinical and Sonographic Analysis of Patients with Psoriasis without

Musculoskeletal Complaints. Preeliminary Results of a Prospective Study:
The PRE-Psa Cohort
Andrea Cuervo1, Julio Ramírez2, Merce Alsina3, Raimon Sanmarti4 and Juan D. Cañete5, 1Arthritis Unit. Rheumatology
Dpt, Arthritis Unit, Rheumatology Dpt, Hospital Clinic of Barcelona and IDIBAPS, Barcelona, Spain, 2Rheumatology
Service, Hospital Clínic de Barcelona, Barcelona, Spain, 3Dermatology Dpt, Hospital Clinic de Barcelona, Barcelona,
Spain, 4Arthritis Unit, Rheumatology Dpt, Hospital Clinic of Barcelona, Barcelona, Spain, 5Arthritis Unit. Rheumatology
Department, Arthritis Unit, Rheumatology Dpt, Hospital Clinic of Barcelona, Barcelona, Spain
SESSION INFORMATION
Background/Purpose: Early diagnosis in psoriatic arthritis (PsA) is mandatory in order to initiate early therapy and
prevent disability. Around 20% of patients with Psoriasis (PsO) routinely visited in Dermatology departments have PsA
previously undiagnosed. The aim of this study is to evaluate the presence of inflammation by clinical examination and
ultrasound in joints and enthesis of patients with PsO without musculoskeletal symptoms.
Methods: Patients with PsO under topic or PUVA therapy without musculoskeletal symptoms were referred to our Arhritis
Unit. Clinical and demographic data were collected. The patients were evaluated for Body Surface Area (BSA), Swollen
Joint Count (SJC) (66 joints), Tender Joint Count (TJC) (68 joints) and enthesis (MASES). Psoriatic Arthritis Impact of
Disease tool questionnaire (PsAID) and Psoriasis Epidemiology Screening tool questionnaire (PEST) were used to assess
the impact of the disease. A comprehensive ultrasound evaluation of 46 joints and 12 enthesis was made (ESAOTE
MylabTwice, 12-18 Mhz probe). Enthesis score was calculated using the Madrid Sonographic Enthesis Index (MASEI) and
a total score for synovitis (synovial hypertrophy and Power Doppler) was also calculated.
Results: 32 patients were included. 18 patients were female (56.3%), mean age (SD) was 48.3 years (14.6) and disease
duration was 17.9 years (15.9). Mean BMI was 24.6 (5.2) and BSA 6.69 (8.7). 8 out of 32 (25%) had severe PsO (systemic
treatment or BSA>10% at any time of evolution). 4 patients (12.5%) had Power Doppler signal and 2 (6.3%) fulfilled
criteria for ultrasound-defined active synovitis (SH>2+PD) despite no signs or symptoms of musculoskeletal disease.
However, although structural alterations such as calcifications and enthesophytes were frequent, no PD was found at any
enthesis. In the univariate analysis, higher BMI (p=0.013), weight (p=0.010), waist (p=0.033) and hip (p=0.014)
circumferences were significantly associated with severe PsO. In the same way, CRP serum levels were also significantly
higher in patients with severe PsO (p=0.027).
Conclusion: Patients with severe PsO had significantly higher CRP serum levels, BMI, weight, waist and hip
circumferences. Of note, 12.5% of PsO patients had subclinical synovitis defined as PD. These patients should be followed
in order to confirm if they develop Psoriatic Arthritis.
Disclosure: A. Cuervo, None; J. Ramírez, Gebro, 2; M. Alsina, None; R. Sanmarti, None; J. D. Cañete, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/clinical-and-sonographic-analysis-of-

patients-with-psoriasis-without-musculoskeletal-complaints-preeliminary-results-of-a-prospective-study-the-pre-psa-cohort
Is There a Relationship between Spondyloarthritis and Periodontitis? a Case-

Control Study
Wilson Bautista-Molano1, Désirée van der Heijde2, Robert B.M. Landewé3, Gloria Lafaurie4, Julieth De Avila4, Rafael
Valle-Oñate5 and Consuelo Romero-Sanchez6, 1School of Medicine, Universidad Militar Nueva Granada and
Rheumatology Department Hospital Militar, Colombia, Bogotá, Colombia, 2Leiden University Medical Center, Leiden,
Netherlands, 3University of Amsterdam and Atrium Medical Center, Amsterdam, Netherlands, 4Unit of Oral Basic
Investigation-UIBO, School of Dentistry, Universidad El Bosque, Colombia, Bogotá, Colombia, 5School of Medicine,
Universidad Militar Nueva Granada and Rheumatology Department Hospital Militar, Colombia, Bogota, Colombia, 6Unit
of Oral Basic Investigation-UIBO, School of Dentistry, Universidad El Bosque, Colombia, BOGOTA, Colombia
SESSION INFORMATION
Background/Purpose:
Knowledge of the existence of an epidemiological association between SpA and periodontitis may fuel pathophysiological
thinking about SpA and if established, have clinical implications. Currently, it is unclear whether SpA patients have a
higher frequency of periodontitis and data in the literature reporting a possible association is limited. . Therefore, the aim of
the present study was to compare the frequency and severity of periodontitis in SpA-patients with healthy-control
individuals, through the evaluation of clinical, serological and microbiological periodontal condition.
Methods: Patients with a diagnosis of SpA (n=78) and bDMARD-naive fulfilling the ASAS classification criteria as well
as 156 healthy-controls matched for age/gender, were included. Two trained and calibrated periodontologists performed the
periodontal clinical assessment. The presence of periodontitis and its severity were determined according to the criteria
established by the Center for Disease Control and Prevention-American Academy of Periodontology (CDC-AAP). The
clinical periodontal variables, IgG1/IgG2 antibodies against P. gingivalis and periodontopathic bacterial identification,
were also established. Comparisons of periodontal characteristics between the SpA-patients and the control-group were
performed using univariable analyses. A logistic regression analyses was performed to calculate the odds ratio (95% CI) for
diagnosis of periodontitis in SpA-patients and matched-controls.
Results: A diagnosis of periodontitis was established in 56% in SpA patients vs. 69% of healthy-controls (p=<0.001).
Severe periodontitis was found in 3% vs 12% in SpA vs healthy-controls respectively (p=<0.001). There was no significant
increase of frequency of any periodontal variable, IgG1/IgG2 antibodies against P. gingivalis or the presence of
periodontopathic bacteria between SpA patients and control-group. Periodontitis was not positively associated with a
diagnosis of SpA (OR: 0.57 95% CI 0.32-1.00, p=0.05) in the logistic regression analyses
Conclusion:
Our results suggest that –unlike the situation in RA- there is not a positive association between SpA and periodontitis in
Colombian patients. We even found a lower prevalence of periodontitis and less severe periodontitis in comparison to
healthy controls. Moreover, all periodontal characteristics evaluated including clinical parameters, antibodies anti P.
gingivalis and bacterial identification were not increased in SpA patients as compared to controls.
Table 1 Characteristics and periodontal variables in patients with spondyloarthritis (SpA) and healthy controls
SpA Controls p-
Characteristics value
(n=78) (n=156)
Age (years) 39.5 ⱡ
39.6 (11.0)
(11.1)
Male gender N (%) 47 (60.3) 94 (60.3) ⱡ
Smoking (currently) N (%) 11 (14.1) 14 (9.0) 0.14
Obesity (BMI ≥30) N (%) 6 (7.6) 16 (10.2) 0.43
Periodontitis (positive)* N 0.01
44 (56.4) 108 (69.2)
(%)
Severity of Periodontitis* N
(%)
Any 34 (43.6) 48 (30.8) 0.01
Mild 11 (14.1) 20 (12.8)
Moderate 31 (39.7) 69 (44.2)
Severe 2 (2.6) 19 (12.2)
Insertion level total mouth <0.001
2.4 (0.5) 2.9 (0.8)
(mm)
CAL average interproximal <0.001
1.9 (0.6) 2.3 (0.8)
(mm)
Total pocket depth mouth 0.29
3.3 (1.7) 3.2 (1.9)
(mm)
Plaque Index (%) 0.4 (0.2) 0.5 (0.2) 0.12
Gingival index (%) 0.3 (0.2) 0.4 (0.5) 0.33
Number of teeth present 26.1 (4.1) 25.5 (5.4) 0.79
P. gingivalis (presence) N (%) 23 (29.4) 71 (45.5) <0.01
T. denticola (presence) N (%) 13 (16.6) 84 (53.8) <0.001
T. forsythia (presence) N (%) 6 (7.6) 75 (48.1) <0.001
IgG1 anti P. gingivalis 1
40 (51.2) 80 (51.2)
(positive) N (%)
IgG2 anti P. gingivalis 0.32
41 (52.5) 74 (47.4)
(positive) N (%)
All values given as mean (SD) unless specified;
ⱡ Age and gender were matching criteria
*Criteria and severity definition according to the Center for Disease Control and
Prevention-American Academy of Periodontology (CDC-AAP)
BMI, body mass index; CAL, clinical attachment loss
Disclosure: W. Bautista-Molano, None; D. van der Heijde, None; R. B. M. Landewé, None; G. Lafaurie, None; J. De
Avila, None; R. Valle-Oñate, None; C. Romero-Sanchez, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/is-there-a-relationship-between-

spondyloarthritis-and-periodontitis-a-case-control-study

Children with Treatment-Naive Enthesitis-Related Arthritis Have Decreased
Fecal Abundance of Faecalibacterium Prausnitzii A2-165 and Bacteroides
Fragilis: A Multi-Center Collaborative Study
Matthew L. Stoll1, Pamela F. Weiss2, Jennifer E. Weiss3, Peter Nigrovic4, Barbara Edelheit5, S. Louis Bridges Jr.6, Maria
I. Danila7, Charles Spencer8, Marilynn Punaro9, Kenneth Schikler10, Andreas Reiff11, Ranjit Kumar12, Randy Q. Cron1,
Casey D Morrow13 and Elliot J. Lefkowitz14, 1Pediatric Rheumatology, University of Alabama at Birmingham,
Birmingham, AL, 2Division of Rheumatology, Center for Pediatric Clincial Effectiveness, Children's Hospital of
Philadelphia, Philadelphia, PA, 3Hackensack University Medical Center, Hackensack, NJ, 4Division of Rheumatology,
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 5Pediatric Rheumatology, Connecticut Childrens
Medical Center, Hartford, CT, 6Clinical Immunology & Rheum, Univ of Alabama, Birmingham, AL, 7University of
Alabama at Birmingham, Birmingham, AL, 8Rheumatology, Nationwide Childrens Hospital/OSU, Columbus, OH,
9Children's Health, Dallas, TX, 10University of Louisville Medical School, Louisville, KY, 11Children’s Hospital of Los
Angeles, Los Angeles, CA, 12Center for Clinical and Translational Sciences, University of Alabama at Birmingham,
Birmingham, AL, 13Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham,
AL, 14Microbiology, University of Alabama at Birmingham, Birmingham, AL
SESSION INFORMATION
Session Title: Spondyloarthropathies and Psoriatic Arthritis – Pathogenesis, Etiology Poster I
Background/Purpose: Prior studies have demonstrated abnormalities in the composition of the gastrointestinal microbiota
in pediatric and adult patients with spondyloarthritis (SpA.) In particular, diminished fecal abundance of Faecalibacterium
prausnitzii and abnormalities in both directions in the abundance of the Bacteroides genus have been identified, mirroring
results in studies of patients with inflammatory bowel disease.
Methods: We obtained fecal specimens from children with treatment-naïve enthesitis-related arthritis (ERA) and healthy
controls from multiple geographic locations, as well as specimens from adult patients with long-standing SpA. All of the
samples underwent sequencing of the 16S ribosomal DNA (rDNA). A subset of the ERA and healthy pediatric fecal
samples were also subjected to shotgun metagenomics sequencing.
Results: Children with ERA (n = 30) and healthy controls (n = 19) underwent 16S rDNA sequencing. Clustering of the
microbiota based upon diagnosis (p = 0.046) was observed, while among ERA patients, there was no clustering by
geographic location. In contrast to previous studies, fecal abundance of F. prausnitzii was slightly higher in the patients
versus controls (10.0% vs 7.8%, p = 0.192); however strain-level differences were observed, with patients having relatively
decreased abundance of the anti-inflammatory A2-165 strain (41% versus 54%, p = 0.084) and an increased abundance of
the control L2/6 strain (28% versus 15%, p = 0.038). Similar trends were observed in adults with long-standing SpA (n =
11) and controls (n = 10): total F. prausniztii 10% in patients versus 6.9% in controls (p = 0.427), while A2-165 as
percentage of F. prausnitzii was 25% in patients versus 41% in controls (p = 0.175).
With respect to B. fragilis, opposite trends were seen among the pediatric versus the adult subjects. Specifically, pediatric
patients with ERA demonstrated increased abundance of B. fragilis compared to controls (2.0% versus 0.45%, p = 0.045),
yet adult subjects demonstrated decreased abundance of the Bacteroides genus (11% versus 26%, p = 0.036) and
specifically of B. fragilis (0.2% versus 1%, p = 0.106).
Shotgun metagenomics sequencing of the fecal DNA in the pediatric subjects did not demonstrate any global pathway
differences. However, it did reveal diminished coverage of the butanoate pathway (abundance normalized to controls of 1
versus 0.72 in ERA, p = 0.037).
Conclusion: Our study supports previous work indicating that decreased fecal abundance of a regulatory strain of F.
prausnitzii may be at least partly responsible for the pathogenesis of SpA, possibly due to decreased production of butyrate,
and suggests that efforts to replenish it in patients with SpA may be a potential therapeutic avenue. In contrast, the
mechanism by which Bacteroides impacts arthritis may differ in pediatric and adult patients, possibly reflecting altered
immunologic development in the former rather than direct pathogenicity or the organism. If this is the case, then
enthusiasm for microbial-based interventions to address this organism may be tempered. Instead, our findings may
underscore the necessity of prevention efforts, such as avoiding unnecessary use of antibiotics in healthy children.
Disclosure: M. L. Stoll, None; P. F. Weiss, None; J. E. Weiss, None; P. Nigrovic, Novartis Pharmaceutical Corporation,
2,Novartis Pharmaceutical Corporation, 5,Sobi, 2,Sobi, 5,UCB, 5,Pfizer Inc, 5,Casebia, 5,UpToDate, 7,American Academy
of Pediatrics, 7; B. Edelheit, None; S. L. Bridges Jr., None; M. I. Danila, None; C. Spencer, None; M. Punaro, None; K.
Schikler, None; A. Reiff, None; R. Kumar, None; R. Q. Cron, SOBI, 5,MedacPHARMA, 5; C. D. Morrow, None; E. J.
Lefkowitz, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/children-with-treatment-naive-

enthesitis-related-arthritis-have-decreased-fecal-abundance-of-faecalibacterium-prausnitzii-a2-165-and-bacteroides-
fragilis-a-multi-center-collaborative-study
Downstream Effects of Apremilast in Human Arthritic Ex Vivo Models

Tue Wenzel Kragstrup1,2, Søren Lomholt2, Morten Aagaard Nielsen2, Line Dam Heftdal2, Peter H. Schafer3 and Bent
Deleuran2,4, 1Randers Regional Hospital, Randers, Denmark, 2Department of Biomedicine, Aarhus University, Aarhus,
Denmark, 3Department of Translational Development, Celgene Corporation, Summit, NJ, 4Department of Rheumatology,
Aarhus University Hospital, Aarhus, Denmark
SESSION INFORMATION
Background/Purpose:
Apremilast (Otezla) is a PDE4 inhibitor approved for the treatment of psoriasis and psoriatic arthritis, but the mechanisms
of action of apremilast are not fully described. The objective of this study was to study the downstream effects of
apremilast on cells of the inflamed joint in ex vivo models of immune mediated inflammatory arthritis. Therefore, we tested
the ex vivo effect of apremilast on the secretion of several cytokines, chemokines and growth factors by synovial fluid
mononuclear cells (SFMCs), fibroblast-like synovial cells (FLSs), osteoclasts, synovial macrophages, and osteoblasts.
Methods:
SFMCs and FLSs were obtained from a study population consisting of patients with active RA, or peripheral SpA with at
least one swollen joint (for obtaining synovial fluid) (n=14). Peripheral blood mononuclear cells (PBMCs) were obtained
from healthy controls and osteoblasts were purchased. SFMCs were cultured for 48 hours with and without addition of
apremilast measuring the secretion of a large panel of cytokines, chemokines and growth factors by the Olink proseek
multiplex interferon panel and commercially available ELISA assays. These effects were compared with the effects of the
TNFα inhibitor adalimumab. Further, FLS-PBMC co-cultures were used to study the secretion of metalloproteinases,
SFMCs cultured for 21 days were used to study inflammatory osteoclastogenesis and macrophage differentiation, and a
mineralization assay was used to study new bone formation.
Results :
In SFMCs cultured for 48 hours, apremilast decreased the production of IL-12B (P<0.00001) CSF1 (P=0.009), sCD6
(P=0.03), sCD40 (P=0.04), and MCP-1 (P=0.02), and increased the production of CXCL5 (P=0.003) dose-dependently. In
sub-analyses, the apremilast induced decrease in cytokine production was greater in cultures with a high lymphocyte count
and in cultures from patients with a low C-reactive protein level. Further, apremilast had a very different response signature
compared with adalimumab, e.g. with a more robust inhibition of IL-12B (P=0.01) and less inhibition of IL-8 (P=0.0001)
(see figure). In FLS-PBMC co-cultures, apremilast decreased MMP3 production (P=0.009). In SFMCs cultured for 21
days, apremilast did not significantly decrease inflammatory osteoclastogenesis (P=0.2). However, apremilast increased the
secretion of IL-10 (P=0.04) without affecting the secretion of MCP-1 (P=0.5). Finally, apremilast did not significantly
decrease mineralization by human osteoblasts (P=0.2).
Conclusion :
This study reveals the downstream effects of apremilast in ex vivo models of arthritis with a strong inhibition of IL-12B.
Further, apremilast induced IL-10 production in synovial macrophages and decreased MMP3 in FLS-PBMC co-cultures.
Our findings could explain some of the efficacy of apremilast seen in IL-12/IL-23 driven immune mediated inflammatory
diseases such as psoriasis and psoriatic arthritis.
Disclosure: T. W. Kragstrup, None; S. Lomholt, None; M. A. Nielsen, None; L. D. Heftdal, None; P. H. Schafer,
Otezla, 1, 9,Otezla, 3; B. Deleuran, Otezla, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/downstream-effects-of-apremilast-in-

human-arthritic-ex-vivo-models
Mir-10b-5p Is a IL-22 Regulator in CD4+T Cells from Ankylosing

Spondylitis
Tae-Jong Kim1, So-Hee Jin2, Liye Chen3, Mohammad Hussein Al-Mossawi3, Anna Ridley3, Takuya Sekine3, Davide
Simone3, Hui Shi3, Frank Penkava3 and Paul Bowness3, 1Rheumatology, Chonnam National University Medical School
and Hospital, Gwangju, Korea, Republic of (South), 2Chonnam National University Medical School and Hospital,
Gwangju, Korea, Republic of (South), 3Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal
Sciences, University of Oxford, Oxford, United Kingdom
SESSION INFORMATION
Background/Purpose:
Emerging data suggest that a single microRNA (miR) can profoundly alter the phenotype and outcome of immune
responses, offering the prospect of therapeutic use. We recently reported a novel Th17 regulator miR-10b-5p that is present
in Th17 cells from patients with Ankylosing Spondylitis (AS). IL-22 is closely related to Th17 cells and also regulated by
IL-23, a key cytokine for IL-17A production. Moreover, IL-22 has been implicated in the regulation of new bone formation
in experimental models. Therefore, we wonder whether miR-10b-5p affects IL-22 production in AS.
Methods:
Primary CD4+ T cells were negatively isolated from PBMCs from AS patients (Miltenyi Biotec). Transfection was
performed with the Neon transfection system (Thermos Fisher Scientific, Germany) according to manufacturer’s
instructions.
The transfection efficiency was evaluated by monitoring FAM (Fluorescein) positive cells using flow cytometry, and qPCR
at 24 h after transfection. miR-10b-5p function was determined by overexpression of miR mimic in CD4+ T cells followed
by intracellular cytokine staining, cytokine measurement, and qPCR. Statistical analysis was performed using Prism 5.0
Software (GraphPad Software, San Diego, USA). A p < 0.05 was considered statistically significant.
Results:
Overexpression of miR-10b-5p reduced both IL-22+CD4+ T cell frequencies and IL-22 production in CD4+ T cells from
patients with AS. To identify the cellular targets of miR-10b-5p, we previously performed RNA-sequencing of CD4+ T
cells transfected with miR-10b-5p together with in silico Target Scan analysis. MAP3K7 was selected as a target gene
because of its known role in cytokine regulation. We then silenced MAP3K7 in CD4+ T cells using siRNA and found the
suppression of IL-22 response, mimicking the effect of miR-10b-5p overexpression.
Conclusion:
Our data suggest that miR-10b-5p suppress IL-22 production by targeting MAP3K7. miR-10b-5p might be a potential
therapeutic candidate for regulation of new bone formation in patients with AS.
Disclosure: T. J. Kim, None; S. H. Jin, None; L. Chen, None; M. H. Al-Mossawi, None; A. Ridley, None; T. Sekine,
None; D. Simone, None; H. Shi, None; F. Penkava, None; P. Bowness, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/mir-10b-5p-is-a-il-22-regulator-in-cd4t-

cells-from-ankylosing-spondylitis
Association of Osteonectin, Osteopontin and Osteocalcin with Inflammation

and Cardiovascular Risk in Patients with Axial Spondyloarthritis
Fernanda Genre1, Javier Rueda-Gotor2, Juan Irure-Ventura3, Sara Remuzgo-Martínez1, Alfonso Corrales1, Begoña
Ubilla1, Veronica Mijares1, Carlos Fernández-Díaz1, Virginia Portilla1, Ricardo Blanco1, Javier Llorca4, J. Gonzalo Ocejo-
Vinyals3, Raquel López-Mejías1 and Miguel Angel González-Gay5, 1Epidemiology, Genetics and Atherosclerosis Research
Group on Systemic Inflammatory Diseases, IDIVAL, Santander, Spain, 2Hospital Universitario Marqués de Valdecilla.
IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain, 3Immunology Division, Hospital Universitario
Marqués de Valdecilla, Santander, Spain, 4Department of Epidemiology and Computational Biology, School of Medicine,
University of Cantabria, and CIBER Epidemiología y Salud Pública (CIBERESP), Santander, Spain, 5Epidemiology,
Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL and School of Medicine,
University of Cantabria, Santander, Spain
SESSION INFORMATION
Background/Purpose: A higher incidence of cardiovascular (CV) risk factors and atherosclerosis has been reported in
axial spondyloarthritis (axSpA) patients1. Since axSpA (particularly AS) is an inflammatory disease characterized by
changes in the osteoproliferative process, a dysregulation in the molecules involved in bone remodeling is highly plausible
in these patients, also affecting vascular calcification in the context of atherosclerosis. Therefore, we aimed to assess the
role of osteonectin (ON), osteopontin (OPN) and osteocalcin (OC), implicated in bone metabolism2, in the development of
subclinical atherosclerosis and its association with CV risk factors in a large cohort of axSpA patients.
Methods: Serum ON, OPN and OC levels were measured by multiplex assays in 171 Spanish axSpA patients (including
both non-radiographic axSpA [nr-axSpA] and AS), recruited from Hospital Universitario Marqués de Valdecilla and
Hospital de Laredo (Spain) who fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification
criteria (for nr-axSpA)3 and also the 1984 modified New York criteria (for AS)4. Patients with history of CV disease,
diabetes mellitus, chronic kidney disease, IBD or psoriasis were excluded. Carotid US was performed to evaluate the
presence of subclinical atherosclerosis. The association of these molecules with the different variables of study were
assessed by ANOVA, partial correlation or Student`s t test, where appropriate, using STATA® v. 11.1. The results were
adjusted by potential confounding factors.
Results: ON and OPN positively associated with ESR at study (p=0.01 and 0.02). Higher ON levels were observed in men
and axSpA patients who smoked (p=0.01), and also correlated with CRP levels at study (p=0.02). In addition, patients with
CRP at diagnosis >3 mg/L showed higher OPN levels. Regarding OC, hypertensive patients displayed higher levels of this
molecule (p=0.02). No association was found between these molecules and markers of subclinical atherosclerosis.
Conclusion: We disclosed an association of ON, OPN and OC with inflammation and CV risk factors, supporting an
implication of these molecules in the development and progression of atherosclerotic disease in axSpA.
[1] Joint Bone Spine 2014;81(1):57-63. [2] Clin Chim Acta 2015;438:401-14. [3] Ann Rheum Dis 2009;68:777–83. [4]
Arthritis Rheum 1984;27:361-8.
FG is a recipient of a Sara Borrell post-doctoral fellowship from the Instituto de Salud Carlos III (ISCIII)(Spain)
(CD15/00095). SR-M is supported by the RETICS Program (RIER) (ISCIII, Spain)(RD16/0012/0009). RL-M is supported
by a Miguel Servet type I programme (ISCIII, Spain)(CP16/00033). This research did not receive any specific grant from
funding agencies in the public, commercial, or not-for-profit sectors.
Disclosure: F. Genre, None; J. Rueda-Gotor, None; J. Irure-Ventura, None; S. Remuzgo-Martínez, None; A.

Corrales, None; B. Ubilla, None; V. Mijares, None; C. Fernández-Díaz, None; V. Portilla, None; R. Blanco, None; J.
Llorca, None; J. G. Ocejo-Vinyals, None; R. López-Mejías, None; M. A. González-Gay, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/association-of-osteonectin-osteopontin-

and-osteocalcin-with-inflammation-and-cardiovascular-risk-in-patients-with-axial-spondyloarthritis
An Oral Tyk2 Inhibitor Effectively Suppresses the Development of Murine

Th17 Cells In Vivo and Prevents Joint Damage in Experimental Ankylosing
Spondylitis
Eric Gracey1,2, Melissa Lim2, Zoya Qaiyum1, Yuriy Baglaenko1,2, Wenyan Miao3, Craig Masse3, William Westlin3 and
Robert D Inman1,4, 1Department of Immunology, University of Toronto, Toronto, ON, Canada, 2Toronto Western Hospital,
University Health Network, Toronto, ON, Canada, 3Nimbus Therapeutics, Cambridge, MA, 4Toronto Western Hospital,
University Health Network, toronto, ON, Canada
SESSION INFORMATION
Background/Purpose:
Th17 cells play an important role in the pathogenesis of ankylosing spondylitis (AS). Tyk2, a member of the Janus Kinase
(JAK) family of signaling molecules, was the first JAK to be associated with AS in genome-wide association studies. Tyk2
plays a crucial role in Th17 cell function through mediating IL-23 intracellular signaling, making Tyk2 an attractive target
for the treatment of AS. Here we examine the expression of Tyk2 at the cellular level in human peripheral blood
mononuclear cells (PBMCs) for evidence of SNP-mediated changes in expression. We further tested a novel, potent and
selective Tyk2 inhibitor, NDI-031407, for therapeutic effect in the SKG mouse model of AS.
Methods:
Flow cytometry on PBMC was carried out on 76 AS patients, 47 healthy controls and 21 RA patients. Tyk2 mRNA was
assessed in unstimulated cells using PrimeFlow and cytokines were assessed in PMA/ionomycin-stimulated cells. SKG
mice were gavaged twice daily with NDI-031407 or methylcellulose vehicle from weeks 1 to 8 post-disease induction.
Mice were scored weekly for clinical presence of peripheral and axial arthritis, dermatitis and blepharitis. Sacroiliitis was
assessed by T1- and T2-weighted MRI. Histology was assessed by H&E staining. Th17 frequency and phenotype were
assessed by flow cytometry in popliteal, mesenteric and sciatic lymph nodes.
Results:
Tyk2 mRNA expression in PBMCs by flow cytometry did not demonstrate significant differences between AS and controls.
Tyk2 expression levels did not stratify by candidate SNPs (rs12720356, rs35164067) and did not correlate with Th17
frequency. NDI-031407 is a small molecule Tyk2 inhibitor that inhibits Tyk2 with a Ki of 0.2 nM, and is 218-, 148-, and
20-fold selective against JAK1, JAK2, and JAK3, respectively. In SKG mice, therapeutic dosing with NDI-031407
significantly reduced the clinical scores of joint and skin inflammation to normal levels (see figure). MRI of the sacroiliac
joint (SIJ) showed joint space narrowing and edema with disease progression and NDI-031407 protected against these SIJ
changes. Enthesitis and bone erosion in the ankle and tail were prevented by Tyk2 inhibition. FACS showed that NDI-
031407 suppressed the expansion of IL-17A+ Th17 cells (vehicle vs NDI-031407; 6.04% vs 2.73% of CD4+ T cells, p=
<0.001) in addition to reducing IL-17F, IL-22, ICOS and Ki67 expression.
Conclusion:
AS-associated Tyk2 SNPs do not impart a difference in Tyk2 expression and likely contribute to AS through promoting
Th17 cell function. Our findings indicate that Tyk2 inhibition can prevent disease progression in SKG mice by reducing
Th17 cells and associated inflammatory cytokines. Future studies aim to unravel the role of Tyk2 in Th17 cell development
to better understand the mechanism behind Tyk2 inhibition. This work provides the first evidence that Tyk2 inhibition
presents as a viable therapeutic target in AS.
Disclosure: E. Gracey, None; M. Lim, None; Z. Qaiyum, None; Y. Baglaenko, None; W. Miao, None; C. Masse, None;
W. Westlin, None; R. D. Inman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/an-oral-tyk2-inhibitor-effectively-

suppresses-the-development-of-murine-th17-cells-in-vivo-and-prevents-joint-damage-in-experimental-ankylosing-
spondylitis
Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) Is a Susceptibility

Factor for Early Axial Spa Meeting the ASAS Classification Criteria: Results
from the Spondyloarthritis Caught Early and DEvenir des Spondyloarthrites
Indifférenciées Récentes Cohorts
Anoek de Koning1, Marjolijn Hameetman2, Corinne Miceli-Richard3, Maxime Dougados4, Désirée van der Heijde5, Fina
Kurreeman6 and Floris van Gaalen7, 1Rheumatology, Leiden University Medical Center, Leiden, Netherlands, 2Department
of Rheumatology, Leiden University Medical Center, Leiden, Netherlands, 3Department of Rheumatology, Hôpital Bicêtre,
Paris, France, 4Department of Rheumatology, Rene Descartes University, Hôpital Cochin, Paris, France, 5Leiden
University Medical Center, Leiden, Netherlands, 6Department of Rheumatology, Leiden University Medical Center,
Leiden, Netherlands, Leiden, Netherlands, 7Rheumatology, LUMC, Leiden, Netherlands
SESSION INFORMATION
Background/Purpose: Genetic research in axSpA is performed in patients with longstanding ankylosing spondylitis (AS).
Early axial spondyloarthritis (axSpA) is a diverse patient group in which a minority of the patients have AS. Therefore, it is
not known if recently identified genetic risk factors for AS are also risk factors for early axSpA. The aim is to evaluate if
ERAP1 and HLA-B*4001 are susceptibility factors for early axSpA.
Methods: Patients with early axSpA meeting the ASAS classification criteria from the SPondyloArthritis Caught Early
(SPACE) cohort (inclusion criteria: back pain for ≥3 months, ≤2 years, onset <45 years) and the DEvenir des
Spondyloarthrites Indifférenciées Récentes (DESIR) cohort (inclusion criteria: inflammatory back pain for ≥3 months, ≤3
years, age <50) were typed for two well established AS genetic risk factors: ERAP1 SNPs (rs30187 (susceptibility),
rs17482078 (protective) and rs10050860 (neutral)1) and HLA-B*4001. Subsequently, for ERAP1 SNPs sub analyses were
performed for AS and non-radiographic axSpA (nr-axSpA) patients. Analysis of weaker AS risk factors was limited by
sample size. For ERAP1, genotyped Dutch healthy controls (n=1085) (data kindly provided by C. Wijmenga and A.
Zhernakova (UMCG)) and published French subjects1 were used as controls. For HLA-B*4001 healthy blood bank donors
from the Netherlands (n=5584) and France (n=10177) were used as controls.
Results: In 486 DESIR patients (mean age 32.5 (SD 8.6); 50% male; 84% HLA-B27+; 18% X-SI+) and 144 SPACE
patients (mean age 29.5 (SD 8); 51% male; 88% HLA-B27+; 24% X-SI+) ERAP1 SNP rs30187 was more common than in
controls (OR 1.2, p=0.01 in meta-analysis; table 1). rs17482078 and rs10050860 were negatively associated with early
axSpA (both OR 0.7 (0.6-0.9) p<0.01 in meta-analysis). Minor allele frequencies were similar for AS patients and nr-
axSpA patients (table 2). Although both cohorts were sufficiently powered, HLA-B*4001 was not positively associated
with early axSpA (OR 0.6 (0.4-0.9) in meta-analysis).
Conclusion: ERAP1 rs30187 is a genetic risk factor for early axSpA patients with and without radiographic sacroiliitis. To
our knowledge this is the first report of genetic risk factor research in early axSpA patients meeting the ASAS criteria.
Larger cohorts are needed to study additional AS risk factors.
ADDIN EN.REFLIST 1. Kadi A, Izac B, Said-Nahal R, Leboime A, Van Praet L, de Vlam K, et al. Investigating the
genetic association between ERAP1 and spondyloarthritis. Ann Rheum Dis. 2013;72(4):608-13.
Disclosure: A. de Koning, None; M. Hameetman, None; C. Miceli-Richard, None; M. Dougados, None; D. van der
Heijde, None; F. Kurreeman, None; F. van Gaalen, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/endoplasmic-reticulum-

aminopeptidase-1-erap1-is-a-susceptibility-factor-for-early-axial-spa-meeting-the-asas-classification-criteria-results-from-
the-spondyloarthritis-caught-early-and-devenir-des
Gene Expression in Cellular Subsets in Psoriatic Disease

Anastasiya Muntyanu1, Fatima Abji2, Remy Pollock1, Vinod Chandran2 and Dafna D Gladman2, 1University of Toronto,
Toronto Western Hospital, Toronto, ON, Canada, 2Rheumatology, University of Toronto, Toronto Western Hospital,
Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose: Psoriatic arthritis is an inflammatory musculoskeletal disease which develops in 30% of patients
with psoriasis. Our previous peripheral blood microarray study identified CXCL10, NOTCH2NL, HAT1, and SETD2 as
differentially expressed between PsA and psoriasis patients without arthritis (PsC). This study aimed to determine gene
expression in leukocyte subsets to elucidate their functions in psoriatic disease.
Methods: Peripheral blood mononuclear cells were isolated using Ficoll paque separation from PsA and PsC patients not
receiving biologic therapy and healthy controls (HC). T cells (CD3+), monocytes (CD14+), and NK cells (CD56+) were
separated by positive selection. mRNA was extracted using RNeasy miniprep kits and qPCR performed with 75ng mRNA
to determine CXCL10, CXCR3, NOTCH2NL, IL-17A, HAT1, and SETD2 gene expression. A two-way ANOVA with
Bonferroni’s post-hoc test was used to determine significant differences (p<0.05).
Results: Gene expression was measured in 15 PsA (mean age 59, 60% males), 15 PsC (mean age 57, 67% males), and HC
(mean age 54, 60% males). Expression of IL-17A in monocytes was 18.42-fold greater in PsA patients than PsC
(p<0.0001) and 31.36-fold greater in PsA than HCs (p<0.0001). There were no other significant differences in gene
expression between disease groups in each given cell type. However, in T cells, CXCL10 was elevated in PsA compared to
PsC (1.42-fold) and HC (2.47-fold). A similar trend was found for the receptor, CXCR3, where expression was higher in
PsA than PsC (1.18-fold) and HC (1.13-fold). Finally, SETD2 expression in PsA was higher than PsC (1.65-fold) and HC
(1.28-fold) in T cells. CXCL10 expression in monocytes (p<0.0001; 11.1-fold) and NK cells (p<0.0001; 2.04-fold) was
higher than in T cells. Expression of CXCR3 was higher in T cells compared to monocytes (p<0.0001; 208.17-fold) and
NK cells (p<0.0001; 1.3-fold). HAT1 was more highly expressed in T cells as compared to monocytes (p=0.0003; 3.41-
fold) and NK cells (p=0.0274; 1.48-fold). Expression of SETD2 was elevated in T cells compared to monocytes (p=0.0007;
3.2-fold) and NK cells (p=0.0082; 1.22-fold). NOTCH2NL expression was elevated in T cells compared to monocytes
(p=0.0154; 2.43-fold).
Conclusion: Genes of interest were differentially expressed in leukocyte subsets. The higher expression of these genes in
PsA compared to PsC and HCs could provide insight into their role in driving the development of PsA. Knowing which cell
types are predominantly involved with expression of certain biomarkers will aid in developing targeted treatments.
Disclosure: A. Muntyanu, None; F. Abji, None; R. Pollock, None; V. Chandran, None; D. D. Gladman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/gene-expression-in-cellular-subsets-in-

psoriatic-disease
Are Choline Metabolites Associated with Inflammation in Psoriatic

Arthritis?
Roxana Coras1,2, Arthur Kavanaugh2, Doquyen Huynh3, Mohit Jain2 and Monica Guma2, 1Medicine, Autonomous
University of Barcelona, Barcelona, Spain, 2Medicine, University of California, San Diego, La Jolla, CA, 3Medicine,
University of California, San Diego, San Diego, CA
SESSION INFORMATION
Background/Purpose: Psoriatic arthritis (PsA) is an inflammatory disease affecting the joints and connective tissue and is
associated with psoriasis of the skin and nails. In our daily clinical routine, patients often report changes in their disease
activity with certain foods, despite the ongoing treatment. Choline metabolism has been recently strongly related to
inflammation. Dietary intake of choline, through two circulating metabolites, trimethylamine (TMA), and trimethylamine
N-oxide (TMAO), are mechanistically linked to cardiovascular inflammation. The objective of this study was to explore the
link between choline metabolites and inflammation in PsA.
Methods: Patients with PsA, diagnosed based on the CASPAR criteria, were recruited from the Rheumatology Outpatient
Clinic at the University of California, San Diego. A thorough clinical examination, including joint and skin disease
evaluations, was conducted. Patients completed a health assessment questionnaire. DAS28, Clinical Disease Index (CDAI)
and Simple Disease Index (SDAI) scores and body surface area (BSA) of psoriasis were calculated. Serum concentration of
choline metabolites: choline, TMA, TMAO, and betaine were determined by Mass Spectrometry. Inflammatory biomarkers
in serum were determined by ELISA. Statistical analysis included means, standard deviation, t-test and Pearson correlation.
Results: 38 patients (average age 47.45 years, standard deviation [SD] 10.29) were recruited. The mean (SDs) of
DAS28PCR was 2.24 (1.29). 27 patients (71.05%) had active skin disease, with an average BSA of 4.73 (SD, 14.5).
23.68% of patients had enthesitis, 5.26% had dactylitis and 47.36% had nail involvement. 65.11% received biological
therapy (46.42% of them in association with a synthetic disease modifying drug DMARD), 13.95% received sDMARD in
monotherapy and 20.9% received symptomatic treatment. We found that TMAO, a choline metabolite, correlated with
parameters of disease activity for both skin (BSA) and joint (DAS28, CDAI, SDAI) (Table 1). Choline, TMA and TMAO
also correlated with inflammatory markers (Table 2). TMAO was higher in patients with active joint disease (CDAI>2.8)
versus patients in remission (CDAI<2.8; p = 0.01) and in patients with higher severity of skin disease (BSA >5%) versus
low severity (BSA <5%; p = 0.03).
Table 1. Correlation between choline metabolites and disease activity
Metabolite DAS28CRP CDAI SDAI BSA Swollen Dactylitis
joints
count
TMAO 0.341** 0.338** 0.377** 0.687*** 0.428*** 0.663***
* p<0.1, ** p<0.05, *** p<0.01
Table 2. Correlation between choline metabolism and inflammatory markers
Metabolite SAA CRP IL6 TNF-RI MMP1 MMP3 Leptin Resistin IL-8
Choline 0.286* 0.367** 0.643*** 0.467***
TMA 0.315* 0.709*** 0.573*** 0.380**
TMAO 0.517*** 0.709*** 0.416** 0.330* 0.385**
Betaine
SAA-Serum amyloid A; CRP-C reactive protein; IL-Interleukin; TNF-RI-Soluble tumor
necrosis alpha receptor type I; MMP-Metalloproteinase. * p<0.1, ** p<0.05, *** p<0.01
Conclusion: In our cohort, choline metabolism was associated with inflammation in PsA patients. Since diet is the main
source of choline, modulating choline food intake might help to better control disease activity in these patients. Further
studies are needed to explore the mechanistic links between choline and TMAO and inflammation.
Disclosure: R. Coras, None; A. Kavanaugh, None; D. Huynh, None; M. Jain, None; M. Guma, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/are-choline-metabolites-associated-

with-inflammation-in-psoriatic-arthritis

Role of Eicosanoids As Biomarkers in Psoriatic Arthritis
Roxana Coras1,2, Arthur Kavanaugh1, Doquyen H. Huynh1, Aladdin Shadyab3, Sara Marsal4, Oswald Quehenberger5 and
Monica Guma1, 1Medicine, University of California, San Diego, La Jolla, CA, 2Medicine, Autonomous University of
Barcelona, Barcelona, Spain, 3Family Medicine and Public Health, University of California, San Diego, La Jolla, CA,
4Rheumatology Research Unit, Vall d'Hebron Hospital, Barcelona, Spain, 5Pharmacology, Medicine, University of
California, San Diego, La Jolla, CA
SESSION INFORMATION
Background/Purpose: Psoriatic arthritis (PsA) is an inflammatory disease affecting the joints and connective tissue and is
associated with psoriasis of the skin and nails. There is no reliable biomarker to identify psoriatic patients at risk of joint
disease or disease progression. Eicosanoids, including prostaglandins and leukotrienes, are biological lipids that are
implicated in various pathological processes including inflammation. We hypothesized that by defining more precisely the
eicosanoid profile in PsA patients, we might identify novel diagnostic or prognostic biomarkers for disease activity and
PsA pathogenesis.
Methods: Patients with PsA, diagnosed based on the CASPAR criteria, were recruited from the Rheumatology Outpatient
Clinic at the University of California, San Diego. A thorough clinical examination, including joint and skin disease
evaluations, was conducted. Patients completed a health assessment questionnaire. DAS28, Clinical Disease Activity Index
(CDAI) and Simple Disease Activity Index (SDAI) scores and body surface area (BSA) of psoriasis were calculated. Serum
eicosanoids were determined by mass spectrometry and were classified in groups according to the enzyme that participates
in synthesis: cyclooxygenase (COX), 5-, 12- or 15-lipoxygenase (LOX), cytochrome P450, or non-enzymatic pathway.
Inflammation markers were determined by ELISA. Statistical analysis included mean, standard deviation and Spearman
correlation.
Results: 43 patients (average age 49.8, standard deviation 10.88) were recruited. Thirty-two (74.41%) had active skin
disease with an average BSA of 4.25 (SD, 13.67). The means (SDs) of DAS28PCR was 2.25 (1.25) and CDAI was 10.69
(11.87). 48.83% of patients had nail disease, 20.93% had enthesitis, and 4.65% had dactylitis. Further, 65.11% received
biological therapy (46.42% of them in association with a synthetic disease modifying drug, such as DMARD), 13.95%
received sDMARD in monotherapy, and 20.9% had symptomatic treatment. Several eicosanoids, especially those in the 12-
15-LOX pathway, significantly correlated with joint disease activity, but not with skin disease activity (Table 1). Several
eicosanoids correlated with serum markers of (IL6, Resistin, EGF, IL1β and IL8), but not with CRP (Table 1). Of note,
there was a weak correlation between CRP and SDAI that didn’t reach statistical significance (p=0.06).
Table 1. Correlation of Eicosanoids with clinical and serum parameters of inflammation
Eicosanoid CDAI SDAI DAS28 BSA CRP IL6 EGF Resistin IL1β IL8
COX PGE2 0.294 * 0.319 ** 0.592 ***
15- 15-HETE 0.259* 0.382*** 0.333** 0.392** 0.499*** 0.428*** 0.399*** 0.533***
LOX
15-HEPE 0.380** 0.364** 0.478*** 0.491*** 0.484*** 0.304** 0.566***
15HETrE 0.317** 0.489*** 0.379** 0.496*** 0.579** 0.638*** 0.310** 0.603***
13HODE 0.318** 0.292*
13HOTrE 0.453*** 0.471*** 0.432*** 0.276* 0.290* 0.342** 0.441***
12- 12-HETE 0.260* 0.383** 0.391** 0.472***
LOX
12-HEPE 0.266* 0.317** 0.539*** 0.501*** 0.512***
Tetranor 0.399*** 0.365** 0.373** 0.386** 0.530*** 0.547***
12-HETE
HXB3 0.350** 0.284* 0.366** 0.440*** 0.485*** 0.290* 0.552***
PGE2-Prostaglandin E; HETE- hydroxyeicosatetraenoic acid; HETrE- hydroxyeicosatrienoic acid; HODE-
Hydroxyoctadecadienoic acid; HOTrE- hydroperoxyoctadecatrienoic acid; HXB3-Hepoxilin B3.* p<0.1,
** p<0.05, *** p<0.01
Conclusion: Eicosanoids, especially in the 12- and 15- LOX pathways, correlated with joint disease activity better than the
CRP, but not with skin disease, suggesting that they may be potential biomarkers of joint activity in psoriatic and PsA
patients. Further studies are needed to determine whether 12- and 15-LOX pathways also play a role in the pathogenesis of
joint inflammation in PsA.
Disclosure: R. Coras, None; A. Kavanaugh, None; D. H. Huynh, None; A. Shadyab, None; S. Marsal, None; O.
Quehenberger, None; M. Guma, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/role-of-eicosanoids-as-biomarkers-in-

psoriatic-arthritis
Genome-Wide DNA Methylation, Transcriptomics, and Proteomics of

Psoriasis and Psoriatic Arthritis in Monozygotic Twins
Angela Ceribelli1, Elvezia Maria Paraboschi2, Natasa Isailovic1, Elena Generali1, Michela Robusto2, Maria De Santis1,
Giulia Cardamone2, Francesco Sacrini3, Antonio Costanzo3, Stefano Duga2 and Carlo Selmi1, 1Rheumatology and Clinical
Immunology, Humanitas Research Hospital, Rozzano (MI), Italy, 2Laboratory of Medical genetics and RNA biology,
Humanitas Research Hospital, Rozzano, Italy, 3Dermatology Unit, Humanitas Research Hospital, Rozzano, Italy
SESSION INFORMATION
Background/Purpose: Psoriatic disease is a chronic inflammatory disorder spanning from skin disease (PsO) to psoriatic
arthritis (PsA) without known serum biomarkers. The genetic background is insufficient to explain disease onset as
illustrated by monozygotic (MZ) twins and epigenetics may contribute to disease susceptibility modulating gene
expression. We analyzed the DNA methylation, transcriptome, and proteomic profile in MZ twins discordant for PsO/PsA.
Methods: MZ twin couples discordant and concordant for PsO/PsA were investigated for (1) genome-wide DNA
methylation (Infinium MethylationEPIC BeadChip), (2) RNA and transcriptome (Illumina TruSeq Stranded mRNA kit),
and (3) proteomics using aptamers (SOMAlogic).Results observed with aptamers were further validated by ELISA.
Results: The epigenetic analysis identified 19 genes consistently differentially methylated and mostly involved in the
pathway of TGF-β and IFN response. Pathway analysis of integrated DNA methylation and transcriptome demonstrated an
enrichment in “transcription regulation”, “innate immunity”, “ATP-binding” and, “Srp-dependent co-translational
proteins”, that may be involved in the psoriatic condition. Serum proteomics reported a significant up- and downregulation
of 10 and 3 proteins, respectively, largely involved in the innate and adaptive immune response, DNA repair and DNA
damage sensors. Validation results showed a significant correlation between the SOMAlogic and ELISA tests for 2 proteins
(respectively r=0.70, p=0.02, and r=0.50, p=0.04) and we confirmed that levels of 3 proteins involved in the regulation of
UV radiation-induced apoptosis and in the cutaneous inflammatory response were elevated in sera from psoriatic disease
patients, albeit not significantly, and one protein involved in hematopoietic and dendritic cell differentiation and apoptosis
was significantly more expressed in both Pso and PsA compared to controls (HC n=2, 20%, Pso+PsA n=18, 60%, p=0.028;
Pso n=10, 66.7%, p=0.02).
Conclusion: We report the first -omics approach in MZ twins discordant for psoriatic disease and suggest that the observed
changes may constitute diasease biomarkers and point to biological pathways with a potential pathogenic role.
Disclosure: A. Ceribelli, None; E. M. Paraboschi, None; N. Isailovic, None; E. Generali, None; M. Robusto, None; M.
De Santis, None; G. Cardamone, None; F. Sacrini, None; A. Costanzo, None; S. Duga, None; C. Selmi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/genome-wide-dna-methylation-

transcriptomics-and-proteomics-of-psoriasis-and-psoriatic-arthritis-in-monozygotic-twins
Role of Mir-21-5p As a Potential Biomarker of Psoriatic Arthritis and

Response to Treatment
Rohan Machhar1, Justine (Yang) Ye1, Vinod Chandran2 and Dafna D Gladman3, 1University of Toronto, Toronto Western
Hospital, Toronto, ON, Canada, 2Rheumatology, University of Toronto, Toronto Western Hospital, Toronto, ON, Canada,
3Rheumatology, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose: Psoriatic arthritis (PsA) is an inflammatory arthritis occurring in patients with psoriasis. miRNA’s
are small non coding RNAs whose main function, at a post transcriptional level, is to modulate the expression of target
genes via translation inhibition or mRNA degradation. A recent study identified miR-215p to be upregulated in early PsA
and early rheumatoid arthritis (RA) and found down regulation post 12 weeks of methotrexate (MTX) treatment. Mir-21-5p
was also found to be upregulated in several inflammatory and autoimmune diseases such as systemic sclerosis, systemic
lupus erythematous, RA, type 1diabetes, and psoriasis. We aimed to determine the role of miR-21-5p as a biomarker for
PsA and response to methotrexate.
Methods: Whole blood RNA samples collected in Tempus tubes from 40 patients with early PsA (<2 years disease
duration and not receiving biologic therapy), 40 patients with PsC who have been confirmed by rheumatologist not to have
PsA (>10 years psoriasis duration, not receiving biologic therapy, and matched to PsA patients on age, sex, psoriasis
duration, and age of psoriasis onset), and 42 HC (matched to patients based on age, sex). RNA was extracted using the
Tempus Spin RNA Isolation Kit with a genomic DNA removal step. miR-21-5p was validated using droplet digital PCR
(ddPCR), a novel and sensitive technology for miRNA quantification. miR-21-5p expression was also measured in 10 PsA
patients before and after 24 weeks of MTX treatment.
Results: The clinical, laboratory and miRNA expression data are presented in Table 1. Significant up regulation of miR-21-
5p was seen in both early PsA and in PsC in comparison to HC (p<0.001). There was more upregulation in early PsA
compared with PsC (p< 0.001), miR-21-5p was significantly down regulated 24 weeks post treatment in 10 patients (p<
0.008) (figure 1).
Conclusion: We have determined the role of miR21-5p as a biomarker for early PsA and response to methotrexate. Our
results support previous work suggesting the potential role of miR21-5P in response to treatment biomarker in early PsA
and as in inflammatory disorder marker.
Fig 1: miR 21-5p expression in PsA patients at baseline and after 24 weeks of therapy (p <0.008).
Table 1: Demographic, clinical and relative expression data
Variable PsA (N=40) PsC (N=40) CTL (N=42) P Value
miR-21-5p* 122.7 (93.1) 58.5 (36.0) 11.5 (9.6) <0.001
Gender - Male 16 (40%) 15 (38%) 15 (38%) 0.97
Gender - Female 24 (60%) 25 (63%) 25 (63%)

Age* 40.7 (11.0) 41.9 (11.0) 43.8 (12.0) 0.002
PASI* 7.1 (10.8) 6.2 (4.4) N/A 0.61
Actively inflamed 6.4 (7.0) NA N/A NA
joints*
CRP (positive), n (%) 6 (15%) 1 (3%) N/A 0.048
*mean±SD; PASI-psoriasis area severity index, actively inflamed joints
tender and/or swollen joints; CRP- C reactive protein.
Disclosure: R. Machhar, None; J. Ye, None; V. Chandran, None; D. D. Gladman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/role-of-mir-21-5p-as-a-potential-

biomarker-of-psoriatic-arthritis-and-response-to-treatment

Investigating the Role of Mechanical Stress in Spondyloarthritis Pathogenesis
Breanna Nguyen1, Robert Colbert2 and Gerlinde Layh-Schmitt1, 1National Institute of Arthritis and Musculoskeletal and
Skin Diseases, National Institutes of Health, Bethesda, MD, 2NIAMS/NIH, Bethesda, MD
SESSION INFORMATION
Background/Purpose: Mechanotransduction is a cell’s ability to translate mechanical stimuli into biochemical signals and
has been implicated in signaling pathways involving differentiation and proliferation. Mechanical stress at entheses and
adjacent tissues has additionally been implicated in the pathogenesis of spondyloarthropathies, such as ankylosing
spondylitis and psoriatic arthritis, by triggering inflammation. However, the mechanisms underlying these processes remain
unclear. This project aims to establish an in vitro system to study the effects of mechanical stress on mesenchymal stem
cells and osteoblasts, specifically examining mineralization and cytokine production.
Methods: Mechanical stress was applied to rat calvarial mesenchymal stem cells (MSCs) using the Flexcell FX-5000
Tension System. This instrument uses a computer-controlled vacuum pump to apply uniform axial strain to cells plated on
silicone bottomed Bioflex plates. For osteogenic differentiation, 3% uniform axial strain was applied to the cells. After
applying strain for 5 days, cells were cultured in osteogenic medium (OS+) to induce differentiation. Mineralization was
measured with Alizarin red stain after 28 days. For measuring cytokine secretion upon stress, MSCs were subjected to 24
hours of 10% strain. ELISA was used to quantify cytokine secretion into cell culture supernatants at 24, 48, and 72h after
stimulation. For all experiments, non-stretched cells were used as controls.
Results: For MSCs cultured in OS+ for 28d, overall mineralization was 2 to 3-fold higher than MSCs cultured in OS-, as
expected. In OS+ conditions, stress resulted in a 12% decrease in mineralization for stretched cells compared to non-treated
controls (p < 0.05). In addition, stress increased secretion of RANTES and IL-6 from MSCs, as determined by ELISA. For
RANTES, stretch led to a 130% increase in production at 24h, a 56% increase at 48h, and a 43% increase 72h after
stimulation (p = 0.06; p < 0.001; p < 0.01, respectively). For IL-6, stretch led to a 324% increase in production at 24h, an
85% increase 48h, and a 55% increase 72h after stimulation (p < 0.01; p < 0.05; p < 0.05, respectively).
Conclusion: These results suggest that mechanical stress can alter osteogenic ability and cytokine secretion from MSCs.
RANTES and IL-6 have been previously shown to play a positive role in bone formation, so further studies are needed to
determine whether these mediators have a biological effect during osteogenesis in this system. Future studies will focus on
optimizing the system and then using it to study the role of ankylosing spondylitis risk genes in MSC and osteoblast
function.
Disclosure: B. Nguyen, None; R. Colbert, None; G. Layh-Schmitt, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/investigating-the-role-of-mechanical-

stress-in-spondyloarthritis-pathogenesis
Reduced Ubiquitination of Misfolded HLA-B27 Is Associated with Inefficient

Degradation By ERAD and Autophagy
Fatemeh Navid1, Gerlinde Layh-Schmitt1, Keith A. Sikora2 and Robert Colbert1, 1National Institute of Arthritis and
Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 2Pediatric Translational Research Branch,
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD
SESSION INFORMATION
Background/Purpose:
The HLA class I allele, HLA-B27, is associated with spondyloarthritis (SpA), an immune-mediated inflammatory disease
affecting the axial skeletal, skin, gut and eyes. HLA-B27 has a tendency to misfold, and accumulate in the endoplasmic
reticulum (ER) and on the cell surface as disulfide-linked dimers. ER accumulation can generate stress resulting in an
unfolded protein response (UPR). The UPR upregulates several pathways that promote folding and secretion and/or ER-
associated degradation (ERAD) of accumulated proteins, which involves retrotranslocation and ubiquitination of target
proteins in the cytosol where they are degraded by proteasomes. Our recent studies suggest that autophagy as well as
ERAD contributes to the disposal of misfolded HLA-B27, yet these pathways are still not sufficient to prevent misfolded
HLA-B27 from accumulating. Since these pathways of protein degradation require substrate ubiquitination, we asked
whether HLA-B27 heavy chains were ubiquitinated using HLA-B7 for comparison.
Methods: Bone marrow derived macrophages from HLA-B27 and human β2m (hβ2m) transgenic rats were examined with
and without IFNγ and proteasome or autophagy inhibitors. Immunoprecipitation, western blotting, and
immunofluorescence were used to measure HLA-B27 heavy chains and ubiquitination mount. Autophagy was activated
using rapamycin, or blocked with bafilomycin. ERAD was inhibited by inhibiting proteasome function with bortezomib.
HLA-B7/hβ2m transgenic rat macrophages were used as controls.
Results: Blocking autophagic flux with bafilomycin resulted in the accumulation of misfolded HLA-B27 dimers and
oligomers as well as monomers, comparable to blocking ERAD with the proteasome inhibitor bortezomib. HLA-B7
monomers also accumulated after blocking each degradation pathway. The proportion of ubiquitinated heavy chains was
~3-fold lower for HLA-B27 compared to HLA-B7. Immunoprecipitation experiments using anti-ubiquitin antibody
followed by blotting for HLA class I heavy chains, further confirmed that HLA-B7 is significantly more ubiquitinated than
HLA-B27. Activation of autophagy with rapamycin rapidly eliminated ~50% of misfolded HLA-B27, while folded HLA-
B27 or HLA-B7 monomeric heavy chains were minimally affected.
Conclusion: These results demonstrate for the first time that both autophagy and ERAD play a role in the elimination of
excess HLA class I heavy chains expressed in transgenic rats. Our results suggest that impaired ubiquitination of HLA-B27
may play a role in the accumulation of misfolded disulfide-linked dimers, whose elimination can be enhanced by activation
of autophagy. Manipulation of the autophagy pathway should be further investigated as a potential therapeutic avenue in
experimental spondyloarthritis.
Disclosure: F. Navid, None; G. Layh-Schmitt, None; K. A. Sikora, None; R. Colbert, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/reduced-ubiquitination-of-misfolded-

hla-b27-is-associated-with-inefficient-degradation-by-erad-and-autophagy
Effect of Anti Tnfα Drugs on the Frequency of Circulating

CD19+CD24hiCD38hi Breg Cells in Ankylosing Spondylitis
M. Belén Bautista-Caro1, Eugenio De Miguel1, Diana Peiteado1, Alejandro Villalba1, Irene Monjo1, Amaya Puig-Kröger2,
Paloma Sanchez-Mateos3, Emilio Martín-Mola1 and Maria Eugenia Miranda-Carus1, 1Rheumatology, Hospital La Paz-
IdiPAZ, Madrid, Spain, 2Immuno-oncology, Hospital Gregorio Marañon, Madrid, Spain, 3Immunology, Hospital Gregorio
Marañon, Madrid, Spain
SESSION INFORMATION
Background/Purpose:
CD19+CD24hiCD38hi B cells demonstrate a regulatory capacity and their frequency is altered in the peripheral blood of
patients with various autoimmune diseases. The pathogenic implication of autoinflammatory and/or autoimmune
mechanisms has been reported in spondyloarthritis (SpA), and an increased frequency of circulating B cells expressing a
regulatory phenotype has been described in SpA (Cantaert T. et al, Arthrits Rheumatol 2012). Therefore our objective was
to study the frequency of CD19+CD24hi CD38hi B cells (Breg) in patients with Ankylosing Spondylitis (AS) naïve for
TNF blockers, and the effect of anti-TNFα drugs on this B cell subset in AS.
Methods:
Peripheral blood was drawn from AS patients naïve for TNFα blockers (AS/nb) (n=42), AS patients who were already
receiving treatment with anti-TNFα drugs (AS/b) (n=59: 37 infliximab, 10 adalimumab, 10 golimumab, 2 certolizumab)
and healthy controls (HC) matched for age and gender (n=101). In addition, six AS/nb patients who were started on anti-
TNFα drugs (2 infliximab, 1 adalimumab, 2 golimumab, 1 certolizumab) donated blood at two time points: right before the
first dose of anti-TNFα was administered and 6 months thereafter. For each of these 6 patients, the same healthy donor
acted as a control on both occasions. After isolation by Ficoll-Hypaque, PBMCs were stained with antibodies to CD3,
CD4, CD19, CD24, and CD38, and examined by cytometry.
Results:
When compared with HC, AS/nb patients demonstrated a significantly increased frequency of Breg cells, which did not
correlate with ASDAS-CRP, serum calprotectin, CRP or ESR values. In contrast, in AS/b patients, the frequency of
circulating Breg cells was not different from HC. The 6 AS/nb patients who started treatment with anti-TNFα drugs
demonstrated a significant reduction of circulating Breg numbers, which were no longer elevated after six months of
treatment. At the same time, a significant decrease of CRP, serum calprotectin and ASDAS-CRP was observed in all 6
patients; in 4 of them, the ∆ASDAS-CRP was > 2.0.
Conclusion:
An increased frequency of circulating CD19+CD24hiCD38hi B cells is observed in AS/nb patients, that does not correlate
not related with disease activity parameters. Treatment with anti-TNFα drugs is able to downmodulate circulating Breg
numbers in AS.
Disclosure: M. B. Bautista-Caro, None; E. De Miguel, None; D. Peiteado, None; A. Villalba, None; I. Monjo, None; A.
Puig-Kröger, None; P. Sanchez-Mateos, None; E. Martín-Mola, Pfizer Inc, Roche, 9; M. E. Miranda-Carus, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effect-of-anti-tnf%ce%b1-drugs-on-the-

frequency-of-circulating-cd19cd24hicd38hi-breg-cells-in-ankylosing-spondylitis
Innate Lymphoid Cells – New Players in Psoriatic Arthritis

Alina Soare1, Stefanie Weber2, Lisa Maul3, Ana Maria Gheorghiu4, Ismail Housni5, Arnd Kleyer6, Markus Luber2, Simon
Rauber2, David Simon6, Juergen Rech6, Georg Schett6, Jörg Distler1 and Andreas Ramming7, 1Department of Internal
Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-
Nürnberg (FAU), Erlangen, Germany, 2Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-
Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen, Erlangen, Germany, 3Department of
Internal Medicine 3 – Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and
University Hospital Erlangen, Erlangen, Germany, 4Carol Davila University of Medicine and Pharmacy,Internal Medicine
and Rheumatology Department ,,Dr.I.Cantacuzino'' Clinical Hospital, Bucharest, Romania, 5Department of Internal
Medicine 3 – Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and
Universitätsklinikum Erlangen, Erlangen, Germany, 6Friedrich-Alexander-University Erlangen-Nürnberg (FAU),
Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen, Germany.,
Erlangen, Germany, 7Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum
Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen, Erlangen,
Germany
SESSION INFORMATION
Background/Purpose: Innate lymphoid cells (ILCs) produce disease-related cytokines including IL-17 and IL-22 and are
therefore of substantial interest in PsA. Spreading the disease from the skin to the joints most likely requires trafficking of
cells through the circulation. Upon perturbation of immune homeostasis, the pool of resident ILCs is replenished by
migration of ILCs into the peripheral blood. Tackling their potential contribution to immunopathology of PsA we
quantified circulating ILC subsets in PsA patients in correlation to disease activity and structural tissue damage.
Methods: 124 patients satisfying the Classification Criteria for Psoriatic Arthritis (CASPAR) and 26 healthy volunteers
were enrolled in the study. Information regarding the tender and swollen joint count of 68 joints, the visual analogue scala
(VAS) of pain and global assessment, presence of plaque psoriasis, psoriatic nail dystrophy, enthesitis, history of
uveitis/iritis, CRP levels, erythrocyte sedimentation rate, imaging results (MRI and high-resolution peripheral quantitative
CT) were collected and disease activity score 28 (DAS28), disease activity in psoriatic arthritis (DAPSA), minimal disease
activity score (MDA) were calculated. MRI and high-resolution peripheral CT were taken and PsA MRI score (PsAMRIS)
was assessed. Flow cytometric analysis was performed and IFNγ-producing ILC1s, IL-4/IL-5-producing ILC2s and IL-
17/IL-22-producing ILC3s were identified among ILCs. Multivariate linear regression and Receiver-Operating
Characteristic (ROC) Curve analysis was performed using the IBM SPSS Statistics software.
Results: Total number of circulating ILCs were increased in PsA patients compared to healthy controls (p˂0,001). Linear
regression analyses of the relationship between disease activity and circulating ILC counts showed that ILC2 negatively (R
= -3732; p < 0.0001) and ILC1 and ILC3 positively correlated with DAPSA score (R = 0.2622, p = 0.0057; R = 0.4092, p <
0.0001 respectively). The strongest correlation was observed when the ratio of ILC2 to ILC3 was analyzed (R = -0.5709; p
< 0.0001). ILC2/3 ratio was also reduced in patients with active psoriatic skin disease, presence of enthesitis or a history of
concomitant uveitis. Extend of synovitis or tenosynovitis or presence of bone erosions or osteophytes on MRI was
inversely correlated with the ILC2/3 ratio (R = -0.6753; p < 0.0001, R = -0.5828; p = 0.0011 and p < 0.001 respectively).
Consistently, presence of erosions and/or osteoproliferation assessed by HR-pQCT was correlated with a significant lower
ILC2/3 ratio. Furthermore, ROC Curve was used to test the performance of the ILC2/3 ratio as marker in differentiating
between remission and disease activity of PsA. Indeed, a cut-off 0.57 exhibited highest sensitivity (92.9%) and a 84.7%
specificity in identifying remission.
Conclusion: We show that perturbed ILC homeostasis is correlated with both composite clinical disease activity scores and
with imaging signs of inflammation and structural damage suggesting pathogenic impact of ILCs in PsA. Further studies
are necessary to validate ILC2/ILC3 ratio as biomarker for immunological disease activity in PsA.
Disclosure: A. Soare, None; S. Weber, None; L. Maul, None; A. M. Gheorghiu, None; I. Housni, None; A. Kleyer,
None; M. Luber, None; S. Rauber, None; D. Simon, None; J. Rech, None; G. Schett, None; J. Distler, 4D Science,
1,Anamar Medical, Active Biotech, Array Biopma, BMS, Bayer Pharma, Boehringer Ingelheim, Celgene, GSK, Novartis,
Sanofi-Aventis, UCB, 2,Actelion Pharmaceuticals US, Active Biotech, Anamar, Bayer Pharma, Boehringer Ingelheim,
Celgene, Galapagos, GSK, Inventiva, JB Therapeutics, Medac, Pfizer, RuiYi, UCB, 5; A. Ramming, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/innate-lymphoid-cells-new-players-in-

psoriatic-arthritis
Prostaglandin E2 and Its Receptor Subtype EP4 Are Involved in Ankylosing

Spondylitis Disease Progression
Archita Srinath1,2,3, Giuliana Guggino4, Ismail Sari5, Fanxing Zeng6, Francesco Ciccia4 and Nigil Haroon5, 1Institute of
Medical Sciences, University of Toronto, Toronto, ON, Canada, 2Genes and Development, University Health Network,
Toronto, ON, Canada, 3Krembil Discovery Tower, Toronto, ON, Canada, 4Rheumatology Unit, University of Palermo,
Palermo, Italy, 5Rheumatology, Toronto Western Hospital, University of Toronto, Spondylitis Clinic, Toronto, ON, Canada,
6University Health Network, Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose: Single Nucleotide Polymorphisms (SNPs) in PTGER4 were found to be associated with
Ankylosing spondylitis (AS) in GWAS. PTGER4 codes for the prostaglandin-E2 receptor EP4. PGE2/EP4 interaction can
affect bone formation and inflammation. We studied serum PGE2 levels and SNPs in PTGER4 in relation to spinal fusion
in AS patients. We further evaluated the interaction of smoking, PGE2 and EP4 in driving IL23 production.
Methods: Patients diagnosed with AS using the modified New York criteria and followed prospectively using a
standardized protocol, were included in this study. Biological samples including serum, gut, synovial and bone marrow
(BM) samples, DNA and RNA were stored and radiographs of the spine obtained every two year to assess progression.
ELISA for Serum PGE2 and immunohistochemistry tissue expression of Prostaglandin-Endoperoxide Synthase 1 (PTGS1),
EP4 and pCREB were performed. Radiographs were scored by modified Stoke Ankylosing Spondylitis Spine
Score(mSASSS). Patients with an increase of ≥ 1 mSASSS unit/year on follow up were deemed progressors. Five PTGER4
single nucleotide polymorphisms (SNPs) satisfying inclusion criteria (associated with AS or related diseases, call rate
above 90%, MAF > 0.1 and not in LD above 0.8) were studied. Immune cell subsets from peripheral blood mononuclear
cells (PBMCs) were analyzed for surface expression of the EP4 receptor. Additionally, PBMCs were incubated with
nicotin, PGE2, or EP4 agonist to determine cytokine expression by flow cytometry and RT-PCR.
Results: Serum PGE2 levels were significantly higher in AS progressors (n=88) than in non-progressors (n = 101)
(p<0.001). In multivariable regression analysis, there was significantly more progression in patients with higher baseline
mSASSS (B =0.02; p = 0.01) and serum PGE2 (B = 0.001; p = 0.002), but lower progression with longer TNF inhibitor use
(B = -0.01; p = 0.03). There was a trend towards higher progression with higher baseline ESR (B = 0.012; p = 0.08). 3) A
total of 172 AS patients had DNA and X-ray data for analysis. Patients with CC genotype of PTGER4 SNP rs6896969 were
significantly more likely to progress compared to AA/AC (OR: 2.45, 95% CI: 1.3 to 4.6; p=0.006). Progressors tended to
more likely be homozygous for the major allele G of the rs4957341 SNP (OR 2.1; 25% CI; 0.98-4.35; p = 0.058). Increased
expression of EP4, PTGS1 and pCREB were observed in the inflamed gut, BM and synovial samples in AS patients. EP4
expression was upregulated in AS monocytes, especially smokers, and the percentage of EP4+ monocytes correlated with
the disease activity evaluated by BASDAI. Sorted EP4+CD14+ cells showed a higher expression of CREB and IL-23
demonstrating the functional relevance of EP4 expression on monocytes. The expression of EP4 is dependent on the
transcription factor AP-2a (TFAP-2a). In vitro stimulation of monocytes with nicotine induced a significant monocyte over-
expression of EP4 and TFAP-2a.
Conclusion: PGE2 and its receptor EP4 are significant players in AS driving both inflammation and spinal fusion. The
complex interaction of smoking, prostaglandin pathway upregulation and Th17 activation via CREB can contribute to the
pathogenesis of AS.
Disclosure: A. Srinath, None; G. Guggino, None; I. Sari, None; F. Zeng, None; F. Ciccia, None; N. Haroon, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prostaglandin-e2-and-its-receptor-

subtype-ep4-are-involved-in-ankylosing-spondylitis-disease-progression
Dyslipidemia Management Is Insufficient in Psoriatic Arthritis Despite

Increased Cardiovascular Morbidity and Mortality
Richard Koch1, JEAN BERNARD RUIDAVETS Sr.2, Yannick Degboe3, Alain Cantagrel3, Adeline Ruyssen-Witrand4,
JEAN FERRIERES5 and Arnaud Constantin3, 1Department of Rheumatology, Purpan Hospital, Toulouse III University,
Toulouse, France, TOULOUSE, France, 2DEPARTMENT OF EPIDEMIOLOGY, URM 1027 INSERM, TOULOUSE
UNIVERSITY HOSPITAL, TOULOUSE, France, 3Department of Rheumatology, Purpan Hospital, Toulouse III
University, Toulouse, France, Toulouse, France, 4Rheumatology, Purpan Hospital, Toulouse III University, Toulouse,
France, 5DEPARTMENT OF CARDIOLOGY, URM 1027 INSERM, TOULOUSE UNIVERSITY HOSPITAL,
TOULOUSE, France
SESSION INFORMATION
Background/Purpose: Psoriatic arthritis (PsA) is associated with increased cardiovascular (CV) morbidity and mortality.
Assessing individual CV risk and achieving the recommended LDL-cholesterol (LDL-C) target could contribute to reduce
the burden of CV disease in PsA. Aims: To compare the prevalence of CV risk factors (CVRFs) and history of CV disease
(CVD) among French PsA patients and age- and sex-matched controls; to quantify individual CV risk using SCORE,
QRISK2 and REYNOLDS risk scores; to assess the proportion of PsA patients or controls achieving the recommended
LDL-C target according to their individual CV risk.
Methods: Observational case-control single-site study. PsA patients (CASPAR criteria), consulting a rheumatologist or
hospitalized in the Rheumatology Department of a French University Hospital between March 2016 and January 2017,
were included in the study after informed consent was obtained. Age- and sex-matched controls (2:1) were extracted from
the Mona Lisa, general population study. CVRF and history of CVD were collected and compared between PsA patients
and controls. Individual CV risk was quantified, using SCORE (with or without using a 1.5 multiplication factor), QRISK2
(with or without including PsA as a CVRF) and REYNOLDS risk scores and compared between PsA patients and controls.
The proportion of PsA patients or controls achieving the recommended LDL-C target according to their individual CV risk
was assessed.
Results: 207 PsA patients and 414 controls were included in this study. CVRF and history of CVD were significantly
increased in PsA patients in comparison with controls (Table1). Individual CV risk was higher in PsA patients in
comparison with controls using SCORE (p=0.002), QRISK2 (p=0.001) and REYNOLDS (p=0.003) risk scores (data not
shown). The proportion of PsA patients or controls achieving the recommended LDL-C target according to their individual
CV risk, quantified using SCORE, was low in both groups (Table 2). Among PsA patients or controls with an individual
risk score ³ 10%, quantified using QRISK2, only 22.9% or 35.8% were respectively treated with a statin.
Conclusion: Our study confirms that the prevalence of CVRF and history of CVD is higher in PsA patients than in
controls. It shows that individual CV risk is higher in PsA patients than in controls, whatever risk score is used for its
quantification. It highlights that a low proportion of PsA patients achieve LDL-C target (SCORE) or initiate a treatment
with a statin (QRISK2) in spite of high individual CV risk.
Table 1. CVRF and history of CVD in PsA patients and controls
PsA Controls
patients
(n=414)
(n=207)
Mean or % Mean SD p
SD
or %
Systolic blood 134 129 22 0.001
15
pressure (mmHg)
Diastolic blood 79 80 12 0.27
11
pressure (mmHg)
BMI (kg/m2) 26.6 4.9 25.2 4.0 0.001
Triglycerides (g/l) 1.24 0.72 1.06 0.63 0.001
LDL (g/l) 1.26 0.38 1.43 0.35 0.001
HDL (g/l) 0.54 0.14 0.59 0.14 0.001
Total cholesterol 2.04 2.23 0.38 0.001
0.43
(g/l)
Hypertension 34.4 26.3 0.03
Diabetes 1 and 2 12.1 7.7 0.09
Dyslipidemia 25.1 42.0 0.001
Smoking 0.04
Never 42.0 48.1
Current 24.2 15.9
Former 33.8 36.0
Metabolic 28.4 11.6 0.001
syndrome
(NCEP2)
Myocardial 5.8 2.9 0.08
infarction
Cerebrovascular 2.4 1.0 0.18
stroke
Peripheral 1.5 0.5 0.23
arterial disease
Cardiovascular
disease 8.7 4.1 0.03
Table 2: Proportion of PsA patients or controls achieving LDL-C target (SCORE)

SCORE PsA % Controls % p
LDL-C n n
Target
SCORE < 122 41 286 22 0.002
5%
50 3.6 63 4.4 0.81
LDL-C
<1.15 g/l 28 13.7 68 3.6 0.27
SCORE 5- 1 3
9%
51 56
LDL-C <
1 g/l 7 2
SCORE ³
10 %
LDL-C <
0.7 g/l
Disclosure: R. Koch, None; J. B. RUIDAVETS Sr., None; Y. Degboe, None; A. Cantagrel, None; A. Ruyssen-Witrand,
None; J. FERRIERES, None; A. Constantin, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/dyslipidemia-management-is-

insufficient-in-psoriatic-arthritis-despite-increased-cardiovascular-morbidity-and-mortality
Functionally Active MAIT Cells in Psoriatic Arthritis: A New Member of the

IL-23/IL-17 Cytokine Network
Siba P. Raychaudhuri1 and Smriti K. Raychaudhuri2, 1Rheumatology Section, Sacramento Veterans Affairs Medical
Center, Sacramento, CA, 2Rheumatology/Immunology, VA Sacramento Medical Center, Davis, CA
SESSION INFORMATION
Background/Purpose: The mucosal-associated invariant T (MAIT) cells recently have been implicated in autoimmune
diseases. Murine model experiments also suggest that MAIT cells are capable of inducing or exacerbating arthritis.
However, their gut origin, effector phenotype and lineage towards IL-23/IL-17 cytokine signatures make them more
relevant for spondyloarthritis rather than RA. More so these cells are predominantly CD8+; thus altogether this
subpopulation of T cells likely to have all the potentials to have a contributing role in the pathogenesis of psoriatic arthritis
(PsA). Here we have explored relevance and functional significance of the MAIT cell in PsA.
Methods: We collected PBMC and synovial fluid mononuclear cells (SFMC) from age/sex matched active untreated PsA
patients (n=10) and normal individuals (n=10). We used two methods to culture and enrich the MAIT cells: (i) the
established method for enrichment of IL-17+ T cell by culturing these cells with rIL-23 for 6 days and (ii) the standard
protocol for MAIT cell culture with PMA/Inomycin. Hi-D FACS studies were done to identify the activated memory
effector CD11a+CD45RO+IL-17+ T cells. MAIT cells were identified as CD3+Vα7.2TCR+CD161high. The percentages of
each cell population and the mean fluorescence intensity (MFI) were analyzed using FlowJo software.
Results: MAIT cells were identified in PBMC and SFMC. In both PsA and controls CD3+IL+17 MAIT cells were
identified in PBMC (<2%). Where as in SFMC it varied between 4%-8% (5.182 ± 0.251%, SD). However we have made
several important observations- (i) Among the IL-17 producing T cells only the MAIT cells were predominantly CD8+ (~
90%), (ii) IL-23R was strongly expressed (~ 20%), and IL-23R was functionally active (iii) rIL-23 induced significant
proliferation of the IL-17+ MAIT cells (Fig 1).
Conclusion: MAIT cells produce multiple inflammatory cytokines (IL-17, IFNγ, and TNFα) thus relevant for several T
cell mediated autoimmune diseases. However Tc17 CD8+ /MAIT cells obviously are more relevant for PsA because of its
MHC class-1 association. Moreover our observation that these cells express functionally active IL-23R brings a new
dimension that once these cells migrates to joint tissue IL-23 can independently regulate these critical Tc17 CD8+ MAIT
cells and thus these cells likely to become a part of the IL-23/IL-17 cytokine network; and there may not be a need for the
MR1 associated presentation of bacterially derived vitamin B metabolites to active these MAIT cells .
Fig 1- A representative FACS plot of rIL-23 induced marked proliferation of the CD3+Vα7.2TCR+CD161highIL-17+ T
cells
Disclosure: S. P. Raychaudhuri, None; S. K. Raychaudhuri, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/functionally-active-mait-cells-in-

psoriatic-arthritis-a-new-member-of-the-il-23il-17-cytokine-network
IL-17 Producing T Cells and Its Dichotomy: A Mixed Response of the Innate
and Acquired Immune System in Psoriatic Arthritis
Siba P. Raychaudhuri1 and Smriti K. Raychaudhuri2, 1Rheumatology Section, Sacramento Veterans Affairs Medical
Center, Sacramento, CA, 2Rheumatology/Immunology, VA Sacramento Medical Center, Davis, CA
SESSION INFORMATION
Background/Purpose: Source of IL-17 in human has been mainly attributed to ab T cells, more specifically to the Th17
cells. However, some reports suggest that cells of the innate immune system: γd T cells and NKT cells may be the major
contributing IL-17 producing cells in psoriatic arthritis (PsA). To have a definite answer; here we have studied arrays of
IL-17 producing T cell phenotypes in PsA including the Mucosal associated invariant T (MAIT) cells.
Methods:
• PBMC and synovial fluid mononuclear cells (SFMC) from age/sex matched active PsA patients (n=15) and normal
individuals (n=15) were collected
• Patients were not on DMARDS or biologics
• rIL-23 induced activated IL-17+ T cells were generated and stained as per our earlier reports (Raychaudhuri SP, etal.
Mol Cell Biochem. 2012 ;359:419-29 ).
• Hi-D FACS studies were done to identify the activated memory effector CD11a+CD45RO+IL-17+ T cells. MAIT
cells were CD3+Vα7.2TCR+CD161high, γd T cells were CD3+γdTCR+, ab T cells were CD3+abTCR+, invariant CD1d-
restricted natural killer (NK) T cells were CD1d/PBS-57 tetramer+CD3+. The percentages of each cell population and the
mean fluorescence intensity (MFI) were analyzed using FlowJo software.
Results:
The percentage of IL-17+ CD3+ T cells was far higher in both PBMC (20.5 ± 0.5%) and SFMC (43± 0.7% ) in PsA
patients compared to 3± 0.5% in PBMC of healthy persons (p<0.001).
Both PBMC and SFMC in PsA patients demonstrated IL-17+ effector memory T cells (TEM) in the following T cell
phenotypes: ab T cells, γd T cells, NKT cells and MAIT cells. The frequency of these CD3+IL-17+ T cells in the PBMC
and SFMC in PsA patients are described in the Table-1 (Table 1). An important observation we noticed that IL-17+ MAIT
cell in SFMC were enriched (5%) compared to 1 % in PBMC and they were predominantly CD8+ (~ 90%).
Conclusion:
· In PsA, pathologic CD11a+CD45RO+IL-17+ T cells are comprised of cells of both the innate and acquired immune
response: ab T cells, γd T cells, MAIT cells and NKT cells.
· However, compared to the other phenotypes, the dominant (~ 80%) IL-17+T cells in PsA (both in PBMC and SFMC)
were conventional T-helper 17 (Th17) CD4+CD11a+CD45RO+abTCR+ T cells (p<0.001%) (Table 1).
· MHC class-1 association, subclinical colitis and enrichment of Tc17 CD8+/MAIT cells in SFMC in PsA could be of
additional pathological significance and needs further evaluation.
Table 1. IL-17 expression (%) in gated CD3+CD11a+CD45RO+ T cells in different T cell phenotypes in SFMC and
PBMC of PsA. αβTCR IL-17+ cells are significantly more than NKT, MAIT and γdTCR, p<0.001.
Table-1 PBMC (% + SD) SFMC (%+ SD)

NKT 15.155 ± 1.275 17.012 ± 2.362
MAIT 1.995 ± 0.089 5.182 ± 0.251
dgTCR 2.907 ± 0.469 1.391 ± 0.229
baTCR 79.943 ± 1.112 76.496 ± 0.224
Disclosure: S. P. Raychaudhuri, None; S. K. Raychaudhuri, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/il-17-producing-t-cells-and-its-

dichotomy-a-mixed-response-of-the-innate-and-acquired-immune-system-in-psoriatic-arthritis
Strain-Dependent IL-17A Secretion By CD4-CD8- DN αβ T Cells Correlates

with Disease Susceptibility in Murine Spondyloarthritis
Imtiyaz Hossain, Mederbek Matmusaev and Joerg Ermann, Division of Rheumatology, Immunology and Allergy,
SESSION INFORMATION
Background/Purpose: Hydrodynamic injection of IL-23 minicircles into adult B10.RIII mice induces an inflammatory
disease with phenotypic features of human spondyloarthritis. Tissue-resident CD4-CD8- double negative (DN) T cells
secreting IL-17A in response to stimulation with IL-23 are thought to be critical in this model. To further dissect disease
pathogenesis, IL-23 minicircle injection into genetically modified mice would be informative. C57BL/6, the background
strain for most genetically engineered mice, has been shown to be less permissive than B10.RIII in several autoimmune or
inflammatory disease models. Here, we tested the susceptibility of C57BL/6 mice to IL-23 minicircle-induced
spondyloarthritis and compared number and function of DN T cells between C57BL/6 and B10.RIII mice.
Methods: Adult C57BL/6 and B10.RIII mice were injected with IL-23 minicircles and monitored clinically for disease
development. IL-23 induction was measured by quantitative PCR (liver tissue) and ELISA (serum). Single cells
suspensions were prepared from blood, liver, spleen, skin and the Achilles tendon enthesis. Cells were analyzed by
multicolor flow cytometry. IL-17A production was measured by intracellular staining after stimulation with IL-23/IL-1β or
PMA/Ionomycin in the presence of Golgi-Stop for 4 hours.
Results: In contrast to B10.RIII mice, C57BL/6 mice were resistant to induction of IL-23 minicircle-induced
spondyloarthritis. While IL-23 expression did not differ between the two strains, C57BL/6 mice failed to develop paw
swelling or psoriasis-like skin changes over the observation period of up to 4 weeks. Frequency and number of DN αβ and
γδ T cells were not different in the five tissues analyzed. However, upon in vitro stimulation, we observed a statistically
significantly higher frequency of IL-17A positive DN αβ T cells in susceptible B10.RIII mice compared with resistant
C57BL/6 animals.
Conclusion: C57BL/6 mice in our animal facility are resistant to IL-23 minicircle-induced spondyloarthritis, which limits
the utility of this model for mechanistic studies. IL-17A secretion by DN αβ T cell but not γδ T cells correlated with strain-
dependent disease susceptibility.
Disclosure: I. Hossain, None; M. Matmusaev, None; J. Ermann, Novartis Pharmaceutical Corporation, 5,UCB,
5,Takeda, 5,SPARTAN/GRAPPA, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/strain-dependent-il-17a-secretion-by-

cd4-cd8-dn-%ce%b1%ce%b2-t-cells-correlates-with-disease-susceptibility-in-murine-spondyloarthritis
Normal Human Enthesis Contains a Resident Population of γδT-Cells

Richard Cuthbert1, Evangelos M. Fragkakis1, Robert Dunsmuir2, Peter Giannoudis3, Elena Jones1, Darren Newton4 and
Dennis McGonagle1, 1Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United
Kingdom, 2Department of Spinal Surgery, National Health Service, Leeds, United Kingdom, 3Academic Department of
Trauma and Orthopaedics, University of Leeds, Leeds, United Kingdom, 4Leeds Institute of Cancer and Pathology,
University of Leeds, Leeds, United Kingdom
SESSION INFORMATION
Background/Purpose:
Recent animal studies have suggested that γδT-cells accumulate at enthesis, secrete IL-17 and are responsible for driving
the spondyloarthritis (SpA) phenotype resulting from IL-23 overexpression in mice (1, 2). In humans examination of the
immunological profile of enthesis has been hampered by lack of tissue. Recently, we used a novel strategy to show that
group 3 innate lymphoid cells are present at the human enthesis (3). Here we extend our methodology to examine the
broader immunological profile of human enthesis and to determine if γδT-cells are also present.
Methods:
Human etheseal soft tissue (EST) and peri-entheseal bone (PEB) was harvested from normal spinous process in patients
undergoing elective spinal orthopaedic procedures. Interspinous EST was dissected from PEB and enzymatically digested,
followed by isolation of mononuclear cells. Flow cytometry was then used to determine the proportion of B-cells (CD45+,
CD19+) NK cells (CD45+, CD3-, CD56+) and T-cells (CD45+, CD3+). T-cells were then sub divided based on expression
of CD4 (T-helper cells), CD8 (Cytotoxic T-cells) and T-cell receptor (TCR) γδ (γδT-cells). For analysis of TCRγδ isoform
cDNA was isolated from peripheral blood, EST and PEB and probed with TCRγδ isoform specific oligonucleotides.
Entheseal data was compared to age-matched peripheral blood from healthy controls.
Results:
Entheseal digests contained on average a lower proportion of T-cells compared to peripheral blood (p=0.018). However, the
proportion of T-cells not expressing either CD4 or CD8 was greater in entheseal tissues (p=0.021). As a proportion of T-
cells, γδT-cells were 6-fold more numerous in EST compared to peripheral blood (p=0.024), and PEB had 3-fold more.
37% of EST γδT-cells expressed CCR6, this compared to 26% and 34% in PEB and peripheral blood respectively. 46% of
EST and 54% PEB entheseal γδT-cells expressed the Vδ1 isoform of the TCR, and clear differences in TCR isoform
expression could be observed between peripheral blood, EST and PEB γδT-cell cDNA.
Conclusion:
γδT-cells are present in normal human enthesis and constitute a greater proportion of the T-cell pool compared to peripheral
blood. A very similar proportion γδT-cells that expressed CCR6, a functional marker for IL-17 production, as was observed
as reported in mice (2). Flow cytometry and transcript analysis indicate a high proportion of γδT-cells expressing the Vδ1
isoform of the TCR, which is also associated with homing to the gut and skin. This is the first description of γδT-cells at the
human enthesis and offers tentative confirmation of findings in mouse models where these cells play a key role in SpA
pathogenesis.
1. Sherlock JP, Joyce-Shaikh B, Turner SP, Chao CC, Sathe M, Grein J, et al. IL-23 induces spondyloarthropathy by acting
on ROR-gammat+ CD3+CD4-CD8- entheseal resident T cells. Nat Med. 2012;18(7):1069-76.
2. Reinhardt A, Yevsa T, Worbs T, Lienenklaus S, Sandrock I, Oberdörfer L, et al. IL‐23‐dependent γδ T cells produce IL‐
17 and accumulate in enthesis, aortic valve, and ciliary body. Arthritis & Rheumatology. 2016.
3. Cuthbert RJ, Fragkakis EM, Dunsmuir R, Li Z, Coles M, Marzo-Ortega H, et al. Human Enthesis Group 3 Innate
Lymphoid Cells. Arthritis Rheumatol. 2017.
Disclosure: R. Cuthbert, None; E. M. Fragkakis, None; R. Dunsmuir, None; P. Giannoudis, None; E. Jones, None; D.
Newton, None; D. McGonagle, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/normal-human-enthesis-contains-a-

resident-population-of-%ce%b3%ce%b4t-cells
Clinical Significance of Non-Albumin Proteinuria for Severity Assessment of

Tubulointerstitial Inflammation in Lupus Nephritis
Oh Chan Kwon1, Seokchan Hong1, Jung Sun Lee2, Byeongzu Ghang1, Doo-Ho Lim3, Wook Jang Seo4, Yong-Gil Kim1,
Chang Keun Lee1 and Bin Yoo1, 1Division of Rheumatology, Department of Internal Medicine, University of Ulsan
College of Medicine, Asan Medical Center, Seoul, Korea, Republic of (South), 2Internal medicine, University of Ulsan
College of Medicine, Asan Medical Center, Seoul, Korea, Republic of (South), 3Division of Rheumatology, Department of
Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea, Republic of (South),
4Seoul Veterans Hospital, Seoul, Korea, Republic of (South)
SESSION INFORMATION
Session Title: Systemic Lupus Erythematosus – Clinical Aspects and Treatment Poster I: Biomarkers and Outcomes
Background/Purpose: Tubulointerstitial inflammation (TI) has been shown to have prognostic significance in renal
outcome of lupus nephritis. Considering that the type of protein excreted in urine is different between glomerular disease
and tubulointerstitial disease, we aimed to determine whether non-albumin proteinuria is associated with severity of TI in
lupus nephritis.
Methods : We included patients with biopsy-confirmed lupus nephritis at a tertiary medical center in Korea from January
2000 to February 2017. Patients were included if their urine protein/creatinine ratio (uPCR) and urine albumin/creatinine
ratio (uACR) were simultaneously measured. All included patients met the ACR criteria for classification of systemic lupus
erythematosus. Clinical and laboratory variables including C3 and C4 levels as well as anti-double strand DNA (anti-
dsDNA) antibody titers were collected. Non-albumin proteinuria was calculated by subtracting uACR from uPCR (uPCR –
uACR). Renal pathology including International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification
2003, activity and chronicity indices, and severity of TI was reviewed. Logistic regression analysis was performed to
identify the clinical and laboratory parameters associated with TI severity.
Results: Of the total 36 patients, 27 (75%) had no -to -mild TI and 9 (25%) had moderate -to -severe TI. 31 (86.1%) had
proliferative type glomerulonephritis (class III ¡¾ V and IV ¡¾ V) and 5 (13.9%) had non-proliferative type
glomerulonephritis (class II and V). In logistic regression analysis, the following factors were significantly associated with
moderate -to -severe TI: uPCR (odds ratio [OR] 1.599, 95% confidence interval [CI] 1.025-2.494, p = 0.039) and non-
albumin proteinuria (uPCR – uACR) (OR 3.558, 95% CI 1.147-11.038, p = 0.028).
Conclusion: In lupus nephritis, non-albumin proteinuria, as assessed by the difference between uPCR and uACR, was
associated with severity of TI, to a more relevant degree than uPCR alone. Thus, measuring non-albumin proteinuria can be
a valuable non-invasive method for assessing the severity of TI in lupus nephritis.
Table 1. Factors associated with TI severity

Odds ratio 95% CI P value
Age 1.034 0.988-1.082 0.148
Female 4.706 0.511-43.361 0.172
uACR 1.596 0.921-2.764 0.095
uPCR 1.599 1.025-2.494 0.039
uAPR 0.154 0.004-6.650 0.330
uPCR – uACR 3.558 1.147-11.038 0.028
Cr 5.235 0.645-42.506 0.121
C3 1.007 0.964-1.052 0.748
C4 0.942 0.750-1.182 0.604
Anti-dsDNA 0.946 0.850-1.054 0.314
GN activity index 1.086 0.883-1.336 0.435
GN chronicity index 1.000 0.283-3.528 >0.999
ISN/RPS class N/A N/A >0.999
(proliferative GN)
Disclosure: O. C. Kwon, None; S. Hong, None; J. S. Lee, None; B. Ghang, None; D. H. Lim, None; W. J. Seo, None; Y.
G. Kim, None; C. K. Lee, None; B. Yoo, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/clinical-significance-of-non-albumin-

proteinuria-for-severity-assessment-of-tubulointerstitial-inflammation-in-lupus-nephritis
Urinary Tumor-Necrosis Factor-like Weak Inducer of Apoptosis Is an

Important Biomarker for Renal Lupus
Michelle Petri1, Daniel Goldman2, Linda Burkly3, Nicolas Wisniacki4, Chris Stebbins3 and Laurence S Magder5,
1Medicine (Rheumatology), Division of Rheumatology, Johns Hopkins University School of Medicine, MD, USA,
Baltimore, MD, 2Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, 3Biogen, Cambridge, MA,
4GlaxoSmithKline, London, United Kingdom, 5Epidemiology and Public health, University of Maryland School of
Medicine, Baltimore, MD
SESSION INFORMATION
Background/Purpose: Tumor-necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) drives release of
proinflammatory mediators from renal tubular and mesangial cells, and has been implicated in the pathogenesis of lupus
nephritis, angiogenesis and fibrosis. We examined the utility of urinary levels of TWEAK (uTWEAK) as a biomarker for
lupus nephritis activity in patients with systemic lupus erythematosus (SLE).
Methods: 296 SLE patients in a longitudinal cohort had urine collected at baseline and analyzed by an ELISA for TWEAK
developed by Biogen. Urine TWEAK (uTWEAK) concentration was normalized by dividing by urine creatinine
concentration. Patients were subsequently seen at regular intervals of three months. At every visit, assessment of disease
activity was recorded using SELENA-SLEDAI, BILAG-2004 and the Physician’s Global Assessment (PGA). Standard of
care laboratory tests were also performed at each visit.
Results: uTWEAK was associated with ethnicity (highest in Asians) and strongly associated with prednisone dose. Table 1
shows the relationship of uTWEAK with organ specific SLE activity. uTWEAK was only associated with renal activity. It
was negatively associated with serum creatinine (r = -0.25, p < 0.00001). The association of uTWEAK with urine
protein/cr was mainly seen after uTWEAK/creatinine ratio of approximately 0.12.
Table 1: Risk of specific types of SLE disease activity by urinary TWEAK levels at the same visit.
SLE Disease Activity Urinary TWEAK / Creatinine Ratio P-value
1 st 2 nd 3 Quartile 4 Quartile (trend)
rd th
(SLEDAI descriptors)
Quartile Quartile
(n=74) (n=74)
(n=74) (n=74)
Renal 7 (9%) 5 (7%) 12 (16%) 14 (19%) 0.030
--Proteinuria > 500 mg 5 (7%) 5 (7%) 10 (14%) 13 (18%) 0.017
--Hematuria 0 (0%) 0 (0%) 1 (1%) 3 (4%) 0.025
--Pyuria 2 (3%) 0 (0%) 3 (4%) 1 (2%) 1.00

Skin 24 (32%) 23 (31%) 19 (26%) 21 (28%) 0.46
Hematologic 1 (1%) 3 (4%) 5 (7%) 3 (4%) 0.29
Musculoskeletal 1 (1%) 2 (3%) 3 (4%) 3 (4%) 0.29
Immunologic 22 (30%) 21 (28%) 22 (26%) 20 (27%) 0.77
uTWEAK at baseline was predictive of renal activity over the next year (Table 2).
Table 2: Risk of specific types of SLE disease activity in visits made in the next year by urinary TWEAK levels.
SLE Disease Activity Urinary TWEAK / Creatinine Ratio P-value1
1st 2nd 3rd Quartile 4th Quartile
Quartile Quartile
(n=228) (n=239)
(n=240) (n=224)
Renal 11 (5%) 18(8%) 36 (16%) 43 (18%) 0.016
--Proteinuria 10 (4%) 12 (6%) 36 (16%) 40 (17%) 0.011
--Hematuria 1 (<1%) 1 (<1%)) 15 (7%) 11 (5%) 0.011
--Pyuria 2 (1%) 9 (4%) 5 (2%) 9 (4%) 0.28

Skin 74 (31%) 69 (31%) 65 (29%) 51 (21%) 0.16
Hematologic 9 (4%) 10 (4%) 10 (4%) 10 (4%) 0.84
Musculoskeletal 8 (3%) 7 (3%) 3 (1%) 15 (6%) 0.35
Immunological 71 (30% 53 (24%) 72 (32%) 72 (30%) 0.80
1 Based on a test for trend, imputing scores of 0,1,2,3 for the consecutive quartiles, accounting for repeated measures on the
same patient using GEE.
Conclusion: In a clinical trial, blocking TWEAK did not improve renal lupus. However, our results show that uTWEAK
still has great utility as a lupus nephritis marker, as uTWEAK is only associated with renal activity and does not correlate
with non-renal activity. In addition, it predicts renal activity over the next year.
Disclosure: M. Petri, Anthera Inc, 5,GlaxoSmithKline, 5,EMD Serono, 5,Eli Lilly and Company, 5,Bristol Meyer Squibb,
5,Amgen, 5,United Rheumatology, 5,Global Academy, 5,Exagen, 2; D. Goldman, None; L. Burkly, Biogen Idec, 3; N.
Wisniacki, GlaxoSmithKline, 3; C. Stebbins, Biogen, 3; L. S. Magder, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/urinary-tumor-necrosis-factor-like-

weak-inducer-of-apoptosis-is-an-important-biomarker-for-renal-lupus
Low Vitamin D Is Associated with Thrombosis in Systemic Lupus

Erythematosus
Michelle Petri1, Wei Fu2 and Daniel Goldman2, 1Medicine (Rheumatology), Division of Rheumatology, Johns Hopkins
University School of Medicine, MD, USA, Baltimore, MD, 2Rheumatology, Johns Hopkins University School of Medicine,
Baltimore, MD
SESSION INFORMATION
Background/Purpose: Low vitamin D is common in systemic lupus erythematosus (SLE). It is also found in
antiphospholipid syndrome. Vitamin D has effects on tissue factor, PAI-1, thrombomodulin and platelet aggregation that
suggest it has an anti-thrombotic role. We asked whether low vitamin D was associated with thrombosis in SLE, adjusting
for lupus anticoagulant.
Methods: A total of 1,392 SLE patients were included in the analysis. At the first visit when vitamin D was measured,
76.7% had levels of 25-hydroxyvitamin D <40 ng/mL. The SLE patients were: 92% female, mean age 42.9 years, and
ethnicity 50% Caucasian, 41% African American. 27% patients had a history of thrombosis; 7% stroke, 4% MI and 14%
DVT.
Results: Vitamin D, measured either as a continuous variable or as “low” (<40 ng/mL) vs. normal, was associated with any
thrombosis and with DVT.
Table 1: Associations of First Vitamin D Measurement with Thrombosis

Positive for Thrombotic No Thrombotic
Event Event
Mean (SD) N (%) Mean N (%)
(SD) P-value
Any Thrombotic Event
Vitamin D (ng/ml) 27.6(15.1) 30.6(14.6) 0.0008
(Mean/SD)
Vitamin D < 40 ng/ml 299(80.4) 759(75.4) 0.064
(N/ %)
Stroke
Vitamin D (ng/ml) 28.9(15.2) 29.9(14.7) 0.5408
(Mean/SD)
Vitamin D < 40 ng/ml 79(75.2) 988(76.9) 0.7914
(N/ %)
Myocardial Infarction (MI)
(SD)
Vitamin D (ng/ml) 30.2(16.9) 29.8(14.7) 0.883
(Mean/SD)
Vitamin D < 40 ng/ml 35(70) 1032(77) 0.3258
(N/ %)
DVT
(SD)
Vitamin D (ng/ml) 25.9(13.4) 30.4(14.9) <0.0001
(Mean/SD)
Vitamin D < 40 ng/ml 171(87.2) 895(75) 0.0002
(N/ %)
We next adjusted for race, age, sex and lupus anticoagulant. Low vitamin D remained associated with DVT.
Table 2 Summary of Adjusted Odds Ratio for Low Vitamin D (< 40 ng/ml)
Dependent Variables Unadjusted OR (95% CI) Adjusted OR (95% CI)
Any Thrombosis 1.33 (0.99,1.79) 1.36 (0.99,1.86)
Stroke 0.91 (0.58,1.45) 0.92 (0.57,1.48)
MI 0.7 (0.38,1.29) 0.8 (0.42,1.53)
DVT 2.28 (1.47,3.54) 2.31 (1.47,3.65)
We next looked prospectively: this analysis excluded thrombotic events before the first vitamin D measurement. It allowed
for vitamin D to be a time-varying variable, as replacement therapy was given if it was low. After adjustment for race, age
and sex, the adjusted hazard ratio remained significant for any thrombosis: 1.75 (1.04,2.92).
Conclusion: Low vitamin D was significantly associated with any thrombosis and with DVT (even after adjustment for
lupus anticoagulant). In prospective models it remained significantly associated with any thrombosis. As supplementation
with vitamin D was proven to reduce thrombosis in an oncology randomized clinical trial, vitamin D replacement should
become routine in SLE patients at risk for thrombosis.
5,Amgen, 5,United Rheumatology, 5,Global Academy, 5,Exagen, 2; W. Fu, None; D. Goldman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/low-vitamin-d-is-associated-with-

thrombosis-in-systemic-lupus-erythematosus
Low Vitamin D Is Associated with End Stage Renal Disease in Systemic

Lupus Erythematosus
Michelle Petri1, Wei Fu2 and Daniel Goldman2, 1Medicine (Rheumatology), Division of Rheumatology, Johns Hopkins
University School of Medicine, MD, USA, Baltimore, MD, 2Rheumatology, Johns Hopkins University School of Medicine,
Baltimore, MD
SESSION INFORMATION
Background/Purpose: Vitamin D insufficiency/deficiency is common in SLE. Replacement therapy may help renal
disease activity. We asked whether low vitamin D predicted later organ damage.
Methods: We considered all follow-up after a patient’s first measure of vitamin D. The first measure of vitamin D usually
occurred in late 2009 or 2010 for existing patients and at the first visit of new patients after that. The patients were
categorized based on their first measure of vitamin D as <20 ng/mL versus 20+ ng/mL. A total of 1,392 SLE patients were
included in the analysis. At the first visit when vitamin D was measured, 27.3% had levels of 25-hydroxy vitamin D <20
ng/ml. The SLE patients were: 92% female, mean age 47.3 years and ethnicity 50% Caucasian, 41% African American.
Results: Risk of lifetime organ damage was calculated, using SLICC/ACR Damage Index.
Table 1: Risk of organ damage adjusted for age, gender and ethnicity.
Categorical Vitamin D (< 20 ng/ml as abnormal)
RR (95% P- Adjusted RR Adj. P-
CI) Value (95% CI) Value
0.97
Ocular Damage (0.76,1.25) 0.83 1.10 (0.86,1.4) 0.4388
Neuropsychiatric 0.95
Damage (0.73,1.24) 0.7222 1.04 (0.79,1.36) 0.7979
1.87
Renal Damage (1.23,2.84) 0.0033 1.66 (1.08,2.54) 0.0206
1.01
Pulmonary damage (0.74,1.38) 0.9321 1.04 (0.77,1.41) 0.7888
Cardiovascular 1.11
Damage (0.77,1.59) 0.5882 1.20 (0.83,1.74) 0.3396
Peripheral Vascular
Damage 1.18 (0.7,2) 0.5346 1.23 (0.75,2) 0.4134
Gastrointestinal 0.91
Damage (0.65,1.26) 0.553 1.04 (0.74,1.46) 0.8093
Musculoskeletal 1.03
Damage (0.82,1.28) 0.8208 1.09 (0.86,1.37) 0.4706
1.69
Skin Damage (1.11,2.57) 0.0145 1.22 (0.8,1.84) 0.3561
1.11
Total Damage (0.97,1.28) 0.1246 1.17 (1.02,1.33) 0.0245
Conclusion: Low vitamin D associated with total damage and with End Stage Renal Disease. As vitamin D
supplementation reduces proteinuria, this further suggests that vitamin D supplementation should be part of treatment of
lupus nephritis. Surprisingly, low vitamin D did not associate with musculoskeletal damage (including with the subtype of
osteoporotic fractures).
5,Amgen, 5,United Rheumatology, 5,Global Academy, 5,Exagen, 2; W. Fu, None; D. Goldman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/low-vitamin-d-is-associated-with-end-

stage-renal-disease-in-systemic-lupus-erythematosus
Vitamin D Deficiency Is Associated with Increased Serum Cholesterol Among

Patients with Systemic Lupus Erythematosus
Michelle Petri1, Daniel Goldman2 and Laurence S Magder3, 1Medicine (Rheumatology), Division of Rheumatology,
Johns Hopkins University School of Medicine, MD, USA, Baltimore, MD, 2Rheumatology, Johns Hopkins University
School of Medicine, Baltimore, MD, 3Epidemiology and Public health, University of Maryland School of Medicine,
Baltimore, MD
SESSION INFORMATION
Background/Purpose: Vitamin D insufficiency/deficiency is common in SLE. In other populations, vitamin D has been
associated with cardiovascular risk factors such as blood pressure and serum cholesterol. We assessed whether there was an
association between serum vitamin D and total serum cholesterol in a large SLE cohort.
Methods: Serum 25-hydroxy vitamin D [25(OH)D] was measured at quarterly clinic visits in a large SLE cohort. 1358
different patients were observed from 1 to 40 visits (the median was 11). The patients were 92% female, 50% Caucasian,
41% African American. Age ranged from 17 to 89 years. When the 25(OH)D level was below 40 mg/ml, the patient was
prescribed supplemental vitamin D, usually 50,000 IU weekly. We explored the association between serum vitamin D
levels and serum cholesterol using longitudinal regression models.
Results: Levels of 25(OH)D below 50 ng/ml were associated with a higher mean cholesterol. There was a significantly
negative linear relationship between vitamin D and mean cholesterol when 25(OH)D was below 50 ng/ml.
Table 1: Slope of Relationship Between 25(OH) Vitamin D and Mean Cholesterol Over Different Ranges of 25(OH)
Vitamin D
Range of 25(OH) Estimated slope (95% Confidence Interval)
Vitamin D Unadjusted P-value Adjusted P-value
0-50 ng/ml -0.37 (-0.42, -0.32) <0.0001 -0.30 (-0.35, -0.24) <0.0001
50+ ng/ml -0.09 (-0.15, -0.02) 0.014 -0.11 (-0.18, -0.03) 0.0037
1 Adjusted for age, age-squared, sex, race, proportion of time on hydroxychloroquine use, corticosteroid use, BMI and
systolic blood pressure.
Conclusion: We observed a decline in total cholesterol as vitamin D increased to the normal range. Vitamin D
supplementation significantly reduced cholesterol, even after adjustment for hydroxychloroquine. Vitamin D, like
hydroxychloroquine, has benefit beyond immunomodulation, in that it reduces multiple cardiovascular risk factors.
5,Amgen, 5,United Rheumatology, 5,Global Academy, 5,Exagen, 2; D. Goldman, None; L. S. Magder, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/vitamin-d-deficiency-is-associated-

with-increased-serum-cholesterol-among-patients-with-systemic-lupus-erythematosus
Urinary Metabolomic Fingerprint As Diagnostic Biomarker for Clinical

Significant Lupus Nephritis
David Herrera Van Oostdam1, Rogelio Flores Ramirez2, Maribel Rodriguez Aguilar2, Mauricio Pierdant Pérez3, Carlos
Abud-Mendoza4, David Martínez-Galla5 and Marco Ulises Martinez-Martinez6, 1Unidad de Investigaciones
Reumatológicas, Hospital Central & Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí,
Mexico, 22. Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología, San Luis Potosí, San Luis Potosi,
Mexico, 3Universidad Autónoma de San Luis Potosí, San Luis Potosi, Mexico, 4Unidad de Investigaciones
Reumatológicas y Osteoporosis, Faculty of Medicine, Universidad Autónoma de San Luis Potosí and Hospital Central, San
Luis Potosí, Mexico, 5Pathology, Hospital Central "Dr. Ignacio Morones Prieto", San Luis Potosí, Mexico, 6Unidad de
Investigaciones Reumatológicas, Faculty of Medicine, Universidad Autónoma de San Luis Potosí and Hospital Central,
San Luis Potosí, Mexico
SESSION INFORMATION
-Background/Purpose: Lupus nephritis (LN) represents the main prognostic factor in systemic lupus erythematosus (LES)
[1]. The clinical significant classes of LN –due to the need of treatment- are the proliferative (III, IV), membranous (V) and
mixed classes (III or IV/V). The aim of the study was to find a urinary metabolomic fingerprint to diagnose classes III, IV
and/or V of LN
-Methods: Cross-sectional study. Inclusion criteria: lupus patients with and without clinical significant lupus nephritis
(classes III, IV, V and mixed classes). Urine samples were screened for metabolites using gas chromatography mass
spectrometry (coupled with electronic nose) and principal component analysis for metabolite selection.
-Results: We included 29 lupus patients, 11 with LN and 18 without LN. Age between groups were 26 years (IQR 14.5) in
patients with LN and 33 (IQR 22.3) in patients without LN (p 0.48). The median SLEDAI score in LN patients was of 13
and 3 in those without NL (p <0.0001). Class IV nephritis was present in 45% of LN patients, mixed class in 36%, and
class V in 18%. The median proteinuria of patients with NL was 1g/L, (IQR 2.7). We observed differences in metabolic
fingerprint in patients with and without LN, with an AUC 90%. Metabolic pathway analysis was conducted, and we found
several pathways involved, like methane, glycolysis, pyruvate and glycerophospholipid pathways. The most significant
metabolites of the PCA that discriminated LN, were 2-nonanone with a sensitivity of 0.87 and specificity of 0.93.
Obtaining the ratio of 2-bromopropane with 2-nonanone, the diagnostic accuracy improved, with a positive likelihood ratio
(LR) of 14 and a negative LR of 0.1.
-Conclusion: We identified a urinary metabolomic fingerprint that involved several metabolic pathways; 2-nonanone and
the ratio of 2-bromopropane/2-nonanone had the best diagnostic accuracy in our study.
-References: 1. Mok CC, Kwok RCL, Yip PSF. Effect of renal disease on the standardized mortality ratio and life
expectancy of patients with systemic lupus erythematosus. Arthritis Rheum. 2013;65:2154–60
Disclosure: D. Herrera Van Oostdam, None; R. Flores Ramirez, None; M. Rodriguez Aguilar, None; M. Pierdant
Pérez, None; C. Abud-Mendoza, Bristol-Myers Squibb, Pfizer Inc, Roche, 5,Bristol-Myers Squibb, Merck-Serono, Pfizer
Inc, Roche, UCB, 8; D. Martínez-Galla, None; M. U. Martinez-Martinez, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/urinary-metabolomic-fingerprint-as-

diagnostic-biomarker-for-clinical-significant-lupus-nephritis
Is Uric Acid Level a Predictor of Long-Term Renal Outcome in Lupus

Nephritis?
Michelle Lopes1, Samara Gavinier2, Elaine Leon2, Vilma Viana2, Eduardo Ferreira Borba1 and Eloisa Bonfa3,
1Rheumatology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, 2Rheumatology, Hospital das
Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR, São Paulo, Brazil,
3Rheumatology Divison, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
SESSION INFORMATION
Background/Purpose: Hyperuricemia has been reported to be associated with chronic kidney disease (CKD) in several
clinical conditions, and recent studies also observed an association between increased uric acid (UA) serum levels and renal
damage in lupus. However, the predictive value of UA for the development of long-term renal dysfunction in lupus
nephritis is unknown. The purpose of this study was to evaluate if the UA level may be considered a predictor of long-term
renal outcome in patients with lupus nephritis.
Methods: 75 biopsy-proven lupus nephritis patients with more than 7 years follow-up were consecutively selected for this
study. Clinical and laboratorial data were obtained using a standardized electronic chart database protocol carried out at 1-6
months interval. UA levels were measured in sera stored at -70ºC for all SLE patients at biopsy during nephritis flare and in
31 patients, for whom sera were available, at 6 and 12 months post-biopsy. The renal outcome was addressed after 7 years
of follow-up to determine if UA was a predictor of good long-term renal outcome (Cr<1.5mg/dL in 7 years). SLE patients
were divided in two groups according to the renal outcome [good outcome (Cr<1.5mg/dL in 7 years) and poor outcome
(Cr≥1.5mg/dL in 7 years)] to assess whether UA levels at different time-points of follow-up were able to differentiate such
groups. ROC curves were plotted to assess UA accuracy.
Results: At baseline, patients had mean SCr of 1.7±1.3 mg/dl, proteinuria of 5.7±4.7 g/24h, albumin of 2.4±0.8 g/dl, and
SLEDAI scores of 9.5±5.0. Almost two thirds of the patients (66%) patients had positive anti-dsDNA and 28 patients
(35%) had SCr≥1.5mg/dl. The distribution of histological classes among studied patients was: class II (6%), class III / IV
(53%) and pure class V (36%). Serum UA levels were not able to differentiate good from poor long-term renal outcomes in
patients with lupus nephritis at any of the time points analyzed: baseline, 6, 12 months (respectively p = 0.96, p = 0.76, p =
0.77). As expected, the ROC curve with higher AUC (12 months) showed a low accuracy (AUC=0.59). The cut-off for UA
was 5.46mg/dL (Sensitivity=0.63, Specificity= 0.65, Positive Predictive Value=0.38, Negative Predictive Value=0.16, 95%
CI=0.2-0.7, p<0.05). The AU was only associated with the current creatinine levels: at baseline (p=0.01), 6 months
(p=0.03) and 12 months (p=0.01).
Conclusion: This study demonstrated that serum uric acid levels in lupus patients reflect solely the current renal function
and it is not a good predictor of long-term renal outcome in lupus nephritis.
Disclosure: M. Lopes, None; S. Gavinier, None; E. Leon, None; V. Viana, None; E. F. Borba, None; E. Bonfa, None, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/is-uric-acid-level-a-predictor-of-long-

term-renal-outcome-in-lupus-nephritis
Unbiased Screening of Urinary Protein Biomarkers for Glomerular

Filtration Rate Normalization
Sanam Soomro1, Samantha Stanley2, Ramesh Saxena3, Michelle Petri4 and Chandra Mohan1, 1Biomedical Engineering,
University of Houston, Houston, TX, 2Biomedical Engineering Department, University of Houston, Houston, TX, 3Internal
Medicine/Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX, 4Medicine
(Rheumatology), Division of Rheumatology, Johns Hopkins University School of Medicine, MD, USA, Baltimore, MD
SESSION INFORMATION
Background/Purpose: To account for glomerular filtration rate, urinary creatinine is routinely used for the normalization
of urine biomarkers related to disease. Because of the small size of this metabolite, antibodies are difficult and expensive to
develop, limiting the applications of disease-specific urine protein biomarkers for antibody-based point of care applications.
Methods: An aptamer-based screening of 1129 proteins in 24 human urine samples (8 active lupus nephritis (LN), 8
inactive LN, 8 healthy controls (HC)) was carried out to identify urine proteins that correlated well with urine creatinine but
not disease.
Results: The screen uncovered 18 proteins that correlated well with urinary creatinine but were similar in patients with or
without nephritis. Further validation in an independent cohort of 48 subjects (16 active LN, 16 inactive LN, 16 HC) showed
a significant positive correlation of urine HVEM, RELT, and Dectin-1 to urinary creatinine. The most promising marker,
urine HVEM, was significantly correlated to urinary creatinine in both white (Pearson r = 0.7229, P = 0.0001) and black
subjects (Pearson r = 0.6111, P = 0.0009). Finally, normalization of other urinary biomarker proteins against urine HVEM
showed comparable fold change and statistical significance as normalization to urinary creatinine.
Conclusion: Instead of the metabolite creatinine, proteins such as HVEM, RELT and Dectin-1 can be used for
normalization of urine biomarkers. The use of proteins instead of metabolites for normalization paves the way towards
novel diagnostic approaches.
Urine HVEM, RELT, and Dectin-1 were validated by ELISA and found to be significantly correlated with urinary
creatinine. HVEM, the most promising marker for GFR normalization, was also used to normalize ALCAM, a biomarker
for SLE, to have comparable fold change and statistical significance as normalization to urinary creatinine.
Disclosure: S. Soomro, None; S. Stanley, None; R. Saxena, None; M. Petri, None; C. Mohan, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/unbiased-screening-of-urinary-protein-

biomarkers-for-glomerular-filtration-rate-normalization
Membrane Attack Complex (MAC) Deposition in Lupus Nephritis Is

Associated with Hypertension and Poor Clinical Response to Treatment
Shudan Wang1, Ming Wu2, Luis Chiriboga3, Briana Zeck4 and H. Michael Belmont5, 1Department of Medicine, Division
of Rheumatology, New York University School Medicine, New York City, NY, 2New York University School of Medicine,
New York, NY, 3Pathology, New York University School Medicine, New York, NY, 4Pathology, New York University
School Medicine, New York City, NY, 5Medicine, New York University School of Medicine, New York, NY
SESSION INFORMATION
Background/Purpose:
LN is characterized by deposition of immune complexes in the kidney. Activation of the classical complement pathway by
dsDNA is believed to play a role in its pathogenesis. The relative importance of C5a generation versus MAC involvement
in tissue injury remains uncertain. We study immunohistochemistry staining for C9 in renal biopsies as a marker for
intensity of kidney damage and clinical response to therapy.
Methods:
Chromogenic immunohistochemistry was performed on formalin-fixed, paraffin-embedded, 4-µm human renal biopsy
sections using unconjugated, murine anti-human Complement C9 (Hycult Biotech, clone X197) from SLE patients who
fulfill 4 ACR or SLICC criteria. Positive control is C3 glomerulopathy and negative control is normal kidney. Clinical
parameters assessed at time of biopsy and 6 months. Student t-test, Fisher’s exact test, and logistic regression were
performed in SAS.
Results:
30 renal biopsies were obtained from SLE patients with LN Class II (2), III (5), IV (8), V (5), III+V (8) and IV+V (2) This
study included 24 women and 6 men, mean age 32.9 ± 12.1 years, with 4 Asians, 9 Blacks, 11 Hispanics and 6 Caucasians.
13/30 (43.3%) biopsies stained positive for glomerular C9 (Figure 1). Patients with +C9 have significantly higher
systolic/diastolic BP, trend towards lower C3, and male gender; known predictors of poor renal outcomes (Table 1). There
was no significant difference for ISN/RPN class, activity or chronicity indices between +C9 vs. –C9 groups. Five (45.5%)
of 11 patients with +C9 did not respond to therapy at 6 months (defined as <50% reduction in proteinuria), compared with
2/15 (13.3%) patients with –C9. No difference in induction or maintenance therapy and compliance to therapy was found
between +C9 and –C9 groups. +C9 patients were significantly more likely to be a non-responder at 6 months (OR=5.3,
95% CI 0.8, 36.4) compared to –C9 patients. After adjusting for systolic BP, compliance to treatment and proteinuria at
time of biopsy in a multivariate logistic model, +C9 patients remain more likely to be non-responders (OR=4.3, 95% CI
0.3, 65.2).
Conclusion:
This study demonstrates that MAC deposition is a biomarker for more intense disease and that targeting C5a may be
insufficient for controlling inflammation and damage in LN. MAC staining may be useful in routine IF studies of suspected
or known lupus renal biopsies to identify patients at risk for aggressive and refractory disease and who may be candidates
for novel therapies targeting terminal complement pathway.
TABLE 1: Comparison of demographics, clinical and laboratory characteristics
Demographics and Clinical Positive for Negative for P- Value
Glomerular C9 Glomerular C9
(n = 13) (n = 17)
Age (µ ± SD years) 34.3 ± 12.5 31.8 ± 12.0 0.577
Male, n (%) 5 (38.5%) 1 (5.9%) 0.061
Ethnicity, n (%)
Asian 2 (15.4%) 2 (11.8%)
Black 3 (23.1%) 6 (35.3%)
0.806
Hispanic 6 (46.1%) 5 (29.4%)
White 2 (15.4%) 4 (23.5%)
Taking Plaquenil, n (%) 9 (69.2%) 14 (82.4%) 0.666

Taking Prednisone, n (%) 8 (61.5%) 11 (64.7%) 1.000
SLEDAI (µ ± SD) 10.7 ± 3.5 10.3 ± 4.2 0.784
Systolic BP (µ ± SD mm/Hg) 133.1 ± 15.3 116.6 ± 12.4 0.003
Diastolic BP (µ ± SD mm/Hg) 82.3 ± 9.5 70.1 ± 15.4 0.018
Laboratory
Serum Creatinine (µ ± SD 1.2 ± 1.2 1.0 ± 1.2 0.690
mg/dL)
Serum Albumin (µ ± SD g/dL) 2.8 ± 0.9 3.0 ± 0.4 0.425
Urine protein (µ ± SD g/24hr) 4.1 ± 3.3 4.2 ± 4.3 0.891
Serum C3, n (%)

C3 ≥ 80 mg/dL 1 (7.7%) 6 (35.3%)
0.104
C3 < 80 mg/dL 12 (92.3%) 11 (64.7%)
Serum C4, n (%)

C4 ≥ 14 mg/dL 3 (23.1%) 7 (41.2%)
0.440
C4 < 14 mg/dL 10 (76.9%) 10 (58.8%)
DsDNA, n (%)
Low (0-75 IU/mL) 6 (46.1%) 7 (41.2%)
Borderline High (76-300 5 (38.5%) 5 (29.4%) 0.721
IU/mL)
High (>300 IU/mL) 2 (15.4%) 5 (29.4%)
Disclosure: S. Wang, None; M. Wu, None; L. Chiriboga, None; B. Zeck, None; H. M. Belmont, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/membrane-attack-complex-mac-

deposition-in-lupus-nephritis-is-associated-with-hypertension-and-poor-clinical-response-to-treatment
A New Histological Index for Predicting a Decline in Kidney Function in

Patients with Lupus Nephritis. a Mexican Cohort Study of 186 Patients with
a Kidney Biopsy
Marco Ulises Martinez-Martinez1, Cesar Eduardo Vallín Orozco2, David Martínez-Galla3 and Carlos Abud-Mendoza4,
1Unidad de Investigaciones Reumatológicas, Faculty of Medicine, Universidad Autónoma de San Luis Potosí and Hospital
Central, San Luis Potosí, Mexico, 2Rheumatology, Hospital Central "Dr. Ignacio Morones Prieto", San Luis Potosí,
Mexico, 3Pathology, Hospital Central "Dr. Ignacio Morones Prieto", San Luis Potosí, Mexico, 4Unidad de Investigaciones
Reumatológicas y Osteoporosis, Faculty of Medicine, Universidad Autónoma de San Luis Potosí and Hospital Central, San
Luis Potosí, Mexico
SESSION INFORMATION
- Background/Purpose: The NIH indexes (of activity and chronicity) were proposed by Austin et al., in 1984. At the
moment, there are therapies which can modify the histology of lupus nephritis; therefore, the markers of prognosis in the
kidney biopsy may have different hazard ratios to the described by Austin et al.
- Methods: We evaluated all the patients in whom a kidney biopsy was performed. DKF was defined as a glomerular
filtration rate (GFR) of ≤ 60 ml/min/m2 in two determinations in the follow-up. Histology was graded from 0-3 for
glomerular or tubular abnormalities weighted by the intensity of damage. Factors associated with the development of DKF
according to the different factors were evaluated through Kaplan-Meier curves and multivariate Cox regression analysis.
Cox regression analysis was used to evaluate independent factors associated with the development of DKF. Independent
factors in the multivariate analysis were used to construct the new index using the hazard ratio of each variable. ROC
curves for survival (Heagerty et al, 2000) were used to evaluate the performance of the new index in comparison with the
activity and chronicity indexes.
- Results: We have followed 186 patients with LN and kidney biopsy, 143 (76.9%) women, mean age at kidney biopsy
was 29.7 ± 12.9 years; classes of LN were: 78 patients (41.3%) class IV, 31 (16.4%) class V, 23 (12.2%) class III/V, 23
(12.2%) class IV/V, 19 (10.1%) class III, and other classes 12 patients; 135 patients (79.5%) have a minimum follow-up of
12 months. Table 1 shows the results of the univariate and the final multivariate model that was used to develop the new
index. ROC curves showed AUC for detecting DKF at 12 moths for activity, chronicity and our new index of 0.59, 0.70
and 0.74 respectively. Figure 1 shows the survival according two groups: low index (new index lower than the median) and
high index.
Table1.
Histological Univariate Univariate Multivariate Multivariate
feature
HR (CI) p-value HR (CI) p-value
Glomerular abnormalities
Cellular 1.06 (0.88- 0.547 NA NA
proliferation 1.28)
Karyorrhexis 0.94 (0.72- 0.364 NA NA
1.13)
Cellular 1.09 (0.96- 0.364 NA NA
crescents 1.22)
Hyaline 0.91 (0.70- 0.453 NA NA
thrombi 1.17)
Leukocyte 1.23 (0.97- 0.059 NA NA
infiltration 1.57)
Glomerular 1.64 (1.33- < 0.001 1.48 (1.14- 0.003
sclerosis 2.03) 1.91)
Fibrous 1.68 (1.27- < 0.001 1.35 (0.99- 0.051
crescents 2.21) 1.82)
Tubulointerstitial abnormalities
Interstitial 1.34 (1.17- < 0.001 1.41 (1.02- 0.038
cell 1.55) 1.94)
infiltration
Interstitial 1.30 (0.97- 0.162 NA NA
fibrosis 1.75)
Tubular 1.35 (1.05- 0.025 NA* NA*
atrophy 1.74)
* Tubular atrophy was no included in the final model.
- Conclusion: We suggest predicting the risk of DKF with glomerular sclerosis, fibrous crescents, and interstitial cell
infiltration. Maybe the other histological characteristics could be modified by the new therapies.
Figure 1.
Disclosure: M. U. Martinez-Martinez, None; C. E. Vallín Orozco, None; D. Martínez-Galla, None; C. Abud-

Mendoza, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-new-histological-index-for-

predicting-a-decline-in-kidney-function-in-patients-with-lupus-nephritis-a-mexican-cohort-study-of-186-patients-with-a-
kidney-biopsy
Baseline Hyperuricemia As a Predictive Value for Development of Lupus

Nephritis in Premenopausal SLE Patients
Doo-Ho Lim1, Seokchan Hong2, Ji Seon Oh3, Yong-Gil Kim2, Chang Keun Lee2, Seung Won Choi1 and Bin Yoo2,
1Division of Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University
Hospital, Ulsan, Korea, Republic of (South), 2Division of Rheumatology, Department of Internal Medicine, University of
Ulsan College of Medicine, Asan Medical Center, Seoul, Korea, Republic of (South), 3Division of Rheumatology,
Department of Internal Medicine, National Medical Center, Seoul, Korea, Republic of (South)
SESSION INFORMATION
Background/Purpose: Although lupus nephritis is a common and serious manifestation of SLE, there have been few
predictive markers for development of lupus nephritis in SLE patients. Serum uric acid level is affected by decreased renal
function, besides several factors such as old age, male, menopause, and drugs. However, it is not yet well known whether
hyperuricemia is independently associated with lupus nephritis in SLE patients with normal glomerular filtration rate
(GFR). The aim of this study was to evaluate the association of baseline serum uric acid level and development of lupus
nephritis.
Methods: We retrospectively reviewed electronic medical records of 101 female SLE patients whose ages at the time of
diagnosis (baseline) were 45 years old or below in a tertiary medical center from January 2000 to March 2015. SLE with
renal involvement was diagnosed when patients met the 2015 ACR/SLICC revised criteria for diagnosis of SLE. We
compared baseline serum uric acid levels of the SLE patients who had nephritis at the time of diagnosis or later (nephritis
group) with the patients who had not developed nephritis (non-nephritis group) during follow-up period.
Results: Among 101 patients, 22 (22%) had hyperuricemia at baseline and 45 (45%) had developed lupus nephritis during
follow-up period (median 6.1 years). There were significant differences in baseline serum uric acid level, GFR, anti-
dsDNA antibody and complement level between non-nephritis group and nephritis group (Table). Interestingly, among 59
patients with normal renal function (baseline GFR ¡Ã 90 mL/min/1.73m2), baseline serum uric acid level was also
significantly higher in the nephritis group than non-nephritis group (Figure 1). Moreover, the patients with hyperuricemia
(uric acid ¡Ã6 mg/dL) at baseline were more likely to develop lupus nephritis than those without hyperuricemia during
follow-up period (64% vs. 39%, p = 0.042) (Figure 2).
Conclusion: These findings suggest that high serum uric acid level at the time of diagnosis may be independently
associated with lupus nephritis even in SLE patients with normal GFR. More careful evaluation would be required for
development of lupus nephritis in hyperuricemic patients.
Disclosure: D. H. Lim, None; S. Hong, None; J. S. Oh, None; Y. G. Kim, None; C. K. Lee, None; S. W. Choi, None; B.
Yoo, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/baseline-hyperuricemia-as-a-predictive-

value-for-development-of-lupus-nephritis-in-premenopausal-sle-patients
Cell Bound Complement Activation Products Distinguish Systemic Lupus

Erythematosus from Other Diseases Among Patients with High Antinuclear
Antibody Titers and Normal Complement
Daniel J. Wallace1, Elena Massarotti2, Rosalind Ramsey-Goldman3, Christopher E. Collins4, Anca Askanase5, Jill P.
Buyon6, Richard Furie7, Sonali Narain7, Amit Saxena8, Kenneth C. Kalunian9, Cristina Arriens10, Chaim Putterman11,
John Conklin12, Roberta Alexander12, Claudia Ibarra12, Tyler O'Malley13, Tarun Chandra14, Joseph Ahearn15, Susan
Manzi16, Arthur Weinstein17 and Thierry Dervieux12, 1Cedars-Sinai Medical Center, UCLA, Los Angeles, CA, 2Brigham
and Women's Hospital, Boston, MA, 3FSM, Northwestern University, Chicago, IL, 4Rheumatology, MedStar Washington
Hospital Center, Washington, DC, 5Department of Medicine, Rheumatology, Columbia University College of Physicians &
Surgeons, New York, NY, 6Rheumatology, NYU Langone Medical Center, New York, NY, 7Northwell Health, Great Neck,
NY, 8NYU Langone Medical Center, New York, NY, 9Division of Rheumatology, Allergy and Immunology, UCSD School
of Medicine, La Jolla, CA, 10Arthritis & Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City,
OK, 11Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY, USA, Bronx, NY, 12Exagen
Diagnostics, Inc., Vista, CA, 13Research and Development, Exagen Diagnostics, Inc., Vista, CA, 14EmpiriQA LLC, Long
Grove, IL, 15Lupus Center of Excellence, West Penn Allegheny Health System, Pittsburgh, PA, 16Medicine, Allegheny
Health Network, Pittsburgh, PA, 17Rheumatology, MedStar Washington Hospital Center/Georgetown University Medical
Center, Washington, DC
SESSION INFORMATION
Background/Purpose: Patients are often referred to the rheumatologist because of elevated anti-nuclear antibody (ANA)
titers. We sought to evaluate the association of cell bound complement activation products (CB-CAPs), low complement
(C3 or C4), and anti-double stranded (ds) DNA with systemic lupus erythematosus (SLE) and ANA titers.
Methods: The cohort (n=1155 adults) consisted of 498 patients with SLE with established disease (all fulfilling the 1997
ACR criteria, 91% females, mean age 41 years) pooled from prior studies of complement activation products, and a control
group of 657 subjects (86% females; mean age 56 years; 314 with rheumatoid arthritis and 343 with other diseases).
Abnormal CB-CAPs consisted of C4d bound to erythrocyte or B-lymphocyte levels above the 99th percentile of normal
healthy. Low complement (C3 or C4) and anti-dsDNA (all confirmed using Crithidia luciliae) were determined using
immunoassays. ANA titers were determined by indirect immunofluorescence, with subjects classified as having negative
(<1:80), intermediate (1:80 to 1:320) or high (≥1:640) ANA status. The sensitivity, specificity, and Youden’s index (J), a
measure of diagnostic effectiveness that combines sensitivity and specificity (J = sensitivity + specificity - 1) of various
markers in distinguishing SLE from non-SLE, were evaluated. J differences were tested using t-tests.
Results: The diagnostic effectiveness of abnormal CB-CAPs, low complement, and anti-dsDNA in distinguishing SLE
from non-SLE is presented in the Table. Overall, abnormal CB-CAPs had a significantly greater association with SLE
(J=0.51) than low complement (J=0.32) and anti-dsDNA (J=0.31) (p<0.01; n=1155). The greater association of abnormal
CB-CAPs in comparison to low complement and anti-dsDNA was statistically significant in the group of subjects with high
ANA (p<0.03), intermediate ANA (p<0.01), and negative ANA (p<0.02). This association was also seen among subjects
with high ANA (J=0.60) compared to intermediate (J=0.45) and negative ANA (J=0.17) (p<0.01). Similar results were
observed for low complement and anti-dsDNA (p<0.01). In the group of subjects with normal complement (309 SLE and
619 non SLE), abnormal CB-CAPs was 50% sensitive and 89% specific while anti-dsDNA was 20% sensitive and 99%
specific (J=0.39 vs 0.19; p<0.01). In the subset of subjects with high ANA and normal complement (117 SLE and 106 non
SLE), abnormal CB-CAPs was 68% sensitive and 82% specific and yielded higher diagnostic value than anti-dsDNA (40%
sensitive and 93% specific) (J=0.50 vs 0.34; p<0.01).
Conclusion: Abnormal CB-CAPs has higher diagnostic performances for SLE than low complement and anti-dsDNA and
is a sensitive and specific measure for SLE in patients with high ANA titers and normal complement levels.
Disclosure: D. J. Wallace, Exagen, 2,Exagen, 5; E. Massarotti, Exagen, 2; R. Ramsey-Goldman, Exagen, 2; C. E.

Collins, Exagen, 2,Exagen, 8; A. Askanase, Exagen, 2; J. P. Buyon, Exagen, 2; R. Furie, Exagen, 2; S. Narain, Exagen,
2; A. Saxena, Exagen, 2; K. C. Kalunian, Exagen, 2; C. Arriens, Exagen, 2; C. Putterman, Exagen, 2; J. Conklin,
Exagen, 3; R. Alexander, Exagen, 3; C. Ibarra, Exagen Diagnostics, Inc., 3; T. O'Malley, Exagen Diagnostics, 3; T.
Chandra, Exagen, 5; J. Ahearn, Exagen, 2,Exagen, 5,Exagen, 7; S. Manzi, Exagen, 2,Exagen, 7,Exagen, 5; A.
Weinstein, Exagen, 2,Exagen, 5,Exagen, 9; T. Dervieux, Exagen, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/cell-bound-complement-activation-

products-distinguish-systemic-lupus-erythematosus-from-other-diseases-among-patients-with-high-antinuclear-antibody-
titers-and-normal-complement
Identification of IRAK4-Dependent Gene Signature As a Biomarker

Candidate for IRAK4 Small-Molecule Inhibitor in Systemic Lupus
Erythematosus
A. Francesca Setiadi1, Kate Senger1, Jason Hackney2, Neta Zuckerman1, Swathi Sujatha-Bhaskar1, George Francis1,
Marian Bryan1, Hans Brightbill1, Ali A. Zarrin1 and Michael J. Townsend1, 1Genentech, South San Francisco, CA,
2Bioinformatics and Computational Biology, Genentech, South San Francisco, CA
SESSION INFORMATION
Background/Purpose: Systemic Lupus Erythematosus (SLE) is a heterogeneous disease. Interleukin-1 receptor-associated

kinase 4 (IRAK4) activity is predicted to affect multiple pathogenic pathways in SLE1. We hypothesized that coordinated
expression of IRAK4-regulated genes reflective of toll-like receptor (TLR) and other upstream stimulation will reflect
activity of the pathway. We aimed to identify a TLR7/8-induced gene signature to identify SLE patients who are more
likely to respond to the inhibition of the IRAK4 pathway.
Methods: To determine candidate genes, we first identified those with impaired response to TLR7 or 8 stimulation by
R848 in patients carrying loss-of-function mutations in IRAK4 (analyzed from GEO: GSE 25742)2. We then selected
differentially-expressed genes that also showed elevated baseline expression in SLE blood vs. healthy controls in 2
datasets: PBMC microarray data from an extra-renal SLE cohort (SLE n=61, HC=20) and whole blood (WB) RNA
sequencing data from a second extra-renal cohort (SLE n=103; HC= 19)3. We then confirmed these genes underwent dose-
dependent down-regulation in response to R848 in healthy human WBs treated with selective IRAK4 small molecule
inhibitor (SMI) compounds.
Results: Our analysis of the GSE 25742 microarray dataset showed 285 genes that displayed significantly lower induction
by R848 in the whole blood from IRAK4-deficient patients vs. healthy controls (FDR<0.05; FC>1.25). The IRAK4-
deficient patients did not upregulate type I interferons (IFNs) in response to R848. Baseline levels of 44 differentially-
expressed genes were up-regulated in blood from SLE vs. healthy controls in both SLE cohorts analyzed. We further
observed that 9 genes were down-regulated in a dose-dependent manner by 2 distinct IRAK4 SMI compounds in the human
whole blood assay. These genes formed an inter-correlating signature in SLE patient blood, and partially overlapped with
the interferon signature. Significant positive correlations were observed between top candidate genes and ISM status, anti-
dsDNA status, and levels of BAFF, anti-RNP and anti-Sm, while significant negative correlations were observed between
the candidate genes and levels of C3 and C4 in both SLE datasets.
Conclusion: We have identified a set of IRAK4-dependent genes with an inter-correlating signature and partial overlap
with the interferon signature, that could potentially serve as biomarkers of the IRAK4 pathway in SLE patient blood
samples.
Disclosure: A. F. Setiadi, Roche Pharmaceuticals, 3,Roche Pharmaceuticals, 1; K. Senger, Roche Pharmaceuticals,

3,Roche Pharmaceuticals, 1; J. Hackney, Roche Pharmaceuticals, 3,Roche Pharmaceuticals, 1; N. Zuckerman, Roche
Pharmaceuticals, 3,Roche Pharmaceuticals, 1; S. Sujatha-Bhaskar, Roche Pharmaceuticals, 3,Roche Pharmaceuticals, 1;
G. Francis, Roche Pharmaceuticals, 3,Roche Pharmaceuticals, 1; M. Bryan, Roche Pharmaceuticals, 3,Roche
Pharmaceuticals, 1; H. Brightbill, Roche Pharmaceuticals, 3,Roche Pharmaceuticals, 1; A. A. Zarrin, Roche
Pharmaceuticals, 3,Roche Pharmaceuticals, 1; M. J. Townsend, Roche Pharmaceuticals, 1,Roche Pharmaceuticals, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/identification-of-irak4-dependent-gene-

signature-as-a-biomarker-candidate-for-irak4-small-molecule-inhibitor-in-systemic-lupus-erythematosus
Tissue-Based Biomarkers in Cutaneous Lupus Erythematosus: Type I IFN

Responsive Protein Mxa and a Marker for Lymphocytic Inflammation
(CD45) Correlate with CLASI Cross-Sectionally and Longitudinally
Taylor L. Reynolds1, Carrie Wager1, Stefan Hamann1, Xueli Zhang1, Galina Marsh1, Cristina Musselli1, Nathalie
Franchimont1, Agnes Gardet1, Robert Dunstan2, Dania Rabah1 and Victoria P Werth3, 1Biogen, Cambridge, MA, 2Abbvie,
Worcester, MA, 3University of Pennsylvania and the VA Medical Center, Philadelphia, PA
SESSION INFORMATION
Background/Purpose: Cutaneous lupus erythematosus (CLE) is the cutaneous manifestation of SLE, affecting 85% of
patients1. CLE is subdivided into acute, subacute and chronic/discoid forms. Discoid lupus erythematosus (DLE) can
present in the absence of SLE, but up to 28% of DLE subjects will progress to SLE2. CLE lesions are characterized by
interface dermatitis and a dermal perivascular immune infiltrate consisting largely of lymphocytes and histiocytes, with
relatively large numbers of plasmacytoid dendritic cells (pDCs), with or without fibrosis. As robust producers of type I
interferon, pDCs may play a central role in the pathogenesis of CLE lesions. To monitor the effect of therapeutic pDC-
specific inhibition, we aimed to develop quantitative interlesional measures of immune infiltrate and Type I IFN pathway
related proteins.
Methods: Patients with lesions consistent with a diagnosis of CLE and treated according to standard of care were recruited
by the Perelman Center for Advanced Medicine at the University of Pennsylvania. Enrolled patients presented with
subacute, chronic (other than discoid) or discoid forms of CLE with or without systemic lupus erythematosus as defined by
≥4 out of 11 classification criteria (n=10 subjects who met SLE criteria out of a total of n=19, mean CLASI = 14.21
(range=1-29). At baseline and week 12, 3-5 mm punch biopsies from active CLE lesions were collected and used for
immunohistochemistry with anti-MxA (MX dynamin-like GTPase), CD45 (hematopoietic cells) and CD303 (BDCA-2)
antibodies. Glass slides were examined, then digitized. Using custom-designed algorithms in Visiopharm (Denmark)
software, percent areas were quantified as the portion of immunoreactive area / total tissue area for epidermis, papillary
dermis and reticular dermis. R and p represent Pearson correlation and p-values.
Results: At baseline (n=19 subjects), CLASI correlated with relative area of epidermal (but not dermal) CD45 (r=0.72,
p=0.0005) and MxA (r=0.61, p=0.0056). Also at baseline, relative area of CD303 correlated with MxA in all skin regions.
Compared with papillary and reticular dermis, MxA was enriched in epidermis. In contrast, CD45+ and CD303+ cells were
most plentiful in papillary and reticular dermis. Biopsies from the second visit (week 12) were available for 14 subjects.
When all skin regions were combined, longitudinal change in CLASI correlated with change in CD45+ (r=0.59, p=0.0255)
and MxA+ relative areas (r=0.61, p=0.0218).
Conclusion:
At a single time point and as indicators of longitudinal change, relative areas of MxA and CD45 are useful tissue-based
biomarkers. They can be used to complement CLASI in the setting of a clinical trial. These findings warrant investigation
of tissue-based quantification of CD45 and MxA for stratification of CLE patients and to augment biopsy evaluation in the
diagnostic setting.
1. Rothfield, N., R.D. Sontheimer and M. Bernstein (2006). “Lupus erythematosus: systemic and cutaneous
manifestations.” Clin Dermatol 24(5)
2. Chong, B. F., J. Song and N. J. Olsen (2012). "Determining risk factors for developing systemic lupus erythematosus
in patients with discoid lupus erythematosus." Br J Dermatol 166(1)
Disclosure: T. L. Reynolds, Biogen Idec, 3,Biogen Idec, 1; C. Wager, Biogen Idec, 3,Biogen Idec, 1; S. Hamann, Biogen
Idec, 3,Biogen Idec, 1; X. Zhang, Biogen Idec, 3,Biogen Idec, 1; G. Marsh, Biogen Idec, 3,Biogen Idec, 1; C. Musselli,
Biogen Idec, 3,Biogen Idec, 1; N. Franchimont, Biogen Idec, 3,Biogen Idec, 1; A. Gardet, Biogen Idec, 3,Biogen Idec, 1;
R. Dunstan, Biogen Idec, 1; D. Rabah, Biogen Idec, 3,Biogen Idec, 1; V. P. Werth, Biogen Idec, 2,Biogen Idec, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/tissue-based-biomarkers-in-cutaneous-

lupus-erythematosus-type-i-ifn-responsive-protein-mxa-and-a-marker-for-lymphocytic-inflammation-cd45-correlate-with-
clasi-cross-sectionally-and-longitudinally
Immunosignature Autoantibody Profiles Provide Mechanistic Insight into

Systemic Lupus Erythematosus and Differentiation from Symptomatically
Overlapping Diseases
Theodore M. Tarasow1, Robert Gerwien1, Jonathan Melnick1, Scott A. Melville1 and Chaim Putterman2, 1HealthTell,
Inc., San Ramon, CA, 2Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY, USA, Bronx, NY
SESSION INFORMATION
Background/Purpose:
Diagnosis and monitoring of patients with SLE usually requires careful evaluation by a rheumatologist. However,
difficulties in accurately quantifing disease and treatment response can make patient care subjective and inconsistent. A
quantitative and reproducible test that facilitates SLE differential diagnosis and disease stratification may help decrease
time to definitive diagnosis and improve treatment outcomes.
The Immunosignature (IS) technology uses a high-density array of 126,000 unique peptides designed to survey an
individual’s antibody repertoire. For autoimmune diseases, differential antibody binding profiles have the potential to
provide accurate differential diagnosis, disease activity, and progression measures as well as provide more comprehensive
autoantigen profiles.
The objective of this study was to use the IS technology to differentiate and characterize the autoantibody profiles in
subjects with SLE from healthy controls and subjects with inflammatory and non-inflammatory diseases that share
symptoms with SLE patients.
Methods:
A well-annotated cohort of 371 serum samples was prospectively collected and included patients with SLE (n=75), RA
(n=95), SS (n=20), OA (n=24), FM (n=22), other disease (OD) (n=76) and healthy controls (HC) (n=59). Subjects with
rheumatological diseases were diagnosed based on ACR criteria. There were no significant differences in gender, race or
ethnicity across all groups. Antibody (IgG)-peptide binding with significant intensity differences between contrasting
groups was identified by Bonferroni adjusted t-test. Support vector machine classifiers were trained using the most
distinguishing peptides. Classifier performance was evaluated by a cross-validation routine that included feature selection,
model training and testing. Distinguishing peptides were mapped to putative autoantigens using a BLAST routine modified
for array amino acid composition.
Results:
The number of peptides significantly different between SLE contrasts and the cross validated classification performance as
measured by the area under the curve (AUC) are shown in the Table. Significant peptides associated with SLE were
mapped to known and novel putative autoantigens, including a known immunogenic epitope of SS-B.
Contrast # Samples Significant cvAUC (95%
Peptides CI)
SLE vs. HC 134 5,121 0.90 (0.88-
0.92)
SLE vs. All 312 684 0.79 (0.77-
Disease* 0.81)
SLE vs. RA 170 201 0.80 (0.76-
0.85)
SLE vs. OA 99 455 0.88 (0.86-
0.91)
SLE vs. FM 97 464 0.83 (0.78-
0.87)
SLE vs. SS 95 0 0.65 (0.60-
0.70)
*All Disease = SLE, SS, OA, FM, and OD (PsA (11),
gout (9), scleroderma (7), DM (6), PM (5), other
connective tissue disorders (38 total, <5 each)).
Conclusion:
Based on these observations, the IS technology can be used to classify subjects with SLE from healthy controls or subjects
with diseases that have common symptoms or are similarly charaterized by underlying immunological dysregulation. The
ability to broadly survey the antibody repertoire within and between diseases allows for the identification of putative
autoantigens and may provide additional approaches to subsetting patients. These results need verification in cohorts from
other sites and validation in blinded studies.
Disclosure: T. M. Tarasow, HealthTell, 3,HealthTell, 1; R. Gerwien, HealthTell, 3,HealthTell, 1; J. Melnick, HealthTell,

3,HealthTell, 1; S. A. Melville, HealthTell, 3,HealthTell, 1; C. Putterman, HealthTell, 2,HealthTell, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/immunosignature-autoantibody-

profiles-provide-mechanistic-insight-into-systemic-lupus-erythematosus-and-differentiation-from-symptomatically-
overlapping-diseases
Soluble Urokinase Plasminogen Activator Receptor (suPAR) Predicts the

Development of Organ Damage over 5 Years in Systemic Lupus
Erythematosus: Results from the Systemic Lupus International
Collaborating Clinics (SLICC) Inception Cohort
Helena Enocsson1, Lina Wirestam1, Jonas Wetterö1, Thomas Skogh1, Ian N. Bruce2,3 and Christopher Sjöwall4,
1Rheumatology, Division of Neuro and Inflammation Sciences, Department of Clinical and Experimental Medicine,
Linköping University, Linköping, Sweden, Linköping, Sweden, 2Central Manchester University Hospital NHS Foundation
Trust and Manchester Academic Health Science Centre, Arthritis Research UK Epidemiology Unit, The University of
Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom, 3NIHR Manchester
Musculoskeletal Biomedical Research Centre, Central Manchester University Hospitals NHS Foundation Trust,
Manchester, United Kingdom, 4Department of Clinical and Experimental Medicine, Linköping University, Sweden,
Linköping, Sweden
SESSION INFORMATION
Background/Purpose:
The urokinase plasminogen activator receptor (uPAR) is expressed on various cell types and plays important roles in
proteolysis, migration and adhesion. Receptor shedding yields a soluble form (suPAR) that has emerged as a promising
severity biomarker in malignancies, inflammatory and infectious diseases. Previously, suPAR was shown to reflect
accumulated organ damage in systemic lupus erythematosus (SLE). Our aim was to investigate suPAR as a potential
predictor of future organ damage in well-characterized patients with recent-onset SLE.
Methods:
A total of 345 patients with SLE (≥4 ACR criteria) were included in this study. All patients originated from the SLICC
inception cohort and were selected based on a minimum of 5-years follow-up and absence of organ damage (SLICC/ACR
damage index; SDI>0) at inclusion. The patients were enrolled within 15 months of SLE diagnosis. Plasma creatinine was
available for 180 patients and estimated glomerular filtration rate (eGFR) was calculated according to the MDRD 4-
Variable Equation. Serum suPAR levels were measured by ELISA (Virogates, Birkerod, Denmark) at inclusion only, and
levels at inclusion were related to SDI after 5-years of follow-up. Age- and sex-matched controls (1:1) were from the
Swedish population.
Results:
Baseline suPAR levels were higher in patients who acquired damage (SDI >1) over a 5-year period (n=33) compared to
patients without damage development (n=246; p<0.001) and controls (n=345; p=0.007) (Fig. 1). There were no significant
differences in suPAR levels with regard to ethnicity (Caucasians vs. non-Caucasians) or sex in patients and controls, but
there was a weak correlation between age and suPAR among controls (p<0.001, r=0.23). No correlations (r>0.2) were
found between suPAR and disease activity (SLEDAI-2K), corticosteroid dose or eGFR in patients. Logistic regression
revealed significant impact of baseline suPAR on future damage (SDI>1) (p=0.014; area under curve, AUC=0.64) and the
predictive value became stronger after adjustment for age, sex, ethnicity and corticosteroid dose (p=0.008; AUC=0.74).
Examining the components of the SDI individually revealed significant impact of suPAR on damage in the musculoskeletal
domain (SDI≥1) (p=0.018; AUC=0.66) also when adjusting for covariates (p=0.020; AUC=0.68).
Conclusion:
Prognostic biomarkers of disease severity in SLE could identify patients in need of tight control and improved treatment
strategies. suPAR has become an interesting option for patient triaging and prognostication in various diseases, and here,
for the first time, it is shown to have predictive potential of damage accrual in SLE. Continued follow-up of patients could
elucidate the association between suPAR and damage in specific organ domains. Furthermore, the possible role of suPAR
as a causative agent in SLE organ damage remains to be investigated.
Disclosure: H. Enocsson, None; L. Wirestam, None; J. Wetterö, None; T. Skogh, None; I. N. Bruce, None; C. Sjöwall,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/soluble-urokinase-plasminogen-

activator-receptor-supar-predicts-the-development-of-organ-damage-over-5-years-in-systemic-lupus-erythematosus-results-
from-the-systemic-lupus-international-collaborat
Systemic Hypertension Is Associated with Presence of Vascular Injury on

Lupus Nephritis Renal Biopsies: A Retrospective Cohort Study
Cianna Leatherwood, Brigham and Women's Hospital, Boston, MA
SESSION INFORMATION
Background/Purpose: Vascular injury in lupus nephritis is often described on renal biopsy, but its clinical correlates are
not well understood. Recent evidence suggests it may be associated with poorer prognosis. We retrospectively investigated
clinical and laboratory characteristics associated with vascular injury on renal biopsy among patients diagnosed with lupus
nephritis.
Methods: We reviewed initial renal biopsy reports performed at a single academic medical center between 1996 and 2015
showing Class II-VI lupus nephritis. Experienced pathologists interpreted the histologic findings. Vascular injury was
defined as arterial or arteriolar thickening of the intima without thrombosis, necrosis or proliferation. The extent of vascular
injury was described as absent, mild, moderate, or severe. Clinical variables including i) hypertension (systolic blood
pressure ≥ 140mmHg or diastolic blood pressure ≥90mmHg), ii) demographics, iii) serum laboratories at the time of biopsy
and iv) medications for 30 days prior to the biopsy were obtained from the medical records. We used univariable analyses
and multivariable logistic regression to model risk of vascular injury on biopsy.
Results: Among 155 initial lupus nephritis biopsies 103 exhibited vascular injury. The average age was 39 years, 84% were
female, 42% were African American and dsDNA was positive in 84%. ISSN lupus nephritis biopsy classes overall were
14% II, 26% III, 33% IV and 26% V, and class was not statistically associated with presence of vascular injury. There were
no statistically significant differences in duration of SLE at biopsy or prior medications between biopsies with or without
vascular injury (Table). Vascular injury was associated with older age [39 (±13) vs. 34 years (±11), p 0.02], elevated
creatinine [1.8 vs 0.97 mg/dL, p 0.0006] and hypertension (36% vs. 19%, p 0.03] in univariable analyses. Presence of
antiphospholipid antibodies and treatment with high dose glucocorticoids, immunosuppressants and ACE inhibitors at the
time of biopsy did not differ between groups. Hypertension remained a strong correlate of vascular injury in a multivariable
model controlling for age, race, sex and creatinine [OR 1.32 (95% CI 1.08, 1.62)].
Conclusion: Systemic hypertension was associated with vascular injury on lupus nephritis renal biopsy in this study.
Further work in characterizing any differences in vascular lesions among patients with and without lupus nephritis is
necessary as understanding the pathogenesis of these lesions may give insight into novel treatment pathways. These
findings may support the importance of aggressive blood pressure management in patients with lupus nephritis.
Table. Univariable Analyses of Clinical Factors Potentially Associated with
Vascular Injury on 155 Initial Lupus Nephritis Biopsies
Vascular Injury No Vascular p-value*
Injury (n=52)
(n= 103)
Age, mean 39 (±13) 34 (±11) 0.02
Duration of SLE at 7.8 (±8) 5.5 (7)
0.16
biopsy (years), mean
Female 87 (84%) 45 (87%) 0.73
Race
White 32 (33%) 18 (35%)
Black 41 (42%) 12 (24%)
Asian 9 (9%) 9 (18%) 0.11
Hispanic 15 (15%) 10 (20%
Other 1 (1%) 2 (4%)
Laboratory Values
Hemoglobin (g/dL), 10.7 (2) 10.7 (2) 0.96
mean
Anti-dsDNA (IU/mL), 141 [43, 454] 254 [50, 1000] 0.14
median
Anti-RNP positive 39 (42%) 23 (49%) 0.4
Antiphospholipid 22 (28%) 13 (28%) 0.98
Antibodies**
C4 (mg/dL), mean 14 (12) 11 (8) 0.26
Creatinine (mg/dL), 1.8 (±2) 0.97 (±1) 0.0006
mean
Clinical Data
Prior high dose 28 (31%) 17 (35%) 0.61
glucocorticoids***
Prior 21 (23%) 10 (21%) 0.73
immunosuppression****
Prior ACE Inhibitor 29 (32%) 18 (38%) 0.53
SBP ≥140mmHg or 38 (36%) 10 (19%) 0.03
DBP≥ 90mmHg
SLICC score, median 3 [1, 6] 2.5 [1,6] 0.14
*Continuous variables evaluated with t-test or Wilcoxon and binary and categorical
variables were assessed using chi-squared tests or Fisher’s exact as appropriate.
** positive vs. negative or not tested
** *glucocorticoid ≥20mg/day for past 30 days
**** receiving azathioprine, cyclophosphamide, mycophenolate mofetil, rituximab,

cyclosporine or tacrolimus at the time of biopsy
Disclosure: C. Leatherwood, None;
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/systemic-hypertension-is-associated-

with-presence-of-vascular-injury-on-lupus-nephritis-renal-biopsies-a-retrospective-cohort-study

Distinct Interferon Scores Are Separately Associated with Activity and Long
Term Sequelae in SLE
Katherine Dutton1, Antonios Psarras2, Md Yuzaiful Md Yusof2, Paul Emery3, Yasser M El-Sherbiny4 and Edward M
Vital1, 1University of Leeds, Leeds, United Kingdom, 2Leeds Institute of Rheumatic and Musculoskeletal Medicine,
University of Leeds, Leeds, United Kingdom, 3NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS
Trust, Leeds, United Kingdom, 4NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals, NHS Trust, Leeds,
United Kingdom
SESSION INFORMATION
Background/Purpose: Type I interferon (IFN-I) has a crucial role in the pathogenesis and activity of Systemic Lupus
Erythematosis (SLE). IFN-I targeted therapies are currently in phase III clinical trials. Early findings suggest that anti-INF-
I therapy responses are superior in individuals with high INF-I signature. In established SLE, the level of IFN-I activity can
be measured using an interferon gene expression score. We previously described two independent interferon gene
expression scores that we called Score A and B. We also previously described a memory B cell flow cytometric marker
(Tetherin) that can be used to measure IFN-I response in B cells. We aimed to describe the clinical phenotype of IFN-high
SLE patients and to correlate this with Score A, Score B and Tetherin levels.
Methods: IFN gene expression Scores A and B as well as memory B cell tetherin were measured in 156 consecutive SLE
patients attending the Leeds SLE clinic. For this preliminary analysis, we selected 59 patients across a spectrum of levels of
IFN assays for detailed retrospective notes review.
Results:
Characteristic Internal Previous Cardiovascular Objective Increased
organ cyclophosphamide Disease flare 3 glucocorticoid
involvement months dose 3 months
before or before or after
after test test**
Number of patients
Yes (n=) 21 13 5 18 15
IFN Score A median (IQR)
No 0.02 (0.40) 0.04 (0.82) 0.03 (0.40) 0.024 0.02 (0.19)
(0.029)
Yes 0.04 (1.15) 0.03 (0.45) 1.00 (0.96) 0.39 (1.08) 0.33 (1.39)
P 0.124 0.913 0.024 0.042 0.030
INF Score B median (IQR)
No 0.12 (0.33) 0.15 (0.42) 0.18 (0.35) 0.17 (0.30) 0.17 (0.30)
Yes 0.28 (0.64) 0.22 (0.48) 0.79 (0.74) 0.34 (0.50) 0.34 (0.50)
P 0.037 0.150 0.019 0.343 0.343
Memory B cell tetherin median (IQR)
No 1318 (2176) 1537 (2787) 1637 (2879) 647 (830) 682 (1174)
Yes 1714 (2866) 1192 (2602) 664 (1186) 3450 3419 (1942)
(1965)
P 0.740 0.666 0.310 <0.001 <0.001
*numerically there was a stepwise increase in score B comparing 0, 1 and 2 internal organs affected but not statistically
significant.
**There were also significant correlations between average dose of prednisolone in over 3 months before and after the
sample date and IFN Score A (Rho = 0.402, p=0.014) and memory B cell tetherin (Rho = 0.537, p<0.001)
There was no substantive relationship between interferon assays and number of previous oral immunosuppressants. There
was a trend to higher tetherin levels in patients with exposure to 1 or more antimalarials (p=0.068).
Conclusion: High interferon is associated with more severe disease. We observed a stronger relationship between Score A
and tetherin with parameters that reflect current disease activity, while long term sequelae were more clearly associated
with Score B. Interferon assays may allow clinicians to better stratify SLE patients for therapy and severity prediction.
Disclosure: K. Dutton, AstraZeneca, 2; A. Psarras, None; M. Y. Md Yusof, None; P. Emery, AstraZeneca, 2,Roche
Pharmaceuticals, 2; Y. M. El-Sherbiny, None; E. M. Vital, Roche, GSK and AstraZeneca., 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/distinct-interferon-scores-are-

separately-associated-with-activity-and-long-term-sequelae-in-sle
Abnormalities in Complement System Are Related to Disease Severity in

Systemic Lupus Erythematosus (SLE)
Cristina Arriens1, Sonali Narain2, Amit Saxena3, Christopher E. Collins4, Daniel J. Wallace5, Elena Massarotti6, John
Conklin7, Roberta Alexander7, Kenneth C. Kalunian8, Chaim Putterman9, Rosalind Ramsey-Goldman10, Jill P. Buyon11,
Anca Askanase12, Richard Furie2, Susan Manzi13, Joseph Ahearn14, Arthur Weinstein15 and Thierry Dervieux7, 1Arthritis
& Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, 2Northwell Health, Great Neck,
NY, 3Rheumatology, NYU Langone Medical Center, New York, NY, 4Rheumatology, MedStar Washington Hospital
Center, Washington, DC, 5Cedars-Sinai Medical Center, UCLA, Los Angeles, CA, 6Brigham and Women's Hospital,
Boston, MA, 7Exagen Diagnostics, Inc., Vista, CA, 8Division of Rheumatology, Allergy and Immunology, UCSD School
of Medicine, La Jolla, CA, 9Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY, USA, Bronx, NY,
10FSM, Northwestern University, Chicago, IL, 11Medicine, New York University School of Medicine, New York, NY,
12Rheumatology, Columbia University, New York, NY, 13Medicine, Allegheny Health Network, Pittsburgh, PA, 14Lupus
Center of Excellence, West Penn Allegheny Health System, Pittsburgh, PA, 15Rheumatology, MedStar Washington
Hospital Center/Georgetown University Medical Center, Washington, DC
SESSION INFORMATION
Background/Purpose: We sought to evaluate the relationships between low complement C3 and C4 proteins, abnormal
complement activation (cell-bound complement activation products [CB-CAPs]), and a Lupus Severity Index (LSI)
instrument recently developed.
Methods: The study was multi-centered and enrolled 500 SLE subjects (mean age 41.0±0.6 [SEM] years; 91% female;
mean disease duration 10.9±0.4 years), all fulfilling the 1982 American College of Rheumatology (ACR) criteria revised in
1997. LSI was determined using the ACR criteria and sub-criteria elements collected from medical records as described
(Bello et al., Lupus Science & Medicine 2016;3:e000136). Serum C3 and C4 levels were determined using standard
immunochemistry techniques. Complement activation was assessed by quantitative flow cytometry, and abnormal
activation was defined as levels of C4d bound to erythrocyte (EC4d) or B-lymphocytes (BC4d) above the 99th percentile of
a control group of normal healthy individuals (>14 and >60 net mean fluorescence intensity [MFI], respectively).
Multivariate linear regression analysis was used to evaluate the contributions of low complement and abnormal CB-CAPs
to LSI, with age and disease duration as covariates. Pearson's Chi-Square and Kruskal Wallis ANOVA tests were used as
appropriate for group comparisons.
Results: In this cohort, median LSI score was 0.596 points (range 0.327-0.938 points, first tertile: 0.544; second tertile:
0.792). Multivariate linear regression analysis revealed that higher LSI scores were associated with abnormal CB-CAPs
(estimate=0.063±0.015 points; p<0.01), low complement (estimate=0.030±0.015; p=0.048), younger age
(estimate=-0.026±0.001 per 10-years increment; p<0.01), and longer disease duration (estimate=0.027±0.003 per 10-years
increment, p<0.01) (Global R2=0.13). Altogether, subjects presenting with both low complement and abnormal CB-CAPs
had higher LSI (median [IQ range]: 0.785 [0.558-0.839]) than those presenting with either abnormality (median [IQ range]:
0.591 [0.526-0.817]) or those presenting with normal complement and normal CB-CAPs (median [IQ range]: 0.546 [0.481-
0.703]) (p<0.001). Figure 1 illustrates the higher frequencies of low complement (p<0.01) and abnormal CB-CAPS
(p<0.01) by LSI tertiles and shows that abnormal CB-CAPs is more prevalent than low complement at all LSI levels
(p<0.01).
Conclusion: These data indicate that abnormalities in the complement system are associated with increased LSI.
Disclosure: C. Arriens, Exagen, 9; S. Narain, Exagen, 2; A. Saxena, Exagen, 2; C. E. Collins, Exagen, 2,Exagen, 8; D. J.
Wallace, Exagen, 2,Exagen, 5; E. Massarotti, Exagen, 2; J. Conklin, Exagen, 3; R. Alexander, Exagen, 3; K. C.
Kalunian, Exagen, 2; C. Putterman, Exagen, 2; R. Ramsey-Goldman, Exagen, 2; J. P. Buyon, Exagen, 2; A. Askanase,
Exagen, 2; R. Furie, Exagen, 2; S. Manzi, Exagen, 2,Exagen, 7,Exagen, 5; J. Ahearn, Exagen, 2,Exagen, 5,Exagen, 7; A.
Weinstein, Exagen, 2,Exagen, 5,Exagen, 9; T. Dervieux, Exagen, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/abnormalities-in-complement-system-

are-related-to-disease-severity-in-systemic-lupus-erythematosus-sle
A Panel of Lupus Biomarkers for the Monitoring of Systemic Lupus

Erythematosus: Performance Characteristics in Distinct SLE Cohorts
Joan T. Merrill1, Thierry Dervieux2, Jill P. Buyon3, Rosalind Ramsey-Goldman4, Kenneth C. Kalunian5, Chaim
Putterman6, John Conklin2, Richard Furie7 and Michelle Petri8, 1Oklahoma Medical Research Foundation, Oklahoma City,
OK, 2Exagen Diagnostics, Inc., Vista, CA, 3Medicine, New York University School of Medicine, New York, NY, 4FSM,
Northwestern University, Chicago, IL, 5Division of Rheumatology, Allergy and Immunology, UCSD School of Medicine,
La Jolla, CA, 6Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY, USA, Bronx, NY, 7Northwell
Health, Great Neck, NY, 8Medicine (Rheumatology), Division of Rheumatology, Johns Hopkins University School of
Medicine, MD, USA, Baltimore, MD
SESSION INFORMATION
Background/Purpose: Antibody titers to double stranded DNA (anti-dsDNA) and complement C3 and C4 proteins have
clinical utility in the routine monitoring of systemic lupus erythematosus (SLE). We evaluated the performance
characteristics of antibody titers to C1q (anti-C1q), and C4d bound to erythrocytes (EC4d) as additional biomarker
candidates in the monitoring of SLE disease activity.
Methods: SLE patients (total 124 patients, mean age 42 years, 97% females) were enrolled from three different cohorts.
The first cohort enrolled 37 subjects, all selected for active disease in the presence of complement activation. The second
and third cohorts enrolled 64 and 24 SLE subjects, respectively. Disease activity was assessed longitudinally using the
Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLE disease activity index (SLEDAI)
without anti-dsDNA and complement components; this modification is referred to as the clinical SELENA-SLEDAI. Also,
the Physician’s Global Assessment of disease activity (PGA: 0-3-point scale) was collected. Antibody titers, serum C3 and
C4 levels were determined using standard immunoassays (low C3/C4 was defined as either C3 or C4 below normal range).
EC4d levels were determined using quantitative flow cytometry and expressed as net mean fluorescence intensity (MFI).
The relationships between fluctuations in SLE disease activity and biomarkers were analyzed using Spearman rank test and
linear mixed effect models with the clinical SELENA-SLEDAI and PGA as the dependent variables and biomarkers as
independent predictor of disease activity fluctuations (autoantibody titers and EC4d levels were log normalized for the
analysis). Marginal R2 were calculated to evaluate the proportion of variance explained by independent variables.
Results: Overall, a total of 624 study visits were collected in the 124 patients. At baseline, both clinical SELENA-SLEDAI
(average 6.0 points) and PGA scores (average 1.0 point) correlated with EC4d levels C3/C4 status, anti-dsDNA and anti-
C1q titers (p<0.01). Linear mixed effect models revealed that changes in EC4d, C3/C4 anti-dsDNA and anti-C1q titers
were all significantly associated with fluctuations in disease activity (p<0.01)(Table I). Of the 124 subjects, 97 of them
presented with either chronically low C3/C4 (n=40) or normal C3/C4 status at all visits (n=57). In this subset, changes in
EC4d levels were associated with fluctuations in clinical SELENA-SLEDAI (estimate 1.2±0.3, marginal R2=8%) and PGA
(estimate 0.2±0.1, marginal R2=9%).
Conclusion: These data indicate that anti-dsDNA, antiC1q, low complement and EC4d are associated with disease
fluctuations in SLE. EC4d correlates with disease activity among subjects with chronically low or normal complement.
Disclosure: J. T. Merrill, Exagen, 5; T. Dervieux, Exagen, 3; J. P. Buyon, Exagen, 2; R. Ramsey-Goldman, Exagen, 2;
K. C. Kalunian, Exagen, 2,Exagen, 5; C. Putterman, Exagen, 2; J. Conklin, Exagen, 3; R. Furie, Exagen, 2; M. Petri,
Exagen, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-panel-of-lupus-biomarkers-for-the-

monitoring-of-systemic-lupus-erythematosus-performance-characteristics-in-distinct-sle-cohorts
Complement Activation in Peripheral Blood in Relation to Lupus,

Antiphospholipid and Rheumatoid Arthritis Autoantibodies: Insights from
Clinical Laboratory Evaluations
Thierry Dervieux1, John Conklin1, JoAnne Ligayon1, Rowena Lafon2, Armida Sace3, Tyler O'Malley4, Roberta
Alexander1 and Claudia Ibarra1, 1Exagen Diagnostics, Inc., Vista, CA, 2Immunochemistry, Exagen Diagnostics, Inc., Vista,
CA, 3Automated Chemistry, Exagen Diagnostics, Inc., Vista, CA, 4Research and Development, Exagen Diagnostics, Inc.,
Vista, CA
SESSION INFORMATION
Background/Purpose: Abnormal activation of the complement system is emerging as a useful biomarker in the evaluation
of patients presenting symptoms of autoimmune rheumatic diseases. We sought to evaluate the relationships between
complement activation and autoantibodies associated with systemic lupus erythematosus (SLE), anti-phospholipid
Syndrome (APS) and rheumatoid arthritis (RA).
Methods: From May 2014 to November 2016, a cohort of 32,404 patients within the United States (mean 51±15 [SD]
years, 86% females) was tested. EDTA whole blood and serum were collected within 48 hours of patient examination and
processed in a CLIA certified/CAP accredited clinical laboratory. C4d bound to erythrocyte or B lymphocyte above the
99th percentile of normal healthy group were defined as abnormal. The panel of 16 autoantibodies (all determined by solid
phase immunoassays) consisted of 6 SLE autoantibodies (high ANA, anti-dsDNA confirmed using Crithidia, anti-U1 RNP,
anti-C1q, anti-ribosomal P, anti-Smith, all IgGs), 6 APS autoantibodies (anti-cardiolipin, anti-β2 glycoprotein 1, anti-
phosphatidylserine/prothrombin complex, IgM and IgG) and 4 RA autoantibodies (anti-CCP, anti-MCV, IgM RF, IgA RF).
The relationships between abnormal complement activation and the presence of the autoantibodies were analyzed on de-
identified patient data using multivariate logistic regression with abnormal complement activation as the dependent variable
and the presence of autoantibodies as predictors. Adjusted odds ratio were calculated for each autoantibody.
Results: Of the 32,404 patients tested 12% of them presented with abnormal complement activation. The overall incidence
of autoantibodies ranged from 1% (anti-Sm) to 22% (ANA). The presence of SLE and APS antibodies were all associated
with abnormal complement activation with adjusted OR ranging from 1.40 for anti-C1q (CI95%: 1.24-1.58) to 4.52 for
anti-dsDNA (CI95%: 3.95-5.17), and from 1.47 for anti-cardiolipin IgG (CI95%: 1.22-1.77) to 3.2 for anti-PS/PT IgM
(CI95%: 3.20-2.92), respectively (p<0.02). Of the 4 RA-associated antibodies, only anti-CCP (adjusted OR=1.25, CI95%:
1.02-1.54) and IgM RF (adjusted OR=1.17, CI95%: 1.04-1.32) were significantly associated with complement activation
(p<0.05). Figure 1 illustrates the relationship between the cumulative presence of lupus, APS and RA autoantibodies, and
abnormal complement activation. Across the cumulative range of SLE and APS associated antibodies, we detected a 319-
fold (CI95%: 240-424), and 120-fold (CI95%: 94-153) increased likelihood of abnormal complement. In contrast, the
cumulative presence of RA autoantibodies yielded minimum impact of the likelihood of abnormal complement activation
(adjusted OR=2.3; CI95%: 2.0-2.7)
Conclusion: These diagnostic immunology data suggest that complement activation in peripheral blood is intimately
related to SLE and APS antibodies.
Disclosure: T. Dervieux, Exagen, 3; J. Conklin, Exagen, 3; J. Ligayon, Exagen Diagnostics, Inc., 3; R. Lafon, Exagen
Diagnostics, Inc., 3; A. Sace, Exagen Diagnostics, Inc., 3; T. O'Malley, Exagen Diagnostics, 3; R. Alexander, Exagen, 3;
C. Ibarra, Exagen Diagnostics, Inc., 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/complement-activation-in-peripheral-

blood-in-relation-to-lupus-antiphospholipid-and-rheumatoid-arthritis-autoantibodies-insights-from-clinical-laboratory-
evaluations
The Presence of Anti-Ro and Anti-La Antibodies Is Associated with

Tubulointerstitial Damage in Lupus Nephritis
Alejandra Londono Jimenez1, Wenzhu Mowrey2 and Anna R. Broder2, 1Internal Medicine, Montefiore Medical
Center/Albert Einstein College of Medicine, Bronx, NY, 2Albert Einstein College of Medicine/Montefiore Medical Center,
New York, NY
SESSION INFORMATION
Background/Purpose: Moderate-to-severe tubulointerstitial damage (TID) is associated with poor renal outcomes in
lupus-related kidney disease, independent of glomerular pathology1. Unlike glomerular damage, TID is not associated with
anti-dsDNA or complement levels and no serologic parameters associated with TID in SLE have been identified to date 2.
The presence of anti-Ro/La antibodies in Sjögren's syndrome is associated with extraglandular manifestations, including
tubulointerstitial nephritis3. Whether anti-Ro/La antibodies are associated with TID in lupus-related kidney disease has not
been studied.
Objective: To study an association between anti-Ro/La antibodies and TID in lupus nephritis (LN).
Methods: We identified all patients who fulfilled ACR and/or SLICC criteria for SLE at a large urban tertiary care center.
Medical history, demographic and laboratory data were ascertained from chart review. Patients were included if they had an
index renal biopsy consistent with LN between January 2005 and July 2015 and had complete data on TID and anti-Ro/La.
All biopsies were reviewed by 2 experienced renal pathologists and TID was classified as mild, moderate or severe when
tubular atrophy and/or interstitial fibrosis involved <25%, 25-50% or >50% of the interstitium, respectively1.
Results: Of the 157 LN patients, 39 (25%) had moderate/severe TID (Table). Moderate/severe TID was associated with
older age, proliferative LN (class III/IV±V) and lower estimated glomerular filtration rate (eGFR) at biopsy. Anti-Ro/La
were present in 11/118 (9%) with none/mild TID vs 11/39 (28%) with moderate/severe TID (p=0.003), and in 13/114 (11%)
with none/mild TII vs. 8/37 (22%) with moderate/severe TII (p=0.12). In the logistic regression model adjusted for age,
eGFR and LN class, dual positivity for anti-Ro/La antibodies was associated with a 3-fold increase in the odds of TID, OR
3.1, 95% CI (1.1-9.1), p=0.04.
Conclusion: Dual anti-Ro/La positivity is associated with moderate/severe TID in patients with biopsy proven LN after
adjusting for age, LN class and eGFR. The presence of only anti-Ro antibodies is not associated with moderate/severe TID.
Understanding the role of anti-Ro/La in the mechanisms underlying TID in LN may lead to novel preventive and
therapeutic strategies.
References:
1. Yu F, et al. Kidney Int 2010;77:820-9.
2. Hsieh, et al. Arthritis Care Res 2011; 63(6):865-74
3. Francois H, et al. Nat Rev Nephrol 2016;12(2):82-93.

Baseline characteristics by TID (none/mild vs.
moderate/severe)
None/Mild
TID Moderate/Severe p-
(n=118) TID (n=39) value
Age, median (IQR), years 26 (17, 37) 41 (25, 53) <0.001
Men, n(%) 21 (18) 10 (26) 0.29
Black Race, n(%) 55 (47) 22 (56) 0.29
Charlson comorbidity
index, median (IQR) 3 (1, 4) 3(1, 4) 0.09
Creatinine (mg/dL), 0.8 (0.6,
median (IQR) 1.2) 1.6 (1, 2.6) <0.001
eGFR mL/min/1.73m2, 91 (61,
median (IQR) 127) 42 (26, 75) <0.001
Protein/Creatinine ratio 2.2 (1.0,
(mg/mg), median (IQR) 4.9) 2.1 (1.5, 5.5) 0.68
LN class n(%)
I/II 10 (9) 0
III/IV ± V 71 (61) 34 (87) 0.008
V 35 (30) 5 (13)
Low C3, n(%) 83 (75) 23 (70) 0.51
Low C4, n(%) 76 (70) 22 (67) 0.69
Elevated dsDNA, n(%) 70 (68) 21 (66) 0.81
Anti-Ro, n(%) 55 (47) 17 (44) 0.74
Anti-Ro and anti-La, n(%) 11 (9) 11 (28) 0.003
Tubulointerstitial
inflammation (TII), n(%) 19 (17) 18 (49) <0.001
Disclosure: A. Londono Jimenez, None; W. Mowrey, None; A. R. Broder, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-presence-of-anti-ro-and-anti-la-

antibodies-is-associated-with-tubulointerstitial-damage-in-lupus-nephritis
ANTI-RO52 KDa and ANTI-RO60 KDa Analysis in Systemic LUPUS

Erythematous Patients to Detect ANTI-RO False-Negatives
Elena Grau Garcia1, Inmaculada Chalmeta Verdejo1, David Gimenez-Romero2, Eztizen Labrador Sanchez1, Merixell
Fernandez Matilla3, Francisco Miguel Ortiz-Sanjuán1, Carlos Feced Olmos1, Nagore Fernandez-Llanio Cornella3, Karla
Arevalo Ruales1, Rosa Negueroles Albuixech1, Jose Ivorra Cortes1, Jorge Juan Fragio Gil1, Isabel Martinez Cordellat1,
Roxana Gonzalez Mazario1, Luis Gonzalez Puig1, Cristina Alcañiz Escandell1, Carmen Najera Herranz1, Ines Canovas
Olmos1, Elvira Vicens Bernabeu1, Jose Eloy Oller Rodriguez1, Jose Antonio Castellano Cuesta3, Victoria Fornes Ferrer4,
David Hervás Marín4, Marta De la Rubia Navarro1 and Jose Andres Roman Ivorra1, 1Rheumatology Department. Hospital
Universitario y Politecnico La Fe, Valencia, Spain, 2Physical-Chemistry Department, UV, Valencia, Spain, 3Rheumatology
Section. Hospital Arnau de Vilanova, Valencia, Spain, 4Biostatistics Unit. IIS La Fe, Valencia, Spain
SESSION INFORMATION
Background/Purpose:
Systemic lupus erythematous (SLE) is an autoimmune disease characterized by immune system disruption with
autoantibodies production. One of the upregulated autoantibodies is the specific to the Ro antigen, a ribonucleoprotein
associated to a small RNA, constituted by the 52KDa and 60 KDa polypeptides, whose epitopes are mainly conformational.
The routine detection method for anti-Ro is an enzyme immunoassay, however, is possible to obtain false-negatives for
anti-Ro and this could be avoided by analyzing both subunits separately. The aim of the present study is to identify false-
negatives for anti-Ro by analyzing both 52KDa and 60 KDa subunits separately, as well as to characterize if there are
clinical or molecular differences in this subgroup of patients compared to anti-Ro negative cases.
Methods:
A cross-sectional, observational study of patients diagnosed of SLE according to SLICC 2012 criteria was performed. In
these patients a complete blood-test was made, and clinical data by personal interview was collected. INF1A, Anti-Ro, anti-
Ro52KDa and anti-Ro60KDa levels where measured by colorimetric methods. Biostatistical analysis was performed with
R 3.3.2.
Results:
We selected 69 SLE patients with negative results for anti-Ro (2.34±4.17 U/mL) out of 142 total SLE patients. A total of 51
patients were negative for both anti-Ro subunits and 18 cases presented positive results (up to 20 pg/mL) for at least one of
them.
Anti-RO52KDa
NEGATIVES POSITIVES Anti-RO60KDa Anti-RO52KDa / Anti-RO60KDa
N=51 POSITIVES N=2 POSITIVES N=8
N=8
Anti-RO [U/mL] Mean
1.92 (3.11) 1.65 (3.2) 0.5 (0.71) 6.15 (8.37)
(DS)
Anti-RO52 KDa
1.26 (1.89) 147.24 (74.25) 1.05 (0.89) 196.82 (50.06)
[pg/mL] Mean (DS)
Anti-RO60 KDa
1.73 (2.71) 6.3 (7.01) 120.96 (111.78) 145.22 (76.69)
[pg/mL] Mean (DS)
The subgroup of patients that exhibit simultaneously high levels of anti-Ro52KDa and anti-Ro60KDa have higher clinical
activity compared to negative anti-Ro cases (75% of active patients against 41.2% in anti-Ro negative patients). However,
no differences in the accumulated damage evaluated by SLICC score between negative anti-Ro cases and patients with at
least one positive subunit were observed.
We analyze serum levels of INF1A cytokine in the four groups of patients, and anti-Ro and subunits negative cases showed
significant lower INF1A levels than the other patients (8.26±14.87 pg/mL and 26.62±40.71 pg/mL respectively; P=0.04).
In addition, patients with high levels of anti-Ro52KDa subunit are those with the highest INF1A levels (anti-Ro 52+/anti-
Ro60- 23.5±47.6pg/mL of INF1A; anti-Ro 52+/anti-Ro60+ 36.4±37.9pg/mL of INF1A).
Conclusion:
In our anti-Ro seronegative patients, a 26% of false-negative cases were detected. These cases with high levels of almost
one anti-Ro subunit showed significantly higher levels of INF1A in contrast to negative cases, supporting the fact that they
are indeed a different group from the negative cases. Moreover, the high INF1A levels could be the reason of the observed
differences in the clinical activity measured by SLEDAI score in both groups.
Disclosure: E. Grau Garcia, None; I. Chalmeta Verdejo, None; D. Gimenez-Romero, None; E. Labrador Sanchez,
None; M. Fernandez Matilla, None; F. M. Ortiz-Sanjuán, None; C. Feced Olmos, None; N. Fernandez-Llanio
Cornella, None; K. Arevalo Ruales, None; R. Negueroles Albuixech, None; J. Ivorra Cortes, None; J. J. Fragio Gil,
None; I. Martinez Cordellat, None; R. Gonzalez Mazario, None; L. Gonzalez Puig, None; C. Alcañiz Escandell, None;
C. Najera Herranz, None; I. Canovas Olmos, None; E. Vicens Bernabeu, None; J. E. Oller Rodriguez, None; J. A.
Castellano Cuesta, None; V. Fornes Ferrer, None; D. Hervás Marín, None; M. De la Rubia Navarro, None; J. A.
Roman Ivorra, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/anti-ro52-kda-and-anti-ro60-kda-

analysis-in-systemic-lupus-erythematous-patients-to-detect-anti-ro-false-negatives
Anti-C1q Antibodies and Disease Activity in a Multi-Ethnic Lupus Cohort

Sameer Bahal1, Debasish Pyne1, Ravindra Rajakariar1, Myles Lewis1, Angela Pakozdi1, Sofia Grigoriadou2 and Andrea
Cove-Smith1, 1Barts Lupus Centre, Barts Health NHS Trust, London, United Kingdom, 2Immunology Department, Barts
Health NHS Trust, London, United Kingdom
SESSION INFORMATION
Background/Purpose:
Anti-C1q antibodies (C1Q Ab) are observed in 30-60% of patients with Systemic Lupus Erythematosus (SLE). A number
of studies have shown that the presence of C1Q Ab correlates with disease activity. In particular C1Q Ab is reported to
strongly correlate with active renal disease with some studies reporting antibody absence having a negative predictive value
of close to 100% for active lupus nephritis (LN) (1). However specificity for active lupus remains controversial and
variations may be due to timing of samples, assay used, cut off values and population studied.
Here we undertook a point-in-time measurement of C1Q Ab in a multi ethnic cohort of SLE patients and investigated
correlations between this and clinical and serologic parameters of SLE.
Methods:
SLE patients attending an inner city Lupus Clinic were involved in the study. Disease activity was calculated using the SLE
Disease Activity Index (SLEDAI 2K); erythrocyte sedimentation rate (ESR), dsDNA Ab, complement levels (C3, C4), and
urine protein creatinine ratio (uPCR) were measured. For patients with biopsy proven LN renal inactivity was defined as a
PCR < 50 mg/mmol. C1Q Ab was quantified by ELISA (Orgentec Diagnostika GmbH). A positive test defined by the
manufacturer is a level above 10 U/ml. Correlation of C1Q Ab levels with disease activity markers was measured using
Pearson’s correlation.
Results:
116 patients were included in the study. All fulfilled the 2012 SLICC criteria for SLE. 103 (89%) were female. There were
38 (32.8%) South Asians (SA), 48 (41.3%) Afro Caribbean (AC) and 25 (21.6%) White Caucasians (WC). C1Q Ab
positivity was present in 29% SA patients, 13% AC patients and 28% WC patients (p=0.06).
There was a positive correlation between C1Q Ab levels and dsDNA levels (r=0.358, p<0.01); whilst a negative correlation
was observed with C3 levels (r=-0.406, p<0.01). No correlation was found with SLEDAI scores(r=0.18, p=0.053), uPCR
(r=0.13, p=0.16) and ESR (r=0.045, p=0.63). Positive C1Q Ab was more common in patients with a history of biopsy
proven LN (32.7%); of these patients, 43% (n=12/28) had inactive LN at the time of sampling with a positive C1q Ab. In
addition, C1Q Ab was present in 15.5% (n=9) of patients with minimally active disease (SLEDAI≤ 4).
Conclusion:
The overall prevalence of C1Q Ab was 23.3% in our lupus cohort, and was present in all ethnic groups. Its presence was
correlated with dsDNA but not with SLEDAI score, ESR and PCR. There was a negative correlation with C3 level. C1Q
Ab was found more commonly in renal than in non-renal patients. Importantly a positive C1Q Ab level was found in 15.5%
of patients with inactive disease defined as SLEDAI≤ 4 and in 43% of LN patients with inactive renal disease (defined as
PCR<50). We would therefore caution against use of C1Q Ab as a stand-alone biomarker for active lupus.
References
1. Fremeaux-Bacchi V, Noel LH, Schifferli JA. No lupus nephritis in the absence of antiC1q autoantibodies? Nephrol Dial
Transplant 2002; 17:2041–2043.
Disclosure: S. Bahal, None; D. Pyne, None; R. Rajakariar, None; M. Lewis, None; A. Pakozdi, None; S. Grigoriadou,
None; A. Cove-Smith, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/anti-c1q-antibodies-and-disease-

activity-in-a-multi-ethnic-lupus-cohort
Endothelial Dysfunction in Systemic Lupus Erythematosus Patients without

Cardiovascular events and Risk Factors: Correlation with Microvascular
Alterations and angiogenic t Cells
Ilaria Cavazzana1, Mara Taraborelli2, Silvia Piantoni3, Ivano Bonadei4, Edoardo Sciatti5, Micaela Fredi6, Marco Metra4,
Angela Tincani7, Franco Franceschini1 and Enrico Vizzardi4, 1Rheumatology and Clinical Immunology, Spedali Civili of
Brescia, Brescia, Italy, 2Internal Medicine; Ospedale Mellini, Chiari (Brescia), Italy, 3Rheumatology and Clinical
Immunology Unit, Spedali Civili, University of Brescia, Brescia, Italy, 4Cardiology Unit, Spedali Civili, University of
Brescia, Brescia, Italy, 5Cardiology Unit, Spedali Civili, University of Brescia, Brsecia, Italy, 6Department of
Rheumatology and Clinical Immunology, Rheumatology and Clinical Immunology, Rheumatology and Clinical
Immunology, Spedali Civili of Brescia, Brescia, Italy, 7Rheumatology and Clinical Immunology, Spedali Civili and
University of Brescia, Brescia, Italy
SESSION INFORMATION
Background/Purpose: early identification of subclinical cardiovascular disease (CVD) in systemic lupus erythematosus
(SLE) patients is mandatory to reduce morbidity and mortality. Endothelial dysfunction (ED) is one of the first steps of the
process leading to atherosclerosis and has been associated with further CVD development. Aim of the study was to assess
the prevalence of ED by a non invasive procedure in SLE patients with early disease without CVD and risk factors, and
correlate ED with nailfold capillary morphology and angiogenic T (angT) cells. AngT cells are a T cell subpopulation,
involved in repair mechanisms of the endothelium, cooperating with endothelial progenitors cells.
Methods: all the consecutive SLE patients, according to SLICC Classification Criteria, with a disease duration less than 5
years, evalued from december 2014 to march 2016 were proposed to participate to the study. Exclusion criteria were
represented by history of CVD, diabetes, chronic renal disease (creatinine clearance<60 ml/min), not controlled systemic
arterial hypertension, current or past smoking (in the last 3 years), hypercholesterolemia (total cholesterol>240 mg/dl),
obesity (body mass index > or =30), statin or beta-blocker use. Each patient underwent a clinical and serological
evaluation, a transthoracic doppler echocardiogram, endothelial function study by endoPAT technique, nailfold
videocapillaroscopy (NVC) and T cell subpopulation study. Characteristics of patients with ED (ED+), defined as reactive
hyperemic index < or= 2, were compared to those of patients without ED (ED-) and normal controls, matched for age, sex
and CV exclusion criteria, by Fisher, T student or Mann-Whitney tests as appropriate.
Results: Among 46 screened SLE patients, 20 patients were enrolled (100% female, 80% caucasian) with a median disease
duration of 14 months (0-68), a mean age of 42 years (±15), and a mean age at diagnosis of 40 years (±16). Arthritis,
cutaneous and hematological features were found in 70%, 55% and 65% of cases, respectively. ANA, antidsDNA and anti-
ENA were found in 100%, 50% and 50% of cases. Anti-cardiolipin and antibeta2glycoprotien I antibodies in 20% and
10%. ED was found in 8 patients (40%). ED didn't correlate with any demographic-clinical-serological-echocardiographic
features. A significantly higher prevalence of ED (p:0.003), vascular stiffness (p:0.02), left ventricular concentric
remodelling (p:0.003), grade I diastolic dysfunction (p:0.04) were found in SLE patients compared to controls.
ED+ patients more frequently showed minor NVC abnormalities (i.e. tortuous,/crossed/enlarged) (p: 0,007), lower capillary
number/mm (p: 0,01) and wider intercapillary distance (p: 0,06) compared to controls. AngT cells were significantly
reduced in SLE patients compared to controls (p: 0,045), but they were increased in ED+ SLE compared to ED- (p: 0,04).
Conclusion: A significant proportion of SLE patients showed signs of ED despite a recent disease and the absence of
cardiovascular risk factors. ED correlates with microvascular alterations by videocapillaroscopy and increased ang T cells,
as marker of endothelium repair.
Disclosure: I. Cavazzana, None; M. Taraborelli, None; S. Piantoni, None; I. Bonadei, None; E. Sciatti, None; M.
Fredi, None; M. Metra, None; A. Tincani, None; F. Franceschini, None; E. Vizzardi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/endothelial-dysfunction-in-systemic-

lupus-erythematosus-patients-without-cardiovascular-events-and-risk-factors-correlation-with-microvascular-alterations-
and-angiogenic-t-cells
Homocysteine Levels Are Independently Associated with Damage Accrual in

Systemic Lupus Erythematosus Patients (SLE)
Paola Zeña-Huancas1, Manuel Ugarte-Gil2,3, Rocío Gamboa-Cárdenas1, Francisco Zevallos1, Mariela Medina1, Victor
Pimentel-Quiroz2, Claudia Elera-Fitzcarrald1, Omar Sarmiento-Velasquez1, Cristina Reategui-Sokolova1, Mariano Cucho-
Venegas1, José Alfaro-Lozano1, Zoila Rodriguez-Bellido1,4, Cesar A. Pastor-Asurza1,4, Graciela S. Alarcón5 and Risto
Perich-Campos4,6, 1Rheumatology, Hospital Guillermo Almenara Irigoyen. EsSalud, Lima, Peru, 2Peru, GLADEL, Lima,
Peru, 3Universidad Cientifica del Sur, Lima, Peru, 4Universidad Nacional Mayor de San Marcos, Lima, Peru, 5University
of Alabama at Birmingham, Birmingham, AL, 6Rheumatology, Hospital Guillermo Almenara Irigoyen, Lima, Peru
SESSION INFORMATION
Background/Purpose:
Homocysteine level is a predictor of the occurrence of cardiovascular diseases, however, its role as a predictor of damage in
SLE has not been studied. The aim of this study is to determine the impact of homocysteine levels on damage accrual in
SLE patients.
Methods:
These analyses were conducted in 145 SLE patient, 136 females and 9 males, followed longitudinally at a single center.
Evaluations were done every six months and included interview, medical records review, physical examination and
laboratory tests. Disease activity was measured with the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index).
Damage accrual was ascertained with the SLICC/ACR damage index (SDI). Univariable and multivariable Cox regression
models were performed to determine if homocysteine levels were associated with damage accrual. The multivariable model
was adjusted for variables known to be associated with this outcome [age at diagnosis, gender, socioeconomic status,
disease duration, SLEDAI, antimalarials and immunosuppressive drugs use, average daily dose and time of exposure to
prednisone (PDN)].
Results:
The patients mean (SD) age at diagnosis was 43,70 (12,09) years, nearly all were Mestizo. At baseline, disease duration
was 7,55 (6,73) years. The SLEDAI was 5,60 (4,34) and the SDI 0,97 (1,35). The average daily dose of PDN was 7,30
(5,78) mg/d and the time of exposure to PDN was 7,36 (6,73) years. Mean homocysteine levels was 10,07 (3.71)
µmoles/liter. Patients were followed for 3.54 (1.27) years, and 75 (51.7%) increased at least one point in the SDI.
Homocysteine level predicted new damage accrual in the univariable and multivariable models [HR 1.08 (CI95%: 1.03-
1.14); p=0.002 and HR: 1.09 (CI95%: 1.02-1.16); p=0.008 respectively.]
Table. Homocysteine level as Predictor of Damage
Accrual In SLE (multivariable analyses)
Variables HR 95% CI p-
value
Homocysteine 1,090 [1,023- 0,008
1,162]
Age at diagnosis, years 1,025 [1,001- 0,045
1,050]
Disease duration, years 1,058 [0,999- 0,054
1,121]
Gender (female) 0,834 [0,292- 0,734
2,380]
Socioeconomic status
High Ref.
Medium status 1,196 [0,602- 0,609
2,378]
Low status 1,129 [0,634- 0,681
2,011]
SLEDAI, median 1,026 [0,969- 0,379
1,086]
Immunosuppressive drugs
use
Never Ref.
Past 0,949 [0,456- 0,888
1,975]
Current 1,474 [0,838- 0,178
2,593]
Hydroxychloroquine use
Never Ref.
Past 0,782 [0,294- 0,622
2,080]
Current 0,558 [0,266- 0,124
1,172]
Prednisone current dose 0,995 [0,955- 0,821
(mg/d) 1,037]
Time of exposure to 1,000 [0,945- 0,998
prednisone, years 1,059]
SDI 0,867 [0,688- 0,229
1,094]
SDI SLICC/ACR damage index, SLEDAI systemic lupus
erythematosus disease activity index
Conclusion:
Homocysteine levels in SLE patients predicted damage accrual independently of other well-known risk factors of damage.
Disclosure: P. Zeña-Huancas, None; M. Ugarte-Gil, None; R. Gamboa-Cárdenas, None; F. Zevallos, None; M.

Medina, None; V. Pimentel-Quiroz, None; C. Elera-Fitzcarrald, None; O. Sarmiento-Velasquez, None; C. Reategui-
Sokolova, None; M. Cucho-Venegas, None; J. Alfaro-Lozano, None; Z. Rodriguez-Bellido, None; C. A. Pastor-
Asurza, None; G. S. Alarcón, None; R. Perich-Campos, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/homocysteine-levels-are-independently-
associated-with-damage-accrual-in-systemic-lupus-erythematosus-patients-sle
Associations between Standard Serological Markers and Different Clinical

Phenotypes in Systemic Lupus Erythematosus
Ilana Abeles1 and Vasileios C. Kyttaris2, 1Division of Internal Medicine, Beth Israel Deaconess Medical Center, Boston,
MA, 2Rheumatology, Beth Israel Deaconess Medical Center, Boston, MA
SESSION INFORMATION
Background/Purpose:
Systemic lupus erythematosus (SLE) affects various body organs making its clinical presentation highly variable. While
previous studies have demonstrated associations between lab abnormalities and individual clinical manifestations of
disease, our study aimed to be more specific and categorized patients into sub-groups based on their unique presentations.
We then investigated associations between immunological/serological abnormalities and exclusive clinical phenotypes of
SLE.
Methods:
Information regarding SLE related clinical symptoms and serological data were collected from 201 patients diagnosed with
SLE. Laboratory abnormalities included: anti-nuclear antibody (Ab), anti-Ro Ab, anti-La Ab, anti-Smith Ab, anti-U1-
ribonucleoprotein Ab, anti-rheumatoid factor Ab, anti-dsDNA Ab, low C3, low C4, anti-cardiolipin Ab, lupus
anticoagulant and beta2-glycoprotein. Patients were classified into clinical subgroups based on manifestation(s) of disease:
arthritis alone (A); mucocutaneous disease alone (B); nephritis alone (C); arthritis + mucocutaneous disease (D); arthritis +
nephritis (E); nephritis + mucocutaneous disease (F); or all 3 (G). Omnibus chi-square tests evaluated associations between
individual lab abnormalities and phenotype with subsequent post-hoc evaluation for significant omnibus tests. Positive and
negative predictive values (PPV, NPV) were also investigated.
Results:
Analyses revealed that anti-Smith, anti-dsDNA antibodies and low levels of C3 and C4 were associated with phenotype G
(p=0.001, Chi-square (χ2)=11.3; p=0.004, χ2=8.3; p<0.0001, χ2=21.4; p<0.0001, χ2=22.5 respectively) with a PPV of
59.4%, 85.3%, 91.2% and 85.3% respectively, and anti-Sm Ab had a NPV of 71.3%. Anti-dsDNA Ab, low C3 and C4
levels were additionally significantly associated with phenotype F (p=0.01, χ2= 6.25; 0.01, χ2=6.48; p=0.01, χ2=6.54
respectively). PPV of anti-dsDNA Ab, low C3 and C4 for F was 93.3%, 91.2%, and 80% respectively and 73.3%
combined. Further, anti-ds-DNA Ab, low C3 and C4 were negatively associated with phenotype B (p<.001, χ2= 15.3;
p<.001, χ2=12.48; p=.014, χ2=6.1, respectively). Low complement levels were also negatively associated with phenotype D
(C3: p=.038, χ2=4.3; C4: p=.011, χ2= 6.54). While nephritis alone was not significantly associated with any markers, anti-
dsDNA Ab, and low complement levels combined had an 80.8% NPV for renal disease.
Conclusion:
Our results suggest that an expanded epitope including anti-dsDNA and anti-Smith antibodies, along with low complement
levels are associated with a broader phenotype in SLE which includes arthritis, nephritis and mucocutaneous involvement.
Anti-dsDNA Ab and low complement levels were also associated with the mucocutaneous disease and nephritis combined
but not nephritis or mucocutaneous disease alone. In fact, these serological markers were negatively associated with
mucocutaneous involvement. These findings suggest that immunological profiles may reflect unique phenotypes of SLE.
Future genetic models that target particularphenotypes of SLE and associated immunologic abnormalities may be useful in
developing new drug therapies.
Disclosure: I. Abeles, None; V. C. Kyttaris, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/associations-between-standard-

serological-markers-and-different-clinical-phenotypes-in-systemic-lupus-erythematosus
Apolipoprotein L1 Risk Variants Associate with Hypertension and Nephritis

Progression Despite Lower dsDNA Titers in Ghanaian Systemic Lupus
Erythematous Patients
Ashira Blazer1, Ida Dzifa Dey2, Sara Rasmussen3, Robert M. Clancy4 and Jill P. Buyon5, 1Internal Medicine Division of
Rheumatology, NYU School of Medicine, New York, NY, 2Internal Medicine, Rheumatology, The University of Ghana,
Accra, Ghana, 3Department of Medicine, Division of Rheumatology, NYU School of Medicine, New York, NY, 4NYU
School of Medicine, New York, NY, 5Rheumatology, New York University School of Medicine, New York, NY
SESSION INFORMATION
Background/Purpose: Two Apolipoprotein L1 (APOL1) risk variants (RV), G1 and G2 are enriched in African
populations due to a conferred resistance to Trypanosoma brucei. This comes with the cost of progressive renal disease by
multiple causes including SLE. Despite the high regional allelic frequencies, APOL1 variant phenotypes have never been
described in a Sub-Saharan African SLE cohort. Further, it is unclear if SLE nephritis progression in RV carriers is driven
by inflammation or intrinsic nephropathy. Accordingly, this prospective longitudinal cohort study evaluated APOL1
genotype-phenotype traits in the context of SLE activity in 72 Ghanaian patients seeking care at Korle bu Teaching
Hospital in Accra, Ghana.
Methods: All 72 patients met 4 ACR criteria for SLE and were stratified by APOL1 genotype using PCR/sequencing as
follows: ancestral (G0/G0), RV heterozygotes (RV/G0), and RV homozygotes (RV/RV). DNA was extracted from saliva,
and ancestry informative markers were performed on a subset of 20 patients to confirm heritage. ANAs were confirmed in
the NYU clinical lab by multiplex analysis. Endpoints collected at three, 6 month intervals included demographics, ACR
criteria, SLEDAI score, vital signs, and lab values as available. To measure SLE serologic activity, dsDNA titers were
completed and in 15 subjects (5 per genotype), interferon (IFN) signature was measured by the WISH cell assay.
Results: The frequencies of the G0, G1, and G2 alleles were 60%, 25%, and 14.5% respectively (meeting Hardy Weinberg
Equilibrium) and principal component analysis confirmed ancestry. Subjects were all female, average age of 32.1 years
with SLE duration of 2.3 years. Data were collected on at least one, two, or three time points on 72, 56, and 30 subjects
respectively. There were no differences in history of nephritis, diabetes, or age across the genotypes. The RV associated
with higher average BPs; 109.9/75.7, 111.3/75.2, and 125.2/85.6 mmHg in the G0/G0, RV/G0, and RV/RV groups
respectively (p: 0.04 systolic; 0.02 diastolic). Only 13% of the cohort took anti-hypertensives regardless of genotype.
Among those with nephritis, RV/RV had increased creatinine: 0.9, 1.1, and 2.5 mg/dL in the G0/G0, RV/G0, and RV/RV
groups respectively (p: 0.03). RV/RV carriers took higher doses of prednisolone (17.2mg) compared to G0/G0 or RV/G0
(11.2mg; 11.8mg respectively), however this did not reach statistical significance and there was no difference in SLEDAI
scores. Despite higher creatinine, RV/RV carriers were less likely to ever have had anti-DNA positivity (11% positive) and
had lower dsDNA titers (10.7 IU/mL) than G0/G0 (41% positive; 57.1 IU/mL) and RV/G0 (43% positive; 95.6 IU/mL)
carriers (p: 0.03). IFN signatures in both G0/G0 and RV/G0 patients were higher than in RV/RV (245.7, 81.3, and 24.3
respectively). G0/G0 or RV/G0 carriers were more likely to have IFN scores above the average value of 109.9 (LR: 4.3; p:
0.04).
Conclusion:
Taken together, RVs associated with higher BP and creatinine in this Ghanaian SLE cohort. Despite having poorer renal
function, RV homozygotes exhibited lower dsDNA titers and lower IFN signatures than G0/G0 or RV/G0 patients
potentially suggesting intrinsic renal disease independent of SLE activity in RV homozygotes.
Disclosure: A. Blazer, None; I. D. Dey, None; S. Rasmussen, None; R. M. Clancy, None; J. P. Buyon, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/apolipoprotein-l1-risk-variants-

associate-with-hypertension-and-nephritis-progression-despite-lower-dsdna-titers-in-ghanaian-systemic-lupus-
erythematous-patients
SSA Antibodies Are Associated with Valvular Abnormalities in SLE Patients

without Clinical Cardiovascular Disease
Elizabeth George1, Thania Perez2, Anca Askanase3 and Laura Geraldino-Pardilla4, 1Rheumatology, Columbia University
College of Physicians and Surgeons, New york, NY, 2Columbia University College of Physicians & Surgeons, New York,
NY, 3Rheumatology, Columbia University College of Physicians & Surgeons, New York, NY, 4Columbia University, New
york, NY
SESSION INFORMATION
Background/Purpose: Cardiovascular involvement including pericardium, conduction system, coronary arteries and
valvular abnormalities are frequent manifestations of SLE. It is estimated to occur in more than 50% of SLE patients and
the prevalence is increasing in the setting of imaging modalities like echocardiogram. Studies have shown approximately
11 times higher risk of any valvular abnormalities in SLE, with mitral valve regurgitation being the most common among
them. The mechanism of injury and risk factors are still not completely understood. While association of antiphospholipid
antibodies and SLE related valve disease is well known, role of other antibodies like SSA and Anti-Smith remains poorly
defined. Recent studies have shown the increased incidence of SSA antibodies in SLE and their positive association with
severe mitral valve regurgitation. Though the detection of the early or minor changes by using echocardiography may be
limited, these parameters are reliable for all-cause mortality and cardiac morbidity. We sought to test the association
between valvular abnormalities and SSA antibodies in SLE patients without clinical cardiovascular disease (CVD).
Methods: Adult SLE patients without clinical CVD continuously seen at a University Lupus Center between April 2016
and March 2017, meeting 1997 ACR classification criteria for SLE were studied. Patient characteristics including
demographics, SLE-specific features, medication use, traditional CVD risk factors, 12-lead electrocardiogram (EKG) were
ascertained. Trans Thoracic Echocardiogram (TTE) was obtained mainly retrospectively from within one year of the date of
enrolment. Univariable and multivariable linear regression models were constructed to test the association of SSA
antibodies with valvular abnormalities.
Results: Sixty-four SLE patients (baseline characteristics in table 1) were studied. In univariable analyses, presence of SSA
antibodies was significantly associated with a higher incidence of any valvular abnormality (OR= 5.8, P = 0.042) , mitral
valve regurgitation ( OR= 3.08, p=0.05) and tricuspid valve regurgitation (TVR) ( OR = 4.95, p= 0.018) . Multivariable
regression models showed the absence of any confounders. There were a total of 54 (84%) valvular abnormalities with
TVR being the most common at 49 (77%).
Conclusion: SSA Antibodies are associated with valvular abnormalities with TVR being most common in SLE patients
without clinical cardiovascular disease
Disclosure: E. George, None; T. Perez, None; A. Askanase, Exagen, 2; L. Geraldino-Pardilla, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/ssa-antibodies-are-associated-with-

valvular-abnormalities-in-sle-patients-without-clinical-cardiovascular-disease
Serum Anti-NR2 Has a Better Specificity Than Sensitivity in Diagnosing

Neuropsychiatric Systemic Lupus Erythematosus (NPSLE)
Seyed-Foad Ahmadi1, Golara Zahmatkesh2, Masoud Majed3 and Sheetal Desai4, 1Department of Medicine, University of
California Irvine, Orange, CA, 2Department of Psychiatry, Charles Drew University of Medicine and Science/UCLA, Los
Angeles, CA, 3Division of Neuroimmunology, Mayo Clinic, Rochester, MN, 4Medicine/Rheumatology, Unviersity of
California, Irvine, Orange, CA
SESSION INFORMATION
Background/Purpose: Anti-NR2, a subclass of anti-NMDA receptor antibodies, is reportedly associated with NPSLE
syndromes. However, its diagnostic accuracy is inconsistent across prior studies. Hence, we aimed to quantitatively
synthesize the data regarding the sensitivity and specificity of anti-NR2 in diagnosing NPSLE.
Methods: We searched PubMed, Embase, CINAHL and the Web of Knowledge. We included the studies of the diagnostic
test accuracy of anti-NR2 for diagnosing NPSLE among patients with SLE, in which they used the ACR case definitions or
other validated tools as their reference standards. Two investigators (SFA, GZ) independently replicated data extraction by
using a standard form, which included an assessment of study quality as well as participant-level data to populate 2×2
contingency tables. For meta-analysis, we used the Hierarchical Summary Receiver Operating Characteristic (HSROC)
model by Rutter & Gatsonis (2001) in Stata 13.0.
Results: We screened 1583 records and eventually included the data from 8 studies with a collective sample of 984 patients
(Figure 1). The pooled data represented a wide range of NPSLE manifestations including acute confusional state, seizure
disorders, cerebrovascular disease, aseptic meningitis, headaches, cognitive dysfunction, psychoses, mood disorders,
movement disorders (chorea), myasthenia gravis, demyelinating syndromes, myelopathy, plexopathy, and mono, poly, and
cranial neuropathies. The reported sensitivities fell within a wider range (5% to 100%) compared to the specificities range
(64% to 92%) (Figure 2). Meta-analysis of the results yielded the following pooled results with their 95% confidence
intervals: Sensitivity 53% (24-80%), Specificity 77% (69-83%), -Likelihood ratio (LR) 0.61 (0.30-1.25), and +LR 2.26
(1.07-4.76) (Figure 3).
Conclusion: Serum anti-NR2 Ab has non-significant sensitivity and -LR, but it has statistically significant specificity and
+LR in diagnosing NPSLE. Thus, patients with suspected NPSLE may benefit from checking their anti-NR2 levels.
Nevertheless, further analyses are needed before recommending anti-NR2 for routine clinical use.
Disclosure: S. F. Ahmadi, None; G. Zahmatkesh, None; M. Majed, None; S. Desai, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/serum-anti-nr2-has-a-better-specificity-

than-sensitivity-in-diagnosing-neuropsychiatric-systemic-lupus-erythematosus-npsle
High Plasma Factor XIII Transglutaminase Activity Inversely Correlates

with SLE Disease Activity Yet Associates with Higher Carotid Artery IMT
and Low CD14+CD16+ Monocyte Levels
Brian Skaggs1, Isao Matsuura2, Elaine Lourenco1, Eloise Olmos3, Jennifer M. Grossman1 and Maureen A. McMahon1,
1University of California-Los Angeles, David Geffen School of Medicine, Division of Rheumatology, Los Angeles, CA,
2Department of Rheumatology, Tokyo Women's Medical University Yachiyo Medical Center, Chiba, Japan, 3Division of
Rheumatology, UCLA David Geffen School of Medicine, Los Angeles, CA
SESSION INFORMATION
Background/Purpose: The transglutaminase Factor XIII (FXIII) stabilizes blood clots through crosslinking fibrin lysine
and glutamine residues at the end of the complement cascade. Enzymatic activity and plasma levels of FXIII appear to be
tightly controlled, as excess FXIII can lead to increased arterial plaque, yet low or absent FXIII leads to thrombosis due to
fibrin instability. In addition, recent data suggest that tissue macrophages could be the main source of plasma FXIII. Anti-
FXIII antibodies have been observed in SLE and correlate with brain hemorrhage, although other clinical correlations
between plasma FXIII and SLE remain unexplored.
Methods: 120 SLE patients were recruited from a pre-existing longitudinal cohort developed to study atherosclerosis in
SLE. Anti-dsDNA, C3 and C4 levels were analyzed in the clinical lab of our university hospital. Carotid ultrasound was
performed to determine the presence or absence of subclinical atherosclerosis and intima-media thickness (IMT). The
Technochrom FXIII kit (Diapharma, West Chester, OH) was utilized to determine plasma FXIII transglutaminase activity.
Plasma monocyte subpopulations were identified by flow cytometry using anti-CD14 and –CD16 fluorescent antibodies
(Biolegend).
Results: 66/120 SLE patients had high plasma FXIII transglutaminase activity (>143% of the mean of the standard curve).
SLEDAI was significantly lower in the high FXIII activity group compared to patients with normal FXIII activity
(2.08±3.9 versus 4.2±3.1, p=0.006). In addition, anti-dsDNA antibody levels were significantly lower in the high FXIII
activity group (87.5±255.7 versus 274.7±323.8, p=0.041). Significantly higher levels of plasma C3 and C4 levels were also
observed in the high FXIII activity group. Taken together, these results show that higher FXIII activity might be a
biomarker for lower SLE disease activity.
In contrast, percentages of CD14+CD16int and CD14+CD16hi plasma monocytes (considered precursors to anti-
inflammatory ‘M2” macrophages) were inversely proportional to FXIII activity (r=-0.54, p=0.008; r=-.064, p=0.005,
respectively), although there was no correlation between classical plasma monocyte levels (CD14+CD16-, ‘M1’
macrophage precursors) and FXIII enzymatic activity. In addition, IMT positively correlated with FXIII activity (r=0.40,
p=0.01). No correlations between carotid plaque presence and FXIII activity were noted.
Conclusion: High plasma FXIII transglutaminase activity correlates with multiple measures of low disease activity in SLE
patients. Conversely, high FXIII activity inversely correlated with low numbers of anti-inflammatory monocytes. Higher
IMT was also observed in patients with high FXIII activity. Careful regulation of FXIII enzymatic activity, and, by
extension, its crucial role in fibrin crosslinking and plaque stabilization, could be dysregulated in a subset of SLE patients
at risk for accelerated atherosclerosis.
Disclosure: B. Skaggs, None; I. Matsuura, None; E. Lourenco, None; E. Olmos, None; J. M. Grossman, Medimmune,
2,AstraZeneca, 2,Aurinia, 2,Genentech and Biogen IDEC Inc., 2; M. A. McMahon, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/high-plasma-factor-xiii-

transglutaminase-activity-inversely-correlates-with-sle-disease-activity-yet-associates-with-higher-carotid-artery-imt-and-
low-cd14cd16-monocyte-levels
The Utility of a Rise in Anti – Double Stranded DNA Antibodies for

Predicting Disease Flares in Systemic Lupus Erythematosus. a Meta-Analysis
Margrét Arna Viktorsdóttir1, Sæmundur Rögnvaldsson1, Þórunn Jónsdóttir2 and Gunnar Tomasson3, 1University of
Iceland, Faculty of Medicine, Reykjavík, Iceland, 2Landspítali University Hospital, Reykjavík, Iceland, 3University of
Iceland, Faculty of Medicine, Reykjavik, IS
SESSION INFORMATION
Background/Purpose: The ability of predicting disease flares in systemic lupus erythematosus (SLE) by serial
measurements of antibodies to double stranded DNA (anti-dsDNA) remains uncertain. Previous studies have found
inconsistent results and clinical guidelines provide vague recommendations regarding this aspect of disease management.
The objective of this study is to assess the diagnostic value of rise in anti-dsDNA for prediction of a disease flare in SLE.
Methods: A MEDLINE search without language restrictions was conducted to identify papers on anti-dsDNA and disease
flares in SLE. Papers that could not be excluded by a review of titles and abstracts were subject to a detailed review. The
primary inclusion criteria were 1) availability of the data to extract the sensitivity and specificity of a rise in anti-dsDNA
for a disease flare and 2) the rise in anti-dsDNA preceded the flare. For each study, the positive and negative likelihood
ratios were calculated and information extracted on disease manifestations and laboratory methods of anti-dsDNA
measurements. Summary estimates with 95% confidence intervals (CI) were calculated with a random effects model and
results expressed with forest plots. Between-study heterogeneity was assessed with I2, which takes a value from 0 to 1 and
refers to the part of the total variability in the meta-analysis that is due to heterogeneity. Meta-regression was used to assess
the impact of the i)publication year, ii)gender proportions, iii)proportion of patients who had renal manifestations,
iv)method- and v)frequency of anti-dsDNA measurements on summary estimates and heterogeneity. Egger's test was used
to assess for publication bias using p-value of <0.05 as cut-off. The trim-and-fill method was used to adjust the summary
estimates for publication bias.
Results:
Literature search identified 1690 papers of which 58 underwent full-text review. Nine studies with a total of 922 patients
were included, of them 256 patients had a rise in anti-dsDNA and 243 had flares. Summary estimates for positive and
negative likelihood ratios for anti-dsDNA rise and subsequent disease flare were 4.15 (95% CI 2.03-8.47) and 0.47 (95%
CI 0.31-0.72) respectively (Figure). There was substantial between-study heterogeneity I2=0.89). Neither disease
manifestations nor the methods anti-dsDNA measurements affected the summary estimates or explained heterogeneity.
Findings were consistent with presence of publication bias (p=0.021). Adjustment for publication bias substantially
attenuated the summary estimates resulting in positive and negative likelihood ratios of 1.90 (95% CI 0.84-4.33) and 0.72
(95% CI 0.46-1.14), respectively.
Conclusion:
A rise in anti-dsDNA has a limited ability for predicting flares in SLE and publication bias may have exaggerated the utility
of serial anti-dsDNA measurements. These findings have direct implications for clinical management of SLE.
Disclosure: M. A. Viktorsdóttir, None; S. Rögnvaldsson, None; Þ. Jónsdóttir, None; G. Tomasson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-utility-of-a-rise-in-anti-double-

stranded-dna-antibodies-for-predicting-disease-flares-in-systemic-lupus-erythematosus-a-meta-analysis
Serum Wisteria Floribunda Agglutinin-Positive Mac-2-Binding Protein Can

Reflect Systemic Lupus Erythematosus Activity
Sung Soo Ahn1, Younhee Park2, Seung Min Jung1, Jason Jungsik Song1, Yong-Beom Park1 and Sang-Won Lee1,
1Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea,
Republic of (South), 2Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea, Republic
of (South)
SESSION INFORMATION
Abstract Background/Purpose : Serum Mac-2-binding protein (M2BP) is elevated in various chronic inflammatory
diseases. Recently, the Wisteria floribunda agglutinin positive-M2BP (WFA+-M2BP) immunoassay has shown promise in
detection of highly glycosylated M2BP. We aimed to evaluate the clinical utility of serum M2BP for assessing disease
activity of systemic lupus erythematosus (SLE), using the WFA+-M2BP immunoassay. Methods : Serum M2BP was
measured in 203 patients with SLE. The associations between SLEDAI-2K and variables was assessed using multivariate
linear regression analysis. The relationship between serum M2BP and laboratory variables related to the SLE disease
activity index (SLEDAI)-2K and inflammatory burdens was evaluated by Pearson¡¯s correlation analysis. Multivariate
logistic regression analysis was used to compare the odds ratios (ORs) of laboratory variables in predicting active SLE.
Results : Eighty patients were classified as having active SLE (SLEDAI-2K ¡Ã 5) and 123 patients as having inactive SLE.
The median serum M2BP was higher in patients with active SLE than those with inactive SLE (2.1 vs. 0.9, p < 0.001)
(Table 1). In multivariate linear regression analysis, serum M2BP, anti-ds DNA, C3, and erythrocyte sedimentation rate
were associated with SLEDAI-2K (Table 2). Serum M2BP was strongly correlated with laboratory variables related to
SLEDAI-2K and inflammatory burdens, compared to other significant variables. Multivariate logistic regression analysis
demonstrated that serum M2BP was more useful in predicting active SLE than other laboratory variables. Conclusion :
Serum M2BP can reflect SLE activity and furthermore, it can predict active SLE. We suggest that serum M2BP may be a
convenient complementary laboratory tool to SLEDAI-2K in the clinical setting. References 1. Nielsen CT, et al. Plasma
levels of galectin-3-binding protein reflect type I interferon activity and are increased in patients with systemic lupus
erythematosus. Lupus Sci Med 2014;1(1):e000026.

Disclosure: S. S. Ahn, None; Y. Park, None; S. M. Jung, None; J. J. Song, None; Y. B. Park, None; S. W. Lee, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/serum-wisteria-floribunda-agglutinin-

positive-mac-2-binding-protein-can-reflect-systemic-lupus-erythematosus-activity
Development of a Multimarker Model for the Detection of Systemic Lupus

Erythematosus Based on New and Traditional Autoantibodies
Petra Budde1, Hans-Dieter Zucht1, Johannes Schulte-Pelkum1, Daniel Wirtz1, Torsten Witte2, Matthias Schneider3 and
Peter Schulz-Knappe1, 1Protagen AG, Dortmund, Germany, 2Clinical Immunology and Rheumatology, Hannover Medical
School, Hannover, Germany, 3Policlinic for Rheumatology & Hiller Research Centre for Rheumatology, Heinrich-Heine-
University Duesseldorf, Duesseldorf, Germany
SESSION INFORMATION
Background/Purpose: Given the heterogeneity of clinical presentations, the diagnosis of Systemic Lupus Erythematosus
(SLE) can be challenging, in particular in those patients presenting with early or incomplete disease, or with overlapping or
atypical features. Autoantibodies (AABs) are important in aiding the clinical diagnosis of SLE, with some few AABs, anti-
double-stranded DNA (dsDNA), anti-Smith (Sm), and anti-ribosomal P (riboP) being highly associated with SLE. As none
of the traditional AABs has sufficient sensitivity to achieve diagnosis of SLE, current testing is based on measuring
multiple AAB assays either in parallel or serial. We have recently identified novel AABs in SLE, which hold promise for
improving diagnostic testing of SLE (1). We have developed quantitative ELISA-prototypes for five new AABs, which
were tested in combination with traditional AABs. The objectives of this study were to evaluate the diagnostic value of
novel AABs and to screen for an optimized combination of novel and traditional AABs using logistic regression to increase
the diagnostic accuracy of SLE testing.
Methods: Serum samples were obtained from 156 SLE patients with European ancestry at the rheumatology department
of the Heinrich-Heine University (Düsseldorf, Germany), and Hannover Medical School (Hannover, Germany). SLE
samples were compared against 126 samples from autoimmune diseases (AID; myositis: n=20; Sjögren’s syndrome (SjS):
n=31; rheumatoid arthritis (RA) n=36; systemic sclerosis (SSc): n=39), and 77 healthy control samples. Prototype bead
based ELISAs were developed for 5recently identified novel antigens. Traditional diagnostic AABs were measured using
IVD ELISAs and included: SSA/Ro60, SSA/Ro52, La/SSB, Sm, RNP, dsDNA, Scl70, CENPB, Jo-1, CCP, phospholipid
and dsDNA. Optimized marker combinations of new and traditional markers were tested using logistic regression and
receiver operating curve analysis (ROC).
Results: When comparing 156 SLE patients with 203 control samples, the area under the curve (AUC) of the five novel
SLE ELISAs ranged from 0.63 to 0.75. A cut-off was set at a specificity of 95% and yielded a sensitivity ranging from
13.5% to 21.2% for the five novel assays. The sensitivity and specificity of new ELISAs was comparable to traditional
ELISAs, which was in this cohort for anti-dsDNA 35% and 97%, anti-Sm 15% and 97%, and anti-RiboP 26% and 97%. A
logistic regression model was used to combine the results of multiple tests. Compared to a logistic regression with
traditional assays, a logistic regression with novel markers achieved higher sensitivity by pertaining high specificity. The
logistic regression model based on a multimarker IVD assay with ten extracted nuclear antigens (ENA) yielded an AUC of
0.87 and a sensitivity of 58% at a specificity of 95%. By contrast, the optimal combination of traditional and novel ELISAs
reached an AUC of 0.92 and a sensitivity of 75% at a specificity of 95%.
Conclusion: This study demonstrates the feasibility of combining test results of novel and traditional AABs using logistic
regression to increase the diagnostic accuracy for SLE. Further studies are required to assess the impact of different
ethnicities on marker selection and algorithm performance.
Disclosure: P. Budde, ProtagenAG, 3; H. D. Zucht, Protagen AG, 3; J. Schulte-Pelkum, ProtageAG, 3; D. Wirtz,

Protagen AG, 3; T. Witte, None; M. Schneider, Protagen AG, 5; P. Schulz-Knappe, ProtagenAG, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/development-of-a-multimarker-model-

for-the-detection-of-systemic-lupus-erythematosus-based-on-new-and-traditional-autoantibodies
An ANA Screening Assay Containing Multiple Antigens Increases the

Sensitivity and Specificity of ANA Testing By Indirect Immunofluorescence
Thomas Karonitsch, Hans Peter Kiener and Günter Steiner, Rheumatology, Medical University of Vienna, Vienna, Austria
SESSION INFORMATION
Background/Purpose:
Indirect immunofluorescence (IIF) on Hep-2 cells is still considered the gold standard for screening of antinuclear
antibodies (ANA), the serological hallmark of connective tissue diseases (CTD). While this method is sensitive it lacks
specificity. Moreover, low-titer ANA subspecificities may escape detection by IIF. It was therefore the aim of this study to
investigate the diagnostic usefulness of an ANA screening assay containing 13 diagnostically relevant antigens.
Methods:
Sera from 265 consecutive patients presenting with symptoms characteristic of connective tissue diseases (but without a
clear diagnosis yet) were analysed by both IIF and the EliA® CTD Screen (Thermo Fisher Scientific) containing the
following antigens: dsDNA, U1-snRNP, Sm, Ro60/SSA, Ro52/TRIM21, La/SSB, ribosomal protein P (ribP),
topoisomerase I (Scl-70), centromere B, RNA polymerase III, fibrillarin, Jo-1, Mi-2, Pm/Scl.
Results:
Among the 265 patients, 90 were positive in IIF and 78 in the CTD Screen; 61 sera were positive in both systems, 17 only
in the CTD Screen and 29 only in the IIF assay. Thus, the CTD Screen increased diagnostic sensitivity of ANA testing by
approximately 6%. In all double positive patients at least one diagnostically relevant antibody was detected, with anti-
Ro/SSA (n=32), anti-Ro52/TRIM21 (n=21) and anti-dsDNA (n=15) antibodies being the most frequently detected ones. In
addition to the antibodies determined by standard routine diagnostics (dsDNA, U1-snRNP, Sm, Ro60/SSA, Ro52/TRIM 21,
La/SSB, topoisomerase I, centromere B, Jo-1) antibodies to ribP, RNA polymerase III and Pm/Scl were detected in one
serum each. Importantly, antibodies were also detected in 15 of the 17 patients exclusively positive in the CTD Screen:
anti-dsDNA (n=7), anti-Ro60/SSA (n=4), anti-U1snRNP (n=2), anti-La/SSB (n=1) and anti-Jo-1 (n=1). In contrast, among
the 29 sera exclusively positive in IIF only two contained a diagnostically relevant antibody (low titwer anti-DNA and anti-
Sm). Clinical evaluation suggested that the majority of CTD Screen pos/IIF negative patients were at high risk for
developing a CTD, particularly primary Sjogren´s syndrome. Most common symptoms were arthralgia (n=13), sicca
syndrome (n=12) and Raynaud´s phenomenon (n=5). These patients require careful monitoring during clinical follow-up
and might have escaped early diagnostic detection due the negative IIF result.
Conclusion: CTD screening assays containing multiple antigens seem to be useful and highly specific diagnostic tools that
increase sensitivity of ANA testing enabling the detection of disease-associated ANA subspecificities in IIF-negative sera.
This may reduce the number of false negative diagnoses enabling the physician to diagnose and treat “ANA negative”
connective tissue diseases at an earlier stage.
Disclosure: T. Karonitsch, None; H. P. Kiener, None; G. Steiner, Thermo Fisher Scientific (Phadia GmbH), 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/an-ana-screening-assay-containing-

multiple-antigens-increases-the-sensitivity-and-specificity-of-ana-testing-by-indirect-immunofluorescence
Does Erythrocyte Sedimentation Rate Reflect and Discriminate Flare from

Infection in Systemic Lupus Erythematosus? Correlation with Clinical and
Laboratory Parameters of Disease Activity
Valentin S. Schäfer1, Katharina Weiss2, Andreas Krause2 and Wolfgang A. Schmidt3, 1Immanuel Krankenhaus Berlin,
Medical Center for Rheumatology Berlin-Buch, Berlin, Germany, 2Medical Centre for Rheumatology Berlin-Buch,
Immanuel Krankenhaus Berlin, Berlin, Germany, 3Medical Center for Rheumatology and Clinical Immunology Berlin-
Buch, Immanuel Krankenhaus Berlin, Berlin, Germany
SESSION INFORMATION
Background/Purpose: ESR is applied for monitoring disease activity in SLE. It is known to be influenced by age and
infections. We aimed at evaluating how ESR correlates with commonly applied disease activity parameters and how
infections influence these results.
Methods: Retrospective analysis of laboratory parameters, clinical activity, infection and serositis in consecutive SLE
patients between 2006 and 2015. Based on the treating physician´s judgement on disease activity and presence of infection,
patients were separated into four groups: flare, infection, both and neither. ESR was correlated to CRP, ferritin, anti-dsDNA
antibodies, C3, serositis and erythrocyturia with proteinuria. For age, ESR, CRP, ferritin and age- and gender-adapted ESR
(ESRp), mean values between groups were compared. ESRp was calculated as the percentage of an ESR cut-off
considering age and gender.
Results: We identified 203 SLE patients with 371 visits, flare n=147, infection n=48, both n=23 and neither flare nor
infection n=153. Correlation coefficients of ESR and other parameters are given in table 1; there was moderate correlation
with CRP (r=0.47-0.58) and weak correlation with other parameters (r<0.2). As shown in figure 1, ESR and CRP levels
were normal in patients in remission, but did not differ between flare, infection or both. ESRp was higher in patients with
flare versus with infection (p=0.01). ESR and CRP lost association to activity in infected patients and, conversely, to
infection in patients with flare. ESRp, serositis and anti-dsDNA antibodies were related to disease activity regardless of
infections (table 2).
Conclusion: ESR is raised in flares, but also in infected and older patients. CRP levels do not enable discrimination
between flare and infection. Both parameters argue against flare and infection when normal. ESRp can help to differentiate
between flare, infection or even both.
Table 1: Correlation coefficients of ESR with other laboratory and clinical parameters
CRP Ferritin C3- Raised erythrocyturia Serositis
reduction anti-
dsDNA- + proteinuria
antibodies
All visits 0.498* 0.256* 0.165* 0.134* 0.186* 0.079
(n=371)
Flare 0.549* 0.268* 0.064 0.101 0.141 0.094
only
(n=147)
Infection 0.468* 0.109 0.172 0.12 0.214 -0.338*
only
(n=48)
Both 0.575* 0.266 0.037 0.205 0.091 -0.09
(n=23)
Silent 0.556* 0.25 0.032 0.082 0.137 -0.016
(n=153)
(Pearson´s r); significant correlation is marked with *.
Table 2: Association of laboratory and clinical parameters with SLE flare and infection
ESR ESRp CRP Ferritin C3-reduction Raised anti- Erythrocyturia Se
dsDNA-
antibodies + Proteinuria
P-value for the association with disease activity

all visits <0.001* <0.001* 0.692 0.405 <0.001* <0.001* 0.002*
(n=371)
without <0.001* <0.001* <0.001* 0.318 <0.001* <0.001* 0.01*
infection
(n=300)
with infection 0.186 <0.001* 0.321 0.713 0.268 <0.001* -
(n=71)
P-value for the association with infections

all visits <0.001* 0.053 <0.001* 0.797 0.384 0.023* 0.831
(n=371)
without activity <0.001* 0.001* <0.001* 0.642 0.281 0.068 1
(n=201)
with activity 0.039 0.052 0.213 0.576 0.255 1 0.506
(n=170)
Figure 1: 95% confidence interval of mean values of age, ESR, ESRp, CRP, and ferritin in SLE groups
Disclosure: V. S. Schäfer, None; K. Weiss, None; A. Krause, None; W. A. Schmidt, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/does-erythrocyte-sedimentation-rate-

reflect-and-discriminate-flare-from-infection-in-systemic-lupus-erythematosus-correlation-with-clinical-and-laboratory-
parameters-of-disease-activity
Selected Nailfold Videocapillaroscopy Changes Are Linked to SLE Onset in a

Cohort of Uctd Subjects
Marianna Meroni1, Carmen Pizzorni2, Alberto Sulli1, Paola Rossi3, Paolo Stobbione3 and Maurizio Cutolo4, 1Research
Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, IRCCS A.O.U. San
Martino-IST, University of Genova, Genoa, Italy, Genova, Italy, 2Research Laboratory and Academic Division of Clinical
Rheumatology, Department of Internal Medicine, University of Genova, IRCCS San Martino, Genoa, Italy, Genoa, Italy,
3Rheumatology Unit, Internal Medicine Department - A.O. S.S. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy,
4Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, IRCCS A.O.U.
San Martino-IST, University of Genova, Genoa, Italy, Genoa, Italy
SESSION INFORMATION
Background/Purpose: Nailfold capillaroscopy (NVC) is a useful, non-invasive, reproducible and cost-effective diagnostic
tool, able to assess the shape of capillaries in the nailfold bed. According to the presence of peculiar abnormalities, it is
essential in the early differential diagnosis of connective tissue diseases (CTDs), mainly “scleroderma-spectrum disorders”
(SSD). Despite its large diffusion, no univocal NVC patterns have been ascribed to undifferentiated connective tissue
disease (UCTD) as well as to systemic lupus erythematosus (SLE). The aim of the study was to evaluate the most common
NVC pictures in a population of UCTD patients and if selected NVC pictures might be linked to SLE onset in these
patients.
Methods: We evaluated a cohort of 42 UCTD-affected women, diagnosed according to 2014 criteria proposed by Mosca et
al. (age, 38 years±46 months; duration of disease, 71±54 months) presenting Raynaud's phenomenon. During the
observational period (3 years), all of the UCTD patients were evaluated every 6 months. We considered the following NVC
parameters/pictures: presence of ectasic capillary loops (diameter ≥20 µm); giant capillaries (diameter ≥50 µm);
hemosiderin deposits; capillary number reduction; meandering capillaries (tortuosity); elongated capillaries; ramified/bushy
capillaries; micro-vascular array disorganization. SLE diagnosis was posed according to the 2012 SLICC/ACR criteria.
Qualitative variables were expressed in frequencies; their association, by non-parametric tests; quantitative variables, by
analysis of co-variance.
Results: Non-specific NVC alterations (for instance, not suggestive of SDD) were detected in 40 (98%) of the UCTD
patients during the observational period. On the other hands, the presence of hemosiderin deposits, ectasic loops, elongated
and ramified capillaries was found associated to the clinical subgroup of UCTD patients that later developed SLE (4/42
subjects, 10%; OR=10.5).
In particular, the independent variables “hemosiderin deposits” (OR=8.32) and “elongated capillaries” (OR 6.28), were
found significantly linked to the SLE onset (p<0.05), whereas the independent variables “tortuosity” (OR=12.16) and
“ramified/bushy capillaries” (OR 9.47) were, at the opposite, predictive for the prosecution of the status of UCTD patient
(p><0.05). ><0.05), whereas the independent variables “tortuosity” (OR=12.6) and “ramified/bushy capillaries” (OR=9.47)
were, at the opposite, predictive for the maintenance of UCTD diagnosis (p<0.05), whereas the independent variables
“tortuosity” (OR=12.16) and “ramified/bushy capillaries” (OR 9.47) were, at the opposite, predictive for the prosecution of
the status of UCTD patient (p><0.05). ><0.05).
Conclusion:
The present study reports NVC pictures that can be more frequently observed in UCTD patients. In addition, the NVC
analysis suggests that the presence of typical capillaroscopic microvascular abnormalities seems more frequently observed
in those UCTD patients that move to SLE.
Disclosure: M. Meroni, None; C. Pizzorni, None; A. Sulli, None; P. Rossi, None; P. Stobbione, None; M. Cutolo, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/selected-nailfold-videocapillaroscopy-

changes-are-linked-to-sle-onset-in-a-cohort-of-uctd-subjects

Impact of Anti-RBP Antibodies on Disease Activity and Quality-of-Life in
Immunosuppressant Naive Systemic Lupus Erythematosus
Rene Bermea1, Tammy Utset2 and Kichul Ko3, 1Medicine, University of Chicago, Chicago, IL, 2Medicine, Section of
Rheumatology, University of Chicago, Chicago, IL, 3Medicine, Section of Rheumatology and Gwen Knapp Center for
Lupus and Immunology Research, University of Chicago, Chicago, IL
SESSION INFORMATION
Background/Purpose: There is a lack of phenotypic data on SLE patients who have never been on immunosuppressive
therapy. Anti-RNA binding protein (anti-RBP) antibodies (anti-Smith, anti-RNP, anti-SSA, anti-SSB) in SLE have been
linked to an upregulation in transcriptional patterns, some thought to contribute to disease. This study sought to
characterize the impact of these autoantibodies on disease activity and quality-of-life in immunosuppressant naïve SLE
patients.
Methods: Retrospective cross-sectional analysis of subjects meeting ACR Classification Criteria for SLE was performed.
Subjects were anti-RBP positive (RBP+) if at least one titer was ≥ 20 (units, ELISA); others were classified as anti-RBP
negative (RBP-). Subjects ever on non-corticosteroid immunosuppression or currently on corticosteroids were excluded.
Baseline characteristics included age, sex, disease duration, anti-dsDNA, C3, C4, and ethnicity (African-American [AA] or
European-American [EA]). A measure of all four anti-RBP titers and most baseline characteristics were necessary for
inclusion. Disease activity was measured using the SLEDAI and quality-of-life indices included the Beck Depression
Inventory (BDI), Fatigue Severity Scale (FSS), Numerical Rating Scale for Pain (NRS-Pain Scale), and the Medical
Outcomes Study Sleep Scale (MOS-SS). Both groups were compared using Mann-Whitney U, two-tailed Fisher’s Exact
tests, and multivariate linear regression.
Results: Forty-one subjects met criteria for inclusion, 29 of which were identified as RBP+ and 12 RBP-. There was no
difference in age, sex, disease duration, anti-dsDNA, C3, or C4 between groups. There were significantly more AA in the
RBP+ group (65.5% vs 16.7%, p <0.01) and EA in the RBP- group (34.5% vs 75.0%, p=0.037). Disease activity and
quality-of-life indices between groups is demonstrated in Figure 1. SLEDAI was significantly worse in RBP+ vs RBP-
subjects (3 vs. 0, p=0.009), a relationship confirmed with multivariate regression (standardized beta coefficient = 0.515, p =
0.017). Similarly, BDI scores were worse in the RBP+ cohort (10 vs. 4, p=0.050). RBP+ subjects trended towards worse
fatigue by FSS (4.67 vs. 2.72, p=0.139) and pain by NRS-Pain Scale (21 vs. 4, p=0.087). MOS-SS sleep indices were also
worse among RBP+ subjects. To account for the difference in ethnicity between groups, a subgroup analysis of EA patients
was conducted and found similar trends in RBP+ patients.
Conclusion: Anti-RBP positive SLE subjects showed worse measures of disease activity and quality-of-life. RBP+
subjects were more likely to be African-American, although similar outcomes were seen in a European-American sub-
analysis. Our study was limited by sample size given our exclusion of immunosuppressed subjects. Further study is needed
to measure these antibodies’ impact on clinical outcomes and response to treatment prospectively.
Disclosure: R. Bermea, None; T. Utset, None; K. Ko, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/impact-of-anti-rbp-antibodies-on-

disease-activity-and-quality-of-life-in-immunosuppressant-naive-systemic-lupus-erythematosus
Variability in Method of Testing for Antinuclear Antibodies (ANA): A Survey

of Participants in the College of American Pathologist’s (CAP) Proficiency
Testing Program
Stanley J. Naides1, Jonathan Genzen2, Gyorgy Abel3, Christine Bashleben4 and Mohammad Qasim Ansari5,
1Immunology, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, 2ARUP Laboratories Inc, Salt Lake City, UT,
3Department of Pathology and Laboratory Medicine, Lahey Clinic Burlington, Burlington, VT, 4College of American
Pathologists, Northfield, IL, 5Department of Pathology and Laboratory Medicine, Louis Stokes VAMC, Cleveland, OH
SESSION INFORMATION
Background/Purpose: A 2010 American College of Rheumatology position paper designated indirect

immunofluorescence assay (IFA) on HEp-2 cells the “gold standard” for ANA testing and that laboratories performing
other methods should state the method used and describe its performance parameters. This study was performed to
determine laboratory practices in ANA testing.
Methods: Supplemental questions were sent to laboratories participating in the College of American Pathologist’s
proficiency testing program for ANA as part of the Special Immunology S-A Survey 2016 to determine the practice of
ANA testing. Of 5847 kits distributed, 1206 (21%) responded to the questionnaire; 942 were in the United States and 264
were international.
Results: ANA screening method varied: 56% IFA, 21% ELISA, 12% multi-bead immunoassay, and 18% “other” methods.
Ordering test name indicated method used in only 32%; only 39% stated method used on the report. Of 644 laboratories,
80% used HEp-2 substrate, 18% HEp-2000 (HEp-2 cell line engineered to overexpress SSA), and 2% “other.” Slides were
prepared manually (67%) or on an automated platform (33%), and examined by direct microscopy (84%) or images
captured by an automated platform (16%). IFA patterns were interpreted by personnel in 95% of laboratories; <1% used
automated image capture and analysis solely; 4% interpreted images both by personnel and an automated platform. 97% of
641 laboratories reporting ANA by IFA provided a titer. Only 51% reported a positive result at the traditional 1:40 dilution.
Titer was reported to endpoint routinely by 43%, only upon request by 23%, or never by 35%. 8% did not report dual
patterns. Of those reporting multiple patterns, 24% did not report a titer with each pattern.
Conclusion: Only slightly more than half of testing laboratories utilize the ACR “gold standard” IFA method with HEp-2
cell substrate.
Disclosure: S. J. Naides, Quest Diagnostics, 3; J. Genzen, None; G. Abel, None; C. Bashleben, None; M. Q. Ansari,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/variability-in-method-of-testing-for-

antinuclear-antibodies-ana-a-survey-of-participants-in-the-college-of-american-pathologists-cap-proficiency-testing-
program
Variability in ICAP (International Consensus on ANA Patterns) Pattern

Reporting in Testing for Antinuclear Antibodies (ANA) By Indirect
Immunofluorescence Assay (IFA)
Stanley J. Naides1, Jonathan Genzen2, Gyorgy Abel3, Christine Bashleben4 and Mohammad Qasim Ansari5,
1Immunology, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, 2ARUP Laboratories Inc, Salt Lake City, UT,
3Department of Pathology and Laboratory Medicine, Lahey Clinic Burlington, Burlington, VT, 4College of American
Pathologists, Northfield, IL, 5Department of Pathology and Laboratory Medicine, Louis Stokes VAMC, Cleveland, OH
SESSION INFORMATION
Background/Purpose: ANA IFA pattern may guide clinical evaluation by directing specific antibody testing. ICAP has
defined consensus ANA IFA patterns and the level of competency required to identify and interpret them. This study was
performed to determine laboratory practices in interpreting and reporting ANA IFA patterns.
Methods: Supplemental questions were sent to laboratories participating in the College of American Pathologist’s
proficiency testing program for ANA as part of the Special Immunology S-A Survey 2016 to determine the practice of
ANA testing. Of 5847 kits distributed, 1206 (21%) responded to the questionnaire; 942 were in the United States and 264
were international.
Results: Of 638 performing ANA by IFA and reporting a pattern, nearly 100% reported nucleolar, 99% homogeneous and
speckled, and 96% centromere, all competent-level ICAP patterns. Only 42% reported nuclear dots (competent-level). 53%
reporting nucleolar pattern further described expert-level subpatterns. Of 519 reporting speckled patterns, only 29%
reported dense fine speckles, a competent-level pattern reportedly found in normals. “Other” speckled was reported by
44%. 4% did not report speckled pattern at all. Of those reporting nuclear dots, 86% differentiated many nuclear dots and
84% few nuclear dots. Nuclear envelope (expert-level) was reported by 18%. Competent-level cytoplasmic patterns were
reported: golgi 69%, mitochondrial 65%, speckles 30%, 17% rods and rings, reticular 12% and polar 10%. Expert-level
cytoplasmic patterns were reported: spindle apparatus 59%, centriole 55%, mid body 45%, and lysosomal 32%. Only 54%
used an internal fluorescence intensity standard.
Conclusion: Pattern reporting practice is variable. Cytoplasmic pattern reporting is limited, possibly reflecting a lack of
consensus that cytoplasmic patterns should be reported in an “antinuclear” antibody test. Failure to use an internal
fluorescence intensity standard by nearly half of the laboratories may increase inter-assay and inter-observer variation in
the threshold for staining positivity and in titer determination.
Disclosure: S. J. Naides, Quest Diagnostics, 3; J. Genzen, None; G. Abel, None; C. Bashleben, None; M. Q. Ansari,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/variability-in-icap-international-

consensus-on-ana-patterns-pattern-reporting-in-testing-for-antinuclear-antibodies-ana-by-indirect-immunofluorescence-
assay-ifa
Positive Direct Coombs’ Test in the Absence of Hemolytic Anemia Predicts

High Disease Activity and Poor Renal Response in Systemic Lupus
Erythematosus
Hironari Hanaoka, Harunobu Iida, Tomofumi Kiyokawa, Yukiko Takakuwa and Kimito Kawahata, Division of
Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki,
Japan
SESSION INFORMATION
Background/Purpose: Direct Coombs' test in the absence of hemolytic anemia was newly included in the immunologic
criterion of the SLICC/ACR 2012 criteria for SLE. Since erythrocyte complement receptor contributes to the clearance of
circulating immunocomplex, the direct Coombs' test in the absence of hemolytic anemia may indicate excessive
immunocomplex production. In this study, we determined its clinical significance in Japanese SLE population.
Methods: Patients who fulfilled SLICC/ACR classification criteria of SLE and visited St. Marianna University Hospital
during Jan to Nov 2016 were prospectively evaluated with direct Coombs' test. Hemolysis was defined as lower
haptoglobin concentration than the normal limit. Clinical features including SLEDAI, treatment, and laboratory findings
were examined. For patients with lupus nephritis class III or IV, we additionally compared renal pathological features and
cumulative complete renal response (CR) rate between patients with positive result for direct Coombs' test in the absence of
hemolytic anemia and those with negative.
Results: Among 186 patients enrolled, 10 (5.4%) patients were positive with direct Coombs' test in the absence of
hemolytic anemia. They had higher SLEDAI (p<0.01), lower CH50 (p<0.01), higher anti-DNA titer (p<0.01) and lower
cumulative CR rate (p=0.03) (Figure 1) comparing to those who were negative. In the renal pathological analysis, a
significantly higher percentage of subendothelial deposit was determined in patients who were positive comparing to those
who were negative (p=0.02). Multivariate analysis indicated that SLEDAI was the independent factor strongly correlated
with the direct Coombs' test (OR 2.44, 95%CI 1.66-4.98, p<0.01) (Table 1).
Conclusion: Direct Coombs' test in the absence of hemolytic anemia might be correlated with high disease activity and
poor renal response in SLE.
Disclosure: H. Hanaoka, None; H. Iida, None; T. Kiyokawa, None; Y. Takakuwa, None; K. Kawahata, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/positive-direct-coombs-test-in-the-

absence-of-hemolytic-anemia-predicts-high-disease-activity-and-poor-renal-response-in-systemic-lupus-erythematosus
Clinical Value of Autoantibodies for Lupus Myelitis and Its Subtypes: A

Systematic Review
Hiroshi Oiwa1, Akira Kuriyama2, Tomoyasu Matsubara3 and Eiji Sugiyama4, 1Rheumatology, Hiroshima City Hiroshima
Citizens Hospital, Hiroshima, Japan, 2General Medicine, Kurashiki Central Hospital, Kurashiki, Japan, 3Neurology,
Hiroshima University Hospital, Hiroshima, Japan, 4Department of Clinical Immunology and Rheumatology, Hiroshima
University Hospital, Hiroshima, Japan
SESSION INFORMATION
Background/Purpose: We conducted a systematic review to investigate the clinical value of clinical characteristics and
autoantibodies, especially lupus-specific antibodies, for lupus myelitis and its subtypes.
Methods: We searched PubMed, EMBASE, and ICHUSHI without language restrictions for case reports or series of lupus
myelitis. We focused on cases reported since 1997, when the revised classification criteria for systemic lupus
erythematosus were published. Associations between patient characteristics including autoantibodies and functional
outcome, survival, and subtypes of myelitis (grey and white matter myelitis) were examined. We attempted to contact
authors to supplement missing information for analysis.
Results: Our search identified 224 cases from 105 articles. White matter myelitis predicted favorable function (odds ratio,
15.18; 99% confidence interval, 3.09 to 151.31; p<0.0001). Anti-nuclear antibody also predicted favorable function
(p=0.007). Age ≥50 years was associated with poor survival outcomes (p=0.007). Grey matter myelitis was associated with
longitudinally extensive transverse myelitis (p<0.001) and anti-double-stranded DNA (p=0.003), and tended to be
associated with anti-β2-glycoprotein I (p=0.011). White matter myelitis tended to be associated with optic neuritis and anti-
neuromyelitis optica antibodies. Although our study might be susceptible to under-reporting of original cases and selection
bias, we aimed to provide a conservative interpretation by setting the statistical significance threshold at p<0.01.
Conclusion: This systematic review confirmed that grey matter myelitis predicted poor functional outcome, and was
associated with longitudinally extensive transverse myelitis and anti-double-stranded DNA antibodies. White matter
myelitis was associated with favorable functional outcomes and may partially represent a complication of neuromyelitis
optica.
Disclosure: H. Oiwa, None; A. Kuriyama, None; T. Matsubara, None; E. Sugiyama, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/clinical-value-of-autoantibodies-for-

lupus-myelitis-and-its-subtypes-a-systematic-review
Detection of dsDNA Antibodies By New Fluoroimmunoassay with

Comparable Diagnostic Sensitivity and Specificity to Farr-Ria
Katja Lakota1,2, Tanja Kveder2, Tinka Svec2, Polona Žigon2, Ales Ambrozic3, Borut Božič2,4, Matija Tomšič2,5, Saša
Čučnik2,4 and Snezna Sodin Semrl1,2, 1Faculty of Mathematics, Natural Science and Information Technology, University
of Primorska, Koper, Slovenia, 2Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia,
3Department of Rheumatology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia, 4Faculty of Pharmacy,
University of Ljubljana, Ljubljana, Slovenia, 5University of Ljubljana, Faculty of Medicine, Ljubljana, Slovenia
SESSION INFORMATION
Background/Purpose:
Antibodies against double-stranded deoxyribonucleic acid (anti-dsDNA) are a useful and valuable serological marker for
diagnosis of systemic lupus erythematosus (SLE). Studies suggest strong correlation between increasing levels of anti-
dsDNA and subsequent flares, particularly renal disease. The radioactive immunoassay (RIA) by FARR (FARR-RIA) has
been utilized as the gold standard in the past for anti-dsDNA determination, detecting mostly high avidity antibodies.
Additionally, enzyme-linked immunoassay (ELISA) and immunofluorescence (Crithidia luciliae) (CLIF) both recognize
also low avidity anti-dsDNA and ELISA also detects antibodies against ssDNA. There is a need for replacing FARR-RIA
with a safer and more environmentally friendly immunoassay. To modify the detection of anti-dsDNA by FARR-RIA, by
replacing the radioactive isotope 14C and other toxic reagents and evaluate the newly developed, environmentally-friendly
fluoroimmunoassay (FIA) for daily laboratory and clinical practice.
Methods: We tested 759 sequentially collected samples for anti-dsDNA testing, with FARR-RIA and FIA (using
Picogreen® as intercalating dye). The group consisted of 146 blood donors, 70 SLE, 25 antiphospholipid syndrome, 28
rheumatoid arthritis, 25 Sjögren’s syndrome and 465 patients with unknown diagnoses. Final results of both methods were
calculated from difference of signal measured between supernatant (S) and precipitate (P) divided by the sum of signals in
S and P.
Results: At cut-off value of 0.35, both diagnostic specificity and sensitivity were comparable using FARR-RIA and FIA.
Diagnostic specificity in both methods was 100%, while diagnostic sensitivity for FARR-RIA and FIA were 50% and 53%,
respectively. Diagnostic accuracy for FIA was slightly lower compared to FARR-RIA, 0.781 vs. 0.887. There was
comparable inter-accuracy of both methods in high positive results (CVFARR-RIA = 11%, CVFIA = 12%), while low
positive results (CVFARR-RIA = 29%, CVFIA = 18%) showed greater variation. We confirmed comparable intra-
repeatability in high positive results (CV = 2% for both methods) and low positive results (CVFARR-RIA = 33%, CVFIA =
28%). At high and low positive results comparable analytical accuracy was observed, while analytical sensitivity was
higher in FIA. Neither ssDNA nor RNA affected the detection of anti-dsDNA. A correlation of 0.626 (p<0.01) was found
between FARR-RIA and FIA positive results.
Conclusion: FIA and FARR-RIA showed comparable diagnostic specificity and sensitivity. Therefore, FARR-RIA could
be replaced with FIA in daily laboratory routine practice for the detection of anti-dsDNA.
Disclosure: K. Lakota, None; T. Kveder, None; T. Svec, None; P. Žigon, None; A. Ambrozic, None; B. Božič, None; M.
Tomšič, None; S. Čučnik, None; S. Sodin Semrl, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/detection-of-dsdna-antibodies-by-new-

fluoroimmunoassay-with-comparable-diagnostic-sensitivity-and-specificity-to-farr-ria
Optimization of a Cost-Effective Diagnostic ANA Algorithm

Mathieu Cauchie1, Bert Vander Cruyssen2, Stefanie Van den Bremt3, Muriel Stubbe4, Xavier Bossuyt5 and Lieve Van
Hoovels3, 1OLV Hospital, Aalst, Belgium, 2Rheumatology, OLV hospital, Aalst, Belgium, 3Laboratory medicine, OLV
Hospital, Aalst, Belgium, 4Rheumatology, OLV Hospital, Aalst, Belgium, 5Laboratory medicine, University Hospital
Leuven, Leuven, Belgium
SESSION INFORMATION
Background/Purpose:
Due to the poor specificity of the anti-nuclear antibodies (ANA) indirect immunofluorescence (IIF) assay, enhanced by the
huge increase in ANA requests by non-rheumatologists, second line identification of specific anti-double stranded DNA
(dsDNA) and anti- extractable nuclear antigen (ENA) is necessary.
Our study aims to objectify a cost-effective diagnostic ANA algorithm, standardizing the work-out of positive ANA IIF
tests in a routine, secondary care setting.
Methods:
The ANA test results reported in our laboratory were retrospectively reviewed over a 9-month period. Positive ANA IIF
test results on NOVA View® (Inova, USA) at 1:80 screening dilution (cut off = 49 Light Intensity Units (LIU)) were
further analysed by dsDNA- (dsDNA-NcX IgG ELISA, Euroimmun, Germany) and ENA-screen (ANA screen 11 IgG
ELISA, Euroimmun). For positive ENA-screen samples, ANA identification was performed with EUROLINE ANA profile
3 (Euroimmun). Based on ROC-curve analysis of LIU versus ENA/dsDNA identification, the LIU cut off at 95%
sensitivity was determined.
Results:
3276 samples of 2916 patients were tested for ANA, of which 49,8% were from the rheumatology ward. 279 (9,6%)
patients had repeated ANA requests. None of the repeated ANA IIF, dsDNA/ENA screen tests had a clinically significant
result. 45,9% patients tested ANA IIF positive, with identification of a specific Ab (dsDNA/ENA) in 11,6% of the patients.
ROC analysis of LIU in function of ENA/dsDNA identification revealed a specificity of 3,0% (2,1-4,3) for the 49 LIU cut
off. A global ANA IIF sensitivity of 94.8% for ENA/dsDNA identification was obtained at a cut off of 88 LIU, with a
specificity of 36,1% (33,6-39,5%) (Table 1). ROC curve analysis for isolated homogeneous, speckled, centromere and
speckled metaphase positive IIF patterns confirmed an acceptable analytical performance and LR’s of ENA/dsDNA
positivity at LIU of 88 (Table 2), in concordance with earlier published LR’s for ANA associated rheumatic disease
positivity. Using this 88 LIU cut off for second line testing, can result in a yearly cost reduction of 5.060€. Introducing a
limitation of the ANA workout to once yearly, if ANA IIF titer and pattern are stable, implies a supplementary cost
reduction of 4.290€.
Conclusion:
Analytical performance analysis reveals a clinical and cost effective cut off for ANA IIF of 88 LIU for the initiation of
second-level testing. If the patient is clinically stable and ANA IIF pattern and titer has not significantly changed, a yearly
repetition of the diagnostic ANA workout is more than clinically sufficient.
Disclosure: M. Cauchie, None; B. Vander Cruyssen, None; S. Van den Bremt, None; M. Stubbe, None; X. Bossuyt,
None; L. Van Hoovels, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/optimization-of-a-cost-effective-

diagnostic-ana-algorithm

Elevated Erythrocyte Sedimentation Rate Among Obese Patients with SLE-
Not Always a Marker of Disease Activity
George Stojan1, Erik Barr2 and Michelle Petri3, 1Medicine, Division of Rheumatology, Johns Hopkins University School
of Medicine, Baltimore, MD, 2Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore,
MD, 3Medicine (Rheumatology), Division of Rheumatology, Johns Hopkins University School of Medicine, MD, USA,
Baltimore, MD
SESSION INFORMATION
Background/Purpose:
Obesity is more common in patients with SLE compared to the general population. The prevalence of obesity among SLE
patients is between 28 and 50 percent. We hypothesized that a higher body mass index was associated with elevated ESR
after adjusting for disease activity, prednisone and immunosuppressive use.
Methods:
Our analysis is based on 2246 different patients who were observed from 1 to 137 visits. The median number of visits per
patient was 15.
The “between-person” association addresses the question of whether those who tend to have high BMI also tend to have
high ESR. To assess this, we calculated the person-specific mean ERS values and plotted them against the person-specific
mean BMIs. \We fit crude and adjusted models to estimate the slope in the expectation of mean ESR per unit difference in
mean BMI. The results are shown in Table 1.
The within-person analysis addresses the question of whether a person tends to have higher ESR when his/her BMI is lower
than his average BMI. To assess this, for each visit, we calculated the difference between the BMI level at that visit and the
person’s average of BMI. Then we modelled the relationship between these differences in BMI and the difference between
the person’s ESR at each visit and the person’s average ESR.
Results:
Table 1: Difference in person-specific mean ESR per 1 unit difference in person-specific mean BMI
Unadjusted Adjusted1
Estimated Estimated
difference in difference in
mean ESR per 1 mean ESR per
unit difference in 1unit difference
mean BMI (95% in mean BMI
Model Effect CI) P-value (95% CI) P-value
Model 1 BMI 0.6 (0.4, 0.7) <0.0001 0.5 (0.4, 0.6) <0.0001
Pooling
across Sex
Model 2 BMI 0.6 (0.5, 0.7) <0.0001 0.5 (0.4, 0.7) <0.0001
Allowing Female 5.0 (-12.2, 22.2) 0.57 3.2 (-12.1, 18.5) 0.68
different
association BMI*Sex -0.5 (-1.1, 0.2) 0.14 -0.3 (-0.9, 0.2) 0.24
by sex
1Adjusted for age, age-squared, race, mean disease activity, mean prednisone dose, proportion of time on
immunosuppressant medication.
Table 2: Difference in ESR at each visit per 1 unit difference in between the person’s BMI at that visit and the person’s
average BMI.
Effect Unadjusted Adjusted1
Estimated Estimated
difference in ESR difference in
(relative to a ESR (relative to
person’s average a person’s
ESR) as a average ESR) as
function of a function of
differences in a differences in a
person’s BMI person’s BMI
(relative to that (relative to that
person’s average person’s average P-
Model BMI) P-value BMI) value
Model 1: BMI -mean 0.04 (-0.01, 0.10) 0.15 0.09 (0.03, 0.15) 0.004
Pooling BMI
across Sex
Model 2 BMI -mean 0.05 (-0.01, 0.11) 0.09 (0.03, 0.15) 0.004
0.12
BMI
Allowing Females 0.004 (-0.54, 0.26 (-0.30, 0.82) 0.36
different 0.99
0.54)
association BMI -mean -0.07 (-0.31, -0.04 (-0.28, 0.78
by sex 0.55
BMI *Sex 0.16) 0.21)
1 Adjusted for age, age-squared, race, disease activity, prednisone dose, immunosuppressant use.
Conclusion:
Patients whose mean BMI is 10 points higher have a mean ESR that is 6mm/hour higher (p<0.0001). The association
between BMI and ESR does not vary by sex and is not affected by adjusting for covariates.
We also found a significant within person association between ESR and BMI: a 1 unit increase in BMI increases the
expected ESR by 0.09mm/hour (p=0.004).
Careful interpretation of clinical data is necessary in obese patients- an elevated ESR may not be a manifestation of disease
activity.
Disclosure: G. Stojan, None; E. Barr, None; M. Petri, Anthera Inc, 5,GlaxoSmithKline, 5,EMD Serono, 5,Eli Lilly and
Company, 5,Bristol Meyer Squibb, 5,Amgen, 5,United Rheumatology, 5,Global Academy, 5,Exagen, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/elevated-erythrocyte-sedimentation-

rate-among-obese-patients-with-sle-not-always-a-marker-of-disease-activity
Distinctive Features of Positive Anti-Cell Antibody Tests on HEp-2 Cells

(HEp-2-ANA) in Patients with Non-Autoimmune Diseases
Renan Agustinelli1, Sílvia H. Rodrigues2, Mônica Prado3, Henrique Mariz4 and Luis Eduardo C. Andrade5,6,
1Rheumatology Division, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, São Paulo, Brazil,
2Rheumatology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo, Brazil,
3Rheumatology Division, Escola Paulista de Medicina - Universidade Federal de São Paulo, Sao Paulo, Brazil, 4Internal
Medicine Department, Hospital das Clínicas - Universidade Federal de Pernambuco, Recife, Brazil, 5Rheumatology
Division, Universidade Federal de São Paulo, São Paulo, Brazil, 6Immunology Division, Fleury Medicine and Health, São
Paulo, Brazil
SESSION INFORMATION
Background/Purpose: The indirect immunofluorescence (IIF) test for anti-cell or antinuclear (ANA) antibodies on HEp-2
cells (HEp-2-ANA) is considered the gold standard method for ANA detection. However, this is a very sensitive test and
detects autoantibodies also in some healthy individuals and patients with non-autoimmune diseases. The establishment of
distinctive HEp-2-ANA features in SARD patients and in healthy individuals has proven to be helpful in the daily medical
practice. However, the HEp-2-ANA test is not expected to be requested for healthy individuals, but rather for those seeking
for medical care due to some health disorder. Therefore, we aimed to determine the frequency and characteristics of
positive HEp-2-ANA tests in individuals affected by a variety of non-autoimmune diseases.
Methods: This is a cross-sectional observational study comparing HEp-2-ANA results in 588 non-autoimmune disease
(NAD) patients, 194 patients with systemic autoimmune rheumatic diseases (SARD) and 1,217 healthy individuals. NAD
group comprised 4 subgroups: 95 patients with malignancy, 148 with infectious diseases, 163 with psychiatric diseases and
152 with multiple co-morbidities (diabetes mellitus, arterial hypertension, and metabolic syndrome). Sera were tested at
1:80 dilution and diluted to the end titer. Slides were analyzed by two independent blinded examiners at x400
magnification. We followed the anti-cell (AC) pattern nomenclature according to the ICAP (International Consensus on
ANA Patterns) recommendations.
Results: A positive HEp-2-ANA result occurred in 102 (18.3%) NAD patients, 170 (87.6%) SARD patients and 150
(12.3%) healthy individuals. The four subgroups of NAD patients did not differ regarding HEp-2-ANA titer or pattern.
HEp-2-ANA titer in NAD patients was higher than in heathy individuals and these two groups had lower titer than SARD
patients. The nuclear dense fine speckled pattern (AC-2) was more frequent in healthy individuals than in NAD patients (p
= 0.029) and was not observed in the SARD group. The nuclear homogeneous (AC-1) and nuclear coarse speckled (AC-5)
patterns were more frequent in SARD patients than in the other groups (p < 0.001). The most common pattern in all groups
was the nuclear fine speckled (AC-4) pattern, which presented a gradient in titer across the three groups (p < 0.001):
healthy individuals and NAD patients had predominantly low and intermediate titer, respectively, and SARD patients had
predominantly high titer.
Conclusion: The pattern and titer of HEp-2-ANA positive tests in NAD patients clearly differ from SARD patients. In
addition, when compared to healthy individuals, NAD patients present positive HEp-2-ANA tests with slightly higher titer
and with lower frequency of the nuclear dense fine speckled (AC-2) pattern.
Disclosure: R. Agustinelli, None; S. H. Rodrigues, None; M. Prado, None; H. Mariz, None; L. E. C. Andrade, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/distinctive-features-of-positive-anti-

cell-antibody-tests-on-hep-2-cells-hep-2-ana-in-patients-with-non-autoimmune-diseases
Anti-RNP/Sm Antibodies Plus Lupus Anticoagulant As Risk Factor for

Thrombosis in Patients with Systemic Lupus Erythematosus
Mari Carmen Zamora-Medina1, Andrea Hinojosa-Azaola2, Carlos Núñez-Álvarez3 and Juanita Romero-Diaz4,
1Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutricion S.Z., Mexico City, Mexico,
2Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City,
Mexico, 3Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion S.Z., Mexico city, Mexico,
4Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico city,
Mexico
SESSION INFORMATION
Background/Purpose: In a previous study, we identify a potential role of anti-RNP/Sm in combination with LA as risk
factor for thrombosis. We aimed to validate this association
Methods: Case-control study of patients with SLE who presented thrombosis after SLE diagnosis and controls with SLE
without thrombosis. All patients fulfilled ³ 4 American College of Rheumatology revised and updated classification criteria
for SLE. Comorbidities, traditional risk factors, clinical variables, disease activity and treatment were evaluated. Also, a
blood sample was drawn to determine antiphospholipid (aPL) and anti-RNP/Sm antibodies. Statistical analysis:
Differences between groups were evaluated with the Student t-test or Mann-Whitney U test for continuous variables; Chi-
square or Fisher’s exact test for categorical variables. Univariate logistic regression analyses and multivariate analyses were
performed. Odds-ratio (OR) and 95% confidence intervals (95% CI) were calculated
Results: 63 cases and 63 controls were studied, 88% women, median age of 40 years and disease duration of 135 months at
study inclusion. No differences were found between groups regarding age, comorbidities, or clinical characteristics at SLE
diagnosis. Patients with thrombosis were more frequently positive for anti-RNP/Sm (83% vs 62%, p=0.001); IgG aCL
(29% vs 11%, p=0.02); IgG anti-B2GPI (21% vs 13%, p=0.02); IgM anti-B2GPI (p=0.02); LA (62% vs 19%, p<0.001); the
combination of anti-RNP/Sm + LA (52% vs 14%, p<0.001), and aPL triple marker (17% vs 2%, p=0.002), compared to
controls. The combination of anti-RNP/Sm + LA (OR 5.98, 95% CI 2.17-16.47, p=0.001); SLEDAI-2K (OR 1.18, 95% CI
1.04-1.32, p=0.007), and prednisone dose (OR 1.08, 95% CI 1.03-1.12, p<0.001) were independently associated with
thrombosis.
Conclusion: This study confirmed an independent association between the combination of anti-RNP/Sm antibodies and
LA with thrombosis. Further studies to identify potential pathogenesis mechanisms of the presence of anti-RNP/Sm and
thrombosis are needed
Disclosure: M. C. Zamora-Medina, None; A. Hinojosa-Azaola, None; C. Núñez-Álvarez, None; J. Romero-Diaz,

None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/anti-rnpsm-antibodies-plus-lupus-

anticoagulant-as-risk-factor-for-thrombosis-in-patients-with-systemic-lupus-erythematosus
Characteristics of Cardiac Diseases in Systemic Lupus Erythematosus and

Risk Factors of Different Echocardiographic Features
Nevin Hammam1,2, Mona H EL zohri3 and Alaa A A Mohamed1, 1Rheumatology, Rehabilitation and Physical medicine,
Assiut University, Faculty of Medicine, Assiut, Egypt, 2Department of Physical therapy, University of Alberta, Edmonton,
AB, Canada, 3Internal medicine department, Assiut University, Faculty of Medicine, Assiut, Egypt
SESSION INFORMATION
Background/Purpose:
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by involvement of different organs in the
body. The cardiovascular (CVD) involvement in SLE is responsible for high morbidity and is often the leading cause of
death. Despite that, little is known about the risks of development of different CVDs in SLE. We aimed to determine the
rate of different echocardiographic findings and their risks and clinical correlates in SLE patients.
Methods:
SLE patients (n=59), fulfilling 4 or more ACR criteria for SLE, attending outpatient Rheumatology clinics, were recruited.
Demographic data, disease characteristics and current medication use were gathered from the patients. Clinical evaluation
with SLE Disease Activity Index (SLEDAI), echocardiography, anthropometric measurements and routine laboratory tests
were done. Mann-Whitney U test, Chi-square test, Fisher exact test and logistic regression analysis were used for statistical
analysis as appropriated.
Results:
The mean age of the patients was 31.4±10.5, and 86.4% of the patients were females. The rate of different
echocardiographic findings was as follow: overall valve lesions (47.5%), pulmonary hypertension (PHT) (18.6%),
pericardial effusion (13.6%) and pericardial thickening (6.8%). The most common valve abnormalities were: mitral regurge
(33.9%), tricuspid regurge (32.2%), mitral thickening (18.6%), and aortic thickening (13.6%) but less common were aortic
regurge (6.8%) and pulmonary regurge (5.1%). The least common were pulmonary stenosis, mitral stenosis, and tricuspid
and pulmonary thickening representing only (1.7%) each. The frequency of occurrence of different echocardiographic
findings with different SLE features is shown in fig1. Univariate and multivariate analyses revealed a significant
association of PHT with age (OR=1.095, p=0.023, CI=1.013 - 1.184), mucocutaneous disease was a negative predictor of
mitral regurge (OR=0.227, p=0.03, CI=0.059 - 0.868) and mitral thickening, (OR=0.046, p=0.032, CI=0.003 - 0.765),
unlike Raynaud phenomenon which is a positive predictor of mitral thickening (OR=14.614, p=0.036, CI=1.199 - 178.1).
Levels of HDL were associated with aortic thickening (OR= 0.907, p=0.05, CI =0.823 - 1). The use of prednisolone
reduced the risk of developing aortic thickening (OR= 0.054, p=0.012, CI=0.006 - 0.53). Pericardial effusion was
associated with metabolic syndrome (OR=12.4, p=0.025, CI=1.367 - 112.5) and high triglycerides levels (OR=1.012,
p=0.028, CI=1.001 - 1.023). The echocardiographic findings showed no association with SLEDAI scores.
Conclusion:
Different laboratory and clinical correlates with different echocardiographic findings reflect the complexity of CVD
mechanisms and warrant further studies to unravel disease pathogenesis.
Fig.1 The frequency of different echocardiographic findings in different SLE features
Disclosure: N. Hammam, None; M. H. EL zohri, None; A. A. A. Mohamed, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/characteristics-of-cardiac-diseases-in-

systemic-lupus-erythematosus-and-risk-factors-of-different-echocardiographic-features
D-Dimer As an Early Marker in Patients with Lupus Mesenteric Vasculitis

Xiaolei Ma1, Bingzhu Hua1, Hong Wang1, Yun Zhu1, Zhiyong Chen1 and Lingyun Sun2, 1Department of Rheumatology
and Immunology, the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China, 2Department
of Rheumatology and Immunology, the Affiliated Drum Tower Hospital, Nanjing University Medical School, nanjing,
China
SESSION INFORMATION
Background/Purpose: No early serum marker of accurate diagnosis of lupus mesenteric vasculitis (LMV) contributes to
the treatment decision-making process. The study was undertaken to evaluate clinical significance of serum D-dimer level
as an early diagnosis marker of LMV patients.
Methods: Thirty-eight systemic lupus erythematosus (SLE) patients who presented with acute and subacute abdominal
pain were retrospectively analyzed and classified into LMV group (n=15) and Non-LMV group (n=23) between January
2006 and January 2016. The patients were evaluated by serum D-dimer level on the first day after admission, abdominal
CT, other laboratory-testing parameters, as well as SLE disease activity index (SLEDAI) during the same period.
Results: No significance difference of the SLEDAI, autoantibodies and laboratory profiles at admission was detected
between two groups. The D-dimer value on the first day of admission was significantly higher in patients with LMV than
those with other causes (P<0.05, P=0.04). In addition, serum D-dimer level was also significantly higher in patients with
long-term (≥7d) gut resting and high-dose steroid therapy (P<0.01, P=0.003). All LMV patients showed good response to
high-dose intravenous steroids and there was no patient required immunosuppressive and surgical therapy.
Conclusion: D-dimer level could be an effective and early serum marker indicating the clinical evolution of LMV. D-dimer
may also assist the treatment determination and prognostic evaluation.
Disclosure: X. Ma, None; B. Hua, None; H. Wang, None; Y. Zhu, None; Z. Chen, None; L. Sun, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/d-dimer-as-an-early-marker-in-patients-

with-lupus-mesenteric-vasculitis
Prevalence and Risk Factors of Depressive Disorders in Chinese Patients

with Systemic Lupus Erythematosus (SLE)
Chi Chiu Mok1, Yan Tung Lilian Lo2, Chi Wai Cheng2 and Kam Shan Poon2, 1Medicine, Tuen Mun Hospital, Hong
Kong, Hong Kong, 2Psychiatry, Castle Peak Hospital, Hong Kong, Hong Kong
SESSION INFORMATION
Background/Purpose:
Depression is common in SLE but most previous studies utilized self-rated scales for evaluation. Formal diagnosis of
depression was not established by psychiatric interviews. This study was conducted to determine the prevalence of
depressive disorders, severity of depressive symptoms and the associated risk factors in Chinese patients with SLE.
Methods:
Adult patients who fulfilled ≥4 ACR criteria for SLE were randomly recruited from the rheumatology out-patient clinics
and hospital admissions in a 6-month period. Psychiatric disorders were diagnosed through a direct interview by a
designated psychiatrist using the Chinese-bilingual Structural Clinical Interview for DSM-IV Axis I disorders, patient
research version (CB-SCID-I/P). The severity of depressive symptoms was assessed by the Hamilton Depressive Rating
Scale (HAM-D). Patients were asked to complete the Beck Depression Inventory (BDI), Medical Outcomes Study Social
Support Survey (MOS-SSS-C) and the WHO Quality of Life Measure-Abbreviated Version. SLE disease activity
(SLEDAI), organ damage (SLICC/SDI) and socio-demographic were collected and correlated with the presence of
psychiatric disorders. Logistic regression was used to study the risk factors for psychiatric disorders in SLE.
Results:
175 SLE patients were studied (95% women, age 39.2±12.4 years, SLE duration 10.3±6.7 years). Twenty-seven (15.4%)
and 37 (21.1%) patients were diagnosed as having a current depressive (52% major depressive disorder, 22% dysthymia)
and anxiety (35% generalized anxiety, 14% panic, 14% phobia, 8% adjustment disorder) disorder, respectively. Patients
with depressive disorders, as compared to those without any psychiatric disorders, had higher SLE activity (p=0.03), were
more likely to have a history of psychiatric diagnosis (p<0.001) and receive financial assistance from the Government
(p=0.04). Independent factors associated with a current depressive disorder were SLEDAI score (1.13[1.02-1.24] per point;
p=0.02), perceived poor social support (p=0.03) and a past history of psychiatric disorders (p=0.003). On the other hand,
being separated/divorced (β=0.19; p=0.02), higher SLEDAI score (β=0.16; p=0.02), shorter SLE duration (β= -0.18;
p=0.02) and a history of psychiatric disorders (β=0.18; p=0.01) were independently associated with higher HAM-D scores,
which reflected the severity of depression. Depressive disorders and severity of depression were associated with poorer
quality of life. ROC analysis showed a cut-off of 14 points of the self-rated BDI had a sensitivity of 89% and a specificity
of 83% for providing good psychometric property for differentiating a current depressive disorder from those without.
Conclusion:
Depressive disorder is prevalent in Chinese patients with SLE. Independent risk factors include more active disease,
perceived poor social support and a past history of psychiatric disorders. Patients with more active SLE, shorter disease
duration, a past history of psychiatric disorders and being separated are associated with more serious depressive symptoms.
The self-rated BDI provides a good screening tool for identifying depressive disorders in SLE patients.
Disclosure: C. C. Mok, None; Y. T. L. Lo, None; C. W. Cheng, None; K. S. Poon, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prevalence-and-risk-factors-of-

depressive-disorders-in-chinese-patients-with-systemic-lupus-erythematosus-sle
Novel Electronic Health Record Method Reveals That dsDNA Antibody-

Negative Systemic Lupus Erythematosus Is Associated with Pain, Sleep, and
Mood Disorders
April Barnado1, Robert Carroll2, Carolyn Casey3, Joshua C. Denny2 and Leslie Crofford1, 1Medicine, Vanderbilt
University Medical Center, Nashville, TN, 2Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN,
3Lehigh Valley Health Network, Allentown, PA
SESSION INFORMATION
Background/Purpose: Systemic lupus is a heterogeneous disease with diverse presentations. Studies have shown that
dsDNA antibodies associate with renal disease. However, less is known about comorbidities in SLE patients without
dsDNA antibodies. Using a large, novel electronic health record (EHR) cohort of SLE patients with a long duration of
follow-up, we sought to identify not only ACR SLE criteria that associate with dsDNA antibody status but also other
comorbidities that might not be assessed in cohort studies. We used a technique that scans across EHR billing codes called
phenome-wide association study (PheWAS) to compare comorbidities in SLE patients with and without dsDNA antibodies.
Methods: We used our validated SLE algorithm of ≥ 4 counts of the SLE ICD-9 code (710.0) and ANA positive > 1:160
while excluding dermatomyositis and systemic sclerosis ICD-9 codes with an internally validated positive predictive value
of 94% and a sensitivity of 86%. We identified SLE cases in a de-identified EHR called the Synthetic Derivative (SD) that
contains over 2.8 million subjects with longitudinal data. SLE subjects have on average 9 years of follow-up. dsDNA status
was defined as positive if ever positive, negative if there was at least 1 assay and all were negative, and measured via
enzyme-linked immunosorbent assays with manufacturer values to determine positivity. Demographics of dsDNA positive
vs. negative subjects were compared using chi-square and Mann-Whitney U tests. PheWAS was performed in dsDNA
positive vs. negative SLE patients using logistic regression adjusting for current age and race and correcting for multiple
testing using Bonferroni (p < 1.35 x 10-4).
Results: Of 1097 SLE subjects, 521 had a positive dsDNA, 503 negative dsDNA, and 73 with missing data. dsDNA
positive subjects were more likely to be African American vs. Caucasian (61% vs. 45%, p < 0.001) and younger at age of
first SLE ICD-9 code (37 ± 17 vs. 43 ± 15, p < 0.001) with no difference in sex (female 51% vs. male 52%, p = 0.58). As
expected, dsDNA positive subjects, compared to dsDNA negative, were more likely to have renal codes including
nephritis, renal failure, and end stage renal disease (Table 1). dsDNA positive subjects were also more likely to have codes
for hematologic and serositis criteria. dsDNA negative subjects were more likely to have codes for sleep, pain, and mood
disorders.
Conclusion: Using a novel EHR technique in a large SLE cohort with longitudinal follow-up, dsDNA positive subjects
were more likely to have codes for renal, serositis, and hematologic involvement. In contrast, dsDNA negative subjects
were more likely to have codes related to neuropsychiatric symptoms. Our results demonstrate that PheWAS can expand
our understanding of SLE disease heterogeneity by uncovering important clinical differences in subgroups of SLE patients.
Table 1.
PheWAS codes Phenotype Phenotype Adjusted Odds p value
present* absent* Ratio for age
and race
(≥ 2 or more (0 instances
instances of of the code) (95%
the code) Confidence
Interval)
Codes favoring dsDNA positive subjects
Nephritis and 162 614 dsDNA positive: 5.95 x 10-12

nephropathy in 4.66
diseases classified
elsewhere (3.00 – 7.22)
dsDNA
negative: 1.00
(ref)
Renal failure 261 614 2.33 1.15 x 10-7
(1.71 – 3.19)
Other anemias 275 585 1.87 7.67 x 10-5
(1.37 – 2.55)
End stage renal 77 614 2.71 4.31 x 10-4
disease
(1.55 – 4.71)
Pleurisy; pleural 130 739 2.00 9.75 x 10-4
effusion
(1.33 – 3.03)
Thrombocytopenia 94 616 2.19 1.31 x 10-3
(1.36 – 3.53)
Codes favoring dsDNA negative subjects
Sleep disorders 124 820 0.48 3.94 x 10-4

(0.32 – 0.72)
Obstructive sleep 41 820 0.30 1.48 x 10-3
apnea
(0.14 – 0.63)
Back pain 196 699 0.59 2.00 x 10-3
(0.42 – 0.82)
Myalgia and 243 682 0.65 5.55 x 10-3
myositis
unspecified (0.48 – 0.88)
Major depressive 57 820 0.44 5.75 x 10-3
disorder
(0.21 – 0.85)
*Subjects with 1 instance of a code are excluded, so total number for each PheWAS code does not add up to the 1097
subjects.
Disclosure: A. Barnado, None; R. Carroll, None; C. Casey, None; J. C. Denny, None; L. Crofford, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/novel-electronic-health-record-method-
reveals-that-dsdna-antibody-negative-systemic-lupus-erythematosus-is-associated-with-pain-sleep-and-mood-disorders
Long-Term Outcomes in Prolonged Low Disease Activity Are Comparable to

Complete Clinical Remission in Systemic Lupus Erythematosus
Konstantinos Tselios1, Dafna D Gladman2, Zahi Touma3, Jiandong Su4, Nicole Anderson2 and Murray Urowitz5,
1Medicine, University of Toronto, Toronto Western Hospital, Toronto, ON, Canada, 2Rheumatology, University of Toronto,
Toronto Western Hospital, Toronto, ON, Canada, 3Rheumatology, University of Toronto, Division of Rheumatology,
Institute of Health Policy, Management and Evaluation, Toronto, ON, Canada, 4University of Toronto, Toronto Western
Hospital, Toronto, ON, Canada, 5Centre for Prognosis Studies in the Rheumatic Diseases, University of Toronto, Toronto
Western Hospital, Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose: Prolonged clinical remission is a desirable, though rare outcome in systemic lupus erythematosus
(SLE). We recently showed that low disease activity (LDA) state confers the same risk as complete remission with regard
to damage accumulation and flare rate at two years. The aim of the present study was to assess the impact of prolonged
LDA (for 10 years) on such outcomes as compared to patients who achieved complete remission.
Methods: The inception cohort of a large lupus clinic (patients enrolled within 18 months of diagnosis) was investigated.
Patients selected had a minimum follow-up of 10 years and no interval greater than 18 months between consecutive visits.
Prolonged clinical remission was defined based on SLEDAI-2K=0 (serology excluded), achieved within the first five years
since diagnosis and maintained for ≥10 years. Prolonged LDA was defined as SLEDAI-2K ≤ 2 (serology excluded) for the
same period. Statistical analysis was performed with SAS 9.0 software; p<0.05 was considered significant.
Results: Of the 883 inception patients, 382 fulfilled the inclusion criteria. Twenty-seven patients (7.1%) achieved
prolonged clinical remission and 48 (12.6%) prolonged LDA. There were no differences regarding demographic, clinical,
and immunological variables at diagnosis and at 10 years. Mean prednisone dose at diagnosis was higher in the patients
who achieved remission. Antimalarial usage was higher in patients with LDA both at diagnosis and at 10 years. The two
groups had comparable cumulative damage over 10 years, flare rate after 10 years, and mortality throughout follow-up.
Details are given in Table 1.
Table 1. Comparison between patients with prolonged remission and LDA
At diagnosis At 10 years
Variable CR (n=27) LDA p CR LDA p
(n=48) (n=27) (n=48)
Age at diagnosis (y) 39±14.1 39.1±14.9 0.976
ACR criteria 4.4±1.4 4.9±1.7 0.199
(mean±SD)
Time to remission or 1.6±1.3 1.8±1.6 0.656
LDA (y)
SLEDAI-2K 10.7±11.6 9.5±10 0.642 1.2±1.6 1.6±1.7 0.305
(mean±SD)
Low complement (n, 9 (33.3%) 16 (33.3%) 1.000 8 (29.6%) 13 (27.1%) 0.97
%)
Anti-dsDNA (n, %) 13 (48.1%) 16 (33.3%) 0.206 6 (22.2%) 12 (25.0%) 0.956
Glucocorticosteroids 17 (63.0%) 33 (68.8%) 0.61 6 (22.2%) 10 (20.8%) 0.888
(n, %)
Mean prednisone dose 16.8±9.5 10.7±8.4 0.028 5.3 ± 3.2 4.6 ± 1.4 0.576
(mg/d)
Cumulative 18.1 ± 13.4 ± 9.1 0.129
prednisone dose (g) 12.4
Antimalarials (n, %) 16 (59.3%) 38 (79.2%) 0.065 11 32 0.029
(40.7%) (66.7%)
Immunosuppressives 9 (33.3%) 16 (33.3%) 1.000 3 (11.1%) 8 (16.7%) 0.514
(n, %)
No Medications (n, 12 19 (39.6%) 0.682
%) (44.4%)
SLICC/DI (mean±SD) 0.26±0.53* 0.33±1.04* 0.73 0.96 ± 1.10 ± 0.636
1.06 1.32
Disease flare after 10 7 (25.9%) 15 (31.3%) 0.627
years
Time to flare (median 12 (11- 11 (10-13) 0.217
in years) 15)
Deceased (n, %) 3 (11.1%) 5 (10.4%) 0.925
* At one year after diagnosis, CR: complete remission, LDA: low disease activity,
SLICC/DI: Systemic Lupus International Collaborating Clinics/Damage Index
Conclusion: Patients with prolonged (>10 years) LDA achieved comparable outcomes as those with complete remission in
the long term. Differences regarding therapeutic approach were observed but did not affect damage accumulation.
Approximately 40% of these patients were able to discontinue all medications 10 years after diagnosis. Prolonged LDA
status is an acceptable treat to target outcome in SLE.
Disclosure: K. Tselios, None; D. D. Gladman, None; Z. Touma, None; J. Su, None; N. Anderson, None; M. Urowitz,
GlaxoSmithKline, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/long-term-outcomes-in-prolonged-low-

disease-activity-are-comparable-to-complete-clinical-remission-in-systemic-lupus-erythematosus
Prolonged Antimalarial Treatment Is Associated with Increased Risk for

Elevated Myocardial Biomarkers in Systemic Lupus Erythematosus
Konstantinos Tselios1, Dafna D Gladman2, Paula Harvey3, Shadi Akhtari3, Jiandong Su4 and Murray Urowitz2,
1Medicine, University of Toronto, Toronto Western Hospital, Toronto, ON, Canada, 2Rheumatology, University of Toronto,
Toronto Western Hospital, Toronto, ON, Canada, 3Cardiology, Women's College Hospital, University of Toronto, Toronto,
ON, Canada, 4University of Toronto, Toronto Western Hospital, Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose: Antimalarial (AM)-induced cardiomyopathy (AMIC) has been rarely reported in systemic lupus
erythematosus (SLE). However, given the large number of patients treated, it seems possible that AMIC is under-
recognized and may run undiagnosed as an ill-defined heart failure syndrome. Specific cardiac biomarkers may identify
patients at risk. We sought to investigate the prevalence and associated factors for such biomarkers in systemic lupus
erythematosus (SLE).
Methods: One hundred sixty eight consecutive patients (153 females) attending a large lupus clinic, without past history of
cardiac disease (heart failure, coronary artery disease, valvulopathy etc.) and/or pulmonary hypertension, were enrolled.
None had chest pain or electrocardiographic (ECG) abnormalities suggestive of acute coronary syndrome. High-sensitivity
cardiac troponin I (cTnI) and B-natriuretic peptide (BNP) were measured simultaneously in serum and plasma samples,
respectively. Patients were categorized according to normal or abnormal BNP and/or cTnI. For the assessment of the
impact of AM duration on abnormal cardiac biomarkers, patients were divided in two groups according to the median
duration of use, which was calculated at 5.6 years in the current cohort. Statistical analysis was performed with SAS 9.0
software; p<0.05 was considered significant.
Results: Sixteen patients (9.5%) had elevated BNP and/or cTnI. Compared to subjects with normal biomarkers, they were
older, had longer disease and AM use duration and more frequently persistent creatine phosphokinase (CPK) elevation.
Details are shown in Table 1.
Table 1. Comparison between BNP/cTnI abnormal and BNP/cTnI normal
patients
VARIABLE BNP/cTnI abnormal (no BNP/cTnI normal P
history of heart disease or
(At assessment) PAH) (n=16) (n=152)
Age (y) 54.7 ±15.1 47.83 ± 12.15 0.037
SLE duration (y) 22.54 ± 10.44 15.45 ± 10.05 0.008
SLEDAI-2K 1.88 ± 2.47 2.79 ± 3.64 0.329
Adjusted Mean
SLEDAI-2K for 2
years prior 2.52±2.96 3.02±3.18 0.549
eGFR < 30ml/min 0 (0%) 3 (2%) 0.571
Hypertension 10 (62.5%) 54 (35.5%) 0.035
Diuretics treatment 5 (31.3%) 8 (5.3%) <0.001
Systolic BP at test
(mmHg) 118.4 ± 21.7 113.5 ± 16.9 0.28
Diastolic BP at test
(mmHg) 71.9 ± 10.1 69.5 ± 11.8 0.444
Abnormal CPK ⌘ 7 (43.8%) 24 (15.8%) 0.008
Cumulative years on
AM 13.66 ± 9.14 7.88 ± 8.02 0.008
AM duration>5.6
years 14 (87.5%) 69 (45.4%) 0.001
Corticosteroids 8 (50%) 70 (46.1%) 0.763
Mean prednisone
(mg/day) 9.4 ± 4.2 7.53 ± 5.1 0.326
Immunosuppressives 10 (62.5%) 87 (57.2%) 0.685
eGFR: estimated glomerular filtration rate, PAH: pulmonary arterial hypertension,
BP: blood pressure, CPK: creatine phosphokinase, AM: antimalarials, CQ:
chloroquine, HCQ: hydroxychloroquine, ⌘ Three abnormal measurements during
the last two years
Multivariable regression analysis showed prolonged AM treatment (>5.6 years) and persistent CPK elevation to be
important predictors for elevated cardiac biomarkers [HR=5.43, 95%CI=1.14-25.9, p=0.034 and HR=4.62, 95%CI=1.22-
17.51, p=0.024, respectively]. Two patients were diagnosed with AMIC on endomyocardial biopsy; both had CPK and
BNP/cTnI elevation.
Conclusion: Approximately 9% of SLE patients had elevated myocardial biomarkers, in the absence of prior cardiac
disease or pulmonary arterial hypertension. Prolonged AM therapy and persistent CPK elevation conferred an increased
risk for abnormal BNP and cTnI, which might predict AMIC.
Disclosure: K. Tselios, None; D. D. Gladman, None; P. Harvey, None; S. Akhtari, None; J. Su, None; M. Urowitz,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prolonged-antimalarial-treatment-is-

associated-with-increased-risk-for-elevated-myocardial-biomarkers-in-systemic-lupus-erythematosus
Long-Term Outcome of Demyelnating Syndrome in Systemic Lupus

Erythematosus: A Longitudinal Study
Jamal A. Mikdashi1 and Ipolia Ramadan2, 1Div of Rheumatology, Univ of Maryland Schl of Med, Baltimore, MD,
2National Institue of Health, Rockville, MD
SESSION INFORMATION
Background/Purpose: Demyelinating syndromes (DS) in systemic lupus erythematosus (SLE) are characterized by
inflammation, demyelination and neurodegeneration. Little is known, however, about the tenet of dissemination in time or
space of DS in SLE. The aim of this study is to evaluate the long-term outcomes in SLE patients with DS in a large SLE
cohort.
Methods: Data of patients with DS were obtained from the SLE cohort at the University of Maryland, between 1996 and
2016. Demographic, clinical features, serological studies, SLE-related treatment, and DS treatment-related exposures,
Expanded Disability Status Scale (EDSS) score at baseline, were included. SLE patients with DS were classified as
Clinically Isolated Syndrome (CIS), [those presenting with optic neuritis, partial myelitis or a brain stem syndrome], and
Radiologically Isolated Syndrome (RIS), [those exhibiting radiological disease with T2/fluid attenuated inversion recovery
or enhancing magnetic resonance imaging (MRI) typical of demyelination as a biomarker of acute inflammatory
activity].The primary outcomes were DS progression, overall survival, cognitive dysfunction and residual disability. The
predictors of DS progression were calculated using multivariable Cox proportional hazards regression analysis models. To
avoid bias, patients were included in the analysis regardless of their duration of follow-up.
Results: 25 SLE cases with DS were identified [mean age; 41.9 + 12.3 years, 80 % African America, 84% women, with a
mean follow up of 6.9 + 1.8 years]. The median baseline EDSS score was 4.5 (range, 1.5-6.5). CIS was observed in 15
cases (60 %) [Optic neuritis n=6 (24%), acute transverse myelitis n=9 (36%)]. Ten patients (40%) had RIS. Two patients (8
%) had neuromyelitis optica syndrome.
Nine patients (36%) had progressive forms of DS, 8 (32 %) had cognitive dysfunction and 9 (36 %) had worsening
disability. Three deaths at follow up, were observed and were considered SLE-related mortality.
Factors associated with progression of DS included, SSA antibody [Odds ratio, 10.5 (95% CI: 1.5-72, p < 0.005)], and
presence of oligoclonal bands on spinal fluid analysis. There were lack of association with INF gene expression, DS
modifying therapy, phospholipid syndrome, or use of hydroxycholorquine.
Worsening disability overtime was associated with spinal cord lesions {OR 34 (95 % CI: 3.5-93.2, p < 0.001)], and CIS
[OR 10.3 (95 % CI 1.0-102, p < 0.008)]. The use of DS modifying therapy tended to be protective, (OR 0.8, 95% CI, 0.6-
0.9, p < 0.051).
Older age (> 40 years) [OR 3.6 (95% CI: 1.7- 67, p < 0.03] and midbrain lesion (OR 2.7, 95 % CI: 1.1-6.5, p < 0.05)] were
associated with cognitive impairment.
Conclusion: More than half of SLE patient with DS remained free from neurological progression for 5 years after DS
diagnosis. Younger age, relapsing form of DS, prior immunotherapies, and lower baseline EDSS score were factors
associated with better outcomes. Identifying novel biomarkers of DS progression in SLE will help develop therapeutic
options and engender mechanisms of neurodegeneration.
Disclosure: J. A. Mikdashi, None; I. Ramadan, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/long-term-outcome-of-demyelnating-

syndrome-in-systemic-lupus-erythematosus-a-longitudinal-study

Prolonged Exposure to Antiphospholipid Antibodies Is Associated with
Endothelial Dysfunction in Patients with Systemic Lupus Erythematosus
In-Woon Baek1, Yune-Jung Park2, Ki-Jo Kim3, Wan-Uk Kim Sr.4 and Chul-Soo Cho1, 1Internal Medicine, Yeouido St.
Mary's Hospital, The Catholic University of Korea, Seoul, Korea, Republic of (South), 2Internal Medicine, St. Vincent's
Hospital, The Catholic University of Korea, Suwon, Gyeonggido, Korea, Republic of (South), 3Internal Medicine, St.
Vincent's Hospital, The Catholic University of Korea, Suwon, Korea, Republic of (South), 4The Catholic University of
Korea, Department of Internal Medicine, seoul, Korea, Republic of (South)
SESSION INFORMATION
Background/Purpose: Antiphospholipid syndrome has been shown to be associated with increased cardiovascular
mortality, but the role of antiphospholipid antibodies (aPL) on endothelial dysfunction remains elusive. We investigated the
association between endothelial dysfunction and aPL in systemic lupus erythematosus (SLE) patients.
Methods: 185 SLE patients and 62 controls were enrolled. Endothelial function was measured by flow-mediated dilatation
(FMD). Cardiovascular risk factors were assessed and quarterly measurement of anti-cardiolipin (aCL) and anti-b2
glycoprotein I Ab were used to calculate time-integrated values throughout disease duration. Circulating endothelial
progenitor cell (EPC), defined by CD34+/KDR+ mononuclear cells, was quantified by flow cytometry.
Results: Median FMD was significantly lower in SLE patient than in controls (6.9 versus 9.3%, P<0.001). In univariate
analysis, older age, hypertension, and persistent positive lupus anticoagulant (LAC) were associated with decreased FMD
in SLE patients (P=0.034, P=0.020, and P=0.028). Time-integrated aCL value (TI-aCL), but not a single value, was
correlated with decreased FMD (P=0.003). Multivariate analysis showed that hypertension and TI-aCL were independent
factors for decreased FMD (P=0.012, P=0.011); addition of positive LAC increased the adjusted probability of decreased
FMD (P=0.003). FMD was correlated with EPC number (r=0.342, P=0.005) and TI-aCL was also an independent factor of
reduced EPC after multiple adjustment (P=0.024). The predicted probability of endothelial dysfunction at median EPC
level was higher in group with high TI-aCL than in group with low TI-aCL (P=0.004).
Conclusion: Cumulative burden of aPL was closely associated with endothelial dysfunction in SLE patients, which was
mediated in part by reduction of EPC.
Disclosure: I. W. Baek, None; Y. J. Park, None; K. J. Kim, None; W. U. Kim Sr., the National Research Foundation of
Korea, 2; C. S. Cho, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prolonged-exposure-to-

antiphospholipid-antibodies-is-associated-with-endothelial-dysfunction-in-patients-with-systemic-lupus-erythematosus
Risk Factors for Neuropsychiatric Systemic Lupus Erythematosus and Its

Recurrence
Ryusuke Anan, Yuko Kaneko, Jun Kikuchi and Tsutomu Takeuchi, Division of Rheumatology, Department of Internal
Medicine, Keio University School of Medicine, Tokyo, Japan
SESSION INFORMATION
Background/Purpose: Neuropsychiatric involvement in systemic lupus erythematosus (NPSLE) is the leading cause of
morbidity and mortality in patients with SLE but not well understood. The aim of this study was to identify risk factors for
NPSLE and its recurrence.
Methods: We enrolled consecutive patients with SLE who had visited Keio University Hospital between 2013 and 2015.
The patients were divided according to the presence or absence of NPSLE, and their clinical characteristics, manifestations,
findings of cerebrospinal, electroencephalographic and neuroimaging examination, treatment and prognosis were
compared. Patients with NPSLE were further divided by the recurrence of NPSLE, and its risk factors were examined.
Results: A total of 302 patients with SLE were enrolled. Two hundred seventy (89%) were female, and the mean age was
49.2 years. Forty-two (14%) patients were diagnosed with NPSLE during the course of SLE according to the ACR case
definitions. The patients with NPSLE had a history of serositis more frequently than those without (37% vs 20%, p=0.03).
Anti-Ro/SSA antibody (76% vs 54%, p=0.02) and anti-phospholipid antibody (55% vs 35%, p=0.03) were more frequently
detected in patients with NPSLE while no difference was found in other autoantibodies including anti-DNA, anti-Sm, anti-
RNP, and lupus anticoagulant. Among NPSLE patients, 22 (52%) had recurrent central nervous involvement. Serologically,
the recurrent group had higher positivity of anti-Ro/SSA antibody than the non-recurrent group (88% vs 59%, p=0.02).
Patients with focal hypoperfusion in single photon emission computed tomography (SPECT) at the first NPSLE had
significantly higher relapse rate than those with diffuse hypoperfusion (86% vs 36%, p=0.02). Patients treated with
intravenous cyclophosphamide at the first NPSLE were at a lower risk of recurrence (12% vs 46%, p=0.01).
Conclusion: Anti-Ro/SSA antibody was a risk for recurrent NPSLE. Patients with focal hypoperfusion of SPECT at the
first NPSLE had significantly higher risk for NPSLE recurrence. Cyclophosphamide is important for preventing the
recurrence of NPSLE.
Disclosure: R. Anan, Chugai Pharmaceutical, 8; Y. Kaneko, AbbVie, Eisai, Daiichi Sankyo, Sanofi, 2,Bristol-Myeres
Squibb, Eli Lily, Janssen, 5,AbbVie, Eisai, Astellas, Chugai Pharmaceutical, UCB, Pfizer, Bristol-Myeres Squibb, Janssen,
Tanabe-Mitsubishi, Ayumi Pharmaceutical, and Takeda Pharmaceutical, Taisho-Ttoyama, 8; J. Kikuchi, Pfizer Inc,
8,Bristol-Myers Squibb, 8,Eisai, 8,AbbVie, 8,Chugai, 8; T. Takeuchi, Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis
Pharma K.K., Mitsubishi Tanabe Pharma Co., Abbivie GK, Nipponkayaku Co.Ltd, Janssen Pharmaceutical K.K., Astellas
Pharma Inc,.Taiho Pharmaceutical Co., Ltd.,, 5,AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd.,
Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Astellas Pharma Inc, and Diaichi Sankyo Co.,Ltd., 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/risk-factors-for-neuropsychiatric-

systemic-lupus-erythematosus-and-its-recurrence
Atherosclerotic Vascular Events in a Multinational SLE Inception Cohort:

Description and Predictive Risk Factors over a 17 Year Period
Murray Urowitz1, Dafna D Gladman2, Nicole Anderson3 and Jiandong Su4, 1Centre for Prognosis Studies in the
Rheumatic Diseases, University of Toronto, Toronto Western Hospital, Toronto, ON, Canada, 2Rheumatology, Toronto
Western Hospital, University of Toronto, Toronto, ON, Canada, 3Rheumatology, University of Toronto, Toronto Western
Hospital, Toronto, ON, Canada, 4University of Toronto, Toronto Western Hospital, Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose: A large multicentre multinational inception cohort was established to study risk factors for
atherosclerosis (AS) in SLE. We aim to describe all vascular events (VE) and determine the predictors of atherosclerotic
vascular events (AVE) in this cohort over a 17 year period.
Methods: Patients enter the cohort within 15 months of SLE diagnosis (≥4 ACR criteria). Clinical and laboratory features
of SLE are collected annually in a standardized protocol from 2000-2017. Patients with <3 years of follow-up or VEs
attributed to other causes were excluded. VEs recorded include myocardial infarction (MI), angina, congestive heart failure
(CHF), intermittent claudication (PVD), transient ischemic attack (TIA), pacemaker insertion and stroke. Diagnosis of a
VE is confirmed using standard clinical criteria, relevant laboratory data and imaging where appropriate. Attribution to AS
was made on the basis of lupus disease being inactive at the time of VE, and/or the presence of typical AS changes on
imaging or pathology and/or evidence of AS elsewhere. Factors associated with AVE were analyzed on patients with AVEs
that occurred after study enrollment using time to event analysis with time dependent covariates and cox proportional
hazard model.
Results: 1848 patients entered the cohort (88.7%F, age at SLE 34.7 ± 13.4 years, disease duration 5.6 ± 4.2 months, mean
follow-up of 7.3 ± 4.5 years). Thus far, there have been 231 VEs in 159 patients. These include: MI (24), angina (31), CHF
(52), pacemaker insertion (9), PVD (20), TIA (29) and stroke (66). 106 VEs were attributed to active lupus and 42 to other
causes. 83 VE in 57 patients were attributed to AS including: MI (17), angina (26), CHF (12), pacemaker (5), PVD (9),
TIA (7), and stroke (7). 14 patients in the AS group had >1 AVE. SLE duration at first AVE was 3.7 ± 3.5 years. Of the 57
AVE patients, 47 had an AVE that occurred after study enrollment.
Table 1. Cohort Characteristics at Enrolment
Patients that
Patient that had
Characteristic did not have a p value
a AVE (N=47)
VE (N=1364)
Male 13 (27.7%) 133 (9.8%) <0.001
Caucasian 34 (72.3%) 663 (48.6%) 0.001
Age at SLE diagnosis
51.82 ± 14.89 33.99 ± 12.93 <0.001
(Mean ± SD)
Smoking 25 (53.2%) 466 (34.2%) <0.001
Hypertension 26 (55.3%) 446 (32.7%) 0.001
Diabetes 3 (6.7%) 46 (3.4%) 0.241
Obese 23 (51.1%) 381 (28.9%) 0.001
Hypercholesterolemia 21 (44.7%) 475 (34.8%) 0.165
Family history of CAD 21 (45.7%) 300 (22.5%) 0.001
SLEDAI-2K (Mean ± 4.13 ± 4.83 5.38 ± 5.33
0.112
SD)
Total ACR Criteria
(Mean ± SD) 4.96 ± 1.21 4.91 ± 1.05 0.683
Serositis 21 (44.7%) 367 (26.9%) 0.007
Renal Disorder 12 (25.5%) 389 (28.5%) 0.655
Neurologic Disorder 3 (6.4%) 55 (4.0%) 0.425
Immunologic 39 (83.0%) 1,044 (76.5%) 0.304

Disorder
116/894
7/35 (20.0%) 0.198
Anticardiolipin (14.5%)
187/926
13/35 (37.1%) 0.026
Lupus Anticoagulant (20.2%)
Treated with oral steroids 32 (68.1%) 928 (69.7%) 0.802
Average daily
corticosteroid dose 14.20 ± 17.58 16.73 ± 17.39 0.327
(Mean ± SD)
Treated with
26 (55.3%) 936 (68.6%) 0.251
antimalarials
Treated with
18 (38.3%) 542 (39.7%) 0.926
immunosuppressives
Table 2. Predictive Risk Factors – Multivariable Analysis
95% Confidence
Predictor Hazard Ratio p value
Interval
Age at SLE <0.001
1.08 1.06, 1.10
diagnosis
ACR Criteria – 0.003
2.47 1.34, 4.54
Serositis
Antimalarial 0.033
0.52 0.28, 0.95
treatment
The classic risk factors at inception were not predictive, but they do increase over time (Figure 1).
Conclusion: Over the follow-up of an inception cohort with SLE there were 83 AVEs in 57 patients of which 47 occurred
after enrollment. Only older age and serositis are significant risk factors for AVE and antimalarials were protective.
However, traditional risk factors increase over time and may have an impact on the development of AVE in the future.
Disclosure: M. Urowitz, None; D. D. Gladman, None; N. Anderson, None; J. Su, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/atherosclerotic-vascular-events-in-a-

multinational-sle-inception-cohort-description-and-predictive-risk-factors-over-a-17-year-period
Lupus Nephritis in Isolation or Accompanied By Extra-Renal

Manifestations: Early Lessons from the Accelerating Medicines Partnership
Judith A. James1, Michelle Petri2, Chaim Putterman3, Betty Diamond4, David Wofsy5, Chun Hao Lee6, Derek Fine6,
Anna R. Broder7, Robert M. Clancy8, Peter M. Izmirly9, Michael Belmont10, Nicole Bornkamp11, Anne Davidson12, Patti
Tosta13, Kenneth C. Kalunian14, Meyeon Park15, Maria Dall'Era16, Richard Furie17, Elena Massarotti18, German T.
Hernandez19, Fernanda Payan-Schober20, Sean M. Connery19, Diane L. Kamen21, Iris Lee22, William Pendergraft III23,
Jennifer H. Anolik24, Ummara Shah25, Soumya Raychaudhuri26, Yvonne C. Lee27, Joel M. Guthridge28, V. Michael
Holers29, Paul J. Utz30, Mina Pichavant31, Rohit Gupta31, Holden T. Maecker32, Michael Weisman33 and Jill P. Buyon34,
1Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 2Medicine
(Rheumatology), Division of Rheumatology, Johns Hopkins University School of Medicine, MD, USA, Baltimore, MD,
3Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY, USA, Bronx, NY, 4Autoimmune and
Musculoskeletal Diseases, The Feinstein Institute for Medical Research, Manhasset, NY, 5Rheumatology, UCSF, San
Francisco, CA, 6Johns Hopkins University, Baltimore, MD, 7Albert Einstein College of Medicine, Bronx, NY, 8NYU
School of Medicine, New York, NY, 9New York University School of Medicine, New York, NY, 10New York University,
NYC, NY, 11Medicine, New York University School of Medicine, New York, NY, 12Autoimmunity and Musculoskeletal
Diseases, Feinstein Institute for Medical Research, Manhasset, NY, 13Immune Tolerance Network, San Francisco, CA,
14Division of Rheumatology, Allergy & Immunology, UCSD School of Medicine Center for Innovative Therapy, La Jolla,
CA, 15University of California San Francisco, San Francisco, CA, 16Medicine/Rheumatology, University of California, San
Francisco, San Francisco, CA, 17Hofstra Northwell, Manhasset, NY, 18Brigham and Women's Hospital, Boston, MA,
19Texas Tech University HSC El Paso, El Paso, TX, 20Texas Tech University HSC El Paso, El Paso, TX,
21Medicine/Rheumatology & Immunology, Medical University of South Carolina, Charleston, SC, 22Temple University
Hospital, Philadelphia, PA, 23Kidney Center, University of North Carolina, Chapel Hill, NC, 24Medicine- Allergy,
Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, 25Division of Rheumatology,
New York University School of Medicine, NYC, NY, 26Divisions of Genetics and Rheumatology, Brigham and Women's
Hospital and Harvard Medical School, Boston, MA, 27Rheumatology Immunology & Allergy, Brigham and Women's
Hospital and Harvard Medical School, Boston, MA, 28Arthritis and Clinical Immunology Program, Oklahoma Medical
Research Foundation, OKC, OK, 29Rheumatology Division, University of Colorado School of Medicine, Aurora, CO,
30Medicine, Stanford University School of Medicine, Stanford, CA, 31Stanford University, Stanford, CA, 32Division of
Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, 33Cedars-Sinai Medical Center
Division of Rheumatology, Los Angeles, CA, 34Rheumatology, New York University School of Medicine, New York, NY
SESSION INFORMATION
Background/Purpose: Lupus nephritis (LN) remains one of the most serious complications of SLE, occurring in up to
50% of patients. Current LN treatments are not sufficiently efficacious, are accompanied by significant off-target toxicities
and result in a high percent of patients progressing to end stage renal disease. Thus, additional efforts are needed to
understand LN at the molecular level, and to identify clinical responsiveness with specific molecular pathways.
Methods: SLE patients with proteinuria and suspected LN (n=105) were enrolled over 15 months by 12 US-based lupus
centers to the RA/Lupus Accelerated Medicines Partnership Phase I program. Demographic, clinical, and therapeutic
information was gathered using standard case report forms and entered into a study-specific database. ACR and SLICC
SLE classification criteria, biopsy information, modified SELENA-SLEDAI, laboratory values and patient reported
outcomes (PROMIS29) were collected. Serum, plasma, PBMCs, total blood leukocytes, urine, urine cells, and renal biopsy
tissue were collected, with non-lesional, non-sun exposed skin biopsies in 25%. Complete renal response was considered
improvement of urine protein to <500mg (or UPCR <0.5) and normal serum creatinine (or up to 125% of baseline) with
prednisone taper, while partial response required improvement of urine protein by ≥50%.
Results: Of the 105 SLE patients recruited, 93 (89%) were female and most were non-Caucasian (n=84; 80%), including
28% Hispanic, 39% African-American, 11% Asian, 2% mixed ethnicity/not reported. Of the SLE renal biopsies (n=105),
75% were ISN Class III, IV, V or mixed. LN patients were on average 33.7 years of age (range: 14-58) with a baseline
urine protein:creatinine ratio of 3.3 (with 34% > 3; n=21), 70% anti-dsDNA positive (n=48), 84% with low complement
levels (n=59) and 39% with Hg < 10 g/dL (n=28). The average SLEDAI was 12.3, with 56% of this group presenting with
global disease activity (e.g. 2 organ systems active in addition to renal, e.g. arthritis, skin, serositis). Analysis of 30 LN
patients with longitudinal information revealed that 33% achieved complete response and 17% partial response to standard
of care (SOC) therapy at 6 months. LN patients with extra renal disease activity were twice as likely to be renal non-
responders to SOC (n=10 NR; n=5 CR/PR) than those LN patients whose disease activity was limited to renal and
immunologic features only (n=6 NR; n=9 CR/PR).
Conclusion: These preliminary findings suggest that renal response to current SOC may occur more often in patients
without other active manifestations of lupus. Significant clinical heterogeneity exists between LN patients emphasizing a
need for deeper molecular phenotyping.
Disclosure: J. A. James, None; M. Petri, Anthera Inc, 5,GlaxoSmithKline, 5,EMD Serono, 5,Eli Lilly and Company,
5,Bristol Meyer Squibb, 5,Amgen, 5,United Rheumatology, 5,Global Academy, 5,Exagen, 2; C. Putterman, None; B.
Diamond, None; D. Wofsy, None; C. H. Lee, None; D. Fine, None; A. R. Broder, None; R. M. Clancy, None; P. M.
Izmirly, None; M. Belmont, None; N. Bornkamp, None; A. Davidson, None; P. Tosta, None; K. C. Kalunian, Pfizer
Inc, Gilead, UCB, Amgen, 2; M. Park, None; M. Dall'Era, None; R. Furie, None; E. Massarotti, Exagen, 5,BMS,
2,Springer Publishing, 7; G. T. Hernandez, None; F. Payan-Schober, None; S. M. Connery, None; D. L. Kamen, None;
I. Lee, None; W. Pendergraft III, None; J. H. Anolik, None; U. Shah, None; S. Raychaudhuri, Pfizer Inc, 2,Roche
Pharmaceuticals, 2; Y. C. Lee, Express Scripts, 1,Pfizer Inc, 2; J. M. Guthridge, None; V. M. Holers, None; P. J. Utz,
None; M. Pichavant, None; R. Gupta, None; H. T. Maecker, None; M. Weisman, None; J. P. Buyon, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/lupus-nephritis-in-isolation-or-

accompanied-by-extra-renal-manifestations-early-lessons-from-the-accelerating-medicines-partnership
Ambulatory Blood Pressure and Skin Sodium Concentrations in Patients

with Systemic Lupus Erythematosus
Daniel Carranza Leon1, Cecilia P. Chung1, Michelle J. Ormseth2, Annette M. Oeser3, Ping Wang4, Adriana Marton1, Jens
Titze3 and C. Michael Stein1, 1Medicine, Vanderbilt University Medical Center, Nashville, TN, 2Rheumatology, Vanderbilt
Medical Center, Nashville, TN, 3Vanderbilt University Medical Center, Nashville, TN, 4Radiology, Vanderbilt University
Medical Center, Nashville, TN
SESSION INFORMATION
Background/Purpose:
Ambulatory 24-hour blood pressure and nocturnal blood pressure measurements are better predictors of cardiovascular risk
than office blood pressure. Patients with systemic lupus erythematosus (SLE) have a high prevalence of hypertension and
cardiovascular events. Recent findings indicate that sodium stored in the skin can be measured with 23Na+ magnetic
resonance imaging (MRI) and plays an important role in both blood pressure and immune regulation. Little is known about
ambulatory blood pressure in SLE and its relationship to skin Na+ is not known.
Methods:
Office blood pressure was measured at study enrollment using standard procedures and ambulatory 24-hour blood pressure
measurements were recorded (Meditech, Budapest, Hungary) in 23 patients with SLE and 23 controls frequency-matched
for age, race, and sex. Skin Na+ content in the lower leg was measured with a 3T 23Na+ knee-coil with a magnetic
resonance imaging scanner (Philips Achieva 3T) in 13 patients with SLE. Phantoms containing aqueous solutions with 10,
20, 30, and 40 mmol/L NaCl were included for calibration. Blood pressure measurements in patients and control subjects
were compared using Wilcoxon-rank sum tests and adjusted for age, race, and sex using a linear regression model.
Spearman correlations were used to assess the correlation between blood pressure measurements and and skin sodium in
SLE patients.
Results:
Results: Office blood pressure was not significantly different in patients with SLE and controls (Table). However,
ambulatory blood pressure measurements, particularly nocturnal measurements, were higher in patients with SLE. In
patients with SLE (n=13), skin Na+ concentrations were 15.0 (IQR 13.3 – 18.4) mmol/L and were significantly correlated
with both office (rho= 0.67, P=0.023) and mean 24-hour systolic blood pressure (rho= 0.62, P= 0.04).
p-
SLE (N=23) Controls (N=23) p-value value*
Age, years 35 (31-52) 35 (26-50) 0.73
BMI, kg/m2 25.9 (22.7-33.8) 24.3 (22.7-26.8) 0.22
Sex female 19 (82.61%) 20 (87.0%) 1.0
Race white 15 (65.2%) 19 (82.6%) 0.31
Smoker never 17 (73.9%) 17 (73.9%) 1.0
24 hr Mean SBP,
mmHg 128.5 (113-139.1) 115 (110.6-121) 0.05 0.04
24 hr Mean DBP,
mmHg 78 (68.9-85.2) 72.4 (66.8-74.9) 0.02 0.04
Awake Mean SBP, 118.5 (114.7-
mmHg 130.2 (115-139.3) 124.7) 0.07 0.07
Awake Mean DBP,
mmHg 82 (70.6-89) 76.1 (70.2-78.6) 0.07 0.07
Sleep Mean SBP,
mmHg 115 (104.7-129) 107 (97.8-112.6) 0.02 0.03
Sleep Mean DBP,
mmHg 68 (58-80) 60.8 (53.6 - 66) 0.008 0.02
Office SBP, mmHg 126 (114-140) 121 (115-127) 0.37 0.43
Office DBP, mmHg 83 (68-90) 82 (73-90) 0.76 0.84
Hypertension, Yes 11 (47.8) 2 (8.7) 0.007
BMI= body mass index, SBP = systolic blood pressure, DBP = diastolic blood
pressure, *Adjusted for age, sex, and race
** Continuous and categorical data expressed as median (interquartile
range) and counts (percent) respectively
Conclusion:
Despite similar office blood pressure measurements, ambulatory blood pressure, particularly nocturnal blood pressure, was
higher in patients with SLE than controls. Skin Na+ levels were correlated with systolic blood pressure in SLE. Studies to
further assess the relationship between skin Na+ and disease activity, blood pressure, and cardiovascular disease in patients
with SLE are needed.
Disclosure: D. Carranza Leon, None; C. P. Chung, None; M. J. Ormseth, None; A. M. Oeser, None; P. Wang, None;
A. Marton, None; J. Titze, None; C. M. Stein, Lupus Research Alliance, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/ambulatory-blood-pressure-and-skin-

sodium-concentrations-in-patients-with-systemic-lupus-erythematosus
Improving the Quality of Care in Systemic Lupus Erythematosis (SLE)

through Time-Structured, Information Technology-Enhanced, Quality
Improvement Indicator-Driven Patient Management
Frank Migliore1, Robert Quinet2, William E. Davis3, Daniel Wray4, Timothy Hilbun5 and Magdelena Budziakowska1,
1Ochsner Clinic Foundation, New Orleans, LA, 2Rheumatology, Ochsner Medical Center, New Orleans, LA, 3University
of Queensland School of Medicine, Brisbane, Australia, 4Twine Clinical Consulting LLC, Park City, UT, 5IS ANALYTICS
NOM, Ochsner Medical Center, New Orleans, LA
SESSION INFORMATION
Background/Purpose:
Gaps exist in SLE patient care in monitoring and management of comorbidities, treatment related toxicities, and disease activity, suggesting a lack
of well-defined systems of care in SLE. Our hypothesis was that a more time structured, IT enhanced, and QI indicator-driven approach to SLE
management would translate to more frequent, comprehensive, and guideline adherent interactions with the lupus patient (“tight” management) that
would lead to improved outcomes.
Methods:
To prompt “tight” management of SLE patients at Ochsner main campus (687 patients - 2014 baseline; 644 patients - 2015 interventional; 581
patients – 2016 post-interventional), the following interventions were implemented:
• Lupus Management Module: SLE specific dashboard embedded into Epic EHR. Dashboard incorporates automated SLE management specific
reminders, alerts (and facilitates ordering appropriate testing/management), test result tracking, and customized assessments (SELENA-SLEDAI,
SLICC- SDI). SLICC-DI assessment is prompted 1x annually. SLEDAI assessment prompted every office visit. The occurrence of flare is prompted
tabulated and based on change in SELENA- SLEDAI assessment. Clinicians have the ability to override or confirm the tabulated occurrence of
flare. Also, clinicians could manually designate the occurrence of flare independently of the automated tracking system.
• Patient Campaigning: Identification of patients due for SLE specific testing or management activities. Of primary importance were to prompt an
office visit at least 1x/6 months and prompt pre office visit lab testing to enable completion of the SELENA- SLEDAI tabulation at the point of care,
thereby enabling and facilitating fully informed management decision making at the point of care.
Results:
These interventions prompted improvement in rate of SELENA-SLEDAI application 1x/6 months (26.35% - 2014 baseline period, 43.79% - 2015
interventional period, 39.93% - 2016 post-interventional period; p < 0.0001), rate of SLICC-SDI application 1x/12 months (22.83% - 2015
interventional period, 34.25% - 2016 post-interventional period; p < 0.0001), rate of performance of ALL appropriate labs 1x/6 months (28.38% -
2014 baseline period, 44.57% - 2015 interventional period, 43.37% - 2016 post-interventional period; p < 0.0001), rate of cardiovascular assessment
1x/12 months (35.95% - 2014 baseline period, 51.71% - 2015 interventional period, 46.30% - 2016 post-interventional period; p < 0.0001), rate of
influenza vaccination 1x/12 months (18.78% - 2014 baseline period, 29.50% - 2015 interventional period, 37.18% - 2016 post-interventional period;
p < 0.0001), rate of lupus flare (16.30% - 2015 interventional period, 12.05% - 2016 post-interventional period; p = 0.0338), and rate of
hospitalization (8.59% - 2014 baseline period, 6.68% - 2015 interventional period, 5.68% - 2016 post-interventional period; p = 0.0466).
Conclusion:
Time structured, IT enhanced, and QI indicator driven interventional modalities prompted more frequent, more comprehensive, guideline adherent
point of care interaction with SLE patients. “Tighter” management resulted in the improved outcomes of both rate of lupus flare and rate of
hospitalization in SLE patients.
Disclosure: F. Migliore, None; R. Quinet, None; W. E. Davis, None; D. Wray, None; T. Hilbun, None; M.
Budziakowska, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/improving-the-quality-of-care-in-

systemic-lupus-erythematosis-sle-through-time-structured-information-technology-enhanced-quality-improvement-
indicator-driven-patient-management
Differential Diagnosis of Autoimmune Diseases, Outlier Detection Plus

Subgrouping in Clinical Trials By High Content Autoantibody Profiling
Peter Schulz-Knappe, Petra Budde and Hans-Dieter Zucht, Protagen AG, Dortmund, Germany
SESSION INFORMATION
Background/Purpose: Early diagnosis as well as initiation of successful treatment are two big challenges in the
management of patients with autoimmune diseases (AID). Overlap of a plethora of clinical symptoms, ranging from multi-
organ involvement, fatique, inflammation to CNS-involvement make differential diagnosis quite challenging. Especially in
early disease these signs are difficult to quantify, hence the lag time from start of disease until clinical diagnosis may be
delayed, sometimes for years. With the growing interest in conducting clinical trials in AID, there is a need for new
biomarkers that can be used to diagnose individual AIDs to reduce the inclusion of patients not carrying the intended
disease, and identify clinical subsets, predict treatment outcome and assess disease activity.
Methods: The autoantibody reactivity pattern in serum of AID patients was analyzed using a Luminex bead-based antigen
array (SeroTag) and 1,600 – 8,000 selected human protein antigens. We screened over 3,000 serum samples from Sjögren’s
Syndrome (n= 350), SLE (n= >1000), SSc (n= >250), RA (n= >1000), and several other AIDs and over 1,000 healthy
individuals to confirm known and to discover novel autoantibodies, create reduced autoantibody panels for differential
diagnosis and disease subgrouping.
Results: Apart from clear confirmation of the known benchmark autoantigens known for many years we have discovered
over 80 novel autoantibodies, which were detected in frequencies of 10 to >25% in selected AIDs. Some novel
autoantibodies are specific for certain diseases, such as the major vault protein in SLE or BICD2 in SSc. Others are present
in several diseases, indicating overlap syndromes. Multiplex panels of 50-100 AABs were generated and tested to allow for
a subgroup definition of Sjögren’s, SLE, and for clear segregation of SjS/SLE overlap syndrome patients. As well,
subgrouping of SSc and early RA patients was achieved.
Conclusion: A set of 100-150 autoantigens, half of them well established, the other half novel, succeed in differential
diagnosis of AID, in some diseases already at early disease stage. This panel has been used in several drug trials to
subgroup SLE, Sjögrens or RA into subgroups. Especially in SLE, outliers in the range of 10-15% of the trial population
were seen which can be used to curate a trial population, eventually to arrive at a more precise assessment of trials primary
objectives.
Disclosure: P. Schulz-Knappe, ProtagenAG, 3; P. Budde, Protagen, 3; H. D. Zucht, Protagen AG, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/differential-diagnosis-of-autoimmune-

diseases-outlier-detection-plus-subgrouping-in-clinical-trials-by-high-content-autoantibody-profiling
Incidence and Variability of Cardiovascular Risk Factors in Female Lupus

Patients: A 3-Year Follow-up
Carolinne Monção1, Leticia Martins1, Marcela Penteado1, Rodrigo Reis2, Fabiana Miranda Moura dos Santos3, CRISTINA
COSTA LANNA3, Antônio Luiz Ribeiro4 and Rosa Weiss Telles4, 1Hospital das Clinicas, Universidade Federal of Minas
Gerais, Belo Horizonte, Brazil, 2Universidade Federal of Minas Gerais, Belo Horizonte, Brazil, 3Medical School,
Universidade Federal of Minas Gerais, Brazil, Belo Horizonte, Brazil, 4Medical School, Universidade Federal of Minas
Gerais, Belo Horizonte, Brazil
SESSION INFORMATION
Background/Purpose: To evaluate the incidence and variability of traditional coronary artery disease (CAD) risk factors in
a cohort of systemic lupus erythematosus (SLE) patients.
Methods: 174 women were included (T0) in this prospective study on SLE atherosclerosis. The following traditional CAD
risk factors were analyzed: hypertension (blood pressure ≥140/90 mmHg or antihypertensive medication), diabetes mellitus
(DM) (fasting glucose ≥ 126mg/dl on at least two occasions or use of oral hypoglycemic agents or insulin), dyslipidemia
(total-cholesterol ≥200mg/dl or HDL <40mg/dl or LDL ≥130mg/dl or use of oral lipid-lowering agents),
hypertriglyceridemia (triglycerides ≥150mg/dl), obesity (body mass index ≥30kg/m2), abdominal obesity (waist
circumference ≥88cm), smoking, positive family history for coronary event. Metabolic syndrome (MetS), according to
Third Report of the NCEP/ATP III criteria, and Framingham risk score (FRS) were computed. The cumulative incidence
between T0 and T1 for all risk factors was investigated. The incidence rate (person-years) for hypertension, DM,
dyslipidemia and hypertriglyceridemia, with a CI95%, were calculated based in the data collected from the medical
records. The frequency of risk factor disappearance at T1 (including the absence of treatment in the definition of
disappearance), among patients with the risk factor at T0, was also described.
Results: The mean (SD) age at T0 of 151 patients reevaluated after 39 (36.5-42.0) months (T1) was 37.8 (11.1) years old,
75.5% non-white. The cumulative incidence, the incidence rate and the disappearance of some risk factors for CAD are
presented in Table 1. The cumulative incidence during follow up were zero for smoking, 3.8% for positive family history
for premature CAD, 16.5% for obesity, 18.8% for MetS and 39.1% for abdominal obesity. Eleven (11.7%) of 143 patients
with low FRS in T0 were classified in high risk category in T1. Considering the risk factors disappearance, 26.0% with
MetS at T0, 16.7% with obesity and 6.3% with abdominal obesity presented without the risk factor at T1. Only 1 (12.5%)
patient within the higher risk of coronary event in 10 years (FRS>10%) at T0 “reduced” the risk to <10% in T1.
Conclusion: The authors identified a significant increase in the incidence of CAD risk factors in lupus patients with a
follow-up of approximately 3 years. Conditions such as hypertension, obesity and DM presented less fluctuation than
dyslipidemia between T0 and T1, raising considerations about the importance of statins use in lupus patients over time.
Table 1. Coronary artery disease risk factors cumulative incidence, incidence rate and disappearance after 39 (37-
42) months, in lupus patients
Risk factor Cumulative Incidence rate Disappearance
incidence* of risk
1000 person- factor**
years
(CI 95%)
Hypertension 18/79 72.1 (38.8- 6/72 (8.3%)
(22.8%) 105.4)
Diabetes 5/143 10.4 (1.3-19.5) 0
mellitus (3.5%)
Dyslipidemia 33/89 133.2 (87.8- 27/62 (43.5%)
(37.1%) 178.6)
LDL- 20/126 49.9 (28.1-71.8) 9/25 (36.0%)
c>130mg/dl (15.9%)
Total 27/122 71.9 (44.8-99.0) 11/29 (37.9%)
Chol>200mg/dl (22.1%)
HDL- 15/111 44.2 (21.8-66.5) 27/40 (43.5%)
c<40mg/dl (13.5%)
TGL>150mg/dl 16/108 49.1 (25.0-73.1) 18/30 (41.9%)
(14.8%)
*Incident case/Number of patients without risk factor at T0.
**Number of patients with disappearance of a risk factor/Number of patients with the risk factor at T0.
Disclosure: C. Monção, None; L. Martins, None; M. Penteado, None; R. Reis, None; F. M. M. dos Santos, None; C. C.
LANNA, None; A. L. Ribeiro, None; R. W. Telles, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/incidence-and-variability-of-

cardiovascular-risk-factors-in-female-lupus-patients-a-3-year-follow-up
Antibodies Against the Chemokine Receptors CXCR3 and CXCR4 Predict

Progressive Lung Fibrosis in Systemic Sclerosis (SSc)
Gabriela Riemekasten1, Elise Siegert2 and Harald Heidecke3, 1Department of Rheumatology, Universitatsklinikum
Schleswig-Holstein, Lubeck, Germany, 2Rheumatology and Clinical Immunology, University Hospital Charité, Berlin,
Germany, 3CellTrend GmbH Luckenwalde, Luckenwalde, Germany
SESSION INFORMATION
Session Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's – Clinical Aspects and Therapeutics Poster I
Background/Purpose: Chemokine receptors CXCR3 and CXCR4 are involved in immune cell migration and in the
pathogenesis of inflammatory fibrosis, a key feature of systemic sclerosis (SSc). It is hypothesized that IgG antibodies (ab)
against these two receptors are present in patients with SSc and associated with clinical findings.
Methods: Anti-CXCR3 and anti-CXCR4 ab levels were measured in 449 sera from 327 SSc patients and in 234 sera from
healthy donors (HD) by ELISA. In SSc, ab levels were compared with clinical data in a cross-sectional and longitudinal
setting. Protein expression of CXCR3 and CXCR4 on PBMC was analyzed in 17 SSc patients and 8 HD by flow cytometry.
Results: Anti-CXCR3 and anti-CXCR4 ab levels were different among SSc subgroups compared to HD and were highest
in diffuse SSc patients. The ab levels strongly correlate with each other (r = 0.85). Patients with SSc-related interstitial lung
disease (SSc-ILD) exhibited higher ab levels, which negatively correlated with lung function parameters (e.g. r = -0.5 and r
= -0.43 for predicted vital capacity, respectively). However, patients with deterioration of lung function showed lower anti-
CXCR3/4 ab levels compared to those with stable disease. Frequencies and median fluorescence intensities (MFI) of
CXCR3+ and CXCR4+ PBMC were lower in SSc patients compared to HD. They correlated with the severity of skin and
lung fibrosis (Fig. 1).
Fig. 1: Frequency of CXCR3-positive CD14+ monocytes among CD14+ monocytes (a) as well as CXCR3 density (b) on
CD14+ monocytes negatively correlated with the predicted percentages of forced vital capacity (FVC). (c) CXCR4 density
on CD4+ T cells correlated with modified Rodnan skin score (mRSS).
Conclusion: Anti-CXCR3/4 ab and their corresponding receptors are linked with severity of lung fibrosis. High ab levels
could serve as marker for SSc-ILD stability suggesting a protective role of these ab in SSc-ILD.
Disclosure: G. Riemekasten, CellTrend, 4; E. Siegert, None; H. Heidecke, Heideckes, 4,Riemekasten, 4.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/antibodies-against-the-chemokine-

receptors-cxcr3-and-cxcr4-predict-progressive-lung-fibrosis-in-systemic-sclerosis-ssc
Safety and Efficacy of Anabasum (JBT-101) in Diffuse Cutaneous Systemic

Sclerosis (dcSSc) Subjects Treated in an Open-Label Extension of Trial
JBT101-SSc-001
Robert F. Spiera1, Laura K. Hummers2, Lorinda Chung3, Tracy M. Frech4, Robyn T. Domsic5, Vivien Hsu6, Daniel E.
Furst7, Jessica K. Gordon1, Maureen D. Mayes8, Robert W. Simms9, Scott Constantine10 and Barbara White10,
1Rheumatology, Hospital for Special Surgery, New York, NY, 2Medical and Rheumatology, Johns Hopkins University,
Baltimore, MD, 3Rheumatology, Stanford University Medical Center, Palo Alto, CA, 4Division of Rheumatology,
University of Utah, Salt Lake City, UT, 5Medicine - Rheumatology, University of Pittsburgh, Pittsburgh, PA,
6Rheumatology, Robert Wood Johnson University Scleroderma Program, New Brunswick, NJ, 7David Geffen School of
Medicine at UCLA, Los Angeles, CA, 8Internal Medicine/Rheumatology, University of Texas Health Science Center at
Houston, Houston, TX, 9Rheumatology, Boston University School of Medicine, Boston, MA, 10Corbus Pharmaceuticals,
Inc., Norwood, MA
SESSION INFORMATION
Background/Purpose: Anabasum (JBT-101) is a selective cannabinoid receptor type 2 agonist that activates resolution of
innate immune responses and limits fibrosis in animal models of SSc. It is a synthetic, oral, non-immunosuppressive small
molecule. Anabasum had acceptable safety and tolerability and showed evidence of clinical benefit in diffuse cutaneous
SSc (dcSSc) in Phase 2 trial JBT101-SSc-001 (NCT02465437). The objective of this study was to provide long-term open-
label safety and efficacy data in dcSSc subjects who received anabasum in that trial.
Methods: Subjects who completed the double-blind placebo-controlled (DBPC) part of JBT101-SSc-001 were eligible to
receive anabasum 20 mg BID in an open-label extension (OLE).
Results: 36/38 (95%) eligible subjects enrolled in the OLE and 34/36 (94%) were on baseline immunosuppressive drugs.
At the time of data cut-off, 1 subject had discontinued from the OLE, the duration of OLE dosing was median 194 days
(range 25, 207 days) and total duration of DBPC + OLE dosing with anabasum was median 234 days (range 28, 295 days).
All 36 subjects had at least one OLE visit ≥ 28 days post baseline. Adverse events (AEs, n = 88) occurred in 28/36 (78%)
subjects in the OLE. Most AEs were mild (55/88, 62%) or moderate (30/88, 34%) in severity and unrelated to anabasum
(75/88, 85%). The AEs that occurred in ≥ 10% of subjects (n, % of subjects) were mild fatigue (5, 14%) and
mild/moderate upper respiratory tract infection (4, 11%). Dizziness occurred in 2 (6%) subjects. Only one subject had
more than mild or moderate AEs. That subject developed renal crisis 7 days after starting 60 mg/day prednisone prescribed
by a non-study physician for suspected temporal arteritis and had 2 severe and 1 life-threatening/serious AEs related to the
renal crisis and deemed unrelated to anabasum. In the period between DBPC and OLE off study product (median 50 days,
range 5 - 360 days), the modified Rodnan skin score (mRSS) was stable in all subjects, subjects treated with anabasum and
subjects treated with placebo during DBPC dosing (Table 1). After 10 weeks of anabasum treatment in OLE (Visit 3 in
OLE), mRSS declined from baseline in these same groups of subjects.
Table 1. Changes in mRSS before and after 10 weeks dosing in OLE

Period Group mRSS change from P, 2-sided paired t
baseline test
Mean (SD)
Off study drug All subjects, N = 36 0.1 (4.1) 0.9372
between DBCP and Subjects previously 0.6 (4.4) 0.5459
OLE dosing treated with anabasum, N
= 23
Subjects previously -0.8 (3.6) 0.4106
treated with placebo, N =
13
On anabasum Visit 1 All subjects, N = 29 -3.2 (3.9) 0.0001
to Visit 3 (10 weeks) Subjects previously -2.5 (3.5) 0.0049
treated with anabasum, N
= 20
Subjects previously -4.8 (4.5) 0.0128
treated with placebo, N =
9
Conclusion: In OLE of Phase 2 trial JBT101-SSc-001, anabasum continues to have acceptable safety and tolerability in
dcSSc with no severe or serious AEs or study discontinuations related to anabasum. The mRSS improved, although open-
label nature of dosing with anabasum is acknowledged. These data support further testing of anabasum for treatment of
dcSSc.
Disclosure: R. F. Spiera, Roche-Genetech, 2,GSK, 2,BMS, 2,Boehringer Ingelheim, 2,Cytori, 2,Chemocentryx, 2,Corbus
Pharmaceuticals, 2,Prism, 2,Roche-Genetech, 5,GSK, 5,Boehringer Ingelheim, 5; L. K. Hummers, None; L. Chung,
Cytori, Actelion, Reata, 5; T. M. Frech, None; R. T. Domsic, None; V. Hsu, None; D. E. Furst, Grant/Research Support:
Amgen,BMS Novartis, Pfizer, Roche/Genentech,Corbus. Consultant:AbbVie, Amgen, BMS, Corbus, Cytori, , Novartis,
Pfizer, Roche/Genentech,. Speakers Bureau(CME or non-promotional only): BMS, Abbvie NO stocks, royalties, direct
fina, 2,see above, 5,see above, 8; J. K. Gordon, Corbus Pharmaceuticals, 2,Cumberland Pharmaceuticals, 2,Bayer
Pharmaceuticals, 2; M. D. Mayes, None; R. W. Simms, None; S. Constantine, Corbus Pharmaceuticals, Inc., 1,Corbus
Pharmaceuticals, Inc., 3; B. White, Corbus Pharmaceuticals, 1,Corbus Pharmaceuticals, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/safety-and-efficacy-of-anabasum-jbt-

101-in-diffuse-cutaneous-systemic-sclerosis-dcssc-subjects-treated-in-an-open-label-extension-of-trial-jbt101-ssc-001
Performance of the American College of Rheumatology Provisional

Composite Response Index in Systemic Sclerosis (CRISS) in the Scleroderma
Lung Study-I
Dinesh Khanna1, Donald P. Tashkin2, Holly Wilhalme2 and Chi-hong Tseng3, 1University of Michigan, Ann Arbor, MI,
2University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, 3Medicine, University of
California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA
SESSION INFORMATION
Background/Purpose: The CRISS has been proposed as a composite outcome measure for trials in systemic sclerosis1.
CRISS is a 2-step process that assigns a probability of improvement for each individual patient on 0.00 [no improvement]
to 1.00. Step 1 assesses clinically meaningful decline in cardio-pulmonary-renal involvement (based on consensus expert
opinion) and assigns a probability of 0.00. For remaining subjects who do not experience a clinically meaningful decline, 5
variables are used over 12 months to calculate probability of improvement. These are: FVC%, mRSS, patient and physician
global assessments (MD GA), and HAQ-DI. Scleroderma Lung Study-I compared oral daily cyclophosphamide (CYC) vs.
placebo (PLA) in subjects with SSc-ILD 2, which showed modest efficacy favoring CYC at 12-month but greater
improvements in patient-reported outcomes. Our objective was to assess if CRISS index can discriminate CYC from PLA
in the SLS-I over 12 months.
Methods: We used patient-level data for this analysis. For Step 2, MD GA was not assessed in the SLS-I. Therefore, linear
regression model was developed to predict MD GA from variables which were similar between the original CRISS cohort
and SLS-I. Stepwise regression (using maximum R2 method) was used to identify the best prediction model for MD GA
and applied to the SLS-1 data. We compared the CYC vs. PLA for the whole population and for the diffuse cutaneous SSc
using the Wilcoxon rank-sum test for CRISS and Student’t t-test for individual variables. In addition, we explored the
proportion of subjects who had a probability score ≥ 0.601 and compared the 2 groups using Chi-square.
Results: The mean (SD) baseline disease duration was 3.2 (2.1) years; 59% had diffuse cutaneous SSc. The prediction
model for MD GA included the FVC (at baseline and 12 month change), mRSS (at baseline and 12 month change), gender,
disease duration, and joint contractures ( R2 of 0.44).
For Step 1, the definition of worsened cardio-pulmonary-renal involvement was met by 9 in CYC vs. 13 in PLA and were
given a CRISS score of 0.0. For the remaining subjects, [60 in CYC and 52 in PLA], we applied Step 2. Using the CRISS
as a continuous measure, CYC was statistically superior to PLA for the whole group (p=0.007) and diffuse SSc (p=0.0.02;
Table). Lack of administration of MD GA in the trial is a limitation of this analysis.
Conclusion: In this post-hoc analysis using individual data from SLS-I, CRISS is able to discriminate CYC from PLA,
supporting its validity in an independent cohort.
1Khanna D. Arthritis Rheum. 2016
2Tashkin et al. N Engl J Med 2008
Table: Performance of individual components of Step 2 in CRISS and overall CRISS in SLS-1
CYC (N=67) Placebo (N=65)
Changed Changed P-
N N
Score Score value
Overall
Δ MRSS, mean 68 -3.65 63 -0.94 0.01
Δ FVC% predicted,
72 -1.39 70 -3.23 0.19
mean
Δ Patient Global,
68 -0.43 63 0.12 0.22
mean
Δ HAQ -DI, mean 68 -0.11 63 0.15 0.001
Δ MD Global, mean 67 0.07 63 0.79 0.01
0.09 0.002
CRISS Index Score
69 (0.00, 65 (0.00, 0.007
(median, IQR)*
0.71) 0.19)
CRISS index ≥ 0.60 19 28% 10 15% 0.09
Diffuse SSc
Δ MRSS, mean 43 -5.30 37 -1.70 0.03
Δ FVC% predicted,
46 -1.23 41 -2.81 0.4
mean
Δ Patient Global,
44 -0.42 37 -0.21 0.73
mean
Δ HAQ -DI, mean 44 -0.13 37 0.15 0.007
Δ MD Global, mean 43 0.04 37 1.03 0.02
0.24 0.005
CRISS Index Score
45 (0.001, 39 (0.00, 0.02
(median, IQR)*
0.96) 0.32)
CRISS index ≥ 0.60 18 40% 9 23% 0.10
*includes Step 1 and Step 2 probability scores
Negative score is improvement in MRSS, Patient Global, HAQ-DI, and Physician Global assessments and worsening in
FVC% predicted
Disclosure: D. Khanna, Actelion, Bayer, BoehringerIngelheim, Chemomab, Corbus, Covis, Cytori,Eicos, EMD Serono,
Genentech/Roche, Gilead, GSK, Sanofi-Aventis,UCB Pharma, 5,NIH/NIAMS, NIH/NIAID,Bayer, BMS,
Genentech/Roche, Pfizer, 2,Eicos, 4; D. P. Tashkin, None; H. Wilhalme, None; C. H. Tseng, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/performance-of-the-american-college-

of-rheumatology-provisional-composite-response-index-in-systemic-sclerosis-criss-in-the-scleroderma-lung-study-i
Survival and Clinical-Capillaroscopic Characteristics of French Canadian

Systemic Sclerosis Patients: Analysis Based on Systemic Sclerosis
Autoantibodies and the Novel Anti-BICD2 Autoantibody
Boyang Zheng1, Michael Mahler2, Jean-Luc Senécal3, France Joyal4 and Martial Koenig5, 1Division of Internal Medicine,
Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada, 2Research and Development, Inova
Diagnostics, San Diego, CA, 3Rheumatology, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, QC,
Canada, 4Internal Medicine, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada, 5Internal
Medicine, Hôpital Notre-Dame du CHUM, Montréal, QC, Canada
SESSION INFORMATION
Background/Purpose:
Systemic sclerosis (SSc) autoantibodies (aAbs) are invaluable for SSc diagnosis and prognosis. Anti-centromere (ACA),
anti-topoisomerase I (ATA) and anti-RNA polymerase III (RNAP) have been incorporated into SSc classification criteria,
whereas anti-Th/To is much less commonly tested. Meanwhile, newly discovered anti-BICD2 seems particularly interesting
in predicting milder SSc.
Our goal was to characterize the aAb profile in French Canadian SSc patients and its correlation with clinical features,
nailfold capillaroscopy (NCM) findings and survival rates.
Methods:
Biobanked sera obtained at first visit from 303 SSc patients were tested for SSc aAbs by indirect immunofluorescence,
ELISA and immunoblotting. Clinical data and NCM findings at first visit were compared by aAb subsets. Survival status
and causes of death were extracted from a previous study (1). Survival was estimated by Kaplan Meier analysis and
additional predictors for mortality were identified.
Results:
In the 303 patients, aAb prevalence was: ACA 35% (n=145), ATA 10% (31), anti-Th/To 7% (21), anti-RNAP 4% (12) and
anti-BICD2 8.9% (27). All anti-BICD2+ patients were also ACA+ and 96% had limited cutaneous SSc (lcSSc). Only the
presence of puffy fingers was more prevalent in anti-BICD2+ patients compared to other ACA+ patients (37% vs 19%
respectively, p=0.04). Diffuse cutaneous SSc (dcSSc) was most prevalent in ATA+ (20%) and anti-RNAP+ (68%) patients.
Pulmonary fibrosis was more strongly associated with ATA than other aAbs (26% vs 9%, p=0.01). On NCM, anti-RNAP+
patients presented earlier capillary dilations after disease onset than other SSc patients (median interval 0.8 years vs 2
years, p=0.03).
Overall, 32 SSc related deaths occurred after a mean (± SD) of 9.8 (± 4.5) years following diagnosis. Risk factors
associated with mortality were dcSSc (OR 2.6, CI 1.3-6.7), lung fibrosis (OR 5.5, CI 2.2-13.6), and anti-SSA/Ro presence
(OR 2.5, CI 1.1-5.8). Kaplan Meier analysis of SSc related deaths showed that only ATA+ patients had a significantly lower
cumulative 15 year survival rate (58%) (Fig. 1, log rank p=0.03), whereas survival was similar between other aAb subsets,
including anti-BICD2.
Conclusion:
These data reaffirm and expand the importance of SSc related aAbs as prognostic markers. ATA are associated with dcSSc,
lung fibrosis and worst survival in comparison to other SSc aAbs. Anti-BICD2 was always associated with ACA. The latter
were both strongly associated with lcSSc and had similar survival rates. The only difference was an increased prevalence of
puffy fingers in anti-BICD2+ patients.
1. Scussel-Lonzetti L, Joyal F, Raynauld JP, Roussin A, Rich E, Goulet JR, et al. Predicting mortality in systemic sclerosis:
analysis of a cohort of 309 French Canadian patients with emphasis on features at diagnosis as predictive factors for
survival. Medicine (Baltimore) (2002);81:154-167.
Disclosure: B. Zheng, None; M. Mahler, Inova Diagnostics, Inc., 3; J. L. Senécal, None; F. Joyal, None; M. Koenig,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/survival-and-clinical-capillaroscopic-

characteristics-of-french-canadian-systemic-sclerosis-patients-analysis-based-on-systemic-sclerosis-autoantibodies-and-
the-novel-anti-bicd2-autoantibody
Symptoms of Autonomic Dysfunction in Systemic Sclerosis Assessed By the

Compass-31 Questionnaire
Brittany Adler1, James Russell2, Laura K. Hummers3 and Zsuzsanna McMahan4, 1Rheumatology, Johns Hopkins
University, Baltimore, MD, 2Neurology, Anatomy and Neurobiology, University of Maryland School of Medicine,
Baltimore, MD, 3Medical and Rheumatology, Johns Hopkins University, Baltimore, MD, 4Department of Internal
Medicine, Johns Hopkins University, Baltimore, MD
SESSION INFORMATION
Background/Purpose:
Autonomic dysfunction is a known complication of systemic sclerosis (SSc) and can affect vascular tone, gastrointestinal
(GI) motility, and heart rate and blood pressure control. We sought to quantify autonomic symptom burden in a large cohort
of patients with SSc and to determine clinical and serologic risk factors that associate with autonomic symptom burden.
Methods:
Patients with SSc were recruited from the Johns Hopkins Scleroderma Center and completed the Composite Autonomic
Symptom Score (COMPASS)-31 questionnaire, which is a validated tool to measure autonomic symptom burden. The
COMPASS-31 scores and subdomain scores in orthostatic, secretomotor, vasomotor, gastrointestinal, urinary, and
puillomotor dysfunction were quantified for each patient. Demographic information, clinical and serologic data, and
Medsger disease severity scores were obtained from the longitudinal Johns Hopkins Scleroderma Center database. We
analyzed the relationship between various features of systemic sclerosis and the total COMPASS-31 scores and subdomain
scores using the student’s t-test for dichotomous variables and linear regression analysis for continuous variables.
Results:
104 patients with SSc completed the COMPASS-31 questionnaire. The average COMPASS-31 score among our SSc cohort
was 24.9 ± 15.5, which was comparable to previously published scores in other diseases known to affect the autonomic
nervous system such as small-fiber polyneuropathy. There was no relationship between the COMPASS-31 score and SSc
subtype or autoantibody status. Patients with severe GI disease reported higher scores in multiple subdomains of the
COMPASS-31, including orthostatic intolerance (p=0.006) and secretomotor dysfunction (p=0.03), compared to patients
with mild or absent GI disease. There was also a dose-response relationship between GI disease severity and autonomic
symptom burden (see Figure).
Conclusion:
We determined that patients with SSc have a significant burden of autonomic symptoms across multiple domains of
autonomic function. All patients with SSc are at risk for autonomic symptoms regardless of SSc subtype or autoantibody
status. We also determined that patients with severe GI disease have more symptoms of dysautonomia, which suggests that
some of the GI disease in systemic sclerosis may be a cause or consequence of autonomic dysfunction.
Disclosure: B. Adler, None; J. Russell, None; L. K. Hummers, None; Z. McMahan, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/symptoms-of-autonomic-dysfunction-

in-systemic-sclerosis-assessed-by-the-compass-31-questionnaire
Clinically Relevant Serum Proteins in Patients with Early Diffuse Cutaneous

Systemic Sclerosis
Guoshuai Cai1, Kelsey S. Flood2, Shervin Assassi3, Elana J. Bernstein4, Robyn T. Domsic5, Jessica K. Gordon6, Faye
Hant7, Elena Schiopu8, Virginia D. Steen9, Tracy M. Frech10, Dinesh Khanna11, Ami A. Shah12, Victoria K.
Shanmugam13, Flavia V. Castelino14 and Monique Hinchcliff15, 1Department of Molecular and Systems Biology, Geisel
School of Medicine at Dartmouth, Hanover, NH, 2Internal Medicine, Northwestern Medicine, Chicago, IL, 3University of
Texas McGovern Medical School, Houston, TX, 4Rheumatology, Columbia University, New York, NY, 5Rheumatology,
University of Pittsburgh, Pittsburgh, PA, 6Rheumatology, Hospital for Special Surgery, New York, NY,
7Medicine/Rheumatology & Immunology, Medical University of South Carolina, Charleston, SC, 8Internal Medicine,
University of Michigan Medical System, Ann Arbor, MI, 9Rheumatology, MedStar Georgetown University Hospital,
Washington, DC, 10Division of Rheumatology, University of Utah, Salt Lake City, UT, 11Division of Rheumatology and
Clinical Autoimmune Center of Excellence, University of Michigan, Ann Arbor, MI, Ann Arbor, MI, 12Rheumatology,
Johns Hopkins University School of Medicine, Baltimore, MD, 13Rheumatology, The George Washington University,
Washington, DC, 14Rheumatology, Harvard Medical School, Boston, MA, 15Rheumatology, Northwestern Medicine,
Chicago, IL
SESSION INFORMATION
Background/Purpose: The Prospective Registry of Early Systemic Sclerosis (PRESS), an 11 center US cohort study of
early diffuse cutaneous systemic sclerosis (dcSSc) patients, was designed to study dcSSc pathogenesis and patient response
to treatments. Modified Rodnan skin score (mRSS), used to quantify skin severity, correlates with mortality. The study
purpose was to identify a serum signature associated with dcSSc and correlated with mRSS.
Methods: Baseline serum samples and clinical data were collected from PRESS subjects at enrollment and healthy
matched controls. Subjects met SSc ACR criteria, had early dcSSc (defined as < 2 years duration since first non-Raynaud
symptom attributed to SSc; swollen hands or sclerodactyly; PLUS 1 or more of the following: present anti-topoisomerase I
or anti-RNA polymerase III serum autoantibodies; proximal skin involvement; tendon friction rubs). Samples were
subjected to a custom Multi-Analyte Profiles (MAP) that uses multiplexed ELISA for serum protein quantification.
Analytes with >40% missing values were excluded. The fold-change in protein expression between early dcSSc versus
control samples was calculated. A t-test was used to test for statistical significance with correction for multiple hypothesis
testing using the Benjamini-Hochberg method. mRSS was fitted to a linear model to assess for correlation with protein
expression.
Results: Characteristics of dcSSc patients and controls were summarized (Table 1). Of 109 analytes, 28 analytes with
missing values were excluded, leaving 81 analytes for analysis. 45 proteins were differentially expressed between early
dcSSc patients and controls at baseline (q-value <0.05, Table 2). ANG-2, IGFBP-2, MIP-3 beta, TNFR2 and myoglobin
had >2 fold-change in dcSSc patients vs. controls (Fig 1). 106 out of 112 (95%) dcSSc patients had baseline mRSS values.
C-reactive protein correlated with mRSS (Fig 1).
Conclusion: We identified 45 proteins with variable expression between early dcSSc patients and healthy controls. Further,
we identified that C-reactive protein expression correlates with mRSS severity, which has also been shown to be associated
with lung disease progression. Future work includes developing a mRSS-predictive model by studying changes in protein
expression in patients with longitudinal mRSS.
Disclosure: G. Cai, None; K. S. Flood, None; S. Assassi, Bayer Healthcare, 2,Biogen Idec, 2,Reata, 5,Boehringer
Ingelheim, 5; E. J. Bernstein, None; R. T. Domsic, None; J. K. Gordon, Corbus Pharmaceuticals, 2,Cumberland
Pharmaceuticals, 2,Bayer Pharmaceuticals, 2; F. Hant, None; E. Schiopu, None; V. D. Steen, None; T. M. Frech, None;
D. Khanna, Actelion Pharmaceuticals Ltd, Bayer, Bristol-Myers Squibb, Covis, Cytori, EMD Serono, Genentech/Roche,
Gilead, GSK, Sanofi-Aventis, 5,NIH K24AR063120, 2; A. A. Shah, None; V. K. Shanmugam, Multiple, 9; F. V.
Castelino, None; M. Hinchcliff, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/clinically-relevant-serum-proteins-in-

patients-with-early-diffuse-cutaneous-systemic-sclerosis
The Association of Pulmonary Hypertension with Isolated Nucleolar Serum

Autoantibodies in Systemic Sclerosis
Kathleen Aren1, Mary A. Carns1, Michael Cuttica2, Julia (Jungwha) Lee3, Virginia D. Steen4 and Monique Hinchcliff5,
1Northwestern University, Feinberg School of Medicine Scleroderma Program, Chicago, IL, 2Northwestern University,
Feinberg School of Medicine, Division of Pulmonary and Critical Care, Chicago, IL, 3Preventive Medicine, Northwestern
University Feinberg School of Medicine, Chicago, IL, 4Division of Rheumatology, Department of Medicine, MedStar
Georgetown University Hospital, Washington, DC, 5Department of Medicine Division of Rheumatology, Northwestern
University Feinberg School of Medicine, Chicago, IL
SESSION INFORMATION
Background/Purpose: Serum antibodies are used to identify SSc patients who may be at higher risk for SSc-PH. The
Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) Registry cohort followed
SSc-PH patients. We assessed the validity of prior reports of association between serum antibodies and PH using data from
PHAROS and the Northwestern Scleroderma Registry (NW).
Methods: Antibody data were compared between PHAROS and NW subjects (mPAP ≥25 mmHg on right heart
catheterization). World Health Organization PH group (pulmonary arterial hypertension/PAH=Group 1, pulmonary venous
hypertension/PVH=Group 2, and PH-interstitial lung disease/PH-ILD=Group 3) was determined. The association between
antibodies and PH was studied using two approaches: 1) antibody distribution was compared between PHAROS and NW
PH subjects; 2) antibody distribution was compared between combined PHAROS and NW PH (in total and by WHO
group) and NW subjects without PH. Chi-square or Fisher’s exact tests were used for comparisons.
Results: Clinical characteristics were similar for 326 PHAROS subjects and 768 NW Registry subjects, 84 with PH
(Table 1). There were significant differences in antibodies between PHAROS and NW subjects, p=0.005 (Table 1). When
the PH groups were combined (n=410) and compared to NW subjects without PH (n=684), the antibodies between the
groups were significantly different, p<0.0001 (Table 2). Subjects in the PH group had a higher percentage of isolated
nucleolar antibodies (21%) compared to the NW subjects (8%). Similar percentages of ACA were found in both groups
(28% for the PH group and 27% for the NW subjects without PH. When the subclassifications of PH groups were
examined, the percentage of isolated nucleolar antibodies remained high in all 3 groups.
Conclusion: Isolated nucleolar serum antibodies were more prevalent in PH subjects compared to non-PH NW subjects.
When the PH groups were examined separately, higher percentages of isolated nucleolar antibodies remained in all 3
groups. Similar percentages of ACA were found in both the PH group and NW subjects without PH, suggesting that
isolated nucleolar antibodies may be a more specific marker for PH than ACA. Screening for isolated nucleolar antibodies
may help to identify patients with SSc who are at higher risk for developing PH.
Table 1: Clinical characteristics and serum autoantibody distribution between
PHAROS and NW subjects
Mean (SD) or n, % PHAROS NW PH p-value
(All WHO (All WHO

groups) groups)
n=326 n=84
Clinical characteristics
Age, years 58 (11) 52 (13) 0.003
Sex, women 262, 80% 70, 83% 0.83
Race/Ethnicity, Caucasian 236, 72% 54, 64% 0.15
SSc Subtype, lcSSc 198, 61% 54, 64% 0.55
mRSS 9 (9) 8 (7) 0.42
SSc disease duration, years 10 (9) 9 (9) 0.54
Serum autoantibodies
Negative 19, 6% 2, 2% 0.005
Anticentromere (ACA) 95, 29% 20, 24%
RNA Polymerase III 14, 4% 9, 11%
Anti-topoisomerase I (Scl- 44, 14% 18, 21%

70)
U1RNP 13, 4% 2, 2%
Isolated nucleolar 78, 24% 9, 11%

antinuclear
Other 63, 19% 24, 29%
Other=multiple antibodies, +ANA (homogenous, speckled, or multiple

patterns)
Table 2: Distribution of autoantibodies in PHAROS and Northwestern
PH (combined, all WHO groups) compared to Northwestern no PH
Autoantibodies PHAROS and NW no PH p-value
NW PH
n, % n=684
(all WHO
groups)
n=410
Negative 21, 5% 19, 3% <0.0001
Anticentromere (ACA) 115, 28% 188, 27%
RNA Polymerase III 23, 6% 130, 19%
Anti-topoisomerase I 62, 15% 151, 22%
(Scl-70)
U1RNP 15, 4% 29, 4%
Isolated nucleolar 87, 21% 54, 8%
pattern
Other 87, 21% 113, 17%
Other=includes multiple antibodies, +ANA (homogenous, speckled, or
multiple patterns)
Table 3: Autoantibodies in the Northwestern no PH group compared to PHAROS and

Northwestern PH (combined), by WHO group
Autoantibodies NW no PH PHAROS and NW PH
PHAROS PHAROS and PHAROS and
n, % N=684 and
NW PVH NW PH-ILD
NW PAH
(Group 2) (Group 3)
(Group 1)
n=74 N=70
n=266
Negative 19, 3% 11, 4% 6, 8% 4, 6%
Anticentromere (ACA) 188, 27% 99, 37% 12, 16% 4, 6%
RNA Polymerase III 130, 19% 16, 6% 6, 8% 1, 1%
Anti-topoisomerase I 151, 22% 22, 8% 13, 18% 27, 39%
(Scl-70)
U1RNP 29, 4% 9, 3% 3, 4% 3, 4%
Isolated nucleolar 54, 8% 55, 21% 19, 26% 13, 19%
pattern
Other 113, 17% 54, 20% 15, 20% 18, 26%
Other= includes multiple antibodies, +ANA (homogenous, speckled, or multiple
patterns)
When comparing distribution of autoantibodies between NW no PH and each PH

group, p<0.0001.
Disclosure: K. Aren, None; M. A. Carns, None; M. Cuttica, None; J. Lee, None; V. D. Steen, None; M. Hinchcliff,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-association-of-pulmonary-

hypertension-with-isolated-nucleolar-serum-autoantibodies-in-systemic-sclerosis

Prediction of Progression of Interstitial Lung Disease in Patients with
Systemic Sclerosis
Wanlong Wu1, Suzana Jordan2, Mike Oliver Becker3, Rucsandra Dobrota3, Shuang Ye4, Britta Maurer5 and Oliver
Distler2, 1Department of Rheumatology, Center of Experimental Rheumatology, University Hospital Zurich; Department of
Rheumatology, Renji Hospital South Campus, Shanghai Jiao Tong University School of Medicine, Zurich, Switzerland,
2Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland, 3Department of Rheumatology, Center of
Experimental Rheumatology, University Hospital Zurich, Zurich, Switzerland, 4Department of Rheumatology, Renji
Hospital South Campus, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, 5Department of
Rheumatology, Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland
SESSION INFORMATION
Background/Purpose:
No data are available to distinguish between progressive and stable patients when mild lung fibrosis is diagnosed in
systemic sclerosis (SSc) patients. This study aimed to identify clinical and laboratory parameters that can predict the
progression of interstitial lung disease (ILD) within 1 year in patients with mild SSc-ILD.
Methods:
Data prospectively collected in our local SSc cohort were analyzed in this observational study. Inclusion criteria were:
diagnosis of SSc fulfilling ACR/EULAR 2013 criteria, diagnosis of ILD by HRCT, < 20% lung involvement extent on
HRCT at the first visit (baseline), available HRCT and pulmonary function tests at baseline and annual follow-up visits
(12±3 months), no concomitant with PAH.
The primary endpoint, progression of ILD was defined if any of the following parameters was fulfilled : > 20% extent of
lung involvement on HRCT at any follow-up visit, decrease in FVC ≥15% within 1 year, or decrease in FVC ≥ 10% and
DLCO ≥ 15% within 1 year.
Candidate predictors for logistic regression were selected by expert opinion based on clinical consideration. Receiver
Operating Characteristic (ROC) curve analysis was performed to determine the optimal cut-off value for each significant
continuous parameter.
Results:
From the 81 patients included, 25 (30.9%) had progression of ILD. Differences of parameters between progressors and
non-progressors were analyzed by univariate analysis (Table 1).
Three candidate predictors reflecting the overall disease severity including worst SpO2 during 6-minute walk test (6MWT),
arthritis ever and modified Rodnan skin score (mRSS) were selected for logistic regression by expert opinion. The final
regression model identified worst SpO2 (p=0.011, OR: 0.78, 95% CI 0.64 to 0.94) and arthritis ever (p=0.002, OR: 7.15,
95% CI 2.01 to 25.48) as independent predictors. The ROC curve analysis identified the best cut-off value for worst SpO2
as 94% (area under the curve: 0.78, sensitivity 0.667, specificity 0.857).
By employing combination of both predictors, the prediction model increased the prediction success rate from 30.9% in the
whole cohort to 100% in the optimized enrichment cohort (Table 2).
Conclusion:
Our study identified exercise-induced SpO2 decline and arthritis ever as independent predictor of progression of mild SSc-
ILD within 1 year. The derived evidence-based prediction model might be helpful for the risk stratification of this subgroup
in clinical practice and cohort enrichment for future clinical trial design.
Disclosure: W. Wu, None; S. Jordan, None; M. O. Becker, None; R. Dobrota, None; S. Ye, Continent Pharmaceutical
Company (China), 2; B. Maurer, AbbVie, Protagen, EMDO, Novartis, German SSc Society, Pfizer, Roche, Actelion,
MSD, 5,mir-29 for the treatment of systemic sclerosis, 9; O. Distler, 4 D Science, Actelion, Active Biotec, Bayer, Biogen
Idec, Boehringer Ingelheim Pharma, BMS, ChemomAb, EpiPharm, Ergonex, espeRare foundation, GSK,Roche-
Genentech, Inventiva, Lilly, medac, MedImmune, Mitsubishi Tanabe, Pharmacyclics, Pfizer, Sanofi, Seroda, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prediction-of-progression-of-

interstitial-lung-disease-in-patients-with-systemic-sclerosis
Progression of Skin Fibrosis Is Associated with Decline in Lung Function in

Patients with Diffuse Cutaneous Systemic Sclerosis: A European
Scleroderma Trials and Research (EUSTAR) Analysis
Wanlong Wu1, Suzana Jordan2, Nicole Graf3, Janethe Pena4, John Curram5, Yannick Allanore6, Marco Matucci-Cerinic7,
Janet E. Pope8, Christopher Denton9, Dinesh Khanna10 and Oliver Distler1, 1Department of Rheumatology, Center of
Experimental Rheumatology, University Hospital Zurich, Zurich, Switzerland, 2Department of Rheumatology, University
Hospital Zurich, Zurich, Switzerland, 3Graf Biostatistics, Winterthur, Switzerland, 4Bayer HealthCare Pharmaceuticals Inc,
Whippany, NJ, 5Bayer Plc, Newbury, United Kingdom, 6Department of Rheumatology, Cochin Hospital, Paris Descartes
University, Paris, France, 7Dept of Medicine/Div of Rheum, University of Florence, Florence, Italy, 8Department of
Medicine, Division of Rheumatology, University of Western Ontario, St Joseph's Health Care, London, ON, Canada,
9Department of Rheumatology, University College London, Royal Free Hospital, London, United Kingdom, 10Division of
Rheumatology, Department of Internal Medicine, Scleroderma Program, University of Michigan, Ann Arbor, MI
SESSION INFORMATION
Background/Purpose:
Previously, we have identified short disease duration (≤15 months) and low baseline modified Rodnan skin score (mRSS)
(≤22/51) as independent predictors of progressive skin fibrosis (>5 mRSS units and ≥25% increment within 1 year) in
patients with diffuse cutaneous systemic sclerosis (dcSSc). While this strategy has resulted in recruitment of more patients
with progression of skin fibrosis in clinical trials, it might lead to recruitment of patients with less severe internal organ
disease. This study was designed to determine whether progression of skin fibrosis is associated with progression of
internal organ disease on longitudinal follow-up of patients with dcSSc.
Methods:
This study analyzed prospectively collected data from the EUSTAR cohort. Inclusion criteria were: diagnosis of SSc
fulfilling ACR criteria, diffuse cutaneous involvement, mRSS ≥7 at baseline visit in 2009 or later, valid mRSS with a time
interval of 12±3 months after baseline visit, and at least one available annual follow-up visit.
Progression of skin fibrosis was defined as an increase in mRSS >5 units and ≥25% from baseline to 12±3 months later.
The outcome was defined as one of the following new events occurring at any follow-up visit based on expert group
consensus: 1) renal crisis; 2) decrease in forced vital capacity (FVC) ≥10%; 3) left ventricular ejection fraction (LVEF)
<45% or decrease in LVEF by >10% for patients with baseline LVEF <50%; 4) pulmonary hypertension (PH) on
echocardiography as judged by the investigator; 5) death.
Kaplan–Meier analyses and log-rank tests were used to compare disease progression between progressors and non-
progressors for up to 6 years of follow-up.
Results:
A total of 871 dcSSc patients were eligible. The median follow-up period was 3.26 years (IQR: 1.49–5.14). Sixty-seven
(7.7%) patients had worsening of skin fibrosis within 1 year (defined as progressors). Cumulatively, 235/666 (35.3%)
patients had a decrease in FVC ≥10%, 96/593 (16.2%) had new PH, 22/564 (3.9%) had worsening LVEF, 16/844 (1.9%)
had a new renal crisis, and 58/871 (6.7%) died. Mean FVC% at baseline was 87.2% ± 20.4%, while 134 (20.1%) patients
had baseline FVC% <70%.
Log-rank tests indicated the probability for a decrease in FVC ≥10% was significantly higher for progressors than non-
progressors (53.2% vs. 33.9%, p=0.004) (Figure). There were non-significant differences in probabilities for new PH (9.5%
vs. 16.7%), worsening LVEF (7.3% vs. 3.6%), new renal crisis (0.0% vs. 2.1%) and death (7.5% vs. 6.6%) between
progressors and non-progressors.
Conclusion:
Progression of skin fibrosis is associated with a decline in lung function in dcSSc patients over follow-up. Our data indicate
that evidence-based criteria for cohort enrichment of progressive skin fibrosis might also be appropriate to recruit more
dcSSc patients at higher risk of lung function decline in future clinical trials.
Disclosure: W. Wu, None; S. Jordan, None; N. Graf, Biotronik AG, 5; J. Pena, Bayer Healthcare Pharmaceuticals Inc, 3;
J. Curram, Bayer Plc, 1,Bayer Plc, 3; Y. Allanore, Actelion Pharmaceuticals US, 2,Bayer AG, 2,Bristol-Myers Squibb,
2,Inventiva, 2,Medac, 2,Pfizer Inc, 2,Roche Pharmaceuticals, 2,Genentech and Biogen IDEC Inc., 2,Sanofi-Aventis
Pharmaceutical, 2,Servier, 2,Actelion Pharmaceuticals US, 5,Bayer AG, 5,Bristol-Myers Squibb, 5,Inventiva, 5,Medac,
5,Pfizer Inc, 5,Roche Pharmaceuticals, 5,Genentech and Biogen IDEC Inc., 5,Sanofi-Aventis Pharmaceutical, 5; M.
Matucci-Cerinic, None; J. E. Pope, Actelion, 2,Bayer AG, 2,Bristol-Myers Squibb, 2,Merck, 2,Pfizer Inc, 2,Roche,
2,Actelion, 5,Bayer AG, 5,Bristol-Myers Squibb, 5,Merck, 5,Pfizer Inc, 5,Roche, 5; C. Denton, Actelion Pharmaceuticals
US, 5,Bayer AG, 5,GlaxoSmithKline, 5,CSL Behring, 5,Merck-Serono, 5,Roche Pharmaceuticals, 5,Genentech and Biogen
IDEC Inc., 5,Inventiva, 5,Sanofi-Aventis Pharmaceutical, 5,Boehringer Ingelheim, 5,Actelion Pharmaceuticals US, 8,Bayer
AG, 8,GlaxoSmithKline, 8,CSL Behring, 8,Merck-Serono, 8,Roche Pharmaceuticals, 8,Genentech and Biogen IDEC Inc.,
8,Inventiva, 8,Sanofi-Aventis Pharmaceutical, 8,Boehringer Ingelheim, 8; D. Khanna, Bristol-Myers Squibb,
2,Genentech/Roche, 2,NIH/NIAMS, 2,NIH/NIAID,, 2,Patient-Centered Outcomes Research Institute, 2,Scleroderma
Foundation, 2,Actelion Pharmaceuticals US, 5,Bayer AG, 5,Cytori, 5,EMD Serono, 5,Genkyotex, 5,Gilead,
5,GlaxoSmithKline, 5,Genentech/Roche, 5,Sanofi-Aventis Pharmaceutical, 5,Seattle Genetics, 5; O. Distler, Actelion,
5,Bayer, 5,Biogen Idec, 5,Boehringer Ingelheim, 5,ChemomAb, 5,espeRare Foundation, 5,Genentech/Roche,
5,GlaxoSmithKline, 5,Inventiva, 5,Lilly, 5,Medac, 5,MedImmune, 5,Mitsubishi Tanabe Pharma, 5,Pharmacyclics,
5,Novartis Pharmaceutical Corporation, 5,Pfizer Inc, 5,Sanofi, 5,Sinoxa, 5,UCB in the area of potential treatments of
scleroderma and its complications, 5,Patent mir-29 for the treatment of systemic sclerosis licensed, 5,Actelion, 2,Bayer,
2,Biogen Idec, 2,Boehringer Ingelheim, 2,ChemomAb, 2,espeRare Foundation, 2,Genentech/Roche, 2,GlaxoSmithKline,
2,Inventiva, 2,Lilly, 2,Medac, 2,Medimmune, 2,Mitsubishi Tanabe Pharma, 2,Pharmacyclics, 2,Novartis, 2,Pfizer Inc,
2,Sanofi, 2,Sinoxa, 2,UCB in the area of potential treatments of scleroderma and its complications, 2,Patent mir-29 for the
treatment of systemic sclerosis licensed, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/progression-of-skin-fibrosis-is-

associated-with-decline-in-lung-function-in-patients-with-diffuse-cutaneous-systemic-sclerosis-a-european-scleroderma-
trials-and-research-eustar-analysis
Ethnic Variation in Systemic Sclerosis Morbidity and Mortality

Sindhu Johnson1, Zareen Ahmad2 and Haifa Al Sheikh3, 1Division of Rheumatology, Toronto Western Hospital, Mount
Sinai Hospital, Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada,
2Toronto Scleroderma Program, Division of Rheumatology, Mount Sinai Hospital, University of Toronto, Toronto, ON,
Canada, 3Division of Rheumatology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose: Systemic sclerosis (SSc) is an uncommon connective tissue disease characterized by pathological
skin thickening and can involve multiple internal organs. Ethnic variations in SSc have been reported in clinical
manifestations, severity of the disease as well as survival. Our aim was to compare the survival and disease manifestations
across ethnicity among SSc patients.
Methods: The Toronto Scleroderma Program is the largest single-center, multiethnic, longitudinal SSc cohort in Canada.
Patients are followed every 6 to 12 months using a standardized protocol. Patients who fulfilled the American College of
Rheumatology-European League Against Rheumatism classification criteria for SSc and are 16 years of age or older were
included in our retrospective cohort study. The study period was 1970–2017. Ethnicity was self-reported and was
categorized as: Caucasian, African-American, Hispanic, Arab, East-Asian, First Nations or Persian. The primary outcome
was the time from diagnosis to death from all causes. Secondary outcomes were differences in disease duration, SSc
subtype, clinical manifestations, and serology. Survival probabilities and median survival times were determined using
Kaplan-Meier survival curves. Cox proportional hazard models were used to estimate adjusted survival.
Results: 1005 subjects were evaluated, the majority of whom were Caucasian (n=745 (74%), African-American n=58
(6%)), South Asian (n=69 (7%)), and East Asian (n=80 (8%)). Compared to Caucasians, East Asians less frequently had
calcinosis (29% versus 9%, p=0.002), and esophageal dysmotility (88% versus 69%, p=0.002); African-Americans more
frequently had interstitial lung disease (31% versus 53%, p=0.007); and First Nation subjects more frequently had diffuse
cutaneous disease (35% versus 56%, p=0.02) and diabetes (5% versus 33%, p=0.03). There were no differences across
ethnicities in the prevalence of pulmonary hypertension, renal crisis, or digital ulcers.
We found no difference in the short-term survival across ethnicities. However, in the long-term, there was trend for
Hispanic subject to have better survival (81.3% (95%CI 63, 100), while First Nations (58.3% (95%CI 25, 100) and South
Asian subjects (52.6% (95%CI 32, 87) had worst survival at 15 years and 20 years, respectively. East Asians appear to have
the longest median survival time 43.3 years.
Conclusion: Ethnic variations in disease SSc disease manifestations are observed. However, in the setting of a universal
health care system, this does not result in significant differences in survival.
Disclosure: S. Johnson, None; Z. Ahmad, None; H. Al Sheikh, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/ethnic-variation-in-systemic-sclerosis-

morbidity-and-mortality
Correlation of the American College of Rheumatology Provisional Composite

Response Index in Systemic Sclerosis with Serum Biomarkers of Fibrogenesis
in an Observational Cohort
Giuseppina Abignano1, Sookhoe Eng2, Maya H. Buch3, Paul Emery4, Dinesh Khanna5 and Francesco Del Galdo2,
1Rheumatology Department of Lucania,, Rheumatology Institute of Lucania (IReL), San Carlo Hospital of Potenza and
Madonna delle Grazie Hospital of Matera,, Potenza, Italy, 2Leeds Musculoskeletal Biomedical Research Centre, Leeds
Teaching Hospitals NHS Trust, Leeds, United Kingdom, 3NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds,
United Kingdom, 4NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, United
Kingdom, 5University of Michigan, Ann Arbor, MI
SESSION INFORMATION
Background/Purpose: The CRISS is a composite index of response in diffuse cutaneous systemic sclerosis (dcSSC). It is a
2-step process for the probability of improvement ranging from 0.0 (no improvement) to 1.0. Patients with decline in
cardio-pulmonary-renal involvement are assigned score 0.0 in step 1. All remainng subjects are scored for improvement in
FVC, mRSS, patient (PT GA) and physician globals (MD GA), and HAQ-DI.
Two independent studies including in total 464 patients from 6 different centres have shown that skin, lung and overall
fibrosis correlate with three serum biomarkers (Procollagen III N terminal pro-peptides (PIIINP), Tissue inhibitor of
Metalloproteinase I (TIMP-1) and Hyaluronic Acid (HA)), either singularly or combined in the ELF Test algorithm. Here
we aimed to determine whether CRISS correlated with the serum concentration of one or more of the ELF biomarkers and
explore the scope to build a combined score with better performance in measuring the probability of clinical response in
dcSSc.
Methods: 31 Consecutive dcSSc patients were included in the study at a single centre. Clinical data and serum were
collected at baseline, at 12 and 24 months. CRISS and ELF score were calculated at the same time points. CRISS scores
were calculated using the publishedd formula and we assessed correlation coefficients between CRISS scores and
biomarkers. Comparison between two groups and correlation were performed using Mann-Whitney and Spearman’s tests,
respectively. P<0.05 was considered statistically significant. Statistical analysis was carried out using GraphPad Prism
Version 7.
Results: Thirty-one dcSSc patients were enrolled (12 M; mean age=50.3 ±11.5). CRISS at 12 months was 0% in 19
patients, whereas in the remaining 12 patients it ranged from 0.1 to 1.0 (median=0.35). Five out of the 12 CRISS
“responders” had a CRISS 24-12 >0.0, the remaining 7 had no further response (CRISS=0). Overall CRISS 24-0 was >0.0
in 16 patients (median=0.065, range=0.01-0.93). No clinical features at baseline were significantly different in the
responders vs non responders at 12 or 24 months, including mRSS, FVC%, DLCO%, autoantibody profile, age, disease
duration, Medsger Severity Score and CRP ( P>0.05 for all). TIMP-1 concentation at baseline was significantly lower in
patients with CRISS>0 vs. CRISS=0 (218.5 vs 265.9 respectively, p= 0.03), similar trend was observed for TIMP-1 at 12
months and CRISS 24 months. Accordingly TIMP-1 at baseline or 12 months statistically significant correlation with
CRISS 24 months ( R=-0.389 and -0.374, respectively; p < 0.05 for both).
Conclusion: This is the first evaluation of CRISS in an a observational setting. Although limited by single centre setting
and low number, we show that in any 12 months interval a proportion between 38 and 51% of patients show a CRISS >0.
Whereas only 6 to 22.5% of patients showed a CRISS>0.10. None of the routinely used clinical parameters can predict
CRISS at 12 months whereas TIMP-1 concentration at baseline is significantly lower in the responders. This needs to be
explored in additional cohorts and opens the possibility to include serum biomarkers of fibrogenesis within a combined
response index for Systemic Sclerosis.
Disclosure: G. Abignano, None; S. Eng, None; M. H. Buch, Pfizer Ltd, 2,Roche Pharmaceuticals, 2,Abbott Immunology
Pharmaceuticals, 5,Sandoz, 5; P. Emery, Pfizer,MSD,Abbvie,BMS,UCB,Roche,Novartis,Samsung, Sandoz, Eli Lilly and
Company, 5; D. Khanna, Actelion, Bayer, BoehringerIngelheim, Chemomab, Corbus, Covis, Cytori,Eicos, EMD Serono,
Genentech/Roche, Gilead, GSK, Sanofi-Aventis,UCB Pharma, 5,NIH/NIAMS, NIH/NIAID,Bayer, BMS,
Genentech/Roche, Pfizer, 2,Eicos, 4; F. Del Galdo, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/correlation-of-the-american-college-of-

rheumatology-provisional-composite-response-index-in-systemic-sclerosis-with-serum-biomarkers-of-fibrogenesis-in-an-
observational-cohort
Cardiopulmonary Exercise Testing to “Detect” Pulmonary Arterial

Hypertension in Systemic Sclerosis
Rosa Casella1, Alessandro Santaniello2,3, Marco Vicenzi1 and Lorenzo Beretta2, 1Cardiovascular Unit, Fondazione
IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy, 2Scleroderma Unit, Referral Center for Systemic
Autoimmune Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy, 3VIA
FRANCESCO SFORZA 28, OSPEDALE MAGGIORE POLICLINICO, MILANO, Italy
SESSION INFORMATION
Background/Purpose:
Pulmonary arterial hypertension (PAH) is one of the leading death causes in SSc patients. To gain a better prognosis,
screening methods are needed to provide an early diagnosis and intervention. The DETECT algorithm is a highly sensitive
tool, however it presents a very low positive predictive value. To reduce the number of unnecessary right heart
catheterizations (RHC), we evaluated the predictive performance of cardiopulmonary exercise testing (CPET) in a
DETECT positive SSc population.
Methods:
Two-hundred-fifty-eight adult SSc consecutive patients attending our Scleroderma Unit were considered. Among those, the
DETECT algorithm was applied to the subjects responding to the application criteria (ACR criteria for SSc, DLco < 60%,
disease duration ≥ 3 years). DETECT positive patients underwent CPET and RHC. CPET was performed on a COSMED
Quark-B2 equipment, on a cycle ergometer with an incremental work rate between 5 and 15 watts per minute up to the
patients’ maximum tolerance.
Pearson’s correlation was used to evaluate linear associations between CPET parameters and mean pulmonary pressure
(mPAP); the difference between PAH vs non-PAH patients for the best parameter was assessed by means of Student’s t-test.
Finally, the sensitivity/specificity trade-off of this parameter was evaluated by ROC analysis.
Results:
The enrolment flow chart is reported in Figure 1. Overall 81 patients were eligible for DETECT screening, 39 were positive
and underwent CPET and RHC (Figure 1). The patients’ clinical characteristics are reported in Table 1. RHC found 12
cases of PAH (30.7%), 1 case of PH due to left heart disease (2.6%) and non-PH in 26 subjects (66.7%).
We found the following significant correlation:
- mPAP-PetCO2@lt (r 0.74, p 0.7*10-7)
- mPAP-VE/VCO2@lt (r 0.8, p 0.1*10-8)
- mPAP-VE/VCO2 slope (r 0.85, p 0.7*10-11)
The VE/VCO2 slope was selected for further investigation.
VE/VCO2 slope statistically differed between PAH and non-PAH patients (mean ± DS: 45.5 ± 4.95 vs 35.11 ± 5.04; p 0.5
*10-5). ROC analysis showed a remarkable performance of the VE/VCO2 slope in detecting PAH in the DETECT
population (AUC 0.955, p 0.7*10-5). A single cut-point value equal to 38.5 of the VE/VCO2 slope was capable of
discriminating PAH and non-PAH patients with a 100% sensitivity and 82% specificity.
Conclusion:
This study shows that CPET can fruitfully be applied to patients screened with the DETECT improve its specificity. The
VE/VCO2 slope determination allows to significantly reduce the number of useless invasive RHC (from 39 to 17), without
increasing missed diagnosis rate.
Disclosure: R. Casella, None; A. Santaniello, None; M. Vicenzi, None; L. Beretta, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/cardiopulmonary-exercise-testing-to-

detect-pulmonary-arterial-hypertension-in-systemic-sclerosis
N-Terminal Pro-Brain Natriuretic Peptide Is Disproportionately Elevated in

Scleroderma Associated Pulmonary Arterial Hypertension Compared to
Idiopathic Pulmonary Arterial Hypertension
Alexander Hannan1, Raed Dweik2, Kristin B. Highland3, Gustavo Heresi4, Adriano Tonelli5, William Messner6 and
Soumya Chatterjee1,7, 1Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, OH, 2Respiratory Institute,
Cleveland Clinic, Cleveland, OH, 3Rheumatology.org, Cleveland Clinic, Cleveland, OH, 4Respiratory Institute -
Pulmonary Medicine, Cleveland Clinic, Cleveland, OH, 5Pulmonary Medicine - Respiratory Institute, Cleveland Clinic,
Cleveland, OH, 6Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, 7Rheumatic and Immunologic Ds,
Cleveland Clinic, Cleveland, OH
SESSION INFORMATION
Background/Purpose: N-Terminal pro-brain natriuretic peptide (NT-proBNP) level tends to correlate with myocardial
wall stress and/or myocardial damage (fibrosis). Hence, it has been promoted as a potential biomarker to support the
diagnosis of pulmonary arterial hypertension (PAH) and help monitor its severity, progression, and response to therapy. A
previous study has noted disproportionately elevated serum NT-proBNP levels among patients with scleroderma associated
PAH (SSc-PAH) compared to similar patients with idiopathic PAH (iPAH).1Our goal was to (1) verify the above results
using a much larger cohort of SSc-PAH and iPAH patients, and (2) to identify possible explanations for this phenomenon.
Methods: A retrospective chart-review was conducted comparing demographic, laboratory, and hemodynamic
[echocardiographic and right heart catheterization (RHC)] data from a total of 862 patients (686 with iPAH and 176 with
SSc-PAH) enrolled in the Cleveland Clinic Pulmonary Hypertension Database. The diagnosis of PAH was confirmed by
RHC, and the diagnosis of SSc was confirmed by a rheumatologist. NT-proBNP levels were measured at the time of the
patient’s first RHC, which was also considered to be the time of PAH diagnosis. Mean pulmonary artery pressure (mPAP)
and pulmonary vascular resistance (PVR) [data from RHC] and estimated right ventricular systolic pressure [data from
transthoracic echocardiogram] were collected in both SSc-PAH and iPAH patients. A multivariate linear regression with a
disease x log(NT-proBNP) interaction term was performed.
Results: In our cohort, at the time of first RHC, SSc-PAH patients were noted to have significantly higher NT-proBNP
levels, yet much lower PVR and mPAP readings compared to similar iPAH patients. Also, there was a significant, positive
correlation between NT-proBNP levels, mPAP, and PVR only in SSc-PAH patients, but not in iPAH patients.
Conclusion: One plausible explanation for higher NT-proBNP levels in SSc-PAH patients is intrinsic subclinical
myocardial damage from SSc-induced fibrosis (which does not occur in early iPAH), in addition to right ventricular wall
stress resulting from the occlusive pulmonary vasculopathy.
Reference: Mathai S et al. Eur Respir J 2010; 35: 95–104
Disclosure: A. Hannan, None; R. Dweik, None; K. B. Highland, None; G. Heresi, None; A. Tonelli, None; W. Messner,
None; S. Chatterjee, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/n-terminal-pro-brain-natriuretic-

peptide-is-disproportionately-elevated-in-scleroderma-associated-pulmonary-arterial-hypertension-compared-to-idiopathic-
pulmonary-arterial-hypertension
Dynamic Prediction of Pulmonary Hypertension Development in Systemic

Sclerosis Patients Using Landmark Analysis – Comparison of Two Models
Svetlana I. Nihtyanova1, Voon H. Ong2, Emma C. Derrett-Smith3, Benjamin Schreiber4, J. Gerry Coghlan4, Bianca
DeStavola5 and Christopher Denton6, 1Division of Medicine, Centre for Rheumatology and Connective Tissue Diseases,
University College London, London, United Kingdom, 2Rheumatology, UCL Division of Medicine, London, United
Kingdom, 3Centre for Rheumatology and Connective Tissue Diseases, UCL Division of Medicine, London, United
Kingdom, 4National Pulmonary Hypertension Service, Royal Free Hospital, London, United Kingdom, 5Faculty of
Population Health Sciences, UCL Institute of Child Health, London, United Kingdom, 6Department of Rheumatology,
University College London, Royal Free Hospital, London, United Kingdom
SESSION INFORMATION
Background/Purpose:
Pulmonary hypertension (PH) contributes substantially to systemic sclerosis (SSc)-related morbidity and mortality. It tends
to develop later in the disease, creating an opportunity for early risk stratification.
Previously published prediction models for PH have been based on cross-sectional data.
We set out to develop a model predicting PH development within 12 months, accounting for disease duration and utilising
time-updated clinical characteristics, including serial measurements of lung function. We compare the use of most recent
lung function results and serial changes in lung function over the preceding 4 years.
Methods:
We used data from a large unselected longitudinal cohort of SSc patients.
Sequential survival analyses with origins set at 6 consecutive landmark (LM) time-points, 12 months apart, starting at 60
months from disease onset were performed. The predictor variables included time-invariant characteristics (sex, subset and
autoantibodies) and LM-specific information (age, presence of organ disease, FVC and DLCO, % predicted). Time to PH
from the LMs was calculated with censoring at 12 months. Analyses were combined using a stratified Cox proportional
hazards model, with each LM representing a stratum.
Results:
The study cohort consisted of 652 SSc patients. Of those 41.3% had diffuse SSc, 14.9% were male and the average age at
disease onset was 48 years. Most patients (96%) either died during follow-up or were followed for over 10 years from
disease onset. At the end of follow-up 13.3% of the subjects had developed PH.
The two final multivariable models both included the values at LM of age, presence of pulmonary fibrosis (PF) and
antibody specificities (anti-U3RNP and anti-RNA polymerase (ARA)). Model 1 used most recent DLCO values, while
Model 2 incorporated patient-specific intercept and slope of DLCO change over the 4 years prior to the LM (Table 1).
Both models were very similar, demonstrating that older age, ARA and anti-U3RNP positivity increase the hazard for PH
development. Lower DLCO, both included as most recent measurement and as intercept and slope for the serial change in
DLCO over the 4 years prior to LM, predicted increased hazard for PH. This effect was attenuated by presence of
clinically-significant PF. None of the estimated effects varied between LM strata.
The two models had very similar fit and discrimination performance with C-index=0.88 for the model with most recent
DLCO and C-index=0.87 for the one using intercept and slope for the linear change in DLCO.
Conclusion:
Our results show that comparatively simple models, using only information on age, autoantibodies and serial DLCO
assessments could be used for risk stratification and prediction of PH development with good discriminating ability. After
validation, this model could be used in clinical practice or for cohort enrichment in clinical trials.
Table 1. Comparison of the two prediction models for PH development

Model 1 Model 2
HR (95% CI) p-value HR (95% CI) p-value
Anti-RNA polymerase antibody 4.9 (1.91, 12.56) 0.001 4.81 (1.87, 12.35) 0.001
Anti-U3RNP antibody 5.97 (1.73, 20.69) 0.005 5.7 (1.62, 20.11) 0.007
Age at landmark, years 1.03 (1.00, 1.06) 0.066 1.03 (1.00, 1.07) 0.043
DLCO last assessment, % 0.9 (0.87, 0.92) <0.001
DLCO last assessment, % x Pulmonary fibrosis 1.05 (1.03, 1.07) <0.001
DLCO intercept, % 0.91 (0.88, 0.94) <0.001
DLCO intercept, % x Pulmonary fibrosis 1.05 (1.03, 1.08) <0.001
DLCO slope, % (standardised) 0.57 (0.42, 0.79) 0.001
Model performance
Akaike information criterion 320.023 325.192
Bayesian information criterion 348.283 359.105
Concordance Index (Harrell's C) 0.8826 0.8724
Disclosure: S. I. Nihtyanova, None; V. H. Ong, None; E. C. Derrett-Smith, None; B. Schreiber, None; J. G. Coghlan,
None; B. DeStavola, None; C. Denton, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/dynamic-prediction-of-pulmonary-

hypertension-development-in-systemic-sclerosis-patients-using-landmark-analysis-comparison-of-two-models
Prospective Validation of the Systemic Sclerosis Skin Symptoms Patient-

Reported Outcome (SSPRO) in a Phase 2 Trial of Anabasum (JBT-101) in
Diffuse Cutaneous Systemic Sclerosis (dcSSc)
Ada Man1, Nancy Dgetluck2 and Barbara White3, 1Rheumatology, University of Manitoba, Winnipeg, MB, Canada,
2Biostatistics, Corbus Pharmaceuticals, Norwood, MA, 3Corbus Pharmaceuticals, Inc., Norwood, MA
SESSION INFORMATION
Background/Purpose: Skin thickening is the defining manifestation of dcSSc. A dcSSc patient’s assessment of their skin
involvement can provide information about how that patient feels and functions in response to treatment. No skin-specific
patient-reported outcome (PRO) measure has been prospectively validated in dcSSc in a clinical trial.
Methods: SSPRO is a validated PRO measure that assesses health-related quality of life (HRQOL) related to skin
involvement in SSc. It has 18 items representing 4 HRQOL scales: physical effects, emotional effects, physical function,
and social effects. All items are scored from 0 (better) to 6 (worse). Anabasum is a preferential cannabinoid receptor type 2
agonist that was tested for safety and efficacy in dcSSc in a double-blind randomized placebo-controlled Phase 2 trial
(JBT101-SSc-001). Efficacy outcomes included the SSPRO, Patient Global Assessment (PtGA), HAQ-DI, Physician
Global Assessment (MDGA), modified Rodnan Skin Score (mRSS), and FVC % predicted. SSPRO baseline scores were
correlated with other baseline outcome scores using Pearson’s Correlation Coefficient. Internal consistency was estimated
using Cronbach’s α. Effect size (ES, ratio of mean change in SSPRO total score from baseline to 12 weeks, to the standard
deviation of the total score at baseline) was calculated to assess the SSPRO’s responsiveness to change.
Results: SSPRO was administered to 41 subjects with dcSSc. Internal consistency was high for the total (0.87) and for all
scale scores (0.92). The SSPRO total and scale scores correlated strongly with PtGA, and moderately with HAQ-DI (except
for the emotion scale) showing convergent validity. SSPRO also correlated moderately with MDGA and weakly with
mRSS. As expected, SSPRO total and scale scores did not correlate with FVC % predicted, showing divergent validity.
The SSPRO total mean score showed a significant difference in anabasum-treated (N = 26) compared to placebo-treated
subjects (N = 15) at 12 weeks, LS means difference (SE) = -16.9 (6.0), P = 0.004 ANCOVA. The ES (n = 41) was
moderate at -0.51, also demonstrating the SSPRO’s responsiveness to change.
Table 1. Correlations of SSPRO with other efficacy outcomes at baseline in a Phase 2 trial of anabasum in dcSSc
Efficacy Physical Emotional Physical

Total Score Social Effects
Outcome Effects Effects Function
PtGA 0.6264 0.5063 0.4823 0.6463 0.5734
HAQ-DI 0.5213 0.5003 0.264 0.5924 0.5814
MDGA 0.5143 0.3711 0.3721 0.5433 0.5513
mRSS 0.4453 0.3781 0.3871 0.3381 0.4333
FVC -0.315 -0.115 -0.242 -0.165 -0.211
1P ≤ 0.05; 2 P ≤ 0.01; 3P ≤ 0.005; 4P ≤ 0.0001
Conclusion: In this clinical trial dcSSc population, SSPRO showed high internal consistency, construct validity, and
responsiveness to change. Moderate and significant correlations of SSPRO scores with PtGA and HAQ-DI scores validate
the usefulness of SSPRO as an outcome measure of how the patient with dcSSc feels and functions. Its weaker but still
significant and directionally concordant correlations with mRSS shows that the SSPRO may provide additional information
on the patient’s experience of their skin involvement that the mRSS does not assess. This is the first prospective validation
of the SSPRO in a clinical trial.
Disclosure: A. Man, None; N. Dgetluck, Corbus Pharmaceuticals, 3; B. White, Corbus Pharmaceuticals, 1,Corbus
Pharmaceuticals, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prospective-validation-of-the-systemic-

sclerosis-skin-symptoms-patient-reported-outcome-sspro-in-a-phase-2-trial-of-anabasum-jbt-101-in-diffuse-cutaneous-
systemic-sclerosis-dcssc
How Effective Is the Home Exercise Program for Hands in Patients with
Systemic Sclerosis: Preliminary Results from a Randomized Controlled,
Single-Blind, Clinical Trial
Neslihan Gokcen1, Suade Ozlem Badak2, Tunay Sarpel3, Yasar Sertdemir4 and Eren Erken2, 1Physical Medicine and
Rehabilitation, Division of Rheumatology, Cukurova University School of Medicine, Adana, Turkey, 2Internal Medicine,
Division of Rheumatology, Cukurova University School of Medicine, Adana, Turkey, 3Physical Medicine and
Rehabilitation, Cukurova University School of Medicine, Adana, Turkey, 4Department of Biostatistics and Medical
Informatics, Cukurova University School of Medicine, Adana, Turkey
SESSION INFORMATION
Background/Purpose: Systemic sclerosis (SSc) represents a heterogeneous autoimmune disease characterized by fibrosis
of skin and internal organs. In particular, thickening of the skin, puffy hands, digital ulcers, calcinosis and joint contractures
has contributed to disease prognosis by decreasing function of the hand and quality of life. The present study aims to
investigate the effectiveness of the hand exercise program and demonstrate its influence on quality of life, as well as
anxiety and depression in SSc patients.
Methods: Thirty female patients with SSc who fulfilled the 2013 ACR/EULAR classification criteria for systemic sclerosis
were included in the study. Patients with neurological disorders, arthritis, myositis, amputation of fingers, serious
contracture resisting hand grip and history of undergoing hand surgery were excluded. Patients were randomized into an
exercise (n=16) and a control (n=14) group. Each group were informed of their disease and given recommended advice
such as avoiding cold and trauma. The exercise group participated in a single hand exercise training applied by a medical
doctor. Hereafter, they were given instructions for the home exercise program. The 8-week intervention consisted of
isometric hand exercise and self-administered stretching repeated 10 times/2 set of training exercises per a day. Each
group’s hand functions were assessed by Hand Mobility in Scleroderma (HAMIS) and Duruöz Hand Index (DHI).
Additionally, all patients were estimated by Short Form 36 (SF-36), The Health Assessment Questionnaire (HAQ), Beck
Anxiety and Beck Depression Inventory. Each group were evaluated at baseline and reassessed after 4 (V1) and 8 (V2)
weeks.
Results: The baseline demographics and disease characteristics between the groups were similar. When comparing V1 and
V2, we established a statistically significant amelioration from baseline measurement of handgrip strength in the exercise
group (p<0.001). Accordingly, values of HAMIS, DHI, HAQ and Beck Depression Inventory were also significantly
improved at V2 (p=0.002, 0.001, 0.001, 0.071, respectively) (Table). The assessment between the two groups at V1 and V2
indicated significant improvement in the exercise group with respect to the controls.
Conclusion: Exercise therapy showed a greater amelioration in the patients’ measurements of handgrip strength, quality of
life and depression in SSc patients, indicating improvement in their hand function when compared to the control group.
Table: Outcome measurement changes in between the two groups at baseline, after 4 week and 8 week.
Outcome Baseline Week 4 Week 8 ptime
mean±SD mean±SD mean±SD
median median median

(min- (min- (min-
max) max) max)
Modified Rodnan E 15.4±8.1 14.3±7.2 13.6±6.6 0.026*
Skin Score
14 (4-33) 12.0 (5- 11.5 (5-
32) 30)
C 15.1±8.8 14.7±8.0 14.9±8.1 0.830
13.5 (3- 13.5 (3- 14.0 (4-

34) 30) 30)
pgroup 0.697 0.728 0.667
HAMIS E 5.3±6.0 2.5±4.8 1.9±3.5 0.002¶
4.5 (0-18) 0 (0-14) 0 (0-13)
C 4.0±5.2 4.0±4.6 4.0±5.2 0.968
3.0 (0-19) 2.5 (0-13) 2.5 (0-18)

pgroup 0.608 0.208 0.257
DHI E 8.0±6.0 5.3±6.8 4.1±6.7 <0.001§
5.0 (0-29) 3.5 (0-22) 1.0 (0-18)

C 13.7±13.4 14.9±13.3 15.1±11.7 0.734
7.0 (0-35) 15.0 (0- 16.5 (0-

32) 30)
pgroup 0.525 0.101 0.013
Valentini activity E 2.4±1.4 1.5±1.4 1.2±1.0 <0.001§
score
2.0 (0.5- 1.0 (0- 1.3 (0-
5) 4.5) 3.5)
C 3.4±1.5 2.3±0.9 2.3±1.8 0.048*
3.3 (1-6) 2.0 (0.5- 2.0 (0-6)

4)
pgroup 0.110 0.028* 0.064
Beck Depression E 19.8±11.6 18.0±11.3 15.0±11.2 0.035*
Inventory
18.0 (2- 18.5 (3- 12.5 (2-
46) 39) 45)
C 23.1±10.3 23.0±11.6 23.7±11.9 0.910
22.5 (3- 24.5 (4- 25.0 (0-

40) 50) 42)
pgroup 0.294 0.240 0.034*
Beck Anxiety E 16.3±9.2 17.0±10.1 13.4±10.2 0.071
Inventory
15.0 (3- 14.5 (6- 9.5 (1-40)
36) 41)
C 25.9±10.3 23.4±11.9 22.1±11.7 0.233
27.5 (6- 22.5 (4- 23.0 (1-

39) 50) 46)
pgroup 0.010* 0.093 0.034*
Dominant E 18.6±6.7 22.3±7.1 24.6±6.8 <0.001§
handgrip strength
(kg) 18.0 (10- 20.5 (14- 23.5 (14-
32) 36) 38)
C 15.5±6.4 18.7±6.8 18.4±6.4 0.843
18.0 (11- 18.0 (9- 17.5 (9-

30) 30) 30)
pgroup 0.984 0.244 0.013*
HAQ E 10.5±7.7 6.3±7.8 4.1±6.2 <0.001§
9.0 (0-26) 2.5 (0-23) 0 (0-18)
C 13.6±13.3 13.8±12.5 13.7±11.7 0.967
8.0 (0-40) 7.0 (0-35) 8.5 (0-32)

pgroup 0.822 0.093 0.007¶
SF-36 Physical E 43.8±25.0 53.4±21.9 67.8±17.1 <0.03*
function
42.5 (5- 50.0(20- 67.5(30-
90) 100) 100)
C 46.8±31.4 39.6±34.5 37.9±30.8 0.312
45.0 (0- 35.0 (0- 40.0 (0-

100) 100) 100)
pgroup 0.886 0.257 0.003¶
Role E 20.3±32.0 40.6±38.6 55.0±38.1 <0.001§
physical
0 (0-100) 25.0 (0- 50.0 (0-
100) 100)
C 14.3±27.2 17.9±28.5 25.0±39.2 0.343
0 (0-100) 0 (0-100) 0 (0-100)

pgroup 0.759 0.077 0.038*
Body pain E 56.8±32.3 56.3±19.7 60.0±21.0 0.853
60.5 (0- 56.0 (30- 60.0 (22-

100) 84) 90)
C 52.7±29.6 53.5±26.0 55.0±29.0 0.881
50.5 (0- 60.0 (10- 61.0 (0-

90) 90) 100)
pgroup 0.728 0.822 0.749
General E 44.7±20.5 45.1±17.0 46.1±18.3 0.917
health
50.0 (0- 45.0 (10- 50.0 (15-
67) 70) 75)
C 44.4±24.5 39.7±23.9 34.8±22.7 0.016*
47.5 (0- 47.5 (0- 46.0 (0-
80) 65) 60)
pgroup 0.886 0.759 0.224
Vitality E 45.9±17.7 43.4±17.5 48.4±15.0 0.488
50.0 (10- 40.0 (15- 50.0 (20-

70) 75) 75)
C 34.3±18.6 39.6±18.1 38.6±21.0 0.281
37.5 (0- 42.5 (5- 45.0 (0-

60) 65) 70)
pgroup 0.093 0.728 0.257
Social E 44.5±20.9 42.9±14.6 46.7±21.0 0.842
functioning
50.0 (0- 50.0 (12- 50.0(13-
75) 63) 100)
C 37.4±22.5 43.0±19.5 37.0±14.4 0.524
37.5 (0- 50.0 (0- 37.0 (12-

75) 75) 62)
pgroup 0.142 0.142 0.142
Role E 33.2±36.5 43.7±20.3 47.8±21.2 0.214
emotional
33.0 (0- 33.0 (0- 33.0(33-
100) 67) 100)
C 33.1±34.5 30.7±27.5 40.4±32.6 0.426
33.0 (0- 33.0 (0- 33.0 (0-

100) 100) 100)
pgroup 0.951 0.101 0.400
Mental E 54.5±16.8 51.3±18.1 48.4±17.5 0.256
health
54.0 (16- 50.0 (28- 54.0 (36-
80) 96) 96)
C 47.4±16.3 49.4±8.7 47.4±15.4 0.905
46.0 (16- 50.0 (36- 50.0 (20-

72) 68) 68)
pgroup 0.240 0.886 0.208
*p<0.05, ¶p<0.01, §p<0.001
E: Exercise group, C: Control group, HAMIS: Hand Mobility in Scleroderma, DHI: Duruöz Hand Index, HAQ: The Health
Assessment Questionnaire, SF-36: Short Form 36.
Disclosure: N. Gokcen, None; S. O. Badak, None; T. Sarpel, None; Y. Sertdemir, None; E. Erken, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/how-effective-is-the-home-exercise-

program-for-hands-in-patients-with-systemic-sclerosis-preliminary-results-from-a-randomized-controlled-single-blind-
clinical-trial

Prediction of Fibrosis Progression in Systemic Sclerosis By Collagen
Biomarkers
Rucsandra Dobrota1, Suzana Jordan2, Pernille Juhl3, Britta Maurer4, Lukas Wildi4, Anne-C. Bay-Jensen5, Morten
Karsdal6, Anne Sofie Siebuhr7 and Oliver Distler2, 1Department of Rheumatology, Center of Experimental Rheumatology,
University Hospital Zurich, Zurich, Switzerland, 2Department of Rheumatology, University Hospital Zurich, Zurich,
Switzerland, 3Nordic Bioscience, Herlev, Denmark, 4Department of Rheumatology, Department of Rheumatology,
University Hospital Zurich, Zurich, Switzerland, 5Biomarkers and Reseach, Nordic Bioscience, Herlev, Denmark,
6Biomarkers and Reseacrh, Nordic Bioscience, Herlev, Denmark, 7Biomarkers and Research, Nordic Bioscience, Herlev,
Denmark, Herlev, Denmark
SESSION INFORMATION
Background/Purpose:
Altered extracellular matrix (ECM) remodeling leading to fibrosis is a key pathogenic process in systemic sclerosis (SSc).
We previously showed that collagen formation and degradation metabolites are deregulated in SSc and that type III
collagen turnover could identify progressive patients (1). Here, we report additional longitudinal analysis exploring
serological collagen biomarkers potential for diagnosis and prediction of progression of skin and lung fibrosis in SSc.
Methods:
Patients (n=174) meeting the 2013 ACR/EULAR classification criteria for SSc and age and sex matched healthy controls
(HC; n=29) were analyzed. 10% decrease in FVC% predicted or increase in mRSS ≥25% and 5 points at 1 year follow up
defined progression. “Stable” were patients not meeting these criteria. Longitudinal clinical assessment and data, and
baseline sera collection were conducted by EUSTAR quality standards. Collagen degradation (C3M, C4M2), BGM (MMP-
degraded biglycan) and collagen formation markers (P1NP, P4NP7S, PRO-C3, PRO-C5, Pro-C6) were measured in serum
by ELISA. Statistical analysis included Mann-Whitney U, Kruskal-Wallis tests, ROC analysis, and binary logistic
regression.
Results:
174 patients with SSc as well as 29 HC were analysed. There were 25 (14%) SSc patients who progressed during 1 year.
Baseline levels of most collagen biomarkers were higher in SSc compared to HC. C3M, C4M2 and PRO-C3 distinguished
well between HC and SSc patients: C3M (AUC 0.90, p<0.001, 95%CI 0.85-0.95), C4M2 (AUC 0.90, p<0.001, 95%CI
0.85-0.94), PRO-C3 (AUC 0.75, p<0.001, 95%CI 0.67-0.83) (Figure 1). In addition to the previously reported ratio of
PRO-C3/C3M (1), C3M and C4M2 predicted 1-year progression: C3M (AUC 0.87, p<0.001, 95%CI [0.79-0.95]), C4M2
(AUC 0.78, p<0.001, 95%CI [0.68-0.88]). A cut-off for PRO-C3/C3M at >1.2 showed a sensitivity of 84% with a
specificity of 78% to predict progressive patients. In logistic regression adjusted for age and sex, PRO-C3M/C3M could
predict decrease of FVC≥10% (OR 3.8, 95%CI [1.5-9.2], p=0.004) and increase of mRSS≥25% and 5 points (OR=2.1,
95%CI [1.0-4.2], p=0.04). Further, PRO-C3/C3M (OR 2.87, 95%CI [1.8-4.5], p<0.001) and C3M (OR 0.69, 95%CI [0.6-
0.8], p<0.001) were identified as significant predictors of progression of skin and lung fibrosis.
Conclusion:
The dysbalance of collagen turnover suggests decreased collagen degradation in progressive vs. stable patients. Markers of
collagen III and IV particularly arise hereby as potential new diagnostic and prognostic biomarkers in SSc.
1. New collagen biomarkers predict progression of fibrosis in systemic sclerosis. R. Dobrota, S. Jordan, P. Juhl, B.
Maurer, L. Wildi, A.-C. Bay-Jensen, M.A. Karsdal, A.S. Siebuhr, O. Distler. Ann Rheum Dis, vol. 76, suppl. 2, 2017:625.
Figure 1. Levels of biomarkers in healthy controls (HC) and patients with systemic sclerosis (SSc)
Disclosure: R. Dobrota, None; S. Jordan, None; P. Juhl, Nordic Bioscience Diagnostic, 3; B. Maurer, AbbVie, Protagen,
EMDO, Novartis, German SSc Society, 2,Pfizer, Roche, Actelion, MSD, 9,mir-29 for the treatment of systemic sclerosis, 9;
L. Wildi, None; A. C. Bay-Jensen, Nordic Bioscience Diagnostic, 3; M. Karsdal, Symic Bio, 1; A. S. Siebuhr, Nordic
Bioscience Diagnostic, 3; O. Distler, 4 D Science, Actelion, Active Biotec, Bayer, Biogen Idec, Boehringer Ingelheim
Pharma, BMS, ChemomAb, EpiPharm, Ergonex, espeRare foundation, GSK,Roche-Genentech, Inventiva, Lilly, medac,
MedImmune, Mitsubishi Tanabe, Pharmacyclics, Pfizer, Sanofi, Seroda, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prediction-of-fibrosis-progression-in-

systemic-sclerosis-by-collagen-biomarkers
Cardiac MRI in Systemic Sclerosis As Prognostic Tool of Cardiac Mortality

in Symptomatic Patients
Silvia Bosello1, Giovanni Canestrari1, Enrico De Lorenzis1, Gerlando Natalello2, Federico Parisi1, Agostino Meduri3,
Riccardo Marano3, Gianfranco Ferraccioli4 and Elisa Gremese5, 1Division of Rheumatology, Università Cattolica -
Fondazione Policlinico Universitario A.Gemelli, Rome, Italy, 2Division of Rhematology, Università Cattolica - Fondazione
Policlinico Universitario A.Gemelli, Rome, Italy, 3Università Cattolica - Fondazione Policlinico Universitario A.Gemelli,
Rome, Italy, 4Institute of Rheumatology, Università Cattolica - Fondazione Policlinico Universitario A.Gemelli, Rome,
Italy, 5Division of Rheumatology - Institute of Rheumatology and Affine Sciences, Università Cattolica - Fondazione
Policlinico Universitario A.Gemelli, Rome, Italy
SESSION INFORMATION
Background/Purpose:
Cardiac involvement is a relevant prognostic determinant of outcome in Systemic Sclerosis (SSc). Since the role of cardiac
MRI (CMR) is still uncertain, we examined the cardiac involvement in symptomatic SSc patients through CMR, and
defined its prognostic role value and its modification over the time.
Methods:
Sixty-two SSc-patients with symptoms of cardiac involvement (dyspnea, palpitations) and/or signs of cardiac failure and
elevation of cardiac enzymes (MB-CK and/or troponin T) underwent C-MRI. Patients were followed for 51.0±27.2 months
and 23 patients underwent a serial C-MRI studies because of modification and/or a worsening of their symptoms and signs.
Results:
CMR demonstrated abnormalities in 67.7% of patients, in particular T2 hyperintensity in 6 (9.7%) patients, while none of
the patients presented early gadolinium enhancement and 20 (32.2%) patients presented late gadolinium enhancement
(LGE). We identified 3 different patterns of distribution of LGE: subepicardial, midwall and subendocardial. Fourteen
patients presented a single pattern of distribution (22.6%), while 6 patients (9.7%) presented more than one: 20.9% of
patients presented a midwall distribution of LGE, 8.1% of patients presented a subepicardial LGE with a linear distribution
pattern and 9.7% presented a subendocardial LGE distribution. Twelve patients (19.4%) showed one hypokinetic area and
three patients akinetic areas. After a mean follow-up of 51.0±27.2 months, 4 patients (6.0%) died for arrhythmias or heart
failure and 75% presented a subendocardial DE distribution pattern (p=0.003).
During the follow-up, 23 SSc patients presented a modification and/or a worsening of their cardiac symptoms and signs and
they repeated the CMR assessment; CMR abnormalities were partially confirmed in 12 in the subsequent evaluation, 5
CMR demonstrated the development of new areas of T2 hyperintensity, subepicardic and subendocardic DE and
ipo/akinesia; finally 7 CMR previously negative remained negative despite new symptoms. Furthermore a statistical
significant reduction of the ejection fraction (EF) of left (59.4±10.6 vs 56.1±11.3, p<0.001) and right ventricles (54.6±12.0
vs 52.1±12.3, p<0.001) was noticed over the time.
Conclusion:
CMR represents a useful tool to assess the cardiac involvement in systemic sclerosis patients with cardiac signs and
symptoms. Yet clear-cut links between each CMR finding and cardiac symptoms needs to be better defined Our data
suggest that CMR offers the most comprehensive assessment of the extension of myocardial damage and identifies patients
with a poor cardiac outcome especially when a subendocardial DE is present. Serial CMR evaluations allow to identify the
new cardiac damage and to follow reduction of EF of both ventricles.
Disclosure: S. Bosello, None; G. Canestrari, None; E. De Lorenzis, None; G. Natalello, None; F. Parisi, None; A.
Meduri, None; R. Marano, None; G. Ferraccioli, None; E. Gremese, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/cardiac-mri-in-systemic-sclerosis-as-

prognostic-tool-of-cardiac-mortality-in-symptomatic-patients
Quantitative CT Evalutation in Diffuse Interstitial Lung Involvement in

Systemic Sclerosis: Usefulness of Lung Texture Analysis to Predict the
Functional Change over Time
Silvia Bosello1, Maria Elena Occhipinti2, Giovanni Canestrari1, Enrico De Lorenzis1, Federico Parisi1, Gerlando
Natalello3, Grazia Leuconeo4, Anna Rita larici4, Chiara De Waure4, Gianfranco Ferraccioli5 and Elisa Gremese6, 1Division
of Rheumatology, Università Cattolica - Fondazione Policlinico Universitario A.Gemelli, Rome, Italy, 2University of
Florence, Florence, Italy, 3Division of Rhematology, Università Cattolica - Fondazione Policlinico Universitario
A.Gemelli, Rome, Italy, 4Università Cattolica - Fondazione Policlinico Universitario A.Gemelli, Rome, Italy, 5Institute of
Rheumatology, Università Cattolica - Fondazione Policlinico Universitario A.Gemelli, Rome, Italy, 6Division of
Rheumatology - Institute of Rheumatology and Affine Sciences, Università Cattolica - Fondazione Policlinico
Universitario A.Gemelli, Rome, Italy
SESSION INFORMATION
Background/Purpose:
The prognosis of patients with scleroderma and interstitial lung involvement (SSc-ILD) can be evaluated by combining
data of pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT), but both methods have
intrinsic limitations. An automated system able to define the extent and pattern of lung parenchyma involvement could be
very useful in clinical practice.
We aimed to evaluate the performance of such an automated system (CALIPER, Imbio LLC, MN) (1-2) in patients with
SSc-ILD together with PFTs parameters and visual scoring of HRCT scans according to Goh’s visual reader based score
(3). Moreover, we aimed to evaluate the prognostic value of CALIPER with respect to PFTs changes over time.
Methods:
Thirty-five scleroderma patients with ILD-SSc were consecutively enrolled. PFTs as well as lung HRCT were performed at
both baseline and at latest follow-up. Quantitative analysis of parenchymal involvement on HRCT was performed by using
CALIPER, which provided data on the relative volume of 5 different parenchymal patterns: normal, ground-glass, reticular,
hyperlucent and honeycombing. Semi-quantitative analysis of the CT scans was performed by two radiologists according to
the Goh’s visual reader based score.
Results:
Quantitative evaluation by CALIPER was successful in 31/35 patients (88.57%), requiring 20 m’ to 30 m’ per patient for
the sofware. The two most common patterns were ground-glass (16.64%) and reticular (4.48%), with a mean disease extent
of 18.8% and a prevalent distribution at middle and lower zones and in peripheral areas.
The correlations between PFTs and the relative volume of ground-glass were good (FVC: r=-0.72, p<0.001; TLC: r=-0.74,
p<0.001; DLCO: r=-0.40, p=0.001), whereas PFTs and the relative volume of reticular pattern showed weaker correlations
(FVC: r=-0.38, p=0.003; TLC: r=-0.42, p=0.02; DLCO: r=-0.31, p=0.02). The relative volume of normal lung had good
correlations with FVC (r=0.63, p<0.001) and TLC (r=0.42, p=0.02).
The concordance between analysis performed by CALIPER and the Goh’s visual score was weak either in the ground-glass
pattern (ICC:0.67, CI95%: 0.50-0.78) or in the reticular pattern (ICC:0.27, CI95%: 0.03-0.48).
Patients were followed-up for 26.0±15.6 months. Considering as clinically relevant a decrease in FVC greater than 10% or
a decrease in FVC between 5-10% together with a decrease in DLco greater than 15%, reductions of lung volumes higher
than -7.2 could predict a functional worsening with a sensitivity of 81% and a specificity of 70% (ROC curve analysis:
AUC: 0.74, 0.54-0.93, p=0.035).
Conclusion:
Quantitative analysis performed by CALIPER arose as a useful tool to determine the extent and disease pattern in patients
with SSc-ILD, correlating with PFT. The discriminatory performance of such an automated program to identify patients
who presented a worsening of lung function suggests that quantitative analysis can help in evaluating response to therapy in
scleroderma patients with ILD.
1. Maldonado F, Eur Respir J 2014; 43: 204–212

2. Bartholmai Brian J. J Thorac Imaging. 2013 September ; 28(5)
3. Goh NSL, Am J Respir Crit Care Med. 2008;177(11):1248–54.
Disclosure: S. Bosello, None; M. E. Occhipinti, None; G. Canestrari, None; E. De Lorenzis, None; F. Parisi, None; G.
Natalello, None; G. Leuconeo, None; A. R. larici, None; C. De Waure, None; G. Ferraccioli, None; E. Gremese, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/quantitative-ct-evalutation-in-diffuse-

interstitial-lung-involvement-in-systemic-sclerosis-usefulness-of-lung-texture-analysis-to-predict-the-functional-change-
over-time
Impact of Detect on Right Heart Catheterization Referral and Results; Data

from a Prospective, Unselected, Systemic Sclerosis Cohort
Anna-Maria Hoffmann-Vold1, Håvard Fretheim2, Anders Heiervang Tennøe2, Oyvind Midtvedt2, Torhild Garen2, Einar
Gude2, Arne K Andreassen2 and Øyvind Molberg2, 1Division of Rheumatology, Oslo University Hospital, Oslo, Norway,
2Oslo University Hospital, Oslo, Norway
SESSION INFORMATION
Background/Purpose: The DETECT calculator has been freely available as a tool for earlier detection and diagnosis of
pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) since 2014. Here, we aimed to evaluate its impact on
PAH incidence rates, risk profile and functional class (FC) of patients at time of PAH diagnosis.
Methods: The study cohort included all patients in the prospective Oslo University Hospital (OUH) SSc cohort who
performed an incident right heart catheterization (RHC) from 2009 and onwards. We grouped the patients in an early cohort
with RHC conducted in 2009-2013, and a DETECT cohort with RHC from 2014-17. PH diagnosis was made by an
experienced cardiologist according to the updated ESC guidelines with mean (m) PAP ≥ 25 mmHg measured by RHC and
borderline PH with a mPAP >19mmHg. Pre and post capillary PHT was defined by PCW above or below 15 mmHg. Risk
stratification at time of diagnosis was done using the low, intermediate and high risk grouping system suggested by ESC in
2016. Patients with ≥ 1 parameter of poor prognosis were considered at high risk and with ≥ 1 parameter of intermediate
prognosis, at intermediate risk.
Results: An incident RHC was available in 161 patients, 77 from the early cohort and 84 from the DETECT cohort.
Clinical and demographic characteristics are shown in Table 1. Absolute numbers of RHC, PAH and borderline PH cases
in the years 2009-2017 are shown in Figure 1. At the time of PAH diagnosis, 27% of the DETECT cohort were in the low
risk group compared to 19% in the early cohort, while 27% and 47% respectively belonged in the high risk groups (p-value
0.219) (Figure 2). We also observed a trend towards lower functional class in the DETECT cohort (Figure 2).
Conclusion: We show that the number of new PAH cases per year has been stable since 2009, with no apparent change
following the introduction of the DETECT algorithm. From 2014 and onwards, we observed a, not significant, increase in
amount of newly diagnosed PAH cases with low risk group, and better functional class status. The total number of RHC
increased from 2014 and onwards, with a concomitant increase in the number of borderline PH cases.
Table 1: Demographics and clinical characteristics

Total cohort 2009-13 2014-17
p-value
(n=161) (n=77) (n=84)
Age at RHC, yrs (SD) 61 (11.8) 59.6 (12.2)62.4 (11.3) 0.137
Time onset to RHC, yrs (SD) 6.6 (8.2) 6.3 (8.3) 6.9 (8.1) 0.634
Follow-up, yrs (SD) 2.9 (2.4) 4.6 (2.2) 1.2 (0.8) <0.001
Females, no (%) 126 (78.8) 60 (77.9) 66 (78.6) 0.582
Ever smoker, no (%) 67 (41.9) 28 (36.4) 39 (46.4) 0.064
Limited cutaneous SSc, no (%) 125 (78.1) 63 (81.8) 63 (75) 0.502
Anti-centromere Ab, no (%) 78 (48.8) 37 (48.1) 34 (40.5) 0.848
Digital ulcers, n (%) 61 (38.1) 31 (40.3) 30 (35.7) 0.911
Scleroderma renal crisis, n (%) 7 (4.4) 4 (5.2) 3 (3.6) 0.562
Baseline modified Rodnan skin score 9.9 (8.8) 9.8 (10.5) 9.9 (9.8) 0.934
Pulmonary hypertension, n (%) 65 (40.6) 35 (45.5) 30 (35.7) <0.001
PAH total, n (%) 31 (19.4) 16 (20.8) 15 (17.9)
PH-ILD, n (%) 20 (12.5) 14 (18.2) 6 (7.1)
Post capillary PH, n (%) 14 (8.8) 5 (6.5) 9 (10.7)
Borderline PH, n (%) 38 (23.8) 19 (24.7) 27 (32.1)
No PH, n (%) 57 (35.6) 23 (29.9) 27 (32.1)
Myocardial infarction, n (%) 14 (8.8) 8 (10.4) 6 (7.1) 0.557
Angina pectoris, n (%) 14 (10.1) 9 (11.7) 5 (6) 0.414
Figure 1: Frequency of conducted incident RHC, PAH, borderline PH and no PH
Figure 2: Risk stratification and functional class
Disclosure: A. M. Hoffmann-Vold, None; H. Fretheim, None; A. Heiervang Tennøe, None; O. Midtvedt, None; T.
Garen, None; E. Gude, None; A. K. Andreassen, None; Ø. Molberg, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/impact-of-detect-on-right-heart-
catheterization-referral-and-results-data-from-a-prospective-unselected-systemic-sclerosis-cohort
Prediction of All-Cause Mortality and Pulmonary Arterial Hypertension

(PAH) Progression in Systemic Sclerosis (SSc), an Echocardiography Study
Anders Heiervang Tennøe1, Anna-Maria Hoffmann-Vold1, Øyvind Molberg1, Håvard Fretheim1, Torhild Garen1, Einar
Gude1, Arne K Andreassen1, Klaus Murbræch2, Svend Aakhus3, Johanna Andreassen2 and Oyvind Midtvedt1, 1Oslo
University Hospital, Oslo, Norway, 2Cardiology, Oslo University Hospital, Oslo, Norway, 3Circulation and Medical
Imaging, Norwegian University of Science and Technology, Trondheim, Norway
SESSION INFORMATION
Background/Purpose: Pulmonary arterial hypertension (PAH) is one of the leading causes of death in systemic sclerosis
(SSc). Annual echocardiograms (echo) are recommended to detect PAH at an early stage, potentially improving outcome.
We aimed to evaluate the potential of baseline echo parameters to predict PAH progression and all-cause mortality.
Methods: The study cohort included all SSc patients from the prospective Oslo University Hospital (OUH) cohort who had
an evaluable baseline protocol echo performed between 2003 and 2016. This echo was analyzed regarding left- and right-
sided systolic and diastolic function. Right heart catheterization (RHC) was performed in patients suspected of PH. PAH
diagnosis was made by an experienced cardiologist with mean pulmonary artery pressure ≥ 25 mmHg, pulmonary capillary
wedge pressure <15mmHg, stable forced vital capacity >70% and <10% lung fibrosis on HRCT. Vital status was available
for all patients and PAH progression, defined by occurrence of new PAH related events were calculated. Cox regression
analyzes were conducted.
Results: In total, 337 SSc patients with baseline echo were included. RHC was conducted in 149 (44.2%) patients and 48
(14.2%) were diagnosed with PAH; of those, 34 patients showed PAH progression. Demographic and clinical
characteristics are summarized in Table 1. Significant results from univariable and multivariable cox analyses of death are
shown in Table 2, and for PAH progression in Table 3. In the final cox regression model for death, age (HR 1.06, 1.03-1.10
95%CI , p<0.001), DLCO (HR 0.97, 0.96-0.98 95%CI , p=0.001), pericardial effusion (HR 2.24, 1.37-3.63 95%CI ,
p<0.001), left atrium area (HR 1.07, 1.01-1.14 95% CI, p=0.024) and tricuspid annular plane systolic excursion (TAPSE)
(HR 0.38, 0.19-0.74 95% CI , p=0.004) were associated (c-index 0.82). PAH progression was associated with age (HR
1.06, 1.02-1.11 95% CI, p=0.005), DLCO (HR 0.97, 0.95-0.99 95% CI, p=0.002), and right atrium area (HR 1.17, 1.10-
1.25 95% CI, p<0.001) (c-index 0.86).
Conclusion: In our large and unselected SSc cohort, impaired baseline right heart function, but not left ventricular systolic
or diastolic parameters, was predictive for both death and PAH progression. Echo may serve as a tool to stratify patients at
risk for PAH and death.
Table 1: Demographic and
clinical characteristics of all SSc
patients, SSc-PAH patients and
deceased patients.
All cases Deceased patients PAH

(n=337) (n=101)
(n=48)
Male, no (%) 57 (17) 25 (25) 8 (17)
ACA, no (%) 172 (55) 39 (39) 38 (83)
lcSSc, no (%) 224 (68) 65 (64) 44 (92)
Death, no (%) 101 (30) - 25 (52)
Age at echo, mean (SD) 58 (14) 64 (12) 64 (11)
Observation period, years, 5.1 (0-14) 3.0 (0-12) 5.3 (0.1-12.3)
median (min,max)
TAPSE, cm (SD) 2.3 (0.5) 2.0 (0.6) 2.0 (0.6)
Right ventricular strain % (SD) 23.0 (6.1) 20.3 (7.1) 19.3 (7.3)
Left atrium area, cm2 (SD) 18 (5) 19 (5) 17 (4)
LV Global longitudinal strain, % 18.4 (3.0) 17.6 (3.5) 18.4 (2.2)
(SD)
LVEF, % (SD) 58 (8) 56 (10) 59 (7)
E-wave, m/s (SD) 0.72 (0.21) 0.72 (0.29) 0.67(0.24)
A-wave, m/s (SD) 0.70 (0.22) 0.77 (0.26) 0.72(0.21)
e’ septal, cm/s (SD) 7.5 (2.6) 5.9 (2.1) 5.7 (2.1)
E/e’ ratio (SD) 10.6 (4.5) 13.0 (6.3) 12.7 (6.1)
Tricuspid regurgitant pressure 34 (21) 44 (25) 50 (26)
(TRp) , mmHg (SD)
Right atrium, area, cm2 (SD) 17 (6) 19 (7) 21 (8)
Fractional area change (FAC), 39 (10) 35 (10) 32 (11)
% (SD)
Pericardial effusion, no (%) 42 (13) 22 (22) 9 (19)
Table 2: Univariable
and multivariable cox
regression analyses
associated with death
Univarable Multivariable
HR 95% CI p-value HR 95% CI p-value
Pericardial effusion 2.09 1.49-2.94 <0.001 1.86 1.18-2.95 0.008
Left atrium, area 1.05 1.01-1.05 0.017 1.08 1.02-1.14 0.008
TAPSE 0.29 0.19-0.45 <0.001 0.44 0.23-0.83 0.011
Right ventricular strain 0.93 0.89-0.98 0.002 0.94 0.88-0.99 0.045
Right atrium, area 1.08 1.05-1.12 <0.001 1.1 1.05-1.15 <0.001
TRp 1.02 1.01-1.03 <0.001 1.02 1.002-1.02 0.019
Table 3: Univariable and
multivariable cox regression
analyses (adjusted for age and
gender) associated with PAH
progression
Univariable Multivariable
HR 95% CI p-value HR 95% CI p-value
Pericardial effusion 2.9 1.76-4.69 <0.001 3.2 1.83-5.55 <0.001
TAPSE 0.17 0.09-0.34 <0.001 0.24 0.12-0.47 <0.001
Right ventricular strain 0.89 0.85-0.95 0.001 0.89 0.84-0.95 <0.001
Right atrium, area 1.17 1.11-1.22 <0.001 1.14 1.08-1.20 <0.001
FAC 0.93 0.89-0.96 <0.001 0.94 0.90-0.97 0.001
Disclosure: A. Heiervang Tennøe, None; A. M. Hoffmann-Vold, None; Ø. Molberg, None; H. Fretheim, None; T.
Garen, None; E. Gude, None; A. K. Andreassen, None; K. Murbræch, None; S. Aakhus, None; J. Andreassen, None;
O. Midtvedt, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prediction-of-all-cause-mortality-and-

pulmonary-arterial-hypertension-pah-progression-in-systemic-sclerosis-ssc-an-echocardiography-study
An International Qualitative Research Study Exploring the Patient

Experience of Raynaud’s Phenomenon in Systemic Sclerosis
John D. Pauling1,2, Robyn T. Domsic3, Lesley Ann Saketkoo4, Celia Almeida5, Tracy M. Frech6, Francesca Ingegnoli7,
Jane Withey8, Hilary Jay8, Emma Dures9, Joanna Robson10, Neil J. McHugh11,12, Ariane L. Herrick13,14, Marco Matucci-
Cerinic15, Dinesh Khanna16 and Sarah Hewlett17, 1Department of Pharmacy and Pharmacology, University of Bath, Bath,
United Kingdom, 2Department of Rheumatology, Royal National Hospital for Rheumatic Diseases, Bath, United Kingdom,
3Medicine - Rheumatology, University of Pittsburgh, Pittsburgh, PA, 4Tulane, New Orleans, LA, 5HAS - Nursing and
Midwifery, University of the West of England, Bristol, United Kingdom, 6Division of Rheumatology, University of Utah,
Salt Lake City, UT, 7Dept. of clinical and community science, Rheumatology, Istituto G. Pini, University of Milan, Milano,
Italy, 8Patient Research Partner, Bath, United Kingdom, 9Academic Rheumatology, Bristol, University of the West of
England, Bristol, Bristol, United Kingdom, 10Rheumatology, University of the West of England (UWE Bristol), Bristol,
United Kingdom, 11Rheumatology, Royal National Hospital for Rheumatic Diseases, Bath, United Kingdom, 12Department
of Pharmacy and Pharmacology, The University of Bath, Bath, United Kingdom, 13Centre for Musculoskeletal Research,
University of Manchester, MAHSC, Salford Royal Hospital, Manchester, United Kingdom, 14School of Translational
Medicine, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom, 15Dept
of Medicine/Div of Rheum, University of Florence, Florence, Italy, 16Department of Medicine, University of Michigan
Scleroderma Program, Ann Arbor, MI, 17UWE Academic Rheumatology, University of West of England, Bristol, United
Kingdom
SESSION INFORMATION
Background/Purpose:
Raynaud’s phenomenon (RP) is consistently ranked highest in patient surveys exploring the frequency and impact of
disease related manifestations of systemic sclerosis (SSc). SSc-RP is an episodic phenomenon and not easily assessed in
the clinical setting. A thorough understanding of the patient experience of SSc-RP is essential if severity and impact are to
be captured using patient-reported outcome (PRO) instruments. We report the findings of an international qualitative
research study to investigate the patient experience of SSc-RP.
Methods:
Focus groups (FGs) comprising patients with SSc-RP (fulfilling 2013 ACR/EULAR classification criteria) were conducted
across 3 scleroderma centers in the United States and United Kingdom, using a topic guide devised by a steering committee
comprising qualitative researchers, SSc patients and SSc experts. Participants were enrolled according to an a priori
purposive sampling framework ensuring we sought the views of a diverse (geographic, cultural and ethnic) and
representative (disease subtype, disease duration, gender and history of digital ulcer disease) cohort of SSc patients. FGs
were audio recorded, transcribed, anonymised and analysed using inductive thematic analysis. Additional FGs were
conducted until thematic saturation was achieved.
Results:
Forty SSc patients participated in 6 focus groups conducted in Bath (n=2), New Orleans (n=3) and Pittsburgh (n=1). The
participant demographics are presented (Table). The patient experience of SSc-RP can be described according to 7 major
inter-related themes comprising; physical symptoms, emotional impact, triggers & exacerbating factors, constant vigilance
& self-management, impact on daily life, uncertainty and adaptation. A conceptual map demonstrating the inter-
relationship of the 7 themes is presented (Figure).
Conclusion:
This is the first qualitative study to explore the patient experience of SSc-RP. The multi-center design and purposive
sampling framework ensured experiences were obtained from a diverse and representative SSc cohort. SSc-RP comprises a
complex interplay of experiences that result in significant physical/emotional distress, disability and altered social
participation which adversely affects health-related quality of life. The themes (and subthemes) identified herein are not
captured using existing PRO instruments for assessing SSc-RP. Work to develop a novel PRO instrument for assessing the
severity and impact of SSc-RP, comprising domains/items grounded in the patient experience of SSc-RP identified in this
work is now underway.
Demographics and clinical feature of
enrolled patients presented according to
purposive sampling framework
Total number of 40
participants:
Disease subtype:
limited 24
diffuse 16
Sex:
Female 34
Male 6
Ethnicity:
White/Caucasian 26
Black/African- 12
American
Hispanic 2
Disease duration
(time since 1st non-
Raynaud’s symptom)
≥3 years 34
<3 years 6
History of DU disease:
Yes 23
No 17
Disclosure: J. D. Pauling, Actelion Pharmaceuticals UK, 2,Actelion Pharmaceuticals UK, 5; R. T. Domsic, None; L. A.
Saketkoo, None; C. Almeida, None; T. M. Frech, None; F. Ingegnoli, None; J. Withey, None; H. Jay, None; E. Dures,
None; J. Robson, None; N. J. McHugh, None; A. L. Herrick, None; M. Matucci-Cerinic, None; D. Khanna, Actelion,
Bayer, BoehringerIngelheim, Chemomab, Corbus, Covis, Cytori,Eicos, EMD Serono, Genentech/Roche, Gilead, GSK,
Sanofi-Aventis,UCB Pharma, 5,NIH/NIAMS, NIH/NIAID,Bayer, BMS, Genentech/Roche, Pfizer, 2,Eicos, 4; S. Hewlett,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/an-international-qualitative-research-

study-exploring-the-patient-experience-of-raynauds-phenomenon-in-systemic-sclerosis

Comparison of Disease Characteristics in Patients with Juvenile-Onset and
Adult-Onset Progressive Systemic Sclerosis
Guzin Karatemiz1, Amra Adrovic2, Sinem Nihal Esatoglu1, Sezgin Sahin2, Kenan Barut2, Gulen Hatemi1, Vedat
Hamuryudan1, Ozgur Kasapcopur2 and Emire Seyahi1, 1Istanbul University, Cerrahpasa Medical Faculty, Department of
Internal Medicine, Division of Rheumatology, Istanbul, Turkey, 2Pediatric Rheumatology, Istanbul University, Cerrahpasa
Medical School, Department of Pediatric Rheumatology, Istanbul, Turkey
SESSION INFORMATION
Background/Purpose: Progressive systemic sclerosis (PSSc) has been known to affect mainly adults of 30-50 years of
age. Juvenile –onset has been reported to be rare and studies comparing clinical differences between juvenile-onset and
adult onset form have been limited (1). One study form North America revealed that there is more skeletal muscle
involvement, more severe cardiac disease, whereas improved survival compared with adult onset pSSc cases (1). Recently,
one multicenter European study revealed that juvenile-onset PSSc showed scleroderma pattern on the capilleroscopy more
frequently than that observed in adult-onset pSSc (2). As there would be also effects of ethnic differences, we aimed to
assess clinical differences between the two forms of pSSc of pediatric and adult rheumatology centers of a tertiary center, in
Turkey.
Methods: Adult onset patients were defined as those who were registered and followed as ‘scleroderma’ at the departments
of adult and pediatric rheumatology at Cerrahpasa Medical Faculty, Istanbul, between 2005 and 2017. Only those with at
least 2 follow-up visits were included in the study. Patients’s charts were re-evaluated retrospectively for demographic and
clinic characteristics.
Results: There were 140 patients with scleroderma diagnosis in the adult outpatient clinic records, and 51 in the pediatric
clinic records. Of these patients, 3 adults and 25 (49 %) pediatric patients had localized scleroderma (p<0.001). We studied
the remaining patients (adults: n=137, juvenile: n =26) who had systemic pattern.
As shown in Table, male/female ratio, median follow-up duration, familial history of chronic inflammatory diseases and the
frequency of sclerodactyly, digital ulcers, Raynaud phenomenon, arrhythmia/heart failure and gastrointestinal involvement
were similar between juvenile and adult onset groups. The frequency of interstitial lung disease, pulmonary artery
hypertension, and serum ANA positivity were significantly more common in the adult onset group. Whereas, joint and
muscle involvements were significantly more common among juvenile onset patients. DMARD use was significantly more
common in the juvenile group, on the other hand, the use of vasodilators was more frequent among adults.
Conclusion: Our results are online with previous reports: juvenile onset patients seem to have a milder form of disease.
Major organ involvement as defined interstitial lung disease and pulmonary artery hypertension was more common among
adult onset patients. On the other hand, as expected, joint involvement and myopathy were major causes of morbidity in the
juvenile group. Contrary to that previously reported, cardiac involvement was not common in the juvenile group.
References:
1) Scalapino K, et al. J Rheumatol. 2006.
2) Ingegnoli F, et al. Microvasc Res. 2015.
Table. Demographic and clinic characteristics of the patients

Adult onset Juvenile onset P
(n= 137) (n =26)

Age at disease onset, mean± SD 38.6 ± 13.4 10.1 ± 4.3 -
Age at diagnosis, mean± SD 43.6 ± 14.0 11.4 ± 3.2 -
Follow-up duration, med. [IQR], years 5 [2.0-7.0] 4 [2.5-6.0] NS
Male/Female 20/117 2/24 NS
Familial history of chronic inflammatory 20 (14.6) 4 (15.4) NS
diseases, n (%)
Sclerodactyly, n (%) 128 (93.4) 25 (96.2) NS
Raynaud phenomenon, n (%) 135 (98.5) 24 (92.3) NS
Digital ulcers, n (%) 55 (41.4) 14 (54.0) 0.001
Interstitial lung disease, n (%) 71 (52.2) 6 (24.0) 0.009
PAH, n (%) 20 (14.9) 0 0.045
Arrhythmia/heart failure, n (%) 14 (10.4) 1 (4.0) NS
Joint involvement, n (%) 20 (14.9) 13 (50.0) <0.001
Skleletal muscle involvement/myopathy n 10 (7.5) 7 (28.0) 0.002
(%)
Gastrointestinal system involvement, n (%) 42 (31.8) 8 (32.0) NS
Arterial hypertension, n (%) 24 (18.2) 0 0.015
ANA positivity, n (%) 119 (93.0) 18 (75.0) 0.007
DMARD use, n (%) 90 (65.7) 25 (96.2) 0.002
Vasodilators, n (%) 113 (82.5) 13 (50.0) <0.001
Disclosure: G. Karatemiz, None; A. Adrovic, None; S. N. Esatoglu, None; S. Sahin, None; K. Barut, None; G. Hatemi,
None; V. Hamuryudan, None; O. Kasapcopur, None; E. Seyahi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/comparison-of-disease-characteristics-

in-patients-with-juvenile-onset-and-adult-onset-progressive-systemic-sclerosis
Autoantibodies to Rpp25 (Th/To) Are Specific Markers for Systemic Sclerosis

and Are Associated with Limited Cutaneous Disease and Young Age at
Disease Onset
Boyang Zheng1, Martial Koenig2, Marychel Tiongson3, Andrea Seaman3, Danilo Villalta4, Gabriella Morozzi5, Nicola
Bizzaro6, Gabriella Pucci7, Michaelin Richards3 and Michael Mahler3, 1Division of Internal Medicine, Centre Hospitalier
de l'Université de Montréal (CHUM), Montreal, QC, Canada, 2Internal Medicine, Hôpital Notre-Dame du CHUM,
Montréal, QC, Canada, 3Research and Development, Inova Diagnostics, San Diego, CA, 4Allergologia e Immunologia
Clinica, AO S. Maria degli Angeli, Pordenone, Pordenone, Italy, 5Chirurgiche e Neuroscienze, Sezione di Reumatologia,
Università di Siena, Dipartimento Scienze Mediche, Siena, Italy, 6Ospedale San Antonio, Tolmezzo, Italy, 7Chirurgiche e
Neuroscienze, Sezione di Reumatologia, Università di Siena, Siena, Italy
SESSION INFORMATION
Autoantibodies to Rpp25 (Th/To) are specific markers for systemic sclerosis and are associated with limited
cutaneous disease and young age at disease onset[MM1]
Boyang Zheng4, Martial Koenig4, Michael Mahler1,

1 Inova Diagnostics, INC. San Diego, CA, USA;
2 Department of Medicine, McGill University, Montreal, Quebec, Canada
Background/Purpose:
Antinuclear antibodies (ANA), present in 80-90% of systemic sclerosis (SSc) patients, are important for disease diagnosis.
Of particular utility are those with SSc-specific and SSc-associated antibodies, including anti Th/To amongst others (i.e.
antibodies to centromere, Scl-70, RNA Pol-III, PM/Scl, Ro52/TRIM21 and U1RNP). However, in a significant minority of
ANA positive SSc patients, no fine specificities are detected using conventional diagnostic protocols. Recently, it was
found that anti-Rpp25 antibodies are an important autoantigenic component of the Th/To complex. However, no FDA
cleared assay is available for the detection of anti-Th/To antibodies. Consequently, the present study aimed to analyze a
large well characterized Canadian SSc patient cohort in comparison to other disease control groups for antibodies to Rpp25
in a standardized assay.
Methods:
Sera from 320 Canadian SSc patients [48 diffuse cutaneous (dc) SSc, 223 limited cutaneous (lc) SSc and 49 sine SSc] and
various disease controls (n=889) were tested for anti-Rpp25 antibodies by a bead based immunoassay (research use only,
Inova Diagnostics, US).
Results:
Anti-Th/To antibodies were significantly more common and present in higher titers in SSc patients compared to all controls
(p<0.05). The prevalence in SSc and in the different control groups is summarized in the figure below.
Receiver operating characteristic (ROC) analysis showed an area under the curve of 0.70 (95% Confidence interval 0.67-
0.73). The sensitivity and specificity for SSc was 9.7% (95% CI 6.9-13.4%) and 99.0% (95% CI 98.1-99.5%), respectively.
The odds ratio for SSc was 10.6 (95% CI 5.1-22.3). Anti-Rpp25 antibodies were present in 0/48 dcSSc (0.0%), in 27/223
lcSSc (12.1%) and in 4/49 (8.2%) sine SSc patients. The difference between lcSSc and dcSSc was significant (p=0.01). In
addition, anti-Rpp25 antibodies were associated with a younger age at SSc disease onset (34.3 vs. 39.8 years; p=0.048).
Conclusion:
Autoantibodies to Rpp25 as part of the Th/To autoantigen show high specificity for SSc and define a subset of SSc with
lcSSc and younger age of disease onset.
[MM1]Check composition of authors
Disclosure: B. Zheng, None; M. Koenig, None; M. Tiongson, None; A. Seaman, Inova Diagnostics, Inc., 3; D. Villalta,
None; G. Morozzi, None; N. Bizzaro, None; G. Pucci, None; M. Richards, Inova Diagnostics, Inc., 3; M. Mahler, Inova
Diagnostics, Inc., 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/autoantibodies-to-rpp25-thto-are-

specific-markers-for-systemic-sclerosis-and-are-associated-with-limited-cutaneous-disease-and-young-age-at-disease-onset
Scleromyxedema Phenotype Pre- and Post-Treatment with Intravenous

Immunoglobulin
Christopher A. Mecoli1, Andrea Fava2, Francesco Boin3 and Laura K. Hummers4, 1Rheumatology, Johns Hopkins
University, Baltimore, MD, 2Johns Hopkins University, Baltimore, MD, 3Rheumatology, University California, San
Francisco, San Francisco, CA, 4Medical and Rheumatology, Johns Hopkins University, Baltimore, MD
SESSION INFORMATION
Background/Purpose: Scleromyxedema is a rare scleroderma mimic that often responds to intravenous immunoglobulin
therapy (IVIG). The clinical and biochemical changes in response to treatment have not been well-characterized.
Methods: 15 patients with scleromyxedema were recruited for the study. Clinical information and blood samples were
obtained immediately before and again 2-3 weeks after receiving IVIG therapy. Clinical information included the modified
modified Rodnan Skin Score (MMRSS) which includes assessing the patients’ back and ears, and visual analog scales to
assess patients’ pain, itch, flexibility, and softness of their skin. In addition, Health Assessment Questionnaire Disability
Index (HAQ-DI) and percent body surface area involved were recorded.
Results: Demographic data and disease characteristics can be found in Table 1. Twelve of the 15 patients were receiving
maintenance IVIG, and three were treatment-naïve. All patients except for one had a monoclonal gammopathy of
undetermined significance (MGUS), 12 of which were IgG lambda, and two were IgG kappa.
Post-treatment, the average MMRSS decreased from 13.6 to 10.3 (p=0.003). Skin flexibility, skin softening and skin global
all improved as assessed using visual analog scales, and were statistically significant (Table 2). Correlation studies
demonstrated that the MMRSS correlated with the Health Assessment Questionnaire-Disability Index (HAQ-DI) R=0.47,
p=0.009). The three treatment-naïve patients had a larger improvement (mean MMRSS 20 ± 5.1 to 13.3 ± 4.7 compared to
patients receiving maintenance IVIG, 11.9 ± 10 to 9.5 ± 8).
The two patients with a history of neurologic complications relating to scleromyxedema had a markedly lower MMRSS of
1 ± 0.8 compared to patients without neurologic complications, 13.6 ± 8.3, p=0.006. Patients with lambda IgG MGUS had
a higher MMRSS compared to those with kappa IgG or no MGUS, 13.3 ± 9.8 compared to 7.8 ± 5.2, p=0.22.
Conclusion: Patients with scleromyxedema have clinical improvement to IVIG in several domains, and the extent of skin
involvement correlates with their HAQ-DI. Patients with a history of neurologic complications of scleromyxedema or non-
IgG lambda MGUS have lower skin scores.
Demographic Data N (%)
Female sex 12 (80)
Age (mean ± SD) 53 ± 11
Caucasian 14 (93)
Neurologic
involvement 2 (13)
IgG MGUS 14 (93)
Lambda 12
Kappa 2
Treatment naïve 3 (20)
Table 1
Pre- Post-
Clinical Parameters IVIG IVIG P-value
(mean) (mean)
Physician Global
Assessment 1.40 1.10 0.100
Body Surface Area
(%) 36.20 25.40 0.090
MMRSS (0-60) 13.60 10.30 0.003
Skin scale pain (0-
100) 17.70 13.70 0.250
Skin scale itch (0-100) 2.10 2.10 1.000
Skin scale flexibility
(0-100), 0=Best 54.00 32.00 0.013
Skin scale softening
(0-100), 0=Best 46.00 26.00 0.022
Skin scale global (0-
100) 45.00 27.00 0.029
HAQ-DI 0.62 0.54 0.400
Table 2
Disclosure: C. A. Mecoli, None; A. Fava, None; F. Boin, None; L. K. Hummers, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/scleromyxedema-phenotype-pre-and-

post-treatment-with-intravenous-immunoglobulin
Treatment with Cyclophosphamide for Systemic Sclerosis-Interstitial Lung

Disease Does Not Lead to a Sustained Improvement in Lung Function in Two
Independent Cohorts
Elizabeth R. Volkmann1, Donald P. Tashkin1, Myung Sim1, Ning Li2, Dinesh Khanna3, Michael Roth4, Philip J.
Clements4, Anna-Maria Hoffmann-Vold5, Daniel E. Furst1, Grace Kim6, Jonathan Goldin1 and Robert Elashoff7,
1University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, 2Biomathematics, University
of California, Los Angeles, Los Angeles, CA, 3University of Michigan, Ann Arbor, MI, 4Medicine, University of
California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, 5Oslo University Hospital, Oslo, Norway,
6Radiology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, 7University of
California, Los Angeles, Los Angeles, CA
SESSION INFORMATION
Background/Purpose: Compared with placebo, treatment with cyclophosphamide (CYC) improved lung function in
patients with systemic sclerosis-related interstitial lung disease (SSc-ILD) after 1 year in Scleroderma Lung Study (SLS) I.1
However, the effects of CYC waned after monitoring patients for an additional year off therapy.2 In SLS II (comparing
CYC and mycophenolate [MMF]), treatment with 1-year of CYC appeared to have a more sustained effect on lung function
over 2-years, although SLS II used a different analysis approach than SLS I.3 To further understand the effects of CYC on
SSc-ILD outcomes, the present analysis directly compared outcomes between the CYC arms of SLS I and II.
Methods: Participants enrolled in the CYC arms of SLS I (N=79) and II (N=73) were included. SLS I and II randomized
participants to oral CYC for 1 year and followed patients for an additional year off therapy (In SLS II, patients received
placebo in the second year). Eligibility criteria for SLS I and II were nearly identical. Outcomes included the FVC%-
predicted and DLCO%-predicted (measured every 3 months) and quantitative radiographic extent of ILD (QILD)
(measured at 1 and 2 years for SLS I and SLS II, respectively). Joint models were created to evaluate the treatment effect
on the course of the FVC/DLCO over 2-years while controlling for baseline disease severity.
Results: SLS II-CYC participants had similar baseline characteristics compared with SLS I-CYC participants in terms of
gender (75% vs. 77% female), disease duration (mean [SD] years: 2.6 [1.8] vs. 3.1 [2.3]), and FVC%-predicted (mean
[SD]: 66.9 [9.9] vs. 67.6 [11.4]), respectively. SLS II-CYC patients were slightly older (mean [SD] years: 52.2 [9.6] vs.
48.4 [12.2]; P=0.037) and had a higher DLCO%-predicted (mean [SD]: 54.5 [14.6] vs. 47.2 [13.9]; P=0.0002) than SLS I-
CYC participants. After adjusting for baseline QILD and FVC%-predicted, there was no difference in the course of the
FVC%-predicted between the CYC arms of SLS I and II (P=0.535), nor the DLCO%-predicted (P=0.172). In both groups,
treatment with CYC led to a significant improvement in the FVC%-predicted from 3-12 months, but no significant
improvement beyond this point (Figure 1). Treatment with CYC had no effect on the DLCO for either group.
Conclusion: Although there are limitations in comparing participants from two trials, the baseline characteristics of the
SLS I and SLS II participants were relatively similar. Treatment with 1 year of oral CYC led to similar improvements in
lung function in both SLS I and II, although the effects were not sustained following CYC cessation. There results suggest
that increasing the duration of ILD therapy may improve outcomes for SSc-ILD patients.
References:
1. NEJM 2006;354:2655-66.
2. Am J Respir Crit Care Med 2007;176:1026-34.
3. Lancet Resp Med 2016;4:708-19.

Figure 1. Course of the FVC%-predicted by CYC treatment
arm based on a joint model analysis.
Disclosure: E. R. Volkmann, None; D. P. Tashkin, None; M. Sim, None; N. Li, None; D. Khanna, Actelion, Bayer,
BoehringerIngelheim, Chemomab, Corbus, Covis, Cytori,Eicos, EMD Serono, Genentech/Roche, Gilead, GSK, Sanofi-
Aventis,UCB Pharma, 5,NIH/NIAMS, NIH/NIAID,Bayer, BMS, Genentech/Roche, Pfizer, 2,Eicos, 4; M. Roth, None; P.
J. Clements, None; A. M. Hoffmann-Vold, None; D. E. Furst, None; G. Kim, None; J. Goldin, None; R. Elashoff,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/treatment-with-cyclophosphamide-for-

systemic-sclerosis-interstitial-lung-disease-does-not-lead-to-a-sustained-improvement-in-lung-function-in-two-
independent-cohorts
Diltiazem Gel As a New Local Treatment for Scleroderma Digital Ulcers

Mohammad Ali Nazarinia1, Elmira Esmaeilzadeh2 and Saeedeh Shenavandeh2, 1Shiraz Geriatric Research Center, Shiraz
University of Medical Sciences, Shiraz, Iran, Shiraz, Iran (Islamic Republic of), 2Department of Internal Medicine,
Division of Rheumatology, Shiraz University of Medical Sciences, Shiraz, Iran., Shiraz, Iran (Islamic Republic of)
SESSION INFORMATION
Background/Purpose: Assessing the effect of Diltiazem gel on healing process of scleroderma digital ulcers and
comparing its effect with Nitroglycerin ointment and placebo.
Methods: Ninety scleroderma patients divided to three groups underwent a single blind randomized clinical trial.
Experimental group 1 received Diltazem gel 2%, experimental group 2 received Nitroglycerin ointment 2% and control
group received Vaseline as placebo. All interventions were applied 2 times per day for 8 weeks. The mean of maximum
diameters of the ulcers was measured for each patient at the beginning and at the end of the study. The site of the ulcers and
the number of new ones were, also, determined for each patient.
Results:
The mean diameter of the ulcers at the end of the study was significantly lower in three studied groups compared to the
beginning of the study (Diltiazem P<0.001, Nitroglycerin P= 0.002 and Control P= 0.027). However, the difference in size
of the ulcers was significantly higher in diltiazem group compared to nitroglycerin and placebo (P= 0.04), especially, in
ulcers at distal part of digits (P=0.32). In addition, number of new ulcers did not differ significantly between three groups.
Moreover, nitroglycerin ointment (42%) was found to induce more complications for patients compared to Diltiazem gel
(28%) and placebo (28%).
Conclusion: Diltiazem gel can be an effective topical therapy with lower complications for treating scleroderma digital
ulcers compared to nitroglycerin ointment and placebo.
Disclosure: M. A. Nazarinia, None; E. Esmaeilzadeh, None; S. Shenavandeh, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/diltiazem-gel-as-a-new-local-treatment-

for-scleroderma-digital-ulcers
Effect of Probiotics on the Gastrointestinal Symptoms and Immune

Parameters in Patients with Systemic Sclerosis: A Randomized, Double-
Blind, Placebo-Controlled Clinical Trial
Thais Marighela1, Maria Izabel Arismendi1, Milena Brunialti2 and Cristiane Kayser1, 1Rheumatology Division,
Universidade Federal de São Paulo, São Paulo, Brazil, 2Division of Infectious Diseases, Universidade Federal de São
Paulo, São Paulo, Brazil
SESSION INFORMATION
Background/Purpose:
Abnormalities in the intestinal microbiota have been associated with several autoimmune diseases, including systemic
sclerosis (SSc). Recent studies have demonstrated the potential of probiotics in modulating the microbioma and the
immune responses in several autoimmune diseases. T cell abnormalities including a predominant T helper type 2 (Th2)
profile and increased levels of Th17 cells have been implicated in the pathogenesis of SSc. The objective of this study was
to evaluate the effects of probiotics on the gastrointestinal (GI) symptoms and immune parameters in patients with SSc.
Methods:
In this double-blind, placebo-controlled, randomized clinical trial 73 patients with SSc (EULAR/ACR criteria from 2013)
with a moderate-to-severe total score (0.5–3.00) on the University of California Los Angeles Scleroderma Clinical Trial
Consortium Gastrointestinal Tract Instrument 2.0 (UCLA GIT 2.0) were randomized to receive probiotics (1 capsule/day of
Lactobacillus paracasei, L. rhamnosus, L. acidophillus and Bifidobacterium lactis, 109 colony-forming units per capsule)
or placebo (identical capsules containing maltodextrin) for 8 weeks. The primary outcome measurement was improvement
in the UCLA GIT 2.0 total score after 8 weeks of treatment. Secondary outcomes included changes in Th1, Th2, Th17 and
regulatory T cells serum levels, immunoglobulin A (IgA), scleroderma Health Assessment Questionnaire (SHAQ) score,
anthropometric parameters, and dietary intake. The frequencies of Th1 (CD3+CD8-IFN-γ+), Th2 (CD3+CD8-IL4+), Th17
(CD3+CD8-IL17+) and regulatory T (CD3+CD4+CD25+Foxp3+) cells in peripheral blood were measured using flow
cytometry. Clinical and immune parameters were assessed at baseline (T0), after four (T4) and eight weeks (T8) of
treatment. The trial was registered on ClinicalTrials.com under the identifier NCT 02302352.
Results:
Thirty-seven patients were randomized to probiotics (mean age 47.7 years) and 36 (mean age 46.1 years) to the placebo
group. After 8 weeks, there was a significant improvement in UCLA GIT 2.0 total score in both groups (p<0.001), but
changes were not different between the two groups (p=0.934). The probiotic group presented a significant decrease in the
serum percentage of Th2 (from 2.2% in T0 to 1.5% in T8) and Th17 (from 2.0% in T0 to 1.4% in T8) cells compared with
the placebo group (from 2.3% in T0 to 2.5% in T8 for Th2; from 1.9% in T0 to 1.9% in T8 for Th17 cells) (p=0.038,
p=0.04; respectively). No significant changes were observed in percentages of Th1 and Treg cells, IgA serum levels, SHAQ
score, anthropometric parameters, and dietary intake after treatment between the two groups. No serious adverse events
were reported.
Conclusion:
In this first randomized, double-blind trial evaluating the effects of probiotics in SSc, there was no reduction in the GI
symptoms with probiotic supplementation compared with placebo. Nonetheless, probiotics showed to reduced the
peripheral percentages of Th2 and Th17 cells in patients with SSc. These results indicate that probiotics have
immunomodulatory effects and anti-inflammatory properties and might represent an innovative therapeutic approach to
SSc patients.
Disclosure: T. Marighela, None; M. I. Arismendi, None; M. Brunialti, None; C. Kayser, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effect-of-probiotics-on-the-

gastrointestinal-symptoms-and-immune-parameters-in-patients-with-systemic-sclerosis-a-randomized-double-blind-
placebo-controlled-clinical-trial
Role of the Six-Minute Walk Test in Systemic Sclerosis: Five Years Evolution
Els Vandecasteele1, Karin Melsens2, Filip De Keyser3, Michel De Pauw4, Ellen Deschepper5, Saskia Decuman6, Yves
Piette2, Kristof Thevissen7, Guy Brusselle8 and Vanessa Smith3, 1Dep of Cardiology, University Hospital Ghent, Ghent,
Belgium, 2Ghent University Hospital, Department of Rheumatology, Ghent, Belgium, Ghent, Belgium, 3Ghent University,
Department of Internal Medicine, Ghent, Belgium, Ghent, Belgium, 4Dep of cardiology, University Hospital Ghent, Ghent,
Belgium, 5Biostatistics Unit, UGent, Ghent, Belgium, 6Department of Internal Medicine, Ghent University, Ghent, Belgium,
7University Hospital Ghent, Ghent, Belgium, 8Gent University, Gent, Belgium
SESSION INFORMATION
Title
Role of the Six-Minute Walk Test in Systemic Sclerosis: five years evolution.
Background/Purpose: Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are the leading causes of
death in Systemic Sclerosis (SSc) patients. Although the six-minute walk test (6MWT) is used for evaluating ILD and PAH
in clinical practice, no data are available on the natural evolution of the six-minute walk distance (6MWD) in SSc patients
without ILD and PAH.
Methods: Prospectively collected data of the first 6MWT (at baseline or at 6-month follow-up) and the 6MWTs at 18-, 30-,
42-, 54-, and 66-month visit of 165 consecutive SSc patients without ILD and PAH, included in the Ghent University
Systemic Sclerosis Cohort between May 2006 and December 2016 were analysed.
Results: The mean 6MWD during the baseline 6MWT of 165 SSc patients without ILD and PAH (35% limited SSc, 56%
limited cutaneous SSc, 9% diffuse cutaneous SSc) was 484.20+/-92.65m with no significant difference in the distance
walked at different follow-up visits as compared to baseline. 96-100% of the SSc patients without ILD and PAH performed a
6MWT during the different follow-up visits.
Conclusion: In SSc without ILD and PAH, the 6MWT is feasible and the 6MWD is clinically stable over a 66 months
period. A 6MWT performed at the time of SSc diagnosis may be used as a reference 6MWD for those SSc patients who
develop ILD or PAH during follow-up.
Table 1. Baseline characteristics of 165 SSc without ILD and PAH.

Characteristic N
Age (years) ° 165 48.02+/-13.19
♀/♂ * 165 124/41 (75.2/24.8)
Raynaud * 165 162 (98.2)
Disease duration since 162 60 (20-176)
first Raynaud (months)#
Disease duration since 137 26 (10-74)
first non-Raynaud
(months)#
LSSc/LcSSc/DcSSc * 165 58/92/15
(35.2/55.8/9.1)
mRSS # 165 3 (0-7)
DAS # 162 0.5 (0-1.5)
HAQ # 141 0.25 (0.00-0.63)
AntiScl70 AB * 165 16 (9.7)
ACA * 165 100 (60.6)
FVC (%pred) # 165 113 (99-126)
DLCO (%pred) # 165 77 (69-88)
Peak TVR (m/s) # 131 2.3 (2.1-2.4)
6MWD (m) ° 165 484.20+/-92.65
°: mean+/-SD, *: n (%), #: median (IQR), mRSS: modified Rodnan Skin Score, DAS: disease activity score, HAQ: health
assessment questionnaire, AntiScl70 AB: anti-topoisomerase I antibodies, ACA: anti-centromere antibodies, FVC: forced
vital capacity, expressed as % of the predicted value, DLCO: diffusing capacity of the lung for carbon monoxide, expressed
as % of the predicted value, Peak TVR: peak tricuspid valve regurgitation velocity, m/s: meter per second, 6MWD: six-
minute walk distance.
Table 2. Evolution of the 6MWD from baseline to the different follow-up visits
N N Tx 6MWD T0 (m) 6MWD Tx(m) Pearson’s Mean Difference P
6MWT visit correlation(95%CI) (m)
mean+/-SD mean+/-SD coefficient
T0 vs 130 130 487.13+/-94.41487.95+/-96.30 0.817 0.82 (-9.19; 0.871
T18 10.83)
T0 vs 98 101 490.62+/-90.31488.07+/-85.98 0.745 -2.55 (-15.20; 0.690
T30 10.10)
T0 vs 77 80 481.56+/-95.56466.52+/-105.490.694 -15.04 (-33.01; 0.100
T42 2.93)
T0 vs 65 68 480.79+/-97.47480.86+/-102.530.765 0.08 (-16.96; 0.993
T54 17.12)
T0 vsT6646 46 480.37+/-90.25483.74+/-95.85 0.564 3.37 (-22.49; 0.794
29.23)
N 6MWT: number of patients performing a six-minute walk test, N Tx visit: number of patients having a follow-up visit at
month x, 6MWD: six-minute walk distance, T0: baseline visit, Tx: x-month visit, m: meter, SD: standard deviation, CI:
confidence interval
Disclosure: E. Vandecasteele, None; K. Melsens, None; F. De Keyser, None; M. De Pauw, None; E. Deschepper, None;
S. Decuman, None; Y. Piette, None; K. Thevissen, None; G. Brusselle, None; V. Smith, Fund for Scientific Research
Flanders, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/role-of-the-six-minute-walk-test-in-

systemic-sclerosis-five-years-evolution

The Histone Demethylase Jumonji Domain-Containing Protein 3 (JMJD3) As
Central Mediator of Fibroblast Activation
Christina Bergmann1, Amelie Brandt1, Clara Dees2, Yun Zhang3, Chih-Wei Chen4, Tatjana Mallano5, Thomas Wohlfahrt6,
Ruifang Liang7, Rosebeth Kagwiria1, Aline Bozec8, Ralf Rieker9, David Abraham10, Andreas Ramming11, Oliver Distler12,
Georg Schett13 and Jörg Distler14, 1Department of Internal Medicine 3 and Institute for Clinical Immunology, Friedrich-
Alexander-University of Erlangen-Nuremberg and University Hospital Erlangen, Erlangen, Germany, 2Department of
Internal Medicine 3 and Institute for Clinical Immunology,, Friedrich-Alexander-University Erlangen-Nürnberg (FAU),
Erlangen, Germany, 3Department of Internal Medicine 3 and Institute for Clinical Immunology, Department of Internal
Medicine 3 and Institute for Clinical Immunology, Friedrich-Alexander-University of Erlangen-Nuremberg and University
Hospital Erlangen, Erlangen, Germany, 4Department of Internal Medicine 3 – Rheumatology and Immunology, Friedrich-
Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen, Erlangen, Germany, Erlangen, Germany,
5Department of Internal Medicine 3 – Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg
(FAU) and University Hospital Erlangen, Erlangen, Germany, 6Department of Internal Medicine 3, Rheumatology and
Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen, Erlangen,
Germany, 7Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen,
Department of Internal Medicine 3 and Institute for Clinical Immunology, Friedrich-Alexander-University of Erlangen-
Nuremberg and University Hospital Erlangen, Erlangen, Germany, 8Department Clinic of Medicine 3 - Immunology und
Rheumatology, University of Erlangen-Nürnberg, Department Clinic of Medicine 3 - Immunology and Rheumatology,
Erlangen, Germany, Erlangen, Germany, 9Department of Pathology, University Clinic Erlangen, Erlangen, Germany,
10Centre for Rheumatology and Connective Tissue, UCL School of Life and Medical Sciences, London, London, United
Kingdom, 11Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany, 12Department of

Rheumatology, University Hospital Zurich, Zurich, Switzerland, 13Department of Internal Medicine 3 – Rheumatology and
Immunology, Department of Internal Medicine 3 and Institute for Clinical Immunology, Friedrich-Alexander-University of
Erlangen-Nuremberg and University Hospital Erlangen, Erlangen, Germany, 14Department of Internal Medicine 3 –
Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU),
Erlangen, Germany
SESSION INFORMATION
Session Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's – Pathogenesis, Animal Models and Genetics Poster
I
Background/Purpose:
Epigenetic modifications are key drivers of chronic fibroblast activation. Trimethylation of histone 3 at lysine residue K27
(H3K27me3) is a repressive modification, that is implicated in fibroblasts activation. Inhibition of H3K27 trimethylation
promotes fibroblast activation. However, the role of H3K27me3 demethylases in fibrosing disorders has not been
characterized. The aim of this study is to characterize the role of JMJD3 in as potential drug target in fibrotic disease.
Methods:
siRNA mediated knockdown and GSKJ4 were used to target JMJD3 in vitro and in vivo. Fibroblast activation was analyzed
by quantifying collagen synthesis and release, stress fiber formation and by scratch assays. The effects of GSKJ4 on
experimental fibrosis were assessed in the Topoisomerase I-mouse model of skin and lung fibrosis and in Bleomycin-
induced skin fibrosis. Inflammatory infiltrates in the skin were assessed by immunofluorescence staining. H3K27me3 of
target genes was analyzed by ChIP.
Results: We demonstrated increased expression of JMJD3 in fibrotic diseases with increased expression of JMJD3 in the
skin of SSc patients and in tissue from patients with liver fibrosis and idiopathic pulmonary fibrosis compared to healthy
controls. The overexpression was particularly pronounced in fibroblasts. JMJD3 was also overexpressed in dermal and
pulmonary fibrosis in TopoI-induced fibrosis and in bleomycin-induced skin fibrosis. Targeting JMJD3 in vitro ameliorated
the activated fibroblast phenotype with decreased collagen release and reduced expression of myofibroblast markers. By
screening for several profibrotic pathways, we identified FRA2 as central downstream mediator of JMJD3 mediated
fibroblast activation. H3K27me3 at the FRA2 promoter was reduced by TGFβ stimulation, which resulted in increased
expression of FRA2. Treatment with GSKJ4 prevented the TGFβ-induced downregulation of H3K27me3 at the FRA2
promoter. The functional importance of FRA2 for JMJD3 regulated fibroblast activation was further highlighted by
knockdown studies: Upon knockdown of FRA2, GSKJ4 loses its inhibitory function on collagen secretion. In vivo, we
observed potent antifibrotic effects of JMJD3 inhibition on dermal and pulmonary fibrosis with reduced fibrotic tissue
remodeling, decreased collagen content and impaired differentiation of resting fibroblasts into myofibroblasts. As GSKJ4
treatment had no effect on B- cell counts in experimental fibrosis. However, GSKJ4 treatment resulted in a slight reduction
of T-cell counts.
Conclusion:
We present first evidence for a dysregulation of JMJD3 in SSc. JMJD3 regulates fibroblast activation by modulating the
levels of H3K27me3 at the FRA2 promoter. Targeted inhibition of JMJD3 reduces the aberrant activation of SSc fibroblasts
and has strong antifibrotic effects in murine models of SSc.
Disclosure: C. Bergmann, None; A. Brandt, None; C. Dees, None; Y. Zhang, None; C. W. Chen, None; T. Mallano,
None; T. Wohlfahrt, None; R. Liang, None; R. Kagwiria, None; A. Bozec, None; R. Rieker, None; D. Abraham, None;
A. Ramming, None; O. Distler, 4 D Science, Actelion, Active Biotec, Bayer, Biogen Idec, Boehringer Ingelheim Pharma,
BMS, ChemomAb, EpiPharm, Ergonex, espeRare foundation, GSK,Roche-Genentech, Inventiva, Lilly, medac,
MedImmune, Mitsubishi Tanabe, Pharmacyclics, Pfizer, Sanofi, Seroda, 2; G. Schett, None; J. Distler, 4D Science,
1,Anamar Medical, Active Biotech, Array Biopma, BMS, Bayer Pharma, Boehringer Ingelheim, Celgene, GSK, Novartis,
Sanofi-Aventis, UCB, 2,Actelion Pharmaceuticals US, Active Biotech, Anamar, Bayer Pharma, Boehringer Ingelheim,
Celgene, Galapagos, GSK, Inventiva, JB Therapeutics, Medac, Pfizer, RuiYi, UCB, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-histone-demethylase-jumonji-

domain-containing-protein-3-jmjd3-as-central-mediator-of-fibroblast-activation
Interferon Siganture in Systemic Sclerosis Lung Microvascular Endothelial

Cells
Fabian A Mendoza1, Sonsoles Piera-Velazquez2, Peter J. Wermuth3, Sankar Addya4, Carol A. Feghali-Bostwick5 and
Sergio A. Jimenez6, 1Rheumatology Division, Department of Medicine, Thomas Jefferson University, Jefferson Institute of
Molecular Medicine and Scleroderma Center, Thomas Jefferson University, Philadelphia, PA, 2Jefferson Institute of
Molecular Medicine and Scleroderma Center., Thomas Jefferson University, Philadelphia, PA, 3Jefferson Institute of
Molecular Medicine, Division of Connective Tissue Diseases and Scleroderma Center, Thomas Jefferson University,
Philadelphia, PA, 4Kimmel Cancer Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA,
5Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC, 6Scleroderma Center
and Jefferson Institute of Molecular Medicine, Thomas Jefferson Univ, Philadelphia, PA
SESSION INFORMATION
I
Background/Purpose:
Systemic Sclerosis (SSc) is characterized by severe fibroproliferative vasculopathy, exaggerated deposition of extracellular
matrix molecules (ECM) in skin and multiple internal organs, and alterations of humoral, cellular and innate immunity.
Vascular changes are responsible for the earliest SSc clinical manifestations; however the mechanisms responsible have not
been elucidated.
The goal of this study was to analyze the gene expression differences between normal and SSc lung microvascular
endothelial cells (EC) to improve the understanding of SSc vasculopathy pathophysiology.
Methods:
Pulmonary microvascular EC were isolated employing immunomagnetic procedures from lungs from patients with SSc
undergoing lung transplantation. Control EC were isolated from autopsies of individuals who died from non-related
pulmonary causes. Following isolation, microarrays were performed in EC from each group. Expression of genes with the
highest differential expression was validated with RT-PCR, Western blots and confocal laser microscopy.
Results:
Interferon-stimulated genes (ISGs) including IFI44L, IFI44, IFI6, IFIH1, IFIT1, displayed the highest differential
expression; being overexpressed in EC obtained from SSc donors. Others genes such as those encoding ECM production
related proteins, genes associated with post-translational methylation and genes for numerous chemokines were also
differentially overexpressed in SSc EC. Increased gene expression and increased protein levels of selected ISGs were
confirmed by Western blots and confocal laser microscopy.
Conclusion:
Numerous ISGs are differentially overexpressed in SSc pulmonary microvascular EC in comparison with normal control
EC. These results suggest that events leading to an interferon response in these cells may play a role in the pathogenesis of
SSc lung vasculopathy.
References
1. Kahaleh B. Vascular Disease in Scleroderma: Mechanisms of Vascular Injury. Rheumatic Disease Clinics of North
America 2008; 34:57–71.
2. Trojanowska M. Cellular and molecular aspects of vascular dysfunction in systemic sclerosis. Nat Rev Rheumatol 2010;
6:453–60.
3. Matucci-Cerinic M, Kahaleh B, Wigley FM. Review: evidence that systemic sclerosis is a vascular disease. Arthritis and
rheumatism 2013; 65:1953–62.
4. Pattanaik D, Brown M, Postlethwaite BC, Postlethwaite AE. Pathogenesis of Systemic Sclerosis. Frontiers in
immunology 2015; 6:272.
Disclosure: F. A. Mendoza, None; S. Piera-Velazquez, None; P. J. Wermuth, None; S. Addya, None; C. A. Feghali-
Bostwick, None; S. A. Jimenez, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/interferon-siganture-in-systemic-

sclerosis-lung-microvascular-endothelial-cells
Genome-Wide DNA Methylation Pattern in Systemic Sclerosis Microvascular

Endothelial Cells: Identification of Epigenetically Affected Key Genes and
Pathways
Shadia Nada1, Ibtissam Gad2, Ali Alqahtani3, Ahmad Assaly2, Sadik Khuder4, Yongqing Wang5, Bashar Kahaleh1 and
Nezam Altorok1, 1Medicine/Rheumatology, University of Toledo, Toledo, OH, 2University of Toledo, Toledo, OH,
3Internal Medicine, University of Toledo, Toledo, OH, 4Department of Medicine, University of Toledo, Toledo, OH,
5Medicine, University of Toledo, Toledo, OH
SESSION INFORMATION
I
Background/Purpose: The etiology of systemic sclerosis (SSc) is not clear, but there is evidence suggesting a critical role
for epigenetic alterations in disease pathogenesis and clinical expression. We sought in this study to characterize the genome
wide DNA methylation signature in SSc Microvascular Endothelial Cells (MVECs).
Methods: We performed a genome-wide DNA methylation study in MVECs derived from 7 diffuse cutaneous SSc (dSSc)
patients compared to 7 age, sex, and ethnicity-matched healthy controls. Cytosine methylation was quantified across the
genome. We divided samples from patients and controls in two groups of matched SSc subjects and controls. Differentially
methylated CpG sites between patients and controls were identified by fold difference in methylation level ≥ 1.2, and false
discovery rate (FDR) adjusted P value <0.01. Moreover, quantitative real-time RT-PCR was performed to assess the
correlation between DNA methylation and gene expression levels in selected genes.
Results: We identified 71,353 differentially methylated CpG sites in SSc-MVECs using Infinium MethylationEPIC
microarray in the first group (0.081% of representative probes), and 33,170 CpG sites in the second group using
HumanMethylation 450 microarray (0.073% of representative probes) in dcSSc-MVEC. Among the two groups of subjects,
we identified differential methylation of 2,455 CpG sites, representing 1,301 genes. Most of the differentially methylated
CpG sites were hypermethylated (1,625 CpG), corresponding to 910 genes. There were 830 hypomethylated CpG sites,
representing 485 genes. Common Hypermethylated genes in SSc MVECs include NOS1, which encodes for nitric oxide
synthase -1, DNMT3A, DNMT3B, HDAC4 and ANGPT2. We also identified hypomethylation of IL17RA, CTNNA3, ICAM2
and SDK1in SSc MVECs. Furthermore, we demonstrate significant inverse correlation between DNA methylation status and
gene expression in the majority of genes evaluated.
Gene ontology analysis of hypermethylated genes demonstrated enrichment of genes involved in homophilic cell adhesion
via plasma membrane adhesion molecules (P= 2.10E-07) and angiogenesis (P= 0.0006). Pathway analysis of
hypomethylated genes includes genes involved in Wnt signaling pathway (P= 0.001), vascular smooth muscle contraction
(P= 0.014) and adherens junctions (P 0.013).
Conclusion : Our data suggest the presence of significant genome-wide DNA methylation aberrancies in SSc-MVEC, and
identify novel affected genes and pathways in SSc MVECs.
Disclosure: S. Nada, None; I. Gad, None; A. Alqahtani, None; A. Assaly, None; S. Khuder, None; Y. Wang, None; B.
Kahaleh, None; N. Altorok, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/genome-wide-dna-methylation-pattern-

in-systemic-sclerosis-microvascular-endothelial-cells-identification-of-epigenetically-affected-key-genes-and-pathways
Novel Machine Learning Classifier Accurately Predicts Intrinsic Molecular

Subsets for Patients with Systemic Sclerosis
Jennifer Franks1, Viktor Martyanov1, Guoshuai Cai1 and Michael L. Whitfield2, 1Department of Molecular and Systems
Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, 2Molecular and Systems Biology, Geisel School of
Medicine at Dartmouth, Hanover, NH
SESSION INFORMATION
I
Background/Purpose: High-throughput gene expression profiling of skin biopsies from patients with systemic sclerosis
(SSc) has identified four “intrinsic” gene expression subsets conserved across multiple cohorts and tissues. These are the
inflammatory, fibroproliferative, normal-like, and limited subsets. In order to classify patients in clinical trials or for
diagnostic purposes, supervised methods that can assign a single sample to a molecular subset are required. Here, we
introduce a novel machine learning classifier which is a robust predictor of intrinsic subset and test it on multiple
independent patient cohorts.
Methods: Three independent SSc cohorts (Milano et al. 2008, Pendergrass et al. 2012, Hinchcliff et al. 2013) with gene
expression data and intrinsic subset assignments were carefully curated and merged to create a training dataset covering a
broad set of 297 skin biopsies representing 97 unique patients. Supervised machine learning algorithms were rigorously
trained and evaluated using repeated three-fold cross-validation. We performed external validation using two independent
SSc datasets: Chakravarty et al. 2015, which contains 16 samples/8 patients and Gordon et al. 2015, which contains 12
samples/6 patients. Additionally, we validated the classifier on a cohort of SSc patients with gene expression data
independently generated by Assassi et al. 2015 (102 samples/97 patients). We used weighted gene co-expression network
analysis and g:Profiler to identify and functionally characterize gene modules associated with the intrinsic subsets.
Results: Repeated cross-fold validation identified gene expression features using multinomial elastic net and incorporated
them into the final model which achieved an average classification accuracy of 88%. All molecular subsets were classified
with high average sensitivity and specificity, particularly inflammatory (83.3% sensitivity, 95.8% specificity) and
fibroproliferative (89.7% sensitivity, 94.1% specificity). Through multiple rounds of external validation, the classifier
maintained an accuracy ranging from 70% to 85%. In a re-analysis of gene expression data from Assassi et al. study, we
identified subsets of patients that represent the canonical inflammatory, fibroproliferative, and normal-like subsets. The
inflammatory subset showed upregulated gene modules enriched in biological processes such as inflammatory response,
lymphocyte activation, and stress response. Similarly, gene modules enriched for cell cycle processes were increased in the
fibroproliferative subset.
Conclusion: We have developed a highly accurate and reliable classifier for SSc molecular subsets for single samples
trained and tested on diverse cohorts comprised of 427 skin biopsies from 208 independent patients. These analyses show
that the intrinsic gene expression subsets are a common feature of SSc found across multiple internal and external validation
cohorts. Machine learning methods provide a robust and accurate mechanism for stratifying intrinsic gene expression subsets
and can be used to aid clinical decision-making and interpretation for SSc patients and in clinical trials.
Disclosure: J. Franks, None; V. Martyanov, None; G. Cai, None; M. L. Whitfield, Corbus, UCB, glaxosmithkline,
5,Celdara medical llc, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/novel-machine-learning-classifier-

accurately-predicts-intrinsic-molecular-subsets-for-patients-with-systemic-sclerosis
Plasmacytoid Dendritic Cells Activated through TLR8 Promote Systemic

Sclerosis
Marie-Dominique Ah Kioon1, Claudio Tripodo2, Alexandra Morquette3, Robert F. Spiera3, Jessica K. Gordon3 and Franck
J. Barrat1, 1Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY, 2Department of Health
Science, Human Pathology, tumor immunology unit, Palermo, Italy, 3Rheumatology, Hospital for Special Surgery, New
York, NY
SESSION INFORMATION
I
Background/Purpose:
Plasmacytoid Dendritic Cells (PDCs) are the key cell type mediating TLR-induced inflammation in several autoimmune
diseases such as lupus, dermatomyositis, lichen sclerosus and cutaneous GVHD. In these diseases, PDC infiltrate the skin
and produce IFNα, contributing to cutaneous lesions. In lupus, IFNα production was due to TLR7 and -9 recognition of
endogenous RNA and DNA respectively. PDCs may also be part of the pathogenesis of systemic sclerosis (SSc). PDCs
traffic to the skin in a mouse model of stiff skin syndrome. Moreover PDCs from SSc patients secrete CXCL4 and their
levels in the serum correlated with skin and pulmonary disease. Although it is well described that PDC infiltrate the skin
following injury or in diseases, little is known about what is controlling PDC trafficking and subsequent activation in the
skin or whether PDCs can play a role in promoting/sustaining inflammation-related fibrosis. The aim of our study was to
identify the nature of PDC activation in SSc patients, the role of TLRs or the impact of CXCL4 on PDC response.
Methods:
For the human studies, blood was obtained from 87 SSc patients and 23 healthy volunteers (HV), and PBMCs were isolated
by density gradient. PDC were then isolated from PBMC by positive selection with BDCA4 magnetic beads or by cell
sorting. In mice, fibrosis was induced by sub-cutaneous injection of bleomycin (BLM) in WT and transgenic mice
expressing human TLR8 (Tg8).
Results: Aberrant expression of TLR8 was observed on SSc PDCs while absent on HV. TLR8 activation in SSc PDCs
significantly induced CXCL4 secretion (p=0.003) compared to unstimulated PDC while TLR9 induction had no effect
(p=0.5). TLR8 activation led to an increase secretion of IFNα and pro-inflammatory IL-6 and TNF. CXCL4 further
increased TLR8-induced IFNα production by PDC (3-fold) (1393±153pg/ml for TLR8-induced PDC vs 5003±747pg/ml for
CXCL4+TLR8-induced PDC) while it had no effect on IL-6 (1390±129pg/ml vs 1365±100pg/ml) and TNF production
(3404±241pg/ml vs 3251±207pg/ml). In mice, following BLM treatment, a significant increase in skin thickness was
observed in WT mice (200±6mm vs 357±3mm, p<0.0001) and further increased in Tg8 mice (396±5mm, p=0.04 vs WT
BLM). Moreover, PDCs accumulation was observed in the skin of WT BLM mice as compared to WT PBS as assessed by
in situ analysis of SiglecH positive cells. PDCs infiltration were further enhanced in the skin of Tg8 mice (p=0.0008) as well
as enhanced expression of IFN related genes, IP10 (p=0.006), IFIT2 and IFI35 (p=0.03).
Conclusion: Taken together our data demonstrate that the secretion of CXCL4 is due to the aberrant presence of TLR8 on
PDCs of SSc patients, and that CXCL4 contributes to excessive IFNα response by TLRs. In mice, TLR8 exacerbates fibrosis
due to an increased PDC infiltration in the skin.
Disclosure: M. D. Ah Kioon, None; C. Tripodo, None; A. Morquette, None; R. F. Spiera, None; J. K. Gordon, None; F.
J. Barrat, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/plasmacytoid-dendritic-cells-activated-

through-tlr8-promote-systemic-sclerosis
Identification of Biomarkers Predictive of Pulmonary Arterial Hypertension

in Systemic Sclerosis
Kathleen D. Kolstad1, Tyson Holmes2, Yael Rosenberg-Hasson2, Andrew Sweatt3, Roham T. Zamanian4, Shufeng Li5,
Virginia D. Steen6, Paul J. Utz7 and Lorinda Chung8, 1Rheumatology, Stanford University Medical Center, Stanford, CA,
2Stanford University Medical Center, Stanford, CA, 3Medicine, Division of Pulmonary and Critical Care, Stanford
University Medical Center, Stanford, CA, 4Stanford University Medical Center, Palo Alto, CA, 5Dermatology, Stanford
University School of Medicine, Stanford, CA, 6Rheumatology, MedStar Georgetown University Hospital, Washington, DC,
7Medicine, Stanford University School of Medicine, Stanford, CA, 8Rheumatology, Stanford University Medical Center,
Palo Alto, CA
SESSION INFORMATION
I
Background/Purpose: Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular abnormalities, immune
system dysregulation, and fibrosis. Pulmonary arterial hypertension (PAH) affects approximately 10% of SSc patients and is
a leading cause of death. We sought to identify cytokines predictive of progression to PAH in SSc.
Methods: Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) is a prospective
registry that includes SSc patients at high risk for PAH based on pulmonary function test and echocardiographic parameters.
Serum was available from 38 high-risk patients for this study. Baseline characteristics were assessed at the time of serum
acquisition. Kaplan-Meier estimates were generated for time to PAH from first non-RaynaudÕs Phenomenon (RP)
symptom. The Luminex (eBioscience) immunoassay (Human 62-plex) was used for serum cytokine profiling. Missing data
were multiply imputed to generate 60 complete datasets. Using multivariable Cox regression, time to PAH was regressed on
a candidate predictor set consisting of all cytokines' preprocessed median fluorescence intensities and four clinical covariates
which had previously been shown to be associated with progression to PAH in the PHAROS cohort (exercise induced O2
saturation, % predicted diffusing capacity for carbon monoxide (DLCO), forced vital capacity/DLCO, systolic pulmonary
artery pressure on echocardiogram) (1). Regression coefficients were estimated by five-fold cross-validated, likelihood-
based boosting.
Results: Baseline characteristics are shown in Table 1. At 1, 5,10, 15, and 20 years after first non-RP symptoms, the rate of
progression to PAH in this high-risk population was 3%, 5%, 15%, 18%, and 31% respectively. Elevated levels of IL-1Beta
(Figure 1) and IL-15 (not shown) correlated with an increased risk of progression to PAH.
Conclusion: These preliminary results identified IL-1Beta and IL-15 as potential biomarkers associated with progression to
PAH in SSc. These may be useful in identifying high-risk patients who warrant early referral to right heart catheterization,
and may provide further insight into the mechanism of disease. We plan to validate our findings in an independent cohort.
1) Hsu et al. Development of pulmonary hypertension in a high-risk population with systemic sclerosis in the Pulmonary
Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) cohort study. Semin Arthritis Rheum.
2014;44(1):55-62.
Disclosure: K. D. Kolstad, None; T. Holmes, None; Y. Rosenberg-Hasson, None; A. Sweatt, None; R. T. Zamanian,
None; S. Li, None; V. D. Steen, None; P. J. Utz, None; L. Chung, Cytori, Actelion, Reata, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/identification-of-biomarkers-predictive-

of-pulmonary-arterial-hypertension-in-systemic-sclerosis

Multi Dimensional Analysis of the Immunome in Systemic Sclerosis Reveals
Functionally Related Abnormalities in MAIT and B Cell Compartments
Bhairav Paleja1, Pavanish Kumar1, Suzan Saidin1, Ahmad Lajam2, Camillus Chua1, Liyun Lai1, Andrea Hsiu Ling Low2
and Salvatore Albani1, 1SingHealth Translational Immunology and Inflammation Centre (STIIC), Duke-NUS Medical
School, Singapore, Singapore, 2Singapore General Hospital, Singapore, Singapore
SESSION INFORMATION
I
Background/Purpose:
Systemic sclerosis (SSc) is an autoimmune disease characterised by excessive fibrosis of skin and internal organs, and
vascular dysfunction. Association of T and B cell subsets have been reported in SSc, however there is lack of systematic
studies of functional relations between immune cell subsets in this disease. This lack of mechanistic knowledge hampers
targeted intervention. In the current study we sought to determine differential immune cell composition and heterogeneity in
peripheral blood of SSc patients compared to healthy controls.
Methods:
SSc patients fulfilling ACR 2013 criteria (n=20, of whom 10 were of diffuse cutaneous subtype; 10 had interstitial lung
disease) and healthy controls (n=10) were included. Mononuclear cells from blood were analysed by mass cytometry using a
36 marker (cell-surface and intracellular) panel to aid in identification of major PBMC lineages including T cells, B cells,
monocytes and NK cells and their subsets. Unsupervised clustering of mass cytometry data was performed using in-house
developed analysis software MARVIS. This software combines dimension reduction and clustering steps to identify all
possible cellular subsets. Further, custom R scripts helped in identifying nodes that were differentially expressed between the
study groups and also phenotype of these nodes.
Results:
Unsupervised clustering performed revealed significant differences in the frequencies of T cell and B cell subsets. Most
strikingly we identify a 3 fold decrease in frequencies of Va7.2+ CD161+ mucosal associated invariant T cells (MAIT) in
SSc patients and 2 fold increase in total B cells, particularly CD19+ CD27- naive cells. A subset of memory CD8+ T cell,
expressing CXCR3 was found to be increased in SSc patients as compared to healthy controls. Transcriptome analysis of
sorted B cell and T cell subsets showed decrease in genes related to survival and increased expression of apoptotic genes in
CD4,CD8 T and MAIT cells from SSc patients. Interestingly, high expression of CXCR3 gene was observed in
transcriptome analysis of CD8+ T cells from SSc patients.
Conclusion:
This study provides an in depth analysis of systemic immune composition in SSc with the potential to delineate mechanisms
of pathogenesis and identify diagnostic and/or therapeutic targets. This is the first demonstration of dysfunction of MAIT
cells in SSc and further characterisation of their function in this context is required.
Disclosure: B. Paleja, None; P. Kumar, None; S. Saidin, None; A. Lajam, None; C. Chua, None; L. Lai, None; A. H. L.
Low, None; S. Albani, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/multi-dimensional-analysis-of-the-

immunome-in-systemic-sclerosis-reveals-functionally-related-abnormalities-in-mait-and-b-cell-compartments
Antisense Long Noncoding RNA HAND2-AS1 and OTUD6B-AS1 Have

Important Roles in the Pathogenesis of Systemic Sclerosis
Miki Takata1, Elena Pachera1, Anastasiia Kozlova1, Astrid Jüngel1, Tobias Messemaker2, Jeska de Vries-Bouwstra2, Tom
W.J. Huizinga3, Fina Kurreeman2 and Oliver Distler4, 1Department of Rheumatology, Center of Experimental
Rheumatology, University Hospital Zurich, Zurich, Switzerland, Zurich, Switzerland, 2Department of Rheumatology,
Leiden University Medical Center, Leiden, Netherlands, Leiden, Netherlands, 3Department of Rheumatology, LUMC,
Leiden, Netherlands, Leiden, Netherlands, 4Department of Rheumatology, Center of Experimental Rheumatology,
University Hospital Zurich, Zurich, Switzerland
SESSION INFORMATION
I
Background/Purpose: Long noncoding RNAs (lncRNAs) represent a class of transcripts longer than 200 nucleotides that
are not translated into proteins. In recent years, antisense (AS) lncRNAs have increasingly been recognized as important
regulators of their sense genes and they have been found to play key roles in the pathogenesis of several diseases. However,
the role of AS lncRNAs in SSc is still unknown. Our previous study identified two AS lncRNAs in SSc skin biopsies
namely HAND2-AS1 and OTUD6B-AS1. Here we aim to characterize the functional relevance of these AS lncRNAs.
Methods: Sense and AS gene expression was analyzed by qPCR in RNA samples of HC and SSc dermal fibroblasts (Fb).
Dermal Fb were stimulated with different profibrotic cytokines and growth factors like TGFβ, PDGF and IL-4 at
physiological concentrations. Function of AS lncRNAs was analyzed by qPCR and Western Blot (WB) in HC dermal Fb and
human pulmonary artery smooth muscle cells (HPASMC) transfected with locked nucleic acid antisense oligonucleotides
(LNA GapmeRs).
Results: RNA sequencing analysis of skin biopsy revealed consistent and significant downregulation of HAND2-AS1 and
OTUD6B-AS1 expression. In SSc and HC dermal Fb, no difference was recorded in the basal level of HAND2-AS1,
HAND2, OTUD6B-AS1 and OTUD6B expression. However, HAND2 and HAND2-AS1 expression in SSc dermal Fb was
significantly downregulated after TGFβ and IL-4 stimulation (n=4-5, p<0.05, up to 0.09 fold reduction). HAND2-AS1
expression was also significantly downregulated after PDGF stimulation (n=4, p<0.05, up to 0.12 fold reduction) and
HAND2 expression had the same trend. OTUD6B expression in SSc dermal Fb was significantly downregulated after PDGF
stimulation (n=7, p<0.05, up to 0.16 fold reduction) and OTUD6B-AS1 expression was also decreased. OTUD6B-AS1
expression was significantly downregulated after IL-4 stimulation (n=4, p<0.05, up to 0.52 fold reduction). Importantly,
HAND2-AS1 knockdown significantly reduced collagen 1A1, fibronectin and α-smooth muscle actin (αSMA) mRNA in
dermal Fb (p<0.05). Downregulation of fibronectin expression was also confirmed after HAND2-AS1 knockdown by WB
analysis (n=4). In contrast to HAND2-AS1, OTUD6B-AS1 knockdown did not affect extracellular matrix production.
However, we observed effects on cell cycle regulation after OTUD6B-AS1 knockdown. OTUD6B-AS1 knockdown in Fb
and HPASMC significantly increased OTUD6B, and cell cycle regulators c-MYC, Cyclin D1 and Cyclin D2 mRNA (n=6,
p<0.05). Upregulation of OTUD6B, c-MYC and Cyclin D1 in HPASMC was also confirmed after OTUD6B-AS1
knockdown by WB analysis (n=2).
Conclusion: This is the first report analyzing the functional role of AS lncRNAs in SSc. These results point to an important
role of HAND2-AS1 in extracellular matrix production and of OTUD6B-AS1 in cell cycle progression.
Disclosure: M. Takata, None; E. Pachera, None; A. Kozlova, None; A. Jüngel, None; T. Messemaker, None; J. de
Vries-Bouwstra, None; T. W. J. Huizinga, None; F. Kurreeman, None; O. Distler, Actelion, 5,Bayer, 5,Biogen Idec,
5,Boehringer Ingelheim, 5,ChemomAb, 5,espeRare Foundation, 5,Genentech/Roche, 5,GlaxoSmithKline, 5,Inventiva,
5,Lilly, 5,Medac, 5,MedImmune, 5,Mitsubishi Tanabe Pharma, 5,Pharmacyclics, 5,Novartis Pharmaceutical Corporation,
5,Pfizer Inc, 5,Sanofi, 5,Sinoxa, 5,UCB in the area of potential treatments of scleroderma and its complications, 5,Patent
mir-29 for the treatment of systemic sclerosis licensed, 5,Actelion, 2,Bayer, 2,Biogen Idec, 2,Boehringer Ingelheim,
2,ChemomAb, 2,espeRare Foundation, 2,Genentech/Roche, 2,GlaxoSmithKline, 2,Inventiva, 2,Lilly, 2,Medac,
2,Medimmune, 2,Mitsubishi Tanabe Pharma, 2,Pharmacyclics, 2,Novartis, 2,Pfizer Inc, 2,Sanofi, 2,Sinoxa, 2,UCB in the
area of potential treatments of scleroderma and its complications, 2,Patent mir-29 for the treatment of systemic sclerosis
licensed, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/antisense-long-noncoding-rna-hand2-

as1-and-otud6b-as1-have-important-roles-in-the-pathogenesis-of-systemic-sclerosis
Increased Expression of the TNF Superfamily Member LIGHT/TNFSF14 and

Its Receptor (TNFRSF14) in Patients with Systemic Sclerosis
Otylia Kowal-Bielecka1, Ewa Gindzienska-Sieskiewicz1, Oliver Distler2, Joanna Reszec3, Suzana Jordan2, Pawel
Bielecki4, Andzrzej Sieskiewicz4, Agnieszka Sulik1 and Krzysztof Kowal5,6, 1Department of Rheumatology and Internal
Medicine, Medical University of Bialystok, Bialystok, Poland, 2Department of Rheumatology, University Hospital Zurich,
Zurich, Switzerland, 3Department of Medical Pathomorphology, Department of Medical Pathomorphology, Medical
University of Bialystok, Bialystok, Poland, 4Department of Otolaryngology, Medical University of Bialystok, Bialystok,
Poland, 5Department of Allergology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland,
6Department of Experimental Allergology and Immunology, Medical University of Bialystok, Bialystok, Poland
SESSION INFORMATION
I
Background/Purpose: The TNF Superfamily member LIGHT (TNFSF14) regulates immune response and angiogenesis.
Moreover, recent studies indicate that interactions of LIGHT with its receptor, TNFRSF14, might also play a role in
regulation of tissue remodeling. Since autoimmunity, vascular injury and fibrosis are key elements of the pathogenesis of
systemic sclerosis (SSc) we hypothesized that LIGHT might be involved in development of SSc. This study was aimed to
assess potential role of LIGHT in SSc through evaluation of: 1). expression of LIGHT and its receptor, TNFRSF14, in skin
biopsies and 2) associations between serum concentration of LIGHT and clinical features in SSc patients.
Methods: Expression of LIGHT and its receptor, TNFRSF14, was investigated by means of immunohistochemistry, and
evaluated semiquantitatively (score from 0 to 3), in skin biopsies from 18 SSc patients and 9 healthy controls. Serum levels
of LIGHT were measured using commercially available ELISA kits in 320 patients with SSc and 50 control subjects.
Results: Expression of both, LIGHT and TNFRSF14 was significantly higher in skin biopsies from SSc patients as
compared with healthy controls (p<0.05). Patients with early SSc (</= 3 years from the first non-Raynaud’s phenomenon,
n=13) showed significantly higher skin expression of TNFRSF14 (p<0.05) and tended to have greater skin expression of
LIGHT (p=0.06) as compared with SSc patients with longer disease (n=5).
The mean serum concentration of LIGHT was significantly higher in SSc patients as compared with the controls (p<0.05).
Moreover, mean serum concentration of LIGHT was significantly higher in SSc patients with digital ulcers (DUs) as
compared with SSc patients without DUs, patients without anti-centromere antibodies (ACA) as compared with those with
ACA, patients with muscle involvement (defined by elevated serum CK levels) compared with patients without CK
elevation and in patients receiving steroids, as compared with those without steroid therapy (p<0,05 for all comparisons). In
addition, the mean concentration of LIGHT was significantly higher in male patients as compared with female SSc patients
(p<0,05). There were also statistically significant (p<0.05) although very weak correlations between serum concentration of
LIGHT and skin involvement (modified Rodnan skin score (mRSS); R-Spearman = 0,13;), erythrocyte sedimentation rate
(ESR; R-Spearman = 0,15), and, inverse, with diffusing capacity of the lungs for CO (DLCO; R-Spearman = -0,22). We
could not find any significant associations between serum LIGHT concentrations and other SSc features, including subtype
of SSc, disease duration, presence of interstitial lung disease, pulmonary hypertension, or other antibodies. In multivariate
regression analysis including, as predictors, DUs, ACA, serum CK elevation, steroid therapy, mRSS, DLCO, ESR, and sex,
only presence of DUs and DLCO were independently associated with serum concentration of LIGHT (p<0,05 for both) .
Conclusion: These data provide the first evidence of overexpression of LIGHT and its receptor in SSc and suggest that
LIGHT-TNFRSF14 axis might contribute to the pathogenesis of SSc. Increased serum concentrations of LIGHT seem to
reflect vascular injury in SSc.
Disclosure: O. Kowal-Bielecka, None; E. Gindzienska-Sieskiewicz, None; O. Distler, 4 D Science, Actelion, Active

Biotec, Bayer, Biogen Idec, Boehringer Ingelheim Pharma, BMS, ChemomAb, EpiPharm, Ergonex, espeRare foundation,
GSK,Roche-Genentech, Inventiva, Lilly, medac, MedImmune, Mitsubishi Tanabe, Pharmacyclics, Pfizer, Sanofi, Seroda, 2;
J. Reszec, None; S. Jordan, None; P. Bielecki, None; A. Sieskiewicz, None; A. Sulik, None; K. Kowal, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/increased-expression-of-the-tnf-

superfamily-member-lighttnfsf14-and-its-receptor-tnfrsf14-in-patients-with-systemic-sclerosis
M10, a Caspase Cleavage Product of the Hepatocyte Growth Factor Receptor,

Downregulates Bone Morphogenetic Protein-9-Induced Smad1/5/8
Phosphorylation and Collagen Production in Human Lung Fibroblasts
Atsushi Noguchi, Ilia Atanelishvili, Tanjina Akter, Richard M. Silver and Galina S. Bogatkevich, Division of
Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, SC
SESSION INFORMATION
I
Background/Purpose: We recently identified M10, a caspase cleavage product of the hepatocyte growth factor receptor, as
an anti-fibrotic peptide that interacts with Smad2 and inhibits TGFβ-induced Smad2 phosphorylation and collagen
production in human lung fibroblasts [1]. While Smad2/3 signaling pathway is mainly activated by TGFβ1 through type I
receptor activin receptor-like kinase (ALK) 5, Smad1/5 signaling pathway is mainly activated by bone morphogenetic
proteins (BMPs), which are other members of TGFβ superfamily, through ALK1/2/3/6 receptors. Recently, BMP9 has been
identified as a pro-fibrotic ligand in mouse embryo fibroblasts [2]. In SSc fibroblasts, ALK1/Smad1/5 pathway is suggested
to play a pivotal role in the regulation of fibrosis [3]. The aims of this study are to investigate the role of BMP9 in SSc lung
fibroblasts and to examine the additional anti-fibrotic mechanisms of M10.
Methods: Fibroblasts were derived from lung tissues obtained at autopsy from SSc patients and from age- race-, and sex-
matched normal subjects. MRC5 human fetal lung fibroblasts were purchased from Sigma. Potential peptide-protein
interactions were modeled in-silico using PepSite [4]. Smad phosphorylation, type I collagen, and smooth muscle α-actin (α-
SMA) expression were determined by immunoblotting and RT-PCR.
Results: Using a computational modulation approach available from PepSite, we found a statistically significant (p <
0.0001) potential interaction of M10 with the BMP9/ALK1/activin receptor type II B (ActRIIB) complex. The most
probable binding sites are located at β-turn motifs in BMP9. We demonstrate that when recombinant BMP9 is added to the
medium, phosphorylation of Smad1/5/8 is rapidly induced in MRC5 cells and SSc lung fibroblasts in a dose-dependent
manner. The expression of type I collagen is upregulated after 48 hours treatment with BMP9 in MRC5 cells and SSc lung
fibroblasts as well as normal lung fibroblasts. The expression of α-SMA is increased in normal lung fibroblasts in a dose
dependent manner. Intriguingly, the anti-fibrotic peptide M10 significantly downregulated BMP9-induced type I collagen
expression and α-SMA expression as well as Smad1/5/8 phosphorylation in lung fibroblasts.
Conclusion: We demonstrate that BMP9 shows pro-fibrotic effects in human fetal lung fibroblasts and in adult lung
fibroblasts obtained from SSc patients and matched normal subjects. M10 peptide has a potential to bind to BMP9 and to
inhibit BMP9-induced collagen production and epithelial-mesenchymal transition through the Smad1/5/8 signaling pathway.
References:
[1] Atanelishvili I, et al. Transl Res. 2016;170:99-111.
[2] Munoz-Felix JM, et al. Cell Signal. 2016;28:1252-61.
[3] Munoz-Felix JM, et al. Cytokine Growth Factor Rev. 2013;24:523-37.
[4] Trabuco LG, et al. Nucleic Acids Res. 2012;40:W423-7.
Disclosure: A. Noguchi, None; I. Atanelishvili, None; T. Akter, None; R. M. Silver, NIH/NIAMS P60 AR062755, 2,SC
SmartState®, 2; G. S. Bogatkevich, NIH/NIAMS P60 AR062755, 2,Scleroderma Foundation, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/m10-a-caspase-cleavage-product-of-the-

hepatocyte-growth-factor-receptor-downregulates-bone-morphogenetic-protein-9-induced-smad158-phosphorylation-and-
collagen-production-in-human-lung-fibroblasts
Mechanisms of Insulin-like Growth Factor-II-Mediated Fibrosis

Sara Garrett1, Justin Thomas2, Eileen Hsu3 and Carol A. Feghali-Bostwick4, 1Medicine/Rheumatology & Immunology,
Medical University of South Carolina, Charleston, SC, 2Eisenhower Medical Center, Rancho Mirage, CA, 3Kaiser
Permanente Medical Group, Mclean, VT, 4Division of Rheumatology and Immunology, Division of Rheumatology and
Immunology, Medical University of South Carolina, Charleston, SC, United States, Charleston, SC
SESSION INFORMATION
I
Background/Purpose: Previous work has shown that insulin-like growth factor (IGF)-II is increased in fibrosing lung
diseases, including idiopathic pulmonary fibrosis (IPF) and scleroderma/systemic sclerosis (SSc)-associated pulmonary
fibrosis. Our goal was to identify the mechanism by which upregulated IGF-II expression contributes to fibrosis in these
conditions.
Methods: Fibroblasts derived from lung tissues of normal donors (NL), patients with IPF, and patients with SSc-associated
pulmonary fibrosis were used. Gene expression, protein expression, phosphorylation, and secretion were analyzed with qRT-
PCR, immunoprecipitation, immunoblotting, and ELISA, respectively, in early passage primary fibroblasts. Antibody,
siRNA, and inhibitors were used to neutralize, knockdown, or block endogenous IGF-II and the IGF-II receptors: IGF-1
receptor (IGF1R), IGF2R, and/or insulin receptor (IR).
Results: The IGF1R, IGF2R, and IR receptors showed lower basal gene expression in SSc fibroblasts. Extracellular matrix
(ECM) transcripts, though unchanged in NL, were dramatically increased in IPF and SSc with IGF-II (200 ng/mL)
stimulation. Activation of IGF1R, assessed via receptor phosphorylation, occurred 5 min following IGF-II. Phosphorylation
decreased by 10 min in NL, but persisted through 10 min in SSc fibroblasts. Phosphorylation was abrogated by antibody-
mediated neutralization of endogenous IGF-II. Dual siRNA knockdown of IGF1R and IR decreased ECM components
collagen and fibronectin in NL and SSc fibroblasts, as did treatment with an IGF1R tyrosine kinase inhibitor. IGF-II
decreased IGF1R and IR transcripts at 6 hr in NL, IPF, and SSc and decreased IGF2R in NL from 1-48 hr. MMP3 transcript
was decreased with IGF-II stimulation in IPF and SSc, whereas TIMP1 transcript and secretion were increased.
Conclusion: Decreased basal receptor pools, ECM component upregulation, and longer receptor activation render
fibroblasts from pathologic lung more sensitive to IGF-II-stimulated fibrosis. Inhibitor studies indicate IGF-II signaling is
mediated by IGF1R and IR, which can form a hybrid receptor. IGF-II causes disruption of steady-state ECM deposition and
breakdown through altered MMP:TIMP levels, promoting a pro-fibrotic milieu in IPF and SSc.
Disclosure: S. Garrett, None; J. Thomas, None; E. Hsu, None; C. A. Feghali-Bostwick, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/mechanisms-of-insulin-like-growth-

factor-ii-mediated-fibrosis
Application of a Novel Computational Approach to Identify New Targets and

Pathways for Therapeutic Intervention in Scleroderma
Elma Kurtagic, Joel Pradines, Anthony Manning and Ishan Capila, Research, Momenta Pharmaceuticals, Inc., Cambridge,
MA
SESSION INFORMATION
I
Background/Purpose:
Systemic Sclerosis (SSc) is a complex autoimmune disease with chronic progressive course and high interpatient variability.
It is characterized by inflammation, vascular dysfunction and fibrosis. Fibrosis of the skin and visceral organs results in
irreversible scarring and ultimately organ failure, accounting for high mortality. There is no approved targeted therapy with
disease-modifying potential. Several translational studies were published, which focused on transcriptional analysis of
samples from SSc patients in order to understand the heterogeneity of underlying disease. We interrogated these datasets
using a novel data analysis methodology that leverages the knowledge of protein interaction networks (STRING) for
deriving biological insights and identifying intervention points into this heterogeneous disease.
Methods:
Publically available datasets composed of gene expression analysis of patient skin biopsies were identified. Datasets were
subjected to sample size and quality assessment. Selected high-quality datasets were analyzed using a novel computational
and statistical method. Namely, each gene was scored for both its differential expression and its known protein interactions
with top differentially expressed genes (DEGs). This approach led to identification of Well-Associated Proteins (WAPs);
gene products that have a significantly large number of known associations to top DEGs, without choosing a threshold for
differential expression. The scoring method corrects for the total number of interactions of each gene and is optimally fast,
enabling false discovery rate (FDR) estimates for each WAP via permutation testing, thus taking into account gene co-
expression. Furthermore, permutation testing was utilized to identify WAPs that correlated with measurable clinical factors.
Results:
Four publically available datasets were analyzed. Key biology pathways associated with SSc were identified. More
importantly, > 100 potential targets/WAPs were identified with FDR score < 0.01%. ~ 75% of the significant WAPs were not
perturbed at the mRNA level and would have been missed via standard statistical methods. Their significant connectedness
to top DEGs in the datasets suggests biologically relevant role in SSc. Robustness analysis revealed that WAP scores were
~40% reproducible across pairs of datasets, as compared to only ~10% for DEG scores. Of the top 100 WAPs obtained by
combining the two largest data sets, 59 were previously targeted providing drug-repurposing opportunities and 41 were
novel targets for drug discovery. Additional analysis identified WAPs (e.g. OSM) that significantly correlated with
measurable clinical factors such as MRSS (global skin score), diffuse disease and some auto-antibodies.
Conclusion:
A novel data analysis methodology was developed, leveraging protein interaction networks to identify WAPs that represent
potentially unique targets for therapeutic intervention in SSc. WAPs are unique as they were reproducibly detected across
multiple publicly available SSc datasets. Additionally, patient sub-populations that may benefit from targeted therapeutics
against selected WAPs were identified.
Disclosure: E. Kurtagic, Momenta Pharmaceuticals Inc., 1,Momenta Pharmaceuticals Inc., 3; J. Pradines, Momenta
Pharmaceuticals Inc., 1,Momenta Pharmaceuticals Inc., 3; A. Manning, Momenta Pharmaceuticals, Inc., 1,Momenta
Pharmaceuticals, Inc., 3; I. Capila, Momenta Pharmaceuticals Inc, 3,Momenta Pharmaceuticals Inc, 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/application-of-a-novel-computational-

approach-to-identify-new-targets-and-pathways-for-therapeutic-intervention-in-scleroderma
Proteomic Analysis of Scleroderma Associated Joint Disease

Chan Kim1, Julio Mantero2, Robert A. Lafyatis3 and Robert W. Simms4, 1Rheumatology and Clinical Epidemiology,
Boston University School of Medicine, Boston, MA, 2Arthritis Center, Boston University School of Medicine, Boston, MA,
3Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA,
4Rheumatology, Boston University School of Medicine, Boston, MA
SESSION INFORMATION
I
Background/Purpose:
The pathophysiology of joint disease in scleroderma, a heterogeneous multisystem disease mostly characterized by fibrosis,
is unknown. We performed proteomic analysis of serum in patients with scleroderma and joint tenderness. Understanding
systemic protein expression in scleroderma may help us understand joint disease in scleroderma. Our goal was to
characterize protein expression differences between scleroderma patients with joint tenderness and scleroderma patients
without joint tenderness.
Methods:
Patients with scleroderma were recruited from the registry at Boston University Medical Center’s Scleroderma Center.
Serum (blood) samples were drawn and were analyzed with SOMAscan for 1129 protein biomarkers. As part of the routine
examination performed by a senior rheumatologist on all registry participants, tender joint count (0-18) was assessed on
physical exam. If a subject had a tender joint count of 2 or more, then that subject had joint disease. If a subject had a
tender joint count of 0, then that subject did not have joint disease. For this study, 40 scleroderma subjects had both
SOMAscan data and tender joint count assessment. One subject with only 1 tender joint count was excluded, so 39 subjects
were analyzed. For analysis, the biomarkers were log2 transformed, and differential expression analyses were performed
using the “limma” package using the R statistical software.
Results:
Among the 39 scleroderma subjects, 9 participants had joint pain (average tender joint count 4.9), and protein expression
was compared between scleroderma participants with joint disease and scleroderma participants without joint disease. The
top 20 most significant biomarkers are shown in table 1. In previous analyses (not shown), similar biomarkers (such as
MMP (matrix metalloproteinase), fibrinogen, tumor necrosis factor), were seen elevated in all scleroderma participants
(compared to normal subjects without scleroderma). Notably, IL-6, cadherin-2 (involved in bone and cartilage formation),
BRF1 (RNA Polymerase III transcription initiation factor subunit) were expressed higher in scleroderma subjects with joint
disease compared to those without joint disease. VEGF-121 (vascular endothelial growth factor) was expressed lower in
scleroderma subjects with joint pain compared to those without joint disease.
Conclusion:
Although scleroderma participants had many protein expression changes due to fibrosis, autoimmunity and vasculopathy,
several biomarkers such as IL-6, cadherin-2, BRF1, VEGF-121 were differentially expressed in scleroderma participants
with joint disease and could provide insight into the pathophysiology of joint disease in scleroderma.
Table 1: Joint disease vs no joint disease

Log Fold Change P Value
MK12 0.375414 0.000385
IL-6 0.425859 0.002113
VEGF121 -0.69485 0.002898
MBL 0.697418 0.003867
ADAM 9 0.920928 0.008789
a1-Antitrypsin 0.459117 0.00907
CDC37 0.173549 0.009931
TSP4 0.472696 0.012891
LDH-H 1 0.32681 0.013691
BRF-1 0.29382 0.014471
MMP-14 0.379094 0.016855
PDGF-BB -0.44877 0.017505
iC3b -0.46833 0.017607
Siglec-9 1.04874 0.020749
Carbonic Anhydrase IV -0.30158 0.023048
Cadherin-2 0.285673 0.024096
MK11 0.265757 0.025145
Thrombospondin-1 -0.34304 0.025595
Fibrinogen 0.429274 0.027908
Macrophage mannose receptor 0.269891 0.029517
Disclosure: C. Kim, None; J. Mantero, None; R. A. Lafyatis, None; R. W. Simms, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/proteomic-analysis-of-scleroderma-

associated-joint-disease
Increased Plasma Levels of Hsp90 Are Associated with More Severe Organ
Involvement in Patients with Systemic Sclerosis
Hana Storkanova1, Sabina Oreska1, Maja Spiritovic1,2, Karel Pavelka1, Jiri Vencovsky1, Jörg Distler3, Ladislav Senolt1,
Radim Becvar1 and Michal Tomcik1, 1Institute of Rheumatology, Department of Rheumatology, 1st Faculty of Medicine,
Charles University, Prague, Czech Republic, Prague, Czech Republic, 2Faculty of Physical Education and Sport, Charles
University, Prague, Czech Republic, Prague, Czech Republic, 3Department of Internal Medicine III and Institute for Clinical
Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, Erlangen, Germany
SESSION INFORMATION
I
Background/Purpose: Our previous study demonstrated that Heat shock protein 90 (Hsp90) is overexpressed in the skin of
patients with systemic sclerosis (SSc), in cultured SSc fibroblasts and preclinical models of SSc in a TGF-β dependent
manner. We showed that Hsp90 is a new regulator of canonical TGF-β signalling and its inhibition prevents the stimulatory
effects of TGF-β on collagen synthesis and dermal fibrosis in three preclinical models of SSc1. The aim of this study was to
evaluate Hsp90 in the circulation of SSc patients and characterize its potential association with skin changes and SSc-related
features.
Methods: A total of 91 patients (78 females; mean age 52.7; disease duration 6.0 years; diffuse cutaneous (dc)SSc / limited
cutaneous (lc)SSc = 38/53) who met the ACR/EULAR 2013 classification criteria for SSc and 85 age- and sex- matched
healthy individuals were included. Plasma Hsp90 levels were measured by ELISA (eBioscience, Vienna, Austria). SSc-
related manifestations were obtained from the Czech Registry of SSc patients. Skin changes were assessed using the
modified Rodnan skin score (mRSS) and EUSTAR SSc activity score was determined. Data are presented as median (IQR,
25. – 75. percentile).
Results: Plasma Hsp90 levels were increased in SSc patients compared to healthy controls [12.5 (9.6–17.9) vs. 9.9 (7.9–
12.6) ng/mL, p = 0.001], but no difference between (lc)SSc and (dc)SSc were detected [13.1 (9.4–18.1) vs. 11.5 (9.5–17.5)
ng/mL, p = 0.316]. Hsp90 levels in all patients positively correlated with CRP (r = 0.313, p = 0.006). Furthermore, Hsp90
concentrations were increased in patients with interstitial lung disease (ILD) compared to those without ILD [12.8 (10.2–
17.9) vs. 10.3 (8.6–16.6) ng/mL, p = 0.045] and were negatively associated with functional parameters of ILD: FVC (r =
-0.299, p = 0.011), FEV1 (r = -0.256, p = 0.031), DLCO (r = -0.303, p = 0.009) and SpO2 (r = -0.317, p = 0.038). In
addition, only in patients with dcSSc, Hsp90 levels positively correlated with the mRSS (r = 0.437, p = 0.006).
Concentrations of extracellular Hsp90 were not significantly affected by other main clinical parameters of SSc.
Conclusion: We demonstrated higher plasma levels of Hsp90 in SSc patients compared to healthy controls. Concentrations
of extracellular Hsp90 increase with higher inflammatory activity, with deteriorated lung functions in ILD and also with the
extent and severity of the skin involvement in patients with diffuse cutaneous SSc. These data further highlight the role of
Hsp90 as a significant regulator of fibroblast activation and tissue fibrosis in SSc.
References: 1Tomcik M et al., Ann Rheum Dis.2014;73(6):1215-22.
Acknowledgement: Supported by AZV – 16-33542A and SVV – 260373.
Disclosure: H. Storkanova, None; S. Oreska, None; M. Spiritovic, None; K. Pavelka, None; J. Vencovsky, Samsung
Bioepis Co., Ltd., Biogen, 5; J. Distler, 4D Science, 1,Anamar Medical, Active Biotech, Array Biopma, BMS, Bayer
Pharma, Boehringer Ingelheim, Celgene, GSK, Novartis, Sanofi-Aventis, UCB, 2,Actelion Pharmaceuticals US, Active
Biotech, Anamar, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, JB Therapeutics, Medac,
Pfizer, RuiYi, UCB, 5; L. Senolt, None; R. Becvar, None; M. Tomcik, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/increased-plasma-levels-of-hsp90-are-

associated-with-more-severe-organ-involvement-in-patients-with-systemic-sclerosis
Elevated MeCP2 Expression in Diffuse Cutaneous Systemic Sclerosis Dermal

Fibroblasts Is Associated with Anti-Fibrotic Effects
Ye He1, Pei-Suen Tsou2, Dinesh Khanna3 and Amr H Sawalha2, 1Rheumatology, University of Michigan, Ann Arbor, MI,
2Division of Rheumatology, University of Michigan, Ann Arbor, MI, 3University of Michigan, Ann Arbor, MI
SESSION INFORMATION
I
Background/Purpose: Systemic Sclerosis (SSc) is a multisystem autoimmune connective tissue disorder characterized by
vascular injury and fibrosis of the skin and internal organs. Methyl-CpG-binding protein 2 (MeCP2) is a transcription
activator or repressor depending on its interacting complexes. Increasing evidence shows that MeCP2 is closely involved in
lung, liver, and kidney fibrosis. In this study, we aim to elucidate the role of MeCP2 in dermal fibroblasts from patients with
SSc.
Methods: Dermal fibroblasts were isolated from healthy controls or patients with diffuse cutaneous SSc (dcSSc). MeCP2
expression was analyzed by qRT-PCR and western blotting. A scratch wound healing assay was used to evaluate fibroblast
migration. MeCP2 overexpression was achieved by transfecting fibroblasts with MeCP2 DNA plasmids, while transfection
with empty vectors was used as control. MeCP2 knockdown was done using MeCP2 siRNA. RNA isolated from dcSSc
fibroblasts after 48hrs of MeCP2 knockdown was sequenced by Ilumina HiSeq2500. Gene pathway analysis was performed
using GeneMANIA and by searching literatures and GeneCards database.
Results: MeCP2 expression was increased by 1.8-fold (p=0.02) in dcSSc fibroblasts (n=6) compared to normal fibroblasts
(n=7) at the protein level. However, no change was observed at the mRNA level, suggesting that dysregulation of MeCP2 in
dcSSc occurs at the post-transcriptional level. Overexpression of MeCP2 in normal fibroblasts inhibited cell migration (n=4,
p=0.02) while MeCP2 knocked down dcSSc fibroblasts showed higher wound repair ability than controls (n=5, p<0.01). In
addition, the mRNA levels of pro-fibrotic genes such as α-SMA and COL1A1 were significantly downregulated in MeCP2
overexpressing normal fibroblasts (n=6, p=0.03) while anti-fibrotic PPAR-γ was upregulated (n=6, p<0.01). Using RNA-seq
we identified 51 differentially expressed genes after MeCP2 knockdown in dcSSc fibroblasts (n=5, ≥1.2 fold or ≤0.8 fold,
adjusted p-value<0.05). 14 out of 51 differentially expressed genes appeared to be involved in fibrosis, among which 5
downregulated genes including ITGB1 and NID2 were shown to be related to COL1A1, and 4 genes, including ITGB1,
PLAU, ADA, and TNFPIA1, were involved in cell migration/adhesion. None of the 14 screened genes were differentially
expressed between normal and dcSSc fibroblasts, suggesting that MeCP2 might suppress fibrosis via balancing the
expression of some of these candidate genes. Moreover, we further confirmed that 9 downregulated fibrosis-related genes
identified by RNA-seq were indeed MeCP2-regulated genes, as they were upregulated when MeCP2 was overexpressed in
normal fibroblasts.
Conclusion: MeCP2 exerts anti-fibrotic effects in dcSSc fibroblasts by reducing cell migration and myofibroblast
differentiation. Whole transcriptome profiling reveals that MeCP2 is involved in cell adhesion and controls extracellular
matrix (ECM)-related genes. Importantly, MeCP2 overexpression in dcSSc fibroblasts appears to be a defense mechanism to
counteract the pro-fibrotic nature of the disease. MeCP2 might be a novel target to restore normal skin function in SSc.
Disclosure: Y. He, None; P. S. Tsou, None; D. Khanna, Bristol-Myers Squibb, 2,Genentech/Roche, 2,NIH/NIAMS,
2,NIH/NIAID,, 2,Patient-Centered Outcomes Research Institute, 2,Scleroderma Foundation, 2,Actelion Pharmaceuticals US,
5,Bayer AG, 5,Cytori, 5,EMD Serono, 5,Genkyotex, 5,Gilead, 5,GlaxoSmithKline, 5,Genentech/Roche, 5,Sanofi-Aventis
Pharmaceutical, 5,Seattle Genetics, 5; A. H. Sawalha, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/elevated-mecp2-expression-in-diffuse-

cutaneous-systemic-sclerosis-dermal-fibroblasts-is-associated-with-anti-fibrotic-effects
A Positive Feedback Loop between Estrogen and IL-6 Leads to Fibrosis in

Human Skin
DeAnna Baker Frost1 and Carol A. Feghali-Bostwick2, 1Medicine, Division of Rheumatology and Immunology, Medical
University of South Carolina, Charleston, SC, 2Division of Rheumatology and Immunology, Division of Rheumatology and
Immunology, Medical University of South Carolina, Charleston, SC, United States, Charleston, SC
SESSION INFORMATION
I
Background/Purpose: Systemic Sclerosis (SSc) is a disease characterized by an increase in the synthesis of extracellular
matrix (ECM) components in various organs, including the skin, resulting in increased morbidity. Like most autoimmune
diseases, SSc has a female predominance that increases during childbearing years. Interestingly, post-menopausal SSc
patients have higher circulating estradiol (E2) levels compared to age-matched controls. E2 exerts pro-fibrotic and pro-
inflammatory activity, increasing ECM components and IL-6, both of which are also increased in SSc patients. Aromatase
(CYP19) is a cytochrome p450 enzyme active in extra-gonadal tissues, including the skin. It is responsible for the
aromatization of androgens into estrogens. Increased activity of aromatase may underlie the increase E2 levels in SSc
patients. Since SSc dermal fibroblasts secrete increased levels of IL-6, and increased E2 levels are reported in SSc patients,
we hypothesized that there is an interplay between E2 and IL-6 contributing to the pro-fibrotic phenotype.
Methods: Human skin in organ culture was stimulated with E2 or IL-6 and its soluble receptor, sIL6R, for 24 or 48 hours.
Transcript levels of aromatase, IL-6, and collagen 1A1 were measured using real-time PCR. Aromatase activity was
measured using an ELISA-based testosterone conversion assay. Statistical significance was determined using ANOVA, with
significance defined as p≤0.05.
Results: Human skin stimulated with E2 or IL-6 + sIL-6R ex vivo showed increased levels of collagen. E2 stimulation also
resulted in increased IL-6 transcript and protein levels. Stimulation of human skin with IL-6 and sIL-6R led to increases in
the levels of aromatase mRNA. Skin samples stimulated with IL-6 and sIL-6R also had increased aromatase activity,
translating into increased conversion of testosterone into estradiol. The aromatase activity decreased significantly after
treatment with anastrozole, an aromatase inhibitor.
Conclusion: Our data show that both E2 and IL-6 exert pro-fibrotic effects in human skin. Our findings further establish the
existence of a positive feedback loop between E2 and IL-6, supporting a pro-fibrotic cycle that leads to increased ECM
production and fibrosis. Our results implicate E2 and IL-6 in dermal fibrosis in SSc. Our results also suggest that effective
therapies for SSc may require concomitant inhibition of E2 and IL-6.
Disclosure: D. Baker Frost, None; C. A. Feghali-Bostwick, None.

View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-positive-feedback-loop-between-
estrogen-and-il-6-leads-to-fibrosis-in-human-skin
Proteomic Analysis of Human Fibroblasts in Systemic Sclerosis Reinforces the

Role of Transforming Growth Factor-ß and Points Toward Epidermal
Growth Factor Receptor / Phosphatidylinositol 3 Kinase Pathway Inhibition
Benjamin Chaigne1, Guilhem Clary2, Morgane Le Gall3, Nicolas Dumoitier4, Sebastien Lofek5, Philippe Chafey2, Pia
Moinzadeh6, Thomas Krieg7, Christopher Denton8 and Luc Mouthon9, 1Service de Médecine Interne, Centre de Référence
Maladies Systémiques Autoimmunes Rares d’Ile de France, hôpital Cochin, DHU Authors, Assistance Publique-Hôpitaux
de Paris, Paris, France, 2INSERM U1016, Institut Cochin,, Paris, France, 3INSERM U1016 Institut Cochin, Paris, France,
4INSERM U1016, Institut Cochin, Equipe Neutrophiles et Vascularites, Paris, France, 5INSERM U1016, paris, France,
6Department of Rheumatology, UCL Division of Medicine, London, United Kingdom, 7Universität zu Köln, Köln,
Germany, 8Department of Rheumatology, University College London, Royal Free Hospital, London, United Kingdom,
9Service de Médecine Interne, Hôpital Cochin, Centre de référence national pour les maladies systémiques autoimmunes
rares d’Ile de France, DHU Authors, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France ;Université Paris
Descartes Sorbonne Paris, Paris, France
SESSION INFORMATION
I
Background/Purpose:
Systemic sclerosis (SSc) is a rare autoimmune connective tissue disorder characterized by autoimmunity, vasculopathy and
fibrosis. Fibrosis is due to an exaggerated activation of fibroblasts by the transforming growth factor-ß (TGF-ß). In this
study we investigated the proteomic response of skin fibroblasts to TGF-ß in patients with SSc.
Methods:
Skin fibroblasts from 4 patients with SSc and 3 healthy controls (HC) were cultured in the presence or in the absence of
TGF-ß. Two-dimensional gel electrophoresis and mass spectrometry (MS) were used to identify proteins differentially
expressed between groups. Ingenuity Pathway analysis (IPA) and Panther softwares were used to analyse identified proteins.
Finally real-time cell analyser (RTCA) was used to assess fibroblast proliferation and viability in order to validate proteins
of interest.
Results:
We identified 687 protein spots differentially expressed between groups. 297 protein spots were analysed by MS. Principal
component analysis revealed significant differences between fibroblasts of patients with SSc and HC when cultured in the
presence or in the absence of TGF-ß. IPA revealed specific process networks such as actin cytoskeleton signalling, integrin
signalling, and remodelling of epithelial adherens junctions. Panther revealed predominant biological processes such as
cellular process, metabolic process and cellular component organization. TGF-ß enhanced the synthesis of fibroblasts’
proteins involved in actin cytoskeleton signalling and integrin signalling. Using IPA and RTCA we identified and validated
the involvement of epidermal growth factor receptor (EGFR) and phosphatidylinositol 3 kinase (Pi3K) in the proliferation
and the viability of fibroblasts from patients with SSc.
Conclusion:
In conclusion, we confirmed that the proteome profile of fibroblasts differs between patients with SSc and HC and
demonstrated that fibroblasts enhance their proteomic phenotype upon stimulation with TGF-ß. We finally highlighted that
EGFR and Pi3K are proteins of interest in fibroblasts from patients with SSc and should be considered as potential targets to
inhibit fibrosis in SSc.
Disclosure: B. Chaigne, None; G. Clary, None; M. Le Gall, None; N. Dumoitier, None; S. Lofek, None; P. Chafey,
None; P. Moinzadeh, None; T. Krieg, None; C. Denton, Actelion, Pfizer, GlaxoSmithKline, Bayer, Sanofi-Aventis,
Boehringer Ingelheim, Genentech-Roche, CSL Behring, Biogen, 5,Actelion, GlaxoSmithKline, Bayer, Genentech-Roche,
CSL Behring, 2; L. Mouthon, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/proteomic-analysis-of-human-

fibroblasts-in-systemic-sclerosis-reinforces-the-role-of-transforming-growth-factor-s-and-points-toward-epidermal-growth-
factor-receptor-phosphatidylinositol-3-kinase-pat
Integrating Analysis of Skin RNA in Situ Hybridization Using Rnascope and

Whole Skin Gene Expression in Systemic Sclerosis Skin to Localize Key
Pathogenic Drivers of Skin Fibrosis
Corrado Campochiaro1, Emma C. Derrett-Smith1, Voon H. Ong2, Gail Pearse3, Katherine Nevin3, Shaun Flint3, Mary
Morse3, Nicolas Wisniacki4 and Christopher Denton5, 1Centre for Rheumatology and Connective Tissue Diseases, UCL
Division of Medicine, London, United Kingdom, 2Rheumatology, UCL Division of Medicine, London, United Kingdom,
3GlaxoSmithKline, Stevenage, United Kingdom, 4ImmunoImflammation, GlaxoSmithKline, Stevenage, United Kingdom,
5Department of Rheumatology, University College London, Royal Free Hospital, London, United Kingdom
SESSION INFORMATION
I
Background/Purpose: Skin gene expression profiling can distinguish SSc from normal skin and can detect different subsets
of disease. Previous studies have reported a cross-sectional relationship between the expression of genes in whole skin and
the modified Rodnan skin score (mRSS). We aim to compare gene expression in early versus late dcSSc and define cells
responsible for the upregulation of candidate genes.
Methods: Total RNA was extracted from forearm skin biopsies of 3 early dcSSc anti-RNA polymerase III positive (ARA+)
patients and 3 late dcSSc ARA+ patients. COMP, chemokine ligand 2 (CCL2), PDGF-A, collagen type I a 1 chain
(COL1A1), interferon Induced Protein 44 (IFI44), IL-6, MMP3, SERPINE, TGF-b and thrombospondin 1 (THBS1) was
measured using quantitative PCR analysis. mRSS was assessed in all patients and correlated with normalized gene
expression. RNA in situ hybridization for a-actin-2 (ACTA2), CCL2, COL1A1, COL3A1, COMP, SERPINE and THBS1
mRNA was performed using RNAscope¨ 2.5 LS Reagent Kit in early dcSSc ARA+ patients (n=2) and healthy controls (HC)
(n=3). Semi-quantitative scoring criteria were applied (score from 0 to 4).
Results: Whole skin relative normalized gene expression of COMP, CCL2, IL-6, SERPINE and THBS1 was significantly (p
< 0.05) higher in early compared to late SSc skin (COMP mean 25049.15 ± 10862.16 vs 5256.47 ± 2380.53; CCL2 mean
1722.04 ± 598.93 vs 638.25 ± 279.96; IL-6 mean 43.98 ± 40.76 vs 11.91 ± 5.44; SERPINE mean 1770.32 ± 704.46 vs
184.48 ± 61.37; THBS1 mean 7190.75 ± 309.89 vs 1176.81 ± 235.35) [Figure 1]. There was a positive correlation between
SERPINE and THBS1 and mRSS (SERPINE r2 = 0.493, p = 0.09; THBS1 r2 = 0.91, p = 0.02). Whole skin relative
normalized gene expression of all the remaining genes, except for IFI44, was also higher in early compared to late patients
although not significantly. RNAscope analysis revealed positive SERPINE staining in subsets of fibroblast-like cells located
in the mid-dermis in early dcSSc only (score 3 and 4 in early dcSSc vs score 0 in HCs). An increased number of THBS1+
and COMP+ fibroblast-like cells (α-smooth muscle actin +) were found in the deep dermis of early dcSSc (score 4 in early
dcSSc pts vs score 0, 2 and 3 in HCs).
Conclusion: SERPINE, THBS1, COMP, CCL2 and IL-6 are upregulated in early compared to late dcSSc patients. THBS1
and COMP are key genes associated with skin involvement and both are TGF-b regulated. RNAscope technology not only
confirmed the upregulation of SERPINE, COMP and THBS1 in early dcSSc, but detected the expression of these genes in
the dermis of patients in subsets of cells. These findings highlight how specific cells may be responsible for the pro-fibrotic
and inflammatory changes typical of the early stages of the disease. Upregulation of fundamental pro-fibrotic and
inflammatory genes could be crucial in the early stages of SSc and specific subsets of cells in the dermis could be the
responsible for this.
Disclosure: C. Campochiaro, None; E. C. Derrett-Smith, None; V. H. Ong, None; G. Pearse, GlaxoSmithKline,

3,GlaxoSmithKline, 1; K. Nevin, GlaxoSmithKline, 3,GlaxoSmithKline, 1; S. Flint, GlaxoSmithKline, 3,GlaxoSmithKline,
1; M. Morse, GlaxoSmithKline, 3,GlaxoSmithKline, 1; N. Wisniacki, GlaxoSmithKline, 1,GlaxoSmithKline, 3; C. Denton,
Actelion, Pfizer, GlaxoSmithKline, Bayer, Sanofi-Aventis, Boehringer Ingelheim, Genentech-Roche, CSL Behring, Biogen,
5,Actelion, GlaxoSmithKline, Bayer, Genentech-Roche, CSL Behring, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/integrating-analysis-of-skin-rna-in-situ-

hybridization-using-rnascope-and-whole-skin-gene-expression-in-systemic-sclerosis-skin-to-localize-key-pathogenic-
drivers-of-skin-fibrosis
Serological Biomarkers of Collagen Formation Is Increased in Systemic

Sclerosis
Pernille Juhl1, Mette Mogensen2, Line Iversen2, Tonny Karlsmark2, Morten Karsdal3, Anne-C. Bay-Jensen4 and Anne Sofie
Siebuhr5, 1Nordic Bioscience, Herlev, Denmark, 2Department of Dermatology, Bispebjerg Hospital, Copenhagen,
Denmark, 3Biomarkers and Reseacrh, Nordic Bioscience, Herlev, Denmark, 4Biomarkers and Reseach, Nordic Bioscience,
Herlev, Denmark, 5Biomarkers and Research, Nordic Bioscience, Herlev, Denmark, Herlev, Denmark
SESSION INFORMATION
I
Background/Purpose: Systemic sclerosis (SSc) is a multisystem, autoimmune disease characterized by immune

dysregulation, vasculopathy and excessive fibrosis of the skin and internal organs. Fibrosis is the pathological state where
the unbalance in ECM turnover is shifted towards increased formation. The main family of ECM protein is collagen and the
excessive fibrosis results in release of ECM fragments to circulation, where they may be quantified as biomarkers. Skin is
rich in type I and III collagen, while type IV, V, VI and VII collagen is present to a lesser amount. The objective is to
investigate if the level of collagen turnover could aid in describing skin fibrosis in SSc.
Methods: SSc patients (n=121) from a cross-sectional study fulfilling the 2013 ACR/EULAR SSc criteria were included
together with non-symptomatic controls (n=9). The study included both limited SSc (ln=79) and diffuse SSC (n=42). The
mean age of the population was 57.4 (SD 11.6) years, 84% were female, mean disease duration was 11.7 (8.9) years and
mean skin score was 11.2 (8.6). Biomarkers of type I, III, IV, V and VI collagen formation (PINP, PRO-C3, P4NP7S, PRO-
C5 and PRO-C6, respectively) and type III, IV, V, VI and VII collagen degradation (C3M, C4M, C5M, C6M and C7M,
respectively) were assessed in serum by competitive ELISAs. Furthermore, a biomarker of a degraded and citrullinated form
of vimentin (VICM) was measured in serum. Statistical differences between non-symptomatic controls and SSc patients was
tested by t- test (Mann-Whitney).
Results: In SSc patients formations biomarkers of type I, VI and VII collagen was significantly increased compared to non-
symptomatic controls (PINP: P=0.02, PRO-C5: P=0.01, PRO-C6: P=0.03) (Figure 1). Formation biomarkers of type III and
VI collagen were not significantly increased. The degradation biomarkers of type III, IV and V collagen were not
significantly increased in SSc patients (Figure 2). However, degradation of type VI and VII collagen (C6M: P=0.02 C7M:
P=0.05) were significantly increased in SSc patients. Furthermore, VICM was also significantly elevated in SSc patients
compared to non-symptomatic controls (P<0.0001).
Conclusion: This pilot study showed that collagen turnover appears to be significantly different between SSc patients and
non-symptomatic controls. Even if the collagen formation is increased, the degradation of all collagens are not. These data
suggest that serological assessment of ECM turnover could be relevant in SSc, and offers area of investigation of disease
pathogenesis.
Disclosure: P. Juhl, Nordic Bioscience Diagnostic, 3; M. Mogensen, None; L. Iversen, None; T. Karlsmark, None; M.
Karsdal, Symic Bio, 1; A. C. Bay-Jensen, Nordic Bioscience Diagnostic, 3; A. S. Siebuhr, Nordic Bioscience Diagnostic,
3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/serological-biomarkers-of-collagen-

formation-is-increased-in-systemic-sclerosis
Molecular Mechanism for the Therapeutic Effect of Extracorporeal Shock

Wave Therapy on Digital Ulcers of Systemic Sclerosis
Yukiko Kamogawa1, Hiroshi Fujii1, Tsuyoshi Shirai1, Tomonori Ishii2 and Hideo Harigae1, 1Department of Hematology
and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan, 2Clinical Research, Innovation and
Education Center, Tohoku University Hospital, Sendai, Japan
SESSION INFORMATION
I
Background/Purpose: Digital ulcers (DUs) are the most common skin manifestations in systemic sclerosis (SSc). DUs in
SSc are not usually caused by vasculitis and are often refractory to conventional immunosuppressive therapies.
Extracorporeal shock wave therapy (ESWT) has been used to treat urinary stones since 1980s. The therapy has also been
applied to treat various diseases such as chronic tendinopathy, ischemic heart disease, and wound healing disorders.
Previously, we reported that the low energy ESWT dramatically improved refractory DUs in SSc (Saito et.al. Tohoku J. Exp.
Med. 238:19, 2016). Because ESWT was applied on palms and forearms distant from DUs, we considered that the healing
effect of ESWT on DUs may be due to enhanced angiogenesis via some angiogenic factors rather than a direct physical
stimulus on ulcers. However, the precise molecular mechanism remains unknown. In this study, we tried to clarify the
molecular basis of shock wave (SW) treatment on dermal endothelial cells using in vitro SW treatment system. We found
that FBJ murine osteosarcoma viral oncogene homolog B (FOSB), which is a component of multipotent transcriptional
factor AP-1, was prominently increased after SW treatment. We also examined the functional consequence of FOSB on
angiogenesis.
Methods: (1) Human Dermal Microvascular Endothelial Cells (HDMECs) were cultured on a cover glass with 2.5%
agarose gel (Fig-1) and treated with SW. RNA was extracted from HDMECs 2 h after SW treatment, and gene expression
profiling was analyzed using microarray (Agilent). (2) FOSB expression after SW treatment was measured using RT-PCR.
(3) FOSB-expressing HDMECs were stimulated with serum, and vascular growth factor A (VEGFA) induction was
evaluated using RT-PCR.
Results: In the culture system shown in Fig-1, HDMECs were stable without any significant detachment or death of cells
after SW treatment. The microarray analysis revealed that FOSB gene expression level was significantly elevated (>10-fold,
p < 0.05) after SW treatment in three independent experiments. In RT-PCR analysis, FOSB gene expression level was also
increased in proportion to SW energy at 1 h after the treatment. Aberrant expression of FOSB in HDMECs increased
VEGFA induction by stimulation with serum (Fig-2)
Conclusion: SW treatment elevated FOSB gene expression in HDMECs, which directly led to increased sensitivity for
VEGFA induction, suggesting that FOSB may be a master regulator responsible for the angiogenic effect of ESWT. This
finding may help in the development of more effective strategies using ESWT for DUs in SSc.
Disclosure: Y. Kamogawa, None; H. Fujii, None; T. Shirai, None; T. Ishii, Chugai, Ono, Pfizer, Mitsubishi-Tanabe,
Astellas, 8; H. Harigae, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/molecular-mechanism-for-the-

therapeutic-effect-of-extracorporeal-shock-wave-therapy-on-digital-ulcers-of-systemic-sclerosis
The Immunophenotyping of Peripheral Blood Associates with Nailfold

Microvascular Changes in Patients with Systemic Sclerosis
Satoshi Kubo1, Shingo Nakayamada2, Maiko Yoshikawa1, Yusuke Miyazaki1, Hiroko Yoshinari3, Yurie Satoh3, Yasuyuki
Todoroki3, Kazuhisa Nakano2, Shigeru Iwata4, Kentaro Hanami1, Shunsuke Fukuyo3, Ippei Miyagawa5, Minoru Satoh6 and
Yoshiya Tanaka7, 1The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan,
Kitakyushu, Japan, 2First Department of Internal Medicine, University of Occupational and Environmental Health, Japan,
Kitakyushu, Japan, 3University of Occupational and Environmental Health, Japan, Fukuoka, Japan, 4First Department of
Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan,
5University of Occupational and Environmental Health, Japan, Kitakyushu, Japan, 6Department of Clinical Nursing, School
of Health Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan, 7The First Department of
Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
SESSION INFORMATION
I
The immunophenotyping of peripheral blood associates with nailfold microvascular changes in patients with
systemic sclerosis
Background/Purpose: Systemic sclerosis (SSc) is a complex disease with autoimmunity and vasculopathy, leading to
subsequent fibrosis. However, little is known about the relationship between immunological abnormality and microvascular
changes. Here, we stratified SSc patients based on peripheral immunophenotyping and investigated the association between
immunophenotyping and vasculopathy in SSc.
Methods: Ninety patients with SSc were enrolled in this study. Nailfold videocapillaroscopy was performed for qualitative
assessment of morphological microvascular. Peripheral blood mononuclear cells were obtained and the phenotype of
circulating B, T, NK and dendritic cells was defined based on flow cytometric analysis for human immune system termed
"the Human Immunology Project". Based on these results, SSc patients were classified into subgroups by cluster analysis.
Results: The proportion of effector T cell was higher in SSc than the healthy control. The proportion of activated Th1 (2.0%
vs 1.3%) and activated Th17 (1.2% vs 0.8%), but not Treg and Tfh, was higher in SSc. On the other hand, the abnormalities
of B cell differentiation in SSc patients were mild. The proportion of plasmablast was comparable and that of naïve B cell
was higher in SSc. However, cluster analysis stratified SSc patients into three subgroups (Figure): patients who showed
almost normal immunophenotype (without abnormality group), patients with high percentage of effector T cell and Th17
cells (T cell-dominant group), and patients with high proportion of plasmablast and effector B cell (B cell-dominant group).
The majority (81%) of SSc patients belonged to the without abnormality group. In contrast, the percentage of patients who
had severe microvascular changes was highest among the T cell-dominant group and the B cell-dominant group.
Conclusion: Immune abnormality in peripheral blood was not necessarily found in all cases of SSc. However, our data
indicated that there are two types of immunological abnormalities associated with the risk of vasculopathy in patients with
SSc. Accumulation of further evidence will not only contribute to elucidate the pathogenesis of SSc but also help the
development of targeted therapy.
Figure. Immune cell characteristics based on statistical cluster analysis in patients with systemic sclerosis:
Immunophenotypes of the three groups. P values by one-way analysis of variance.
Disclosure: S. Kubo, Bristol-Myers Squibb, 8,Pfizer Inc, 8,Takeda Pharmaceutical Company Ltd, 8; S. Nakayamada,
Bristol-Myers Squibb, 8; M. Yoshikawa, None; Y. Miyazaki, None; H. Yoshinari, None; Y. Satoh, None; Y. Todoroki,
None; K. Nakano, None; S. Iwata, None; K. Hanami, None; S. Fukuyo, None; I. Miyagawa, None; M. Satoh, None; Y.
Tanaka, Mitsubishi-Tanabe, Takeda, Bristol-Myers, Chugai, Astellas, Abbvie, MSD, Daiichi-Sankyo, Pfizer, Kyowa- Kirin,
Eisai, Ono, 2,Daiichi-Sankyo, Astellas, Pfizer, Mitsubishi-Tanabe, Bristol-Myers, Chugai, YL Biologics, Eli Lilly, Sanofi,
Janssen, UCB, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-immunophenotyping-of-peripheral-

blood-associates-with-nailfold-microvascular-changes-in-patients-with-systemic-sclerosis
The αV Integrin Inhibitor Abituzumab Inhibits Myofibroblast Differentiation

Eileen Samy1, Yin Wu1, Georgianna Higginbotham2, Roland Grenningloh2 and Daigen Xu2, 1TIP Immunology, EMD
Serono Research & Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica, MA, 2EMD
Serono Research & Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica, MA
SESSION INFORMATION
I
Background/Purpose: Scleroderma is a progressive fibrotic multi-organ disease characterized by the hardening and
tightening of the skin and connective tissues. TGF-β1 is a potent mediator of fibroblast to myofibroblast transition (FMT),
which contributes to increased extracellular matrix deposition and is the main driver of disease. There is substantial evidence
for crosstalk between αV integrins and TGF-β during these processes. TGF-β is secreted in a latent form which contains a
Latency Associated Peptide (LAP) region. The LAP of TGF-β1 contains an Arg-Gly-Asp (RGD) motif, which interacts with
the integrins αVβ1, αVβ3, αVβ5, αVβ6 and αVβ8 resulting in activation of TGF-β1. Abituzumab is a human antibody
specific for αV and therefore inhibits ligand binding of these five integrins. The goal of this study was to determine if
abituzumab can block TGF-β activation and FMT in vitro and thus have potential as a scleroderma therapeutic.
Methods: Expression of integrins and myofibroblast markers in human lung fibroblasts was analyzed by RT-PCR in the
presence and absence of abituzumab. In addition, we examined the ability of abituzumab to block FMT in an epithelial cell
(NCI-H358 or Calu3)/fibroblast co-culture, mimicking the potential interaction of epithelial cells and fibroblasts in tissues
undergoing fibrosis.
Results: Analysis of integrin expression showed that human lung fibroblasts express ITGB1>ITGB5>ITGB8>ITGB3. TGF-
β-induced FMT caused an increase in the expression of ITGB5, and to a lesser extent ITGB1 and ITGB3. TGF-β treatment
increased myofibroblast marker genes in lung fibroblasts, and immunofluorescence staining revealed increased αVβ5 and a-
SMA expression. Abituzumab treatment of fibroblast cultures showed a reduction in the increased αSMA expression, as
well as production of IL-6 and collagen gel contraction, demonstrating an ability for abituzumab to block TGF-β-induced
FMT. Co-culture of epithelial cells with fibroblasts resulted in induction of αSMA and multiple mRNA transcripts that are
markers for FMT, as well as increased IL-6 production. In this system, these markers were reduced by abituzumab treatment,
demonstrating that αV integrins play a role in FMT.
Conclusion: Results reported here indicate abituzumab has the potential to block TGF-β-induced FMT and thus
development of fibrosis. It may potentially be an efficacious drug for treatment of scleroderma.
Disclosure: E. Samy, EMD Serono, Inc, 3; Y. Wu, EMD Serono, Inc, 3; G. Higginbotham, EMD Serono, Inc, 3; R.
Grenningloh, EMD Serono, Inc, 3; D. Xu, EMD Serono, Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-%ce%b1v-integrin-inhibitor-

abituzumab-inhibits-myofibroblast-differentiation
Transcriptome Sequencing Reveals Genetic Polymorphisms Associated with

Ssc Gene Expression Subtypes
Guoshuai Cai1, Bhaven K. Mehta2, Mengqi Huang2, Jennifer Franks1, Tammara A. Wood1, Kathleen D. Kolstad3,
Marianna Stark4, Antonia Valenzuela5, David Fiorentino6, Robert W. Simms7, Nicole Orzechowski8, Lorinda Chung9 and
Michael L. Whitfield2, 1Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover,
NH, 2Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, 3Rheumatology, Stanford
University Medical Center, Stanford, CA, 4Stanford University, Stanford, CA, 5Immunology and Rheumatology, Stanford
University, Palo Alto, CA, 6Department of Dermatology, Stanford University School of Medicine, Palo Alto, CA,
7Rheumatology, Boston University School of Medicine, Boston, MA, 8Dartmouth-Hitchcock Medical Center, Lebanon, NH,
9Rheumatology, Stanford University Medical Center, Palo Alto, CA
SESSION INFORMATION
I
Background/Purpose: Systemic sclerosis (SSc) is a complex disease characterized by substantial genotypic and phenotypic
heterogeneity. Four molecular gene expression subsets have been identified from SSc skin, including inflammatory,
fibroproliferative, normal-like, and limited. Genome-wide association studies have identified genetic variants associated
with disease risk. However, these studies were not designed to interrogate genetic changes underlying specific gene
expression subtypes. Here, our objective was, by RNA-seq in SSc skin, to identify potential genetic variants associated with
specific gene expression subtypes and disease phenotypes.
Methods: We generated RNA-seq data from skin biopsies of 42 patients with SSc and 14 healthy controls. Variants were
detected and filtered by quality, sequencing depth, minor allele frequency, and potential deleterious effects on gene function.
Gene burden tests were used to identify susceptibility loci in cases compared to healthy controls, as well as in healthy
controls of a European population from the phase III 1000 Genomes Project (N=503). We further quantitated gene
expression and used an additive genetic model to identify gene expression associated variants. Variants enriched in each of
the SSc molecular subsets were detected by Fisher's exact test.
Results: We identified 267 potentially deleterious variants in 253 genes in patients with SSc, including 30 genes (e.g. IRF6,
NCF2, IL37) enriched in immunological processes and 10 genes (e.g. ITGB4, COL5A1, LAMA3) significantly enriched in
extracellular matrix-related pathways. We found variants enriched in each of the inflammatory (35 variants),
fibroproliferative (7 variants), and normal-like (45 variants) subsets. Potentially deleterious variants in IL37 were enriched
in patients with diffuse skin involvement and were significantly correlated with increased gene expression of IL6 and STAT3
in patient samples. Consistently, HapMap B cell lines harboring deleterious IL37 variants showed increased expression of
IL6 upon immune stimulation.
Conclusion: This study demonstrates the value of RNA-seq for identifying genetic variants associated with SSc gene
expression subsets. Results indicate genetic variants can be associated with each of the intrinsic gene expression subset and
may influence innate immune responses and ECM deposition. The identified IL37 variant may modulate SSc pathogenesis
by increasing expression of the IL-6 pathway.
Disclosure: G. Cai, None; B. K. Mehta, None; M. Huang, None; J. Franks, None; T. A. Wood, Celdara Medical, LLC, 5;
K. D. Kolstad, None; M. Stark, None; A. Valenzuela, None; D. Fiorentino, None; R. W. Simms, None; N. Orzechowski,
None; L. Chung, Cytori, Actelion, Reata, 5; M. L. Whitfield, Corbus, UCB, glaxosmithkline, 5,Celdara medical llc, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/transcriptome-sequencing-reveals-
genetic-polymorphisms-associated-with-ssc-gene-expression-subtypes
Circulating Fibrocytes in Systemic Sclerosis Patients and Healthy Subjects:

An in Vitro Study
Maurizio Cutolo1, Paola Montagna2, Stefano Soldano2, Amelia Chiara Trombetta3, Paola Contini4, Vanessa Smith5,
Barbara Ruaro2, Alberto Sulli3 and Renata Brizzolara2, 1Research Laboratory and Academic Division of Clinical
Rheumatology, Department of Internal Medicine, IRCCS A.O.U. San Martino-IST, University of Genova, Genoa, Italy,
Genoa, Italy, 2Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine,
University of Genova, IRCCS San Martino, Genoa, Italy, Genoa, Italy, 3Research Laboratory and Academic Division of
Clinical Rheumatology, Department of Internal Medicine, IRCCS A.O.U. San Martino-IST, University of Genova, Genoa,
Italy, Genova, Italy, 4Division of Clinical Immunology, Department of Internal Medicine, University of Genova, Genoa,
Italy, Genova, Italy, 5Faculty of Internal Medicine, Ghent University, Ghent, Belgium
SESSION INFORMATION
I
Background/Purpose:
Circulating fibrocytes seem to exert immunomodulatory effects, expressing class II major histocompatability complex
molecules (HLA-DP, -DQ, and -DR) and could have a role in fibrosing diseases (i.e. systemic sclerosis, SSc), due to the
capacity of such cells to migrate into affected tissues (through CXCR4/CXCL12 interaction) and to differentiate into
fibroblasts/myofibroblasts, then inducing matrix protein deposition and fibrosis [1-4].
The aim of this study was to isolate fibrocytes from peripheral blood mononuclear cells (PBMCs) of SSc patients and
healthy subjects (CNTs) and comparing both after having identified them by fluorescence-activated cell sorter analysis
(FACS) (using their specific markers: the leukocyte common antigen CD45, collagen I (COL I), the chemokine receptor
CXCR4 and HLA-DR [2]).
Methods:
Blood samples were collected, after signed informed consent, at basal time (T0), from 11 SSc patients (treated only with
different vasodilator drugs) and 5 CNTs. In addition, PBMCs, isolated from 9 SSc patients and 5 CNTs, were cultured on
fibronectin-coated plates [5]. The non-adherent cells were removed and after 8 days (T8) of culture (standardized time) the
adherent spindle shaped cells were lifted through incubation in 0.05% EDTA (ice-cold). Fibrocyte identification was
performed by FACS, using anti-CD45, anti-COL I, anti-CXCR4 and anti-HLA-DR monoclonal antibodies.
Results:
FACS analysis revealed that, at T0, among the CD45+ cells, the percentage of fibrocytes, identified as CD45+, COL I+,
CXCR4+ was 1.0±1.2 % in SSc patients and 0.5±0.2 % in healthy subjects (CNTs). In addition, the HLA-DR expression on
fibrocytes in both CNTs and SSc patients showed low values (22.1±21.1 % and 13.1±4.7 %, respectively).
After 8 days (T8) of culture, fibrocytes presented adherent and spindle shaped morphology and FACS analysis demonstrated
that the percentage of fibrocytes CD45+, COL I+, CXCR4+ increased up to 52.8±27.1% in SSc patients and up to 61.9±24.4
in CNTs, compared to T0.
Therefore, at T8 of culture, the HLA-DR+ expression on fibrocytes in SSc patients and CNTs strongly increased (90.1±22.7
% and 97.9±1.9, respectively), compared to T0.
Conclusion:
Circulating fibrocytes, identified as CD45, COL I and CXCR4 positive cells, resulted in very low percentage in peripheral
blood at basal time, but after 8 days of culture in proper conditions, the percentage of differentiated fibrocytes increased up
to 50 times in SSc (and CNTs), whereas the HLA-DR expression increased up to 68% in SSc and 85% in CNTs. Data
suggest that circulating fibrocytes might be an early cellular targets in presence of fibrositing diseases.
References:
1. Blakaj and Bucala. Fibrogenesis & Tissue Repair 2012;5:S6. 2. Chesney J et al. Proc. Natl. Acad. Sci. 1997; 94:6307–
6312. 3. Bucala R. Mol Med 2015;21:S3–S5. 4. Brunasso A.M. et al. F1000Research 2016;5:723. 5. Pilling D et al. J
Immunol Methods 2009; 351:62–70.
Disclosure: M. Cutolo, None; P. Montagna, None; S. Soldano, None; A. C. Trombetta, None; P. Contini, None; V.
Smith, None; B. Ruaro, None; A. Sulli, None; R. Brizzolara, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/circulating-fibrocytes-in-systemic-

sclerosis-patients-and-healthy-subjects-an-in-vitro-study
Differences between Temporal Artery Biopsy-Positive and Biopsy-Negative

Giant Cell Arteritis: A Comparative Cohort Study
Matthew J. Koster1, Karthik Yeruva1, Cynthia S. Crowson2 and Kenneth J. Warrington1, 1Rheumatology, Mayo Clinic,
Rochester, MN, 2Health Sciences Research, Mayo Clinic College of Medicine and Science, Rochester, MN
SESSION INFORMATION
Session Title: Vasculitis Poster I: Large Vessel Vasculitis
Background/Purpose: Giant cell arteritis (GCA) is the most common systemic vasculitis in patients aged 50 years or older.
The presence of cranial features and an abnormal temporal artery biopsy have historically been the primary focus for
diagnosis of this condition. A notable percentage of patients with GCA have negative temporal artery biopsies. Few cohort
studies exist comparing the presentation and outcome of patients based on biopsy positivity.
Methods: Patients with temporal artery biopsy-negative GCA diagnosed between 1/1/1998 and 12/31/2013 were identified
retrospectively. Final diagnosis was confirmed by consensus among two rheumatologists and a physician abstractor. Clinical
characteristics, treatment course and outcomes were compared to a cohort of biopsy-positive patients with GCA (n=286)
from the same institution.
Results:
110 patients with temporal artery biopsy-negative GCA were identified. Unilateral biopsies were performed in 73, bilateral-
sequential in 10, and bilateral same day in 27 cases. Median duration between steroid initiation and biopsy was 3 days.
Median length of first biopsy was 14mm and second biopsy (if performed) was 22mm. Among biopsy-negative patients with
advanced imaging within 6-months of diagnosis, 67% (41/61) had evidence of large vessel vasculitis.
Patients with biopsy-negative GCA were younger (72.0±9.0 vs 75.0±7.6; p=0.001), met fewer ACR criteria (≥3 criteria 64%
vs 95%; p<0.001) and had a shorter time from symptom onset to diagnosis (median 1.1 vs 2.1 months; p<0.001). Vascular
risk factors evaluated at diagnosis showed a higher rate of pre-existing hypertension and obesity among patient with biopsy-
negative GCA but similar rates of smoking and diabetes mellitus. Frequency of headache and vision loss at time of
presentation were similar between groups. However, biopsy-negative GCA patients had more temporal artery tenderness
(35% vs 16%; p<0.001) and arm claudication (13% vs 2%; p<0.001) but less frequent jaw claudication (19% vs 52%;
p<0.001). Anorexia, fatigue, and arthralgia were also more commonly noted in biopsy-negative patients. Baseline CRP was
lower among patients with negative biopsies (44.3±53.6 vs 70.4±63.9 mg/L; p<0.001).
Initial prednisone dose was similar among both cohorts. Although cumulative glucocorticoid (GC) was lower in biopsy-
negative patients at 1 year (6.3±2.6 vs 7.2±2.7 g; p=0.004), cumulative GC doses at 2-years and 5-years were equivalent.
Biopsy-positive patients (5-years, 56±3%) were able to discontinue GC sooner than biopsy-negative patients (5-years,
30±5%; p<0.001). The number of relapses, time-to-first relapse, annual relapse rate and mortality did not differ based on
biopsy positivity.
Conclusion: While similarities are present, there are notable differences in clinical presentation between biopsy-positive and
-negative GCA. Although current ACR criteria underperform in patients with biopsy-negative GCA, imaging studies are
often useful for confirmation of diagnosis. Further studies are needed to confirm and understand the observed variability in
GC duration.
Disclosure: M. J. Koster, None; K. Yeruva, None; C. S. Crowson, None; K. J. Warrington, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/differences-between-temporal-artery-

biopsy-positive-and-biopsy-negative-giant-cell-arteritis-a-comparative-cohort-study
Safety Events in Giant Cell Arteritis and Rheumatoid Arthritis Patient

Populations
Sara Gale1, Sophie Dimonaco2, Huong Trinh1, Katie Tuckwell2, Neil Collinson2, John H. Stone3, Khaled Sarsour1, Jinglan
Pei4, Jennifer H. Best1, Christine Birchwood4 and Shalini Mohan1, 1Genentech, South San Francisco, CA, 2Roche Products,
Ltd., Welwyn Garden City, United Kingdom, 3Massachusetts General Hospital Rheumatology Unit, Harvard Medical
School, Boston, MA, 4Genentech, Inc., South San Francisco, CA
SESSION INFORMATION
Background/Purpose: Recent clinical trial findings have shown efficacy for tocilizumab (TCZ) in treating giant cell
arteritis (GCA).1,2 TCZ was approved for the treatment of GCA in the US in 2017 and of rheumatoid arthritis (RA) in the
EU in 2009 and in the US in 2010, and it has a well-characterized safety profile in RA patients (pts). However, the safety
profile of TCZ in GCA pts may differ from that observed in RA pts due to differences in the underlying disease and the
higher dosing of glucocorticoids (GCs) used to treat GCA. This study describes the incidence rates (IRs) of safety events in
GCA pts or RA pts in a general healthcare claims database and in the TCZ clinical development program to contextualize
the observed safety profile of TCZ in GCA.
Methods: Adverse events of special interest (AESI) IRs for TCZ in adult GCA and RA pts were estimated from a US-based
MarketScan administrative healthcare claims database. GCA pts were ≥50 years and received ≥2 prescriptions for oral GCs
(the first within 6 months of diagnosis); for comparability, only RA pts who were ≥50 years were included. AESI included
infections, hepatic events, gastrointestinal (GI) perforation, demyelination, cardiovascular events, bleeding events, and
malignancies. AESI IRs were also calculated for a pooled population of RA pts who received TCZ in clinical trials and for
GCA pts who received TCZ in the GiACTA clinical trial.1-3 Risks for AESI among GCA pts vs RA pts in the claims
database, adjusted for age and oral GC use, were estimated with Poisson regression.
Results: The healthcare claims database included 4804 GCA pts (mean [SD] age, 73.4 [9.8] years; follow-up, 3.89 [3.12]
years) and 15,164 RA pts (mean [SD] age, 60.3 [8.17] years; follow-up, 4.52 [3.78] years). IRs of myocardial infarction,
stroke, GI perforation, and hepatic events in TCZ-naive GCA pts from the healthcare claims database (Table) exceeded IRs
in TCZ-naive RA pts from healthcare insurance claims. Consistent with this, AESI IRs in TCZ-treated GCA pts (n = 149,
~138 PY) in the GiACTA clinical trial were different from those in TCZ-treated RA pts (n = 7647; mean [SD] age, 52 [12.6]
years; ~22,394 PY) in the pooled clinical trial population. GCA pts were at higher risk than RA pts for all AESI in the US
claims database after adjusting for age and oral GC use.
Conclusion: TCZ-naive GCA pts from the healthcare claims analysis had higher AESI IRs than TCZ-naive RA pts. Clinical
trial data for TCZ in RA pts and GCA pts reflect these findings and suggest differences in the underlying disease burdens
associated with RA and GCA. The higher doses and longer courses of GCs used in GCA may also influence the incidence of
AESI. Future analyses are needed to determine how differences in patient demographics may further differentiate the safety
profile of TCZ between RA pts and GCA pts. References: 1Stone H et al. Arthritis Rheumatol. 2016;68:S10 abstr. 2Stone JH
et al. N Engl J Med. In press. 3Villiger PM et al. Lancet. 387(10031):1921.
Disclosure: S. Gale, Genentech/Roche, 1,Genentech/Roche, 3; S. Dimonaco, Roche Products Ltd., 1,Roche Products Ltd.,
3; H. Trinh, Genentech, 3; K. Tuckwell, Roche, 1,Genentech, 3; N. Collinson, Roche Products Ltd., 1,Roche Products Ltd.,
3; J. H. Stone, Roche, 2,Roche, 5; K. Sarsour, Genentech, 3; J. Pei, Roche, 1,Genentech, 3; J. H. Best, Roche,
1,Genentech, 3; C. Birchwood, Genentech, 3; S. Mohan, Genentech, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/safety-events-in-giant-cell-arteritis-and-
rheumatoid-arthritis-patient-populations
Assessment of Treatment Response By 18f-Fludeoxyglucose Positron Emission

Tomography (FDG-PET) in Patients with Large Vessel Vasculitis (LVV)
Shubhasree Banerjee1, Sara Alehashemi2, Ali Cahid Civelek3, Elaine Novakovich4, Armin Bagheri5, Ashkan Malayeri3,
Mark Ahlman3 and Peter C. Grayson6, 1Fellowship and training branch, NIAMS/NIH, Bethesda, MD, 2Rheumatology,
National Institutes of Health, Bethesda, MD, 3Radiology and Imaging Sciences, National Institutes of Health, Bethesda,
MD, 4Systemic Autoimmunity Branch, NIAMS, National Institutes of Health, Bethesda, MD, 5Vasculitis Translational
Research Program, NIAMS, NIH, Bethesda, MD, 6Research, National Institutes of Health, Bethesda, MD
SESSION INFORMATION
Background/Purpose:
Disease activity in large vessel vasculitis (LVV) is traditionally assessed by clinical and serological (ESR, CRP) parameters.
Imaging assessment, including FDG-PET, may also be useful to monitor LVV. The study objective was to determine if
currently available therapies for LVV impact disease activity as assessed by clinical, serologic, and imaging-based
parameters.
Methods:
Patients with giant cell arteritis (GCA) or Takayasu’s arteritis (TAK) were recruited into a prospective, observational cohort.
All subjects in this study underwent ≥2 FDG-PET/CT scans at 6-month intervals. Serologic assessment (ESR, CRP), clinical
assessment [physician global assessment (PGA)] and imaging assessment (PETVAS) was determined at each visit. PETVAS
is a global summary score of arterial FDG uptake assessed qualitatively relative to liver activity in 9 vascular beds with
higher scores indicating more vascular inflammation. Clinical and imaging assessments were performed blinded to each
other. Treatment status between visits was categorized as increased, decreased, or unchanged. Treatment change was defined
as change in daily prednisone by ≥5mg or addition/50% dose change of a DMARD or biologic therapy. Paired Wilcoxon test
was used to compare changes in PETVAS, ESR, CRP and PGA with change in overall therapy and with addition/increase in
specific medications.
Results:
FDG-PET/CT was performed in 33 patients with LVV (GCA=21; TAK=12) over 98 visits. Interval treatment changes
involved glucocorticoids (n=32), methotrexate (n=13), tocilizumab (n=7), TNF inhibitors (n=7), or another DMARD/
biologic (n=6). Increased, decreased, or unchanged therapy was recorded over 27, 13, and 23 visit intervals respectively.
There was simultaneous glucocorticoid reduction with DMARD increase over 2 intervals, which were excluded from
analysis. In the increased treatment group, a significant reduction in PETVAS score (p<0.01), inflammatory markers
(p<0.01) and PGA (p=0.01) was noted. In the decreased treatment group, PETVAS scores increased (p=0.05) but there was
no change in ESR (p=0.3), CRP(p=0.2), or PGA (p=0.28). In the unchanged treatment group, PETVAS (p=0.88), ESR
(p=0.8), CRP (p=0.6) and PGA (p=0.48) remained unchanged. In terms of specific therapies, addition of tocilizumab,
resulted in significant reduction in PETVAS (p=0.01), acute phase reactants (p=0.01) and PGA (p=0.03), whereas TNF
inhibitors and methotrexate addition/dose increase had variable effects on clinical, serological, and imaging parameters.
Conclusion:
Similar to clinical and serologic assessment, vascular inflammation assessed by FDG-PET improves with increased
treatment and is stable without change in therapy. Unlike clinical and serological assessment, which did not change with
reduction in treatment over a 6 month interval, vascular inflammation assessed by FDG-PET worsens with decreased
therapy. Specific medications may affect vascular FDG uptake differently. These findings suggest that FDG-PET is useful to
monitor treatment response and may be a more sensitive biomarker to detect disease recurrence in the setting of treatment
reduction compared to clinical and serologic assessment.
Disclosure: S. Banerjee, None; S. Alehashemi, None; A. C. Civelek, None; E. Novakovich, None; A. Bagheri, None; A.
Malayeri, None; M. Ahlman, None; P. C. Grayson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/assessment-of-treatment-response-by-

18f-fludeoxyglucose-positron-emission-tomography-fdg-pet-in-patients-with-large-vessel-vasculitis-lvv
Short and Long-Term Follow-up with Tocilizumab in Giant Cell Arteritis.

National Multicenter Study of 49 Patients of Clinical Practice
Lucia C. Domínguez-Casas1, Javier Loricera1, Jose L. Hernández2, Santos Castañeda3, Vicente Aldasoro4, María Varela-
García5, Rosario Ibañez-Bosch5, Antonio Mera6, Eva Pérez-Pampin6, Alicia Humbría7, Jaime Calvo-Alén8, Elena
Aurrecoechea9, Javier Narváez10, Amalia Sánchez-Andrade11, Paloma Vela12, Elvira Diez Alvarez13, Clara Moriano14,
Cristina Mata15, Pau Lluch16, Concepción Moll17, Íñigo Hernández-Rodríguez18, Vanesa Calvo-Río1, José Andrés Román-
Ivorra19, Carlos Vazquez20, Alfonso Corrales1, MC Gonzalez-Vela21, Francisco Ortiz-Sanjuán22, Belén Atienza-Mateo1,
José Luis Martín-Varillas1, Miguel Angel González-Gay23 and Ricardo Blanco1, 1Rheumatology, Hospital Universitario
Marqués de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain, 2Internal Medicine, Hospital
Universitario Marqués de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain, 3Hospital
Universitario La Princesa. IIS-IP. Madrid. Spain, Madrid, Spain, 4Hospital Alto Deba. Mondragón. Spain, Mondragon,
Spain, 5Rheumatology, Complejo Hospitalario de Navarra. Navarra. Spain, Navarra, Spain, 6Rheumatology, Complejo
Hospitalario Universitario de Santiago. Galicia. Spain, Santiago de Compostela, Spain, 7Rheumatology, Hospital
Universitario La Princesa. IIS-IP. Madrid. Spain, Madrid, Spain, 8Rheumatology, Hospital de Sierrallana. Torrelavega.
Cantabria. Spain, Alava, Spain, 9Rheumatology, Hospital de Sierrallana, Torrelavega. Cantabria. Spain, Torrelavega, Spain,
10Rheumatology Department, Hospital de Bellvitge. Barcelona. Spain, L’Hospitalet de Llobregat, Spain, 11Hospital
Universitario Lucus Augusti. Lugo. Spain, Lugo, Spain, 12Reumatología, Hospital General Universitario de Alicante.
Alicante. Spain, Alicante, Spain, 13Complejo Asistencial Universitario de León. León. Spain, León, Spain, 14Rheumatology,
Complejo Asistencial Universitario de León. León. Spain, Leon, Spain, 15Rheumatology, Hospital de Laredo. Laredo. Spain,
Laredo, Spain, 16Rheumatology, Hospital Mateu Orfila. Menorca. Spain, Menorca, Spain, 17Rheumatology., Hospital Mateu
Orfila. Menorca. Spain, Menorca, Spain, 18Rheumatology, CHUVI Vigo. Galicia. Spain, Vigo, Spain, 19Rheumatology,
Hospital Universitario La Fe. Valencia. Spain, Valencia, Spain, 20Rheumatology, Hospital Miguel Servet. Zaragoza. Spain,
Zaragoza, Spain, 21Pathology Anatomy, Hospital Universitario Marqués de Valdecilla. IDIVAL. Santander. Universidad de
Cantabria. Spain, Santander, Spain, 22Rheumatology., Hospital Universitario La Fe. Valencia. Spain, Valencia, Spain,
23Rheumatology, Hospital Universitario Marqués de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain,
Johannesburg, South Africa
SESSION INFORMATION
Background/Purpose: Randomized clinical trial has shown the efficacy of tocilizumab (TCZ) in Giant cell arteritis (GCA).
However this data are of selected cases of clinical trial and only a short follow-up have been published. Our aim was to
assess the short and long-term efficacy/side effects in clinical practice
Methods: Multicenter open-label study on 49 GCA patients treated with TCZ [iv; 8 mg/kg/monthly (n=45), and
subcutaneously; 162 mg/week (n=4)]. We assessed the short and long-term efficacy/safety and the optimization of TCZ
dose.
Results: We included 49 patients (39 women/10 men), mean age 73±9 years. The main clinical features at TCZ onset were:
polymyalgia rheumatica (n=31), headache (25), asthenia (17), constitutional syndrome (15), jaw claudication (5), and visual
loss (6). Besides corticosteroids and before TCZ, 43 patients had also received several conventional immunosuppressive
and/or biologic drugs. 45 of 49 patients achieved a rapid and maintained clinical improvement after TCZ (Table). After a
median follow-up of 18 [IQR, 7-28] months we observe a reduction of the median of: a) C-reactive protein; b) ESR; and c)
prednisone dose. In this follow-up period, the outcome of patients was as follows: a) discontinuation of TCZ due to
sustained remission(n=8); b) dose reduction due to improvement (8) or side effects (4); c) withdrawal of TCZ because of
side effects (9); and d) the same dose that at onset (19). TCZ was discontinued due to: severe neutropenia; recurrent
pneumonia; colon adenocarcinoma; cytomegalovirus infection; Alzheimer´s disease and atrioventricular blockade;
hypertensive crisis during infusion; myelodysplastic syndrome; colon neoplasm and overall health deterioration. The latter
patient died because of stroke. Another patient also died after the second TCZ infusion due to stroke in the context of an
infective endocarditis. In another one, the dose had to be reduced by recurrent urinary tract infection. In other two patients
TCZ was reduced because of moderate neutropenia (one of them also developed cellulitis) and another patient developed
diverticulitis.
Conclusion: TCZ therapy leads to a rapid and maintained improvement in patients with refractory GCA and/or with
unacceptable side effects related to corticosteroids. However, the risk of neutropenia and infection should be kept in mind
when using this biologic agent in patients with GCA
TABLE
Baseline Month 6 Month 12 Month 18 Month 24
Clinical improvement, % (n) 100 (43/43)** 97 (32/33)** 91 (20/22)** 100 (16/16)*
Laboratory markers, median
[IQR]
ESR (mm/1st/h) 43 [18-66] (46) 16 [2-5]** (38) 5 [2-8.5]** (28) 2 [2-15.5]** 6 [2-12.5]** (16)
(20)
CRP (mg/dl) 1.9 [1.1-3.2] 0.1 [0.1-0.2]** 0.1 [0.1-0.3]** 0.1 [0.1-0.6]* 0.2 [0.1-0.3]**
(49) (41) (29) (18) (16)
Dose of corticosteroids, median 15 [10-30] (49) 5 [2.5-7.5] (47) 2.5 [0-5] (33) 2.5 [0-5] (23) 2.5 [0-5.6] (17)
[IQR]
The number of patients with available data is shown in parentheses
* p <0.05 ** p < 0.01 vs. baseline (Wilcoxon test)The number of patients with available data is shown in parentheses
Disclosure: L. C. Domínguez-Casas, None; J. Loricera, None; J. L. Hernández, None; S. Castañeda, None; V.

Aldasoro, None; M. Varela-García, None; R. Ibañez-Bosch, None; A. Mera, None; E. Pérez-Pampin, None; A.
Humbría, None; J. Calvo-Alén, None; E. Aurrecoechea, None; J. Narváez, None; A. Sánchez-Andrade, None; P. Vela,
None; E. Diez Alvarez, None; C. Moriano, None; C. Mata, None; P. Lluch, None; C. Moll, None; Í. Hernández-
Rodríguez, None; V. Calvo-Río, None; J. A. Román-Ivorra, None; C. Vazquez, None; A. Corrales, None; M. Gonzalez-
Vela, None; F. Ortiz-Sanjuán, None; B. Atienza-Mateo, None; J. L. Martín-Varillas, None; M. A. González-Gay, None;
R. Blanco, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/short-and-long-term-follow-up-with-

tocilizumab-in-giant-cell-arteritis-national-multicenter-study-of-49-patients-of-clinical-practice
A Patient Based Reliability Exercise of Omeract Ultrasound Definitions in

Giant Cell Arteritis
Valentin S. Schäfer1, Stavros Chrysidis2, Christian Dejaco3, Christina Duftner4, Annamaria Iagnocco5, George A. W.
Bruyn6, Greta Carrara7, MA D'Agostino8, Eugenio De Miguel9, Andreas P Diamantopoulos10, Ulrich Fredberg11, Wolfgang
Hartung12, Alojzija Hočevar13, Tanaz A. Kermani14, Matthew J. Koster15, Tove Lorenzen16, Pierluigi Macchioni17, Marcin
Milchert18, Uffe Møller Døhn19, Chetan Mukhtyar20, Cristina Ponte21, Sofia Ramiro22, Carlo Alberto Scirè23, Lene
Terslev24, Kenneth J. Warrington15, Bhaskar Dasgupta25 and Wolfgang A. Schmidt26, 1Immanuel Krankenhaus Berlin,
Medical Center for Rheumatology Berlin-Buch, Berlin, Germany, 2Department of Rheumatology, Hospital of Southwest
Denmark, Esbjerg, Denmark, 3Rheumatology and Immunology, Medical University Graz, Graz, Austria, 4Department of
Internal Medicine, Clinical Division of Internal Medicine II, Medical University Innsbruck, Innsbruck, Austria, 5Academic
Rheumatology Unit, Università degli Studi di Torino, Torino, Italy, 6Rheumatology, MC Groep, Loenga, Netherlands,
7Epidemiology Unit, Italian Society for Rheumatology, Milano, Italy, 8Rheumatology, Versailles-Saint Quentin en Yvelines
University, Boulogne-Billancourt, France, 9Medicine, Universidad Autonoma Madrid, MADRID, Spain, 10Martina Hansens
Hospital, Bærum, Oslo, Norway, 11Diagnostic Centre, Silkeborg Regional Hospital, 8600 Silkeborg, Denmark,
12Department of Rheumatology/Clinical Immunology, Asklepios Medical Center, 93077 Bad Abbach, Germany,
13Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia, 14Rheumatology, University of
California Los Angeles, Los Angeles, CA, 15Rheumatology, Mayo Clinic, Rochester, MN, 16Diagnostic Centre, Region
Hospital Silkeborg, Silkeborg, Denmark, 17Arcispedale Santa Maria Nuova, Reggio Emilia, Italy, 18Pomeranian Medical
University, Szczecin,, Szczecin, Poland, 19Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup,
Copenhagen Center for Arthritis Research (COPECARE), Glostrup, Denmark, 20Norfolk and Norwich University Hospital,
Norwich, United Kingdom, 21Rheumatology Department, Hospital de Santa Maria - Centro Hospital Lisboa Norte, Lisbon,
Portugal, 22Rheumatology, Department of Rheumatology, LUMC, Leiden, Netherlands, Leiden, Netherlands, 23Italian
Society for Rheumatology, Milan, Italy, 24Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine
Diseases, Rigshospitalet, Denmark, Copenhagen, Denmark, 25Rheumatology, Southend University Hospital NHS
Foundation Trust, Southend, UK, Westcliff-on-Sea, United Kingdom, 26Medical Center for Rheumatology and Clinical
Immunology Berlin-Buch, Immanuel Krankenhaus Berlin, Berlin, Germany
SESSION INFORMATION
Background/Purpose: To test the reliability of recently established consensus-based ultrasound definitions for normal and
vasculitic temporal and axillary arteries in patients with giant cell arteritis (GCA) and in controls.
Methods: A preliminary one-day meeting was held in Southend, United Kingdom. One year later, a full three-day meeting
according to OMERACT ultrasound group guidelines for patient based reliability testing was conducted in Berlin, Germany.
This meeting included a 6-hour training session for standardization of examination technique and ultrasound machine
settings. In both exercises 6-18 MHz linear ultrasound transducers of high quality ultrasound machines were used. Bilateral
common superficial temporal arteries with frontal and parietal branches as well as axillary arteries were examined at two
time points by 12 sonographers for normal findings, halo sign and compression sign using consensus-based definitions. In
the preliminary meeting, 4 patients had longstanding established GCA, 1 patient had severe arteriosclerosis; and 1 normal
control was included. In the second meeting, 4 GCA patients with more recent diagnosis and 2 healthy controls were
examined. Inter- and intra-observer reliability was calculated.
Results: In the preliminary exercise, inter-reader reliabilities were fair to moderate for the overall diagnosis of GCA (Light’s
kappa, 0.29-0.51) and poor to fair for identifying vasculitis in the respective anatomical segments (Light’s kappa, 0.02-0.46).
Intra-reader reliabilities were moderate (Cohen’s kappa, 0.32-0.64). In the main exercise, inter-reader reliability was good to
excellent (Light’s kappa, 0.76-0.86) for the overall diagnosis of GCA and moderate to good (Light’s kappa, 0.46-0.71) for
identifying vasculitis in the respective anatomical segments. Intra-reader reliability was excellent for diagnosis of GCA
(Cohen’s kappa, 0.91) and good (Cohen’s kappa, 0.71-0.80) for the anatomical segments.
Conclusion: The patient based reliability for ultrasound definitions of halo and compression sign of temporal and for halo
sign of axillary artery is good to excellent in recent onset GCA. Training of a standardized examination protocol is crucial
for achieving specific results and good inter- and intra-observer reliabilities. The reliability in established disease requires
further study.
Disclosure: V. S. Schäfer, None; S. Chrysidis, None; C. Dejaco, Merck Sharp and Dohme GmbH, 5,Merck Sharp and
Dohme GmbH, 7,Merck Sharp and Dohme GmbH, 8; C. Duftner, None; A. Iagnocco, None; G. A. W. Bruyn, None; G.
Carrara, None; M. D'Agostino, BMS, AbbVie, Novartis, 8; E. De Miguel, None; A. P. Diamantopoulos, Roche
Pharmaceuticals, 8,BMS, 8; U. Fredberg, None; W. Hartung, None; A. Hočevar, None; T. A. Kermani, None; M. J.
Koster, None; T. Lorenzen, None; P. Macchioni, None; M. Milchert, None; U. M. Døhn, None; C. Mukhtyar, None; C.
Ponte, None; S. Ramiro, None; C. A. Scirè, None; L. Terslev, None; K. J. Warrington, None; B. Dasgupta, None; W. A.
Schmidt, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-patient-based-reliability-exercise-of-

omeract-ultrasound-definitions-in-giant-cell-arteritis
Serum IL-6, SAA and Calprotectin As Biomarkers in Giant Cell Arteritis and
Polymyalgia Rheumatica
Yannick van Sleen, Marjolein Hoekstra, Johan Bijzet, Wayel H. Abdulahad, Annemieke M.H. Boots and Elisabeth
Brouwer, Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen,
Groningen, Netherlands
SESSION INFORMATION
Background/Purpose: GCA and PMR are closely related inflammatory diseases. The diagnostic criteria of both disorders
depend on a combination of clinical features and elevated ESR or CRP levels. ESR and CRP are also used to monitor
disease activity. These biomarkers, however, are not disease specific and not consistently elevated in all GCA and PMR
patients. Previously, serum levels of IL-6, SAA and calprotectin were found to be increased in small scale cross-sectional
GCA and PMR studies. Calprotectin expression was also found in neutrophils and macrophages in temporal artery biopsies
(TABs) of GCA patients. The aim of this study was to identify and compare the values of IL-6, SAA and calprotectin as
biomarkers for diagnosing GCA and PMR, monitoring disease activity and predicting disease course.
Methods: Serum concentrations of IL-6, SAA and calprotectin were determined by ELISA in 36 newly diagnosed GCA
patients (C-GCA (TAB+) or LV-GCA (PET/CT+)) and 27 newly diagnosed PMR patients (fulfilling the Chuang-Hunder
criteria), before start of glucocorticoid treatment. Thirty age- and sex matched healthy controls were included as well.
Follow-up sera from patients were tested again 3 months (n= 21 for GCA and n= 21 for PMR) and 1 year (n= 23 for GCA
and n= 16 for PMR) after the start of treatment. TABs (n=17) from GCA patients were stained with anti-calprotectin and
anti-CD15 by immunohistochemistry.
Results: Baseline levels of IL-6, SAA and calprotectin in GCA and PMR patients were higher compared to healthy controls.
Treatment decreased the levels of IL-6 and SAA in both GCA patients and PMR patients, but serum levels of calprotectin
decreased in PMR patients only. Relapse free survival between the groups with relatively low and high levels of the serum
markers did not differ. IL-6 correlated with CRP, and SAA correlated with both CRP and ESR. Calprotectin did not correlate
with IL-6, SAA, CRP or ESR, suggesting an IL-6 independent pathway. Interestingly, calprotectin levels were also elevated
in GCA and PMR patients with normal ESR or CRP levels. Immunohistochemical staining of TABs showed calprotectin
expression in all TABs (Fig. 1). Only a minority of calprotectin positive cells were CD15+ neutrophils.
Conclusion: Serum levels of IL-6, SAA and calprotectin discriminate GCA and PMR patients from healthy controls at the
group level. In addition, serum levels of IL-6 and SAA decrease with treatment induced remission in GCA and PMR
patients. None of the biomarkers tested at baseline predicted future relapse. Serum calprotectin could be a potential marker
for silent ongoing vascular inflammation in GCA patients. The diagnostic value of serum IL-6, SAA and especially
calprotectin as biomarkers should be further examined and validated.
Fig. 1: Calprotectin expression in the TAB of a GCA patient (DAB/brown).
Disclosure: Y. van Sleen, None; M. Hoekstra, None; J. Bijzet, None; W. H. Abdulahad, None; A. M. H. Boots, None; E.
Brouwer, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/serum-il-6-saa-and-calprotectin-as-

biomarkers-in-giant-cell-arteritis-and-polymyalgia-rheumatica
European League Against Rheumatisms Recommendations for the Use of

Imaging in Large Vessel Vasculitis in Clinical Practice
Christian Dejaco1, Sofia Ramiro2, Christina Duftner3, Florent L. Besson4, Thorsten Bley5, Daniel Blockmans6, Elisabeth
Brouwer7, Marco A. Cimmino8, Eric Clark9, Bhaskar Dasgupta10, Andreas P Diamantopoulos11, Haner Direskeneli12,
Annamaria Iagnocco13, Thorsten Klink5, Lorna Neill14, Cristina Ponte15, Carlo Salvarani16, Riemer Slart17, Madeline
Whitlock18 and Wolfgang A. Schmidt19, 1Rheumatology, Hospital of Bruneck, Bruneck, Italy, 2Rheumatology, Department
of Rheumatology, LUMC, Leiden, Netherlands, Leiden, Netherlands, 3Department of Internal Medicine, Clinical Division
of Internal Medicine II, Medical University Innsbruck, Innsbruck, Austria, 4Department of Nuclear Medicine, CHU Bicêtre,
AP-HP, Université Paris-Sud, Paris, France, 5University of Würzburg, Würzburg, Germany, 6General Internal Medicine,
University Hospital Gasthuisberg, Leuven, Belgium, 7Rheumatology and Clinical Immunology, University of Groningen,
University Medical Center Groningen, Groningen, Netherlands, 8Research Laboratory and Academic Unit of Clinical
Rheumatology, Department of Internal Medicine, University of Genova, Genova, Italy, 9PMRGCAuk, London, United
Kingdom, 10Rheumatology, Southend University Hospital NHS Foundation Trust, Southend, UK, Westcliff-on-Sea, United
Kingdom, 11Rheumatology, Martina Hansens Hospital, Bærum, Oslo, Norway, 12Departement of İnternal Medicine,
Division of Rheumatology, Marmara University, Istanbul, Turkey, 13Academic Rheumatology Unit, Università degli Studi di
Torino, Torino, Italy, 14PMRGCAuk, Dundee, United Kingdom, 15Instituto de Medicina Molecular (IMM), Rheumatology
Research Unit, Lisbon, Portugal, 16Rheumatology Unit, Arcispedale Santa Maria Nuova - IRCCS; Università di Modena e
Reggio Emilia, Reggio-Emilia, Italy, 17University of Groningen, Enschede, Netherlands, 18Southend University Hospital,
Southend, United Kingdom, 19Medical Center for Rheumatology and Clinical Immunology Berlin-Buch, Immanuel
Krankenhaus Berlin, Berlin, Germany
SESSION INFORMATION
Background/Purpose: Modern imaging modalities including ultrasound, magnetic resonance imaging (MRI), computed
tomography (CT) and 18F-FDG positron emission tomography (PET/CT) have been increasingly used in primary large
vessel vasculitis (LVV) including giant cell arteritis (GCA) and Takayasu arteritis (TAK). However, there is still significant
controversy and uncertainty about when to use which imaging technique, and whether imaging might be helpful during
follow-up to assess disease activity and damage. We aimed to develop EULAR recommendations for the use of imaging
modalities in LVV in clinical practice.
Methods: The EULAR Standardised Operating Procedures have been followed. A systematic literature review was
conducted to retrieve data on the role of imaging in LVV. Based on evidence and expert opinion, the task force consisting of
20 experts (physicians, a health care professional and patients) from 12 EULAR countries developed recommendations, with
consensus obtained through informal voting. The final level of agreement was voted anonymously.
Results: A total of 12 recommendations have been formulated (Table). The task force recommends an early imaging test in
patients with suspected LVV, assuming high expertise and prompt availability of the imaging technique. Ultrasound has been
suggested as the first choice imaging modality in GCA, because of a good performance of the test, easy access, absence of
radiation and other procedural risks, and low resource use. MRI, and in case of predominant large vessel (LV)-GCA, PET
and CT, might be alternatives to ultrasound. For TAK, MRI is the preferred imaging modality, because of the absence of
radiation exposure and the possibility to assess simultaneously the vessel wall and luminal changes of the aorta and its
proximal branches. PET, CT and ultrasound can be used as alternatives.
In patients with a suspected flare of LVV, imaging might be helpful to assess disease activity. The frequency and choice of
imaging modalities for long-term monitoring of structural damage remains an individual based decision. All imaging should
be performed by a trained specialist using appropriate equipment, operational procedures and settings.
Conclusion: These are the first EULAR recommendations providing up-to-date guidance on the role of imaging in the
diagnosis and monitoring of patients with (suspected) LVV.
Statement LoE LoA
1. In patients with suspected GCA, an early imaging test
is recommended to complement the clinical criteria for 9.2
diagnosing GCA, assuming high expertise and prompt 1 (2.1)
availability of the imaging technique. Imaging should not 90% ≥8
delay initiation of treatment.
2. In patients in whom there is a high clinical suspicion
of GCA and a positive imaging test, the diagnosis of GCA
may be made without an additional test (biopsy or further 9.4
imaging). In patients with a low clinical probability and a 2 (1.0)
negative imaging result, the diagnosis of GCA can be 90% ≥8
considered unlikely. In all other situations, additional
efforts towards a diagnosis are necessary.
3. US of temporal ± axillary arteries is recommended as 9.7
the first imaging modality in patients with suspected (0.6)
predominantly cranial GCA*. A non-compressible ’halo’ 1
sign is the US finding most suggestive of GCA. 100%
≥8
4. High resolution MRI of cranial arteriesǂ to investigate 9.2
mural inflammation may be used as an alternative for GCA 2 (1.1)
diagnosis if US is not available or inconclusive.
90% ≥8
5. CT and PET are not recommended for the assessment 9.5
of inflammation of cranial arteries. 5 (1.2)
95% ≥8
6. US, PET, MRI and/or CT may be used for detection of 3 (PET, 9.8
mural inflammation and/or luminal changes in extracranial CT) -5 (0.6)
arteries to support the diagnosis of LV-GCA. US is of (US,
limited value for assessment of aortitis. 100%
MRI) ≥8
7. In patients with suspected TAK, MRI to investigate
mural inflammation and/or luminal changes should be used 9.1
as the first imaging test to make a diagnosis of TAK, 3 (1.4)
assuming high expertise and prompt availability of the 90% ≥8
technique.
8. PET, CT and/or US may be used as alternative 9.4
3 (CT) –
imaging modalities in patients with suspected TAK. US is (0.8)
of limited value for assessment of the thoracic aorta. 5 (PET,
100%
US)
≥8
9. Conventional angiography is not recommended for the 9.8
diagnosis of GCA or TAK as it has been superseded by the (0.6)
previously mentioned imaging modalities. 5
100%
≥8
10. In patients with LVV (GCA or TAK) in whom a flare 9.4
is suspected, imaging might be helpful to confirm or (0.8)
exclude it. Imaging is not routinely recommended for 5
patients in clinical and biochemical remission. 100%
≥8
11. In patients with LVV (GCA or TAK), MRA, CTA
and/or US may be used for long-term monitoring of 9.3
structural damage, particularly to detect stenosis, occlusion, (1.2)
5
dilatation and/or aneurysms. The frequency of screening as
well as the imaging method applied should be decided on 95% ≥8
an individual basis.
12. Imaging examination should be done by a trained 5 9.8
specialist using appropriate equipment, operational (0.6)
procedures and settings. The reliability of imaging, which 100%
has often been a concern, can be improved by specific ≥8
training. Suggestions for technical and operational
parameters are depicted in Box 1.
LoA, level of agreement; CT, computed tomography; GCA, giant cell arteritis; LV-GCA, large vessel GCA; LoE, Level of
evidence according to the Oxford Centre for Evidence Based Medicine; LVV, large vessel vasculitis; MRI, magnetic
resonance imaging; PET, 18F-FDG positron emission tomography; TAK, Takayasu arteritis; US, ultrasound
*cranial symptoms of GCA include headache, visual symptoms, jaw claudication, swelling and/or tenderness of temporal
arteries; ǂcranial arteries: superficial temporal, occipital and facial, usually all visible in one examination in MRI.
Disclosure: C. Dejaco, None; S. Ramiro, None; C. Duftner, None; F. L. Besson, None; T. Bley, None; D. Blockmans,
None; E. Brouwer, None; M. A. Cimmino, None; E. Clark, None; B. Dasgupta, None; A. P. Diamantopoulos, Roche
Pharmaceuticals, 8,Bristol-Myers Squibb, 8; H. Direskeneli, None; A. Iagnocco, None; T. Klink, None; L. Neill, None; C.
Ponte, None; C. Salvarani, None; R. Slart, None; M. Whitlock, None; W. A. Schmidt, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/european-league-against-rheumatisms-

recommendations-for-the-use-of-imaging-in-large-vessel-vasculitis-in-clinical-practice
Damage and Predictors of Damage in Takayasu’s Arteritis

Antoine G. Sreih1, Tanaz A. Kermani2, David Cuthbertson3, Simon Carette4, Nader A. Khalidi5, Curry L. Koening6, Carol
A. Langford7, Carol A. McAlear8, Paul A. Monach9, Larry W. Moreland10, Christian Pagnoux11, Philip Seo12, Kenneth J.
Warrington13, Steven R. Ytterberg13 and Peter A. Merkel1,14, 1Division of Rheumatology, University of Pennsylvania,
Philadelphia, PA, 2Division of Rheumatology, University of California, Los Angeles, CA, 3Biostatistics and Informatics,
Department of Pediatrics, University of South Florida, Tampa, FL, 4Mount Sinai Hospital, University of Toronto, Toronto,
ON, Canada, 5Rheumatology, McMaster University, Hamilton, ON, Canada, 6Rheumatology, University of Utah, Salt Lake
City, UT, 7Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, OH, 8University of Pennsylvania,
Philadelphia, PA, 9Boston University School of Medicine, Boston, MA, 10Rheumatology & Clinical Immunology,
University of Pittsburgh, Pittsburgh, PA, 11Rheumatology-Vasculitis clinic, Mount Sinai Hospital, University of Toronto,
Toronto, ON, Canada, 12Medicine, Johns Hopkins University, Baltimore, MD, 13Rheumatology, Mayo Clinic, Rochester,
MN, 14Biostatistics, Epidemiology, and Bioinformatics, University of Pennsylvania, Philadelphia, PA
SESSION INFORMATION
Background/Purpose: Information regarding the degree and the predictors of damage in patients with Takayasu’s arteritis
(TAK) is limited. This study aimed to characterize damage and identify predictors of damage in patients with TAK.
Methods: Patients with TAK enrolled in a multicenter, longitudinal study were included. Measures of disease damage,
including the Vasculitis Damage Index (VDI) and the Large-Vessel Vasculitis Index of Damage (LVVID), were assessed at
baseline and follow-up visits. Results from patients with a diagnosis of TAK made within 6 months prior to entry to the
cohort were also separately analyzed. Kaplan-Meier survival curves were used to analyze development of new damage.
Univariate statistics and multivariate Cox regression modeling was used to analyze clinically-relevant baseline predictors of
new damage.
Results: The study included 128 patients with TAK: 94% female, 89% Caucasian, and median duration of follow-up 3.5
years (1.9, 6.2). At entry into the cohort, 113 patients (88%) had at least one damage item recorded on VDI and LVVID
[VDI median score 3 (IQR: 1-5)] and [LVVID median score: 2 (1-4)]. 31/128 (24%) of patients had a diagnosis of TAK
made within 6 months prior to study entry, 81% of whom had at least 1 item documented on VDI and LVVID. During the
follow-up period 96 patients (75%) accrued at least one new damage item, most of which occurred in the first year of
follow-up (Figure 1). The cardiac and peripheral arterial systems accounted for most of the damage captured at baseline and
follow-up. Results of univariate and multivariate analysis of clinically-relevant baseline predictors are shown in Table 1.
Patients with new-onset disease (diagnosed ≤ 6 months within study entry) had a higher risk of new damage than patients
with longer disease duration. The use of glucocorticoids was not associated with development of new damage.
Conclusion: Damage predominantly related to disease rather than treatment is present in the majority of patients with TAK,
even within 6 months of diagnosis. Although damage accrues more commonly early in the disease course, the majority of
patients with TAK continue to accrue new damage, mostly related to disease, even after several years of follow-up. Future
research should address the question of whether treatment of TAK during the early stages of the disease reduces
accumulation of disease-related damage.
Figure 1. Time to development of new damage on the Vasculitis Damage Index or the
Large Vessel Vasculitis Index of Damage in 128 patients with Takayasu’s arteritis
Table 1. Baseline predictors of new damage during follow-up for
patients with Takayasu’s arteritis
Predictors of Univariate analysis Multivariate analysis
damage
Hazard p Hazard p
95% CI 95% CI
Ratio value Ratio value
0.592- 0.526-
Age > 35 at baseline 0.940 0.794 0.861 0.553
1.494 1.411
Duration of the
1.397- 1.025-
disease 2.343 0.001 1.957 0.041
3.930 3.738
(≤6 months)
Presence of damage 0.888- 0.636-
1.943 0.096 1.512 0.349
at baseline 4.252 3.595
0.698- 0.396-
Sex 0.698 0.439 1.060 0.907
0.280 2.835
0.540- 0.638-
Race 1.129 0.747 1.381 0.412
2.360 2.992
No disease activity
0.395- 0.448-
Physician Global 0.629 0.050 0.747 0.263
1.001 1.246
Assessment=0
No glucocorticoids 0.456- 0.418-
0.729 0.185 0.681 0.122
at baseline 1.164 1.109
No
0.994- 0.709-
immunosuppressive 1.579 0.053 1.239 0.451
2.508 2.164
therapy at baseline
No previous flare at 0.925- 0.678-
1.471 0.102 1.200 0.531
baseline 2.339 2.124
Disclosure: A. G. Sreih, None; T. A. Kermani, None; D. Cuthbertson, None; S. Carette, None; N. A. Khalidi, None; C.
L. Koening, None; C. A. Langford, None; C. A. McAlear, None; P. A. Monach, None; L. W. Moreland, None; C.
Pagnoux, None; P. Seo, GlaxoSmithKline, 5; K. J. Warrington, None; S. R. Ytterberg, None; P. A. Merkel, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/damage-and-predictors-of-damage-in-

takayasus-arteritis
Longitudinal Angiographic Findings in Patients with Takayasu’s Arteritis

Antoine G. Sreih1, Tanaz A. Kermani2, David Cuthbertson3, Simon Carette4, Lindsy J. Forbess5, Nader A. Khalidi6, Curry
L. Koening7, Carol A. McAlear8, Paul A. Monach9, Larry W. Moreland10, Christian Pagnoux11, Philip Seo12, Robert F.
Spiera13, Kenneth J. Warrington14, Steven R. Ytterberg14, Carol A. Langford15 and Peter A. Merkel16,17, 1Rheumatology,
University of Pennsylvania, Philadelphia, PA, 2Division of Rheumatology, University of California, Los Angeles, CA,
3Biostatistics and Informatics, Department of Pediatrics, University of South Florida, Tampa, FL, 4Mount Sinai Hospital,
University of Toronto, Toronto, ON, Canada, 5Medicine, Division of Rheumatology, Cedars-Sinai Medical Center, Los
Angeles, CA, 6Rheumatology, McMaster University, Hamilton, ON, Canada, 7Rheumatology, University of Utah, Salt Lake
City, UT, 8University of Pennsylvania, Philadelphia, PA, 9Boston University School of Medicine, Boston, MA,
10Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, 11Rheumatology-Vasculitis clinic, Mount
Sinai Hospital, University of Toronto, Toronto, ON, Canada, 12Medicine, Johns Hopkins University, Baltimore, MD,
13Rheumatology, Hospital for Special Surgery, New York, NY, 14Rheumatology, Mayo Clinic, Rochester, MN, 15Rheumatic
and Immunologic Diseases, Cleveland Clinic, Cleveland, OH, 16Biostatistics, Epidemiology, and Bioinformatics, University
of Pennsylvania, Philadelphia, PA, 17Division of Rheumatology, University of Pennsylvania, Philadelphia, PA
SESSION INFORMATION
Background/Purpose : Longitudinal data on the type, progression, and predictors of arterial lesions in patients with
Takayasu’s arteritis (TAK) is limited. This study aimed to characterize lesions of large arteries in patients with TAK and
identify predictors of new lesions.
Methods: Clinical, laboratory, and imaging data from patients with TAK enrolled in a prospective, multicenter, longitudinal
study and/or a randomized clinical trial were included in this study. Lesions were defined as “new or worse” or “improved”
arterial aneurysm, stenosis, or occlusion as determined by angiography (83% Magnetic Resonance Angiogram, 23%
Computerized Tomography Angiogram, and 4% Conventional Angiogram). Clinical features were defined as the presence of
any symptom or sign attributed to vasculitis. Logistic regression was used to analyze the association of baseline (visit 1)
variables with new/worse or improved lesions.
Results : The study included 175 patients with TAK: 93% female, 85% Caucasian, mean (±SD) age at diagnosis = 34.4±13.4
years, and mean (±SD) follow-up = 3.8±3.1 years. At baseline, the most frequently affected arteries were subclavian (73% of
patients), abdominal aorta (44%), thoracic aorta (42%), and common carotid (37%) (Figure 1). In 123 patients with serial
imaging, new or worse arterial lesions were noted in 35 patients (28%) predominantly in the subclavian, common carotid,
renal, and iliac territories. 96 % of patients with new lesions were either on prednisone and/or other immunosuppressive
agents. Improved stenotic lesions, mostly of the subclavian and common carotid arteries, were noted in 16 patients (13%) at
follow-up. Clinical features of active disease were absent in 40% of visits at which a new lesion was detected. The mean
levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) did not differ between the immediate prior visit
versus the visit at which a new lesion was detected (ESR mean ± SD= 24.6 ± 4.0 and mean CRP ± SD =12.2 ± 2.8 mg/L at
prior visit vs. ESR= 23.5 ± 3.9 and CRP= 9.5 ± 2.8 mg/L at lesion visit, p= 0.63 and 0.12 for ESR and CRP respectively).
There were no differences in age, sex, ethnicity, presence of a flare prior to the onset of new lesion, or disease duration in
patients with or without new/worse lesions and with or without improved lesions.
Conclusion : Among patients with TAK, large arterial abnormalities are common both at presentation and follow-up. One in
3 patients will continue to develop new or worsening arterial lesions while on treatment with 40% exhibiting no clinical or
laboratory changes. Lesions involving the subclavian and carotids are more likely to improve during follow-up. These
findings raise concerns about the current definition of active disease in TAK and have implications for the management of
patients with TAK and the design and conduct of clinical trials in TAK.
Figure 1. Distribution of arterial lesions at baseline and follow-up visits for patients with Takayasu’s arteritis
Disclosure: A. G. Sreih, None; T. A. Kermani, None; D. Cuthbertson, None; S. Carette, None; L. J. Forbess, None; N.
A. Khalidi, None; C. L. Koening, None; C. A. McAlear, None; P. A. Monach, Genentech and Biogen IDEC Inc.,
2,GlaxoSmithKline, 2,Bristol-Myers Squibb, 2; L. W. Moreland, None; C. Pagnoux, None; P. Seo, GlaxoSmithKline, 5; R.
F. Spiera, None; K. J. Warrington, None; S. R. Ytterberg, None; C. A. Langford, None; P. A. Merkel, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/longitudinal-angiographic-findings-in-

patients-with-takayasus-arteritis
Smoking As a Risk Factor for Giant Cell Arteritis: A Systematic Review and
Meta-Analysis
David Brennan1, Patompong Ungprasert2, Kenneth J. Warrington2 and Matthew J. Koster2, 1Internal Medicine, Mayo
Clinic, Rochester, MN, 2Rheumatology, Mayo Clinic, Rochester, MN
SESSION INFORMATION
Background/Purpose: Tobacco smoking is a well-established risk factor for the development of several autoimmune
diseases such as rheumatoid arthritis and systemic lupus erythematosus. A similar association between smoking and giant
cell arteritis (GCA) has been suspected but remains unclear due to limited study size and conflicting epidemiologic data. In
order to further investigate the association between smoking and the development of GCA we conducted a systematic
review and meta-analysis.
Methods: Two investigators (D.B. and M.K.) independently searched published studies indexed in MEDLINE and
EMBASE from inception to February 2017 using the terms “giant cell arteritis,” “temporal arteritis,” “cranial arteritis,” and
“Horton disease.” Recent conference abstracts available online were also reviewed. The following inclusion criteria were
used: 1) original observational study comparing patients with GCA to healthy controls; 2) inclusion of smoking history; 3)
provision of absolute numbers and/or statistical comparisons with 95% confidence intervals. Study eligibility was
independently determined by the two investigators, with disagreements reviewed by a third investigator (P.U.) and resolved
by consensus. RevMan 5.3 software was used for the data analysis. Point estimates and standard errors were extracted from
individual studies and were combined by the generic inverse variance method of DerSimonian and Laird. Given the high
likelihood of between-study variance, we used a random-effect model rather than a fixed-effect model. Statistical
heterogeneity was assessed using the Cochran's Q test.
Results: The initial search yielded 3312 articles. Of these, thirteen studies (8 prospective and, 5 retrospective case-control
studies) with unique cohorts were identified and included in the primary analysis (ever vs. never smoking history). Patients
in the GCA cohort were more likely to have a history of smoking with an odds ratio of 1.19 (95% CI, 1.01 – 1.39) [Figure
1A]. Considerable heterogeneity was present (I2 = 85%). Five of these studies included information on current smoking
status. One additional study, which only reported current smoking status, was also included. The GCA cohort showed an
association with current tobacco use with an odds ratio of 1.18 (95% CI, 1.01 – 1.38) [Figure 1B].
Conclusion: Our study demonstrated a statistically significant increased risk of GCA among smokers compared to non-
smokers.
Disclosure: D. Brennan, None; P. Ungprasert, None; K. J. Warrington, None; M. J. Koster, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/smoking-as-a-risk-factor-for-giant-cell-

arteritis-a-systematic-review-and-meta-analysis
Prevalence of Relapses of Giant Cell Arteritis in Patients Treated with

Corticosteroids: A Meta-Analysis
Alexandra Addario1, Quitterie Reynaud2,3, Maxime Samson4, Mathilde Francois3, Stéphane Durupt3, Francois Gueyffier1,
Michel Cucherat1, Isabelle Durieu2,5 and Jean-Christophe Lega3,6, 1Equipe Evaluation et Modélisation des Effets
thérapeutiques, Lyon 1 University, Lyon, France, 2HESPER group, Lyon 1 University, Lyon, France, 3Department of
Internal and Vascular Medicine, Lyon Sud Hospital, Hospices Civils de Lyon, Lyon, France, 4Department of Internal
Medicine and Clinical Immunolgy, Hôpital François Mitterrand, CHU de Dijon, Dijon, France, 5Department of Internal and
Vascular, Lyon Sud Hospital, Hospices Civils de Lyon, Lyon, France, 6Equipe Evaluation et Modélisation des Effets
thérapeutiques, UMR CNR 5558, Lyon 1 University, Lyon, France
SESSION INFORMATION
Background/Purpose: The relapse rate of giant cell arteritis (GCA) in the patients treated by corticosteroids (CS) varied
widely in observational series and randomized trials. The purpose of this systematic review was to (i) estimate the
prevalence of relapse and (ii) explain the heterogeneity of relapse rate in patients receiving CS alone.
Methods: We searched from PubMed up to April 2017. Two investigators independently extracted data. The prevalence of
relapse was pooled by random effect model. Heterogeneity (I2 >50%) was explored by meta-regression.
Results: A total of 37 cohorts (6 trials) totalizing 16839 patients were selected. The overall prevalence of relapse was 43%
(95% confidence interval [CI] 0.37-0.50) with a high heterogeneity (I2 =90%). The year of publication was positively
associated with relapse (37 studies, rate increase of 6.1% for one decade, p =0.02) (Figure 1). The length of CS
administration was negatively correlated with the relapse rate (15 studies, rate decrease of 1.1% for one additional month, p
=0.04) (Figure 2), but not with the initial CS dose at diagnosis (P =0.46) or time of follow-up (p=0.12). The patients
included in the control arms of randomized trials testing immunosuppressive drugs relapsed more frequently (62%, CI 47-
75) compared to those in observational studies (40%, CI 33-47) (p =0.006).
Conclusion: The relapse rate of GCA remains high without improvement across decades. The relapse rate might be related
to the duration of CS administration rather than initial dose at induction. Our results challenged the schedules of CS
administration used in randomized trials as standard of care and questioned the size of estimated efficacy of methotrexate
and tocilizumab.
Figure 1
Figure 2
Disclosure: A. Addario, None; Q. Reynaud, None; M. Samson, None; M. Francois, None; S. Durupt, None; F.
Gueyffier, None; M. Cucherat, None; I. Durieu, None; J. C. Lega, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prevalence-of-relapses-of-giant-cell-

arteritis-in-patients-treated-with-corticosteroids-a-meta-analysis
Mast Cell Mediated Inhibition of Systemic IL-6 in candida Albicans Water-

Soluble Fraction (CAWS) Induced Model of Large Vessel Vasculitis
Mingcai Zhang1, Mehrdad Maz2, Don Smith3, Noriko Miura4, Naohito Ohno5, Kottarappat Dileepan6 and Jason Springer7,
1Department of Orthopedics, University of Kansas Medical Center, Kansas City, KS, 2Allergy, Clinical Immunology, and
Rheumatology, Division of Allergy, Clinical Immunology and Rheumatology, Department of Internal Medicine, University
of Kansas Medical Center, Kansas City, KS, 3University of Kansas Medical Center, Kansas City, KS, 4School of Pharmacy,
Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan, 5Tokyo University of Pharmacy and Lift Sciences, Tokyo,
Japan, 6Department of Medicine, University of Kansas Medical Center, Kansas, KS, 7Department of Internal Medicine,
Division of Allergy, Clinical Immunology, & Rheumatology, Kansas University Medical Center, Kansas City, KS
SESSION INFORMATION
Background/Purpose: In forms of large vessel vasculitis (LVV) systemic IL-6 has been shown to follow disease activity.
Furthermore, IL-6 inhibition is an effective treatment for giant cell arteritis, a form of LVV. Our group has demonstrated that
systemic mast cell degranulation results in inhibition of LPS-induced systemic IL-6 production. Further studies
demonstrated that this effect may be mediated through stimulation of histamine-1 receptor (H1R). The purpose of this study
was to determine if mast cell degranulation could inhibit systemic production of IL-6 in a mouse model of vasculitis
(Candida albicans water-soluble fraction induced model or CAWS).
Methods: Two month old male C57BI6/J mice were randomized to 4 groups (n=4/group). Mice were given intraperitoneal
injections of either: a) normal saline (controls), b) CAWS extract, c) compound 48/80 (C48/80, systemic mast cell
degranulation agent), or d) CAWS + C48/80. Injections were given on five consecutive days. Animals were sacrificed at 30
days for measurements of systemic TNF-α, INF-γ and IL-6 by ELISA as well as aortic expression of messenger RNAs
coding for IL-6, suppressor of cytokine signaling-1 (SOCS1), INF-γ, IL-10 and TNF-α. Two tailed student’s T-test were used
for comparisons with p<0.05 considered significant.
Results: CAWS mice had significantly higher systemic IL-6 levels compared to controls (345.2 pg/ml±132.9 vs
56.4pg/ml±19.3,p<0.001). Mice injected with C48/80 + CAWS had significantly lower IL-6 compared to CAWS alone
(177.3pg/ml±113.6 vs 345.2pg/ml±132.9,p=0.02). There was significantly higher systemic INF-γ in both the CAWS and
CAWS+C48/80 compared to controls. No difference in TNFα was observed between the groups. No significant differences
were observed in aortic IL-6 expression between groups. Comparing CAWS+C48/80 to CAWS alone, there was
significantly higher aortic expression of both SOCS1 (p<0.001) and TNF-α (p=0.03).
Conclusion: The results demonstrate that systemic mast cell degranulation inhibits systemic IL-6 levels in a mouse model of
LVV. This was not accompanied by reduced aortic expression of IL-6 suggesting that this effect is occurring in other tissues,
possibly the liver. Mast cell degranulation was also associated with increased aortic expression of SOCS-1, a negative
inhibitor of IL-6 signaling, suggesting that mast cells may play a direct role in IL-6 signaling as well. Since our prior studies
suggest mast cells mediate IL-6 production through H1R stimulation, future research will be devoted to determining if H1R
inhibition can inhibit the formation of LVV in a mouse model.
Acknowledgements: Endowment from Division of Allergy, Clinical Immunology and Rheumatology and Basic Science
Research Development Award from Department of Medicine, University of Kansas Medical Center
Disclosure: M. Zhang, None; M. Maz, None; D. Smith, None; N. Miura, None; N. Ohno, None; K. Dileepan, None; J.
Springer, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/mast-cell-mediated-inhibition-of-

systemic-il-6-in-candida-albicans-water-soluble-fraction-caws-induced-model-of-large-vessel-vasculitis
Markers of Inflammation and Patient-Reported Measures As Predictors of

Relapse in Giant Cell Arteritis
Tanaz A. Kermani1, Antoine G. Sreih2, Gunnar Tomasson3, David Cuthbertson4, Renee Borchin5, Simon Carette6, Lindsy
J. Forbess7, Nader A. Khalidi8, Curry L. Koening9, Carol A. McAlear10, Paul A. Monach11, Larry W. Moreland12, Christian
Pagnoux6, Philip Seo13, Robert F. Spiera14, Kenneth J. Warrington15, Steven R. Ytterberg15, Carol A. Langford16 and Peter
A. Merkel17,18, 1Rheumatology, University of California Los Angeles, Los Angeles, CA, 2Rheumatology, University of
Pennsylvania, Philadelphia, PA, 3University of Iceland, Faculty of Medicine, Reykjavik, IS, 4Biostatistics and Informatics,
Department of Pediatrics, University of South Florida, Tampa, FL, 5University of South Florida, Tampa, FL, 6Division of
Rheumatology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada, 7Medicine, Division of Rheumatology,
Cedars-Sinai Medical Center, Los Angeles, CA, 8Rheumatology, McMaster University, Hamilton, ON, Canada,
9Rheumatology, University of Utah, Salt Lake City, UT, 10University of Pennsylvania, Philadelphia, PA, 11Boston
University School of Medicine, Boston, MA, 12Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh,
PA, 13Medicine, Johns Hopkins University, Baltimore, MD, 14Rheumatology, Hospital for Special Surgery, New York, NY,
15Rheumatology, Mayo Clinic, Rochester, MN, 16Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, OH,
17Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, 18Biostatistics, Epidemiology, and
Bioinformatics, University of Pennsylvania, Philadelphia, PA
SESSION INFORMATION
Background/Purpose: The significance of increasing erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in
clinically asymptomatic individuals with giant cell arteritis (GCA) is controversial. Patient-reported outcomes may be useful
in distinguishing disease states but have not been well studied in GCA. This study evaluated the association of changes in
ESR, CRP, and patient-reported measures as predictors of subsequent relapse in patients with GCA.
Methods: Data from patients with GCA enrolled in a multicenter, longitudinal cohort and/or a clinical trial were included.
Subjects were followed with standardized clinical assessments including symptoms attributed to vasculitis, patient global
assessment (PtGA) on an 11 point numberical scale (0-10) and The Short Form Health Survey (SF-36). Physical component
scores (PCS) and mental component scores (MCS) were calculated from SF-36 and normalized to the general population
(mean ± SD=50 ± 10) with lower scores indicating poorer outcomes. Relapse was defined as presence since the last visit of
any symptom attributable to vasculitis by the treating physician. Robust generalized estimating equations in logistic
regression models were used to evaluate the association between change in PtGA, PCS, MCS, ESR, CRP from the visit prior
to relapse with subsequent relapse.
Results: The study included 202 patients; 149 (74%) women; mean age at diagnosis = 71.6±8.3 years. All subjects met ACR
classification criteria modified to include subjects with angiographic evidence of large-vessel vasculitis. Temporal artery
biopsy was positive in 135/163 (82%) in whom it was performed. In the multivariable model, increase in PtGA (OR 1.18,
95% CI 1.08, 1.28), decrease in PCS (OR 1.05; 95% CI 1.02, 1.08), and increase in ESR (OR 1.03, 95% CI 1.00, 1.05) were
all associated with relapse (Table 1). Change in MCS or CRP were not associated with relapse (Table 1). Increase in ESR or
CRP was not associated with relapse in subjects when there was no change in PtGA from prior visit (change in PtGA <1)
(Table 1).
Conclusion: In GCA increases in ESR are not associated with relapse if PtGA is unchanged. Where patient-reported
measures worsen compared to a prior visit, a change in ESR is significant and is associated with an increased risk of relapse.
Changes in PtGA are more strongly associated with relapse than ESR or PCS. Changes in CRP are not associated with
relapses, regardless of patient-reported measures. Patients’ self-reports are important in the clinical assessment of disease
activity in GCA and in predicting relapse as currently defined. These results support the incorporation of patient-reported
outcomes into disease assessment in clinical trials and practice for GCA.
Table 1. Multivariate analysis evaluating predictors of relapse in
202 patients with giant cell arteritis
Variable Model 1 with all Model 2 with no
variables OR change in PtGA OR
(95%CI) (95% CI)
Age, years 1.0 (1.0, 1.0) 1.0 (1.0, 1.0)
Male sex 0.45 (0.25, 0.81) 0.44 (0.19, 1.02)
Caucasian ethnicity 1.34 (0.47, 3.82) 1.07 (0.29, 3.90)
Unit increase ESR, 1.03 (1.00, 1.05) 1.02 (0.99, 1.06)
mm/hour
Unit increase CRP, mg/L 1.01 (0.98, 1.04) 1.00 (0.95, 1.05)
Unit increase PtGA 1.18 (1.08, 1.28) N/A
Unit decrease MCS 1.02 (0.99, 1.04) N/A
Unit decrease PCS 1.05 (1.02, 1.08) N/A
OR = odds ratio; CI = confidence interval; PtGA = patient global
assessment;
ESR = erythrocyte sedimentation rate; CRP = C-reactive protein;
MCS = mental component score; PCS = physical component score;
N/A = not applicable
Disclosure: T. A. Kermani, None; A. G. Sreih, None; G. Tomasson, None; D. Cuthbertson, None; R. Borchin, None; S.
Carette, None; L. J. Forbess, None; N. A. Khalidi, None; C. L. Koening, None; C. A. McAlear, None; P. A. Monach,
None; L. W. Moreland, None; C. Pagnoux, None; P. Seo, None; R. F. Spiera, None; K. J. Warrington, None; S. R.
Ytterberg, None; C. A. Langford, None; P. A. Merkel, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/markers-of-inflammation-and-patient-

reported-measures-as-predictors-of-relapse-in-giant-cell-arteritis
Pre-Clinical Evidences of Immunomodulatory Activities of Tuftsin-

Phosphorylcholine on Samples from Patients with Giant Cell Arteritis in
Comparison to Corticosteroids
Stefania Croci1, Martina Bonacini1, Francesco Muratore2,3, Andrea Caruso3, Antonio Fontana4, Luigi Boiardi3, Alessandra
Soriano3,5, Alberto Cavazza6, Luca Cimino7, Lucia Belloni1, Maria Parmeggiani1, Miri Blank8,9, Yehuda Shoenfeld8,9 and
Carlo Salvarani2,3, 1Unit of Clinical Immunology, Allergy and Advanced Biotechnologies, Arcispedale Santa Maria Nuova-
IRCCS, Reggio Emilia, Italy, Reggio Emilia, Italy, 2University of Modena and Reggio Emilia, Italy, Modena, Italy, 3Unit of
Rheumatology, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy, Reggio Emilia, Italy, 4Unit of Vascular
Surgery, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy, Reggio Emilia, Italy, 5Campus Bio-Medico,
University of Rome, Italy, Roma, Italy, 6Unit of Pathology, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy,
Reggio Emilia, Italy, 7Unit of Ocular Immunology, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy, Reggio
Emilia, Italy, 8Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel, Ramat-Gan,
Israel, 9Sackler Faculty of Medicine, Tel-Aviv University, Israel, Tel-Aviv, Israel
SESSION INFORMATION
Background/Purpose: Tuftsin-PhosphorylCholine (TPC) is a novel bi-specific molecule which has shown

immunomodulatory effects in experimental mouse models of lupus, colitis and arthritis but data in human autoimmune
diseases are lacking. The present study aimed to investigate the effects of TPC in vitro on samples from patients with a
suspicion of giant cell arteritis (GCA), an inflammatory disease of large- and medium-sized arteries.
Methods: Effects of TPC were determined in vitro on peripheral blood mononuclear cells (PBMCs) and temporal artery
biopsies (TABs) obtained from six patients who underwent TABs because of a suspicion of GCA. Patients were naïve from
therapy. 3 patients had inflamed TABs (GCA). 3 patients had normal TABs and received a different diagnosis (controls).
GCA patients satisfied the ACR criteria for GCA. TPC was provided by TPCera (Jerusalem, Israel). Treatment with
dexamethasone was included as standard of care. To model in vitro the inflammatory state, PBMCs were activated with
CD3/CD28 beads for 48 hours and with phorbol 12-myristate 13-acetate (PMA) plus ionomycin for 4 hours in presence of
different doses of TPC or dexamethasone. T helper (Th) cell subsets were analyzed by intracellular flow-cytometry. Cell
viability was assessed by the WST-1 assay. To analyze the effects at tissue level, TABs were cut in fragments, placed in
culture medium with TPC or dexamethasone in matrigel drops for 5 days. Levels of 18 cytokines in supernatants of TABs
and CD3/CD28 activated PBMCs were quantified with the Procarta Plex Th1, Th2, Th9, Th17, Th22, Treg cytokine panel.
Data were calculated relative to untreated cells. Column statistics, one-sample t test with an hypothetical value of 100 was
used.
Results: Supernatants of PBMCs activated through CD3/CD28 and treated with TPC showed significant lower
concentrations of IL-1beta, IL-9, IL-12(p70), IL-13 (>80% decrease), IL-2, IL-5, IL-6, IL-17A, IL-21, IL-23, IFNgamma,
TNFalpha, GM-CSF (60-75% decrease) and to a lesser degree of IL-18, IL-22, IL-27. Treatment with TPC had no
significant effects on IL-10. It had similar effects on PBMCs from GCA and control patients with the exception of IL-17A
which was down-regulated only in PBMCs from GCA patients. IL-1beta, IL-13, IL-17A, IL-18 were detected only in
supernatants from inflamed TABs and were significantly down-regulated by TPC treatment. IL-2, IL-5, IL-6, IL-10,
TNFalpha were detected in supernatants both from inflamed and normal TABs: IL-6 was down-regulated by TPC treatment
while no differences were found in IL-2, IL-5, IL-10 and TNFalpha. TPC and dexamethasone treatments had similar effects
on cytokine production by CD3/CD28 activated PBMCs and TABs. Neither TPC nor dexamethasone treatments modified
the percentage of Th1, Th17 and Th22 cell subsets induced by PMA plus ionomycin. Both TPC and dexamethasone
treatments slightly reduced viability in unstimulated PBMCs while did not have any effects on viability of CD3/CD28
activated PBMCs.
Conclusion: TPC treatment in vitro remarkably down-regulated the production of several cytokines by CD3/CD28 activated
PBMCs and TABs, similarly to dexamethasone, supporting further studies to validate the potential use of TPC in
autoimmune diseases.
Disclosure: S. Croci, None; M. Bonacini, None; F. Muratore, None; A. Caruso, None; A. Fontana, None; L. Boiardi,
None; A. Soriano, None; A. Cavazza, None; L. Cimino, None; L. Belloni, None; M. Parmeggiani, None; M. Blank,
TPCera, 9; Y. Shoenfeld, TPCera, 9; C. Salvarani, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/pre-clinical-evidences-of-

immunomodulatory-activities-of-tuftsin-phosphorylcholine-on-samples-from-patients-with-giant-cell-arteritis-in-
comparison-to-corticosteroids
Aortic Dilatation in Patients with Large Vessel Vasculitis: A Longitudinal

Case Control Study Using Positron Emission Tomography/Computed
Tomography
Filippo Crescentini1, Francesco Muratore2, Lucia Spaggiari3, Giulia Pazzola1, Luigi Boiardi1, Nicolò Pipitone1 and Carlo
Salvarani4, 1Rheumatology Unit, Arcispedale Santa Maria Nuova - IRCCS, Reggio Emilia, Italy, 2Rheumatology Unit,
Arcispedale Santa Maria Nuova - IRCCS; Università di Modena e Reggio Emilia, Reggio Emilia, Italy, 3Radiology Unit,
Arcispedale Santa Maria Nuova - IRCCS, Reggio Emilia, Italy, 4Rheumatology Unit, Arcispedale Santa Maria Nuova -
IRCCS; Università di Modena e Reggio Emilia, Reggio-Emilia, Italy
SESSION INFORMATION
Background/Purpose: To evaluate aortic diameter and predictors of aortic dilatation using FDG-PET/CT in a longitudinally
followed cohort of patients with large vessel vasculitis (LVV) compared with controls.
Methods: All consecutive patients with LVV who underwent at least 2 PET/CT scans between January 2008 and May 2015
were included. The first and last PET/CT study of each patient was independently evaluated by a radiologist and a nuclear
medicine physician. The diameter of the aorta was measured at 3 different levels: ascending, descending thoracic and
infrarenal aorta. Aortic dilation was defined as a diameter of >4 cm in the ascending, ≥4 cm in the descending thoracic and
≥3 cm in the infrarenal aorta. Aortic FDG uptake was graded at the same levels using a 0-3 semiquantitative scale and was
reported as negative (score 0 or 1) or positive (score 2 and 3). Patients younger than 50 years at symptoms’ onset were
classified as Takayasu arteritis (TAK), while those older than 50 years as giant cell arteritis (GCA). 29 age- and sex-matched
patients with lymphoma who underwent at least 2 PET/CT in the same time interval without evidence of aortic FDG uptake
were selected as controls.
Results: 93 patients with LVV were included in the study. 53% of patients were newly-diagnosed; the remaining 47% had a
median disease duration of 34 months. At first PET/CT, the mean (SD) diameter of descending thoracic aorta was
significantly higher in LVV patients compared with controls [28.07 (4.40) vs 25.60 (3.59) mm, p=0.012]. At last PET/CT,
after a median time of 31 months, patients with LVV compared with controls had higher diameter of ascending [35.41 (5.54)
vs 32.97 (4.11) mm, p=0.029] and descending thoracic aorta [28.42 (4.82) vs 25.72 (3.55) mm, p=0.007] and more
frequently had aortic dilatation [19% vs 3%, p=0.023]. Significant predictors of aortic dilatation were male sex [OR 7.27,
p=0.001], and the diameter of ascending [OR 2.03, p<0.001], descending thoracic [OR 1.57, p<0.001] and infrarenal [OR
1.25, p=0.005] aorta at first PET/CT study. Positive aortic FDG uptake, diasese activity and elevated inflammatory markers
at first PET/CT were not associated with an increased risk of aortic dilatation. Results remained unchanged when the
analysis were restricted to the 48 newly-diagnosed LVV patients.
According to age at symptoms onset, 56% of patients were classified as GCA and 44% as TAK. At first PET/CT, GCA
compared with TAK patients had shorter disease duration, more frequent positive aortic FDG uptake and higher level of
inflammatory markers. Compared with TAK, GCA patients had higher aortic diameter at all 3 levels evaluated in both first
and last PET/CT study. However there were no differences in the proportion of patients with aortic dilatation (at last
PET/CT 23% in GCA vs 15% in TAK, p=0.306). Results remained unchanged when the analysis were restricted to the
newly-diagnosed patients.
Conclusion: Patients with large vessel vasculitis are at increased risk of aortic dilatation compared with age- and sex-
matched controls. Significant predictors of aortic dilatation are male sex and aortic diameter at first imaging study. Positive
aortic FDG uptake at first PET/CT is not associated with increased risk of aortic dilatation.
Disclosure: F. Crescentini, None; F. Muratore, None; L. Spaggiari, None; G. Pazzola, None; L. Boiardi, None; N.
Pipitone, None; C. Salvarani, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/aortic-dilatation-in-patients-with-large-

vessel-vasculitis-a-longitudinal-case-control-study-using-positron-emission-tomographycomputed-tomography

Glucocorticoid Use and Adverse Events in Patients with Polymyalgia
Rheumatica in a Contemporary Population-Based Cohort
Izzat Shbeeb1, Divya Challa1, Shafay Raheel2, Cynthia S. Crowson3 and Eric L. Matteson4, 1Division of Rheumatology,
Mayo Clinic, Rochester, MN, 2Rheumatology, Mayo Clinic, Rochester, MN, 3Division of Biomedical Statistics and
Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 4Rheumatology, Mayo Clinic College
of Medicine and Science, Rochester, MN
SESSION INFORMATION
Background/Purpose:
To investigate the use of glucocorticoids (GC) and related adverse events (AE) in a long-term, geographically-defined cohort
of patients with polymyalgia rheumatica (PMR).
Methods:
Using a population-based inception cohort, details of GC therapy were abstracted from medical records of all patients
diagnosed with PMR in 2000-2014. Age- and sex-matched comparators without PMR were identified from the same
underlying population. Cumulative and daily dosage of GC, rate of disease relapse, occurrence of GC-related AE, and rate of
GC discontinuation were analyzed.
Results:
The study included 359 patients with PMR and 359 comparators. The median time to taper below 5mg/day for 6 months was
1.44 years (95% confidence interval [CI]:1.36-1.62), while the median time to permanent discontinuation was 5.95 years
(95%CI:3.37-8.88). GC dosage permanent discontinuation (solid line), reaching <5 mg/day for 6 months (dashed line), and
reaching <10 mg/day for 6 months (dotted line are depicted in Figure 1, top panel. Relapse rates according to time after
PMR diagnosis are shown in Figure 1, bottom panel. The mean cumulative dose of GC at 2 and 5 years was 4.0 grams (g)
(standard deviation [SD] 3.5g) and 6.3g (SD 9.8g), respectively. The mean daily dose of GC at 2 and 5 years was 6.1 mg/day
(SD 7.6) and 7.2 mg/day (SD 9.5), respectively. There were no differences in rates of AE between patients with PMR and
comparators for diabetes mellitus, hypertension, hyperlipidemia, or hip, vertebral or Colles fractures (p>0.2 for all).
Cataracts were more common in patients with PMR than comparators (hazard ratio:1.72; 95%CI:1.23-2.41).
Conclusion:
The duration of GC therapy in patients with PMR is often protracted. Relapse rates are highest in the early stages of therapy.
GC-related AE are not more common in PMR than comparators, except for cataracts.
Disclosure: I. Shbeeb, None; D. Challa, None; S. Raheel, None; C. S. Crowson, None; E. L. Matteson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/glucocorticoid-use-and-adverse-events-

in-patients-with-polymyalgia-rheumatica-in-a-contemporary-population-based-cohort
Metotrexate in the Treatment of Giant Cell Arteritis: To be or Not to be

Ignacio Castaño1, Irene Monjo2, Alejandro Balsa3, Diana Peiteado2, Sara García-Carazo4 and Eugenio De Miguel1,
1Medicine, Universidad Autonoma Madrid, MADRID, Spain, 2Rheumatology, Hospital Universitario La Paz, MADRID,
Spain, 3Rheumatology, Hospital La Paz-IdiPAZ, Madrid, Spain, 4Rheumatology, La Paz University Hospital, Madrid, Spain
SESSION INFORMATION
Background/Purpose:
The high-dose glucocorticoids (GCs) are the mainstay of treatment in Giant Cell Arteritis (GCA). Patients treated with
greater GC dosages are at the greatest risk of morbidity. Immunosuppressive agents have been trialled in an effort to reduce
toxicity from GCs and to improve efficacy of treatment. The results of one meta-analysis with the three trials that included
methotrexate (MTX) showed a weak benefit in those patients receiving MT), but the results were heterogeneous, with one
trial showing significant benefit, while the other two did not (1). In this sense, our main objective was to study the efficacy
and safety of MTX adjunct to GCs in the treatment of GCA.
Methods:
New-onset giant-cell arteritis initiating treatment of the disease was included in a retrospective observational study to
compare treatment efficacy and safety. According to the treatment received the patients were divided two groups: a) GCs
alone and b) MTX and GCs. To avoid bias, in group b, only patients who started MTX in the first trimester of treatment
were included. As efficacy outcome the number of relapses and the cumulative dose of GCs at 6, 12 and 24 months were
collected. For safety, the number of emergency room visits, hospitalization admissions and treatment related side adverse
events were investigated in the follow-up.
Results:
Among the 147 patients included in the study, 64 (43.5%) received GCs alone (mean age 78.6±7.5 years) and 83 (56.5%)
received GCs and MTX as an adjuvant treatment at some time during follow-up. 52 of these 83 patients (mean age 78.5±8.0
years) received MTX in the first trimester after diagnosis (group b). In the MTX group 43 patients received a dose of 7.5-
15mg/week and 9 patients received a dose ≥15mg/week. Compared with only GCs treatment, MTX introduced in the first
three months therapy did not reduce the rate of relapses, 51% in MTX group vs. 37.7% in the GCs group (p<0.09). The
mean cumulative dose of prednisone was higher in the MTX group than in prednisone alone group (table). Patients in the
MTX group, at any dose, presented a higher incidence of hospital admissions and hospital admissions by infections
(p<0.05).
Methotrexate (MTX) vs. Glucocorticois (GCs) groups: Cumulative GCs doses

6 months 12 months 24 months Relapse Yes/NO
(%)
MTX Mean 4726,50 6312,50 8168,18 25/24
Std. Deviation 1447,06 1776,33 2347,28
(51%)
n 50 48 44
GCs Mean 3724,31 5096,10 6825,16 37/61 (37.7%)
Std. Deviation 2024,89 2626,29 3718,70
n 108 100 96
p value .002 .004 .029 .087
Conclusion:
Whilst MTX have been used in an effort to reduce toxicity from GCs and to improve efficacy of treatment our observational
study shows that there is no benefit from adjunct MTX in GCA either in terms of efficacy or toxicity.
(1) Mahr AD, Jover JA, Spiera RF et al. Adjunctive methotrexate for treatment of giant cell arteritis: an individual patient
data metaanalysis. Arthritis Rheum 2007; 56(8):2789–2797.
Disclosure: I. Castaño, None; I. Monjo, None; A. Balsa, None; D. Peiteado, None; S. García-Carazo, None; E. De
Miguel, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/metotrexate-in-the-treatment-of-giant-

cell-arteritis-to-be-or-not-to-be
Negative Temporal Artery Biopsies: Comparison between Biopsy-Negative

GCA and Non-GCA Patients
Karthik Yeruva1, Kenneth J. Warrington1, Cynthia S. Crowson2 and Matthew J. Koster1, 1Rheumatology, Mayo Clinic,
Rochester, MN, 2Health Sciences Research, Mayo Clinic College of Medicine and Science, Rochester, MN
SESSION INFORMATION
Background/Purpose: Temporal artery biopsy (TAB) plays a key role in diagnosis of giant cell arteritis (GCA). However,
approximately 15-20% of patients ultimately diagnosed with GCA have negative biopsies. Among patients with negative
TAB, it is often challenging to identify patients with GCA from those with an alternate (non-GCA) diagnosis. Therefore, we
sought to compare TAB-negative GCA with patients receiving a non-GCA alternate diagnosis.
Methods: Two cohorts were retrospectively identified through direct medical record review. The first cohort consisted of
patients with TAB-negative GCA diagnosed between 1/1/1998 and 12/31/2013. The second cohort included all patients with
a negative TAB performed between 1/1/2009 and 12/31/2010 in which a non-GCA alternate diagnosis was provided after a
minimum of 6 months of follow up. Final diagnoses were confirmed by consensus among two rheumatologists and a
physician abstractor. Baseline characteristics were compared between the two cohorts using chi-square and rank sum tests.
Results: 110 patients with TAB-negative GCA and 195 non-GCA patients with a negative TAB were identified. Alternate
diagnoses for non-GCA patients are listed in Table 1. Age, sex, number of days on glucocorticoids prior to biopsy, and
biopsy length were similar in both groups. Time from first symptom to diagnosis was longer in non-GCA patients [mean
(SD); 2.6 (2.5) vs 1.5 (2.1) months; p<0.001] and fewer non-GCA patients fulfilled ≥3 ACR criteria for GCA (27% vs 64%;
p<0.001). Although headache was the primary symptom in both cohorts (66% TAB-negative GCA; 68% non-GCA), patients
with biopsy-negative GCA had more frequent anorexia, fatigue, fever, polymyalgia rheumatica, temporal artery tenderness
and claudication (jaw, arm, or leg). Baseline transient (5% TAB-negative GCA; 6% non-GCA; p=0.58) and permanent (3%
TAB-negative GCA; 3% non-GCA; p=0.86) vision loss were infrequently observed. ESR was higher in TAB-negative GCA
patients [64.0 (35.1) vs 55.2 (67.4) mm/hr; p=0.002] compared to non-GCA patients but CRP did not differ [44.3 (53.6) vs
43.8 (61.9) mg/L; p=0.39].
Conclusion: In this cohort, neither headache nor vision loss at presentation were associated with an ability to discriminate
between diagnosis of TAB-negative GCA compared to patients without GCA. ACR criteria may be helpful in identifying
patients with TAB-negative GCA. Among patients with negative TAB, constitutional symptoms and claudication (jaw/limb)
were more frequently associated with an ultimate diagnosis of TAB-negative GCA.
Disclosure: K. Yeruva, None; K. J. Warrington, None; C. S. Crowson, None; M. J. Koster, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/negative-temporal-artery-biopsies-

comparison-between-biopsy-negative-gca-and-non-gca-patients
Characteristics and Treatment Outcomes of Giant Cell Arteritis with Large-

Vessel Lesions in a Nationwide, Retrospective Cohort Study in Japan
Takahiko Sugihara1, Hitoshi Hasegawa2, Haruhito Uchida3, Hajime Yoshifuji4, Yoshikazu Nakaoka5, Yoshiko Watanabe6,
Eisuke Amiya7, Masanori Konishi8, Yasuhiro Katsumata9, Yoshinori Komagata10, Taio Naniwa11,12, Takahiro Okazaki13,
Yoshiya Tanaka14, Tsutomu Takeuchi15, Masayoshi Harigai16, Yoshihiro Arimura17 and Mitsuaki Isobe8,18, 1Department of
Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan, 2Department of Hematology, Clinical
Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Ehime, Japan, 3Department of
Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and
Pharmaceutical Sciences, Okayama, Japan, 4Department of Rheumatology and Clinical Immunology, Graduate School of
Medicine, Kyoto University, Kyoto, Japan, 5Osaka University Graduate School of Medicine, Osaka, Japan, 6First
Department of Physiology, Kawasaki Medical School, Kurashiki, Japan, 7Department of Cardiovascular Medicine,
University of Tokyo Graduate School of Medicine, Tokyo, Japan, 8Department of Cardiovascular Medicine, Tokyo Medical
and Dental University, Tokyo, Japan, 9Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan, 10First
Dept. of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan, 11Division of Rheumatology, Dept of
Internal Medicine,, Nagoya City University Hospital, Nagoya, Japan, 12Department of Respiratory Medicine, Allergy and
Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, 13Internal Medicine,
St. Marianna University School of Medicine, Kawasaki, Japan, 14The First Department of Internal Medicine, University of
Occupational and Environmental Health, Kitakyushu, Japan, 15Division of Rheumatology, Department of Internal Medicine,
Keio University School of Medicine, Tokyo, Japan, 16Division of Epidemiology and Pharmacoepidemiology of Rheumatic
Diseases, Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan, 17First Department of Internal
Medicine, Kyorin University School of Medicine, Tokyo, Japan, 18Sakakibara Heart Institute, Tokyo, Japan
SESSION INFORMATION
Background/Purpose: Giant cell arteritis (GCA) often affects aorta or its branches, but it is unclear whether the large-vessel
(LV) lesions are associated with treatment outcomes. The objective of this study was to evaluate clinical features of GCA
with LV lesions and their associations with treatment outcomes in Japanese patients with GCA.
Methods: From a retrospective, multi-center, nationwide registry of GCA and Takayasu arteritis (TAK), we selected 137
newly diagnosed GCA patients who were treated with glucocorticoids (GCs) and 4 relapsed patients who were treated with
GCs between 2007 and 2014. Differential diagnosis of GCA and elderly-onset TAK was made by the discretion of the site
investigators, while 110 out of the 141 patients satisfied the ACR classification criteria for GCA. The primary outcomes
were achievement of remission (disappearance of clinical symptoms with normal C-reactive protein) and remission at low
dose GCs (prednisolone (PSL) ≤7.5mg/day).
Results: Imaging examinations were performed in 100 of the 141 GCA, and 69 of them had LV lesions. Stenosis and
aneurysm of the aorta or its branches were detected in 18 (26%) and 9 (13%) of the 69 GCA patients, respectively. On the
other hand, inflammatory lesion of arterial wall was detected in 51 (74%) patients with enhanced CT, MRI or PET-CT. Of
the 69 GCA patients with LV lesions, 34 had inflammatory lesions in left subclavian artery (a.), 29 in right subclavian a., 29
in left carotid a., 23 in right carotid a., 21 in ascending thoracic aorta, 31 in aortic arch, 32 in descending thoracic aorta, and
35 in abdominal aorta. We compared GCA patients with LV lesions by imaging (LVL group, n=69) and the others (non-LVL
group, n=72) for clinical features and treatment response. Headache, abnormal temporal artery, jaw claudication, visual
disturbance, and musculoskeletal manifestations were observed in 39%, 39%, 25%, 12% and 52% of the LVL group and in
81%, 75%, 47%, 38% and 65% of the non-LVL group. Initial PSL doses (mean ± standard deviation) were 0.78 ± 0.21 and
0.75 ± 0.25 mg/kg/day, and concomitant immunosuppressive drugs were used in 48% and 33% throughout observational
period of two years, for the LVL group and the non-LVL group, respectively. Remission was achieved in 94% and 96% of
the LVL group and the non-LVL group, and relapse-free survival rates were not significantly different between the two
groups. The log-rank test showed cumulative rate of remission at low dose GCs was significantly lower in the LVL group
compared to the non-LVL group.
Conclusion: LV lesions in Japanese patients with GCA were mostly limited to inflammation of arterial wall without stenosis
or aneurysm formation, but were associated with poorer treatment outcomes.
Disclosure: T. Sugihara, Takeda Pharmaceutical Co. Ltd., Mitsubishi-Tanabe Pharma Co., Chugai Pharmaceutical Co.,
Ltd., Ayumi Pharmaceutical Co., Ltd., UCB Japan Co. Ltd, Astellas Pharma Inc., Janssen Pharmaceutical K.K., Pfizer Japan
Inc., and Bristol Myers Squibb K.K, 5; H. Hasegawa, None; H. Uchida, None; H. Yoshifuji, None; Y. Nakaoka, Chugai,
Takeda, 2,Chugai, Daiichi Sankyo, MSD, Kowa, 8,Chugai, 5; Y. Watanabe, None; E. Amiya, None; M. Konishi, None; Y.
Katsumata, Chugai Pharmaceutical Co., Ltd., Astellas Pharma Inc., Takeda Pharmaceutical Company Limited., Bayer
Yakuhin, Ltd., AYUMI Pharmaceutical Corporation, 5; Y. Komagata, None; T. Naniwa, Chugai, Eisai, Tanabe-Chugai,
Eisai, Tanabe-Mitsubishi, Ono, Teijin, Chugai, Eisai, Tanabe-Mitsubishi, Ono, Teijin, Daiichi-Sankyo, 2,Chugai, Eisai,
Tanabe-Mitsubishi, Ono, Teijin, Pfizer, Janssen, Abbvie, Astellas, 5; T. Okazaki, None; Y. Tanaka, Mitsubishi-Tanabe,
Takeda, Daiichi-Sankyo, Chugai, Bristol-Myers, MSD, Astellas, Abbvie, Eisai, 2,Abbvie, Chugai, Daiichi-Sankyo, Bristol-
Myers, Mitsubishi-Tanabe, Astellas, Takeda, Pfizer, Teijin, Asahi-kasei, YL Biologics, Sanofi, Janssen, Eli Lilly,
GlaxoSmithKline, 8; T. Takeuchi, Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe
Pharma Co., Abbivie GK, Nipponkayaku Co.Ltd, Janssen Pharmaceutical K.K., Astellas Pharma Inc,.Taiho Pharmaceutical
Co., Ltd.,, 5,AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Mitsubishi Tanabe Pharma Co., Pfizer
Japan Inc., and Astellas Pharma Inc, and Diaichi Sankyo Co.,Ltd., 8; M. Harigai, Eisai Ltd, Takeda Ltd, Teijin, 2,Eli Lilly
and Company, BMS, Chugai, Janssen, 5; Y. Arimura, None; M. Isobe, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/characteristics-and-treatment-outcomes-

of-giant-cell-arteritis-with-large-vessel-lesions-in-a-nationwide-retrospective-cohort-study-in-japan
Presentation and Outcome of Large-Vessel Vasculitis Diagnosed between 50

and 60 Years: Case-Control Study Based on 183 Cases
Laure Delaval1,2, Aurélie Daumas3, Maxime Samson4, Mikael Ebbo5, Hubert de Boysson6, Eric Liozon7, Henry Dupuy8,
Alexis Regent9, Mathieu Puyade10, Daniel Blockmans11, Estibaliz Lazaro12, Ygal Benhamou13, Karim Sacre14, Alice
Bérezné15, Loïc Guillevin2,9,16 and Benjamin Terrier17,18,19, 1National Referral Center for Rare Systemic Autoimmune
Diseases, Hôpital Cochin, AP–HP, Université Paris Descartes, paris, France, 2Internal medicine, Cochin University Hospital,
paris, France, 3Department of Internal Medicine, Aix-Marseille Université, La Timone University Hospital, AP-HM,
Marseille, France, 4Department of Internal Medicine and Clinical Immunology, Hôpital François Mitterrand, CHU de Dijon,
Dijon, France, 5internal medicine, Aix-Marseille Université, La Timone University Hospital, AP-HM, Paris, France,
6Department of Internal Medicine, Caen University Hospital, Caen, France, 7Departement of Internal Medicine, Limoges
University Hospital, Limoges, France, 8Department of Internal Medicine, Haut-Lévêque Hospital, Pessac, France, 9National
Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, AP–HP, Université Paris Descartes, Paris, France,
10Department of Internal Medicine, University Hospital of Poitiers, Poitiers, France, 11General Internal Medicine,
University Hospital Gasthuisberg, Leuven, Belgium, 12Department of Internal Medecine and Clinical Immunology,
Bordeaux University Hospital, Pessac, France, 13Department of internal medicine, University Hospital of Rouen, Rouen,
France, 14Department of Internal Medicine, Bichat Hospital, Paris, France, 15Department of internal medicine, CHR
Annecy-Genevois, Metz-Tessy, France, 16French Vasculitis Study Group (FVSG), Paris, France, 17Service de Médecine
Interne, Hôpital Cochin, Centre de référence national pour les maladies systémiques autoimmunes rares d’Ile de France,
DHU Authors, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France, Paris, France, 18Internal Medicine, Cochin
University Hospital, Paris, France, 19French Vasculitis Study Group (FVSG), paris, France
SESSION INFORMATION
Background/Purpose: Primary large-vessel vasculitis (LVV) include giant cell arteritis (GCA) and Takayasu arteritis (TA).
Age at onset is commonly used to distinguish GCA and TA. TA usually occurs before 50 years, whereas GCA occurs after
age 50. However, GCA onset before age 60 remains very rare, reason why LVV between age 50 and 60 could be difficult to
classify.
Methods: We conducted a national, retrospective study including patients with LVV, defined by histological (temporal
artery biopsy) and/or imaging (circumferential thickening and/or hypermetabolism on FDG PET/CT) evidence of
inflammatory vascular disease, and aged between 50 and 60 years at onset (LVV50-60). Cases were compared to controls
with GCA aged over 60 years (LVV>60), and matched on gender with a ratio of 1:1.
Results:
We included 183 patients (136 women). Initial symptoms of LVV were: constitutional symptoms in 144 (79%) cases,
cephalic symptoms in 133 (73%), polymyalgia rheumatica in 55 cases (30%), peripheral limb ischemic manifestations in 42
(23%), ocular signs in 32 (17%), stroke in 4 cases (2%) and mesenteric ischemia in 2 cases (1%). Temporal artery biopsy
showed evidence of vasculitis in 78 (43%) cases.
Computed tomography (CT) angiography was performed in 102 (56%) cases and was abnormal in 74%, involving aorta in
83% (thoracic 29%, abdominal 8% and both 63%), subclavian artery in 26%, iliofemoral artery in 18% and carotid artery in
14%. Isolated aortitis was observed in 38%.
FDG PET/CT scan was performed in 105 (57%) cases, showing hypermetabolism in 90%. Overall, aortitis was noted on CT
angiography and/or FDG-PET/CT in 113 (78%) cases, without any cephalic symptoms in 22%.
All patients received glucocorticoids. After a median follow-up of 43.8 months, 78 (31%) patients required second-line
therapy, 27 (18%) three-line, and 14 (9%) more lines. Overall, 35% received methotrexate and 12% biological agent (anti-
TNFa and/or IL-6 blockade). Fifteen patients required surgery (bypass surgery or angioplasty). At the end of follow-up, only
45% had discontinued glucocorticoids.
Case-control comparison showed that LVV50-60 had more frequent peripheral limb ischemic manifestations (23 vs 5%,
P<0.0001), and less frequent cephalic symptoms (72 vs 90%, P<0.0001) and ocular signs (17 vs 27%, P=0.04). CT
angiography and FDG PET/CT scan were more frequently abnormal in LVV50-60 (41 vs 23%, P<0.0001; and 51 vs 27%,
P=0.007, respectively), with aorta being more frequently involved (78 vs 47%, P<0.0001). LVV50-60 received a median of 2
lines of treatment compared to one in LVV>60 (P=0.0002). LVV50-60 had more frequent surgery (10 vs 0%, P<0.0001),
received more frequent biological agents (12 vs 3%, P=0.003), and had at last follow-up higher median prednisone dose (8.8
vs 6.5 mg/d, P=0.048) and lower frequency of patients with prednisone <7.5 mg/d (71 vs 83%, P=0.01) compared to
LVV>60.
Conclusion: Primary LVV onset between 50 and 60 years identifies a subset of patients with more frequent aorta and
peripheral limb vascular involvement compared to patients with LVV onset after 60. LVV between 50 and 60 were also
characterized by more refractory disease requiring more methotrexate and/or biological agent.
Disclosure: L. Delaval, None; A. Daumas, None; M. Samson, None; M. Ebbo, None; H. de Boysson, None; E. Liozon,
None; H. Dupuy, None; A. Regent, None; M. Puyade, None; D. Blockmans, None; E. Lazaro, None; Y. Benhamou,
None; K. Sacre, None; A. Bérezné, None; L. Guillevin, None; B. Terrier, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/presentation-and-outcome-of-large-

vessel-vasculitis-diagnosed-between-50-and-60-years-case-control-study-based-on-183-cases
Temporal Arteritis Revealing Antineutrophil Cytoplasmic Antibody–

Associated Vasculitides: A Retrospective Study of 50 Cases
Laure Delaval1,2, Maxime Samson3, Flora Schein4, Christian Agard5, Olivier Aumaître6, Alban Deroux7, Henry Dupuy8,
Cyril Garrouste9, cedric landron10, Francois Maurier11, Pascal Cathebras12, Loïc Guillevin2,13,14 and Benjamin
Terrier15,16,17, 1National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, AP–HP, Université
Paris Descartes, paris, France, 2Internal medicine, Cochin University Hospital, paris, France, 3Department of Internal
Medicine and Clinical Immunology, Hôpital François Mitterrand, CHU de Dijon, Dijon, France, 4Internal medicine,
University Hospital St Etienne, Saint Etienne, France, 5Internal Medicine Department, Nantes University Hospital, Nantes,
France, 6CHU Pitié-Salpêtrière - Department of Internal Medicine 2. Referal center for SLE/APS, Paris, France, 7Internal
Medicine, CHU de Grenoble, Grenoble, France, 8Department of Internal Medicine, Haut-Lévêque Hospital, Pessac, France,
9Nephrology, CHU, Clermont-Ferrand, France, 10service de médecine interne, CH Poitiers, CHU Poitiers, poitiers, France,
11Internal Medicine, Sainte-Blandine de Metz Hospital, Metz, France, 12Internal Medicine, University Hospital St Etienne,
St Etienne, France, 13French Vasculitis Study Group (FVSG), Paris, France, 14National Referral Center for Rare Systemic
Autoimmune Diseases, Hôpital Cochin, AP–HP, Université Paris Descartes, Paris, France, 15Service de Médecine Interne,
Hôpital Cochin, Centre de référence national pour les maladies systémiques autoimmunes rares d’Ile de France, DHU
Authors, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France, Paris, France, 16French Vasculitis Study Group
(FVSG), paris, France, 17Internal Medicine, Cochin University Hospital, Paris, France
SESSION INFORMATION
Background/Purpose: Giant cell arteritis (GCA) is a non-necrotizing granulomatous arteritis involving large vessels,
whereas antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) are a group of necrotizing vasculitis
involvement small and medium-size vessels. AAV can be revealed by temporal arteritis (TA) leading to cephalic symptoms
and misdiagnosis of GCA, whereas therapeutic management and prognosis strongly differ between these two entities.
Methods: We conducted a retrospective multicenter study including patients with symptomatology of TA revealing AAV.
We compared these cases (TA-AAV) to controls with GCA randomly selected with a ratio of 1:2.
Results:
Fifty patients (26 women, mean age 70 years) were included. Initial symptoms of TA were: cephalic symptoms suggesting
GCA in 44 (88%) cases, polymyalgia rheumatica symptoms and cough in 15 (30%) each, and ocular manifestations in 8
(16%). All patients without cephalic symptoms had inflammation on TAB consistent with GCA. However, 33 (66%) patients
presented at initial presentation atypical symptoms for GCA: ENT involvement in 16 (32%), renal involvement (haematuria,
proteinuria or acute renal faillure) in 13 (26%), pulmonary involvement (nodule, alveolar condensation or alveolar
hemorrhage) in 9 (18%), peripheral neuropathy in 8 (16%), abdominal pain and cutaneous manifestations in 5 (10%) each,
episcleritis in 3 and cardiac involvement in 2. ANCA were screened at initial presentation in 33 cases, and were found in
88%, targeting MPO in 62% and PR3 in 38%.
Overall, diagnosis of AAV was made after a median time of 15.2 months (range 1.1-201), after initial flare in 20 (40%), after
refractory disease in 13 (26%) and after vasculitis relapse in 17 (34%). AAV diagnoses were GPA, PAM and EGPA in 31, 16
and 3 cases, respectively. Manifestations leading to AAV diagnoses by physicians were common, including pachymeningitis
in 4 cases. Once AAV diagnosis was made, all patients received glucocorticoids, in combination with immunosuppressive
agents in 84% (cyclophosphamide, rituximab, azathioprine or methotrexate). After median follow-up of 43.2 months, 14
patients presented a relapse of the AAV and 5 patients died.
To identify AAV in patients with TA manifestations, we compared TA-AAV with GCA patients. AAV patients were slightly
younger than GCA (70 vs. 74 years, P=0.01), and had more frequently: peripheral neuropathy (16 vs. 0%, P<0.001), lung
involvement (40 vs. 16%, P=0.002), ENT (34 vs. 0%, P<0.001) and renal involvement (37 vs 0%, P<0.001). Histologically,
TAB from AAV had significantly more fibrinoid necrosis (23 vs. 0%, P<0.001) and adventitial vasculitis (23 vs. 0%,
P<0.001) and less frequently granulomatous inflammation (13 vs. 40%, P=0.01), disruption of the internal elastic membrane
(45 vs. 69%, P=0.04) and giant cells (29 vs. 60%, P=0.01)).
Conclusion: Diagnosis of AAV should be considered in patients presenting with cephalic symptoms, especially in case of
unusual manifestations and in case of necrosis or adventitial vasculitis on TAB. ANCA testing should also be performed in
all patients with TA manifestations before retaining GCA diagnosis.
Disclosure: L. Delaval, None; M. Samson, None; F. Schein, None; C. Agard, None; O. Aumaître, None; A. Deroux,
None; H. Dupuy, None; C. Garrouste, None; C. landron, None; F. Maurier, None; P. Cathebras, None; L. Guillevin,
None; B. Terrier, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/temporal-arteritis-revealing-

antineutrophil-cytoplasmic-antibody-associated-vasculitides-a-retrospective-study-of-50-cases
Altered Phenotype of Platelets and Neutrophils Toward Neutrophil-Platelet

Interaction in Circulation of Small and Large Vessel Vasuculitis
Kotaro Matsumoto1, Hidekata Yasuoka2, Komei Sakata1, Keiko Yoshimoto1,3, Katsuya Suzuki1,4, Kunihiro Yamaoka1 and
Tsutomu Takeuchi1, 1Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine,
Tokyo, Japan, 235 Shinanomachi, Shinjuku, Keio University School of Medicine, Tokyo, Japan, 3Keio University School of
Medicine, Clinical and Translational Research Center, Tokyo, Japan, 4Division of Rheumatology, Department of Internal
Medicine, Keio University School of Medcine, Tokyo, Japan
SESSION INFORMATION
Background/Purpose: Neutrophils play an important role in the pathogenesis of necrotizing vasculitis, and activation of
neutrophil is one of important triggers of the disease process. Recent reports suggest that platelets can stimulate neutrophils
directly via aggregation by these cells or indirectly via chemokines produced by platelets. Thus, we hypothesized that
activation of neutrophils by platelets may contribute to the progression of vasculitis. Our aim of this study is to clarify the
phenotype alteration of circulating platelets and neutrophils toward aggregation in patients with vasculitis.
Methods: Untreated patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and large
vessel vasuculitis (LVV) who visited Keio University Hospital between 2015 and 2017 were consecutively involved and
compared with 33 healthy controls (HC). Patients with AAV and LVV fulfilled 2012 Revisited International Chapel Hill
Consensus Normenclature or American College of Rheumatology 1990 criteria. Platelet-rich plasma and neutrophils were
isolated from heparinized whole blood using gradient centrifugation. Expression levels of CD62P on platelets and CD41a on
neutrophils which involved in platelet-neutrophil interaction were analyzed by FACS. The correlation between expression
levels of CD62P and CD41a on these cells and clinical parameters of the patients were also analyzed.
Results: Four microscopic polyangitis (MPA), 2 granulomatosis with polyangitis (GPA) as AAV, and 5 giant cell arteritis
(GCA), 3 Takayasu arteritis (TAK) as LVV were involved. As of AAV, mean age was 67 ± 8 years, 62% male, mean BVAS
15 ± 2, mean neutrophil counts 6,654 ± 1,262 /μL, and mean platelet counts 34 ± 6 × 104/μL. As of LVV, mean age 66 ± 4
years, 53% male, mean neutrophil counts 5,507 ± 600 /μL, and mean platelet counts 36 ± 5 × 104/μL. The treatment was
started with 1 mg/kg/day of prednisolone for all patients. Proportion of CD62P+ platelets was remarkably higher in AAV
(2.5 ± 0.09 versus 1.7 ± 1.0, p = 0.05) and LVV (3.2 ± 1.1 versus 1.7 ± 1.0, p = 0.005) compared with HC. Moreover,
proportion of CD62P+ platelets was tended to be decreased by immunosuppressive treatment (2.6 ± 0.7 versus 2.0 ± 0.6, p =
0.1) along with improvement of disease activity. In addition, proportion of CD41a+ neutrophils also tended to be higher in
AAV and LVV compared with HC (27 ± 8.8 versus 20 ± 5.8, p = 0.07), and decreased by the treatment (29 ± 9.2 versus 18 ±
6.8, p = 0.07). Interestingly, proportion of CD41a+ neutrophils was significantly and positively correlated with CD62P+
platelets (r2 = 0.8, p = 0.04) and ANCA titer (r2 = 0.9, p = 0.003) in AAV patients.
Conclusion: Phenotype of circulating platelets and neutrophils are altered toward cell to cell contact and associate with
disease activity. These results suggest that platelet-neutrophil interaction is involved in the disease process of vasculitis.
Disclosure: K. Matsumoto, None; H. Yasuoka, None; K. Sakata, None; K. Yoshimoto, None; K. Suzuki, None; K.
Yamaoka, None; T. Takeuchi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/altered-phenotype-of-platelets-and-

neutrophils-toward-neutrophil-platelet-interaction-in-circulation-of-small-and-large-vessel-vasuculitis
Acetylcholinesterase Is Highly Expressed in the Inflamed Vessel Wall of

Patients with Giant Cell Arteritis
Philip Therkildsen1, Berit Dalsgaard Nielsen1, Kresten Krarup Keller2, Torben Steiniche3, Lars Christian Gormsen4, Ib
Tønder Hansen5 and Ellen-Margrete Hauge6, 1Department of Rheumatology, Aarhus University Hospital, Aarhus C,
Denmark, 2Rheumatology, Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark, 3Department of
Histopathology, Aarhus University Hospital, Aarhus C, Denmark, 4Nuclear Medicine and PET Center, Department of
Nuclear Medicine and PET Center, Aarhus University Hospital, Århus C, Denmark, 5Department of Rheumatology, Aarhus
University Hospital, Aarhus, Denmark, 6Department of Rheumatology, Department of Rheumatology, Aarhus University
Hospital, Aarhus, Denmark
SESSION INFORMATION
Background/Purpose: The temporal artery biopsy (TAB) remains the gold standard in the diagnosis of giant cell arteritis
(GCA). However, TABs are false-negative in 40% of cases. Cellular studies have shown that activated immune cells
upregulate the expression of acetylcholinesterase (AChE). If AChE is upregulated in the active GCA vessel wall, it may
potentially improve the TAB as a diagnostic tool. The purpose was to investigate the in-situ expression of AChE in the
vessel wall of patients with TAB-positive GCA and compare to non-GCA patients. Methods: In this histological case-
control study, TABs from a total of 24 TAB-positive GCA and 44 TAB-negative non-GCA patients were retrospectively
included from the period 2012-2015. Only positive TABs showing clear transmural inflammation were included. Clinical
data were obtained from electronic patient records to confirm or dismiss clinical diagnosis. Immunohistochemical methods
were used to determine the AChE expression and verified using positive/negative controls. The histological inflammation
and AChE expression were assessed and graded on 0-1-2 scale by a pathologist, blinded to clinical data. Solitary AChE
staining of the media was not included in the assessment. Results: All positive TABs showed ACHE expression, 10/24
showed high AChE expression (grade 2) and 14/24 showed moderate AChE expression (grade 1). No non-specific AChE
expression was observed outside the media in any of the negative TABs from non-GCA patients (i.e. grade 0). The AChE
expression was in 79% agreement with the histological inflammation. Prednisolone treatment did not suppress the AChE
expression. Neither the AChE expression, nor the histological inflammation showed correlation with any clinical findings.
Clinical characteristics of included patients are shown in table 1. Conclusion: High to moderate AChE expression was
observed in all 24 biopsies from TAB-positive GCA patients, and the AChE expression was in good agreement with the
histological inflammation. No false positive staining was observed in any of the 44 TABs from TAB-negative non-GCA
patients. This indicates that AChE could be a potential biomarker in GCA and may play a significant role in the
inflammatory process in GCA.
Table 1: Baseline characteristics

Variables Positive Negative Negative p
biopsy biopsy biopsy value
diagnosed diagnosed diagnosed
with GCA with PMR with other
N=24 N=21 disease1
N=23
Age (mean (95% CI), 70.1 (67.5- 71.6 (67.5- 68.7 (64.1-0.565
years) 72.8) 75.6) 73.3)
Females - no. (%) 16/24 (67) 11/21 (52) 13/23 (57) 0.613
Time from symptoms to 41 (27-63) 70 (37-132) 83 (40-170)0.198
hospital admission (median
(95% CI), days)
Cumulative prednisolone 204 (136- 136 (81-231) 197 (73-535) 0.672
dose before biopsy (median 308)
(95% CI), mg)
Fulfilled ACR criteria for 23/24 (96) 2/21 (10) 7/23 (30) 0.000*
GCA - no. (%)
Localized headache2 - no. 17/22 (77) 2/18 (11) 9/20 (45) 0.000*
(%)
Abnormal temporal artery3 14/23 (61) 4/18 (22) 9/19 (47) 0.047*
- no. (%)
ESR (mean (95% CI), 73.9 (62.2- 39.1 (25.6- 40.3(25.0- 0.000*
mm/hour) 85.5) 52.6) 55.6)
CRP (median (95% CI), 65.8 (44.8- 33.3 (20.9- 8.0 (3.8-16.6) 0.000*
mg/l) 96.5) 53.0)
Continuous variables are expressed as mean (95% CI); in cases of logarithmic
transformation, data are expressed as median (95% CI). Binomial variables are
expressed as number (percentage). * Statistical significant
1 Cancer, osteo arthritis, infection, or ischemic vascular disease.
2 New unilateral headaches localized in either the occipital, frontal or temporal
region.
3 Tenderness, thickening or decreased pulse of the temporal artery.
Disclosure: P. Therkildsen, None; B. D. Nielsen, None; K. K. Keller, None; T. Steiniche, None; L. C. Gormsen, None; I.
Tønder Hansen, None; E. M. Hauge, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/acetylcholinesterase-is-highly-expressed-

in-the-inflamed-vessel-wall-of-patients-with-giant-cell-arteritis

Measurement of Serum Cytokines during the Apparent Remission State of
Takayasu Arteritis – What Do Cytokines Tell Us?
Bruna Savioli1, Bruno Salu2, Marlon Vilela2, Maria Luiza Vilela Oliva2 and Alexandre W.S. Souza3,4, 1Internal Medicine -
Rheumatology Division, Universidade Federal de São Paulo - Escola Paulista de Medicina, São Paulo, Brazil,
2Biochemistry, Universidade Federal de São Paulo - Escola Paulista de Medicina, São Paulo, Brazil, 3Rheumatology
Div/Dept of Med, Escola Paulista de Medicina - Universidade Federal de São Paulo, Sao Paulo, Brazil, 4Internal Medicine,
Universidade Federal de São Paulo, São Paulo, Brazil
SESSION INFORMATION
Background/Purpose: The definition of remission in Takayasu arteritis (TA) is a challenge in clinical practice, since
smoldering arterial inflammation may occur without overt signs and symptoms of disease activity in TA. There is an unmet
need for biomarkers in TA to predict disease progression in patients considered in remission. Thus, this study aims to
evaluate serum cytokines in TA patients and to analyze associations with disease phenotypes and therapy during the
remission state.
Methods: Thirty-four consecutive TA patients with stable disease during the last 6 months were evaluated for serum levels
of pro-inflammatory (TNFα, IL-1β, IL-6), anti-inflammatory (IL-2, IL-10), Th1 (IL-12, IFNγ), Th2 (IL-4, IL-5, IL-13), Th9
(IL-9), Th17 (IL-17A, IL-17E, IL-17F, IL-21, IL-23) and Th22 (IL-22) cytokines by the multiplex technique.
Results: Serum TNFα, IL-17F, IL-21 and IL-23 were significantly higher in patients with stable disease presenting
angiographic type V compared with other angiographic types while serum IL-17E, IL-17F, IL-22 and IL-23 were higher in
TA patients with previous ischemic events. Similar levels of cytokines were observed in TA patients with and without aortic
aneurysmal disease, and in TA patients with and without therapy with prednisone, immunosuppressive or biological agents.
However, by multivariate linear regression analysis, serum IL-4 (β = 0.064; p = 0.004), IL-6 (β = 14.12; p = 0.006), IL-17A
(β = 11.09; p = 0.012), IL-17E (β = 0.064; p = 0.003), IL-17F (β = 0.028; p = 0.016), IL-21 (β = 26.16; p = 0.007), IL-22 (β
= 0.062; p = 0.012) and IL-23 (β = 1.86; p = 0.002) levels were independently associated with angiographic type V.
Moreover, an independent association was also found between ischemic events and serum IL-17E (β = 0.044; p = 0.005), IL-
22 (β = 0.039; p = 0.029) and IL-23 (β = 1.16; p = 0.006). Daily prednisone dose was associated with lower serum IL-4 (β =
-0.002; p = 0.002), IL-6 (β = -0.28; p = 0.010), IL-17A (β = -0.22; p = 0.021), IL-17E (β = -0.001; p = 0.003), IL-22 (β =
-0.001; p = 0.011) and IL-23 levels (β = -0.03; p = 0.005), whereas the use of an immunosuppressive simultaneously with a
biological agent led to lower serum IL-4 (β = -0.044; p = 0.024), IL-17E (β = -0.046; p = 0.017) and IL-23 (β = -0.98; p =
0.048) levels.
Conclusion: A predominant Th17 response seems to be ongoing in TA patients with extensive arterial involvement (i.e.
angiographic type V) or previous ischemic events, despite the remission state. Therapy has a significant impact on serum
levels of several cytokines in TA. These findings highlight the potential role of Th17 response in the pathophysiology of TA.
Disclosure: B. Savioli, None; B. Salu, None; M. Vilela, None; M. L. Vilela Oliva, None; A. W. S. Souza, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/measurement-of-serum-cytokines-

during-the-apparent-remission-state-of-takayasu-arteritis-what-do-cytokines-tell-us
PET-CT Findings and Clinical Outcomes in Takayasu Arteritis – Does 18F-

Fluorodeoxyglucose Uptake in Arteries Predict Relapses?
Anna Larissa Faria Janes1, Míriam Fang Castro1, Bruna Savioli1, Anne Elisabeth Diniz Arraes1, Emilia Sato2 and
Alexandre W.S. Souza3, 1Internal Medicine - Rheumatology Division, Universidade Federal de São Paulo - Escola Paulista
de Medicina, São Paulo, Brazil, 2Rheumatology Division, Universidade Federal de Sao Paulo, Sao Paulo, Brazil,
3Rheumatology Div/Dept of Med, Escola Paulista de Medicina - Universidade Federal de São Paulo, Sao Paulo, Brazil
SESSION INFORMATION
Background/Purpose: PET-CT scan with 18F-Fluorodeoxyglucose (18F-FDG) has been frequently used as a tool to assess
disease activity in Takayasu arteritis (TA) and increased 18F-FDG uptake in arteries is considered a surrogate marker of
ongoing arterial inflammation. A previous cross-sectional study showed an association between the maximal standardized
uptake value (SUVmax) in TA and disease activity in TA. To date, it is not known whether 18F-FDG uptake in arteries is
associated with disease progression in TA with the development of new angiographic lesions. This study aims to evaluate
associations between 18F-FDG uptake in arteries from TA and the risk to develop relapses, ischemic events, sustained
remission (i.e. absence of disease activity and complete withdrawal of glucocorticoids for at least 6 months), new
angiographic lesions and the need to change therapy in TA patients.
Methods: TA patients underwent PET-CT scan with 18F-FDG with arterial uptake measured by the SUV and SUVmax in
arterial walls to asses disease activity and were longitudinally assessed for disease activity using Kerr’s criteria and for the
development of new angiographic lesions by magnetic resonance angiography and/or by computerized tomography
angiography.
Results: Amongst 36 TA patients initially evaluated by 18F-FDG PET-CT scan, 32 were longitudinally followed for a
median of 83.5 months. The median SUVmax value in arteries was 1.57 (1.16-2.23). At baseline, 20 TA patients (62.5%)
had SUVmax ≥ 1.3, whereas 11 TA patients (34.4%) had active disease by Kerr’s criteria. At follow-up, 23 (71.9%) patients
had at least one disease relapse at a median of 17.0 months and new arterial lesions were observed in 14 (43.8%) cases.
There were no differences regarding the baseline SUV value in arteries that developed and arteries that did not develop new
angiographic lesions in TA patients. A higher frequency of disease relapses (85.0% vs. 50.0%, p = 0.049) and the need for
changing immunosuppressive therapy (85.0% vs. 41.7%, p = 0.018) was observed in TA patients with SUVmax ≥1.3 at
baseline compared with those with SUVmax <1.3. No differences regarding SUVmax ≥1.3 in arteries and the development
of ischemic events, sustained remission and new angiographic lesions were found in TA patients. Using the Kaplan-Meier
curve, a trend for a higher frequency of relapses was observed in TA patients with SUVmax ≥1.3 (p = 0.056) by the log rank
test. No independent associations were found between baseline SUVmax ≥1.3 and the risk of relapses (HR = 1.07; 95CI:
0.39-2.92; p = 0.892) or between baseline SUVmax ≥1.3 and the risk of developing new angiographic lesions in (HR = 0.24;
95CI: 0.02-2.57; p = 0.239) by the multivariate Cox’s proportional hazard analysis.
Conclusion: There is no association between arterial SUV and development of new arterial lesion in TA, but arterial
SUVmax in TA patients is marginally associated with a higher frequency of disease relapses and with the need for changing
immunosuppressive therapy.
Arraes AE, de Souza AW, Mariz HA, et al. (18)F-Fluorodeoxyglucose positron emission tomography and serum cytokines
and matrix metalloproteinases in the assessment of disease activity in Takayasu's arteritis. Rev Bras Reumatol 2016;56:299-
308.
Disclosure: A. L. Faria Janes, None; M. Fang Castro, None; B. Savioli, None; A. E. Diniz Arraes, None; E. Sato, None;
A. W. S. Souza, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/pet-ct-findings-and-clinical-outcomes-in-

takayasu-arteritis-does-18f-fluorodeoxyglucose-uptake-in-arteries-predict-relapses

Sensorineural Hearing Loss in Takayasu’s Arteritis
Ugur Kimyon1, Sinem Nihal Esatoglu1, Ebru Kara2, Ahmet Atas2, Elif Emel Gunay2, Emine Deniz Gozen2, Emin
Karaman2, Vedat Hamuryudan1, Hasan Yazici1 and Emire Seyahi1, 1Istanbul University, Cerrahpasa Medical Faculty,
Department of Internal Medicine, Division of Rheumatology, Istanbul, Turkey, 2Istanbul University, Cerrahpasa Medical
Faculty, Department of Otorhinolaryngology, Istanbul, Turkey
SESSION INFORMATION
Background/Purpose: Sensorineural hearing loss has been reported to be increased in several chronic autoimmune and
non-autoimmune diseases such as systemic lupus erythematosus (SLE), progressive systemic sclerosis, rheumatoid arthritis,
small vessel vasculitides, ankylosing spondylitis and Behçet’s syndrome. We had sporadically noted several degrees of
sensorineural hearing loss among our Takayasu’s arteritis (TA) patients. While, some revealed this in their past history,
others had relapsing attacks of hearing loss independent of or associated with vascular relapses. We formally investigated the
frequency and type of hearing loss among TA patients and suitable controls.
Methods: The study was done in two parts. In the first part, consecutive TA and SLE patients seen at outpatient clinic along
with apparently healthy controls were administered a standardized questionnaire that assessed hearing loss, tinnitus and
episodic vertigo. In the second part previously registered TA and SLE patients for another study (1-2), were called to
specifically for otological examination and audiometry tests that included pure-tone air and bone conduction, speech
audiometry and acoustic reflex threshold test.
Results: In the first part, 73 patients with TA, 107 patients with SLE and 133 healthy controls were studied as shown in
Table 1. The frequency of those with hearing deficit/loss, tinnitus and vertigo were significantly more common among both
TA and SLE patients (Table 1). While the frequency of those with hearing deficit/loss was similar in TA and SLE, those with
tinnitus and vertigo were significantly most common in TA.
Audiometry tests revealed that, several degrees of hearing loss were present in 36.6 % of the patients with TA and 25.0 % of
the patients with SLE (Table 2). This was mostly due to sensorineural hearing loss in both groups (TA: 31.7 %; SLE: 20.0
%) and high –frequency type was the most common pattern. Moreover, those TA patients with sensorineural hearing loss did
not show any specific vascular pattern.
Conclusion: We are unaware of previous surveys of sensorineural hearing loss in TA. Our study shows that audiovestibular
system is considerably affected in TA, similar to that observed in SLE. The fact that there was no clear vascular pattern
among patients with hearing loss, suggest that small vessel vasculitis was probably the cause of this hearing loss.
Table 1. Results of the questionnaire survey
Takayasu’s arteritis SLE Healthy controls p value
(n = 73) (n = 107) (n= 133)
Mean age 43.7 ± 11.0 44.0 ± 10.3 42.5 ± 8.3 NS

Disease duration, med [IQR] 7 [3-12] 8 [3-11] NA NS
Hearing deficit/loss, n (%) 20 (27.4) 21 (19.6) 4 (3.0) 0.001
Tinnitus, n (%) 37 (50.7) 34 (31.8) 16 (12.0) 0.001
Vertigo, n (%) 39 (53.4) 38 (35.5) 19 (14.3) 0.001
Table 2. Results of the audiometry tests
Takayasu’s arteritis, SLE p value
(n = 41) (n = 20)
Mean age 41.3 ± 8.9 42.1 ± 10.3 NS
Disease duration, med [IQR] 6 [4-11] 7 [3-11] NS
Hearing loss, n (%) 15 (36.6) 5 (25.0) NS
Sensorineural type, n (%) 12 (29.3) 4 (20.0)
Conductive type, n (%) 3 (7.3) 1 (5.0)
Disclosure: U. Kimyon, None; S. N. Esatoglu, None; E. Kara, None; A. Atas, None; E. E. Gunay, None; E. D. Gozen,
None; E. Karaman, None; V. Hamuryudan, None; H. Yazici, None; E. Seyahi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/sensorineural-hearing-loss-in-takayasus-

arteritis
Cardiovascular Risk Factors and Comorbid Diseases in Takayasu’s Arteritis

Helin Masyan, Sinem Nihal Esatoglu, Ayse Merve Celik, Vedat Hamuryudan, Hasan Yazici and Emire Seyahi, Istanbul
University, Cerrahpasa Medical Faculty, Department of Internal Medicine, Division of Rheumatology, Istanbul, Turkey
SESSION INFORMATION
Background/Purpose: In addition to the occlusive vasculitis, hypertension and accelerated atherosclerosis are probably risk
factors of the cardiovascular complications in Takayasu arteritis (TA). Although, management of traditional cardiovascular
risk factors is recommended to diminish these cardiovascular complications, we still do not know whether traditional risk
factors and other comorbid conditions are increased or operative. We looked at the frequency of traditional atherosclerotic
risk factors and comorbid conditions among pts with TA.
Methods: Between March and December 2016, we studied consecutive 88 TA pts and 81 systemic lupus erythematosus
(SLE) pts. In addition, 111 hospital workers were studied as healthy controls. Participants were interviewed with the help of
a standardized questionnaire that assesses the presence of traditional atherosclerotic risk factors. The presence of
atherosclerosis was not separately assessed. The presence of comorbid conditions was also assessed with the help of the
Charlson comorbidity index. Additionally, Framingham coronary heart disease risk score was calculated; however, this was
done only for women, because there were only a few male patients in the study cohort and male gender is an independent
risk factor in this calculation.
Results: As shown in Table 1, among the Framingham components, only hypertension was significantly more frequent in
TA. When only females were analyzed, Framingham risk score was more likely to be higher only in TA. Framingham score
of SLE pts was found to be similar to that of the healthy controls, despite an increased frequency of hypertension observed
among SLE pts. Additionally, familial history of cardiovascular diseases and sudden death were significantly more common
among the TA pts compared to the SLE pts and healthy controls. Pericardial/pleural and renal diseases were more frequently
observed among the SLE pts, (Table 2). On the other hand, cardiovascular and chronic pulmonary diseases were more
common in TA pts. The frequency of inflammatory upper/lower back pain and rheumatologic diseases were increased in
both TA and SLE. However, inflammatory bowel diseases (IBD) were only observed among the TA pts.
Conclusion: Among the traditional atherosclerotic risk factors, only hypertension appears to be increased among the TA pts.
The frequencies of IBD and inflammatory upper/lower back pain are substantially high and deserves further scrutiny.
Moreover, the increased incidence of cardiovascular and rheumatologic diseases among the first-degree relatives of TA pts
suggest that genetic mechanisms may play role in TA.
Table 1. The demographic features and cardiovascular risk factors among females
Takayasu arteritis SLE Healthy controls p value
(n = 77) (n =77) (n =87)

Age, mean ± SD 44.5 ±12.6 42.5 ±12.4 44.6 ± 11.4 0.454
Smoking (current and past), n (%) 24 (31) 33 (45) 37 (42) 0.160
Body mass index, mean ± SD 26 ± 5 26 ± 6 26 ± 5 0.987
Total cholesterol, mg/dl 192 ± 47 186 ± 44 193 ± 36 0.580
HDL cholesterol, mg/dl 56 ± 14 59.5 ± 19 57 ± 15 0.470
Hypertension, n (%) 44 (57) 24 (31) 19 (22) <0.0011
Diabetes mellitus, n (%) 7 (9) 8 (10) 12 (14) 0.612
Familial history of cardiovascular diseases, n 36 (47) 16 (21) 22 (25) 0.0012
(%)
Familial history of sudden death, 20 (26) †† 11 (14) 10 (11.5) 0.0363
n (%)
Framingham risk score, median [IQR] 4.1 [1.8-9.4] 3.3 [1.3-5.8] 3.2 [1.1-5.9] 0.056
1TA–Healthy controls and SLE-Healthy controls, p <0.05; 2TA –SLE and TA-Healthy controls, p <0.05; 3 TA-SLE and TA-
Healthy controls, p <0.05
Table 2. Comorbid diseases and accompanying rheumatologic diseases across the groups
Takayasu arteritis SLE Healthy controls p value
(n = 88) (n =81) (n=111)

Female/male 77/11 77/4 87/24 0.00411
Age, mean ± SD 44.0 ±12.3 42.3±12.3 44.3 ± 11.7 0.482
Disease duration, median (IQR) 7 [3-12.8] 7 [4-14] - 0.213
Chronic pulmonary diseases, n (%) 11 (12.5) 2 (2.5) 5 (4.5) 0.01722
Cardiovascular diseases, n (%) 38 (43.2) 18 (22.2) 10 (9.0) <0.00133
Renal diseases, n (%) 12 (13.6) 21 (25.9) 8 (7.2) 0.00144
Neurologic diseases, n (%) 14 (15.9) 9 (11.1) 4 (3.6) 0.01255
Thyroid diseases, n (%) 12 (13.6) 20 (24.7) 24 (21.6) 0.172
Antidepressant drug use, n (%) 26 (29.5) 30 (37.0) 19 (17.1) 0.00766
Rheumatologic diseases 19 (21.6) 16 (19.8) 1 0.768
Crohn’s disease/Ulcerative colitis 9 (10.2) 0 0
Ankylosing spondylitis 3 0 0
Behçet’s syndrome 3 0 0
Takayasu’s arteritis 0 1 0
Rheumatoid arthritis 1 2 0
Psoriasis 3 3 1
Anti-phospholipid syndrome 0 7 0
Sjögren’s syndrome 0 3 0
Inflammatory upper/lower back pain 21 (23.9) 23 (28.4) 6 (5.4) <0.0017
Pericarditis/pleuritis 7 (8.0) 13 (16.0) 0 0.0018
Family history of rheumatologic diseases 26 (29.5) 23 (28.4) 5 (4.5) <0.0019
1: TA-Healthy controls and SLE-Healthy controls, p<0.05; 2 TA-SLE and TA-Healthy controls, p<0.05; 3 TA-Healthy
controls and SLE-Healthy controls, p<0.05; 4 SLE-TA and SLE-Healthy controls, p<0.05; 5 TA-Healthy controls and SLE-
Healthy controls, p<0.05; 6 TA-Healthy controls and SLE-Healthy controls, p<0.05;7 TA-Healthy controls and SLE-Healthy
controls, p<0.05; 8 TA-Healthy controls and SLE-Healthy controls, p<0.05; 9 TA-Healthy controls and SLE-Healthy controls,
p<0.05
Disclosure: H. Masyan, None; S. N. Esatoglu, None; A. M. Celik, None; V. Hamuryudan, None; H. Yazici, None; E.
Seyahi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/cardiovascular-risk-factors-and-

comorbid-diseases-in-takayasus-arteritis
The Efficacy and Safety of the Anti-IL-6 Receptor Antibody Tocilizumab

for Polymyalgia Rheumatica Patients with Resistance or Intolerance to
Glucocorticoids and Methotrexate
Manami Hirata1, Akiko Ueno2, kazuyuki fujita2, Nobuyuki Shibutou2 and Masahiro Yamamura3, 1Center for
Rheumatology, Okayama Saiseikai General Hospital, Okayama, Japan, 2Centor for Rheumatology, Okayama Saiseikai
General Hospital, Okayama, Japan, 3Okayama Saiseikai General Hospital, Okayama, Japan
SESSION INFORMATION
Background/Purpose: Some patients show inadequate responses to initial glucocorticoids (GC) doses or relapses during
GC tapering and develop side effects of GCs. The 2015 EULAR/ACR recommendations for the management of PMR has
been proposed, in which early introduction of methotrexate (MTX) in addition to GCs was recommended for such GC-
resistance or GC-intolerance. A recent trial of tocilizumab (TCZ) in patients with newly diagnosed PMR, conducted in
Europe and the United States, has shown its efficacy and safety. To determine the efficacy and safety of TCZ for patients
with resistance or intolerance to GCs and/or MTX.
Methods: Sixty patients had been diagnosed with having PMR since 2011. The patients are all compatible with the 2012
EULAR/ACR provisional classification criteria for PMR, and had been treated first with GC and then, if they were resistant
or intolerant to GC, were added MTX, similarly to the 2015 EULAR/ACR recommendations for the management of PMR.
In GCs and MTX resistant patients we assessed the efffects of tocilizumab plus GCs and MTX. The disease activity were
measured by PMR-AS.
Results: There were 16 patients with GC/MTX resistant or intolerant PMR (26.7%). Of them, 8 patients with PMR agreed
to the proposal of TCZ addition, and their therapeutic responses to TCZ and its safety were determined. They were at the age
of 69.1 ± 11.3, including two males and six females. Before TCZ addition, the patients were treated with prednisolone (PSL)
at 6.9 ± 2.4 mg/day plus MTX at 6.0 ± 4.1 mg/week, and serum CRP were at 1.0 ± 1.1 mg/dL. After 9.3 ± 6.6 months of
TCZ treatment, PSL and MTX had been reduced to 0.9 ± 1.2 mg/day and 2.3 ± 3.3 mg/week, respectively, with CRP at 0.02
± 0 mg/dL. GCs were able to be withdrawn in 5 patients, and MTX were addtionally withdrawn in 2 patients. Two patients
reached drug-free remission, as judged from MR-AS (< 1.5). During TCZ therapy, each one patient showed the worsening of
depression and occlusion of the central retinal vein.
Conclusion: These results indicate that TCZ may provide a therapeutic option for patients with severe PMR who were
resistant or intolerant to GC and additional MTX.
Disclosure: M. Hirata, None; A. Ueno, None; K. fujita, None; N. Shibutou, None; M. Yamamura, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-efficacy-and-safety-of-the-anti-il-6-

receptor-antibody-tocilizumab-for-polymyalgia-rheumatica-patients-with-resistance-or-intolerance-to-glucocorticoids-and-
methotrexate
Serological Immune-Inflammatory Markers of the First RCT about

Tocilizumab to Treat Giant Cell Arteritis
Andrea Gloor1, Daniel Yerly2, Stefan Kuchen3, Sabine Adler4, Stephan Reichenbach1, Michael Seitz5 and Peter M.
Villiger6, 1Rheumatology, University hospital, Bern, Switzerland, 2Rheumatology, Uiversity hospital, Bern, Switzerland,
3Department of Rheumatology, Immunology and Allergology, University Hospital Bern, Bern, MD, Switzerland,
4Rheumatology, University Hospital Bern, Bern, Switzerland, 5Rheumatology, Clinical Immunology & Allergology,
University Hospital, Bern, Switzerland, 6Rheumatology, Immunology and Allergology, University Hospital Bern, Bern,
Switzerland
SESSION INFORMATION
Background/Purpose: As published in The Lancet online, March 4, 2016, the first randomized, placebo-controlled trial
(RCT) about tocilizumab (TCZ) in giant cell arteritis (GCA) showed clinical efficacy of the anti-IL-6R biologic agent in the
induction and maintenance of remission for 52 weeks (ClinicalTrials.gov registration number: NCT01450137). So far
nothing is known about the profile of biomarkers in complete remission controlled by TCZ. In this study we compared a
large variety of biomarkers in complete remission induced by TCZ plus glucocorticoids (GC; early phase of the study)
versus complete remission induced by TCZ monotherapy (late phase of the study), and we compared the data with age-
matched healthy controls.
Methods:
Serum levels of 18 biomarkers were quantified using Multiplex technology (R&DSystems and Invitrogen) at weeks 0, 4, 12
and 52 of the RCT. TCZ concentrations were determined by QPS, Groningen, The Netherlands. Sex and age matched
healthy individuals were included as controls (CTRL).
Results: TCZ plasma concentrations reached a plateau by week 20. Several molecules did not display a discrete pattern over
time (sCD25, adiponectin, resistin, leptin, BAFF, IFNa, YKL-40, TNF-R2, hsCRP, sICAM-1, CD163) or remained
undetectable (IL17a, IL28A, Il-11, IL-20, VCAM-1). MMP-3 and Pentraxin-3 showed a decline over time and reached
almost normal values at the end of the study. Their concentrations correlated with TCZ plasma levels and inversely with GC
dose. None of the parameters predicted flare after study end.
Conclusion: The analysis of a wide variety of immune-inflammatory markers documents a persistent subclinical disease
activity during co-medication of TCZ and GC, but a near normalization of most values under TCZ monotherapy. In
conclusion the results corroborate the advantage of anti-IL-6R therapy over GCs.
Disclosure: A. Gloor, None; D. Yerly, None; S. Kuchen, None; S. Adler, None; S. Reichenbach, None; M. Seitz, None;
P. M. Villiger, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/serological-immune-inflammatory-

markers-of-the-first-rct-about-tocilizumab-to-treat-giant-cell-arteritis
Epidemiological Study of Giant Cell Arteritis Using a Japanese

Administrative Database
Eishi Uechi and Kiyohide Fushimi, Department of Health Policy and Informatics, Tokyo Medical and Dental University
Graduate School, Tokyo, Japan
SESSION INFORMATION
Background/Purpose: The giant cell arteritis (GCA) management requires the administration of high-dose glucocorticoid
(GC) at the introduction remission and the gradual reduction of the dosage. However, the long-term usage of GC can cause
several side effects such as diabetes, osteoporosis and infections. Since patients with GCA are mainly elderly, the risk of side
effects due to high doses or long-term administration of GC is greater. However, in clinical practice, the protocol of tapering
GC depends on the judgment of an individual clinician. There is no research describing the clinical practice of GCA and GC
tapering. Therefore, this study describes the background of patients with GCA and its management using the nationwide
clinical database in Japan.
Methods: This was a retrospective cohort study using the Diagnosis Procedure Combination (DPC) database, a nationwide
inpatient database of Japan. We identified patients who received treatment for GCA (ICD10 code: M316) between 2010 and
2013 and tracked patient data up to 180 days after hospitalization and confirmed the treatment situation of GCA.
Results: 875 patients were hospitalized for GCA treatment from 2010 to 2013., 135 patients with age less than 50 years or
no GC administration were excluded from the study and 740 patients were analyzed. 354 patients were followed until 90
days after admission and 220 patients were followed until 180 days after admission (Figure 1). The average patient age was
75 years, the mean body weight was 52 kg, and the complications were 27.6% (204/740) of diabetes, 10.4% (77/740) of
gastrointestinal ulcers, and 6.8% (50/740) of malignancy. The GC dosage at the start of the treatment was 36.4 mg of
prednisolone. The usage of pulse GC and immunosuppressant was 14.2% (105/740) and 11.6% (86/740), respectively. Of
all, 69.7% (516/740) were prevented from osteoporosis. Although the mean GC dosage at the beginning was less than the
key study protocol average and the recommended guideline, the dosage of GC after 90 days of admission was high (17.6 vs.
7.8 vs. 15 mg; Figure 2). The patientsf age (>74 years) significantly affected the GC dosage reduction after 90 days of
admission (P < 0.045)). However, none of the hospital type (university hospital or an educational institution approved by the
Japan College of Rheumatology), immunosuppressant combination, patient comorbidity affected the GC tapering at 90 days.
Conclusion: Many patients with GCA present with comorbidities. However, the tapering of GC dosage was slower than the
main study protocol. Prophylaxis of complications due to GCs was not sufficiently undertaken.
Disclosure: E. Uechi, None; K. Fushimi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/epidemiological-study-of-giant-cell-

arteritis-using-a-japanese-administrative-database
B Cells in Giant Cell Arteritis: a Novel Target for Treatment?

Jacoba C. Graver1, Maria Sandovici2, Wayel H. Abdulahad2, Erlin A. Haacke3, Annemieke M.H. Boots2 and Elisabeth
Brouwer4, 1Rheumatoloy and Clinical Immunology, University of Groningen, University Medical Center Groningen,
Groningen, Netherlands, 2Rheumatology and Clinical Immunology, University of Groningen, University Medical Center
Groningen, Groningen, Netherlands, 3Pathology and Medical Biology, University of Groningen, University Medical Center
Groningen, Groningen, Netherlands, 4Department of Rheumatology and Clinical Immunology, University of Groningen,
University Medical Center Groningen, Groningen, Netherlands
SESSION INFORMATION
Background/Purpose: Giant cell arteritis (GCA) is the most common type of systemic vasculitis. Currently, two forms of
GCA are described: a cranial(C)-GCA (temporal arteritis) and a systemic, large-vessel (LV)-GCA. Late complications of
LV-GCA are aortic aneurysms or aortic rupture. Based on the analysis of temporal artery tissue, GCA is postulated to start at
the adventitial site and to be T cell-mediated. In the temporal artery infiltrates, T cells clearly outnumber B cells. However,
our report on a disturbed homeostasis of B cells in newly diagnosed C-GCA patients shows evidence for a putative role of B
cells in GCA.1 Recently, the presence of B cells organized in artery tertiary lymphoid organs (ATLOs) has been described in
C-GCA.2 The immunopathological role of B cells in both forms of GCA is underexplored and it is unknown whether B cells
are present in the vessel wall of patients with LV-GCA. The objective of this study was to assess the presence and
organization of B cells in the aorta of patients with LV-GCA.
Methods: Aorta tissue samples of 11 histologically-proven LV-GCA patients who underwent surgery due to an aortic
aneurysm were studied by immunohistochemistry. Staining was performed with antibodies against CD20 (B cells), CD3 (T
cells), CD21 (follicular dendritic cells (FDC)), PNAd (high endothelial venules (HEV)), bcl6 (germinal centers), and CD138
(plasma cells). None of the patients was receiving immunosuppressive treatment at the time of surgery. For comparison 22
aorta samples from age- and sex-matched atherosclerosis patients with an aortic aneurysm were included.
Results: Aorta tissues of LV-GCA patients showed massive infiltration of B cells (see fig. 1). The infiltrating B cells were
mainly found in the adventitia and were organized into high density B cell areas. In contrast to the temporal artery, B cells
outnumbered T cells in the aorta. Besides the presence of T cells, FDC, germinal centers, plasma cells, and HEV were
documented at the areas of B cell infiltrates, which are typical for organized ATLOs.
Conclusion: Aorta tissues from patients with histologically-proven LV-GCA showed massive and organized B cell
infiltrates mostly located in the adventitia. The mere presence of B cells at the site of inflammation prompts further
investigation into the role of B cells in the pathogenesis of GCA.
1. van der Geest KSM, Abdulahad WH, Chalan P, et al. Disturbed B cell homeostasis in newly diagnosed giant cell
arteritis and polymyalgia rheumatica. Art Rheumatol. 2014;66(7):1927-1938.
2. Ciccia F, Rizzo A, Maugeri R, et al. Ectopic expression of CXCL13, BAFF, APRIL and LT-β is associated with
artery tertiary lymphoid organs in giant cell arteritis. Ann Rheum Dis. 2016;0:1-9.
Fig. 1. Aorta from a LV-GCA patient with organized high density
CD20+ B cells areas in the adventitia (DAB/brown).
Disclosure: J. C. Graver, None; M. Sandovici, None; W. H. Abdulahad, None; E. A. Haacke, None; A. M. H. Boots,
None; E. Brouwer, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/b-cells-in-giant-cell-arteritis-a-novel-

target-for-treatment
Assessing the Possible Link between Varicella Zoster Virus and Giant Cell
Arteritis Using Clinical Assessment, Serology and Biopsy Antigen Detection –
Interim Results from the Giant Cell Arteritis and PET Scan (GAPS) Cohort
Anthony Sammel1, Katherine Nguyen2, Susan Smith3, Christopher Little3, Janice Brewer2 and Rodger Laurent2,
1Rheumatology, Royal North Shore Hospital, St Leonards, Sydney, Australia, 2Royal North Shore Hospital, St Leonards,
Sydney, Australia, 3Raymond Purves Bone and Joint Research Laboratories, Kolling Institute, Sydney, Australia
SESSION INFORMATION
Background/Purpose: Recent studies have suggested that giant cell arteritis (GCA) may be triggered by reactivation of
varicella zoster virus (VZV) based on high rates of VZV antigen detected in temporal artery specimens. We attempted to
replicate these findings and further validate the possible link between VZV and GCA by assessing clinical and serological
markers of acute infection.
Methods: 24 patients suspected of having GCA were recruited prior to temporal artery biopsy (TAB) between July 2016 and
April 2017. Patients were clinically evaluated for active and past VZV infection and had serum tested for VZV IgM and
IgG. All were treated with high dose corticosteroids for at least one week while awaiting TAB and were followed clinically
for at least one month. Formalin fixed biopsies were cut into a minimum of four sections and were stained using a mouse
derived antibody against VZV antigen and reported by two experienced, blinded immunohistochemistry researchers.
Results: Mean age was 68 and 17 (71%) were female. 23 (96%) reported headache, 15 (63%) scalp tenderness and nine
(38%) visual disturbance. Inflammatory changes were seen on seven (29%) biopsies; four had mural inflammation and three
had limited periadventitial small vessel vasculitis (SVV). 16 (67%) met ACR criteria for GCA and 11 (46%) were assessed
by the treating clinician as having definite or probable (>= 50% chance) GCA at two-week follow-up. No patients had
clinical features of herpes zoster (shingles) at the time of enrolment. Six (25%) reported a history of zoster, 22 (92%)
chickenpox and none had received the adult zoster vaccine. A single patient developed zoster ophthalmicus one week after
commencing corticosteroids with subsequent ipsilateral biopsy showing SVV. All 24 biopsies stained negative for VZV
antigen by immunohistochemistry. Of the 23 who had VZV serology, all were IgM negative. 21/23 (91%) were VZV IgG
positive consistent with past exposure.
Conclusion: VZV antigen was not detected in biopsy specimens. IgM serology was negative in all 23 tested patients. Only
one patient developed herpes zoster on follow-up. These interim results do not support a link between VZV and GCA.
Disclosure: A. Sammel, Arthritis Australia, 2; K. Nguyen, None; S. Smith, None; C. Little, None; J. Brewer, None; R.
Laurent, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/assessing-the-possible-link-between-

varicella-zoster-virus-and-giant-cell-arteritis-using-clinical-assessment-serology-and-biopsy-antigen-detection-interim-
results-from-the-giant-cell-arter
Prevalence and Distribution of Vascular FDG Uptake on Positron Emission

Tomography (PET)-CT in Patients Suspected of Having Giant Cell Arteritis –
Interim Results from the Giant Cell Arteritis and PET Scan (GAPS) Study
Anthony Sammel1, Edward Hsiao2, Katherine Nguyen3, Geoffrey Schembri2, Leslie Schrieber3, Peter Youssef4, Beatrice
Janssen3 and Rodger Laurent3, 1Rheumatology, Royal North Shore Hospital, St Leonards, Sydney, Australia, 2Royal North
Shore Hospital, St Leonards, Australia, 3Royal North Shore Hospital, St Leonards, Sydney, Australia, 4Royal Prince Alfred
Hospital, Camperdown, Sydney, Australia
SESSION INFORMATION
Background/Purpose: Positron emission tomography (PET)-CT scan can assess large vessel vasculitis in giant cell arteritis
(GCA). It has a reported sensitivity of 80% for biopsy positive disease but the superficial temporal, occipital and vertebral
arteries have not previously been assessed due to difficulties with spatial resolution.
Methods: 41 patients suspected of having GCA between May 2016 and April 2017 underwent fluorine-18 fluoro-2-
deoxyglucose (FDG) time-of-flight PET-CT scan within 72 hours of commencing corticosteroids and before clinically
guided temporal artery biopsy (TAB). Patients were imaged from the vertex of the head to the diaphragm with 1mm CT slice
reconstruction. FDG uptake was graded at 16 vascular sites using a semi-quantitative scale defined as zero (less than or
equal to blood pool), one (minimally increased), two (clearly increased) or three (very marked uptake) by one of two
blinded, experienced nuclear medicine physicians. Arterial calcification, shoulder region FDG uptake, infection and cancer
were also reported.
Results: Mean age was 70 and 29 (71%) were female. Headache (88%), jaw claudication (34%), PMR (32%) and visual
disturbance (29%) were common reported symptoms. Median CRP was 16 mg/L (range 1 – 299) and ESR was 36 mm/hr
(range 5 – 130). Eight (20%) patients had mural inflammation on biopsy, four (10%) had limited periadventitial small vessel
vasculitis and one had unequivocal thoracic aortitis on CT scan and did not undergo TAB. 28 (68%) had negative biopsies.
30 (73%) met the 1990 ACR criteria for GCA and 18 (44%) were assessed by the treating clinician as having definite or
probable (>= 50% chance) GCA at two-week follow-up. 28 (68%) had at least grade one uptake in one or more vascular
territory and 14 (34%) had at least grade two uptake. The carotid (44%), vertebral (32%) and superficial temporal (27%)
arteries were the most affected. 6 (15%) patients had increased uptake isolated to the vertebral, temporal or occipital arteries.
Shoulder region uptake was detected in 23 (56%) of patients, infection in three (two sinusitis, one pneumonia) and lung
cancer in three. Vascular calcification did not globally correlate with increased FDG uptake (Spearman’s correlation
coefficient = 0.05).
Conclusion: 68% of patients initially suspected of having GCA had at least mild increased FDG uptake on PET-CT scan.
This compared with only 30% with inflammatory changes on biopsy. Increased uptake was commonly seen in the vertebral
and temporal arteries which have not previously been assessed in PET-CT studies. Long-term follow-up will determine the
clinical role of this protocol in GCA.
Disclosure: A. Sammel, Arthritis Australia, 2; E. Hsiao, None; K. Nguyen, None; G. Schembri, None; L. Schrieber,
None; P. Youssef, None; B. Janssen, None; R. Laurent, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prevalence-and-distribution-of-vascular-

fdg-uptake-on-positron-emission-tomography-pet-ct-in-patients-suspected-of-having-giant-cell-arteritis-interim-results-
from-the-giant-cell-arteritis
Sensitivity of Temporal Artery Biopsy in Giant Cell Arteritis: Systematic

Literature Review and Meta-Analysis of Clinical Data
Emma Rubenstein1, Carla Maldini2, Solange Gonzalez-Chiappe3, Sylvie Chevret4 and Alfred Mahr3, 1Internal medicine,
University Hospital Saint-Louis, Paris, France, 2Rheumatology, Hospital Córdoba, Cordoba, Argentina, 3Internal Medicine,
University Hospital Saint-Louis, Paris, France, 4Biostatistics, University Hospital Saint-Louis, Paris, France
SESSION INFORMATION
Background/Purpose: Temporal artery biopsy (TAB) is a reference test for establishing a diagnosis of giant cell arteritis
(GCA). A subset of patients with a clinical diagnosis of GCA does not show the characteristic histopathological signs,
possibly because of technical artifacts or true phenotypic differences. The proportion of TAB-positive GCA cases varies
across studies, and the lack of consensus on the sensitivity of TAB hampers comparisons with the performance of non-
invasive diagnostic tests. In addition, the patient or study characteristics potentially influencing the sensitivity of TAB are
not known. We performed a systematic literature review and meta-analysis to estimate the sensitivity of a positive TAB in
GCA and identify factors involved in its variations.
Methods: We searched MEDLINE, EMBASE and CENTRAL databases for articles reporting TAB in GCA that were
published from 1990 to 2016, with no language restriction. Eligibility criteria included studies with at least 30 GCA cases
fulfilling the 1990 ACR criteria. From eligible publications, two independent researchers extracted the main demographic,
clinical and study design characteristics and the number of TAB-positive cases among all cases with interpretable results for
TAB. By meta-analysis, we computed the pooled proportion of TAB-positive GCA cases by a random-effects model with
logit transformation. The extent of variability between studies was assessed by the I2 statistic. Subgroup and meta-regression
analyses were used to examine the effect of covariates (e.g., clinical, geographic, temporal and study descriptors) on TAB
positivity.
Results: Among 3642 screened publications, 108 met the eligibility criteria. After publications with overlapping patient
populations were removed, 43 studies (3836 GCA patients in total) were used for analysis. The pooled proportions of TAB
positivity in GCA for all studies combined and within subgroups are shown in the Table. The proportion of TAB-positive
GCA did not notably differ by patient or study characteristics on subgroup or meta-regression analysis.
Conclusion: The estimated proportion of 70% TAB-positive GCA provides a reference for the sensitivity of TAB in GCA.
The unexplained high between-study heterogeneity could result from differences in TAB sampling and processing methods
or histopathologic criteria applied or varying propensities to diagnose TAB-negative GCA.
Disclosure: E. Rubenstein, None; C. Maldini, None; S. Gonzalez-Chiappe, None; S. Chevret, None; A. Mahr, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/sensitivity-of-temporal-artery-biopsy-in-

giant-cell-arteritis-systematic-literature-review-and-meta-analysis-of-clinical-data
The Presence of Giant Cells in the Temporal Artery Biopsy Is Associated with
Reduced Risk of Future Large Vessel Involvement in Patients with Biopsy-
Proven Giant Cell Arteritis
Nazanin Naderi1,2, Aladdin Mohammad3,4,5, Minna Willim4,6, Jan-Åke Nilsson1,6 and Carl Turesson1,6, 1Rheumatology,
Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden, 2Department of Rheumatology, Danderyd
Hospital, Stockholm, Sweden, 3Department of Renal Medicine, Vasculitis and Lupus Clinic, Addenbrooke's Hospital,
Cambridge, United Kingdom, 4Rheumatology, Department of Clinical Sciences, Lund, Lund University, Lund, Sweden,
5Department of Rheumatology, Skåne University Hospital, Lund, Sweden, 6Department of Rheumatology, Skåne University
Hospital, Malmö, Sweden
SESSION INFORMATION
Background/Purpose: Giant cell arteritis (GCA) is a systemic disease with extensive vascular involvement. The
mechanisms underlying the diversity of GCA phenotypes are incompletely understood. The purpose of this study was to
investigate predictors of large vessel involvement (LVI) in a population based cohort of patients with GCA.
Methods: Patients with biopsy-proven GCA were identified using a regional pathology register. Patients with positive
temporal artery biopsies (TAB) performed between 1997 and 2010 who were diagnosed with GCA in two defined areas of
the region were included. A structured review of histopathology reports and case records through July 2016 of all the
identified patients was performed. Reports of all relevant radiological and clinico-physiological studies were reviewed, and
cases with LVI were identified according to a pre-specified protocol. LVI was defined as aneurysm, ectasia or stenosis of the
aorta or its main branches. Patients were censored at the date of first LVI, death, migration from the area or July 29, 2016.
Event free survival was estimated using the Kaplan-Meier method. Potential predictors of LVI were also examined using
Cox regression models.
Results: A total of 274 patients with biopsy-proven GCA (77 % women) were included. The mean age at GCA onset was
75.7 years (standard deviation (SD) 8.1). Fifty-one patients (19 %) had documented LVI during the follow-up. The median
time from diagnosis of GCA to detection of LVI was 4.5 years (interquartile range 0.6-7.4). There were 32 patients with
aortic involvement (63% of those with LVI; 12 % of all GCA cases). LVI occurred to a similar extent in women and men
(75th percentile of LVI-free survival 12.9 and 13.1 years, respectively; p=0.96). Survival free of LVI was significantly longer
in patients with giant cells present in the TAB (75th percentile 13.7 vs 6.7 years; p=0.014). There was a trend towards
reduced risk of LVI with increasing age at GCA diagnosis (hazard ratio (HR) 0.81 per SD; 95 % confidence interval 0.61-
1.08). Other histopathology features, visual symptoms, platelet count, CRP, ESR or symptoms of polymyalgia rheumatica
had no significant impact on the risk of LVI. In age-adjusted analysis, the presence of giant cells in the TAB was associated
with a reduced risk of LVI (HR 0.48; 95 % CI 0.27-0.86).
Conclusion:
Clinical features of GCA had no major impact on the risk of LVI. However, the negative association with giant cells in the
biopsy suggests that patients with LVI constitute a subset of GCA with particular disease mechanisms.
Disclosure: N. Naderi, None; A. Mohammad, None; M. Willim, None; J. Å. Nilsson, None; C. Turesson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-presence-of-giant-cells-in-the-

temporal-artery-biopsy-is-associated-with-reduced-risk-of-future-large-vessel-involvement-in-patients-with-biopsy-proven-
giant-cell-arteritis
Mortality Risk and Cause-Specific Mortality in Polymyalgia Rheumatica: A

Shafay Raheel1, Cynthia S. Crowson2 and Eric L. Matteson3, 1Rheumatology, Mayo Clinic, Rochester, MN, 2Health
Sciences Research, Mayo Clinic College of Medicine and Science, Rochester, MN, 3Rheumatology, Mayo Clinic College of
Medicine and Science, Rochester, MN
SESSION INFORMATION
Background/Purpose: To determine mortality risk in polymyalgia rheumatic (PMR) and compare cause-specific mortality
rates among patients with PMR to age- and sex-matched comparators from the same population.
Methods: The study cohorts included all incident cases of PMR in a geographically-defined area diagnosed between 1970
and 2014 and non-PMR subjects from the same underlying population with similar age, sex and calendar year of index.
Patients were followed until death, migration, last contact or December 31, 2014. Risk factors obtained by retrospective
chart review among patients diagnosed in 2000-2014 included: morning stiffness, shoulder, hip and neck ache, anorexia,
fatigue, weight loss, fever, erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor positivity, smoking status
and education. The underlying cause of death was coded from national mortality statistics and grouped according to ICD
9/10 chapters. Cox models were used for analysis.
Results: A total of 760 PMR and 760 non-PMR subjects (66% female; mean age 73.7 years for both) were followed for
medians of 9.3 and 7.6 years, respectively, during which 444 PMR and 460 non-PMR subjects died. The overall
standardized mortality ratio (SMR) in PMR patients was 0.81 (95% confidence interval [CI]: 0.74-0.89; Figure 1). The SMR
remained consistent over the time period (Figure 2). Among patients with PMR there were fewer deaths from cancer (70 vs
88; hazard ratio [HR]: 0.67; 95% CI: 0.49-0.92), and neurological causes (16 vs 38; HR: 0.35; 95% CI: 0.20-0.63) than those
without PMR. Risk factor analyses among 377 patients (with 109 deaths) diagnosed in 2000-2014 showed age (HR: 1.14 per
10 year increase; 95% CI: 1.11, 1.18) and male sex (HR: 1.82; 95% CI: 1.23, 2.71) were associated with higher mortality.
No other significant risk factors were identified.
Conclusion: Survival among patients with PMR is not worse than the general population. Further research needs to be done
in order to determine factors associated with improved survival in these patients.
Disclosure: S. Raheel, None; C. S. Crowson, None; E. L. Matteson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/mortality-risk-and-cause-specific-

mortality-in-polymyalgia-rheumatica-a-population-based-cohort-study
Incidence of Herpes Zoster in Patients with Polymyalgia Rheumatica: A

Shafay Raheel1, Cynthia S. Crowson2 and Eric L. Matteson3, 1Rheumatology, Mayo Clinic, Rochester, MN, 2Health
Sciences Research, Mayo Clinic College of Medicine and Science, Rochester, MN, 3Rheumatology, Mayo Clinic College of
Medicine and Science, Rochester, MN
SESSION INFORMATION
Background/Purpose: To determine the incidence, time trends and, severity of herpes zoster in a population-based
incidence cohort of patients with polymyalgia rheumatic (PMR) compared to individuals without PMR from the same
population.
Methods: All incident cases of PMR in a geographically-defined area diagnosed between 1990 and 2014 were identified.
Patients were followed by retrospective chart review until death, migration, last contact or December 31, 2015. The medical
records of all patients with codes for herpes zoster (HZ) were reviewed to confirm the diagnosis, to ascertain the extent of
skin disease (single or multidermatomal lesions) and to determine the outcome of HZ infection (extent of organ
involvement/ complications and hospitalizations).
Results: The study included 541 patients with PMR and 541 subjects without PMR. The average age at PMR incidence
(index date for the non-PMR cohort) was 74 years, and 349 (65%) subjects were female in each cohort. The median follow
up was 8.5 years in PMR group and 7.3 years in non-PMR groups. During follow-up, 67 patients with PMR and 41 patients
without PMR developed HZ. The cumulative incidence of HZ was higher in PMR patients compared to non-PMR subjects
(14.3%±1.8 at 10 years in PMR vs. 10.4%±1.8 at 10 years in non-PMR; p<0.05; Figure 1). Therefore, patients with PMR
were more likely to develop HZ than those without PMR (hazard ratio: 1.51; 95 % confidence interval: 1.03 – 2.23). HZ
rates by decade among patients with PMR were 1.0, 2.0 and 1.2 per 100 person-years [py] compared to 0.6, 1.6 and 0.9 per
100 py among non-PMR in 1990-1999, 2000-2009 and 2010-2016, respectively. The decline in HZ incidence after year
2006 likely reflects the introduction and use of zoster vaccine in this time period (Figure 2). Complications of HZ occurred
at a similar rate in both cohorts. Rate of vision impairment and multidermatomal involvement was higher in PMR group but
this did not reach statistical significance.
Conclusion: The incidence of HZ in PMR is increased compared to the general population. Patients with PMR should be
evaluated for shingles vaccination. Further research needs to be done in order to understand the determinants of increased
incidence of HZ in PMR patients.
Disclosure: S. Raheel, None; C. S. Crowson, None; E. L. Matteson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/incidence-of-herpes-zoster-in-patients-

with-polymyalgia-rheumatica-a-population-based-cohort-study
Clinical Presentation and Outcome of Orbital Mass in Antineutrophil

Cytoplasmic Antibody-Associated Vasculitides
Cécile-Audrey Durel1, Arnaud Hot2, Ludovic Trefond3, Olivier Aumaître4, Grégory Pugnet5, Maxime Samson6, Sébastien
Abad7, Alexandre Belot8, Claire Blanchard-Delaunay9, Pascal Cathebras10, Pascal Cohen11, Fleur Cohen12, Vincent
Cottin13, Bruno Crestani14, Stéphanie Dumonteil15, Claire de Moreuil16, Stéphane Durupt17, Jean-Gabriel Fuzibet18,
Margaux Garzaro-regard19, Nicolas Girszyn20, Bertrand Godeau21, Eric Hachulla22, Yvan Jamilloux23, Patrick Jego24,
Estibaliz Lazaro25, Thomas Le Gallou26, Eric Liozon27, Thierry Martin28, Thomas Papo29, Antoinette Perlat26, Pascal
Pillet30, Karim Sacre31, Pascal Sève32, Loïc Guillevin for the French Vasculitis Study Group33 and Benjamin Terrier11,
1Internal Medicine, Hôpital Edouard Herriot, lyon, France, 2Internal Medicine, Hopital Edouard Herriot, Lyon, France,
3Internal medicine, CHU Gabriel-Montpied, clermont-ferrand, France, 4CHU Pitié-Salpêtrière - Department of Internal
Medicine 2. Referal center for SLE/APS, Paris, France, 5Service de Médecine Interne, CHU de Toulouse, Toulouse,
Toulouse, France, 6Dijon University Hospital, Dijon, France, 7Internal medicine, Hôpital Avicennes, avicennes, France,
8Pediatric Rheumatology, CHU lyon, Hospices Civils de Lyon, HFME, lyon, France, 9Internal Medicine, Centre Hospitalier,
Niort, France, 10Internal Medicine, University Hospital St Etienne, St Etienne, France, 11Service de Médecine Interne,
Hôpital Cochin, Centre de référence national pour les maladies systémiques autoimmunes rares d’Ile de France, DHU
Authors, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France, Paris, France, 12Department of Internal Medicine
2. Referal center for SLE/APS, Hôpital Pitié-Salpêtrière, AP-HP, UPMC Univ Paris 06 & French National Reference Center
For Systemic Lupus and Antiphospholipid Syndrome, Paris, France, 13Louis Pradel Hospital, Claude Bernard University
Lyon 1, Lyon, France, 14Pneumologie A, Hôpital Bichat - Claude Bernard, Paris, France, 15Internal medicine, CHU de
Limoges, Limoges, France, 16CHU de Brest, Brest, France, 17Department of Internal and Vascular Medicine, Lyon Sud
Hospital, Hospices Civils de Lyon, Lyon, France, 18Internal medicine, Hôpital l'Archet, Nice, France, 19Internal medicine,
CHU de Nice, Nice, France, 20CHU de Rouen, Rouen, France, 21Internal medicine, Hôpital Henri-Mondor, Créteil, France,
22CHU Lille, Département de Médecine Interne et Immunologie Clinique, F-59000 Lille, France, Lille, France, 23Internal
medicine department, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France, 24Medecine Interne, CHU
Rennes, Rennes, France, 25service de médecine interne et maladies infectieuses, CHU de Bordeaux, Pessac, France,
26Internal medicine, CHU de Rennes, Rennes, France, 27Departement of Internal Medicine, Limoges University Hospital,
Limoges, France, 28Cnrs UPR9021, Department of Clinical Immunology and Internal Medicine, Strasbourg University
Hospital, IBMC CNRS UPR9021, Strasbourg, France, 29Paris Bichat, Paris, France, 30Paediatrics, Hôpital Pellegrin,
University Hospital of Bordeaux, Bordeaux, France, 31Department of Internal Medicine, Bichat Hospital, Paris, France,
32Internal medicine, Internal medicine department, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France,
33Service de Médecine Interne, Centre de Référence Maladies Auto-Immunes et Auto-Inflammatoires Systémiques Rares,
Hôpital Cochin, Paris, France
SESSION INFORMATION
Background/Purpose: Orbital mass is a rare ophthalmologic manifestation of antineutrophil cytoplasmic antibody

(ANCA)-associated vasculitides (AAV) that remains a therapeutic challenge. This study aimed to describe clinical
presentation, therapeutic management and outcome of orbital mass in the setting of AAV.
Methods: We conducted a nationwide retrospective study including 59 patients with AAV fulfilling the American College
of Rheumatology criteria or Chapel Hill Consensus Conference definitions and orbital mass based on clinical and
radiological features. Clinical, biological, radiological and histological characteristics, treatment use and efficacy, and
outcome, were analyzed.
Results: Fifty nine patients (33 women) were included. Fifty-six (95%) patients had granulomatosis with polyangiitis
(GPA), two eosinophilic granulomatosis with polyangiitis, and one microscopic polyangiitis, with histological evidence of
vasculitis found in 52 (90%) patients. Fifty-one (86%) patients were ANCA-positive, with a specificity against PR3 in 71%.
Median age at AAV diagnosis and orbital mass onset were 46 and 49 years, respectively, with 46% patients presenting
orbital mass concomitantly to AAV diagnosis, 41% patients during AAV course, and 13% previous to AAV diagnosis.
Orbital mass was unilateral in 80% patients. Exophthalmia revealed orbital mass in 54 (93%) patients, while loss of visual
acuity was noted in 20 (35%) and diplopia in 21 (36%). Fifty-six (95%) patients had a systemic disease at the time of orbital
mass, with a median BVAS at 9. Orbital biopsy was performed in 32 (54%) patients, showing lymphoplasmocytic infiltrate
in 65%, extravascular granulomas in 48% and necrotizing vasculitis in 36%. Four patients had histological evidence of
IgG4-related disease. All but one patient received corticosteroids as first-line therapy, in combination with
immunosuppressive agents in 82%. First-line immunosuppressive agents comprised cyclophosphamide in 24 patients (42%),
rituximab in 11 (19%), methotrexate in 5 (9%), mycophenolate mofetil in 4 (7%), azathioprine in 2 (4%), and TNF
antagonist in one (2%). Complete response was noted in 15 (27%) cases, partial response in 27 (48%), stabilization in 10
(18%) cases, and worsening in 4 (7%) cases. Among patients with complete response, seven (47%) were MPO-ANCA
positive. Twenty seven patients (47%) required a second line of treatment because of relapse in 16 patients (59%) after a
median delay of 13 months and refractory course in 11 cases (41%). Six of these 27 patients (22%) received corticosteroids
alone as first line. All patients were treated with corticosteroids and one or combined immunosuppressive agent(s). After a
median follow-up of 68 months after orbital mass diagnosis, ophthalmologic sequelae included visual impairment in 28%
with blindness in 17%, orbital muscular extension on MRI with diplopia in 36%, and naso-sinusal bone defect on MRI in
22%.
Conclusion: Orbital mass represents a therapeutic challenge during AAV, especially during GPA. This rare manifestation is
associated with refractory course and high-frequency of sequelae, in particular blindness. Histological findings could help
physicians to manage orbital mass.
Disclosure: C. A. Durel, None; A. Hot, None; L. Trefond, None; O. Aumaître, None; G. Pugnet, None; M. Samson,
None; S. Abad, None; A. Belot, None; C. Blanchard-Delaunay, None; P. Cathebras, None; P. Cohen, None; F. Cohen,
None; V. Cottin, None; B. Crestani, None; S. Dumonteil, None; C. de Moreuil, None; S. Durupt, None; J. G. Fuzibet,
None; M. Garzaro-regard, None; N. Girszyn, None; B. Godeau, None; E. Hachulla, None; Y. Jamilloux, None; P. Jego,
None; E. Lazaro, None; T. Le Gallou, None; E. Liozon, None; T. Martin, None; T. Papo, None; A. Perlat, None; P.
Pillet, None; K. Sacre, None; P. Sève, None; L. Guillevin for the French Vasculitis Study Group, None; B. Terrier,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/clinical-presentation-and-outcome-of-

orbital-mass-in-antineutrophil-cytoplasmic-antibody-associated-vasculitides
Incidence in Large Vessel GCA in Northern Italy during a 11-Year Period

Luigi Boiardi1, Giovanna Restuccia2, Pierluigi Macchioni3, Pamela Mancuso4, Mariagrazia Catanoso5, Francesco
Muratore6, Filippo Crescentini1, Giulia Pazzola1, Nicolò Pipitone1 and Carlo Salvarani7, 1Rheumatology Unit, Arcispedale
Santa Maria Nuova - IRCCS, Reggio Emilia, Italy, 2Rheumatology Unitn, Arcispedale S Maria Nuova, IRCCS, 42100, Italy,
3Rheumatology, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy, 4Interinstitutional Epidemiology Unit, Azienda USL
di Reggio Emilia (Local Health Authority) and Azienda Ospedaliera IRCCS di Reggio Emilia,, Reggio Emilia, Italy,
5Rheumatology Service, Arcispedale S Maria Nuova-IRCCS, Reggio Emilia, Italy, 6Rheumatology Unit, Arcispedale Santa
Maria Nuova - IRCCS; Università di Modena e Reggio Emilia, Reggio Emilia, Italy, 7Rheumatology Unit, Arcispedale
Santa Maria Nuova - IRCCS; Università di Modena e Reggio Emilia, Reggio-Emilia, Italy
SESSION INFORMATION
Background/Purpose: there are few studies regarding the incidence of large vessel GCA (LV GCA). Purpose: to
investigate the incidence in patients diagnosed with large vessel GCA in the Reggio Emilia Area from 2005 through to 2016.
Methods: All patients with incident large vessel GCA diagnosed between 1 January 2005 and 31 December 2016 and living
in the Reggio Emilia area, were identified by capture and re-capture checking of computerized discharge diagnosis codes
(ICD10) and using outpatients databases from rheumatology, internal medicine, surgery, pathology, imaging departments of
Reggio Emilia Hospital as well as by examining the Reggio Emilia district database for rare diseases. To be included in the
study, patients must satisfy the following 2 criteria: Age at disease onset ≥ 50 years; evidence of large-vessel vasculitis by
angiography, MRA, CTA, PET/CT and/or ultrasonography; we included in the study also patients associating biopsy proven
gca to evidence of LVV at the imaging.
Results: There were 81 incident cases of LV GCA (57 women) during the 11-year study period; Mean ± SD age at diagnosis
was 70 ± 9 years. Incidence per 100,000 persons aged ≥50 years was 3.38 (95% confidence interval [95% CI 2.69, 4.20]).
Incidence was significantly higher in women (4.39 [95% CI 3.25, 5.53) than in men (2.19 [95% CI 1.31, 3.07]) (p <0.0036).
Incidence rates significantly increased by 11.1% every 3 years from 2.86 (2005-2007) to 4.06 (2014-2016). The highest
incidence in women and in man was observed in the 70–79 years age group (women 3.55 [95% CI 2.17,5.48; men 2,48 95%
CI 1.24.,4.43).
Conclusion: The incidence of LV GCA in the Reggio Emilia area was 3.38 and it was lower than that of patients with
biopsy proven GCA (5.8) (1); the incidence of LV GCA was signicantly higher in women as in biopsy proven GCA and
increase during the follow-up period.
References
(1) Catanoso M, Macchioni P, Boiardi L, Muratore F, Restuccia G, Cavazza A, Pipitone N, Mancuso P, Luberto F, Salvarani
C. Incidence, Prevalence, and Survival of Biopsy-Proven Giant Cell Arteritis in Northern Italy During a 26-Year Period.
Arthritis Care Res (Hoboken). 2017 Mar;69(3):430-438
Disclosure: L. Boiardi, None; G. Restuccia, None; P. Macchioni, None; P. Mancuso, None; M. Catanoso, None; F.
Muratore, None; F. Crescentini, None; G. Pazzola, None; N. Pipitone, None; C. Salvarani, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/incidence-in-large-vessel-gca-in-

northern-italy-during-a-11-year-period
Comparison between Giacta Trial and a Multicenter Series of Giant Cell

Arteritis Patients from Clinical Practice with Tocilizumab
Nuria Vegas-Revenga1, Javier Loricera1, Antonio Mera2, Eva Pérez- Pampín2, Santos Castañeda3, Lucia C. Domínguez-
Casas1, José Luis Martín-Varillas4, Belén Atienza-Mateo4, MC Gonzalez-Vela1, Jose L. Hernández5, Miguel Angel
González-Gay4 and Ricardo Blanco4, 1Hospital Universitario Marqués de Valdecilla. IDIVAL. Santander. Universidad de
Cantabria. Spain, Santander, Spain, 2Rheumatology, Complejo Hospitalario Universitario de Santiago. Galicia. Spain,
Santiago de Compostela, Spain, 3Hospital Universitario de La Princesa, Madrid. Spain, Madrid, Spain, 4Rheumatology,
Hospital Universitario Marqués de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain,
5Internal Medicine, Hospital Universitario Marqués de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain,
Santander, Spain
SESSION INFORMATION
Background/Purpose: GiACTA study is a randomized, phase III controlled clinical trial of tocilizumab (TCZ) in giant cell
arteritis (GCA) (1,2). Our aim was to compare GiACTA trial data from those of a national multicenter series of patients with
GCA from the clinical practice, focusing on the baseline characteristics of the patients.
Methods: Differences between the GiACTA study and clinical practice series were assessed. In the latter, the diagnosis of
GCA was established by the ACR-1990 criteria and in the GiACTA trial by the ACR modified criteria. In the clinical
practice study TCZ was used at standard IV dose (8 mg/kg/month) while in the GiACTA trial it was given subcutaneously
(162 mg every 1 or 2 weeks). Quantitative variables were expressed as mean±SD and they were compared by the Student’s
t-test. Dichotomous variables were expressed as percentages and compared using the chi-square test.
Results: At TCZ onset, in the clinical practice series there were a significantly greater (TABLE): a) duration of GCA, b)
polymyalgia rheumatica frequency, c) ESR, and d) previous conventional immunosuppressants (mainly MTX). There was
also a non-statistically significant lower sustained remission. The mean dose of prednisone at the TCZ onset was lower in
patients from the clinical practice. In comparing only GiACTA patients with relapsing-GCA versus those of the clinical
practice these differences remained unchanged, except for the GCA duration. PET/CT was performed more frequently in the
series of the clinical practice.
Conclusion: Patients receiving TCZ in the clinical practice study have several baseline clinical and laboratory differences
when compared to those included in the GiACTA trial.
TABLE
GiACTA GiACTA
GiACTA (overall) vs (relapsing)
GiACTA (only
overall (n= relapsing- Clinical Clinical vs Clinical
251) Practice Practice Practice
GCA;
n=132) (n= 49) p p
Women / men 188/63 99/33 39/10 0.60 0.65
Age, mean (SD) 69 (8.2) 69.1 (8) 73 (9) 0.002 0.005
Inclusion criteria ACR 1990 ACR 1990 ACR 1990
modified modified
Newly diagnosed GCA/ 119/132 0/132 0/49 <0.0001 <0.0001
recurrent GCA
Time (months) from GCA 9.1 (16.8) 16.9 (20.3) 26.4 (30.9) 0.0004 0.05
diagnosis, mean (SD)
Signs/symptoms of GCA at 98 (39) 59 (44.7) 31 (63.3) 0.003 0.04
TCZ onset#
PMR, n (%) 49 (19.5) 40 (30.3) 31 (63.3) <0.0001 0.0001
Unilateral blindness, n (%) 4 (1.6) 4 (3) 1 (4.5) 0.69 0.88
Bilateral blindness, n (%) 1 (0.4) 1 (0.8) 1 (4.5) 0.74 0.95
Amaurosis fugax, n (%) 2 (0.8) 1 (0.8) 1 (2.0) 0.98 0.95
Blurred vision, n (%) 14 (5.6) 10 (7.6) 0 (0) 0.19 0.11
ESR, mean (SD) 24 (19.4); n= 26.8 (19.6) 44.3 (33.8) 0.0002 0.001
246
CRP, mean (SD) 7.5 (13.4); 8.4 (15.4) 4.2 (6.8) 0.01 0.01
n= 250
Positive TAB, n (%) 156 (62.1) 82 (62.1) 32 (65.3) 0.78 0.82
Imaging techniques, n (%) 138 (55) 70 (53) 29 (59.2) 0.70 0.57
Positive MRA, n (%) 8 (3.2) 4 (3) 3 (6.1) 0.56 0.60
Positive CT scan, n (%) 13 (5.2) 7 (5.3) 1 (2.0) 0.98 0.59
Positive PET/CT scan, n 97 (38.7) 42 (31.8) 26 (53.1) 0.08 0.01
(%)
Patients on corticosteroids 251 (100) 132 (100) 48 (98.0) 0.36 0.60
at study onset, n (%)
Dosage of prednisone at recent GCA: 30.2 (12) 22.8 (17.6) <0.0001 0.008
TCZ onset, mean (SD) 40 (13.1)
relapsing
GCA:
30.2(12)
Patients who had received 27 (10.8) 23 (17) 43 (87.7) <0.0001 <0.0001
traditional
immunosuppressant agents,
n (%)
Patients who had received
- - 2 (4.1)
biologic therapy, n (%)
TCZ route SC SC IV
Sustained remission, n (%)
82 (54.6) - 19 (38.8) 0.51
§
Severe infection, n (%)§ 9/150 (6) - 5 (10.2) 0.49
# includes localized headache, TA, or scalp tenderness, jaw claudication, new or worsened extremity claudication.
§ In RCT patients with active TCZ therapy were only considered
*p<0.05
References:
1.- Stone J et al. Arthritis Rheumatol.2016; 68 (suppl 10). http://acrabstracts.org/abstract/efficacy-and-safety-of-tocilizumab-

in-patients-with-giant-cell-arteritis-primary-and-secondary-outcomes-from-a-phase-3-randomized-double-blind-placebo-
controlled-trial/.
2.- Tuckwell K et al. Semin Arthritis Rheum. 2016 Nov 15. pii: S0049-0172(16)30275-X
Disclosure: N. Vegas-Revenga, None; J. Loricera, None; A. Mera, None; E. Pérez- Pampín, None; S. Castañeda, None;
L. C. Domínguez-Casas, None; J. L. Martín-Varillas, None; B. Atienza-Mateo, None; M. Gonzalez-Vela, None; J. L.
Hernández, None; M. A. González-Gay, None; R. Blanco, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/comparison-between-giacta-trial-and-a-

multicenter-series-of-giant-cell-arteritis-patients-from-clinical-practice-with-tocilizumab
Extension of Affected Vascular Territories in Secondary Aortitis Is Associated

to Different Clinical Subtypes?
Nuria Vegas-Revenga1, Javier Loricera1, Diana Prieto Peña1, Isabel Martínez-Rodríguez1, Jose Ignacio Banzo2, Monica
Calderón Goercke3, Jesus Gonzalez- Vela1, Jose L. Hernández1, Vanesa Calvo-Río1, Lucia C. Domínguez-Casas1, José Luis
Martín-Varillas3, Belén Atienza-Mateo3, MC Gonzalez-Vela1, Miguel Angel González-Gay1 and Ricardo Blanco3,
1Hospital Universitario Marqués de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain,
2Nuclear Medicine, Hospital Universitario Marqués de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain,
Santander, Spain, 3Rheumatology, Hospital Universitario Marqués de Valdecilla. IDIVAL. Santander. Universidad de
Cantabria. Spain, Santander, Spain
SESSION INFORMATION
Background/Purpose:
Aortitis is characterized by inflammation of the aortic wall. Aortitis may be associated with different conditions.
Our aim was to assess if the different vascular territories affected in aortitis is associated to different underlying diseases or
to different clinical subtypes.
Methods:
Retrospective study of 38 patients with non-infectious aortitis diagnosed by PET/CT. Whole-body FDG-PET uptake was
assessed 180 minutes after injection of 7 MBq/Kg of 18F-FDG. Images were visually evaluated according to the intensity of
the 18F-FDG uptake by the vessel wall at the supraaortic trunks (ST), thoracic aorta (TA), abdominal aorta (AA), iliac
arteries (IA) and arteries of lower limbs (LL).
Results:
Thirty-eight patients (28 women/10 men) with a mean age of 68±11 years were assessed. The underlying conditions were:
giant cell arteritis (n=24), Takayasu arteritis (n= 3), spondiloarthropathie (n=3), Sjögren syndrome (n=3), ulcerative colitis
(n=2), sarcoidosis (n=1), rheumatoid arthritis (n=1), and polyarteritis nodosa (n=1).
A total of 190 vascular territories were evaluated, observing FDG-uptake in 122 (64.2%): ST (n=28, 22.3%), TA (n=38,
31.1%), AA (n=26, 21.3%), IA (n=13, 10.7%), and LL (n=17, 13.9%).
Four out of 38 patients (10.5%) had FDG-uptake in a single vascular territory (TA), 10 (26.3%) in 2 territories, 6 (15.8%) in
3, 10 (26.3%) in 4, and 8 (21.1%) in the 5 territories. The most common affection was observed in the 5 territories (n=8),
ST/AA (n=6), ST/TA/AA/LL (n=5), ST/TA/AA (n=4) and ST/TA/AA/IA (n=4). Significative differences were observed
between the extension of the affection (≤2 vs >2 territories) and the number of months from the symptoms onset to the
diagnosis (79.1±59.9 vs 24.5±33.4 months; p=0.003). Differences regarding age, sex underlying disease, C-reactive protein,
ESR, or treatment were not observed.
Conclusion:
In patients with secondary non-infectious aortitis, the PET/CT demonstrated a frequent involvement of several vascular
territories in addition to aorta, mainly ST. The extension of the vascular affection did not relate to the severity of the clinical
syndrome.
Disclosure: N. Vegas-Revenga, None; J. Loricera, None; D. Prieto Peña, None; I. Martínez-Rodríguez, None; J. I.
Banzo, None; M. Calderón Goercke, None; J. Gonzalez- Vela, None; J. L. Hernández, None; V. Calvo-Río, None; L. C.
Domínguez-Casas, None; J. L. Martín-Varillas, None; B. Atienza-Mateo, None; M. Gonzalez-Vela, None; M. A.
González-Gay, None; R. Blanco, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/extension-of-affected-vascular-

territories-in-secondary-aortitis-is-associated-to-different-clinical-subtypes
Correlation between the Routine Assessment of Patient Index Data (RAPID3)

and Inflammatory Markers in Patients with PMR
Tiffany Kolniak1, Joshua Baker2, Abhijeet Danve3 and Shiv Tej Sehra4, 1Internal Medicine, Mount Auburn Hospital,
Harvard Medical School, Cambridge, MA, 2Rheumatology, University of Pennsylvania, Philadelphia, PA, 3Yale University,
New Haven, CT, 4Rheumatology, Mount Auburn Hospital, Harvard Medical School, Cambridge, MA
SESSION INFORMATION
Background/Purpose: The routine assessment of patient index data (RAPID3) was developed for monitoring and prognosis
of patients with Rheumatoid Arthritis and has since been extended for use in other rheumatologic disorders including
ankylosing spondylitis, psoriatic arthritis and Sjogren’s disease. The purpose of this study was to evaluate the correlation
between the RAPID3 and inflammatory markers as well as the physician global assessment of disease (PGA) in patients
with polymyalgia rheumatica (PMR).
Methods: Twenty-one patients, including four new cases and seventeen previously diagnosed cases of PMR, were enrolled
in the study over a one year period. Each patient completed a RAPID3 questionnaire, had a clinical examination by a
rheumatologist and had routine laboratory testing for sedimentation rate (ESR) and C-reactive protein (CRP) as part of
routine care at each clinical visit. PGA was collected as active v. inactive disease. The rheumatologist was blinded to the
results of the RAPID3 at the time of the visit. The independent associations between RAPID3 and other clinical variables
were determined by multivariable linear regression models incorporating generalized estimating equations.
Results: Data was gathered for a total of 53 visits. The patients included in the study were all Caucasian and majority were
female (66.7%). The average age was 76 ± 12. The average daily prednisone dose over the course of the year was 5.6 ± 5.1
mg. 43.6% of visits were considered in remission according to the scores on the RAPID3. Nineteen percent of visits had
normal ESR and CRP and 75% were felt to be inactive by the treating rheumatologist. In univariate analysis, higher scores
on the RAPID3 were correlated with higher ESR [B 0.095 (0.026, 0.17) p=0.008], female sex [B: 4.03 (0.70, 7.37) p=0.02]
and physician global scores [B: 7.75 (4.45, 11.1) p<0.001]. In multivariable models, only female sex and physician global
were independently associated with RAPID3 score. PGA strongly associated with ESR [B: 11.8 (3.21, 20.36) p<0.001].
Conclusion: The RAPID3 is modestly correlated with inflammatory markers and is strongly associated with physician
global assessment of disease activity in PMR. Female sex was also independently associated with higher RAPID3 scores in
this population. Further study of the use of RAPID3 in the assessment of disease activity in PMR is of value to determine its
potential use as a rapid and easily accessible screening tool for active disease.
Table: Multivariable linear regression model with generalized estimating

equations evaluating associations between clinical variables and RAPID3
scores in PMR.
Association with
RAPID3
(N=21, Obs=53)
B (95% CI) P Value
Age 0.024 (-0.19, 0.24) 0.83
Female 3.94 (0.35, 7.53) 0.03
Physician Global 7.47 (3.85, 11.1) <0.001
ESR -0.036 (-0.16, 0.087) 0.57
Disclosure: T. Kolniak, None; J. Baker, None; A. Danve, None; S. T. Sehra, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/correlation-between-the-routine-

assessment-of-patient-index-data-rapid3-and-inflammatory-markers-in-patients-with-pmr
Risks of Non-Cardiovascular Corticosteroid Related Adverse Events and

Cancer in Giant Cell Arteritis: A French Population-Based Cohort Study
Minh Phuong Do1, Grégory Pugnet2, Guillaume Moulis3, Gregory Guernec4, Maryse Lapeyre-Mestre5 and Laurent
Sailler6, 1Faculté de Médecine, Toulouse University, Laboratoire de Pharmacoepidemiologie, Equipe émergente,UMR
INSERM 1027, Toulouse, France, 2Department of Internal Medicine, Toulouse University Hospital, University of Toulouse,
INSERM UMR 1027, Toulouse, France, 3Internal Medicine, Toulouse University Hospital, Toulouse, France, 4Faculté de
Médecine, Toulouse University, UMR INSERM 1027, Toulouse, France, 5UMR 1027, INSERM-University of Toulouse,
Toulouse, France, 6Medecine Interne, CHU Toulouse, Toulouse, France
SESSION INFORMATION
Background/Purpose:
Corticosteroid related adverse events are a main concern in patients suffering from giant cell arteritis. Conflicting results are
reported on this topic, recurrent events are usually not taken into account and direct comparisons with the general population
are scarce. We investigated non-cardiovascular corticosteroid related adverse events and cancer risks in an incident GCA
patients cohort, the Midi-Pyrénées (southwest France) APOGEE cohort.
Methods:
APOGEE is an administrative database cohort of 103 incident GCA patients (median age : 77 [51-91] years ) and 606 age-
and sex-matched controls included between January 2005 and December 2008. The risk of events was compared between
patients and controls during the first 36 months of follow-up using Cox models for single events and a linear negative
binomial regression model for multiple events (infections and hospitalizations). Generalized estimating equations were used
to compare the risk of occurrence across 6-months time periods.
Results:
More than 1 Charlson comorbidity was present before diagnosis in 35% and 46,6% of GCA and control patients,
respectively (p=0,03). The hazard ratios (HR) and incidence rate ratios (IRR) of main events are reported in table 1. The risk
of any corticosteroid-related events was increased by 49.6% in GCA patients, but it was significant only during the 24
months following diagnosis of GCA. Recurrent (≥2) infections occurred in 61.2% of GCA patients versus 46.7% (p<0.001).
The rate ratio of infections was increased and stable throughout the follow-up. Age over 75 years and sex were not
significantly associated with the risk of infection but suffering ≥1 comorbidity was (IRR = 1.187, p<0.01). Infection was the
main cause of hospitalization in GCA patients. The risk of hospitalization for any cause (excluding the first hospitalization
corresponding to GCA diagnosis) was increased (50.5% vs 35,5%, p<0,001) and repeated hospitalizations were more
frequent (p<0.001) in GCA patients. Presence of comorbidities was the sole independent predictor of the risk of
hospitalization. The initial prednisone dose (<60 mg prednisone vs ≥ 60 mg/d) was not associated with the occurrence of any
adverse event.
Conclusion:
Muskuloskeletal events were rare in the setting of osteoporosis prevention. Overall, the risk of serious (leading to
hospitalization) or repeated infections is a concern. The increased risk of cancer was unexpected.
Table 1 : risk of new corticosteroid related events and cancer in GCA patients (compared to age and sex matched controls).
De novo events p-value HR, IC 95%
Cancer <0.05 2.33 [1.03-5.22]
Diabetes mellitus <0.01 2.60 [1.35-5.03]
Glaucoma <0.001 2.41 [1.45-4.03]
Cataract (after 1 year) <0.05 2.14 [1.08-4.23]
Cutaneous <0.05 1.28 [1.01-1.63]
Neuropsychiatric <0.01 1.48 [1.11-1.95]
Musculoskeletal 0.28
IRR , IC 95%
Infections <0.05 1.27 [1.07-1.50]
Hospitalizations <0.05 1.79 [1.26-2.53]
Disclosure: M. P. Do, None; G. Pugnet, None; G. Moulis, None; G. Guernec, None; M. Lapeyre-Mestre, None; L.
Sailler, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/risks-of-non-cardiovascular-
corticosteroid-related-adverse-events-and-cancer-in-giant-cell-arteritis-a-french-population-based-cohort-study
Prognostic Value of Positron Emission Tomography in a Prospective,

Longitudinal Cohort of Patients with Large Vessel Vasculitis
Peter C. Grayson1, Sara Alehashemi2, Armin Bagheri3, Ali Cahid Civelek4, Thomas Cupps5, Mariana J. Kaplan6, Ashkan
Malayeri4, Peter A. Merkel7, Elaine Novakovich8, David A. Bluemke4 and Mark Ahlman4, 1National Institute of Arthritis,
Musculoskeletal and Skin Disease (NIAMS), Bethesda, MD, 2Rheumatology, National Institutes of Health, Bethesda, MD,
3Vasculitis Translational Research Program, NIAMS, NIH, Bethesda, MD, 4Radiology and Imaging Sciences, National
Institutes of Health, Bethesda, MD, 5Rheumatology, Georgetown University, Bethesda, MD, 6NIAMS/NIH, Bethesda, MD,
7University of Pennsylvania, Philadelphia, MN, 8Systemic Autoimmunity Branch, NIAMS, National Institutes of Health,
Bethesda, MD
SESSION INFORMATION
Background/Purpose: While several studies have examined the potential of 18F-flurodeoxyglucose (FDG) positron
emission tomography (PET) to help establish a diagnosis of large vessel vasculitis (LVV), the role of FDG-PET to monitor
disease activity over time and predict clinical outcomes remains unclear. The study objective was to assess the clinical value
of FDG-PET in a prospective cohort of patients with large-vessel vasculitis (LVV) and disease comparators.
Methods: Patients with Takayasu’s arteritis (TAK) and giant cell arteritis (GCA) were studied, along with a comparator
group consisting of patients with hyperlipidemia, diseases that mimic LVV, and healthy controls. All participants underwent
clinical evaluation and FDG-PET imaging, and patients with LVV underwent serial imaging at six-month intervals.
Performance characteristics of FDG-PET interpretation were calculated to differentiate clinically active LVV from disease
comparators and from clinical remission. Multivariable logistic regression in a mixed effects model was used to identify
clinical factors associated with FDG-PET interpretation. A qualitative summary score based on global arterial FDG uptake
in specific arterial territories was developed (the PET Vascular Activity Score – PETVAS). PETVAS was used to study
associations between FDG-PET activity and clinical characteristics and to predict relapse.
Results: 170 FDG-PET scans were performed in 115 patients (LVV=56; comparators=59). FDG-PET differentiated patients
with clinically active LVV and disease comparators with a sensitivity=85% (95%CI: 69-94%) and specificity=83% (95%CI:
71-91%). FDG-PET scans were interpreted as active vasculitis in the majority of patients with LVV in clinical remission (41
of 71, 58%). Clinical disease activity status, disease duration, body mass index, and glucocorticoid use were independently
associated with FDG-PET scan activity. Among 39 patients who underwent FDG-PET during remission, clinical relapse
requiring a change in medical management was more common in patients with a high versus low PETVAS (45% versus
11%, p=0.03) over a median follow-up of 15 months.
Conclusion: FDG-PET provides information about vascular inflammation that is complimentary to, and unique from,
clinical assessment in LVV. Use of FDG-PET to detect subclinical vascular inflammation in LVV during remission has
prognostic value.
Disclosure: P. C. Grayson, None; S. Alehashemi, None; A. Bagheri, None; A. C. Civelek, None; T. Cupps, None; M. J.
Kaplan, None; A. Malayeri, None; P. A. Merkel, None; E. Novakovich, None; D. A. Bluemke, None; M. Ahlman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prognostic-value-of-positron-emission-
tomography-in-a-prospective-longitudinal-cohort-of-patients-with-large-vessel-vasculitis
Discrepancies between Clinical- and Imaging-Based Assessments of Disease

Activity in Takayasu’s Arteritis
Peter C. Grayson1, Mark Ahlman2, Kathleen Marinelli3, Renee Borchin4, Simon Carette5, Nader A. Khalidi6, Carol A.
Langford7, Carol A. McAlear8, Paul A. Monach9, Christian Pagnoux5, Kenneth J. Warrington10, Steven R. Ytterberg10 and
Peter A. Merkel11, 1National Institute of Arthritis, Musculoskeletal and Skin Disease (NIAMS), Bethesda, MD, 2Radiology
and Imaging Sciences, National Institutes of Health, Bethesda, MD, 3NIAMS, National Institutes of Health, Bethesda, MD,
4University of South Florida, Tampa, FL, 5Division of Rheumatology, Mount Sinai Hospital, University of Toronto,
Toronto, ON, Canada, 6Rheumatology, McMaster University, Hamilton, ON, Canada, 7Rheumatic and Immunologic
Diseases, Cleveland Clinic, Cleveland, OH, 8University of Pennsylvania, Philadelphia, PA, 9Boston University School of
Medicine, Boston, MA, 10Rheumatology, Mayo Clinic, Rochester, MN, 11Biostatistics, Epidemiology, and Informatics,
SESSION INFORMATION
Background/Purpose: To study the relationship between clinically-determined disease activity and vascular inflammation
assessed by positron emission tomography (PET) in patients with TakayasuÕs arteritis (TAK).
Methods: Patients with new or relapsing TAK were evaluated at 5 centers. Whole body 18F-flurodeoxyglucose (FDG)PET-
CT imaging was performed during a period of clinical disease activity. Clinical assessments were performed blinded to PET
scan findings. A single nuclear medicine physician interpreted all of the PET scans, blinded to clinical data, to determine
presence of active vasculitis based on degree of arterial FDG uptake. Classification and regression tree analysis (CART)
defined predictors of PET scan activity. Elevated acute phase reactants (ESR>30mm/hr, CRP>10mg/L), prednisone dose at
time of imaging, ongoing use of other immunosuppressive agents for >1 month at time of clinical assessment, interval
between clinical and imaging assessments, and clinical features of disease activity (vascular vs nonspecific) were studied
within the CART models. Vascular features included asymptomatic disease progression by angiography. Non-specific
features of disease activity were defined as constitutional symptoms accompanied by elevated acute phase reactants in the
absence of signs or symptoms of vascular involvement.
Results: Clinical assessments were performed in 25 patients with TAK, and PET scans were performed a mean of 7 days
later. FDG-PET findings were suggestive of active vasculitis in 13 of 25 patients (52%). Interval increase in glucocorticoid
therapy between clinical assessment and imaging occurred in 4/13 (31%) patients with an active scan and 5/12 (42%)
patients with an inactive scan (p=0.69). CART analysis predicted FDG-PET scan activity with 84% accuracy based upon 3
variables: clinical features of disease activity, prednisone dose at the time of imaging, and use of a non-glucocorticoid
immunosuppressive agent (Figure). Acute phase reactants and time interval delay between clinical and imaging
assessments were not predictive within the model. Clinical features of disease were the strongest determinant of vascular
activity on FDG-PET. Among patients with vascular symptoms of disease activity, use of <10mg daily prednisone at the
time of imaging assessment and treatment with glucocorticoid monotherapy were associated with increased probability of
active vasculitis on FDG-PET.
Conclusion: Clinical features of disease and treatment status are associated with different findings on vascular FDG-PET
scan in TAK. Clinical studies that incorporate imaging-based assessment of disease activity in TAK should ideally obtain
baseline imaging studies prior to the initiation of glucocorticoid therapy and should consider exclusion of patients with
exclusively non-specific symptoms of disease activity.
Disclosure: P. C. Grayson, None; M. Ahlman, None; K. Marinelli, None; R. Borchin, None; S. Carette, None; N. A.
Khalidi, None; C. A. Langford, None; C. A. McAlear, None; P. A. Monach, None; C. Pagnoux, None; K. J.
Warrington, None; S. R. Ytterberg, None; P. A. Merkel, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/discrepancies-between-clinical-and-

imaging-based-assessments-of-disease-activity-in-takayasus-arteritis
The Incidence Rate of Deep Vein Thrombosis and/or Pulmonary Embolism in

Patients with Giant Cell Arteritis – Single Center Observational Study
Rok Jese1, Alenka Mavri2, Ziga Rotar1, Natasa Kejzar3, Sonja Praprotnik1, Matija Tomsic1 and Alojzija Hočevar1,
1Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia, 2University Medical Centre
Ljubljana, Ljubljana, Slovenia, 3Faculty of Medicine, Institute for Biostatistics and Medical Informatics, University of
Ljubljana, Ljubljana, Slovenia
SESSION INFORMATION
Background/Purpose: Recent studies have indicated a higher incidence of deep vein thrombosis (DVT) and pulmonary
embolism (PE) in patients with giant cell arteritis (GCA)1,2. Our objective was to determine the incidence rate of concurrent
DVT and PE in our prospectively followed GCA patient cohort.
Methods: We performed an analysis of our prospectively collected incipient cohort of patients with GCA from December
1st 2011 to December 1st 2016 at a single secondary/tertiary rheumatology center. The proportion of patients who were
diagnosed with concurrent DVT or PE was determined based on patients’ reports and electronic or paper medical records, in
addition to clinical and laboratory features of each patient. The DVT and/or PE were defined as concurrent when diagnosed
within a time frame extending from 6 months prior until 6 months after the diagnosis of GCA. The cumulative incidence rate
of DVT and PE in population aged 50 years and above from the same well defined geographical region in years 2012 to
2015 was acquired from the local electronic DVT/PE registry. Ultimately, standardized incidence ratios (SIR) for DVT and
PE with respective 95% confidence intervals (CI) were calculated using Fisher’s exact test.
Results: During the 5-year observation period, we identified 83 new GCA cases (median age 73.8 (IQR 66.6–78.8) years,
70% female, 47% ever smokers). Sixty-eight (82%) patients fulfilled the 1990 ACR classification criteria for GCA; the
remaining 18% had imaging evidence of large vessel vasculitis. We identified a single patient with PE and no patients with
DVT within the prespecified one-year time frame. The 79-year-old non-smoking female was diagnosed with PE 1 week after
GCA diagnosis and had a history of arterial hypertension, diabetes and hypercholesterolemia. She had no traditional
antiphospholipid antibodies, however we detected IgA subtype antibodies against antiprothrombin/phosphatidilserine
complex. No patients were diagnosed with DVT or a PE more than 6 months prior to the diagnosis of GCA. The average
incidence rate for concurrent DVT/PE in our GCA cohort was 12.0 per 1000 patient-years, whereas the average incidence
rate for DVT/PE in the general population aged 50 years and above, residing in the same region, was 2.4 per 1000 patient-
years (565 cases/235.800 residents per year). The SIR was 5.0 (95% CI 0.13–27.86; p=0.362).
Conclusion: Contrary to the recent reports, the incidence rate of DVT and PE was not significantly different in our GCA
cohort than in the general population of comparable age and residence. Because of the small patient number and only one
thrombotic event in our cohort, further monitoring is warranted to confirm or exclude the association between GCA and
DVT/PE.
References:
1. Arthritis Rheumatol. 2017 Jan;69(1):176-184.
2. Ann Rheum Dis. 2016 Jan;75(1):148-54.
Disclosure: R. Jese, None; A. Mavri, None; Z. Rotar, None; N. Kejzar, None; S. Praprotnik, None; M. Tomsic, None;
A. Hočevar, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-incidence-rate-of-deep-vein-

thrombosis-andor-pulmonary-embolism-in-patients-with-giant-cell-arteritis-single-center-observational-study
Seasonal Variation in Giant Cell Arteritis and Polymyalgia Rheumatica

Hospitalizations: Data from Nationwide Inpatient Sample
Paras Karmacharya1, Dilli Poudel2, Pragya Shrestha3, Rashmi Dhital4 and Raju Khanal4, 1Division of Rheumatology,
Mayo Clinic, Rochester, MN, 2Internal Medicine, Reading Health System, WEST READING, PA, 3Internal medicine,
Reading Health System, West Reading, PA, 4Internal Medicine, Reading Health System, West Reading, PA
SESSION INFORMATION
Background/Purpose: Most studies looking at seasonal variations in giant cell arteritis (GCA) note a seasonal trend, but
show disparity on timing. Concurrent peaks of GCA and polymyalgia rheumatica (PMR) have been described by some
studies questioning a common precipitating agent. We aimed to analyze the seasonal variation of GCA and PMR in the US
using a large inpatient database.
Methods: We used Nationwide Inpatient Sample (NIS) database to identify patients aged ≥ 18 years from 2009-11 with a
diagnosis of GCA and PMR with ICD-9-CM codes 446.5 and 725 in the first 3 positions. We used the Edwards’ recognition
and estimation of cyclic trend method to study the seasonal patterns of GCA and PMR hospitations stratified by age. Z-test
was used to compare seasonal incidences
Results:
A total of 57728 and 242862 hospitalizations with a diagnosis of GCA and PMR respectively were reported from 2009-11.
A significant seasonal variation was observed with highest number of GCA hospitalizations in summer (peak/low ratio
1.092, 95% CI 1.067-1.118, p<0.0001) and most significant peaks seen in age group 65-69 (peak/low ratio 1.092, 95% CI
1.067-1.118, p<0.0001) (Figure 1). No significant seasonal variation was seen with PMR hospitalizations.
Conclusion:
Our study found peak GCA hospitalizations in summer months which is concurrent with trends seen in Israel and England
but differ from other studies showing peaks in late winter and autumn. Interestingly, no similar pattern was observed in
closely related disorder, PMR. A better understanding of these patterns could lead to identification and possibly control of
potential environmental triggers in the genetically predisposed population.
Figure 1. Graph showing seasonal trend for GCA and PMR, 2009-2011
Disclosure: P. Karmacharya, None; D. Poudel, None; P. Shrestha, None; R. Dhital, None; R. Khanal, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/seasonal-variation-in-giant-cell-arteritis-

and-polymyalgia-rheumatica-hospitalizations-data-from-nationwide-inpatient-sample
Long Term Efficacy and Safety of Intravenous and Subcutaneous Biologics in

Large Vessels Vasculitis: 21 Patients Belonging to a Single Italian Center from
2011 to 2017
Paola Toniati1 and Angela Tincani2, 1RHEUMATOLOGY, SPEDALI CIVILI, BRESCIA, Italy, 2University and Spedali
Civili of Brescia, Brescia, Italy
SESSION INFORMATION
Background/Purpose:
Large vessels vasculitis (LVV) is the most common form of primary vasculitis comprising giant cell arteritis (GCA) and
Takayasu arteritis (TAK) and aortitis.
Methods:
We collect retrospectively 21 patients affected by LVV, resistant to conventional therapy and treated with intravenous or
subcutaneous biologics. Four patients were affected by GCA, with positive temporal artery biopsy; nine patients were
affected by TAK according to 1990 ACR criteria and eight patients were affected by aortitis (two with associated
retroperitoneal fibrosis), diagnosed with a positive 18F-FDG-PET scan, indicating active LVV with aortic involvement. Data
from 18F-FDG PET and CT or MRI associated with improvement of clinical and inflammatory index (ESR and PCR) were
used as a criteria of response to treatment. Our aim is to demonstrate the long term efficacy and safety of biologics in LVV.
Results:
The mean age of 21 patients were 57 year (18-87). Five patients were men with mean age of 65 year (32-79), 16 were
women with mean age of 55.3 year (18-87).The mean follow-up time of patients was 29 months (2-79). Eighteen patients
out of 21 (86%), suffered an aortic involvement at diagnosis discovered with 18F-FDG-PET scan. These patients were
checked yearly with imaging using 18F-FDG-PET with a semiquantitative analysis. 18F-FDG-PET scan follow-up data
were available in 12 patients. Tocilizumab (TCZ) was used in 19 patients for a medium period of follow-up period of 25
months (2-60). All patients started with EV TCZ (8 mg/kg/4w), then five patients passed to subcutaneous TCZ reducing the
dose to 162 mg/2w. Seventeen patients demonstrated a good response with clinical improvement, reduction of inflammatory
index and sparing of steroid dose. Two TAK patients experienced a failure treatment (new stenosis) one after one and the
other after 4 year of treatment each. Infliximab was used in 3 patients and suspended in all three patients for infusive
reactions, after three (one patient) and six month (2 patients) of treatment. Adalimumab (ADA) was used in 2 patients: one
patient responded well with a negative PCR and a negative 18F-FDG-PET scan after one year of treatment and maintain
stable remission without steroid, lasting 79 months; the other patient started the treatment three month ago. Golimumab 100
mg/m was used in one TAK patient, resistant to TCZ, with achieving a stable clinical and imaging remission (no new
stenosis) during the last year. This patient refused steroid assumption. The side effects were bronchitis affecting two patients
with TCZ and one patient with ADA and golimumab each. One patient with aortitis retroperitoneal fibrosis suspended TCZ
after two infusions for acute cholecystitis. Mean steroid dose at the beginning of biologics treatment were 30 mg/day (50-0).
Mean steroid dose at the last follow-up was 7 mg/day (32-0).
Conclusion:
In these group of 21 patients biological treatments demonstrated longterm efficacy and acceptable safety profile and
important steroid sparing effect.
Disclosure: P. Toniati, None; A. Tincani, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/long-term-efficacy-and-safety-of-

intravenous-and-subcutaneous-biologics-in-large-vessels-vasculitis-21-patients-belonging-to-a-single-italian-center-from-
2011-to-2017
Radiological Disease Activity Is the Major Determinant for Physicians While

Deciding Active Disease in Takayasu Arteritis
Gokce Kenar1, Sedanur Karaman2, Pinar Cetin3, Handan Yarkan4, Berrin Zengin1, Gercek Can1, Merih Birlik5 and Fatos
Onen1, 1Rheumatology, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey, 2Internal Medicine, Dokuz Eylul
Universty, izmir, Turkey, 3Rheumatology, Dumlupınar University School of Medicine, Kutahya, Turkey, 4Rheumatology,
Dokuz Eylul University Faculty of Medicine, İzmir, Turkey, 5Rheumatology, Dokuz Eylul University Faculty of Medicine,
izmir, Turkey
SESSION INFORMATION
Background/Purpose:There are no valid followup parameters in the assessment of disease activity in Takayasu
arteritis(TA).We investigated the impact of incorporation of vascular imaging into ITAS in the assessment of disease activity
in TA
Methods: 52 patients who fulfilled the ACR criteria were included. Physician global assessment(PGA),Kerr,et alÕs
criteria(K,eC) and ITAS2010/ITAS-A scores were evaluated in all patients(1,2).All the patients were followed using 3-6
monthly USG and 6-12 monthly MR angiography (MRA). Radiological activity(Rad) was defined based on the presence of
any of the 3 parameters including new vessel involvement by any imaging technique(5 points), the increase in vessel wall
thickness USG (3 points) and vessel wall edema on MRA(3 points). Then we incorporated these scores with ITAS-A to
obtain a composite disease activity index (ITAS-A-Rad)(table1).
Results: Total 410 visits of 52 TA patients(mean age 50.7, F:92.3%, mean followup duration: 6.4 ± 2.9 yrs) were
evaluated.Radiological assessment was done in 359 visits.Patients were categorized as having active disease in 194 visits
(47.4%) according to PGA and 72 visits (17.5%) according to K,eC.The agreement between them was fair (66%,_:0.29).Rad
parameters were determined in 105 out of 359 visits.The total agreement was found to be 83% (_:0.58) between the
radiological disease activity and K,eC and 76% (_:0.52) between the RAD and PGA.Mean ITAS-A-Rad scores were
significantly higher in visits with active disease compared to visits with inactive disease according to both PGA and
K,eC(table2).The ITAS-A-Rad was significantly correlated with all the other activity parameters including ITAS2010, ITAS-
A, and APRs.There were 43 visits with new vessel involvement by any of the two imaging techniques;all visits included
patients with active disease based on both PGA and Kerr et al criteria. The agreement between ITAS2010 and PGA was fair
(69%,_0.38).When acute phase reactant was added (ITAS-A), it did not improve (68%,_0.34). But the agreement between
ITAS-A-Rad and PGA (72%,_0.50) and also K,eC(82%,_:0.56)was found to be moderate. When only ITAS-A-USGor only
ITAS-A-MRAwas used, the agreement with PGA remained unchanged (73%,_0.45 and 76%,_0.52 respectively).When
responsiveness to change of ITAS-A-Rad score was evaluated by serial visits of patients,it was found that the mean value of
the score was discriminative for disease activity according to PGA in 9 of 11 visits(Figure1)
Conclusion: This study suggest that ITAS A Rad, a modified ITAS2010 score may be used to be a valuable foIlow-up
parameter in the assessment of disease activity in TA
Disclosure: G. Kenar, None; S. Karaman, None; P. Cetin, None; H. Yarkan, None; B. Zengin, None; G. Can, None; M.
Birlik, None; F. Onen, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/radiological-disease-activity-is-the-

major-determinant-for-physicians-while-deciding-active-disease-in-takayasu-arteritis
TGF-β-Induced Epigenetic Silencing of SOCS3 Facilitates STAT3 Signaling to

Promote Fibroblast Activation and Tissue Fibrosis in Systemic Sclerosis
Clara Dees1, Yun Zhang2, Sebastian Poetter1, Christina Bergmann3, Andreas Ramming4, Oliver Distler5, Georg Schett6 and
Jörg Distler7, 1Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-
Nuremberg, Erlangen, Germany, 2Department of Internal Medicine 3 and Institute for Clinical Immunology, Department of
Internal Medicine 3 and Institute for Clinical Immunology, Friedrich-Alexander-University of Erlangen-Nuremberg and
University Hospital Erlangen, Erlangen, Germany, 3Department of Internal Medicine 3 and Institute for Clinical
Immunology, Friedrich-Alexander-University of Erlangen-Nuremberg and University Hospital Erlangen, Erlangen,
Germany, 4Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-
Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen, Erlangen, Germany, 5Department of
Rheumatology, University Hospital Zurich, Zurich, Switzerland, 6Friedrich-Alexander-University Erlangen-Nürnberg
(FAU), Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen,
Germany., Erlangen, Germany, 7Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum
Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany
SESSION INFORMATION
Session Title: Plenary Session I
Session Type: ACR Plenary Session
Session Time: 11:00AM-12:30PM
Background/Purpose: Tissue fibrosis caused by pathological activation of fibroblasts is a major hallmark of systemic
sclerosis (SSc). Although fibroblast activation is initially driven by external factors, prolonged activation can render
fibroblasts independent of external stimuli. Accumulating evidence suggests that epigenetic alterations play a central role to
establish the persistently activated phenotype of fibroblasts. In the present study, we tested the hypothesis that epigenetic
silencing of SOCS expression may contribute to the aberrant activation of JAK2 / STAT3 signaling in SSc, and that re-
establishment of the endogenous, SOCS-dependent control of JAK / STAT signaling may prevent aberrant fibroblast
activation and ameliorate tissue fibrosis.
Methods: DNA methylation was evaluated by methylation-specific PCR and MeDIP assays. 5-aza-2’-deoxycytidine (5-
aza) was used to inhibit DNA methyltransferases (DNMTs). Knockdown analyses were done by nucleofection of siRNA in
vitro and by fibroblast-specific knockout mice in vivo.
Results: SOCS3 was strongly downregulated in skin of SSc patients compared to healthy individuals. Chronically increased
levels of TGFβ induced an SSc-like phenotype and reduced the levels of SOCS3 in normal fibroblasts to a level comparable
with SSc fibroblasts. These findings suggested that epigenetic mechanisms may account for the reduced expression of
SOCS3. Indeed, methylation analyses demonstrated a prominent promoter hypermethylation of SOCS3 in SSc fibroblasts
and in normal fibroblasts exposed to persistently high levels of TGFβ. Mechanistically, chronically increased levels of TGFβ
promoter hypermethylation of the SOCS3 promoter by induction of DNMT3A. Pharmacological inhibition of DNMTs or
selective knockdown of DNMT3A restored the normal expression of SOCS3 and reduced fibroblast activation and collagen
release. Knockdown of SOCS3 in normal dermal fibroblasts induced an SSc-like phenotype with increased activation of
JAK2-STAT3 signaling, enhanced expression of myofibroblast markers and increased collagen release. Fibroblast-specific
knockout of SOCS3 promoted JAK2-STAT3 signaling and aggravated tissue fibrosis in bleomycin- and TGFβRIact-induced
dermal fibrosis. Vice versa, forced overexpression of SOCS3 inhibited TGFβ-induced JAK2-STAT3 signaling and reduced
TGFβ-mediated fibroblast activation. Overepxression of SOCS3 also ameliorated the endogenous activation of SSc
fibroblasts. Moreover, treatment with DNMT inhibitors or fibroblast-specific knockdown of DNMT3A re-activated the
expression of SOCS3, reduced JAK2-STAT3 signaling and exerted potent antifibrotic effects in bleomycin- and TGFβRIact-
induced dermal fibrosis.
Conclusion: We demonstrate that chronic activation of TGFβ signaling perturbs the epigenetic control of STAT signaling
by DNMT3A-induced silencing of SOCS3 expression in SSc. Re-establishment of the endogenous regulation of STAT
signaling, either by forced expression of SOCS3 or by pharmacologic inhibition of DNMTs, prevents aberrant STAT3
signaling, inhibits TGFβ-induced fibroblast activation and collagen release and ameliorates experimental fibrosis.
Disclosure: C. Dees, None; Y. Zhang, None; S. Poetter, None; C. Bergmann, None; A. Ramming, None; O. Distler, 4 D
Science, Actelion, Active Biotec, Bayer, Biogen Idec, Boehringer Ingelheim Pharma, BMS, ChemomAb, EpiPharm,
Ergonex, espeRare foundation, GSK,Roche-Genentech, Inventiva, Lilly, medac, MedImmune, Mitsubishi Tanabe,
Pharmacyclics, Pfizer, Sanofi, Seroda, 2; G. Schett, None; J. Distler, 4D Science, 1,Anamar Medical, Active Biotech,
Array Biopma, BMS, Bayer Pharma, Boehringer Ingelheim, Celgene, GSK, Novartis, Sanofi-Aventis, UCB, 2,Actelion
Pharmaceuticals US, Active Biotech, Anamar, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva,
JB Therapeutics, Medac, Pfizer, RuiYi, UCB, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/tgf-%ce%b2-induced-epigenetic-

silencing-of-socs3-facilitates-stat3-signaling-to-promote-fibroblast-activation-and-tissue-fibrosis-in-systemic-sclerosis
Temporary Methotrexate Discontinuation for 2 Weeks Improves

Immunogenicity of Seasonal Influenza Vaccination in Patients with
Rheumatoid Arthritis: A Randomized Clinical Trial
Jin Kyun Park1, Kichul Shin2, You-Jung Ha3, Yun Jong Lee4, Eun Young Lee5, Yeong Wook Song6, Yunhee Choi7, Kevin
Winthrop8 and Eun Bong Lee9, 1Division of Rheumatology, Seoul National University Hospital, Seoul, Korea, Republic of
(South), 2Kyungnam villa #102, Division of Rheumatology, Department of Internal Medicine, SMG-SNU Boramae Medical
Center, Seoul, Korea, Republic of (South), 3Yonsei University College of Medicine, Seoul, Korea, Republic of (South),
4Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam,
Korea, Republic of (South), 5Division of Rheumatology, Department of Internal Medicine, Seoul National University, Seoul,
Korea, Republic of (South), 6Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of
Convergence Science and Technology, and College of Medicine, Seoul National University, Seoul, Korea, The Republic of,
Seoul, Korea, Republic of (South), 7Division of Medical Statistics, Medical Research Collaborating Center, Seoul National
University College of Medicine, Seoul, Korea, Republic of (South), 8Oregon Health & Science University, Portland, OR,
9Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
Korea, Republic of (South)
SESSION INFORMATION
Background/Purpose: Methotrexate (MTX), a widely used immune-suppressive agent, decreases vaccine response in
patients with rheumatoid arthritis (RA). We investigated whether a temporary MTX discontinuation for 2 weeks after
vaccination improves the efficacy of seasonal influenza vaccination in RA patients.
Methods: In this prospective, multicenter, randomized, parallel-group trial, RA patients taking stable dose of MTX were
randomly assigned at a ratio of 1:1 to continue MTX (MTX-continue group) or to suspend MTX for 2 weeks after
vaccination (MTX-hold group). All participants were vaccinated with seasonal quadrivalent influenza vaccine containing
H1N1, H3N2, B-Yamagata, and B-Victoria. The primary outcome was frequency of satisfactory vaccine response, defined as
≥4-fold increase in hemaglutination inhibition (HI) antibody titer at 4 weeks after vaccination against ≥2 of 4 vaccine
strains. Secondary endpoints included seroprotection rate, fold-change in antibody titers relative to baseline in geometric
mean titer (GMT).
Results: We enrolled 320 patients between Oct 7, 2016 and Jan 9, 2017. The modified intention-to-treat population
consisted of 316 patients (156 in the MTX-continue group and 160 in the MTX-hold group). Higher proportion of patients in
MTX-hold group achieved satisfactory vaccine response compared to MTX-continue group (75.5% vs. 54.5%, p < 0.001)
(Figure). Post-vaccination seroprotection rate was higher for all 4 antigens in the MTX-hold group than the MTX-continue
group (H1N1: 75.6% vs. 86.3%, p=0.016; H3N2: 62.2% vs.78.1%, p=0.002; B-Yamagata: 74.4% vs. 88.1%, p=0.002; B-
Victoria: 60.9% vs. 75.6%, p= 0.005). Similarly, the MTX-hold group achieved higher fold increase of post-vaccination HI
antibody titer in GMT [95% CI] for each antigen (H1N1: 4.6 [3.7- 5.7] vs. 6.7 [5.4 - 8.3], p=0.017; H3N2: 4.3 [3.5 - 5.3] vs.
8.0 [6.4 - 9.9], p <0.001; B-Yamagata: 3.1 [2.6 - 3.8] vs. 5.6 [4.7- 6.6], p<0.001; B-Victoria: 2.9 [2.4- 3.4] vs. 5.7 [4.9 - 6.7],
p<0.001). Vaccine was well tolerated. Disease activity after vaccination did not differ between both groups.
Conclusion:
Temporary MTX discontinuation for 2 weeks after vaccination improves the immunogenicity of seasonal influenza
vaccination in RA patients without increasing RA disease activity.
Trial registration: [www.clinicaltrials.gov, protocol number NCT02897011].
Disclosure: J. K. Park, None; K. Shin, None; Y. J. Ha, None; Y. J. Lee, None; E. Y. Lee, None; Y. W. Song, None; Y.
Choi, None; K. Winthrop, Pfizer, UCB, Abbvie, Eli Lilly and Company, Amgen, BMS, 5,Pfizer, BMS, 2; E. B. Lee, Green
Cross Corp, 2,Pfizer Inc, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/temporary-methotrexate-discontinuation-

for-2-weeks-improves-immunogenicity-of-seasonal-influenza-vaccination-in-patients-with-rheumatoid-arthritis-a-
randomized-clinical-trial
The Impact of the Duration of Bisphosphonate Drug Holidays on Hip

Fracture Rates
Jeffrey R. Curtis1, Rui Chen2, Zixu (Eric) Li2, Tarun Arora2, Kenneth Saag3, Nicole C. Wright4, Shanette Daigle2,
Meredith Kilgore5 and Elizabeth Delzell6, 1Rheumatology & Immunology, University of Alabama at Birmingham,
Birmingham, AL, 2University of Alabama at Birmingham, Birmingham, AL, 3Department of Medicine, Veterans
Administration San Diego Healthcare System/UC San Diego, San Diego, CA, 4Epidemiology, University of Alabama at
Birmingham, Birmingham, AL, 5Health Care Organization & Policy, University of Alabama at Birmingham, Birmingham,
AL, 6Retired - University of Alabama at Birmingham, Birmingham, AL
SESSION INFORMATION
Background/Purpose: Given FDA warnings, drug holidays (temporary or permanent discontinuation) of bisphosphonates
(BPs) after long-term (3-5 years) continuous therapy is becoming increasingly common in the United States (US). However,
the benefits and risks of stopping BPs, and the optimal timing to restart, remain unclear. We conducted a population-based
cohort study of women on long term BP therapy to evaluate the rate of hip fracture following a drug holiday.
Methods: We used Medicare data (2006-2014) to identify all women with medical and pharmacy coverage who initiated a
BP and were at least 80% adherent for ≥3 years (‘baseline’), at which follow-up time began. Patients using other bone
therapies (e.g. denosumab, estrogen, teriparatide, calcitonin) were excluded or censored if they started after follow-up began.
We calculated crude rates of hip fracture for continuing BP therapy and among those who discontinued, for categories of
time since discontinuing (i.e., length of drug holiday), extending up to 3 years. We used Cox proportional hazards models to
evaluate the risk of discontinuing per the length of the drug holiday, using age as the time axis and controlling for potentially
confounding factors, with and without adjusting for death as a competing risk.
Results: We identified 156,236 women who were highly adherent, long-term BP users. The mean (SD) age was 78.5 (7.5)
years. The most commonly used BPs were alendronate (71.7% ever use, 52% exclusive use) and zoledronic acid (16.2%
ever use, 8.9% exclusive use). During a median (IQR) follow up of 2.1 (1.0, 3.3) years, 62,676 (40.1%) of women stopped
BP therapy for at least 6 months or more. Among these women, 7,947 (12.7%) subsequently restarted any BP. Overall,
16,904 (10.8 %) died.
A total of 3,745 hip fractures occurred during follow-up. Hip fracture rates were lowest among women who were current
users, and gradually increased as the length of the drug holiday increased, achieving their maximum with a drug holiday >2
years (Table).
Conclusion: In a large cohort of U.S. women, a BP drug holiday greater than 2 years was associated with a significantly
increased risk for hip fracture of up to 39% compared to continued BP use.
Table: Hip fracture Rate By Duration of BP Drug Holiday, Adjusting for Competing Risk of Death
Time since Bisphosphonate Number of hip Crude Incidence Rate per Adjusted* Hazard Ratio
Discontinuation (yrs) fractures, n 1,000 person-years (95% CI)
0 (i.e. current use) 1958 9.6 (9.2, 10.1) 1.0 (reference)
>0 to <= 3 months 530 13.1 (12.0, 14.3) 1.29 (1.17, 1.42)
>3 months <=1 year 539 12.0 (11.0, 13.1) 1.12 (1.02, 1.24)
>1 to <=2 years 422 13.3 (12.0, 14.6) 1.21 (1.09, 1.35)
>2 to <=3 years 235 15.7 (13.7, 17.8) 1.39(1.21, 1.59)
*adjusted for age, region, race, rural or urban, median income, calendar year, comorbidity(fragility fracture, charlson
comorbidity index score), DXA, number of physician visits, care by a rheumatologist or endocrinologist, long term care
residence, vitamin D deficiency, glucocorticoids, and proton pump inhibitors
Disclosure: J. R. Curtis, AbbVie, Roche/Genentech, BMS, UCB, Myraid, Lilly, Amgen, Janssen, Pfizer, Corrona,
5,Amgen, Pfizer, Crescendo Bio, Corrona, 9; R. Chen, Amgen, 2; Z. Li, Amgen, 2; T. Arora, Amgen, 2; K. Saag, Amgen,
Merck and Radius, 5,Amgen, Merck, 2; N. C. Wright, None; S. Daigle, None; M. Kilgore, Amgen, 2; E. Delzell, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-impact-of-the-duration-of-

bisphosphonate-drug-holidays-on-hip-fracture-rates

Unraveling Race and Social Context in Understanding Disparities in Lupus
Mortality in the United States
Titilola Falasinnu1, Yashaar Chaichian2, Latha Palaniappan3 and Julia F Simard4, 1Health Research and Policy, Stanford
University, Stanford, CA, 2Medicine, Immunology & Rheumatology Division, Stanford School of Medicine, Stanford, CA,
3Stanford University Medical Center, General Medical Disciplines, Stanford, CA, 4Division of Epidemiology, Health
Research and Policy Department, Stanford School of Medicine, Stanford, CA
SESSION INFORMATION
Background/Purpose: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is a source of
significantly decreased life expectancy in the United States. Women and racial/ethnic minorities account for an increasingly
disproportionate number of cases, with genetic factors regarded as potentially causative. The role of social and environment
contexts has received little attention. We examined SLE mortality rates across eight groups of race-county combinations of
the US population, developed by Murray et al in 2006, that are referred to as the “Eight Americas”. We examined SLE
mortality in the Eight Americas over time to assess whether the impact of race is attenuated when the social and geographic
context is also considered. We also examined whether age at death in SLE decedents differs across the Eight Americas, and
explicated patterns of disease comorbidities among SLE decedents in the Eight Americas.
Methods: Using death certificate data from the National Center for Health Statistics Multiple Cause of Death (MCOD)
database, SLE-related deaths were identified via International Classification of Diseases, 10th revision (ICD-10) codes:
M32.1, M32.9, and M32.8. Annual SLE-related mortality rates and mortality rate ratios were calculated for each of the Eight
Americas using America 3 as the reference category. Average Annual Percent Change (AAPC) in mortality rates
summarized trends over a fixed predetermined interval. To examine trends in associated causes of death listed in the death
certificates of SLE decedents, we calculated Proportionate Mortality Ratios (PMRs) for the top causes of death (derived
from the literature) among SLE patients. Statistical analyses were performed using SAS version 9.4.
Results: There were 24,773 SLE-related deaths between 2003 and 2014. Mortality was highest among blacks in three race-
geographical contexts (Americas 6, 7, & 8). Age at death was lowest (~48 years) for blacks and Asians, regardless of
geographical context, and highest among low-income rural whites (~65 years). Blacks and Asians were also more likely to
have infectious diseases listed as associated causes of death, a finding consistent across geographical contexts, while whites
were more likely to have cardiovascular diseases and neoplasms reported as associated causes of death.
Conclusion: Blacks sharing the same social and geographical contexts as whites were disproportionately more likely to die
young and exhibit severe patterns of mortality. Although blacks inhabited three vastly different geographical and social
contexts, SLE mortality parameters did not vary among socially advantaged and disadvantaged blacks. Together, these
findings suggest that race may transcend social and geographical parameters as a key determinant of SLE mortality.
Disclosure: T. Falasinnu, None; Y. Chaichian, None; L. Palaniappan, None; J. F. Simard, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/unraveling-race-and-social-context-in-

understanding-disparities-in-lupus-mortality-in-the-united-states
Performance on Quality Measures in the RISE Registry and the Merit-Based

Incentive Payment System (MIPS)
Jinoos Yazdany1, Tracy Johansson2, Rachel Myslinski3 and Salahuddin Kazi4, 1Medicine/Rheumatology, University of
California San Francisco, San Francisco, CA, 2Practice, Advocacy & Quality, American College of Rheumatology, Atlanta,
GA, 3Governance & Ethics Specialist, Amer College of Rheumatology, Atlanta, GA, 4University of Texas Southwestern,
Dallas, TX
SESSION INFORMATION
Background/Purpose: Under the new Medicare Access and CHIP Reauthorization Act (MACRA), the quality of care
rheumatologists provide will have financial repercussions through the Merit Based Incentive Program (MIPS). MIPS will
score providers across four domains: Quality, Clinical Practice Improvement, Advancing Care Information and Cost. In this
study, we sought to evaluate performance on quality measures for practices participating in the Rheumatology Informatics
System for Effectiveness (RISE) registry in the first quarter of 2017 and to develop a prototype dashboard for RISE to assist
clinicians in understanding their MIPS performance.
Methods: The RISE informatics platform continuously collects data from the electronic health records (EHRs) of
participating practices, allowing centralized aggregation and analysis of quality measures. Measures in the areas of
rheumatoid arthritis, drug safety, preventive care and gout were examined. For the first quarter of 2017 (the initial period
eligible for MIPS reporting), we calculated performance on quality measures, defined as the percentage of eligible patients
receiving recommended care. We also developed a prototype dashboard for RISE that will display scores across the four
MIPS domains to help clinicians track their performance over time.
Results: Data from 548,990 patients across 491 clinicians and 109 practices was examined. Most rheumatologists were in a
group practice (72%); 26% were in solo practice and 2% part of a larger health system. Mean (SD) patient age was 59 (16)
years, 75% were female, 21% were racial/ethnic minorities. Performance on measures varied significantly across practices
(Table). For 2 of 5 measures for which the Medicare program has set national benchmarks, average performance of RISE
practices exceeded targets in the first quarter of 2017. Quality measures that make up the MIPS quality domain were
combined with simulated information for other MIPS domains to develop a MIPS dashboard prototype for RISE, displayed
in the Figure.
Conclusion: We found significant variation in performance on quality measures in the first quarter of 2017 across RISE
practices, with some practices having already achieved a very high level of performance. We anticipate that the MIPS
dashboard prototype will go-live on the RISE user interface in late 2017 and will aid rheumatologists in proactively
monitoring their MIPS score.
Table. Performance on Quality Measures in the RISE Registry in 2017.

Electronic Measure Average Pratice-level CMS
Quality denominatorperformanceperformancebenchmark
(N) across
Measure patients (percentile)
(eCQM)
(%)
50th 100th
Rheumatoid 95,662 46.2 43.6 83.8
arthritis:
95,662 45.6 42.6 85.9
Assessment
of Disease 95,662 91.0 93.9 95.7
Activity
Functional
Status
Assessment
DMARD
Drug Safety 9,684 57.9 65.9 78.6 9.0
TB 159,370 5.7 2.8 0 9.0

screening pre-
biologic 159,370 0.1 0 0
1+ High-
Risk
Medication in
Elderly*
2+ High-
Risk
Medications in
Elderly*
Preventive 280,725 77.9 87.4 92.3 89.7
Care
231,846 41.7 34.3 59.0 57.8
Tobacco
screening and 58,594 62.9 62.4 74.8 68.5
counseling
BMI
documentation,
follow-up plan
Blood
pressure
management
Gout 2,487 32.1 36.4 47.1
Serum urate 3,251 30.0 26.5 47.5

monitoring
1,098 64.2 80 95.7
Serum urate
target <6.8
mg/dL
Serum urate
lowering
therapy
*Lower number indicates higher performance
Figure. Prototype Merit Based Incentive Payment System (MIPS) Dashboard for the RISE registry.
Disclosure: J. Yazdany, None; T. Johansson, None; R. Myslinski, None; S. Kazi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/performance-on-quality-measures-in-the-

rise-registry-and-the-merit-based-incentive-payment-system-mips
Interferon-Alpha Disrupts Tolerance in a Mouse Model of B Cell Anergy

Dario Ferri1, Yuriy Baglaenko2, Kieran Manion2, Nan-Hua Chang2 and Joan E. Wither3, 1Immunology, University of
Toronto, Toronto, ON, Canada, 2Genetics and Development, Krembil Research Institute, University Health Network,
Toronto, ON, Canada, 3Rheumatology, University of Toronto, Toronto Western Hospital, Toronto, ON, Canada
SESSION INFORMATION
Session Title: B Cell Biology and Targets in Autoimmune Disease
Session Type: ACR Concurrent Abstract Session
Background/Purpose: Systemic Lupus Erythematosus (SLE) is characterized by the production of anti-nuclear antibodies
that deposit within tissues leading to organ damage. A central mediator of SLE pathogenesis is interferon-alpha (IFNα),
which is elevated in the serum of SLE patients. IFNα has been shown to enhance B cell signaling and promote the survival
of B cells. It also plays a major role in the induction of B cell activating factor (BAFF). While past studies have explored the
indirect effects of IFNα through BAFF on B cell tolerance, little work has focused on how IFNα itself directly affects this
process. We hypothesize that elevated levels of IFNα directly contribute to the breach of B cell tolerance in SLE. To address
this question, we have obtained an adenoviral vector encoding mouse IFNα (mDEF201), which we are using to induce
sustained elevations of serum IFNα in several well characterized mouse models of B cell tolerance.
Methods: IgHEL/sHEL double transgenic mice, with transgenes encoding anti-hen egg white lysozyme (HEL) Ig and
soluble HEL were injected IV with 107 PFU of Ad-mIFNα (mDEF201) or Ad-dI70-3 (empty control vector). At 2 weeks
post-treatment immune cell populations in the spleen and bone marrow were examined by flow cytometry, and anti-HEL
antibody production was measured by ELISA. Serum levels of IFNα were quantified by ELISA and tissue-specific IFN-
induced gene expression was assessed by qRT-PCR.
Results: 6-8 week old C57BL/6 mice administered with mDEF201, but not Ad-dI70-3, showed robust elevations of serum
IFNα from 48h to 2 weeks post infection. At 2 weeks post injection expression of several IFN-inducible genes (2-5’ Oas,
Pkr, Mx1, Ifit1, Irf7, Isg15), but not Baff, was elevated in the liver, bone marrow and spleen of infected mice. B cell
homeostasis and activation were altered in IgHEL/sHEL mice following administration of mDEF201. At 2 weeks post
infection mice displayed increased proportions of total splenic B cells (B220+CD19+). Infected mice also displayed an
increase in the proportion of mature B cells (B220+CD93-) and decreased proportions of immature transitional 1 and 2 B
cells (CD24+CD21-/int). Upregulation of the B cell activation marker B7.2 (CD86+) and down regulation of surface IgMa
was observed on mature B cells in infected mice suggestive of enhanced B cell signalling. At 2 weeks post infection mice
also displayed increased proportions of germinal center B cells (B220+GL7+CD95+). Upregulation of CD86 and enhanced
maturation of the B cell compartment was not seen following infection of mice with Ad-dI70-3. Anti-HEL IgMa antibody
production was increased 2 weeks post infection signifying a breach of B cell tolerance in IgHEL/sHEL mice. No
differences in T cell populations or activation state were seen suggesting that the observed effects on B cells occurred largely
from altered B and not T cell function.
Conclusion: IFNα may be playing an important role in breaching B cell tolerance in SLE not only through the induction of
BAFF but also through its direct actions on B cells. Further research into the effects of IFNα on these processes may prove
IFNα to be a more effective therapeutic target than BAFF for SLE patients.
Disclosure: D. Ferri, None; Y. Baglaenko, None; K. Manion, None; N. H. Chang, None; J. E. Wither, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/interferon-alpha-disrupts-tolerance-in-a-

mouse-model-of-b-cell-anergy
Single Cell Analysis Reveals Heterogeneity of Type I IFN Gene Expression in

Developing Autoreactive B Cells
Jennie Hamilton1, PingAr Yang2, Qi Wu3, Bao Luo4, Shanrun Liu5, Jun Li6, Mark Walter7, Eleanor Fish8, Hui-Chen Hsu3
and John D. Mountz9, 1Medicine/Division of Clinical Immunology and Rhematology, University of Alabama at
Birmingham, Birmingham, AL, 2Department of Medicine, Clinical Immunology & Rheumatology, University of Alabama at
Birmingham, Birmingham, AL, 3Department of Medicine, University of Alabama at Birmingham, Birmingham, AL,
4Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham,
Birmingham, AL, 5Biochemistry & Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL,
6Medicine, University of Alabama at Birmingham, Birmingham, AL, 7Microbiology, University of Alabama at
Birmingham, Birmingham, AL, 8University Health Network & Department of Immunology, University of Toronto, Toronto
General Research Institute, Toronto, ON, Canada, 9University of Alabama at Birmingham, Department of Medicine,
Birmingham, AL
SESSION INFORMATION
Background/Purpose: B cell development involves passage through a formative transitional B cell stage in the spleen. In
SLE, self-nucleic acid reactive B cells fail to be deleted at the transitional B cell stage but the factors promoting specific
expansion of these autoreactive cells are unknown. Transitional B cells have been shown to exhibit dysregulated type I
interferon (IFN) in SLE, and a sub-population of transitional and naïve B cells from SLE patients were recently shown to
express high levels of IFNα. The purpose of these studies was to investigate if B cell endogenous type I IFN can act in an
autocrine manner to promote survival and development of autoreactive transitional B cells.
Methods: Wild type C57BL/6 (B6), B6-CD45.1, CD45.2 B6-Rag1–/–, and BXD2 were obtained from Jackson Lab. B6-
IFNβ-/- mice were provided by Dr. Fish. A 1:1 ratio of bone-marrow cells was used to reconstitution. Type1 interferon-α or
IFNβ stimulation or blockade was carried out using validated sources. Single-cell QRT-PCR was carried out using a
Fluidigm-BioMark system on FACS-sorted T1 B cells. Hierarchical clustering was carried out using ClustVis.
Results: Examination of all B cells subsets in B6 and BXD2 mouse spleen revealed that transitional stage 1 (T1) B cells
expressed high levels of type I IFNα genes and IFNβ in both strains. T1 B cells from BXD2 lupus-prone mice overexpressed
IFNβ relative to B6 mice, and intriguingly, T1 B cells expressed IFNβ at levels comparable to pDCs. T1 B cells from both
B6 and BXD2 mice also exhibited higher expression of IFNαR1 and expressed CD86 and CD69 upon IFNβ stimulation.
TLR7 responses following stimulation with CL264 was highly dependent upon this endogenous IFN-β in T1 B cells, but not
in other B cell subpopulations. Single-cell examination of Ifnb-/- vs. Ifnb+/+ T1 B cells revealed heterogeneous expression
of IFNβ in WT T1 B cells and distinct gene expression signatures that required endogenous IFNβ. IFNβ-/- T1 B cells
exhibited significantly lower expression of CD86, TLR7, and PKR, and type I IFN genes. Single cell analysis of
autoimmune BXD2 T1 B cells that overexpressed IFNβ revealed that IFNβ is expressed in early T1 B cell development with
subsequent upregulation of TLR7 and IFNαs. Functional analysis of Ifnb+/+ and Ifnb-/- B cells derived from double
chimeric mice revealed that IFNβ was required for development of germinal center, autoreactive, and IgG class switched
anti-DNA, anti-La and anti-Histone autoAb producing B cells.
Conclusion: Together, these data highlight the role of IFNβ in shaping T1 B cell responses in the mouse spleen, including
their survival and responses to TLR7. Notably, they indicate that these effects are mediated through the endogenous
expression of IFNβ in T1 B cells. This mechanism suggests that endogenous IFNβ-expressing T1 B cells are initially
autonomous and that their expression of IFNβ plays a key role in regulating their responsiveness to external factors,
including externally-derived type 1 IFNs and TLR7. In lupus, overexpression of IFNβ in T1 B cells may promote the
development of autoreactive mature B cells leading to the generation of polyreactive self-antigen-reactive mature B cells.
Disclosure: J. Hamilton, None; P. Yang, None; Q. Wu, None; B. Luo, None; S. Liu, None; J. Li, None; M. Walter, None;
E. Fish, None; H. C. Hsu, None; J. D. Mountz, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/single-cell-analysis-reveals-

heterogeneity-of-type-i-ifn-gene-expression-in-developing-autoreactive-b-cells
Chronic Cutaneous Lupus Erythematosus Patients Have a Breakdown in

Autoreactive VH4.34 Antibody Tolerance While Maintaining Tolerance to
dsDNA and Chromatin
Scott Jenks1, Regina Bugrovsky1, Xiaoqian Wang1,2, Aisha Hill3, Chungwen Wei4, S. Sam Lim5, Ignacio Sanz6 and
Cristina Drenkard5, 1Emory University School of Medicine and Lowance Center for Human Immunology, Atlanta, GA,
2Division of Rheumatology and Lowance Center for Human Immunology, Emory University School of Medicine, Atlanta,
GA, 3Medicine, Emory University School of Medicine, atlanta, GA, 4Medicine, Emory University School of Medicine,
Atlanta, GA, 5Division of Rheumatology, Emory University School of Medicine, Atlanta, GA, 6Rheumatology and Lowance
Center for Human Immunology, Emory University School of Medicine and Lowance Center for Human Immunology,
Atlanta, GA
SESSION INFORMATION
Background/Purpose: While the contribution of humoral immunity to SLE is well established, the role it plays in chronic
cutaneous lupus erythematosus (CCLE) is less clear. One characteristic of SLE is a breakdown of tolerance in autoreactive
VH4.34 antibodies that are recognized by the rat anti-human idiotypic antibody 9G4 (9G4+). 9G4+ antibodies have germ
line encoded autoreactive specificity for glycolipids found on red blood cells and B cells. Despite a high frequency of naive
9G4+ B cells, healthy control donors (HC) have low amounts of serum 9G4+ IgG. In contrast, many SLE patients have high
levels of serum 9G4+ IgG that is associated with higher disease activity and highly correlated with anti-dsDNA and a
substantial proportion of anti-dsDNA antibodies are 9G4+. The purpose of this study was to compare 9G4+ IgG and
associated SLE auto-antibodies between CCLE patients and SLE patients.
Methods: We analyzed samples from 36 HC and 52 patients with primary CCLE, 44 SLE with CCLE, and 303 SLE without
CCLE. Cases with a validated diagnosis of either discoid, panniculitis, tumidus or chilblain lupus were included as CCLE.
The ACR criteria and attending rheumatologist/dermatologist judgement were used to classify CCLE cases as primary or
associated with SLE. We used ELISA to measure 9G4 with the rat monoclonal 9G4, and goat anti-human IgG. Anti-dsDNA
and anti-chromatin IgG were measured using commercial ELISA kits. B cell binding 9G4+ was evaluated ex-vivo by flow
cytometry.
Results:
41% of SLE patients were positive for 9G4 IgG and had significantly higher serum concentration than HC (p<0.001)
Surprisingly, CCLE patients also had high levels of 9G4+ IgG, 38% were positive and serum concentrations were
significantly higher than HC (p<0.001) and did not statistically differ from SLE patients. In contrast, while many SLE
patients had anti-dsDNA (48%) and anti-chromatin (52%), few CCLE patients were positive for these specificities (12% and
21%) and the concentration was significantly lower for both (p<0.001). Consequently, 9G4+ IgG concentration was highly
correlated with both anti-dsDNA (p<0.001, r=0.48) and anti-chromatin (p<0.001, r=0.45) concentration in SLE patients but
not in CCLE patients. CCLE patients, however, did have auto-reactive 9G4+, as B cell binding antibodies were similar
between SLE and CCLE patients.
Conclusion: Our study confirms the correlation between 9G4+ IgG and anti-dsDNA in SLE and extends this to anti-
chromatin. Surprisingly, CCLE patients had high levels of 9G4+ IgG but not anti-dsDNA. This suggests a two-step model of
9G4 tolerance in SLE, the breakdown of general tolerance of germline encoded autoreactive VH4.34 antibodies and a
subsequent development of 9G4+ specific for dsDNA. CCLE patients clearly have a defect in the first step and the
mechanism of this defect is potentially shared between CCLE and SLE. However, the second step is not shared, as CCLE
patients with 9G4+ IgG do not have high levels of anti-dsDNA. Regulation of this step may help determine if otherwise
immunologically similar patients may develop SLE or CCLE. Because the specificity of 9G4+ in CCLE is unknown, it
remains to be determined whether these antibodies contribute directly to CCLE disease
Disclosure: S. Jenks, None; R. Bugrovsky, None; X. Wang, None; A. Hill, None; C. Wei, None; S. S. Lim, None; I. Sanz,
None; C. Drenkard, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/chronic-cutaneous-lupus-erythematosus-

patients-have-a-breakdown-in-autoreactive-vh4-34-antibody-tolerance-while-maintaining-tolerance-to-dsdna-and-chromatin
Citrulline-Polyspecific B Cell Antigen Receptors Arising from Somatic

Hypermutation within Clades Demonstrate Pathogenicity in Rheumatoid
Arthritis
Philip J. Titcombe1,2, Gustaf Wigerblad3, Natalie Sippl3, Na Zhang1, Anna K. Shmagel4, Peter Sahlström5, Yue Jack
Zhang1, Laura Barsness Motschenbacher1, Yogita Ghodke-Puranik6, Monika Hansson7, Lena Israelsson5, Timothy B.
Niewold8, Lars Klareskog9, Camilla Svensson10, Khaled Amara7, Vivianne Malmström11 and Daniel L. Mueller1,
1Medicine/Rheumatic and Autoimmune Diseases, University of Minnesota Medical School, Minneapolis, MN,
2Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden, 3Department of Medicine,
Solna, Karolinska Institutet, Stockholm, Sweden, 4Rheumatic & Autoimmune Diseases, University of Minnesota Medical
School, Minneapolis, MN, 5Dept. of Medicine, Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden, 6Colton
Center for Autoimmunity, New York University, New York, NY, 7Department of Medicine, Rheumatology Unit, Karolinska
Institutet, Stockholm, Sweden, 8Rheumatology and Immunology, Mayo Clinic, Rochester, MN, 9Rheumatology unit,
Department of Medicine, Karolinska Institutet, Stockholm, Sweden, 10Physiology and Pharmacology, Karolinska Institutet,
Stockholm, Sweden, 11Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden
SESSION INFORMATION
Background/Purpose: Citrulline–modified proteins arising from the post-translational modification of arginine residues are
recognized as primary rheumatoid arthritis (RA) autoantigen targets based on the strong association of anti-citrullinated
protein antibodies (ACPA) with RA disease development. Nevertheless, the repertoire of citrullinated protein–specific B cell
antigen receptors (BCRs) has not previously been directly assessed.
Methods: 89 subjects from the IRB-approved University of Minnesota ACPA+ RA cohort who met the 2010 ACR/EULAR
criteria for RA provided blood samples and clinical data for use in this study. Citrullinated filaggrin peptide CFC1 and
citrullinated a-enolase peptide CEP-1 were used in the construction of tetramer sets designed to specifically capture and
characterize autoreactive citrullinated protein–specific B cells in the unaltered, polyclonal repertoire of RA patients.
Citrullinated peptide tetramer–bound B cells were subjected to flow cytometric cell sorting and single cell IGH, IGK, and
IGL gene sequencing for B cell lineage determinations. BCR gene sequences were also expressed as recombinant human
monoclonal antibodies, and tested for their ability to bind to citrullinated peptides and proteins. Finally, select human V-(D)-
J sequences were expressed as recombinant mouse monoclonal antibodies to test their ability to prolong endotoxin-induced
arthritis.
Results: Tetramer–binding CFC1– and CEP-1–specific IgD– CD27+ switched-memory B cells were found in increased
numbers in the blood of RA subjects who also demonstrated high titers of anti-CFC1 and/or –CEP-1 serum antibodies,
respectively (5.7-fold increase for CFC1, Pvalue < 0.01; 5.3-fold increase for CEP-1; Pvalue = 0.01). The frequency of
CFC1–specific switched-memory B cells was also positively associated with the duration of disease (p= 0.02), the presence
of subcutaneous nodules (p = 0.02), and the DAS28-ESR disease activity index (p = 0.01). Citrullinated peptide tetramer–
specific BCRs had highly mutated immunoglobulin (Ig) heavy and light chain complementarity determining region (CDR)
sequences, biased V-region gene usage, and conserved CDR3 junction lengths. Parsimonious clustering of related IGH, IGK,
and IGL nucleotide sequences demonstrated that the clonal expansion of rare individual B cell lineages occurs in association
with progressive amino acid sequence divergence. Recombinant human monoclonal antibodies generated from citrullinated
peptide tetramer–sorted B cells within extended clades confirmed target peptide antigen–binding for most clones, yet
citrulline–dependent cross-reactivity to a broad set of distinct citrullinated peptides and proteins implicated in RA was also
observed. Finally, a pair of citrullinated protein–specific recombinant monoclonal antibodies with cross-reactive
autoantigen–binding profiles promoted arthritis in mice.
Conclusion: Broad anti-citrullinated protein antibody specificities in RA may arise from a restricted repertoire of B cell
clades with evolving and divergent citrulline–polyspecific BCRs.
Disclosure: P. J. Titcombe, None; G. Wigerblad, None; N. Sippl, None; N. Zhang, None; A. K. Shmagel, None; P.
Sahlström, None; Y. J. Zhang, None; L. Barsness Motschenbacher, None; Y. Ghodke-Puranik, None; M. Hansson,
None; L. Israelsson, None; T. B. Niewold, EMD Serono and Janssen, Inc, 2; L. Klareskog, None; C. Svensson, None; K.
Amara, None; V. Malmström, None; D. L. Mueller, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/citrulline-polyspecific-b-cell-antigen-

receptors-arising-from-somatic-hypermutation-within-clades-demonstrate-pathogenicity-in-rheumatoid-arthritis
Generation of an Efficient CRISPR-Cas9 Editing Technique in Human

Primary B Cells for the Targeted Study of Autoimmune Susceptibility Genes
Yuriy Baglaenko1, Dario Ferri2, Juan Carlos Zuniga-Pflucker3 and Joan E. Wither2,4,5, 1Genetics and Development,
Krembil Research Institute, University Health Network, Toronto, ON, Canada, 2Immunology, University of Toronto,
Toronto, ON, Canada, 3Biological Sciences, Sunnybrook Research Institute, Toronto, ON, Canada, 4Krembil Research
Institute, University Health Network, Toronto, ON, Canada, 5Genetics and Development, Toronto Western Research
Institute, Toronto Western Hospital, Toronto, ON, Canada
SESSION INFORMATION
Background/Purpose:
Autoimmunity is a complex, poly-genic disorder that culminates in multi-organ damage. In systemic lupus erythematosus
(SLE), the prototypic autoimmune disorder, a breakdown of tolerance leads to erroneous immune cell activation and the
production of disease-causing autoantibodies. B cell functional abnormalities appear to be central to this process and many
of the lupus susceptibility genes identified by genome wide association studies (GWAS) are predicted to impact B cell
selection, differentiation, signaling, and proliferation. However, their precise mechanisms of action in human B cells remain
to be defined. A major challenge preventing the application of GWAS data to therapeutic potential is that animal models
often do not recapitulate human phenotypes. In fact, a number of identified autoimmune disease-related genes are known to
have differential expression in mice and humans. For this reason, it is important to investigate gene function directly in
primary human B cells. To date, the methods for investigating gene function in human B cells has been limited by the
relative rarity of many susceptibility alleles and ineffective or transient RNA silencing approaches. CRISPR-Cas9
technology, which uses customizable guide RNAs (gRNA) to direct the cutting of DNA by Cas9 enzymes, presents an
unexplored opportunity for studying gene function directly in primary human lymphocytes. The aim of this study was to
develop a robust CRISPR-Cas9 method for studying gene function directly in peripheral human B cells isolated from
PBMCs.
Methods:
Primary human B cells were isolated from healthy donors using Ficoll-Paque gradients followed by negative magnetic
sorting of B cells. Isolated B cells were nucleofected with CRISPR-Cas9 ribonuclear protein complexes and cultured on
BAFF and CD40L expressing OP9 stroma for 7 days. Function was assessed by calcium flux assays and phoshosignaling
using a flow cytometer.
Results:
Taking advantage of recent advances in genome editing technologies, we were able to successfully and robustly knockout
CD22 in primary human B cells from healthy donors, achieving an average efficiency of 35% as measured by loss of cell
surface expression. Using this highly adaptable system, we show that gRNA selection can have a profound impact on
knockout efficiency and that B cell lines are not an effective proxy for this process. Consistent with the literature, knockout
of CD22 in primary B cells resulted in the generation of activated/memory B cells with significantly increased expression of
CD86. Furthermore, knockout of CD22 resulted in increased basal activation and as a consequence, total B cells had a
reduced capacity for pSyk and pPLCγ signaling. Supporting this observation, IgD+ B cells were hyperresponsive to IgM
stimulation with an increased capacity for calcium fluxing.
Conclusion: These findings demonstrate, for the first time, the ability to robustly knockout genes directly in primary human
B cells. Using this approach, the role of CD22 in maintaining naïve B cells was confirmed in healthy donors. This
methodology allows for the targeted study of autoimmune-related genes and their impact on B cell function.
Disclosure: Y. Baglaenko, None; D. Ferri, None; J. C. Zuniga-Pflucker, None; J. E. Wither, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/generation-of-an-efficient-crispr-cas9-

editing-technique-in-human-primary-b-cells-for-the-targeted-study-of-autoimmune-susceptibility-genes
B Cell Receptor Sequencing of Anti-Citrullinated Protein Antibody

Expressing B Cells Indicates a Selective Advantage for the Introduction of N-
Glycosylation Sites during Somatic Hypermutation
Rochelle D. Vergroesen1, Linda Slot1, Lise Hafkenscheid1, Marvyn T. Koning2, Ellen I.H. van der Voort3, Christine A.
Grooff1, George Zervakis2, Tom W.J. Huizinga1, Theo Rispens4, Hendrik Veelken2, Rene E.M. Toes1 and Hans U.
Scherer3, 1Rheumatology, Leiden University Medical Center, Leiden, Netherlands, 2Hematology, Leiden University
Medical Center, Leiden, Netherlands, 3Department of Rheumatology, Leiden University Medical Center, Leiden,
Netherlands, 4Immunopathology, Sanquin Research, Amsterdam, Netherlands
SESSION INFORMATION
Background/Purpose:
The vast majority (>90%) of anti-citrullinated protein antibodies (ACPA) of the IgG isotype in serum and synovial fluid of
patients with rheumatoid arthritis carry N-linked glycans in the antibody variable region. This remarkable degree of Fab-
glycosylation is absent from ACPA-depleted control IgG and from autoantibodies in other diseases. N-glycosylation requires
a specific amino acid consensus sequence in the protein backbone (termed an N-glycosylation site), which is very rare in
germline-encoded variable region genes. Here, we analysed the B cell receptor (BCR) repertoire of ACPA-expressing B
cells to understand the molecular basis for this remarkable glycosylation.
Methods:
We used anchoring reverse transcription of immunoglobulin (Ig) sequences and amplification by nested PCR (ARTISAN) to
obtain full-length rearrangements of ACPA-expressing B cells. ACPA-expressing B cells and non citrulline-reactive control
B cells were obtained from peripheral blood of patients with established RA by antigen-specific tetramer staining and
fluorescence activated cell sorting. Cells were either sorted in pools, or sorted as single cells. Somatic mutations and N-
glycosylation sites were identified in the sequence reads using IMGT (High)V-QUEST. Paired heavy and light chain
sequences (HC/LC) were used to model the spatial positioning of N-glycosylation sites.
Results:
Sequence analysis of pools of cells identified 97 unique ACPA-IgG clones derived from n=8 donors. 87 unique ACPA-IgG
clones were retrieved from single cell analysis (n=6 donors). In both datasets, over 80% of ACPA-IgG clones contained N-
glycosylation sites in both HC and LC. All sites were created by somatic mutations. The mutation rate did not correlate with
the number of N-glycosylation sites, and their distribution across the variable region and their preference differed from the
pattern seen in controls. Structural modelling predicted N-glycosylation sites on the exterior of the antibody molecule.
Conclusion:
ACPA-expressing B cells generate BCRs with a high frequency of N-glycosylation sites. Frequency and localization of sites
suggest that ACPA-expressing B cells gain a selective survival advantage by acquiring glycans in the variable domain,
thereby escaping from putative checkpoints in B cell selection.
Disclosure: R. D. Vergroesen, None; L. Slot, None; L. Hafkenscheid, None; M. T. Koning, None; E. I. H. van der Voort,
None; C. A. Grooff, None; G. Zervakis, None; T. W. J. Huizinga, None; T. Rispens, None; H. Veelken, None; R. E. M.
Toes, None; H. U. Scherer, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/b-cell-receptor-sequencing-of-anti-
citrullinated-protein-antibody-expressing-b-cells-indicates-a-selective-advantage-for-the-introduction-of-n-glycosylation-
sites-during-somatic-hypermutation
Rheumatoid Arthritis and Risk for Chronic Obstructive Pulmonary Disease

or Asthma Among Women during 38 Years of Prospective Follow-up
Jeffrey A. Sparks1, Tzu-Chieh Lin2, Carlos Camargo3, Medha Barbhaiya4, Sara K. Tedeschi5, Karen H. Costenbader2,
Benjamin Raby6, Hyon K. Choi7 and Elizabeth Karlson4, 1Rheumatology, Immunology, and Allergy, Brigham and Women's
Hospital and Harvard Medical School, Boston, MA, 2Division of Rheumatology, Immunology and Allergy, Brigham and
Women's Hospital and Harvard Medical School, Boston, MA, 3Emergency Medicine, Massachusetts General Hospital and
Harvard Medical School, Boston, MA, 4Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and
Harvard Medical School, Boston, MA, 5Division of Rheumatology, Immunology and Allergy,, Brigham and Women's
Hospital and Harvard Medical School, Boston, MA, 6Pulmonary Medicine, Brigham and Women's Hospital and Harvard
Medical School, Boston, MA, 7Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital,
SESSION INFORMATION
Session Title: Epidemiology and Public Health I: Lung, Bone, and Infection Outcomes
Background/Purpose : Rheumatoid arthritis (RA) has been associated with increased risk for chronic obstructive
pulmonary disease (COPD) and asthma, but these findings may have been confounded by smoking behaviors occurring
before and after RA diagnosis. Citrullination of proteins in the airways is important in both RA and COPD etiology so may
link these diseases beyond smoking. Marginal structural modeling (MSM) is a statistical method to control for factors, such
as smoking, on the causal pathway for an outcome, such as COPD or asthma. We investigated whether RA increases risk for
COPD or asthma using MSM to adjust for smoking occurring before RA onset or mediating these respiratory morbidities
after RA diagnosis.
Methods : Within the prospective NursesÕ Health Study (n=121,701 women; 1976-2014), we identified an incident RA
cohort and matched each woman with RA to 10 non-RA comparators by age and year of RA diagnosis (index date). All RA
cases met the 1987 ACR classification criteria. We excluded women with prevalent COPD or asthma at baseline. Data were
obtained through biennial questionnaires and medical records. We used MSM to determine the independent effect of RA on
incident self-reported COPD or asthma, adjusting for time-varying covariates by inverse probability weighting. Smoking
was categorized as fixed pre-index intensity/duration (0, >0 to 10, 10.1 to 20, or >20 pack-years) and time-varying post-
index status (never, past, or current). In subgroup analyses, we separately investigated seropositive RA and seronegative RA
for risk of COPD or asthma.
Results : We identified 843 women with incident RA during 38 years of follow-up in the NHS, matched to 8,399
comparators without RA. Mean age was 59.8 years and mean follow-up after index date was 18.6 years (SD 9.0) for RA and
18.8 years (SD 9.5) for comparators. During 173,484 person-years of follow-up after index date, we identified 68 (8.1%)
incident COPD and 40 (4.7%) asthma cases among women with RA, and 459 (5.5%) COPD and 268 (3.2%) asthma cases
among comparators. RA was associated with increased risk of COPD (HR 1.52, 95%CI 1.17-1.97, Table) and asthma (HR
1.55, 95%CI 1.11-2.16) compared to comparators matched to age and year at index date. After adjustment for time-varying
covariates, including smoking before and after index date, RA was significantly associated with COPD (HR 1.68, 95%CI
1.36-2.07), but not asthma (HR 1.11, 95%CI 0.59-2.09), compared to non-RA. Women with seropositive RA (HR 1.74,
95%CI 1.36-2.23) and seronegative RA (HR 1.62, 95%CI 1.09-2.40) had similar increased risk for COPD compared to
comparators.
Conclusion : In this large prospective cohort study with time-varying measures throughout long-term follow-up, RA was
associated with increased risk for incident COPD, but not asthma, independent of smoking and other lifestyle factors. These
results provide rationale to investigate the effect of RA-specific factors beyond smoking on COPD risk.
Disclosure: J. A. Sparks, None; T. C. Lin, None; C. Camargo, None; M. Barbhaiya, None; S. K. Tedeschi, None; K. H.
Costenbader, None; B. Raby, None; H. K. Choi, None; E. Karlson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rheumatoid-arthritis-and-risk-for-

chronic-obstructive-pulmonary-disease-or-asthma-among-women-during-38-years-of-prospective-follow-up
Rates of New-Onset Pulmonary Disease Among Patients with Systemic Lupus

Erythematosus in Sweden
Lindsy J. Forbess1, Michael Weisman2 and Julia F Simard3, 1Medicine, Division of Rheumatology, Cedars-Sinai Medical
Center, Los Angeles, CA, 2Cedars-Sinai Medical Center Division of Rheumatology, Los Angeles, CA, 3Division of
Epidemiology, Health Research and Policy Department, Stanford School of Medicine, Stanford, CA
SESSION INFORMATION
Background/Purpose: Our goal was to examine lung disease and types of pulmonary manifestations observed in patients
with SLE. We studied population-based register data from Sweden to determine the incidence of pulmonary diagnoses
among incident and prevalent SLE patients compared to the general population.
Methods: Using data from a linkage of Swedish registers we identified patients with SLE (at least 2 SLE coded discharge
diagnoses and at least 1 SLE-specific discharge diagnosis by a specialist who manages SLE) and matched them to
individuals from the general population on age, sex, and county of residence when the SLE index case first presented with
SLE. Pulmonary diagnoses were identified using ICD codes from the National Patient Register’s (NPR) discharge diagnoses
for inpatient and outpatient visit data. Those with a history of pulmonary disease were excluded. Individuals were followed
until they had their first pulmonary diagnosis, died, emigrated, or reached the study end. We calculated incidence rates and
corresponding 95% confidence intervals (95% CI) overall and by type of pulmonary disease, for incident (2003-2013) and
prevalent SLE (2001-2013). To be classified as incident SLE, an individual’s first SLE diagnosis code had to occur in 2003
or later. Cox proportional hazards models estimated hazard ratios (HR) and 95% CIs for the association between SLE and
pulmonary disease in age and sex adjusted models. Sensitivity analyses assessed the robustness of results using semi-
automated approach to quantitative probabilistic bias analysis to account for potential bias due to unmeasured confounding
by smoking.
Results: 3,209 incident SLE cases were identified using NPR data in Sweden contributing a median 4.8 person-years of
follow-up time (vs. 5.1 among non-SLE comparators). We also identified a contemporary cohort of 6,908 individuals with
prevalent SLE. The incidence rate for new onset pulmonary disease (about 14 cases per 1000 person-years) was similar in
prevalent and incident SLE. Those with incident SLE had a nearly six-times higher rate of new onset pulmonary disease
compared to the non-SLE comparator (HR=5.80 (4.84,6.95)) and were comparable in male and female patients. Incident and
prevalent SLE was associated with an increased rate of interstitial lung disease (ILD), (HR=19.0 (10.7, 34.0) and 14.3 (10.8-
18.8), respectively). Bias due to unmeasured confounding by smoking was unlikely to explain our findings in sensitivity
analyses.
Conclusion: Lung disease is common among SLE patients, and particularly increased when compared to the general
population. Clinicians caring for SLE patients should have a heightened suspicion for lung disease, including ILD, even
early within the disease course.
Table. Relative risk of pulmonary disease among SLE compared to non-SLE general population comparators overall and by
type of pulmonary disease, presented as age- and sex-adjusted hazard ratios and 95% confidence intervals.
Prevalent SLE Incident SLE
6908 SLE 3209 SLE
37046 non-SLE 17658 non-SLE

Any pulmonary disease 5.42 (4.90-5.99) 5.80 (4.84-6.95)
By specific pulmonary
disease
14.27 (10.84-
Interstitial lung disease 19.04 (10.66-34.00)
18.78)
ARDS and hemorrhage 5.78 (3.94-8.48) 5.34 (2.72-10.49)
Pleural disorders 4.64 (3.92-5.49) 5.91 (4.43-7.89)
Pulmonary hypertension 6.75 (4.74-9.61) 6.14 (3.19-11.82)
Pulmonary embolism 3.77 (3.12-4.55) 3.78 (2.64-5.40)
Diseases of the upper
4.19 (3.04-5.79) 3.10 (1.66-5.79)
airway
Pulmonary edema 4.32 (2.80-6.65) 3.30 (1.40-7.80)
Disclosure: L. J. Forbess, None; M. Weisman, None; J. F. Simard, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rates-of-new-onset-pulmonary-disease-

among-patients-with-systemic-lupus-erythematosus-in-sweden
Use of Bisphosphonate and Risk of Incident Atrial Fibrillation in a

Population-Based Study
Shanshan Sheehy1, Christine Peloquin2 and Tuhina Neogi3, 1Clinical Epidemiology Research & Training Unit, Boston
University, Boston, MA, 2Boston University School of Medicine, Boston, MA, 3Clinical Epidemiology Research and
Training Unit, Boston University School of Medicine, Boston, MA
SESSION INFORMATION
Background/Purpose:
Bisphosphonates remain the first-line agent prescribed medication for the prevention and treatment of osteoporosis. Apart
from concern about atypical fractures, another concern about risk of atrial fibrillation has been raised. However, data
regarding the relation of specific types of bisphosphonate use to risk of atrial fibrillation has been conflicting, and this has
been reflected in contradicting conclusions from different meta-analyses. We sought to evaluate this risk using more
contemporary data in a population-based cohort in which data on use of different types of bisphosphonates were available.
Methods:
We conducted a propensity score matched cohort study based on a UK population-based general practitioner database (The
Health Improvement Network (THIN) database). From Jan 1, 1998 until Dec 31, 2014, we included 107,282 women who
were age 50-89 years, who were free of atrial fibrillation or atrial flutter, and with no prior use of bisphosphonate within 2
years prior to study entry. Incident bisphosphonate users were defined as women with first bisphosphonate prescription.
Comparators were women without bisphosphonate use prior to the 1-year cohort accrual block, with the index date randomly
assigned within the 1-year accrual block. Incident atrial fibrillation was defined using READ codes. We performed an intent
to treat analysis using Cox proportional hazards model, stratified by the 1 year cohort accrual blocks.
Results:
During a median of 4.5 years of follow up, we identified 53,641 pairs of bisphosphonate initiators and PS-matched
comparators, whose mean age was 70. The crude incident rate of atrial fibrillation was 8.63 per 1000 person years for
bisphosphonate initiators, and 8.7 per 1000 person years for comparators, with an adjusted hazard ratio of 1.01 (95%CI:
0.95-1.08). When restricted only to the commonly used bisphosphonates alendronate, ibandronate, and risedronate, the
hazard ratio comparing initiators vs. comparators was 1.05 (95%CI: 0.99-1.11). Results were similar when current vs. past
bisphosphonate users were compared, and when further stratified by calendar year to account for secular trends.
Conclusion:
In this large UK general population, use of bisphosphonate was not associated with risk of atrial fibrillation.
Disclosure: S. Sheehy, None; C. Peloquin, None; T. Neogi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/use-of-bisphosphonate-and-risk-of-

incident-atrial-fibrillation-in-a-population-based-study
Mortality Post Hip Fracture in Rheumatoid Arthritis Compared to General

Population Controls, a Population-Based Study
C. Allyson Jones1, Pierre Guy2, Hui Xie3, Eric C. Sayre4 and Diane Lacaille5,6, 1Physical Therapy, University of Alberta,
Edmonton, AB, Canada, 2Department of Orthopaedics, University of British Columbia / Centre for Hip Health and Mobility,
Vancouver, BC, Canada, 3Biostatistics, Faculty of Health Sciences, Simon Fraser University / Arthritis Research Canada,
Burnaby, BC, Canada, 4Arthritis Research Canada, Richmond, BC, Canada, 5University of British Columbia, Arthritis
Research Canada, Richmond, BC, Canada, 6Arthritis Research Canada/ University of British Columbia, Vancouver, BC,
Canada
SESSION INFORMATION
Background/Purpose: In prior work, we found a higher incidence of hip fractures in RA than age and sex matched general
population controls (4.1 vs. 2.9 per 1000 PY). To assess burden of disease, we compared age- and sex-adjusted all-cause
mortality post hip fracture in RA and general population controls.
Methods: We conducted a retrospective study of a population-based incident RA cohort, using administrative health data.
Using physician billing data, we identified all people with RA onset between 1997 and 2009 in a Canadian province.
Controls (with no diagnosis of RA or other inflammatory arthritis) were randomly selected from the general population,
matched 2:1 to RA cases on birth yr, gender and index yr. RA patients and controls with prior hip fractures, pathological
fractures or Paget’s disease were excluded. Hip fractures were identified using hospitalization data (ICD9-CM codes 820.0,
820.2; ICD10-CA codes S72.0, S72.1, S72.2), from ≤25 codes defining reason for admission or complications during
hospitalization. RA individuals and controls were followed from incident hip fracture to death, last health care use, or study
end (Dec. 2014). Mortality data was obtained from Vital Statistics. Cox-proportional hazard models, adjusted for age and
sex, compared mortality risk in RA vs. controls with a hip fracture.
Results: The cohort included 60,101 incident RA cases and 120,462 controls, of whom 2463 (4.1%) RA individuals and
3566 (3.0%) controls sustained an incident hip fracture and make up the study sample (78% females in RA and 81%s in
controls; mean (SD) age at time of fracture: 78.9(10.9) yrs for RA and 82.1(9.0) yrs for controls). Crude all-cause mortality
rate post hip fracture was 5.9% (n=143) and 8.2% (n=288) at 30 days; and 19.9% (n=481) and 24.5% (n=854) at 1-yr, for
RA and controls, respectively. After age and sex adjustment, RA persons with hip fractures had a 17.5% lower risk of death
than persons without RA at 30-days and 10.2% lower risk at 1-yr. The mean age at death for 30-day mortality was 83.9 yrs
for RA and 86.1 yrs for controls.
Conclusion: Despite a higher incidence of hip fractures in RA, the 30-day and 1-year post hip fracture all-cause mortality
was lower in RA than controls, after adjusting for sex and age at time of fracture. Further research is needed to understand
whether mortality differences are related to co-morbidities, differences in post-op care, or other characteristics influencing
post-fracture mortality risk.
Disclosure: C. A. Jones, None; P. Guy, None; H. Xie, None; E. C. Sayre, None; D. Lacaille, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/mortality-post-hip-fracture-in-

rheumatoid-arthritis-compared-to-general-population-controls-a-population-based-study
Optimal Regimens of Sulfamethoxazole-Trimethoprim for Chemoprophylaxis

of Pneumocystis Pneumonia in Patients with Systemic Rheumatic Diseases:
52-Week Follow-up of a Non-Blinded, Randomized Controlled Trial
Masayoshi Harigai1,2, Masako Utsunomiya2,3,4, Hiroaki Dobashi5, Toshio Odani6,7, Kazuyoshi Saito8,9, Naoto
Yokogawa10, Kenji Nagasaka11,12, Kenchi Takenaka3,11, Makoto Soejima11,13, Takahiko Sugihara14, Hiroyuki Hagiyama15,
Shinya Hirata16, Kazuo Matsui17,18, Yoshinori Nonomura19, Masahiro Kondo20, Fumihito Suzuki13,21, Makoto Tomita22,
Mari Kihara23, Waka Yokoyama3, Fumio Hirano24, Hayato Yamazaki3, Ryoko Sakai2,25, Toshihiro Nanki2,26, Ryuji
Koike2,3, Hitoshi Kohsaka3 and Nobuyuki Miyasaka3, 1Division of Epidemiology and Pharmacoepidemiology of
Rheumatic Diseases, Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan, 2Department of
Pharmacovigilance, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan,
3Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University,
Tokyo, Japan, 4Department of Rheumatology, Musashino Red Cross Hospital, Tokyo, Japan, 5Internal Medicine Division of
Hematology, Rheumatology, and Respiratory Medicine, Kagawa University, Kagawa, Japan, 6Third Department of Internal
Medicine, Obihiro-Kosei General Hospital, Hokkaido, Japan, 7Molecular Physiology and Therapeutics Branch/Adeno-
Associated Virus Biology Section, National Institute of Dental and Craniofacial Research (NIDCR)/ National Institutes of
Health (NIH), Bethesda, MD, 8Tobata General Hospital, Fukuoka, Japan, 9The First Department of Internal Medicine,
University of Occupational and Environmental Health, Kitakyushu, Japan, 10Department of Rheumatic Diseases, Tokyo
Metropolitan Tama Medical Center, Tokyo, Japan, 11Department of Rheumatology, Ome Municipal General Hospital,
Tokyo, Japan, 12Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences,, Tokyo Medical and
Dental University, Tokyo, Japan, 13Department of Rheumatology, Soka Municipal Hospital, Saitama, Japan, 14Department
of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan, 15Department of Rheumatology,
Yokohama City Minato Red Cross Hospital, Kanagawa, Japan, 16Department of Hematology, Rheumatology, and Infectious
Disease, Kumamoto University, Kumamoto, Japan, 17Department of Rheumatology, Kameda Medical Center, Chiba, Japan,
18Department of Internal Medicine, Takikawa Municipal Hospital, Hokkaido, Japan, 19Department of Rheumatology, Tokyo
Kyosai Hospital, Tokyo, Japan, 20Department of Rheumatology, Faculty of Medicine, Shimane University, Shimane, Japan,
21Department of Rheumatology, JA Toride Medical Center, Ibaraki, Japan, 22Clinical Research Center, Tokyo Medical and
Dental University, Tokyo, Japan, 23Department of Rheumatology, Tokyo Medical and Dental University, Tokyo, Japan,
24Departments of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University,
Tokyo, Japan, 25Division of Epidemiology and Pharmacoepidemiology of Rheumatic Diseases, Institute of Rheumatology,
Tokyo Women’s Medical University, Tokyo, Japan, 26Division of Rheumatology, Department of Internal Medicine, Toho
University School of Medicine, Tokyo, Japan
SESSION INFORMATION
Background/Purpose: Sulfamethoxazole-trimethoprim (SMX/TMP) is a standard drug for the prophylaxis of Pneumocystis

pneumonia (PCP), but is sometimes discontinued due to adverse events (AEs). We have previously reported the results of
this non-blinded, randomized, non-inferiority trial up to week 24 to explore an effective SMX/TMP regimen for PCP with a
low drug discontinuation (d/c) rate. We here report the results at week 52.
Methods: Adult patients with systemic rheumatic diseases who started prednisolone >0.6 mg/kg/day were randomized into
three groups and treated up to week 24: a single-strength group (SS, SMX/TMP of 400/80 mg daily), half-strength group
(HS, 200/40 mg daily), and escalation group (ES, started with 40/8 mg daily, raising incrementally to 200/40 mg daily).
After week 24, attending physicians determined the use of SMX/TMP including doses, intervals, and treatment duration.
The observation period was up to week 52 irrespective of the use of SMX/TMP. The primary endpoint was non-incidence
rates (non-IR) of PCP at week 24. Secondary endpoints were PCP non-incidence rate at week 52, treatment d/c rate, and
AEs. We estimated the non-incidence rates of PCP using the exact confidence interval as a post-hoc analysis and analyzed
treatment d/c rates using the Kaplan-Meier method and log-rank test.
Results: Of 183 patients randomly allocated at a 1:1:1 ratio into the three groups, 58 patients in SS, 59 in HS, and 55 in ES
started SMX/TMP and were analyzed. Of the 172 patients who started SMX/TMP, 32, 46, and 38 at week 24, and 29, 43,
and 34 at week 52 were receiving SMX/TMP as allocated. No cases of PCP were reported up to week 52. Estimated non-IR
of PCP in patients who received daily SMX/TMP of 200/40 mg, either starting at this dose or increasing incrementally, was
96.8–100%. From week 0 to 52, the overall d/c rate was significantly lower in HS compared to that in SS (22.7% vs 47.2%,
p = 0.004) (Figure). The d/c rates due to AEs were significantly lower in HS (19.1%, p = 0.007) and ES (20.3%, p = 0.007)
compared to that in SS (41.8%). The IR of AEs requiring dose reduction of SMX/TMP (p = 0.007) and AEs of special
interest (p = 0.001) at week 52 were different among the three groups with significantly higher IR in SS compared to HS and
ES. Almost all AEs requiring dose reduction of SMX/TMP and AEs of special interest were reported by week 24.
Conclusion: The combined group of HS and ES had an excellent estimated non-IR of PCP at week 52 and both were
superior in safety to SS. From the perspective of feasibility and drug d/c rates, the daily half-strength regimen is suggested to
be optimal for prophylaxis of PCP in patients with systemic rheumatic diseases.
Disclosure: M. Harigai, Eisai Ltd, Takeda Ltd, Teijin, 2,Eli Lilly and Company, BMS, Chugai, Janssen, 5; M. Utsunomiya,
None; H. Dobashi, None; T. Odani, None; K. Saito, None; N. Yokogawa, None; K. Nagasaka, Chugai Pharmaceutical
Co., Ltd., 5; K. Takenaka, None; M. Soejima, None; T. Sugihara, Takeda Pharmaceutical Co. Ltd., Mitsubishi-Tanabe
Pharma Co., Chugai Pharmaceutical Co., Ltd., Ayumi Pharmaceutical Co., Ltd., UCB Japan Co. Ltd, Astellas Pharma Inc.,
Janssen Pharmaceutical K.K., Pfizer Japan Inc., and Bristol Myers Squibb K.K, 5; H. Hagiyama, None; S. Hirata, None;
K. Matsui, None; Y. Nonomura, None; M. Kondo, None; F. Suzuki, None; M. Tomita, None; M. Kihara, None; W.
Yokoyama, None; F. Hirano, Chugai Pharmaceutical Co., Ltd.; Ono Pharmaceuticals; Mitsubishi Tanabe Pharma Co.; UCB
Japan; CSL Behring; Towa Pharmaceutical Co., Ltd.; Abbvie Japan Co., Ltd.; Japan Blood Products Organization; Ayumi
Pharmaceutical Co.; and Nippon Kayaku Co., Ltd, 3,Astellas Pharma Inc, 5; H. Yamazaki, None; R. Sakai, None; T.
Nanki, Eisai, Eli Lilly, Bristol-Myers, Ono, Novartis, 2,UCB, Eisai, Chugai, 5,Mitsubishi-Tanabe, Eisai, Astellas, Janssen,
AbbVie, Pfizer, UCB, Ayumi, 8; R. Koike, None; H. Kohsaka, CHUGAI PHARMACEUTICAL CO.,LTD., 2,GSK,
5,CHUGAI PHARMACEUTICAL CO.,LTD., 8; N. Miyasaka, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/optimal-regimens-of-sulfamethoxazole-

trimethoprim-for-chemoprophylaxis-of-pneumocystis-pneumonia-in-patients-with-systemic-rheumatic-diseases-52-week-
follow-up-of-a-non-blinded-randomized-controlled
Risk of Serious Infection in Patients with Rheumatoid Arthritis Treated with

Biologic Vs. Non-Biologic Dmards
Gulsen Ozen1, Sofia Pedro2, Bryant R. England3, Bella Mehta4, Frederick Wolfe2 and Kaleb Michaud1, 1Rheumatology,
University of Nebraska Medical Center, Omaha, NE, 2National Data Bank for Rheumatic Diseases, Wichita, KS, 3Division
of Rheumatology & Immunology, Department of Internal Medicine, Nebraska-Western IA VA Health Care System &
University of Nebraska Medical Center, Omaha, NE, 4Rheumatology, Hospital for Special Surgery/Weill Cornell Medical
College, New York, NY
SESSION INFORMATION
Background/Purpose: Serious infections (SIs) are a major concern in RA patients, significantly contributing to increased
mortality. We examined the SI risk associated with bDMARDs compared to csDMARDs in a US-wide observational RA
cohort.
Methods: RA patients initiating bDMARDs or csDMARDs from 2001 through 2016 in the National Data Bank for
Rheumatic Diseases (NDB) were assessed for SIs (infection + intravenous antibiotics, hospitalization or death). DMARDs
were categorized into 3 groups: (1) csDMARDs-reference (bDMARD naive) (2) TNF inhibitors (TNFi) (3) Non-TNFi
biologics (abatacept, rituximab, tocilizumab, and anakinra). Each patient contributed to the last DMARD reached. Followup
continued until the first SI, DMARD discontinuation, death, or end of study period. SIs were attributed to the corresponding
DMARD group when the treatment was ongoing or discontinued ≤3 months before SI. Propensity scores (PS) reflecting the
probability of receiving a specific DMARD were calculated using multinomial logistic regression models with
characteristics at treatment initiation. PS was added to the Cox models as a continuous variable along with time-varying
confounders (age, disease duration, comorbidities, HAQ, pain and patient global scores, weighted cumulative exposure
[WCE] of glucocorticoids [GC], prior sDMARDs and bDMARDs counts) of which changes over time might alter the SI
risk.
Results: 694 (5.9%) first SIs were identified in 11,623 RA patients during a 27,552 patient-years of follow-up. TNFi and
non-TNFi biologics-initiators had significantly higher disease activity, disability, and comorbidity scores than csDMARDs
initiators. Crude incidence rate (95% CI) in TNFi group was non-significantly higher than csDMARD and non-TNFi
biologic initiators (Figure). The PS-only adjusted model showed a non-significant SI risk increase with TNFi (HR
1.11[0.91-1.34], P= 0.309) and non-TNFi biologics (HR 1.26 [0.95-1.68], P= 0.102) whereas further adjustment for time-
varying confounders revealed significantly increased risk of SI with both TNFi (HR 1.33 [1.05-1.68], P= 0.019) and non-
TNFi (HR 1.48 [1.02-2.16], P= 0.041) compared to csDMARDs. Other factors associated with SI are presented in Table.
Conclusion: TNFi and non-TNFi biologics were associated with an increased SI risk in RA compared to csDMARDs. In
addition to DMARDs, older age, comorbidity burden, pulmonary disease, higher disability, disease activity, and cumulative
GC exposure were predictive of SI. Assessment and modification of these factors should be completed before and during
bDMARD treatment to minimize SI risk.
Table. Risk of serious infections in rheumatoid arthritis by treatment:
results from the Cox proportional hazard models with propensity scores*
and time–varying confounders
Adjusted HR (95% CI) P value
Age, years
<50 Reference -
50-64 1.39 (1.03-1.89) 0.034
≥65 2.31 (1.70-3.12) <0.001
Annual income > $45,000 0.70 (0.57-0.84) 0.001
Rheumatic disease 1.20 (1.13-1.26) <0.001
comorbidity index
Selected comorbidities
Diabetes 1.15 (0.94-1.41) 0.174
Pulmonary disease 1.46 (1.21-1.77) <0.001
Disease duration, years 1.00 (0.99-1.01) 0.852
HAQ disability 1.27 (1.10-1.47) 0.001
Pain scale 1.04 (1.00-1.08) 0.050
Patient global scale 1.06 (1.02-1.11) 0.008
WCE-prednisone 1.33 (1.22-1.45) <0.001
Count of prior 1.11 (1.05-1.17) <0.001
csDMARDs
Count of prior 0.90 (0.80-1.02) 0.095
bDMARDs
DMARD groups
csDMARDs Reference -
TNFi 1.33 (1.05-1.68) 0.019
Non-TNFi biologics 1.48 (1.02-2.16) 0.041
* Propensity score was estimated based on the following characteristics at the
time of treatment initiation: age, gender, ethnicity, insurance, annual income,
RA disease duration, smoking status, rheumatic diseases comorbidity index,
HAQ, pain and patient global scores, GC use, prior csDMARDs and bDMARDs
counts, prior serious infection, and calendar year.
WCE=Weighted cumulative exposure of glucocorticoid as prednisone equivalent

doses: The weights assigned to past doses were estimated using a flexible cubic
spline-based method.
Disclosure: G. Ozen, None; S. Pedro, None; B. R. England, None; B. Mehta, None; F. Wolfe, None; K. Michaud, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/risk-of-serious-infection-in-patients-

with-rheumatoid-arthritis-treated-with-biologic-vs-non-biologic-dmards
The Role of Personality in Patients with Fibromyalgia

Andrew Seto1, Teresa Wu1, Lori Lyn Price2,3,4,5, Xingyi Han6, William F. Harvey1 and Chenchen Wang7, 1Tufts Medical
Center, Boston, MA, 2Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA,
3Clinical Care Research, Tufts Medical Center, Boston, MA, 4Biostatistics Research Center, Institute for Clinical Research
and Health Policy Studies, Tufts Medical Center, Boston, MA, 5Tufts Clinical and Translational Science Institute, Tufts
University, Boston, MA, 6Public Health and Community Medicine, Tufts University, Boston, MA, 7Rheumatology, Tufts
Medical Center, Boston, MA
SESSION INFORMATION
Session Title: ARHP Psychosocial Impact on Rheumatic Disease
Session Type: ARHP Concurrent Abstract Session
Background/Purpose:
Previous studies investigating the potential associations between personality and clinical symptoms in fibromyalgia (FM)
patients have found mixed results. The purpose of this study was to clarify whether personality dimensions are associated
with clinical symptoms, mindfulness, self-efficacy, social support, and outcome expectations among adult patients with FM.
Methods:
We performed a secondary analysis using baseline data from a randomized controlled comparative effectiveness trial
between Tai Chi and aerobic exercise for FM. Personality was assessed using the NEO-Five Factor Inventory, a validated
measure of 5 basic personality factors: agreeableness, conscientiousness, extraversion, neuroticism, and openness.
Fibromyalgia syndrome was evaluated using the validated revised Fibromyalgia Impact Questionnaire (FIQR). Other
measures included symptom severity, anxiety, depression, stress, health-related quality of life, social support, self-efficacy,
mindfulness, and outcome expectations for exercise. Multivariable linear regression was performed to assess the associations
between personality dimensions and measures of health and FM impact, while controlling for age, gender, body mass index
(BMI), and living situation.
Results:
The sample consisted of 92 participants, with 95% female, mean age 52 years (SD 12), BMI 30 kg/m2 (6), 52% white, 94%
had a high school degree, and mean duration of body pain 14 years (11). After adjusting for covariates using multivariable
linear regression, neuroticism was significantly associated with FIQR and symptom severity (Table 1). Higher neuroticism
was also associated with higher levels of anxiety, depression, and stress, and worse mental component quality of life, lower
self-efficacy, mindfulness, and social support. Higher conscientiousness and extraversion were associated with better mental
component quality of life and mindfulness, and lower symptom severity, anxiety, depression, and stress. Higher
conscientiousness was associated with better self-efficacy and outcome expectations. Higher extraversion was associated
with better social support. More openness was associated with better outcome expectations, mindfulness, and lower levels of
depression. Agreeableness was not significantly associated with any outcome. None of the 5 personality dimensions were
associated with physical component of quality of life.
Conclusion:
Personality was significantly correlated with FM impact, a variety of health outcomes, and strongly associated with self-
efficacy and mindfulness. Higher neuroticism was associated with worse psychosocial factors, suggesting this subset of
patients may benefit from individualized treatment that takes personality into consideration. Results further elucidate
characteristics of FM patients and highlight the importance of personality in the management of FM.
Table 1. Associations Between Personality and Fibromyalgia Impact, Psychosocial Factors, and Health Outcomes
Dependent Variable Personality Dimension
Beta (p-value)*
Agreeableness Conscientiousness Extraversion Openness Neuroticism
FIQR† -0.04 (0.91) -0.44 (0.12) -0.61 (0.05) -0.35 (0.25) 0.81 (0.002)
Symptom Severity† 0.04 (0.27) -0.07 (0.02) -0.07 (0.03) 0.003 (0.94) 0.08 (0.008)
HADS-Anxiety† -0.09 (0.19) -0.17 (0.002) -0.14 (0.03) -0.01 (0.84) 0.32 (<0.0001)
HADS-Depression† -0.03 (0.75) -0.20 (0.0012) -0.36 (<0.0001) -0.13 (0.047) 0.32 (<0.0001)
Perceived Stress † -0.18 (0.22) -0.49 (<0.0001) -0.38 (0.004) -0.02 (0.90) 0.68 (<0.0001)
SF-36 Mental 0.42 (0.06) 0.77 (<0.0001) 0.80 (<0.0001) 0.29 (0.12) -1.05 (<0.0001)
Component Score
SF-36 Physical -0.28 (0.07) -0.17 (0.17) -0.11 (0.45) -0.026 (0.84) 0.18 (0.14)
Component Score
Medical Outcomes 0.03 (0.11) 0.03 (0.10) 0.04 (0.02) 0.03 (0.13) -0.049 (0.001)
Study Social Support
Survey
Chronic Pain Self- -0.046 (0.26) 0.08 (0.009) 0.07 (0.06) 0.014 (0.69) -0.07 (0.02)
Efficacy
Outcome Expectations 0.02 (0.12) 0.03 (0.03) 0.01 (0.43) 0.03 (0.01) -0.008 (0.51)
for Exercise
Five Facet Mindfulness 0.64 (0.10) 1.39 (<0.0001) 1.35 (<0.0001) 0.87 (0.007) -1.52 (<0.0001)
Questionnaire -Total
Note: FIQR = Revised Fibromyalgia Impact Questionnaire; HADS = Hospital Anxiety and Depression Scale; SF-36 =
Short Form-36, a measure of quality of life
Bolded p-values indicate statistical significance (p-value < 0.05)
*All models were adjusted for age, gender, BMI, and living situation
†Higher scores indicate worse health
Disclosure: A. Seto, None; T. Wu, None; L. L. Price, None; X. Han, None; W. F. Harvey, None; C. Wang, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-role-of-personality-in-patients-with-

fibromyalgia
Social Support, Stress and Health Outcomes in Systemic Lupus

Erythematosus: Georgians Organized Against Lupus (GOAL) Cohort
Charmayne M. Dunlop-Thomas, S. Sam Lim, Gaobin Bao and Cristina Drenkard, Division of Rheumatology, Emory
University School of Medicine, Atlanta, GA
SESSION INFORMATION
Background/Purpose: Stress can influence immune and neuroendocrine processes, and may lead to poor outcomes in
people with systemic lupus erythematosus (SLE). Social support can potentially reduce the negative influences of stress on
disease outcomes. We examined the relationships between stress and disease outcomes and whether social support mitigates
those relationships in SLE.
Methods: We examined cross-sectional data from GOAL, a large population-based cohort of patients with validated SLE
from Atlanta, Georgia. Since 2011, participants respond annually to validate self-administered health outcome surveys.
Social Support was assessed with the Patient-Reported Outcomes Measurement Information System Social Support Short
Form 4a (Emotional, Informational and Instrumental). We used Cohen’s Perceived Stress Scale 4 (PSS-4), Systemic Lupus
Activity Questionnaire (SLAQ) and the Patient Health Questionnaire-9 (PHQ) for depression severity. Analysis of
covariance (ANCOVA) was used to examine the effect of social support (categorical) on the linear relation between
perceived stress and disease outcomes.
Results: Among 670 participants (93.9% women, 80.0% Black; mean age 48.4), mean(SD) scores were 7.20(2.55) for
PSS-4, 15.18(8.66) for SLAQ, and 7.18(5.92) for PHQ-9. Mean(SD) social support scores were 52.03(9.28) for
instrumental, 52.80(10.73) for informational, and 55.45(9.33) for emotional support. Stress was significantly associated
with disease activity and depression. Instrumental support was the only social support construct that modified the effect of
stress on disease activity. Neither emotional, informational nor instrumental support influenced the association between
stress and depression. However, at a given stress level, participants with low social support have significantly worse disease
activity and depression.
Conclusion: In a population-based SLE cohort with large numbers of Blacks, there was an elevated level of perceived stress
and moderate to severe disease activity, with 30% endorsing moderate to severe depression. Instrumental social support may
buffer the association between disease activity and stress. Recognizing the importance of developing more instrumental
resources, such as transportation and home care services may contribute significantly to improving SLE health outcomes.
Table 1. ANCOVA analysis of disease activity or depression and perceived stress score
by social support categories

Categorical Low Support High Support Intercept Slope
group
Relation (Score<=50) (Score>50) difference difference
(Social
Support) Intercept Slope Intercept Slope Difference P Difference P
Disease - -
Activity Emotional 7.76 1.19 5.54 1.19 2.12 0.0010
- -
vs. Informational 8.84 1.13 5.91 1.13 2.93 <.0001
Perceived -0.51 0.041

Instrumental 11.21 0.86 4.20 1.37 7.02 0.0004
Stress
Depression Emotional -0.10 1.12 -1.62 1.12 1.53 0.0002 - -
vs. - -
Informational 0.04 1.11 -1.27 1.11 1.40 0.0009
Perceived - -
Stress Instrumental -0.08 1.13 -1.43 1.13 1.35 0.0013
Disclosure: C. M. Dunlop-Thomas, None; S. S. Lim, None; G. Bao, None; C. Drenkard, No commercial interest, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/social-support-stress-and-health-
outcomes-in-systemic-lupus-erythematosus-georgians-organized-against-lupus-goal-cohort
Effectiveness of Brief Group Psychoanalytic Psychotherapy in Patients with

Systemic Lupus Erythematosus and Follow-up
Emilia Sato1,2, Céu Conceiçao3, Ivone Meinão4 and Sergio Blay5, 1Rheumatology Division. Escola Paulista de Medicina,
Universidade Federal de Sao Paulo, Sao Paulo, Brazil, 2Rheumatology Div/Dept of Med, Escola Paulista de Medicina -
Universidade Federal de São Paulo, Sao Paulo, Brazil, 3Medicine, Escola Paulista de Medicina, Universidade Federal de São
Paulo, Sao Paulo, Brazil, 4Medicine, Universidade Federal de São Paulo, Sao Paulo, Brazil, 5Psychiatry, Escola Paulista de
Medicina, Universidade Federal de São Paulo, Sao Paulo, Brazil
SESSION INFORMATION
Background/Purpose: There are few studies evaluating the effectiveness of psychotherapy in Systemic Lupus
Erythematosus (SLE) patients.
Objectives: To evaluate the effectiveness of brief group psychoanalytic psychotherapy (BGPP) in improving quality of life,
anxiety and depression levels and coping strategies in SLE. Methods: Prospective, randomized clinical trial (number
NCT01840709), including 80 SLE patients in a tertiary hospital. Patients were randomized into two groups: therapy (TG
n=37) and control (CG n=43). Both groups received standard clinical treatment. TG received BGPP, weekly for 20
consecutive weeks performed by a specialized psychologist. CG remained in the waiting list. Assessments: at baseline (T1),
after 20th weeks (T2), and 24 months after the end of the study (T3). Damage and disease activity were assessed by
SLICC/ACR-DI score and SLEDAI-2k score, respectively. Self-administered questionnaires supervised by a blind evaluator
were used to evaluate symptoms (SLE-SSC), quality of life (SLEQOL), anxiety and depression (HAD) and coping strategies
(CIS). Inclusion criteria: female gender; SLE (ACR-1997 classification criteria), age ≥ 18 years, minimum follow-up of six
months and signing consent form approved by Institutional Ethic Committee. Exclusion criteria: illiterate patients, physical
and mental comorbidities that preclude the attendance, and external psychological treatment. Statistical analysis: intent to
treat analysis. Comparisons of variance between groups over time (ANOVA repeated measures). SPSS version 17. p <0.05
was considered significant.
Results: At baseline, TG and CG were homogeneous in all variables, including medication. In T2, TG showed significant
improvement in the majority of domains of SLEQOL (Table 1), all domains of HAD (Table 2) and several domains of CIS
(Table 3). Some of benefits were maintained at the 24-month follow-up after the end of the therapy, including the most
appropriate coping strategies to face the disease. No significant differences were observed in medication and clinical
variables.
Conclusion: This study showed effectiveness of BGPP in improving quality of life, depression, anxiety and coping
strategies to deal with stress in SLE patients, and some of the benefits were maintained in a long follow-up.
Disclosure: E. Sato, None; C. Conceiçao, None; I. Meinão, None; S. Blay, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effectiveness-of-brief-group-

psychoanalytic-psychotherapy-in-patients-with-systemic-lupus-erythematosus-and-follow-up
Social Support in Couples-Focused Physical Activity Interventions for People

with Hip or Knee Osteoarthritis: What Kinds of Partner Support Are
Associated with Increases in Physical Activity and Reductions in Sedentary
Behavior?
Christine Rini1, Liubov Arbeeva2, Stephanie Bahorski2, Cynthia Khan3, Rebekah Layton2, Derek Hales2, Julie Upchurch2,
Shelby Rimmler2, Ida Griesemer2, Mary Altpeter2, Dana Carthron4, Todd Schwartz2 and Leigh F. Callahan5, 1Biomedical
Research, Hackensack University Medical Center, Hackensack, NJ, 2University of North Carolina at Chapel Hill, Chapel
Hill, NC, 3Econometrica, Inc., Bethesda, MD, 4Michigan State University, East Lansing, MI, 5Thurston Arthritis Research
Center, University of North Carolina at Chapel Hill, Chapel Hill, NC
SESSION INFORMATION
Background/Purpose: Physical activity (PA) reduces joint symptoms in people with osteoarthritis (PWOA), but most
PWOA get insufficient PA. They would benefit from small but sustained increases in PA, but PA interventions usually elicit
short-lived increases. Social support is a reliable predictor of PA, and partners (e.g., a spouse) can provide support that helps
PWOAs make lasting increases in PA (e.g., by providing encouragement or joining in PA). Yet, partner support may also fail
to provide intended resources (i.e., PWOAs may appraise it as “ineffective”--a poor match for their need for a certain quality
and quantity of support). Partners may also provide solicitous support that hinders behavior change (e.g., well-intentioned
discouragement of activity in favor of rest). The purpose of this dyadic study was to examine these aspects of partner
support for PA, as reported by PWOA (“support received”) and their partner (“support provided”).
Methods: 173 couples, with PWOAs who had hip or knee OA and were insufficiently active, completed a couples-focused
PA intervention with 3-hours of in-person education and 12-weeks of workbook activities. They also completed
questionnaires and wore accelerometers at baseline and at 1-week and 3-, 6-, and 12-months post-intervention. We used
multilevel modeling to examine support received and provided as predictors of PWOAs’ moderate to vigorous PA (MVPA)
and sedentary behavior across these timepoints.
Results: Models adjusted for sociodemographic covariates revealed that PWOAs’ MVPA at each timepoint was higher for
PWOAs who reported receiving more encouragement for PA from their partner (p<.01) and those who reported that their
partner joined in their PA (p =.02). PWOAs’ MPVA was also higher when partners reported joining in their PA (p=.03).
PWOAs’ appraised effectiveness of this support did not moderate its association with MVPA, nor were partners’ solicitous
behaviors (as reported by PWOAs or partners) associated with MVPA. In addition, an interaction showed a negative
association between partner-reported solicitous support and PWOA sedentary behavior when PWOAs appraised this support
as relatively ineffective (i.e., a poor match for their needs). This association was attenuated among PWOAs who appraised
the effectiveness of their partner’s solicitous support more favorably (i.e., a better match for their needs; p=.02). A similar
interaction occurred for partner-provided joining in PA (p=.048).
Conclusion: These findings highlight different pathways by which to change MVPA and sedentary behavior and have
implications for designing couples-based PA interventions that elicit lasting behavior change that thus ensure that PWOAs
get the health benefits of PA.
Disclosure: C. Rini, None; L. Arbeeva, None; S. Bahorski, None; C. Khan, None; R. Layton, None; D. Hales, None; J.
Upchurch, None; S. Rimmler, None; I. Griesemer, None; M. Altpeter, None; D. Carthron, None; T. Schwartz, None; L.
F. Callahan, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/social-support-in-couples-focused-

physical-activity-interventions-for-people-with-hip-or-knee-osteoarthritis-what-kinds-of-partner-support-are-associated-
with-increases-in-physical-activity-and
The Mediational Role of Helplessness in Psychological Outcomes in Systemic

Lupus Erythematosus
Desiree R Azizoddin1, Sarah D. Mills2, Perry M. Nicassio3, Geraldine Zamora Racaza4 and Michael Weisman5, 11611 W
Harrison, 1611 W Harrison, Chicago, IL, 2SDSU/UC San Diego Joint Doctoral Program in Clinical Psychology, San Diego,
CA, 3Cousins Center for PNI, UCLA, LA, CA, 4Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA,
5Cedars-Sinai Medical Center Division of Rheumatology, Los Angeles, CA

SESSION INFORMATION
Background/Purpose: Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease affecting multiple organs,
leading to a significant impact on health-related quality of life. Theoretical models are critical to understanding the
mechanisms behind the relationships between pain and psychosocial variables and can be used to help guide future research
and treatment among patients with SLE. Thus, the present study examined whether helplessness is a mediator of the
relationship between pain and three types of psychological distress among patients with SLE; specifically anxiety,
depression, and perceived stress.
Methods: A convenience sample was obtained of patients aged 18 years and above diagnosed with SLE according to ACR
1982 guidelines at a large medical center in Southern California. Assessment included the Lupus Patient-Reported Outcome
tool, Arthritis Helplessness Index, Perceived Stress Scale-10, and Hospital Anxiety and Depression Scale. Multiple
mediation analysis was completing using an SPSS macro called “PROCESS.”
Results: The cohort of 136 patients had a mean age of 48.6 years (SD = 13.87), and was mostly female (92.6%) and
Caucasian (44.9%). The direct effect of pain vitality on anxiety symptoms was -0.074, p < .001; the relationship between
pain vitality and anxiety symptoms was significantly decreased when helplessness was included in our model, ab = -.041,
BCa 95% CI [-0.073, -.015]. The direct effect of pain vitality on depressive symptoms was -0.069, p < .001; the relationship
between pain vitality and depressive symptoms was significantly decreased when helplessness was included in our model,
ab = -.035, BCa 95% CI [-0.502, -.212]. The direct effect of pain vitality on stress was -0.038, p < .01; the relationship
between pain vitality and stress was significantly decreased when helplessness was included in our model, ab = -.041, BCa
95% CI [-0.063, -.027].
Conclusion: Consistent with studies conducted in other autoimmune populations, findings suggested that helplessness fully
mediated the relationship between pain and measures of anxiety, depression, and perceived stress. These results provide a
theoretical model to better understand mechanisms that may help explain the relationship between pain and psychological
distress in this population. Despite the moderate to low reports of perceived stress, the high reports of perceived
helplessness, anxiety and depressive symptoms suggest a need for intervention to improve self-efficacy and reduce
psychological distress.
Table 1. Demographic Characteristics of sample (n = 136) and results
of multiple mediation analysis assessing relationship between
LupusPRO-Pain Vitality
Demographics M (SD) N (%) Range
Age 48.6 (13.8) 18-81
Education in years 15.2 (2.8) 8-24
Annual Income ($)
<15K 11 (8.1)
15-25K 16 (11.9)
25-39K 12 (8.8)
40-60K 13 (9.6)
60-75K 13 (9.6)
75-100K 21 (15.4)
>100K 49 (36.3)
Female 126 (92.6)
Race/Ethnicity
White 61 (44.9)
Hispanic 25 (18.4)
African American 19 (14.0)
Asian/Pacific Islander 29 (15.7)
Other Mixed Race/Ethnicity 11 (8.1)
Marital Status
Married/Lives with partner 76 (55.9)
Single/Never married 54 (25.7)
Divorced/Separated/Widowed 22 (16.2)
Disease Activity: Active 62 (45.9)
Disease Duration 16.9 (11.9) 0-55
Anxiolytic Use 35 (25.9)
Antidepressant Use 34 (25.2)
Medication Use
Prednisone Use 59 (43.7)
Immunosuppressant Use 87 (64.4)
Cytotoxic 24 (17.8)
Biologic 62 (45.9)
HADS-Depression 5.4 (4.0) 43 (23.1%) 0-21
HADS-Anxiety 7.7 (4.1) 61 (41%) 0-21
PSS 17.8(6.3) 0-40
LupusPRO-Pain Vitality 56.6(27.3) 0-100
AHI-Helplessness 14.5(5.4) 5-30
Mediational Direct
Effect Indirect Effect
Analysis without with Helplessness Boot BCa 95%
mediator SE Mediator SE CI
-.050,
Depression -.069 .011 -.035 .007
-.021
-.073,
Anxiety -.074 .021 -.041 .015
-.015
-.063,
PSS -.038 .013 -.043 .009
-.027
Note. HADS N% pertains to participants reporting a score of 8 or
above for depression and anxiety subscale. SE: Standard Error of the
estimate BCa, bias corrected and accelerated.
Disclosure: D. R. Azizoddin, None; S. D. Mills, None; P. M. Nicassio, None; G. Z. Racaza, None; M. Weisman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-mediational-role-of-helplessness-in-

psychological-outcomes-in-systemic-lupus-erythematosus
“Suddenly You Are a Person at Risk of Developing Rheumatoid Arthritis!”

Different Perspectives of Individuals on Predictive Testing – Results of an
International Qualitative Interview Study
Erika Mosor1, Michaela Stoffer2, Günter Steiner3, Karim Raza4, Rebecca J Stack4, Gwenda Simons4, Marie Falahee4,
Georg Schett5, Matthias Englbrecht6, Josef S. Smolen2, Axel J. Hueber6 and Tanja Stamm7, 1Section for Outcomes
Research, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna,
Austria, 1090 Vienna, Austria, 2Division of Rheumatology, Department of Internal Medicine III, Medical University of
Vienna, Vienna, Austria, Vienna, Austria, 3Rheumatology, Medical University of Vienna, Vienna, Austria, 4Department of
Rheumatology, University of Birmingham and Sandwell & West Birmingham Hospitals NHS Trust, Birmingham, UK,
Birmingham, United Kingdom, 5Rheumatology and Immunology, Department of Internal Medicine 3, Universitätsklinikum
Erlangen, Erlangen, Germany, Erlangen, Germany, 6Department of Medicine 3, Rheumatology and Immunology, University
of Erlangen-Nuremberg, Erlangen, Germany, 7Section for Outcomes Research, Center for Medical Statistics, Informatics,
and Intelligent Systems, Medical University of Vienna, Vienna, Vienna, Austria
SESSION INFORMATION
Background/Purpose: People at risk of developing rheumatoid arthritis (RA) may be candidates for interventions aimed at
preventing RA development [1]. The identification of such at risk populations includes testing for genetic and other (e.g.
autoantibody) biomarkers. However, little is known about the perspectives of at risk individuals on these tests, how they
react and cope when identified as having an elevated risk status and what support they need. This study was undertaken to
address this gap in the current knowledge.
Methods: A qualitative interview study with people who were informed of being at risk of developing RA was conducted.
People either took part in a predictive test for RA as part of an extended health examination, or were patients with clinically
suspect arthralgia. The interview schedule explored perceptions of RA risk and different types of predictive tests. All
interviews were audio-recorded, transcribed verbatim and analyzed using thematic analysis.
Results: A total of 34 individuals (rheumatoid factor and/or ACPA positive) from three different European countries, who
previously had been informed that they had an elevated risk of developing RA participated in the study. Analysis of the
interview data revealed five overarching themes related to predictive testing in the context of RA (Figure).
There were differences between the perceptions of arthralgia patients and asymptomatic individuals. People suffering from
pain were much more frightened and worried when informed of being at risk of developing RA. As a consequence, they
reported that they modified their lives to a larger extent and had greater knowledge about RA than those without any
symptoms who were surprised, but kept calm and did not envisage changing their lifestyle as a consequence of being tested
positive. Almost all participants in this study preferred precise predictive tests in the context of RA. However, more than
half of them reported that they would refuse synovial biopsy or preventive medication. Recommendations for predictive
testing in the field of RA were given, which could promote uptake of preventive strategies.
Conclusion: Participants showed a variety of views about predictive testing in the context of RA risk and offered specific
suggestions that should be incorporated into service design and delivery in the context of future predictive testing
programmes. These findings may also be relevant to prediction and prevention in the context of other diseases where
multiple genetic risk factors interact with environmental risk factors to drive disease development.
1. van Steenbergen, H.W., T.W. Huizinga, and A.H. van der Helm-van Mil, The preclinical phase of rheumatoid
arthritis: what is acknowledged and what needs to be assessed? Arthritis Rheum, 2013. 65(9): p. 2219-32.
Disclosure: E. Mosor, None; M. Stoffer, None; G. Steiner, Thermo Fisher Scientific (Phadia GmbH), 2; K. Raza, None;
R. J. Stack, None; G. Simons, None; M. Falahee, None; G. Schett, None; M. Englbrecht, None; J. S. Smolen, AbbVie,
Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, Glaxo, ILTOO, Janssen, Eli Lilly and Company,
Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, UCB, 5,AbbVie, Janssen, Eli Lilly and
Company, MSD, Pfizer, Roche, 2,AbbVie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, Glaxo,
ILTOO, Janssen, Eli Lilly and Company, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis,
UCB, 8; A. J. Hueber, None; T. Stamm, AbbVie, Janssen, MSD, Novartis, and Roche, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/suddenly-you-are-a-person-at-risk-of-

developing-rheumatoid-arthritis-different-perspectives-of-individuals-on-predictive-testing-results-of-an-international-
qualitative-in
Tumor TIF1 Mutations and Loss of Heterozygosity Related to Cancer

Associated Myositis
Iago Pinal-Fernandez1, Berta Ferrer-Fabregas2, Ernesto Trallero-Araguas1, Eva Balada1, Maria Angeles Martinez3, Jose
Cesar Milisenda4, Gloria Aparicio-Español5, Moises Labrador-Horrillo1, Vicente Garcia-Patos1, Josep Maria Grau-Junyent4
and Albert Selva O'Callaghan6, 1Internal Medicine, Autoimmune Diseases Unit. Vall d´Hebron Hospital, Barcelona, Spain,
2Pathology, Vall d´Hebron, Barcelona, Spain, 3Immunology, Immunology Department, Barcelona, Spain, 4Muscle Research
Group and Ciberer, Hospital Clinic Provincial, Barcelona, Spain, 5Dermatology, Vall d´Hebron Hospital, Barcelona, Spain,
6Internal Medicine, Hospital Universitari General Vall d'Hebron, Barcelona, Spain
SESSION INFORMATION
Session Title: Muscle Biology, Myositis and Myopathies
Background/Purpose: To analyze the influence of genetic alterations and differential expression of the TIF1 genes in the
pathophysiology of cancer-associated myositis (CAM).
Methods: Whole exome sequencing of paired blood and tumor DNA samples from anti-TIF1g positive CAM patients and
controls were analyzed for the presence of somatic mutations and copy number changes in the TIF1 genes. To better
understand the genesis and maintenance of the autoimmune process we also studied the expression of TIF1g in the different
tissues involved in CAM (skin, muscle, and tumor) calculating the immunohistochemical H-score.
Results: Six out of 7 tumors from anti-TIF1g positive patients showed somatic mutations or loss of heterozygosity in one or
more of the 4 TIF1 genes compared with just one myositis control tumor (86% vs. 17%, p=0.03). Compared with control
tumors from non-myositis patients, tumors from both anti-TIF1g positive (H-score 255 vs. 196, p=0.01) and anti-TIF1g
negative CAM patients (H-score 251 vs. 152, p=0.03) showed more intense TIF1g staining, without significant differences
between anti-TIF1g positive and negative patients. Compared with anti-TIF1g negative patients, TIF1g muscle staining was
more intense in anti-TIF1g positive patients (H-score 22 vs. 5, p=0.03), while the skin of both myositis and control patients
showed intense TIF1g staining.
Conclusion: Mutations of TIF1 genes in tumors with high expression of TIFg may trigger myositis. We hypothesize that an
intense antineoplastic immune response may cause a rapid depletion of tumor neo-antigen shifting the target of immune cells
experiencing affinity maturation towards the wild-type form of the antigen, abundantly expressed in the skin and muscle of
these patients.
Disclosure: I. Pinal-Fernandez, None; B. Ferrer-Fabregas, None; E. Trallero-Araguas, None; E. Balada, None; M. A.

Martinez, None; J. C. Milisenda, None; G. Aparicio-Español, None; M. Labrador-Horrillo, None; V. Garcia-Patos,
None; J. M. Grau-Junyent, None; A. Selva O'Callaghan, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/tumor-tif1-mutations-and-loss-of-

heterozygosity-related-to-cancer-associated-myositis
Immune Checkpoint Inhibitors and Inflammatory Myopathies: Data from the

US Food and Drug Administration Adverse Event Reporting System
Xerxes Pundole, Mohsin Shah, Noha Abdel-Wahab and Maria Suarez-Almazor, Section of Rheumatology and Clinical
Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston,
TX, USA, Houston, TX
SESSION INFORMATION
Background/Purpose:
Immune checkpoint inhibitors have become standard of care for many malignancies. Although these therapies are effective,
they can activate the immune system resulting in adverse consequences. Inflammatory myopathies are increasingly being
appreciated as one of the adverse phenotypes stemming from immune checkpoint inhibitor therapy, but few reports have
been described in the literature. We aimed to analyze rates and disproportionality using drugs from the US Food and Drug
Administration (FDA) Adverse Events Reporting System (FAERS).
Methods:
We ran a query on AERSMine, an open access web based application designed to mine the FAERS database from the first
quarter (Q1) of 2004 to the fourth quarter (Q4) of 2016, in a total of 8,864,346 reports. We ran queries to obtain the number
of cases and to calculate the rates and measures of disproportionality; proportional reporting ratios [PRRs] and safety signals
[information components (IC)]. Search terms included immune checkpoint inhibitors, namely ipilimumab, nivolumab and
pembrolizumab. Inflammatory myopathy terms searched were myositis, dermatomyositis and polymyositis. We used Evans
2001 criteria to detect a signal which includes a PRR of 2 or greater, a x2 of 4 or more and at least 3 reports.
Results:
The FAERS files from 2004 Q1 to 2016 Q 4 contain 42, 94 and 24 inflammatory myopathy reports for ipilimumab,
nivolumab and pembrolizumab respectively. Myositis (n=28; x2=71.4; PRR=4.5; IC=2.2), dermatomyositis (n=9; x2=33.8;
PRR=6.2; IC=2.6) and polymyositis (n=5; x2=5.5; PRR=3.2; IC=1.7) showed disproportionality signals in relation with
ipilimumab. Reports with nivolumab showed similar results with myositis (n=78; x2=847.2; PRR=13.1; IC=3.7),
dermatomyositis (n=5; x2=6.8; PRR=3.6; IC=1.8) and polymyositis (n=11; x2=54.1; PRR=7.4; IC=2.9). There were 3
reports of Nivolumab and necrotizing myositis with a x2 of 88.7 and a PRR of 47.3. Pembrolizumab demonstrated a
disproportionality signal with myositis (n=24; x2=177.3; PRR=9.7; IC=3.3). There were 2 reports of necrotizing myositis
with pembrolizumab and no reports of dermatomyositis or polymyositis with pembrolizumab.
Conclusion:
Inflammatory myopathies are disproportionally related with immune checkpoint inhibitors. To the best of our knowledge
this is the first study to evaluate adverse events in relation with immune checkpoint inhibitors using the FDA FAERS data.
All results are hypothesis generating and usual caveats and limitations of pharmacovigilance data mining should be applied
while interpreting the results.
Disclosure: X. Pundole, None; M. Shah, None; N. Abdel-Wahab, None; M. Suarez-Almazor, Bristol-Myers Squibb, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/immune-checkpoint-inhibitors-and-

inflammatory-myopathies-data-from-the-us-food-and-drug-administration-adverse-event-reporting-system
Autoantibodies Predict Long Term Survival in Myositis Associated Interstitial

Lung Disease
Silvia Martinez1, Rohit Aggarwal2,3 and Chester V. Oddis4, 1Internal Medicine, UPMC, pittsburgh, PA, 2Department of
Medicine / Rheumtology, University of Pittsburgh Medical Center, Pittsburgh, PA, 3Rheumatology, University of Pittsburgh,
Pittsburgh, PA, 4Rheumatology/Clinical Immunology, Unviersity of Pittsburgh/University of Pittsburgh Medical Center,
Pittsburgh, PA
SESSION INFORMATION
Background/Purpose: Interstitial lung disease (ILD) significantly contributes to morbidity and mortality in adult
polymyositis (PM) and dermatomyositis (DM). Myositis associated autoantibodies (MAA) are associated with unique
clinical phenotypes and patient outcomes. In particular, the anti-tRNA synthetase autoantibodies (anti-synAbs) are
associated with high rates of ILD. Our aim was to determine predictors of survival in myositis associated ILD (MA-ILD)
and to evaluate differences related to autoantibody (autoAb) subsets.
Methods: PM and DM subjects with ILD or with the antisynthetase (anti-syn) syndrome with ILD were consecutively
identified from the University of Pittsburgh (UPITT) CTD registry which encompasses more than three decades of
prospective data linked to a sample repository collected on outpatients and inpatients with various autoimmune diseases. PM
and DM patients met probable or definite Bohan and Peter criteria and the anti-syn patients possessed one of the 8 known
anti-syn autoAbs (i.e. anti-Jo-1, PL-7, PL-12, EJ, OJ, KS, Zo and Tyr). ILD was radiographically defined by characteristic
xray or high-resolution computerized tomography findings. Death or transplant was determined from the registry or
electronic medical record. Kaplan Meier and log rank tests were used to determine survival rates and differences between
autoAb groups. Cox proportional hazards model was used to determine survival differences after controlling for co-variates
including age at diagnosis, gender, ethnicity and baseline FVC%.
Results: 369 patients met criteria for MA-ILD and 306 (83%) had positive autoAbs. Overall, 63% (231/369) had MAAs and
54% (198/369) had a positive the anti-syn autoAb. The most common autoAb subset in the entire autoAb (+) cohort was
anti-Jo-1(124/306; 41%). The overall 5 and 10 year survival of MA-ILD was 80% at 5 years and 72% at 10 years. Patients
with an MAA had better survival compared to MAA (-) subjects (5 and 10 year survival 80% vs. 72%; 72% vs. 58%,
p=0.003). Among MAA (+) patients, those with anti-syn autoAbs had better survival compared to those with non-anti-syn
autoAbs (5 and 10 years survival 80% vs. 73%; 73% vs. 61%, p=0.004). Among the entire anti-syn autoAb (+) subjects,
those with anti-Jo-1 had a better survival than those patients with 1 of the 7 other anti-syn autoAbs (5 and 10 year survival
86% vs. 72%; 77% vs. 65%, p=0.04).
Conclusion: Myositis patients with MAA, particularly anti-syn autoAbs have better survival rates compared to those
without autoAbs. Among anti-syn autoAb (+) patientÕs Jo-1 positivity confers a better survival. Myositis-associated
autoAbs predict survival and long-term prognosis in myositis.
Disclosure: S. Martinez, None; R. Aggarwal, Pfizer Inc, 2,Bristol-Myers Squibb, 2,Mallinckrodt, 2,Genentech and Biogen
IDEC Inc., 2,Momenta, 2,Bristol-Myers Squibb, 5,Octapharma, 5,Mallinckrodt, 5; C. V. Oddis, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/autoantibodies-predict-long-term-

survival-in-myositis-associated-interstitial-lung-disease
RNAseq Detection of Gene Dysregulation in PBMCs from Juvenile

Dermatomyositis, Positive for p155/140 Myositis Specific Antibody
Chiang-Ching Huang1, Victoria Hans2, Dong Xu3, Megan L. Curran4,5, Gabrielle A. Morgan6, Elisha D.O. Roberson7 and
Lauren M. Pachman8,9, 1Biostatistics, Joseph J. Zilber School of Public Health,, Milwaukee, WI, 2CureJM Center of
Excellence, Stanly Manne Research Center, Chicago, IL, 3Pediatric Rheumatology, Stanley Manne Research Center,
Chicago, IL, 4Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, 5Division of Rheumatology,
Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, 6Cure JM Program of Excellence in Myositis
Research, Chicago, IL, 7Depts. of Medicine and Genetics, Division of Rheumatology, Washington University, St. Louis,
MO, 8Cure JM Program of Excellence in Juvenile Myositis Research, Stanley Manne Children’s Research Institute,
affiliated with Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, 9Pediatric Rheumatology, Northwestern
University Feinberg School of Medicine, Chicago, IL
SESSION INFORMATION
Background/Purpose: Children with Juvenile Dermatomyositis (JDM) have variable responses to the available
immunosuppressive drugs, with less than optimal outcomes, making it essential to characterize their variable inflammatory
response. It is recognized that Myositis Specific Antibodies (MSA) are each associated with different clinical features and
disease course, but scarce information is available comparing the differences in genetic regulation among these MSAs . The
purpose of this study was to compare RNASeq data from PBMCs obtained from untreated children with new onset JDM
positive for p155/150 — the most common MSA — with the RNASeq data from age related controls, as well as JDM who
were either positive for MJ or who did not have a recognized MSA. Clinically, children with p155/140 often follow a more
variable and recurrent disease course than those patients with other MSA’s.
Methods: Newly diagnosed, untreated children with JDM were recruited for this IRB approved study (2008-13457), after
obtaining age-appropriate informed consent: there were 75% girls, mean age 7.2 ±4.1; Mean DAS=12/20, while the controls
had 80% girls, but were slightly older, 16.9±2.9. JDM disease activity was assessed using the Disease Activity Scores (DAS)
which range from 0-20. MSA were determined by immunoblot and immunoprecipitation, (Oklahoma Research Laboratory):
4 of the JDM were positive for p155/140, 2 were MJ+, and 2 were negative for MSA, compared with 5 healthy pediatric
controls. RNASeq libraries were generated from PBMC RNA using the Clontech stranded high input ribosomal depletion
total RNA kits. The samples were sequenced on either an Illumina HiSeq2500 or HiSeq300 in paired-end mode. Serum
levels of antibody to specific cytokines were determined by Mesoscale.
Results: The untreated JDM had active disease with a mean DAS-total=12.1. The RNASeq data identify 96 genes (adjusted
p-value < 0.05) differentially expressed between JDM who were p155/140+ and JDM who either had anti-MJ antibody or
were negative for MSA. The overall expression pattern of these genes is also different from the healthy controls. Pathway
and gene ontology analysis reveals significant enrichment of this gene list in immune response, especially the interferon
signaling (P=2*10-15). We identified among this gene list, OSA1,2,3, TNF, MX1,2, TRIM 14, 22, 25, IFNG, TNFαA1P3,
TNFSF-10, TGFBR3, IL-2RB, and others, clearly indicating enhanced immune activation in the children positive for
p155/140. Determination of some of the many cytokines involved in the JDM inflammatory pathway showed significant
increases in p155/140 sera vs controls: Interferon- γ: p= 0.013, IL-10:p= 0.0056, IL-6: p=0.026; IL-8: p=0.011; TNF-α
p=0.003892.
Conclusion: We have shown, for the first time, using RNASeq, that the MSA, p155/140 not only identifies children with
JDM who will have a difficult diseases course — but that this MSA is also associated with specific enhanced immune
activation. Speculation: Further definition of the specific differences in gene activation associated with the individual
MSA’s may lead to more targeted therapeutic interventions, and may provide a means of assessing the child’s response to
therapy.
Disclosure: C. C. Huang, None; V. Hans, None; D. Xu, None; M. L. Curran, None; G. A. Morgan, None; E. D. O.
Roberson, None; L. M. Pachman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rnaseq-detection-of-gene-dysregulation-

in-pbmcs-from-juvenile-dermatomyositis-positive-for-p155140-myositis-specific-antibody
Anti-TIF-1 Antibody Positivity Is Associated with a Five-Fold Increase in

Cancer Risk in the Idiopathic Inflammatory Myopathies
Alexander Oldroyd1,2, Jamie C Sergeant1,3, Paul New4, Neil J. McHugh5,6, Zoe Betteridge5, Janine Lamb7, William
Ollier7, Robert Cooper4,7,8 and Hector Chinoy2,9, 1Arthritis Research UK Centre for Epidemiology, Centre for
Musculoskeletal Research, Manchester Academic Health Science Centre, University of Manchester, Manchester, United
Kingdom, 2NIHR Manchester Biomedical Research Centre, Central Manchester NHS Foundation Trust, Manchester, United
Kingdom, 3Centre for Biostatistics, University of Manchester, Manchester Academic Health Science Centre, Manchester,
United Kingdom, 4MRC/ARUK Centre for Integrated Research into Musculoskeletal Ageing, University of Liverpool,
Liverpool, United Kingdom, 5Department of Pharmacy and Pharmacology, The University of Bath, Bath, United Kingdom,
6Royal National Hospital for Rheumatic Diseases, Bath, UK, Bath, United Kingdom, 7Division of Population Health, Health
Services Research and Primary Care, University of Manchester, Manchester Academic Health Science Centre, Manchester,
United Kingdom, 8Department of Rheumatology, Aintree University Hospital, Liverpool, United Kingdom, 9Department of
Rheumatology, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Salford, United
Kingdom
SESSION INFORMATION
Background/Purpose:
There is an increased cancer risk associated with the idiopathic inflammatory myopathies (IIM). Studies have identified that
positivity for the autoantibody against transcriptional intermediary factor 1 (anti-TIF-1 Ab) confers an even greater cancer
risk in the IIMs. Investigating the temporal relationship between anti-TIF-1 Ab positivity and cancer onset in a large
longitudinal IIM cohort will be inform future cancer screening practice. This study aimed to characterise the temporal
relationship between anti-TIF-1 Ab positivity and cancer onset in a large UK-based adult IIM cohort.
Methods:
Data from adults with a Bohan & Peter-verified diagnosis of IIM from the UKMYONET study were analysed. Anti-TIF-1
Ab (alpha and gamma serosubtype) positive and negative patients were included. Each patient was followed up until they
either developed cancer or were censored due to death. UKMYONET recruitment began in 1999, and cancer occurrence
linkage was carried out up until December 2016 through the UK Health and Social Care Information Centre. Cancer
associated myositis (CAM) was defined as an incident cancer occurring three years either side of the onset of IIM. The
cumulative incidence of cancer after IIM onset was estimated according to Kaplan-Meier methods for the anti-TIF-1 Ab
positive and negative cohorts. Hazard ratios for the time to cancer diagnosis by anti-TIF-1 Ab positivity were calculated
using a Cox-regression model adjusted for age, gender and smoking status.
Results:
Data from 711 IIM cases were analysed, with a total of 8009 person-years follow up (Table 1); 55 (8%) of the IIM cases
were anti-TIF-1 Ab positive, and all had dermatomyositis. A higher proportion of the anti-TIF-1 Ab positive cohort
developed CAM, compared to the anti-TIF-1 Ab negative cohort: 38% vs 8%. Even after only one year of follow up, the
proportion of the anti-TIF-1 Ab positive patients developing cancer (27%) exceeded the three year proportion of the anti-
TIF-1 Ab negative cohort (8%). Cox proportional modelling revealed that anti-TIF-1 Ab positivity was significantly
associated with an increased hazard of an associated cancer following IIM onset: HR 3.4 (95% CI 2.2, 5.4). Breast (33%),
ovarian (19%) and lymphoma (14%) were the three most common cancers in the anti-TIF-1 Ab positive patients, whereas
breast (20%), bowel (14%), lung (6%) and cervix (6%) were the most common sites in anti-TIF-1 Ab negative patients.
Conclusion:
This study has helped to characterise the temporal relationship between anti-TIF-1 Ab positivity and cancer onset. The
findings that earlier cancer onset is associated with anti-TIF-1 Ab positivity, and that associated cancer types differ, are
potentially of clinical significance, and appear to suggest a specific cancer screening approach in anti-TIF-1 Ab positive
patients.
Table 1 – Baseline demographics and time to cancer confirmation in anti-TIF-1 Ab positive and negative cohorts
Total cohort n = Anti-TIF-1 Anti-TIF-1
711 Ab positive, negative, n =
= 55 656
Female (%) 438 (61.6) 44 (80.0) 394 (60.1)
Smokers (%) 237 (33.3) 17 (30.9) 220 (33.5)
CAM* (%) 72 (10.1) 21 (38.2) 51 (7.8)
Proportion of patients with 36 (5.1) 7 (12.7) 29 (4.4)
cancer preceding IIM onset**
(%)
Proportion of patients with 36 (5.1) 14 (25.5) 22 (3.4)
cancer following IIM onset***
(%)
Median age at IIM onset (years, 61.8 (51.9, 69.1) 62.3 (55.2, 53.2 (42.6,
(IQR) 65.9) 63.9)
Median age at cancer onset 60.9 (50.4, 68.6) 60.3 (52.2, 61.0 (50.4,
(years, IQR) 67.2) 69.5)
Median time to cancer onset 1.9 (0.0, 8.0) 0.8 (0.0, 2.2) 1.7 (0.0, 5.1)
(years, IQR)
Cumulative proportion with
cancer onset in years after IIM
onset (%, 95% CI):
0.5 year after IIM onset 6.2 (4.4, 7.9) 14.5 (4.7, 5.5 (3.7, 7.2)
23.4)
1 year after IIM onset 7.5 (5.5, 9.4) 27.3 (14.5, 5.8 (4.0, 7.6)
38.1)
2 years after IIM onset 9.0 (6.9, 11.1) 34.5 (20.7, 6.9 (4.9, 8.8)
46.0)
3 years after IIM onset 10.1 (7.9, 12.3) 38.2 (23.9, 7.8 (5.7, 9.8)
49.8)
*CAM = cancer associated myositis – cancer occurring within 3 years either side
of an IIM onset
** Defined as cancer occurring less than 3 years prior to IIM onset
*** Defined as cancer occurring less than 3 years after IIM onset
IIM = idiopathic inflammatory myopathy
IQR = interquartile range
CI = confidence interval
Disclosure: A. Oldroyd, None; J. C. Sergeant, None; P. New, None; N. J. McHugh, None; Z. Betteridge, None; J.
Lamb, None; W. Ollier, None; R. Cooper, None; H. Chinoy, Novartis Pharmaceutical Corporation, 5,Novartis
Pharmaceutical Corporation, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/anti-tif-1-antibody-positivity-is-

associated-with-a-five-fold-increase-in-cancer-risk-in-the-idiopathic-inflammatory-myopathies

Predictive Modeling of Mortality in Polymyositis/Dermatomyositis Patients
with Interstitial Lung Disease Based on Combination of Serum Myositis-
Specific Autoantibodies and Conventional Biomarkers
Takahisa Gono1, Kenichi Masui2, Yasushi Kawaguchi3, Kei Ikeda4, Atsushi Kawakami5, Maasa Tamura6, Yoshinori
Tanino7, Takahiro Nunokawa8, Yuko Kaneko9, Shinji Sato10, Katsuaki Asakawa11, Naoshi Nishina9 and Masataka
Kuwana1, 1Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan,
2Department of Anesthesiology, National Defense Medical College School of Medicine, Tokorozawa, Japan, 3Institute of
Rheumatology, Tokyo Women's Medical University, Tokyo, Japan, 4Department of Allergy and Clinical Immunology, Chiba
University Hospital, Chiba, Japan, 5Department of Immunology and Rheumatology, Division of Advanced Preventive
Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki City, Japan, 6Department of
Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Yokohama, Japan,
7Department of Pulmonary Medicine, Fukushima Medical University School of Medicine, Fukushima, Japan, 8Department
of Rheumatic Diseases, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan, 9Division of Rheumatology, Department
of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, 10Division of Rheumatology, Department of
Internal Medicine, Tokai University School of Medicine, Isehara, Japan, 11Division of Respiratory Medicine, Niigata
University Medical and Dental Hospital, Niigata, Japan
SESSION INFORMATION
Background/Purpose: Interstitial lung disease (ILD) is one of the leading causes of mortality in patients with polymyositis
or dermatomyositis (PM/DM). Since clinical courses and outcomes of ILD are highly variable among PM/DM patients with
ILD, disease subsetting is essential in deciding management regimens, by offering opportunity to identify patients who have
a greater risk of mortality, especially early in the disease course. In this regard, myositis-specific autoantibodies (MSAs)
correlate with unique subsets of PM/DM-associated ILD, but potential utility of other serum biomarkers routinely measured
in clinical practice, such as CRP and ferritin, in predicting prognosis is also reported. The aim of this study is to establish
predictive modeling of mortality in patients with PM/DM-associated ILD using a large cohort data.
Methods: This study was conducted using a database of a multicenter retrospective cohort of patients with PM/DM-ILD
(JAMI cohort), which involved 44 institutions across Japan. We enrolled 487 patients based on adult-onset definite or
probable PM/DM including clinically amyopathic DM (CADM), ILD confirmed by imaging study, and availability of serum
samples at diagnosis. Anti-melanoma differentiation-associated gene 5 (MDA5) and anti-amynoacyl tRNA synthetase
(ARS) antibodies were detected by enzyme linked immunosorbent assay and RNA immunoprecipitation, respectively. CRP,
ferritin, KL-6 and surfactant protein-D (SP-D) were chosen as serum biomarkers for PM/DM-ILD. Independent risk factors
for all-cause mortality were identified by Cox regression analysis using MSAs and serum biomarkers, including CRP,
ferritin, KL-6 and surfactant protein-D (SP-D) as explanatory variables. The backward selection method was applied;
explanatory variables were eliminated when p value was > 0.10.
Results: The overall survival rate was 83% at 1 year. The survival rate was significantly lower in patients with anti-MDA5
than in those without (P<0.0001). The cut-off values of individual serum biomarkers for predicting mortality determined by
the receiver operating characteristic curve were CRP ≥1 mg/dl, ferritin ≥500 ng/ml, KL-6 ≥1000 mg/dl and SP-D <100
ng/ml. The presence of anti-MDA5 (hazard ratio [HR] = 3.0, 95% confidence interval 1.6-5.7), CRP ≥1 mg/dl (HR = 2.4,
1.4-4.0), KL-6 ≥1000 mg/dl (HR = 2.0, 1.3-3.3) and ferritin ≥500 ng/ml (HR = 1.8, 1.0-3.2) were identified as risk factors
for poor prognosis. Our modeling showed that the predicted mortality rates were 1.8%, 8%, 22%, 44% and 54% in patients
with zero, one, two, three and all four risk factor score, respectively (Figure 1).
Conclusion: We successfully generated predictive modeling of mortality in patients with PM/DM-associated ILD using
convenient serum biomarkers. This model is potentially useful in identifying the patients with high mortality risk, which
apparently require intensive treatment
Disclosure: T. Gono, Astellas, Japan Blood Products Organization, 8; K. Masui, None; Y. Kawaguchi, None; K. Ikeda,
None; A. Kawakami, None; M. Tamura, None; Y. Tanino, None; T. Nunokawa, None; Y. Kaneko, AbbVie, Eisai, Daiichi
Sankyo, Sanofi, 2,Bristol-Myeres Squibb, Eli Lily, Janssen, 5,AbbVie, Eisai, Astellas, Chugai Pharmaceutical, UCB, Pfizer,
Bristol-Myeres Squibb, Janssen, Tanabe-Mitsubishi, Ayumi Pharmaceutical, and Takeda Pharmaceutical, Taisho-Ttoyama,
8; S. Sato, Medical & Biological Laboratories, Co., Ltd, 8; K. Asakawa, None; N. Nishina, None; M. Kuwana, Astellas,
2,Medical & Biological Laboratories, Co., Ltd, 7,Astellas, Medical & Biological Laboratories, Co., Ltd, Japan Blood
Products Organization, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/predictive-modeling-of-mortality-in-

polymyositisdermatomyositis-patients-with-interstitial-lung-disease-based-on-combination-of-serum-myositis-specific-
autoantibodies-and-conventional-biomarkers
Rapid and Sustained Pain Improvement in Rheumatoid Arthritis Patients

Treated with Baricitinib Compared to Adalimumab or Placebo
Peter C. Taylor1, Roy Fleischmann2, Elizabeth Perkins3, Jeffrey Lisse4, Baojin Zhu4, Carol L Gaich4, Xiang Zhang4,
Douglas E. Schlichting4, Christina L. Dickson4 and Tsutomu Takeuchi5, 1NDORMS, University of Oxford, Oxford, United
Kingdom, 2University of Texas Southwestern Medical Center, Dallas, TX, 3Rheumatology, Rheumatology Care Center,
Birmingham, AL, 4Eli Lilly and Company, Indianapolis, IN, 5Keio University School of Medicine, Tokyo, Japan
SESSION INFORMATION
Session Title: Pain – Basic and Clinical Aspects Oral
Background/Purpose:
Assessment of pain improvement during treatment for rheumatoid arthritis (RA) may help frame patient expectations and
may be useful to clinical decision-making and discussions between providers and their patients. Baricitinib (BARI) 4 mg
once daily was associated with significant clinical improvements in the Phase 3 study, RA-BEAM, in active RA patients
with an inadequate response to methotrexate (MTX) compared with adalimumab (ADA) and placebo (PBO).1 The objective
of this post hoc analysis was to evaluate the time and likelihood of achieving different levels of pain control with BARI
relative to ADA and PBO.
Methods:
1305 patients on stable background MTX were randomized 3:3:2 to PBO, BARI 4 mg, or ADA 40 mg. The patient’s
assessment of pain was assessed with a 0-100 mm visual analog scale (VAS) at each study visit. The likelihood of achieving
≥30%, ≥50%, and ≥70% pain VAS improvement through Week 24 and the median time when 50% of patients achieved
these pain improvement thresholds were assessed with Cox proportional hazards models and the cumulative incidence
estimate.2 Pain improvement was analyzed by baseline pain VAS subgroup (≤median, >median). Analyses were not adjusted
for multiplicity.
Results:
BARI-treated patients were more likely to achieve at least 30%, 50%, and 70% pain improvement than PBO and ADA with
HR of 1.7, 1.9, and 2.5, respectively (p<0.001) compared to PBO, and 1.1 (p=0.145), 1.2 (p=0.032), and 1.3 (p=0.003)
compared to ADA. The median time for 50% of patients to achieve at least 30%, 50%, and 70% pain improvement,
respectively, was 1.9,4.0, and 12.4 weeks for BARI, 2.0,7.9, and 20.0 weeks for ADA, and 4.6, 14.0, and >24 weeks for
PBO (Table). The cumulative incidence for achieving 50% pain improvement is presented (Figure). The effects of BARI on
pain improvement were consistent regardless of baseline pain severity. In contrast, pain improvement for patients treated
with ADA or PBO varied by baseline pain severity (Table).
Conclusion:
BARI demonstrated faster and greater pain improvement than ADA or PBO through Week 24. In addition, unlike ADA and
PBO, BARI showed consistent improvement regardless of baseline pain severity.
References:
1Taylor et al. New Engl J Med 2017;376:652-62
2Gooley TA Statist Med 1999
Disclosure: P. C. Taylor, AbbVie, Eli Lilly and Company, Galapagos, GlaxoSmithKline, Pfizer, UCB, Biogen, Sandoz,
Novartis, and Janssen, 5,Celgene, Eli Lilly and Company, Galapagos, UCB, Abide Therapeutics, 2; R. Fleischmann,
AbbVie, Amgen, Astra Zeneca , Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly and Company, Novartis, Roche, Sanofi-
Aventis, Pfizer, UCB, 5; E. Perkins, Amgen, Medac, Eli Lilly and Company, 5; J. Lisse, Eli Lilly and Company, 1,Eli Lilly
and Company, 3; B. Zhu, Eli Lilly and Company, 1,Eli Lilly and Company, 3; C. L. Gaich, Eli Lilly and Company, 1,Eli
Lilly and Company, 3; X. Zhang, Eli Lilly and Company, 1,Eli Lilly and Company, 3; D. E. Schlichting, Eli Lilly and
Company, 1,Eli Lilly and Company, 3; C. L. Dickson, Eli Lilly and Company, 1,Eli Lilly and Company, 3; T. Takeuchi,
Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Abbivie GK,
Nipponkayaku Co. Ltd, Janssen Pharmaceutical K.K., Astellas Pharma Inc,. Taiho Pharmaceutical Co., Ltd, 5,AbbVie GK.,
Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Astellas
Pharma Inc, and Diaichi Sankyo Co.,Ltd, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rapid-and-sustained-pain-improvement-

in-rheumatoid-arthritis-patients-treated-with-baricitinib-compared-to-adalimumab-or-placebo
Trends and Predictors of Chronic Opioid Use in Individuals with RA

Yvonne C. Lee1, Joel Kremer2, Hongshu Guan3, Jeffrey D Greenberg4 and Daniel H. Solomon5, 1Rheumatology
Immunology & Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 2The Center for
Rheumatology, Albany Medical College, Albany, NY, 3Rheumatology, Brigham and Women's Hospital and Harvard
Medical School, Boston, MA, 4NYU School of Medicine, New York, NY, 5Brigham and Women's Hospital and Harvard
SESSION INFORMATION
Background/Purpose: The opioid epidemic is a major public health concern, requiring urgent action. However, little is
known about chronic opioid use among individuals with RA. We examined trends in chronic opioid use in RA patients from
2002-2015 and identified clinical factors predicting chronic opioid use.
Methods: RA patients were identified from a large multicenter US registry. Opioid use was ascertained from surveys
obtained at routine clinical visits, as often as once every 3 months. The primary outcome was chronic opioid use, defined as
any opioid use reported during at least 2 consecutive study visits. Cox Proportional Hazards regression models were
performed to identify associations between patient characteristics and incident chronic opioid use. Subgroup analyses were
performed among RA patients with no pain at study entry and RA patients with at least 1 documentation of opioid use from
2002-2015.
Results: Among 31,993 individuals with data on opioid use from at least 2 visits, chronic opioid use increased from 7.4% in
2002 to 15.5% in 2014 and decreased to 11.3% in 2015 (Figure). Among the 25,054 individuals who were not taking
opioids at baseline, longer disease duration, higher RA disease activity, worse disability, more pain, biologic DMARD use,
corticosteroid use and antidepressant use were significantly associated with increased risk of chronic opioid use (Table).
Asian race and a greater number of past DMARDs were associated with lower risk of chronic opioid use. Similar results
were observed in a sensitivity analysis with chronic opioid use defined as at least 3 consecutive reports of opioid use. In a
subgroup analysis of RA patients with no pain at baseline (N = 6,580), being female (HR 1.37, 95% CI 1.07-1.75) and being
on both Medicare and Medicaid (HR 2.03, 95% CI 1.00-4.12) were associated with chronic opioid use, whereas RA disease
duration and disability were no longer associated with chronic opioid use. In a subgroup analysis of RA patients with at least
1 report of opioid use during the study period (N = 6,758), the risk of progression to chronic opioid use was most strongly
predicted by high disease activity (HR 2.56, 95% CI 2.02-3.24) and high pain (HR 1.36, 95% CI 1.14-1.64).
Conclusion: Among individuals with RA, chronic opioid use doubled from 2002 to 2014 but did not increase in 2015.
Worse RA disease characteristics predicted increased risk of chronic opioid use, whereas a higher number of past DMARDs
was associated with a lower risk of chronic opioid use. Future studies are needed to determine whether aggressive treatment
of inflammatory disease leads to a decrease in chronic opioid use.
Table. Multivariable, time-updated, adjusted hazards ratios for the association
between patient characteristics and incident chronic opioid use among individuals
with RA, from 2002-2015 (N = 25,054).
Patient Characteristic Multivariable Adjusted
Hazards Ratio (95% CI)

Age 1.00 (0.99-1.00)
Sex
Male Ref
Female 1.04 (0.96-1.13)
Race
White Ref
Hispanic 0.97 (0.79-1.18)
Black 1.01 (0.84-1.21)
Asian 0.46 (0.33-0.66)
Other 0.99 (0.79-1.25)
Insurance
Private Ref
Medicaid 1.16 (0.98-1.37)
Medicare 1.14 (1.00-1.30)
Both Medicaid and Medicare 1.14 (0.87-1.49)
None 0.92 (0.65-1.29)
RA duration
<5 years Ref
5-10 years 0.98 (0.88-1.10)
>10 years 1.15 (1.04-1.28)
CDAI category
Remission (less than or equal to 2.8) Ref
Low (>2.8-10) 1.75 (1.51-2.02)
Moderate (>10-22) 2.73 (2.30-3.24)
High (>22) 3.79 (3.13-4.59)
HAQ Disability Index
Less than or equal to 0.5 Ref
0.5-1.0 1.27 (1.15-1.40)
> 1.0 1.18 (1.03-1.36)
Pain
None Ref
Low 1.73 (1.50-1.99)
Moderate 2.10 (1.76-2.51)
High 2.40 (2.01-2.88)
Number of previous DMARDs used 0.85 (0.82-0.88)
Biologic DMARD use 1.45 (1.32-1.59)
Corticosteroid use 1.28 (1.17-1.39)
Antidepressant use 1.66 (1.53-1.81)
Disclosure: Y. C. Lee, Express Scripts, 1,Pfizer Inc, 2; J. Kremer, Abbvie, Amgen, BMS, Genentech, GSK, Eli Lilly and
Company, Novartis,Pfizer, 5,Abbvie, Genentech, Eli Lilly and Company, Novartis, Pfizer, 2,Genentech and Biogen IDEC
Inc., 8,Corrona, 1,Corrona, 3; H. Guan, None; J. D. Greenberg, corrona, LLC, 1,Corrona, LLC, 3,Genentech, Janssen,
Novartis, Pfizer, Eli Lilly, 5; D. H. Solomon, Amgen, 2,Lilly, 2,AstraZeneca, 2,Abbvie, 2,Genentech, 2,Pfizer, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/trends-and-predictors-of-chronic-opioid-
use-in-individuals-with-ra
Relation of Pain Sensitization to Low Physical Function: The Multicenter

Osteoarthritis Study
Joshua Stefanik1,2, Daniel White3, Carrie Brown4, Laura Frey-Law5, Michael Nevitt6, Cora E. Lewis7 and Tuhina Neogi2,
1Physical Therapy, Northeastern University, Boston, MA, 2Clinical Epidemiology Research and Training Unit, Boston
University School of Medicine, Boston, MA, 3Department of Physical Therapy, University of Delaware, Newark, DE,
4Boston University School of Public Health, Boston, MA, 5University of Iowa, Iowa City, IA, 6Department of
Epidemiology & Biostatistics, University of California San Francisco School of Medicine, San Francisco, CA, 7University
of Alabama Birmingham, Birmingham, AL
SESSION INFORMATION
Background/Purpose: Peripheral and central sensitization (alterations in pain signaling) are related to heightened pain
severity and can be present in knee osteoarthritis (OA). Sensory input plays an integral role in motor function, and the pain
adaptation theory recognizes the impact of pain on motor function. However, it is unknown if sensitization independently
contributes to alterations in physical function beyond the effect of pain severity. We examined the relation of sensitization to
low physical function in older individuals with or at risk for knee OA independent of pain severity.
Methods: The MOST Study is a NIH-funded cohort of persons with or at risk of knee OA. Two sensitization measures were
assessed: 1) Temporal summation (a marker of central sensitization) was defined as being present when, after touching the
skin of the right wrist with a 60g monofilament repeatedly at 1Hz for 30s, the participant reported new or increased pain at
the wrist. 2) Pressure pain threshold (PPT) is a marker of peripheral +/- central sensitization at sites of
disease/inflammation, or of central sensitization when assessed at an otherwise normal area. PPT was assessed with an
algometer (1 centimeter (cm)2 tip) as the point at which the participants indicated that the pressure first changed to slight
pain. Three trials (0.5 kilograms (kg)/s) at each anatomic site were averaged. PPT was assessed at the right wrist and index
patella (i.e., knee with the worst knee pain). PPT was divided into sex-specific tertiles. Low physical function was assessed
by gait speed and WOMAC function (0-68 scale). Gait speed was calculated from the 20-meter walk test (meters
(m)/second(s)). Gait speed and WOMAC function were dichotomized at 1.0 m/s and >28/68, respectively, which are
standard definitions of low physical function. Logistic regression models were used to determine the relation of temporal
summation and PPT to physical function while adjusting for age, sex, BMI, clinic site, depressive symptoms,
catastrophizing, and knee pain severity.
Results:
2171 participants were included: mean±SD age and BMI were 67.9±7.8 and 30.7±5.9, respectively; 60% were female.
Temporal summation was present at the wrist in 42.2% of participants. The mean PPT at the wrist and index patella were
3.4±1.5 and 5.0±2.2 kg/cm2, respectively. 53.3% and 10.9% of participants had low physical function as defined by slow
walking and WOMAC, respectively. In general, participants with temporal summation at the wrist and low PPTs at the wrist
and index patella were more likely to have slow walking (Table). Participants with low PPTs at the patella were more likely
to have low WOMAC physical function.
Conclusion: Measures of pain sensitization are related to physical function. The relation is independent of knee pain
severity and provides support that peripheral and central nervous system alterations may not only affect pain severity, but
also physical function.
Table. Relation of measures of sensitization to physical function

Sensitization Measure Adjusted* OR (95% CI) for Gait Speed (Outcome)
(Exposure) 20-m walk <1.0 m/s WOMAC Function >28
1.5 1.1
Presence of Temporal Summation: Wrist
(1.2, 2.0) (0.8, 1.6)
PPT Wrist (kg/cm2):
Lowest Tertile
Middle Tertile 1.4 (1.0-2.0) 1.4 (0.9-2.1)
Highest Tertile 1.3 (0.9-1.8) 1.0 (ref) 1.3 (0.8-2.0) 1.0 (ref)
PPT Index Patella (kg/cm2):
Lowest Tertile
Middle Tertile 1.6 (1.1-2.3) 1.8 (1.1-2.8)
Highest Tertile 1.1 (0.8-1.7) 1.0 (ref) 1.3 (0.8-2.1) 1.0 (ref)
*Adjusted for age, sex, BMI, clinic site, depressive symptoms, catastrophizing, and knee pain severity
Disclosure: J. Stefanik, None; D. White, None; C. Brown, None; L. Frey-Law, None; M. Nevitt, None; C. E. Lewis,
None; T. Neogi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/relation-of-pain-sensitization-to-low-

physical-function-the-multicenter-osteoarthritis-study
Identification of Clinically Relevant Pain Profiles in Individuals with Active

RA
Alyssa Wohlfahrt1, Zhi Zhang1, Bing Lu2, Clifton O. Bingham III3, Marcy B. Bolster4, Wendy Marder5, Larry W.
Moreland6, Kristine Phillips7, Tuhina Neogi8 and Yvonne C. Lee9, 1Rheumatology, Immunology and Allergy, Brigham and
Women's Hospital, Boston, MA, 2Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard
Medical School, Boston, MA, 3Rheumatology, Johns Hopkins University, Baltimore, MD, 4Division of Rheumatology,
Massachusetts General Hospital, Harvard Medical School, Boston, MA, 5Internal Medicine-Rheumatology, University of
Michigan, Ann Arbor, MI, 6Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh, PA,
7Rheumatology, Vanderbilt University Medical Center, Nashville, TN, 8Clinical Epidemiology Research and Training Unit,
Boston University School of Medicine, Boston, MA, 9Rheumatology Immunology & Allergy, Brigham and Women's
Hospital and Harvard Medical School, Boston, MA
SESSION INFORMATION
Background/Purpose: Despite DMARD treatment, many RA patients continue to suffer from pain. Defining distinct pain
phenotypes may advance the use of therapies targeted at specific pain mechanisms. This study identified pain profiles among
RA patients with active disease, with the goal of informing treatment decisions to improve pain outcomes.
Methods: 146 RA patients with active disease were identified from 5 academic medical centers. Trained assessors
performed joint and tender point counts. Patient-reported measures of pain, fatigue, sleep and psychological distress were
assessed. Quantitative sensory testing was done to evaluate pain sensitivity (pressure pain thresholds), central pain
sensitization (temporal summation) and descending pain inhibition (conditioned pain modulation). A principle components
analysis (PCA) was performed to identify variables explaining the most variance. These variables were used in a hierarchical
cluster analysis to identify pain phenotypes. General linear and logistic regression models were used to identify differences
in clinical characteristics.
Results: Based on PCA, 20 variables were included in the cluster analysis, which identified 3 pain profiles (Figure): 1)
low pain and temporal summation with low psychological distress, fatigue, and sleep problems (N = 48, 32.9%); 2)
moderate pain and high temporal summation with moderate psychological distress, fatigue, and sleep problems (N = 44,
30.1%) and 3) moderate pain and temporal summation with high psychological distress, fatigue and sleep problems (N = 54,
37.0%). Catastrophizing and patient global differed across groups, with the low pain group (cluster 1) having the lowest
levels of both (Table). NSAID use differed across groups, with the highest frequency of use in the high temporal summation
group (cluster 2). Disease duration, CRP and swollen joint count did not differ across groups.
Conclusion: Among RA patients with active disease, 3 pain phenotypes emerged that may inform treatment decisions.
Patients with moderate pain and high temporal summation (cluster 2) may benefit from strategies to reduce central
sensitization, whereas patients with moderate pain and high psychological distress/fatigue/sleep problems (cluster 3) may
benefit from treatments to improve mood and sleep. The finding that NSAID use was highest in the group with high
temporal summation is interesting, given a study showing that COX-2 inhibition decreases temporal summation and
improves pain (Arendt-Nielsen 2016). Future studies are needed to determine the role of pain phenotypes in directing pain
management.
Disclosure: A. Wohlfahrt, None; Z. Zhang, None; B. Lu, None; C. O. Bingham III, None; M. B. Bolster, None; W.
Marder, None; L. W. Moreland, None; K. Phillips, None; T. Neogi, None; Y. C. Lee, Express Scripts, 1,Pfizer Inc, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/identification-of-clinically-relevant-pain-

profiles-in-individuals-with-active-ra
Identifying Pain Susceptibility Phenotypes in Those Free of Knee Pain with or

at Risk for Knee Osteoarthritis and Their Relation to Developing Knee Pain
Lisa Carlesso1, Neil Segal2, Laura Frey-Law3, Yuqing Zhang4, Na Lu5, Cora E. Lewis6, Michael C. Nevitt7 and Tuhina
Neogi5, 1School of Rehabilitation, Université de Montréal, Montreal, QC, Canada, 2University of Kansas, Shawnee, KS,
3UIowa, Iowa City, IA, 4Clinical Edpidemiology Reserach and Training Unit, Boston University School of Medicine,
Boston, MA, 5Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, MA,
6University of Alabama Birmingham, Birmingham, AL, 7Epidemiology and Biostatistics, University of California, San
Francisco, San Francisco, CA
SESSION INFORMATION
Background/Purpose: It is well recognized that factors beyond structural features contribute to the pain experience in
people with knee osteoarthritis (OA). Independent of structural pathology, characteristics such as psychological factors,
sleep, and sensitization may increase the risk of developing pain. We examined the relation of pain susceptibility phenotypes
to incident pain in people free of pain, but with or at risk of knee OA using indicators of psychological and
neurophysiological aspects of pain.
Methods: We used data from the Multicenter Osteoarthritis (MOST) Study, a NIH-funded longitudinal prospective cohort of
3026 older adults with or at risk of knee OA. We identified subjects who were free of frequent knee pain (FKP) (pain on
most days during the past month) at both the clinic visit and a telephone screen ~1 month before the clinic visit. We
excluded subjects who had a total knee replacement or possible peripheral neuropathy. We used latent class analysis to
determine groupings (phenotypes) of baseline psychological and neurophysiological characteristics likely to influence pain
(widespread pain, sleep, pain catastrophizing, positive affect, depressive symptoms and quantitative sensory testing (pressure
pain thresholds (PPT), temporal summation (TS)). We assessed the relation of these phenotypes to incident consistent FKP
(CFKP) (i.e., pain at both the clinic visit and telephone screen ~30 days prior) 2 years later using logistic regression, and
examined predictors of class membership (age, sex, education, race, BMI, comorbidities, radiographic knee OA).
Results: 852 participants met inclusion criteria (mean age; 67.1; mean BMI 29.5 kg/m2, 55% women); 87 (11%) developed
incident CFKP over 2 years. We identified 3 classes (phenotypes) that we labeled as “low”, “moderate” and “high” risk
phenotypes based on prevalence of pain risk factors. PPT was a distinguishing characteristic of the high-risk group, while
psychological factors were not (Figure 1A). Those in the moderate and low risk groups had significantly lower incidence of
CFKP over 2 years OR (95% CI) 0.53 (0.21, 0.86) and OR 0.62 (0.27, 0.96) respectively, compared with the high-risk
group. Women were more likely to be in the moderate and high risk groups compared to the low, while those with older age
were more likely to be in the high-risk group only (Figure 1B).
Conclusion: In this cohort free of frequent knee pain with or at risk of knee OA, 3 pain susceptibility phenotypes were
identified based on psychological and neurophysiological indicators that were associated with differential risk of developing
knee pain, irrespective of structural disease. The high-risk pain susceptibility group was predominated by neurophysiological
evidence of sensitization. Women were more likely to have higher risk pain susceptibility phenotypes suggesting that sex
specific pain phenotypes may be an avenue for future study.
Disclosure: L. Carlesso, None; N. Segal, None; L. Frey-Law, None; Y. Zhang, None; N. Lu, None; C. E. Lewis, None;
M. C. Nevitt, None; T. Neogi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/identifying-pain-susceptibility-

phenotypes-in-those-free-of-knee-pain-with-or-at-risk-for-knee-osteoarthritis-and-their-relation-to-developing-knee-pain
Effective Treatment of Persistent Arthritis Pain Requires Co-Modulation of

TNF and Type I Interferon
Sarah Woller1, Tony Yaksh2 and Maripat Corr3, 1Anesthesiology, UCSD, La Jolla, CA, 2Anesthesiology 0818, UCSD, La
Jolla, CA, 3Division of Rheumatology, Allergy, and Immunology, UCSD, La Jolla, CA
SESSION INFORMATION
Background/Purpose: Pain persisting beyond the resolution or control of clinical signs of rheumatoid arthritis (RA)
decreases quality of life for millions of people. Unfortunately, this pain does not respond well to typical analgesics, and,
while tumor necrosis factor (TNF) is a pivotal cytokine in RA, the persistence of pain in the face of anti-TNF treatment
indicates that control of this cytokine alone is insufficient to treat this pain. We have shown that in the K/BxN serum transfer
model male C57Bl/6 (WT) mice develop transient inflammation and a corresponding tactile allodynia (TA), which persists
beyond the resolution of inflammation. Here, we aimed to understand the role of TLR4 associated spinal cytokines,
specifically TNF and interferon (IFN) β in the development of this persistent, post-inflammatory pain state, which is
mediated through Toll-like receptor (TLR) 4 signaling.
Methods: K/BxN sera (100μl) was injected into male WT, Tnf-/-, Tlr4-/-, and Ifnar1-/- mice on Days 0 and 2. Ankle width
and withdrawal thresholds were examined over 28 days. Separate groups of mice were injected intrathecally (IT) with anti-
TNF antibody or with IFNβ.
Results: In male mice, there is a pivotal time (~2 weeks) beyond which administration of a TNF inhibitor or a TLR4
antagonist can no longer abrogate the neuropathic pain state in this animal model. Hence, we examined spinal cords from
arthritic mice on day 10 for differences in gene expression of key inflammatory cytokines associated with allodynia in male
Tlr4-/- and WT mice, as the WT male mice develop persistent pain, but the Tlr4-/- do not. We found IFNβ transcripts
decreased in WT mice (average fold change (AFC): 0.41) and were increased in Tlr4-/- mice (AFC: 18.84). In contrast, TNF
transcripts increased in WT mice (AFC 1.33), and remained unchanged in Tlr4-/- mice (AFC 0.96). The levels of mRNA
expression for IL-1β and IL-6 were equivalent between the two strains.
To further understand the roles of TNF and IFNβ in K/BxN-induced arthritis and pain, we assessed male Ifnar1-/- and Tnf-/-
mice. The inflammatory phase TA was attenuated in Ifnar1-/- mice (1.18g relative to 0.5g in WT males, p <0.05); however,
these mice developed persistent TA while the late phase TA was reduced in Tnf-/- mice (1.29g relative to 0.74g in WT males,
p < 0.05), suggesting neither TNF nor IFNβ is completely responsible for the persistent pain state. Next, male WT mice
were injected IT with anti-TNF antibody or with IFNβ. Neither pharmacologic treatment alone affected TA (p >0.05).
However, when Tnf-/- male mice were given IT IFNβ, we saw a persistent reversal in TA. Finally, WT male mice were
treated with the combination of both anti-TNF and IFNβ and showed a reversal in their persistent pain state, with a day 28
threshold of 1.4g relative to 0.27g in vehicle treated controls (p < 0.05).
Conclusion: These results suggest that the pharmacological co-modulation of TNF and IFNβ is necessary for the treatment
of persistent arthritis-related pain.
Disclosure: S. Woller, None; T. Yaksh, None; M. Corr, NIH, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effective-treatment-of-persistent-

arthritis-pain-requires-co-modulation-of-tnf-and-type-i-interferon
CD11b+Gr1dim tolerogenic Dendritic Cell-like Cells Suppress the Progression

of Interstitial Lung Disease in SKG Mice
Sho Sendo1, Jun Saegusa1, Hirotaka Yamada2, Yoshihide Ichise2, Ikuko Naka3, Yo Ueda2, Takaichi Okano2, Soshi
Takahashi4, Kengo Akashi5, Akira Onishi6 and Akio Morinobu4, 1Rheumatology and Clinical Immunology, Kobe
University Graduate School of Medicine, Kobe, Japan, 2Department of Rheumatology and Clinical immunology, Kobe
University Graduate School of Medicine, Kobe, Japan, 3Department of Clinical Pathology and Immunology, Kobe
University Graduate School of Medicine, Kobe, Japan, 4Department of Rheumatology and Clinical Immunology, Kobe
University Graduate School of Medicine, Kobe, Japan, 5Department of Rheumatology and Clinical Immnology, Kobe
University Graduate School of Medicine, Kobe, Japan, 6Department for Rheumatology and Clinical Immunology, Kobe
University Graduate School of Medicine, Kobe, Japan
SESSION INFORMATION
Session Title: Rheumatoid Arthritis – Animal Models
CD11b+Gr1dim tolerogenic Dendritic Cell-like Cells Suppress the Progression of Interstitial Lung Disease in SKG
Mice
Background/Purpose: SKG mice develop interstitial lung disease (ILD) resembling rheumatoid arthritis-associated ILD
(RA-ILD) in human. We identified a new cell population, CD11b+Gr1dim cells, in the lung of zymosan A (ZyA)-treated
SKG mice. The purpose of this study is to elucidate the origin and the function of CD11b+Gr1dim cells, in the pathogenesis
of ILD in SKG mice.
Methods: We assessed the severity of ZyA-induced ILD in SKG mice histologically, and examined lung-infiltrating cells by
flow cytometry. Total lung cells and isolated monocytic myeloid-derived suppressor cells (M-MDSCs) were cultured in vitro
with GM-CSF (and IL-4). The proliferation of CSFE-labeled naïve T cells co-cultured with isolated CD11b+Gr1dim cells
and MDSCs was evaluated by flow cytometry. In vitro-generated CD11b+Gr1dim cells were transferred to ZyA-treated SKG
mice.
Results: Histological analysis revealed that ZyA-treated mice developed various severity of ILD; HS1: 25%, HS2: 50% and
HS3: 25%. MDSCs, Th17 cells, and group 1 and 3 innate lymphoid cells (ILC1s and ILC3s) were increased in the lungs; the
proportion of these cells varied with ILD severity. In this process, we found that a unique cell population, CD11b+Gr1dim
cells, was expanded in the lungs with diffusely affected area greater than 60%. About half of the CD11b+Gr1dim cells
expressed CD11c, and the cells were morphologically DC-like. The CD11b+Gr1dim cells were induced from M-MDSCs
with GM-CSF in vitro and were considered tolerogenic because they suppressed T-cell proliferation and expressed high
levels of PD-L1. The regulatory function of CD11b+Gr1dimcells was partially canceled by addition of Anti-TGF-beta
neutralizing antibody when generating them. The CD11b+Gr1dim cells have never described previously and termed
CD11b+Gr1dim tolerogenic dendritic cell-like cells (CD11b+Gr1dim tolDC-LCs). Furthermore, adoptive transfer of
CD11b+Gr1dim tolDC-LCs significantly suppressed the progression of ILD in SKG mice.
Conclusion: CD11b+Gr1dim tolDC-LCs were differentiated from M-MDSCs, and could suppress the progression of ILD in
SKG mice.
Disclosure: S. Sendo, None; J. Saegusa, None; H. Yamada, None; Y. Ichise, None; I. Naka, None; Y. Ueda, None; T.
Okano, None; S. Takahashi, None; K. Akashi, None; A. Onishi, None; A. Morinobu, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/cd11bgr1dim-tolerogenic-dendritic-cell-
like-cells-suppress-the-progression-of-interstitial-lung-disease-in-skg-mice
iNKT Mediated Immunoregulatory Feedback Control Development of

Autoimmune Arthritis in Mice
Mattias N. D. Svensson1,2, Meng Zhao3, Mitchell Kronenberg3 and Nunzio Bottini1,2, 1Department of Medicine,
University of California San Diego, La Jolla, CA, 2Cellular Biology, La Jolla Institute for Allergy and Immunology, La
Jolla, CA, 3Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA
SESSION INFORMATION
Background/Purpose: Invariant Natural Killer T cells (iNKT) express an invariant T cell receptor (TCR) alpha chain and
recognize lipid antigens – such as alpha-GalCer (aGC), presented by CD1d. iNKT cells differentiate in the thymus into one
of three distinct populations: iNKT1, iNKT2 and iNKT17, which are analogous to Th1, Th2 and Th17. In arthritis iNKT
cells have been found to either promote or suppress disease, an effect that could be attributed to involvement of distinct
populations of iNKT cells. However, the differentiation and function of iNKT subsets during arthritis have not been
explored. We use the Zap70-mutant BALB/c SKG mouse, which develops autoimmune arthritis due to defective thymic
selection of CD4 T cells, to explore iNKT cell subsets during arthritis development.
Methods: Arthritis induced by mannan injection was evaluated in NKT deficient (CD1d-/-) and NKT sufficient (CD1d+/-)
SKG mice. Also, iNKT cells were depleted in SKG mice by injection of an NKT cell-depleting antibody two days before
arthritis onset. CD4 SKG T cells were adoptively transferred into RAG2-KO mice, alone or in combination with thymic
iNKT cells. aGC was injected once on the day of arthritis onset in WT and IFNy-/- SKG mice. Flow cytometry was used to
evaluate iNKT cells in arthritic joints and the development of iNKT cells in the thymus of SKG and WT BALB/c mice.
Results: In SKG mice disease severity correlated with a reduced frequency of iNKT1 (r=-0.7914, P=0.0003) and an
expansion of iNKT17 (r=0.7938, P=0.0003) in arthritic joints. Furthermore, in SKG mice deficient for iNKT cells, either
following genetic deletion of CD1d or by antibody mediated depletion, severity of arthritis was exacerbated (P=0.009 and
P=0.03 respectively). In line with these results, adoptive transfer of SKG iNKT cells ameliorated development of arthritis in
RAG2-KO mice in co-transfer of CD4 SKG T cell (P=0.01). SKG mice showed an altered thymic development of iNKT
subsets, with an increased frequency of iNKT1 (P<0.0001) and reduced frequencies of iNKT2 (P=0.0002) and iNKT17
(P=0.0016). Activation of iNKT cells in vivo using aGC ameliorated arthritis in SKG mice (P=0.05) through an IFNγ
dependent mechanism.
Conclusion: We identify an immune regulatory mechanism by which arthritogenic abnormalities of CD4 T cell selection are
associated with enhanced development of arthritis-protective iNKT1 and propose that activation of iNKT1 could be a
beneficial therapeutic intervention in rheumatoid arthritis.
Disclosure: M. N. D. Svensson, None; M. Zhao, None; M. Kronenberg, None; N. Bottini, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/inkt-mediated-immunoregulatory-

feedback-control-development-of-autoimmune-arthritis-in-mice

Functionally Distinct Pathogenic Subsets of Fibroblasts Exist within the
Inflamed Synovial Membrane and Mediate Specific Aspects of Inflammatory
Disease Pathology
Adam Paul Croft1, Joana Campos2, Loriane Savary2, Emma Bishop2, Jason Turner1, Guillaume Desanti2, Francesca
Barone3, Andrew Filer3 and Chris Buckley2, 1Institute of Inflammation and Ageing, University of Birmingham,
Birmingham, United Kingdom, 2University of Birmingham, Birmingham, United Kingdom, 3Institute of Inflammation and
Ageing (IIA), University of Birmingham, Birmingham, United Kingdom
SESSION INFORMATION
Background/Purpose: Fibroblasts are key effector cells in the persistence of synovial inflammation and joint damage. It is
not yet known whether specific subsets of synovial fibroblasts exist, and if so, if they are responsible for the distinct
fibroblast mediated features observed in inflammatory arthritis such as invasion of cartilage, bone damage, and persistence
of inflammation. Using selective cell deletion strategies and adoptive cellular transfer we demonstrate the presence of
functionally distinct subsets of synovial fibroblasts that mediate specific aspects of joint pathology.
Methods: Flow cytometry of digested synovial tissue was performed to determine the expression of fibroblast subsets using
a cassette of distinct cell surface makers. Bulk transcriptomics was performed using ultra-low input RNAseq. We utilized a
transgenic mouse in which FAP expressing cells were conditionally ablated (FAP-DTR) by administration of diphtheria
toxin. Poly-arthritis was performed using either the KRN serum transfer model. Mice were scored for clinical signs of
arthritis and MicroCT was performed to evaluate inflammatory bone changes.
Results:
We identified distinct populations of fibroblasts defined by their expression of a cassette of cell surface markers including:
podoplanin (PDPN), fibroblast activation protein (FAP), VCAM-1, Cadherin-11 and Thy1.2. Bulk transcriptomic analysis of
these targeted subpopulations of cells revealed distinct transcriptional signatures which associated with whether the
fibroblast subsets were located in the lining or sub-lining layers of the synovium. Synovial inflammation was associated with
activation and selective expansion of these cell subsets with distinct compartments of the synovial membrane. Within the
intimal layer of the synovium FAP+ PDPN+ Thy 1- fibroblasts highly express MMPs, proteases and were found within
pannus tissue invading articular cartilage and bone. In contrast, PDPN+ FAP+ Thy1+, cells rapidly expand within the sub-
intimal layer and express pro-inflammatory cytokines, chemokine and survival factors associated with the recruitment and
retention of leucocytes.
Utilising their shared expression of FAP we selectively deleted these cells using the FAP-DTR mouse. The deletion of these
cells in vivo lead to attenuation of synovial inflammation, inhibited leucocyte accumulation and protected against
inflammatory bone damage and remodelling. Consistent with these findings the adoptive transfer of FAP+, PDPN+ Thy1+
cells into arthric mouse joints lead to a more severe and persistent inflammatory arthritis, ehereas injection of FAP+ PDPN+
Thy1- cells did not.
Conclusion: Synovial inflammation is associated with the expansion, activation and differentiation of fibroblasts into
pathogenic distinct functional subsets of cells that regulate those specific aspects of inflammatory joint pathology. Direct
targeting of specific pathogenic subsets of synovial fibroblasts may provide a novel, non-immunosuppressive approach to
the treatment of inflammatory arthritis.
Disclosure: A. P. Croft, None; J. Campos, None; L. Savary, None; E. Bishop, None; J. Turner, None; G. Desanti, None;
F. Barone, None; A. Filer, None; C. Buckley, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/functionally-distinct-pathogenic-subsets-
of-fibroblasts-exist-within-the-inflamed-synovial-membrane-and-mediate-specific-aspects-of-inflammatory-disease-
pathology
IL-9-Producing Innate Lymphoid Cells – Keyplayers That Orchestrate

Resolution of Chronic Inflammation in Arthritis
Simon Rauber1, Markus Luber1, Stefanie Weber1, Lisa Maul2, Alina Soare3, Thomas Wohlfahrt1, Aline Bozec4, Martin
Herrmann5, Mario Zaiss2, Ursula Fearon6, Douglas J. Veale7, Juan Canete8, Oliver Distler9, Felice Rivellese10, Costantino
Pitzalis10, Georg Schett11, Jörg Distler3 and Andreas Ramming12, 1Department of Internal Medicine 3, Rheumatology and
Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen, Erlangen,
Germany, 2Department of Internal Medicine 3 – Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-
Nürnberg (FAU) and University Hospital Erlangen, Erlangen, Germany, 3Department of Internal Medicine 3 –
Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU),
Erlangen, Germany, 4Department Clinic of Medicine 3 - Immunology und Rheumatology, University of Erlangen-Nürnberg,
Department Clinic of Medicine 3 - Immunology and Rheumatology, Erlangen, Germany, Erlangen, Germany, 5Medicine III,
Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital
Erlangen, Osterreich, Germany, 6Trinity College Dublin, Department of Molecular Rheumatology, Trinity College Dublin,
Dublin, Ireland, 7Rheumatology, St. Vincent's University Hospital, Dublin 4, Ireland, 8Rheumatology, Hospital Clínic and
IDIBAPS, Barcelona, Spain, 9Department of Rheumatology, Center of Experimental Rheumatology, University Hospital
Zurich, Zurich, Switzerland, 10Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute,
Barts and The London, School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom,
11Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Department of Internal Medicine 3 – Rheumatology and
Immunology, Universitätsklinikum Erlangen, Erlangen, Germany., Erlangen, Germany, 12Department of Internal Medicine 3
– Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg
(FAU) and University Hospital Erlangen, Erlangen, Germany
SESSION INFORMATION
Background/Purpose: Transition from acute to chronic inflammation is a key step in the pathogenesis of inflammatory
disease but incompletely characterized to date. Similar to the onset phase of inflammation, resolution of inflammation is
actively regulated but coordinated by mediators diverse as those that initiate inflammation. Here we identified IL-9-
producing Type 2 Innate lymphoid cells (ILC2s) as key regulators in the interaction between innate and adaptive immune
responses that orchestrate resolution of inflammation in arthritis.
Methods: Wild-type and Il9 deficient mice were analyzed in three different models of arthritis, namely antigen induced
arthritis (AIA), serum induced arthritis (SIA) and monosodium urate crystal (MSU) induced arthritis model, followed by
histomorphometric analyses of inflammation, cartilage damage, bone damage, and micro-computed tomographies. For
synovial tissue analyses (ILC2, IL-9-expressing cells) samples from untreated active RA patients (N=19) and RA patients in
remission receiving treatment with DMARDs (methotrexate N=15, TNF inhibitors: N=5) were analyzed (N=19). In addition,
a longitudinal biopsy cohort of 10 early (<12 months disease duration) RA patients receiving synovial biopsies at baseline
and 6 months after start of anti-rheumatic therapy was analyzed. For the analysis of circulating ILC2s a cohort of 111 RA
patients was analyzed. 63 of these 111 patients received a follow-up assessment of circulating ILC2s 6 to 12 months after
baseline assessment.
Results: In the absence of IL-9, ILC2s did not proliferate and arthritis transformed into a chronic disease with persistent
joint swelling, chronic synovial inflammation, excessive cartilage destruction and bone loss. Treatment with recombinant IL-
9 led to proliferation and activation of ILC2s and promoted ILC2-dependent activation of regulatory T cells (Treg). This
cell/cell contact dependent interaction between ILC2s and Tregs via GITR and ICOS resulted in suppression of Th17 driven
inflammation and thereby also crucially influenced tissue damage and bone loss. The course of acute inflammation in
response to MSU crystals was not affected by IL-9. IL-9-producing ILC2s increased during resolution of RA both in the
synovial membrane as well as in the peripheral blood. IL-9+ ILC2 counts were very low in the synovium of active RA
patients, in whom IL-9 production was mostly confined to lineage (Lin) positive cells. In contrast, RA patients in remission
(DAS28 < 2.6) showed a strong upregulation of Lin- IL-9+ ILC2s. Also the longitudinal analysis of synovial tissue of RA
patients showed a switch of the cellular source of IL-9 from Lin+ IL-9+ cells during active disease to Lin- IL-9+ ILC2s after
successful treatment with anti-rheumatic drugs over 6 months.
Conclusion: IL-9 driven activation of ILC2s might thus provide a novel therapeutic anchor to induce resolution of chronic
inflammatory disease such as arthritis and to restore immune homeostasis. Current cytokine-targeting strategies exclusively
suppress the activation pathways rather than fostering resolution of disease, our data provide evidence for a new concept in
inflammatory medicine by modifying cytokine pathways relevant for resolution of inflammation.
Disclosure: S. Rauber, None; M. Luber, None; S. Weber, None; L. Maul, None; A. Soare, None; T. Wohlfahrt, None;
A. Bozec, None; M. Herrmann, None; M. Zaiss, None; U. Fearon, None; D. J. Veale, AbbVie, Actelion, Bristol-Myers
Squibb, Janssen, MSD, Novartis, Pfizer Inc, Roche, UCB, 2,AbbVie, Actelion, Bristol-Myers Squibb, Janssen, MSD,
Novartis, Pfizer Inc, Roche, UCB, 8; J. Canete, Gebro, 2; O. Distler, 4 D Science, Actelion, Active Biotec, Bayer, Biogen
Idec, Boehringer Ingelheim Pharma, BMS, ChemomAb, EpiPharm, Ergonex, espeRare foundation, GSK,Roche-Genentech,
Inventiva, Lilly, medac, MedImmune, Mitsubishi Tanabe, Pharmacyclics, Pfizer, Sanofi, Seroda, 2; F. Rivellese, None; C.
Pitzalis, None; G. Schett, None; J. Distler, 4D Science, 1,Anamar Medical, Active Biotech, Array Biopma, BMS, Bayer
Pharma, Boehringer Ingelheim, Celgene, GSK, Novartis, Sanofi-Aventis, UCB, 2,Actelion Pharmaceuticals US, Active
Biotech, Anamar, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, JB Therapeutics, Medac,
Pfizer, RuiYi, UCB, 5; A. Ramming, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/il-9-producing-innate-lymphoid-cells-

keyplayers-that-orchestrate-resolution-of-chronic-inflammation-in-arthritis
Lasp-1 Regulates Cell-Matrix and Cell-Cell Contacts in Arthritic Mouse

Models
Denise Beckmann1, Annika Krause2, Uwe Hansen1, Hans Peter Kiener3, Thomas Kamradt4, Catherine S. Chew5, Thomas
Pap2 and Adelheid Korb-Pap1, 1Institute of Musculoskeletal Medicine, University Hospital Muenster, Muenster, Germany,
2Institute for Musculoskeletal Medicine, University Hospital Muenster, Muenster, Germany, 3Rheumatology, Medical
University of Vienna, Vienna, Austria, 4Institute of Immunology, University Hospital Jena, Jena, Germany, 5Institute of
Molecular Medicine and Genetics, Medical College of GA, GA, GA
SESSION INFORMATION
Background/Purpose: In rheumatoid arthritis (RA) the attachment of synovial fibroblasts (SF) to articular cartilage is an
important prerequisite in the process of cartilage degradation. The actin-associated protein Lasp-1 is involved in processes of
actin organization and polymerization and focal adhesion turnover, respectively. Therefore, we investigated its role in
regulating cell-cell contacts and ECM interactions of synovial fibroblasts in RA.
Methods: Lasp-1 expression was analysed in tissue from RA patients, in hind paws of arthritic mouse models such as the
hTNFtg and G6PI mouse model by using WB and immunohistochemistry. Furthermore, Lasp-1-/- mice were interbred with
hTNFtg mice and offsprings were analysed for the progression of joint destruction by clinical evaluation and histopathology.
Cell spreading as well as migration characteristics of SF derived from wild type (wt), Lasp-1-/-, hTNFtg and Lasp1-/-hTNFtg
mice were analysed by live cell imaging and TEM. Cell-matrix interactions as well as cell-cell contacts of isolated SF from
all different genotypes were investigated in an electrical cell/substrate impedance sensing assay (ECIS). Additionally, we
used an in vitro 3D organ culture system for functional analyses.
Results: Lasp-1 expression levels were significantly increased in human and murine RA tissue as well as in arthritic SF in
comparison to healthy controls. Evaluation of Lasp-1-/-hTNFtg mice revealed a milder arthritis score, less cartilage
degradation and reduced SF attachment to articular cartilage compared to hTNFtg mice. Results of cell spreading and
migration analyses demonstrated alterations in spreading morphology and cell-cell contacts and a significantly reduced
migration rate of Lasp-1-/- SF and Lasp-1-/-hTNFtg SF compared to healthy controls. Immunofluorescence showed an
unstructured and irregular cytoskeleton in cells with Lasp-1 deletion compared to other cells, confirmed by TEM. ECIS
analysis demonstrated increased cell-cell contact formation in Lasp-1-/- compared to wt SF (+22% vs wt SF) and prolonged
cell-cell interactions of Lasp-1-/-hTNFtg SF in comparison to hTNFtg SF. Histological sections of the 3D matrices
demonstrated that wt SF formed an organised synovial structure comparable with healthy synovial tissue in vivo whereas in
matrices with hTNFtg SF, this synovial architecture was not seen. Interestingly, Lasp-1 deletion in the hTNFtg background
resulted in an organised cellular lining layer comparable with wt SF matrices.
Conclusion: Lasp-1 regulates the migratory behaviour of synovial fibroblasts and their invasion into cartilage matrix in
rheumatoid arthritis by controlling the dynamics of cell-matrix and cell-cell contacts.
Disclosure: D. Beckmann, None; A. Krause, None; U. Hansen, None; H. P. Kiener, None; T. Kamradt, None; C. S.
Chew, None; T. Pap, Orthogen, 5; A. Korb-Pap, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/lasp-1-regulates-cell-matrix-and-cell-

cell-contacts-in-arthritic-mouse-models
Interferon-Alpha Overexpression Triggers an Expansion of Highly

Suppressive Regulatory T Lymphocytes Protecting Against Experimental
Arthritis
Matthieu Ribon1,2, Katarzyna Matyja2,3, Roxane Hervé2,3, Delphine Lemeiter2,3, François Santinon2,3, Ken Tsumiyama4,
Shunichi Shiozawa4, Marie-Christophe Boissier3,5,6, Natacha Bessis2,3 and Patrice Decker2,3, 1li2P, University of Paris 13,
Sorbonne Paris Cité, Bobigny, France, 2UMR 1125, INSERM, Bobigny, France, 3Li2P, University of Paris 13, Sorbonne
Paris Cité, Bobigny, France, 4Department of Medicine, Rheumatic Diseases Unit, Kyushu University Beppu Hospital,
Beppu, Japan, 5Rheumatology Department, Assistance Publique – Hôpitaux de Paris (AP-HP), Avicenne Hospital, Bobigny,
France, 674 rue Marcel Cachin, INSERM, Bobigny, France
SESSION INFORMATION
Background/Purpose: Type I interferons (IFN-I) can be both anti- and pro-inflammatory. Among them, IFN-α inhibits
normal Th17 differentiation, whereas it is pathogenic in lupus. The role of IFN-I is controversial in rheumatoid arthritis
(RA) and experimental models. An IFN-I signature has been reported in RA patients, the signification of which is unclear. In
mice, IFN-I enhance or inhibit arthritis development according to IFN subtype, arthritis model and kinetics. We have
evaluated the therapeutic effect of early IFN-α production in collagen-induced arthritis (CIA).
Methods: CIA was induced by 2 immunizations with collagen/CFA. Disease development was studied in conditional
transgenic mice over-expressing mouse IFN-α1 after cessation of doxycyclin (Dox) administration (Tet-off system). IFN-α1-
negative littermates were used as controls. All mice express endogenous IFN-α. All mice received Dox. Arthritis was
followed by clinical evaluation. Inflammation/bone destruction were estimated by histology. Pain was followed by stance
and Von Frey tests. Plasma cytokines/anti-collagen antibodies were measured by Luminex/ELISA. Leukocytes sub-
populations and Th1/Th2/Th17 polarization were analyzed by flow cytometry. Bone marrow cells were cultured with M-
CSF/RANKL to evaluate osteoclast differentiation and activity. CD4+CD25+ regulatory T cells (Treg) and CD4+CD25-
effector T cells (Teff) were purified by magnetic sorting. Treg ATPase activity was determined in vitro by a luminescent
assay. Treg inhibition of Teff activation was measured by flow cytometry/ELISA in co-cultures. The in vivo therapeutic
capacity of purified Treg was estimated by adoptive transfer.
Results: Induction of mouse IFN-α1 production before the first or even before the second immunization resulted in CIA
protection and lower pain parameters. Anti-collagen antibody production was lower in IFN-α1+ mice. Likewise, IFN-α1+
mice produced less IL-6 but more IL-5. Protection was associated with decreased polarization to Th17 and lower IL-17
secretion capacity and increased polarization to Th2 and IFN-γ-positive Th1 and NK cells. On the contrary,
osteoclastogenesis and osteoclast activity were decreased in IFN-α1+ mice. CIA protection in IFN-α1-overexpressing mice
was associated with impaired B cells while increased CD86+ PMN in the bone marrow and particularly with an expansion of
Treg with a higher CD39/CTLA-4 expression, higher ATPase activity and a higher capacity to inhibit Teff proliferation and
cytokine secretion. Most importantly, adoptive transfer of those highly suppressive Treg purified from CIA IFN-α1+ mice
impaired CIA development in recipients in comparison to adoptive transfer of Treg purified from CIA IFN-α1- mice.
Conclusion: This is the first study analyzing the impact of IFN-α on CIA development. Early induction of IFN-α1
production and even after the first immunization (i.e., seropositive mice) nearly completely protects against arthritis,
highlighting a therapeutic window. Protection is associated with an expansion of more suppressive Treg able to confer
protection upon adoptive transfer. This work better defines the role of IFN-α and shows its potent modulatory effect in
inflammatory arthritis.
Disclosure: M. Ribon, None; K. Matyja, None; R. Hervé, None; D. Lemeiter, None; F. Santinon, None; K. Tsumiyama,
None; S. Shiozawa, None; M. C. Boissier, None; N. Bessis, None; P. Decker, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/interferon-alpha-overexpression-triggers-

an-expansion-of-highly-suppressive-regulatory-t-lymphocytes-protecting-against-experimental-arthritis
Highly Sensitive Cardiac Troponin-I in Peripheral Blood Predicts

Cardiovascular Events in Patients with Rheumatoid Arthritis
George Karpouzas1, Joel Estis2, Long Pham3, John Todd2 and Matthew Budoff4, 1Division of Rheumatology, Harbor-
UCLA Medical Center, Torrance, CA, 2Singulex, Alameda, California, Alameda, CA, 3Rheumatology, Harbor-UCLA
Medical Center, Torrance, CA, 4Cardiology, Harbor-UCLA Medical Center, Torrance, CA
SESSION INFORMATION
Session Title: Rheumatoid Arthritis – Clinical Aspects I: Cardiac Comorbidities
Background/Purpose: Cardiac troponins (cTn) are specific biomarkers of myocardial injury; their measurement with
highly-sensitive assays and at subthreshold levels for myocardial infarction (MI) diagnosis, predicts greater risk of both fatal
and non-fatal coronary heart disease, heart failure hospitalization, and overall mortality in the general population. We
previously reported that highly-sensitive cardiac troponin-I (cTnI>1.5pg/ml), independently predicted occult coronary
plaque burden and composition on coronary computed tomography angiography (CTA) in patients with established
rheumatoid arthritis (RA). We now explore whether high cTnI predicts cardiovascular events in the same cohort after five
years of follow-up.
Methods: One hundred and fifty RA patients without prior diagnosis of cardiovascular disease (CVD) underwent a baseline
64-slice CTA for plaque evaluation between 3/2010-3/2011. Blood was collected for cTnI and other biomarker assessments
at the time of the CTA. Subjects were followed for a mean of 60±26 months for incident CV events. Composite rates of
ischemic [cardiac death, non-fatal MI, ischemic stroke, peripheral arterial ischemia] as well as non-ischemic [new onset
heart failure hospitalization] CV events were the study end-points. Cox regression analysis evaluated the association
between high cTnI (>1.5pg/ml) and CV events in raw and several adjusted models; hazards ratios (HR) were calculated as
an estimate of CV event risk associated with high cTnI.
Results: Eleven patients suffered incident events (1.54/100PY): 8 were ischemic, including 1 cardiac death, 3 MI, 2 strokes,
and 2 peripheral arterial ischemic events requiring emergent revascularizations; the 3 non-ischemic events were new onset,
hospitalized, systolic heart failure. cTnI was higher in patients with events compared to those without [2.6 (2.1-4.4) vs. 1.5
(1.0-2.4) pg/ml, p=0.006]. High cTnI predicted risk of incident CV events (Figure 1, p=0.03) independently of demographic
and traditional cardiac risk factors (Table 1). Additionally, patients with low cTnI (=<1.5pg/ml) were 82% less likely to
suffer a CV event. No events occurred in patients with both low cTnI and low interleukin-6 (=<2.85pg/ml).
Conclusion: Highly-sensitive cTnI may provide prognostic information on long-term CV event risk assessment in RA
patients without symptoms or known history of CV disease.
Disclosure: G. Karpouzas, None; J. Estis, Singulex, 3; L. Pham, None; J. Todd, Singulex, 3; M. Budoff, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/highly-sensitive-cardiac-troponin-i-in-

peripheral-blood-predicts-cardiovascular-events-in-patients-with-rheumatoid-arthritis
Baseline Troponin Levels Are Associated with Mortality in a Cohort of

Patients with Inflammatory Polyarthritis: Results from the Norfolk Arthritis
Register
Sarah Skeoch1,2, Paul Welsh3, James M Gwinnutt4,5, Jennifer Humphreys4, Jacqueline Chipping6, Alex J Macgregor7,
Suzanne M Verstappen4,5, Deborah P.M. Symmons8, Naveed Sattar9 and Ian N. Bruce4,10, 1Arthritis Research UK Centre
for Epidemiology, Centre for Musculoskeletal and Dermatology Research, Faculty of Medicine, Biology and Health,
University of Manchester, Manchester, United Kingdom, 2NIHR Manchester Musculoskeletal Biomedical Research Centre,
Central Manchester Hospitals NHS Foundation Trust, Manchester, United Kingdom, 3nstitute of Cardiovascular and
Medical Sciences, University of Glasgow, Glasgow, United Kingdom, 4Arthritis Research UK Centre for Epidemiology,
Centre for Musculoskeletal and Dermatology Research, Faculty of Medicine, Biology and Health, United Kingdom,
University of Manchester, Manchester, United Kingdom, 5Manchester Academic Health Science Centre, Manchester, United
Kingdom, 6Norwich Medical School, University of East Anglia, Norwich, United Kingdom, 7Rheumatology, Norfolk and
Norwich University Hospital, Norwich, United Kingdom, 8Centre for Musculoskeletal Research, Faculty of Biology,
Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Arthritis Research UK
Centre for Epidemiology, Manchester, United Kingdom, 9Institute of Cardiovascular and Medical Sciences, University of
Glasgow, Glasgow, United Kingdom, 10NIHR Manchester Musculoskeletal Biomedical Research Centre, Central
Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom
SESSION INFORMATION
Background/Purpose: Serum troponin is used in clinical practice in the diagnosis of acute myocardial infarction. Recent
studies have found that high sensitivity assays can predict cardiovascular (CV) events in the general population. We sought
to evaluate the association of troponin and mortality in a cohort of inflammatory polyarthritis (IP) patients.
Methods: Patients recruited between 2000 and 2009 to the Norfolk Arthritis Register, an IP inception cohort (inclusion
criteria: 2 or more swollen joint for 4 or more weeks, aged over 16 years) had CV risk factors and IP characteristics recorded
at inclusion and blood samples stored. High sensitivity troponin I (Tn-I) was measured on baseline samples, using an
automated clinical assay (Abbott, UK). Patients were flagged with the national death register and cause of death classified
using ICD10 codes. Patients were followed until death or December 2016. Tn-I was log transformed for analysis.
Association with all-cause and CV mortality was tested using Cox regression. Further Cox regression models were
performed for CV mortality, with adjustment for CV then IP factors. Subgroup analyses were performed in those with no
prior CV events and in those who met ACR/EULAR 2010 criteria for rheumatoid arthritis. The cohort was split into tertiles
based on Tn-I levels and Kaplan Meier curves were used to explore differences in CV mortality.
Results: 1022 patients were evaluated. Baseline characteristics are seen in Table 1. 158 deaths occurred during 11,237
person years follow up, 37 were CV deaths. Tn-I levels were associated with all-cause and CV mortality (HR[95%CI]:
1.71[1.46, 2.00] and 2.03[1.58, 2.61] per 1 unit increase in log Tn-I ). Results from adjusted regression models are seen in
Table 2.The association with CV mortality remained on adjustment for CV and IP factors. In both subgroup analyses, a
significant association between Tn-I and CV mortality was found. Survival curves are seen in Figure 1. Patients in the
highest tertile had a 7.7 fold increased risk of CV death compared to those in the lower tertiles (HR [CI 95%]: 7.78[3.56,
17.0]).
Conclusion: Tn-I levels are associated with CV mortality in IP, independent of CV risk factors and the association is not
explained by baseline IP disease characteristics or inflammation. The role of Tn-I in CV risk prediction warrants further
investigation.
Disclosure: S. Skeoch, None; P. Welsh, None; J. M. Gwinnutt, None; J. Humphreys, None; J. Chipping, None; A. J.
Macgregor, None; S. M. Verstappen, None; D. P. M. Symmons, None; N. Sattar, Novartis Pharmaceutical Corporation,
5,Roche Pharmaceuticals, 2; I. N. Bruce, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/baseline-troponin-levels-are-associated-

with-mortality-in-a-cohort-of-patients-with-inflammatory-polyarthritis-results-from-the-norfolk-arthritis-register
Utility of Carotid Ultrasound Compared to Framingham Risk Score in

Predicting Cardiovascular Mortality in Rheumatoid Arthritis
Pankhuri Gupta1, Agustin Escalante2, Daniel F. Battafarano3, Jose Felix Restrepo2 and Inmaculada del Rincon2,
1Rheumatology, University of Texas Health Science Center at San Antonio, SAN ANTONIO, TX, 2Internal Medicine-
Rheumatology, University of Texas Health Science Center at San Antonio, San Antonio, TX, 3Medicine, San Antonio
Military Medical Center, San Antonio, TX
SESSION INFORMATION
Background/Purpose: Rheumatoid arthritis (RA) patients have a greater risk of cardiovascular (CV) mortality compared to
general population. Traditional CV risk factors may be less accurate in predicting CV mortality in RA patients. We
examined the performance of the CV risk factors compared to carotid ultrasound measures of intima-media thickness (IMT)
in predicting CV mortality in a RA cohort.
Methods: We recruited patients who met the 1987 ACR criteria for RA from private, public and military rheumatology
practices. We measured carotid IMT using high resolution ultrasound. Baseline data on traditional CV risk factors which
included systolic blood pressure, diabetes, smoking, high density lipoprotein and total cholesterol were collected. For
Framingham CV risk, we used published tables to calculate the predicted 10-year risk of coronary heart disease, based on
the above risk factors. We then divided Framingham risk score into three categories defined as low (<10%), intermediate
(10-20%) and high (>20%) risk of CV mortality. We also divided IMT into risk groups of low (IMT < 1.0 mm), intermediate
(IMT 1.0-1.5 mm) and high (IMT > 1.5 mm). Patients were followed prospectively until they either died or reached the
censoring date of Nov 12, 2015. Certificates were obtained for all deaths, and cause of death classified as CV according to
established criteria. We then plotted area receiver operator characteristic (ROC) curves, calculated the area under the curve
(AUC) and compared curves using Stata 8.2. We also computed the Net Reclassification Index (NRI).
Results: We followed 1,194 RA patients for 7,062 patient years. During this time, 113 CV related deaths occurred, for a CV
mortality rate of 1.6 per 100 patient-years. Both the Framingham risk score and the carotid IMT were significantly
associated with CV mortality. Patients in the high Framingham risk group had a CV mortality rate of 5.7 per 100 patient
years, while those in the lower risk group had a CV mortality rate of 0.8 per 100 patient years. Patients in high IMT category
had a CV mortality rate of 5.8 per 100 patient years, while those in the low IMT category had a CV mortality rate of 0.6 per
100 patient years. The ROC area for the Framingham risk score was 0.7695 and while that of carotid IMT was 0.7760
(P=ns). When combined the Framingham risk score with the carotid IMT, the ROC curve area increased to 0.8096 (P <
0.0001, Figure). The carotid IMT added to the Framingham risk score, correctly reclassified 12.6% of the patients (NRI of
0.126, p=0.01).
Conclusion: Our findings suggest that carotid ultrasound measures of IMT significantly increase accuracy of CV mortality
predictions in RA patients over Framingham risk score.
Disclosure: P. Gupta, None; A. Escalante, None; D. F. Battafarano, None; J. F. Restrepo, None; I. del Rincon, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/utility-of-carotid-ultrasound-compared-

to-framingham-risk-score-in-predicting-cardiovascular-mortality-in-rheumatoid-arthritis
Detection of Left Ventricular Regional Function in Rheumatoid Arthritis

Patients without Cardiac Symptons, As Assessed By Feature Tracking
Cardiac Magnetic Resonance Imaging
Hitomi Kobayashi1, Yasuyuki Kobayashi2, Isamu Yokoe3, Akiyuki Kotoku4, Atsuma Nishiwaki5, Kaita Sugiyama6,
Noboru Kitamura5 and Masami Takei5, 1Division of Heamatology and Rheumatology, Nihon University School of
Medicine, Tokyo, Japan, 2Advanced Biomedical Imaging Informatics, St.Marianna University School of Medicine,
Kawasaki, Japan, 3Rheumatology, Kyoundo Hospital, Sasaki Institute, Tokyo, Japan, 4Advanced Biomedical Imaging
Informatics, St. Marianna University School of Medicine, Kawasaki, Japan, 5Division of Hematology and Rheumatology,
Nihon University School of Medicine, Tokyo, Japan, 6Nihon University School of Medicine, Tokyo, Japan
SESSION INFORMATION
Background/Purpose: Cardiac involvements cause of morbidity and mortality globally in rheumatoid arthritis (RA).
Myocardial disease is typically clinically silent, only manifesting as myocardial dysfunction after an extended preclinical
phase. Feature tracking (FT) cardiac magnetic resonance (CMR) imaging could reliably be used to assess myocardial
function in patients with early dysfunction. Left ventricular (LV) global longitudinal peak systolic strain (GLS) is prognostic
of adverse cardiovascular outcomes in various patient populations. Global circumferential peak systolic strain (GCS) is a
predictor of congestive heart failure. We sought to measure GLS and GCS by using FT-CMR approach in RA patients
without cardiac symptoms. Furthermore, we aimed to evaluate the association of GLS and GCS with RA status and severity.
Methods: RA patients and controls without cardiac symptoms were enrolled. RA patients and control subjects with no
history and/or clinical findings of systemic and pulmonary hypertension, coronary artery disease, valvular heart disease,
atrial fibrillation, diabetes mellitus, and dyslipidemia underwent a non-contrast CMR. Patients with RA were administered
non-biologic disease-modifying antirheumatic drugs (nbDMARDs) or biologic DMARDs (bDMARDs). All subjects
underwent evaluation of LV regional function, as measured by FT-CMR. GLS and GCS were calculated in the sixteen
segments of the whole LV. Group comparisons were made using the Wilcoxon rank sum test, Fisher’s exact test and Steel
test where appropriate.
Results: We compared 90 patients with RA (95% women; mean age, 59.5±9. 0 years) with 30 healthy controls (100%
women; mean age, 55.7±4.5 years). No statistically significant differences were observed in the characteristics between the
patients and the healthy controls in cardiovascular risk (CV )factors. GCS was significantly reduced by 31% in the RA group
compared to controls (p=0.011). Furthermore, GCS was significantly lower in the nbDMARD than in the bDMARD group
(p=0.04). GCS in the RA group was associated with the Simplified Disease Activity Index (SDAI) and levels of matrix
metalloprotease 3 (MMP3) (p=0.03, p=0.02, respectively). GCS in the RA group was not associated with CV risk factors or
other RA status. GLS in the RA group was significantly reduced by 21% compared to the control group (p=0.05). GCS in
the RA group was not associated with CV risk factors or RA status. GLS tended to be lower in the bDMARD group than in
the nbDMARD group. GLS tended to be associated with only the SDAI.
Conclusion: This prospective study is among the largest studies of LV regional dysfunction in RA, assessed by FT-CMR,
and the only study to explore the multivariable associations of RA characteristics with CMR-assessed GSC and GLS.
Subclinical LV regional dysfunction was prominent in the RA patients without cardiac symptoms. We demonstrated the
association of GCS with disease activity and MMP3. Longitudinal studies are required to track whether the regional
dysfunction we observed predict those destined to develop clinical cardiac involvements.
Disclosure: H. Kobayashi, None; Y. Kobayashi, None; I. Yokoe, None; A. Kotoku, None; A. Nishiwaki, None; K.
Sugiyama, None; N. Kitamura, None; M. Takei, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/detection-of-left-ventricular-regional-

function-in-rheumatoid-arthritis-patients-without-cardiac-symptons-as-assessed-by-feature-tracking-cardiac-magnetic-
resonance-imaging
Coronary Microvascular Dysfunction in Rheumatoid Arthritis Compared to

Diabetes Mellitus in Patients without Obstructive Coronary Artery Disease
Katherine P. Liao1, Gabrielle Cremone2, Ethan Lam2, Zhi Yu1, Jon M. Hainer3, Victoria Morgan3, Courtney Bibbo3 and
Marcelo Di Carli3, 1Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard
Medical School, Boston, MA, 2Rheumatology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA,
3Nuclear Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
SESSION INFORMATION
Background/Purpose:
Patients with DM have increased coronary microvascular dysfunction (CMD) compared to the general population, leading to
higher rates of cardiac death despite normal perfusion scans. While CMD is also thought to play a role in excess
cardiovascular (CV) risk in RA, studies are limited. CMD can be detected using coronary flow reserve (CFR), calculated
using data from clinically available stress myocardial perfusion PET scans. A pathognomonic sign of CMD is a patient with
normal perfusion on a stress test, but impaired CFR. The objective of this study was to compare the frequency of CMD in
RA compared to DM among subjects with normal perfusion scans.
Methods:
We performed a retrospective study within a tertiary care hospital registry of patients who received stress myocardial
perfusion PET scans as part of routine clinical care between 1/1/2006-1/1/2016. The registry contains data on
demographics, CV risk factors, stress test results (normal vs abnormal perfusion), CFR, and adjudicated mortality
outcomes. RA patients were identified using a validated algorithm and their medical records were reviewed to confirm
prevalent RA at the time of the stress test. We created a DM comparison group, matching to RA by age, gender, race, and
year of stress test. Among patients with normal perfusion scans, we compared the distribution of CFR in RA compared to
DM, and their mean CFRs using the student’s t-test. We performed chi-square tests to determine whether an impaired CFR
(CFR<2) was associated with a higher proportion of all-cause mortality in the RA and DM groups.
Results:
We studied 49 RA and 163 DM patients with normal perfusion scans. The RA patients had a mean age of 64.4 years at the
time of their scan, 59.2% white, 51% seropositive. There was no significant difference between the age, gender,
hypertension, dyslipidemia, family history of CVD, or smoking status between the RA and DM groups. The mean CFR was
2.02 for RA and DM, with a similar distribution of CFR between the two groups (p=0.98) (Figure). During a median
follow-up of 5.4 years, DM with impaired CFR had a significantly higher all-cause mortality than those with normal CFR
(p=0.02); a similar trend was observed in RA (p=0.29) (Table).
Conclusion:
In patients undergoing clinically indicated stress tests with normal perfusion scans, we observed a similar distribution of
CMD in RA compared to DM. These data suggest that CMD may contribute to the excess CV risk in RA as in DM. CFR,
calculated from clinically available stress myocardial perfusion PET scans is a promising imaging biomarker to guide CV
risk assessment in RA.
Disclosure: K. P. Liao, None; G. Cremone, None; E. Lam, None; Z. Yu, None; J. M. Hainer, None; V. Morgan, None;
C. Bibbo, None; M. Di Carli, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/coronary-microvascular-dysfunction-in-

rheumatoid-arthritis-compared-to-diabetes-mellitus-in-patients-without-obstructive-coronary-artery-disease
Myocardial Abnormalities Improve in RA Patients Treated Actively – a

Cardiac MRI Follow-up Study
Riitta Koivuniemi1,2, Mia Holmström3, Antti Kuuliala2, Sari Kivistö3 and Marjatta Leirisalo-Repo1,2, 1Rheumatology,
University of Helsinki, Helsinki, Finland, 2Rheumatology, Helsinki University Hospital, Helsinki, Finland, 3Radiology,
HUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
SESSION INFORMATION
Background/Purpose:
Patients with RA are prone to develop myocardial dysfunction, in which chronic inflammation is suggested to play an
important role. We have previously shown myocardial abnormalities on cardiac MRI (cMRI) in active RA.
Methods:
We collected 2 RA groups: a) patients with untreated active early RA (ERA; n=30) starting conventional synthetic
DMARDs (csDMARDs, n=28) or biological DMARDs (bDMARDs, n=2) and b) patients with CRA (n=28) with active RA
and were candidates for bDMARDs. Patients with coronary artery disease, diabetes or smoking, and aged >70 years were
excluded. Before and after one-year DMARD therapy, the patients (n=58) underwent cMRI. Sex and age-matched 22 FM
patients and 35 healthy volunteers underwent cMRI once. cMRI (1.5T or 3T) included analyses of T1 relaxation times, late
gadolinium enhancement (LGE), and cardiac functions.
Results:
Of ERA patients, 77% used csDMARDs combinations (60% used MTX-SSZ-HCQ combination). Of CRA patients, 86%
used anti-TNF therapy. In RA patients, LGE was detected as frequently at baseline as at follow-up (67%). None of FM
patients had LGE. Over time, DAS28-crp (mean+SD) declined in ERA (3.7+1.0 vs 2.0+1.0; p<0.001) and in CRA (3.3+1.1
vs 2.6+0.9; p=0.002). At baseline, cardiac function was impaired in RA patients compared with FM patients or healthy
volunteers. In RA patients, cardiac function improved over study-period (Table 1). ERA patients experienced improvement
in LV TPFR (496+96 mms vs 445+126; p=0.010) and in RV ESV (36+8 ml/m2 vs 34+7; p=0.043). In CRA, no significant
improvement was observed in cardiac functions. T1 time did not improve in ERA patients, but it improved in nine CRA
patients who underwent 3.0 T cMRI (1168+21 ms vs 1125+67; p=0.044).
Table1. Cardiac MRI in RA patients (n=58) over study-period

Baseline Follow-up p-value
mean+SD mean+SD
LV EF% 59+4 59+5 0.477
LV ESV, ml/m2 34+6 33+8 0.449
LV EDV, ml/m2 82+11 81+11 0.645
LV TPFR, ms 472+99 445+106 0.035
LV mass (mg/m2) 52+11 54+17 0.568
SV index, ml/ m2 48+6 48+6 0.929
RV EF% 59+6 60+6 0.065
RV ESV, ml/m2 34+9 32+8 0.006
RV EDV, ml/m2 81+12 78+11 0.022
T1 relaxation time (1.5T cMRI) 1038+90 1047+76 0.274
(n=22)
T1 relaxation time (3.0T cMRI) 1122+81 1113+81 0.395
(n=28)
LV= left ventricle, RV=right ventricle, ESV = end-systolic volume, EDV=end-diastolic volume, SV=stroke volume, EF =
ejection fraction, TPFR = time to peak filling rate
Conclusion:
Patients with active RA show myocardial abnormality on cMRI at baseline: prolonged myocardial T1 relaxation times
suggesting diffuse inflammation or fibrosis, LGE indicating local myocardial scars, and impairments of myocardial
functions. After 1-year treatment, targeting to remission, myocardial functions improved in early RA patients in parallel with
decreasing RA activity. In some CRA patients, T1 time improved. Active rheumatological inflammation seems to be
deleterious to the myocardium.
Disclosure: R. Koivuniemi, None; M. Holmström, None; A. Kuuliala, None; S. Kivistö, None; M. Leirisalo-Repo,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/myocardial-abnormalities-improve-in-ra-
patients-treated-actively-a-cardiac-mri-follow-up-study
Type I High-IFN Gene Signature in Associated with Higher Essdai at

Enrollmment and Follow-up in the Prospective Multicenter Assess Cohort of
395 Patients
Jacques-Eric Gottenberg1, Pierre-Etienne BOST2, Benno Schwikowski2, Raphaele Seror3, Valérie Devauchelle-Pensec4,
Philippe Dieudé5, Jean-Jacques Dubost6, Anne Laure Fauchais7, Vincent Goeb8, Eric Hachulla9, Pierre Yves Hatron10,
Claire Larroche11, Véronique Le-Guern12, Jacques Morel13, Aleth Perdriger14, Emmanuelle Dernis15, Stephanie Rist
Bouillon16, Alain Saraux17, Damien Sène18, Jean Sibilia19, Olivier Vittecoq20, Gaetane Nocturne21, Sarah TUBIANA22,
Philippe Ravaud23 and Xavier Mariette24, 1Department of Rheumatology, Strasbourg University Hospital, Strasbourg,
France, 2Pasteur Institute, System biologique, PARIS, France, 3Department of Rheumatology, Assistance Publique–
Hopitaux de Paris, Hôpitaux Universitaires Paris-Sud, Le Kremlin Bicêtre, France, 4Department of Rheumatology, Brest
University Hospital, Brest, France, 5Rheumatology, Hôpital Bichat, Paris, France, 6Rheumatology department CHU
Clermont-Ferrand, Clermont-Ferrand, France, 7Rheumatology, Limoges, France, 8Rheumatologie, Rheumatology
Department CHU Teaching Hospital Amiens, Amiens, France, 9CHU Lille, Département de Médecine Interne et
Immunologie Clinique, F-59000 Lille, France, Lille, France, 10Internal Medicine, Lille, France, 11Internal Medicine, Paris,
France, 12service de médecine interne, Department of Internal Medicine, Referral Center for Rare Autoimmune and
Systemic Diseases, Hôpital Cochin, AP–HP, Université Paris Descartes, Paris, France, 13Rheumatology, CHU Lapeyronie
and Montpellier University, Montpellier, France, 14Service de Rhumatologie, CHRU de Rennes, Rennes, France, 15Service
de Rhumatologie, CH du Mans, Le Mans, France, 16Rhumatologie, Hopital La Source, La Source, France, 17Rheumatology,
Brest University Hospital, Brest, France, 18Department of Internal Medicine, Pitié-Salpêtrière Hospital, Paris, France,
19Department of Rheumatology, Strasbourg University Hospital, Strasbourg, France, 20INSERM U905 & Normandy
University, Institute for Research and Innovation in Biomedicine, Rouen, France, 21INSERM U1184, IMVA, Paris Sud
University,LabEx LERMIT, Le Kremlin Bicêtre, France, 22CRB Bichat, PARIS, France, 23Hôpital Hôtel Dieu, Paris,
France, 24Université Paris-Sud, AP-HP, Hôpitaux Universitaires Paris-Sud, Paris, France
SESSION INFORMATION
Session Title: Sjögren's Syndrome I: Clinical Assessment and Trial Outcomes
Background/Purpose:
The type I interferon (IFN) signature is a hallmark of the pathogenesis of primary Sjögren’s syndrome (pSS). However, little
is known regarding the clinical utility of assessing this signature in a large cohort of patients prospectively followed up.
Methods:
395 patients with pSS were enrolled in the « ASSessment and Evolution of Systemic complications in primary Sjögren’s
syndrome ». Patients have been followed up every year ever since and completed their 5-year follow-up. At baseline, along
evaluation of clinical disease activity using international scores, ESSDAI and ESSPRI, serum B-cell activation biomarkers,
and whole blood RNA were collected in all enrolled patients. The type I IFN signature was evaluated using the gene
expression of IFI27, IFI44 et OAS3 (ref1).
Results:
IFN-high signature is associated with an earlier onset of the disease and a higher systemic disease activity at enrollment
The type I interferon signature was assessed in 366 patients at enrollment. 187 patients (51.1%) had a high IFN signature
and 179 had a low IFN signature (49.9%). Patients with a high IFN signature had a significantly earlier onset of symptoms
(median age at first symptoms: 44 [34 ;54] years versus 50 [42 ;58] years in patients with low IFN signature, p< 0.0001).
ESSDAI was significantly higher in high-IFN patients (4 [2 ;8] versus 2 [1 ;7] in low-IFN patients, p=0.01). ESSPRI tended
to be lower in high IFN patients (5.3 [3.3 ; 6.7] vs 5.7 [4.2 ;7.3], p= 0.07. IFN-high patients had significantly more
frequently active hematological and biological domains of ESSDAI (71.9% and 72.1%, respectively) than IFN-low patients
(47.6 and 34.5%, respectively, p<0.0001 for both comparisons) and tended to have more frequently active lymphadenopathy
(80 vs 52.8%, p= 0.1), glandular (66.7 vs 50%, p= 0.2) and muscle (80 vs 53%, p= 0.37) domains of ESSDAI.
IFN high signature is associated with a higher systemic disease activity during the prospective follow-up
Median ESSDAI during the 5-year follow-up was significantly higher in IFN-high than IFN-low patients (3.6 [2 ;7.33] vs
2.8[1 ;6], p=0.003).
Among the 5 patients who developed a lymphoma during the prospective follow-up , 4 out of 5 (80%) were IFN-high at
enrollment (versus 50.6% in patients without lymphoma and 43.8% in patients with a history of lymphoma).
Immunological correlates
High IFN signature was highly associated with anti-SSA and anti-SSB antibodies (9.4% in anti-SSA/SSB negative patients,
66.7% in anti-SSA-positive only patients and 87.5% in anti-SSA and anti-SSB-positive patients, p< 0.0001).
IFN score was inversely correlated with components of the hematological domain and C3, C4 and was significantly
correlated with IgG (r= 0.53, p< 0.0001), kappa and lambda free light chains of Ig (r=0.46 and 0.48, p< 0.0001 for both), RF
(r= 0.45,p< 0.0001), beta-2 microglobulin (r= 0.61, p<0.0001), and BAFF(r=0.36, p< 0.0001).
Conclusion:
IFN gene signature is associated with a more active and systemic disease in a 5-year multicenter prospective cohort and with
increased serum markers of B-cell activation. This reinforces the rationale to target type I IFN in pSS-related systemic
complications.
Ref 1 Petri M, Behrens T et al Lupus 2009
Disclosure: J. E. Gottenberg, BMS, Gilead, Medimune,Pfzer SanofiAventis, Ucb, 2; P. E. BOST, None; B. Schwikowski,
None; R. Seror, None; V. Devauchelle-Pensec, Roche-Chugai provided me tocilizumab for the SEMAPHORER study, 2; P.
Dieudé, None; J. J. Dubost, None; A. L. Fauchais, None; V. Goeb, Roche SAS, 5,Chugai Pharma France, 5; E. Hachulla,
None; P. Y. Hatron, None; C. Larroche, None; V. Le-Guern, None; J. Morel, None; A. Perdriger, None; E. Dernis,
None; S. Rist Bouillon, None; A. Saraux, None; D. Sène, None; J. Sibilia, None; O. Vittecoq, None; G. Nocturne, None;
S. TUBIANA, None; P. Ravaud, None; X. Mariette, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/type-i-high-ifn-gene-signature-in-

associated-with-higher-essdai-at-enrollmment-and-follow-up-in-the-prospective-multicenter-assess-cohort-of-395-patients
Effect of Rituximab on a Salivary Gland Ultrasound Score in Primary

Sjögren’s Syndrome: Results of Multicentre Double-Blind Randomised
Controlled Trial Sub-Study
Benjamin Fisher1, Colin Everett2, John Rout3, John O'Dwyer2, Paul Emery4, Costantino Pitzalis5, Wan-Fai Ng6, Andrew
Carr7, Colin Pease2, Elizabeth Price8, Nurhan Sutcliffe9, Jimmy Makdissi10, Anwar Tappuni10, Nagui Gendi11, Frances
Hall12, Sharon Ruddock2, Catherine Fernandez2, Claire Hulme2, Kevin Davies13, Christopher J. Edwards14, Peter
Lanyon15, Robert J. Moots16, Euthalia Roussou17, Linda Sharples18, Michele Bombardieri19 and Simon Bowman20,
1Rheumatology Research Group, University of Birmingham, Birmingham, United Kingdom, 2University of Leeds, Leeds,
United Kingdom, 3Birmingham Dental Hospital, Birmingham, United Kingdom, 4NIHR Leeds Biomedical Research Centre,
Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom, 5Centre for Experimental Medicine and Rheumatology,
William Harvey Research Institute, Barts and The London, School of Medicine and Dentistry, Queen Mary University of
London, London, United Kingdom, 6Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United
Kingdom, 7Newcastle Dental Hospital, Newcastle, United Kingdom, 8Great Western Hospital, Swindon, United Kingdom,
9Royal London Hospital, London, UK, London, United Kingdom, 10Barts Health NHS Trust, London, United Kingdom,
11Basildon and Thurrock University Hospital, Basildon, UK, Basildon, United Kingdom, 12School of Clinical Medicine,
University of Cambridge, Cambridge, United Kingdom, 13University of Sussex, Brighton, United Kingdom, 14University of
Southampton, Southampton, United Kingdom, 15University of Nottingham, Nottingham, United Kingdom, 16University of
Liverpool, Liverpool, United Kingdom, 17Barking Havering and Redbridge University hospitals NHS Trust, London, United
Kingdom, 18London School of Hygiene and Tropical Medicine, London, United Kingdom, 19Centre for Experimental
Medicine and Rheumatology, William Harvey Research Institute, Queen Mary University of London, UK, London, United
Kingdom, 20Department of Rheumatology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK,
Birmingham, United Kingdom
SESSION INFORMATION
Background/Purpose: B lymphocytes are important in the pathogenesis of primary Sjögren’s syndrome (PSS), but two
phase III trials (TEARS and TRACTISS) of the B cell depleting agent rituximab (RTX) failed to show an effect on their
primary endpoints in PSS. It is possible that RTX may lack efficacy in a non-stratified PSS population, but other
explanations for these negative results include the choice and timing of primary outcome. In a small single-site salivary
gland ultrasound (SGUS) substudy in TEARS, more subjects in the RTX arm demonstrated improvement in parotid gland
echostructure. Importantly, SGUS is an operator-dependent technique and we sought to compare the effects of RTX versus
placebo on SGUS in PSS, in a multicentre, multiobserver randomised double-blind substudy of TRACTISS.
Methods: All subjects fulfilled 2002 American-European Consensus Group Criteria for PSS, were anti-Ro antibody
positive, had symptomatic oral dryness and fatigue, some residual salivary flow, and evidence of systemic disease if disease
duration was greater than 10 years. Subjects also consenting to SGUS were randomised to 1000mg RTX or placebo given at
weeks 0, 2, 24 and 26, and scanned at baseline and weeks 16 and 48. Sonographers completed a 0-11 total ultrasound score
(TUS) comprising domains of echogenicity, homogeneity, glandular definition, glands involved, and size of hypoechoic foci.
Baseline-adjusted values of TUS were analysed over time, modelling change from baseline at each time point. For each TUS
domain we fitted a repeated measures logistic regression model to model the odds of a response in the RTX arm (defined as
a 1 point improvement) as a function of the baseline score, age category, disease duration and time point.
Results: 66 patients (49.6% of the total study population) consented to SGUS, and 52 (39.1%; n=26 RTX and n=26 placebo)
completed the baseline and at least one follow-up visit. Estimated baseline-adjusted TUS at week 16 was 6.2 (95% CI 5.4-
7.0) for placebo and 5.0 (95% CI 4.4-5.6) for RTX, and at week 48, 6.1 (95% CI 5.5-6.6) and 4.8 (95% CI 4.2-5.4)
respectively. Estimated between group differences (RTX-placebo) in baseline adjusted TUS were -1.2 (95% CI -2.1 to -0.3;
p=0.0099) and -1.2 (95% CI -2.0 to –0.5; p=0.0023) at weeks 16 and 48. Glandular definition was the only domain to show
statistically significant improvement with an OR of 6.8 (95% CI 1.1-43.0; p=0.043) at week 16 and 10.3 (95% CI 1.0-105.9;
p=0.050) at week 48. Improvement of ≥1 point in TUS was associated with improvement in oral dryness VAS at week 16
(diff=15.9; CI 1.5 to 30.3; p=0.030) but not week 48.
Conclusion: TUS differed between study arms, favouring RTX. This encourages further research into both B cell depletion
therapies in PSS and SGUS as an imaging biomarker in PSS clinical trials.
Disclosure: B. Fisher, Novartis, Roche, Virtualscopics, 5; C. Everett, None; J. Rout, None; J. O'Dwyer, None; P. Emery,
See notes, 5; C. Pitzalis, None; W. F. Ng, Pfizer, UCB, MedImmune, Takeda and Sanofi, 5; A. Carr, None; C. Pease,
None; E. Price, None; N. Sutcliffe, None; J. Makdissi, None; A. Tappuni, None; N. Gendi, None; F. Hall, None; S.
Ruddock, None; C. Fernandez, None; C. Hulme, None; K. Davies, None; C. J. Edwards, Celgene Corporation, Pfizer,
Roche, Samsung, 2,Celgene Corporation, Pfizer, Roche, Samsung, 5,Abbott, GSK, Pfizer, Roche, 8; P. Lanyon, None; R. J.
Moots, None; E. Roussou, None; L. Sharples, None; M. Bombardieri, GSK, Amgen/MedImmune and UCB, 5; S.
Bowman, I have consulted in the field of Sjogren's for: AstraZeneca/Meddimmune, BMS, Celgene, Eli Lilly, Glenmark,
GSK, MTPharma, Novartis, Ono, Takeda, UCB, xtlbio). Roche provided Rituximab for the TRACTISS Study, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effect-of-rituximab-on-a-salivary-gland-

ultrasound-score-in-primary-sjogrens-syndrome-results-of-multicentre-double-blind-randomised-controlled-trial-sub-study
Serum Autoantibody Profiling of Primary Sjoegren’s Syndrome Patients

Reveals Novel Biomarkers Associated with the Disease, Disease Activity, and
Clinical Response to VAY736
Petra Budde1, Julie Doucet2, Hans-Dieter Zucht1, Remi Kazma2, Paul Maguire2, Alexandre Avrameas2, Marie-Anne
Valentin2, Stephen Oliver2, Peter Schulz-Knappe1 and Alessandra Vitaliti2, 1Protagen AG, Dortmund, Germany,
2Translational Medicine, Novartis Institutes for Biomedical Research, Basel, Switzerland
SESSION INFORMATION
Background/Purpose:
Overexpression of B cell activating factor (BAFF) in salivary glands contributes to the pathogenesis of primary Sjögren’s
syndrome (pSS) by promoting autoantibody (AAB) production. Treatment of pSS patients with VAY736, an anti-BAFF
receptor mAb, appears promising and was associated with a depletion of circulating B cells and a positive therapeutic effect
[1]. In addition to the classical anti-SS-A/Ro and anti-SS-B/La, a broader set of AABs may reflect B cell disturbances in pSS
and could serve as markers during clinical development of novel pSS therapeutics. In this study, we explored novel AABs in
pSS patients and healthy controls (HCs) and we tested their associations with the disease, disease activity, and clinical
response to VAY736.
Methods: Reactivity of AABs to 1,596 antigens was measured in serum samples from 27 pSS patients from a placebo-
controlled trial at baseline and post-treatment week 12 and from 50 age and gender-matched HCs. Patients were treated at
baseline with a single dose of VAY736 at 10 mg/kg (n=12), 3 mg/kg (n=6), or placebo (n=9). First, to identify AABs
associated with pSS, 3 different methods compared AAB levels at baseline between pSS patients and HCs: Wilcoxon rank
sum test, significance analysis of microarrays, and comparison of the 90th quantiles between groups. Second, to identify
AABs associated with pSS activity, Pearson correlation of AABs with EULAR Sjögren’s Syndrome Disease Activity Index,
secondary outcomes, and salivary and serum BAFF were tested, using baseline and week 12 levels as well as relative
changes. Third, VAY736 treatment-specific changes in AAB levels were investigated using linear mixed-effects models
adjusting for dosage, age, and gender effects.
Results:
Of 1,596 antigens, 36 were significantly different between pSS patients and HCs for at least one of the 3 tests, including the
known SS-A/Ro and SS-B/La (significant for all 3 tests) as well as novel antigens. SS-A/Ro and SS-B/La AABs were not
associated with disease activity or response to treatment. However, 48 AABs were significantly correlated with pSS activity
combining all treatment arms, and 12 AABs had baseline values that correlated with change in pSS activity upon VAY736
treatment (unadjusted p<0.05). Interestingly, 51 serum AABs correlated with BAFF saliva levels (│r│> 0.55), but not with
BAFF serum levels. The genes encoding novel antigens are involved in apoptotic, anti-viral, metabolic, inflammatory, blood
coagulation and B-cell processes, suggesting a possible link to the disease pathology. Finally, there was no reduction in
AABs levels in response to VAY736.
Conclusion: In conclusion, we identified new AABs in pSS patients that have the potential to serve as markers of diagnosis,
pSS activity, or as predictors of clinical outcome measures. Further large-scale studies are needed to confirm the value of
these markers.
1. Dörner T et al. Arthritis Rheum 2016; 68(suppl S10):4051
Disclosure: P. Budde, Protagen AG, 3; J. Doucet, Novartis Pharma AG, 3; H. D. Zucht, Protagen AG, 3; R. Kazma,
Novartis Pharma AG, 3; P. Maguire, Novartis Pharma AG, 3; A. Avrameas, Novartis Pharma AG, 3; M. A. Valentin,
Novartis Pharma AG, 3; S. Oliver, Novartis Pharma AG, 3; P. Schulz-Knappe, ProtagenAG, 3; A. Vitaliti, Novartis
Pharma AG, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/serum-autoantibody-profiling-of-

primary-sjoegrens-syndrome-patients-reveals-novel-biomarkers-associated-with-the-disease-disease-activity-and-clinical-
response-to-vay736
Epidemiologic Subsets Drive a Differentiated Clinical and Immunological

Presentation of Primary Sjögren Syndrome: Analysis of 9302 Patients from
the Big Data International Sjögren Cohort
Soledad Retamozo1,2,3, Pilar Brito-Zerón3,4, Margit Zeher5, Kathy L. Sivils6, Raphaele Seror7, Thomas Mandl8, Xiaomei
Li9, Chiara Baldini10, Jacques-Eric Gottenberg11, Debashish Danda12, Roberta Priori13, Luca Quartuccio14, Gabriela
Hernandez-Molina15, Aike A. Kruize16, Seung-Ki Kwok17, Marie Wahren-Herlenius18, Sonja Praprotnik19, Damien Sene20,
Roberto Gerli21, Roser Solans22, Yasunori Suzuki23, David A. Isenberg24, Maureen Rischmueller25, Gunnel Nordmark26,
Guadalupe Fraile27, Piotr Wiland28, Hendrika Bootsma29, Takashi Nakamura30, Valeria Valim31, Roberto Giacomelli32,
Valérie Devauchelle-Pensec33, Benedikt Hofauer34, Michele Bombardieri35, Virginia Fernandes Moça Trevisani36, Daniel
S. Hammenfors37, Steven E. Carsons38, Sandra Gofinet Pasoto39, Jacques Morel40, Tamer Gheita41, Fabiola Atzeni42,
Cristina F. Vollenweider43, Belchin Kostov44, Xavier Mariette45 and Manuel Ramos-Casals46, 1Rheumatology Unit,
Hospital Privado Universitario de Córdoba, Institute University of Biomedical Sciences University of Córdoba (IUCBC),
Cordoba, Argentina, 2Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Córdoba, Consejo
Nacional de Investigaciones Científicas y Técnicas (INICSA-UNC-CONICET), Cordoba, Argentina, 3Laboratory of
Systemic Autoimmune Diseases “Josep Font”, CELLEX, Institut d’Investigacions Biomèdiques August Pi i Sunyer
(IDIBAPS), Department of Systemic Autoimmune Diseases, ICMID, Hospital Clinic, Barcelona, Barcelona, Spain,
4Autoimmune Diseases Unit, Department of Medicine, Hospital CIMA- Sanitas, Barcelona., Bacelona, Spain, 5Division of
Clinical Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Debrecen, Hungary, 6Arthritis and
Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 7Center for Immunology of
Viral Infections and Autoimmune Diseases, Assistance Publique – Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Le
Kremlin-Bicêtre, Université Paris Sud, INSERM, Paris, France, Paris, France, 8Department of Rheumatology, Skåne
University Hospital, Malmö, Sweden, Lund, Sweden, 9Department of Rheumatology and Immunology, Anhui Medical
University Affiliated Provincial Hospital, China, Hefei, Anhui, China, 10Internal Medicine, Rheumatology Unit, University
of Pisa, Pisa, Italy, 11Department of Rheumatology, Strasbourg University Hospital, Université de Strasbourg, CNRS,
Strasbourg, France, Strasbourg, France, 12Clinical Immunology & Rheumatology, Christian Medical College, Vellore, India,
Vellore, India, 13UO Complessa Reumatologia, Policlinico Umberto I Università Sapienza di Roma, Rome, Italy,
14Rheumatology Clinic, DSMB, University of Udine, Udine, Italy, Udine, Italy, 15Immunology and Rheumatology, Instituto
Nacional de Ciencias Médicas y Nutrición SZ, mexico city, Mexico, 16Rheumatology & Clinical Immunology, University
Medical Center Utrecht, Utrecht, Netherlands, 17seungki73@catholic.ac.kr, Division of Rheumatology, Department of
Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of (South), 18Unit of
Experimental Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm,
Sweden, Stockholm, Sweden, 19Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia,
20Service de Médecine Interne 2, Hôpital Lariboisière, Université Paris VII, Assistance Publique-Hôpitaux de Paris, 2, Paris,
France, Paris, France, 21University and Azienda Ospedaliera of Perugia, Perugia, Italy, 22Autoimmune Systemic Diseases
Unit, Department of Internal Medicine, Hospital Vall d'Hebron, Autonomous University of Barcelona, Spain, Barcelona,
Spain, 23Division of Rheumatology, Kanazawa University Graduate School of Medicine, Ishikawa, Japan, Kanazawa, Japan,
24Centre for Rheumatology Research, Division of Medicine, University College London, London, United Kingdom,
25Rheumatology, The Queen Elizabeth Hospital, South Australia, Adelaide, Australia, 26Department of Medical Sciences,
Section of Rheumatology, Uppsala University, Uppsala, Sweden, Uppsala, Sweden, 27Autoimmune Diseases Department,
Hospital Ramón y Cajal, Madrid, Spain, 28Department and Clinic of Rheumatology and Internal Medicine, Medical
University, Wroclaw, Poland, 29Rheumatology and Clinical Immunology, University of Groningen, University Medical
Center Groningen, Groningen, Netherlands, 30Department of Radiology and Cancer Biology, Nagasaki University School of
Dentistry, Nagasaki, Japan, 31Rheumatology, Department of Medicine, Universidade Federal do Espírito Santo, Vitória,
Brazil, Vitória, Brazil, 32University of L'Aquila, L'Aquila, Italy, 33Department of Rheumatology, Brest University Hospital,
Brest, France, 34Hals-Nasen-Ohrenklinik und Poliklinik, Technische Universität München, München, Germany, München,
Germany, 35Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Queen Mary
University of London, UK, London, United Kingdom, 36UNIFESP, Sao Paulo, Brazil, San Paulo, Brazil, 37Department of
Rheumatology, Haukeland University Hospital, University of Bergen, Bergen, Norway, 38NYU Winthrop University
Hospital, Department of Medicine, Mineola, NY, 39Internal Medicine, Division of Rheumatology - Faculdade de Medicina
da Universidade de São Paulo, São Paulo, Brazil, São Paulo, Brazil, 40Department of Rheumatology, Teaching hospital and
University of Montpellier, France, Montpellier, France, 41Rheumatology, Rheumatology Department, Faculty of Medicine,
Cairo University, Egypt, Cairo, Egypt, 42Rheumatology Unit, ASST Fatebenefratelli - Sacco, L. Sacco University Hospital,
Milano, Italy, 43Rheumatology, German Hospital, Buenos Aires, Argentina, Buenos Aires, Argentina, 44Primary Care
Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Primary Care Centre Les Corts,
CAPSBE, Barcelona, Spain, 45Université Paris-Sud, AP-HP, Hôpitaux Universitaires Paris-Sud, Paris, France, 46Laboratory
of Systemic Autoimmune Diseases “Josep Font”, CELLEX, Institut d’Investigacions Biomèdiques August Pi i Sunyer
(IDIBAPS), Department of Systemic Autoimmune Diseases, ICMID, Hospital Clinic, Barcelona, Spain, Barcelona, Spain
SESSION INFORMATION
Background/Purpose: To analyse whether epidemiologic factors (such as gender or age at diagnosis of the disease) are
associated with particular disease expressions and define some specific subsets in patients with primary Sjögren syndrome
(SS).
Methods: The Big Data Sjögren project is an international, multicentre registry formed in 2014 to take a “high-definition”
picture of the main features of primary SS at diagnosis by merging international SS databases using a Data-Sharing
methodological approach. By January 2017, the database included 9302 consecutive patients recruited from 21 countries of
the five continents. The main features at diagnosis (time of criteria fulfilment) or at recruitment were collected and analysed.
Results: Of the 9032 patients, 8680 (93%) were women and 622 (7%) were men with a mean age at diagnosis of primary SS
of 50 years; 76% were Caucasian. The frequency of fulfilment of the 2002 criteria was: 92% for dry eye, 93% for dry
mouth, 88% for positive salivary gland biopsy, 93% for positive ocular tests, 85% for positive oral tests and 71% for positive
Ro/La autoantibodies. Other immunological tests included positive ANA (81%), RF (49%), low C4 levels (13%), low C3
levels (14%) and cryoglobulins (7%). Men with primary SS presented a higher frequency of White ethnicity (83% vs 76% in
women, p < 0.001) and rheumatoid factor (54% vs 49%, p = 0.017), and a lower frequency of dry eyes (89% vs 92%, p =
0.011) and dry mouth (90% vs 94%, p = 0.026) in the multivariate model analysis. Patients with a younger onset (< 35
years) showed a lower frequency of White ethnicity (69% vs 77% in aged > 35 yrs, p < 0.001), dry eyes (86% vs 93%, p <
0.001) and positive ocular tests (81% vs 85%, p = 0.001), and a higher frequency of anti-Ro/La autoantibodies (84% vs
70%, p < 0.001), ANA (89% vs 80%, p < 0.001), RF (62% vs 47%, p < 0.001) and low C3 levels (19% vs 13%, p < 0.001)
in the multivariate model analysis. Patients with an elderly onset (> 70 years) showed a higher frequency of White ethnicity
(85% vs 75% in aged < 70 yrs, p < 0.001), positive oral tests (82% vs 76%, p = 0.003) and a lower frequency of anti-Ro/La
autoantibodies (62% vs 72%, p < 0.001) and low C3 levels (9% vs 14%, p < 0.001) in the multivariate model analysis.
Conclusion: In the largest reported cohort of primary SS patients diagnosed homogeneously around the world according to
the 2002 AE criteria, we found that primary SS is a disease that can be presented heterogeneously at diagnosis, depending on
specific epidemiologic features such as gender, age and ethnicity.
Disclosure: S. Retamozo, None; P. Brito-Zerón, None; M. Zeher, None; K. L. Sivils, None; R. Seror, None; T. Mandl,
None; X. Li, None; C. Baldini, None; J. E. Gottenberg, None; D. Danda, None; R. Priori, None; L. Quartuccio, None;
G. Hernandez-Molina, None; A. A. Kruize, None; S. K. Kwok, None; M. Wahren-Herlenius, None; S. Praprotnik,
None; D. Sene, None; R. Gerli, None; R. Solans, None; Y. Suzuki, None; D. A. Isenberg, EMD Serono, Inc, 5; M.
Rischmueller, None; G. Nordmark, None; G. Fraile, None; P. Wiland, Celltrion Inc., 2; H. Bootsma, None; T.
Nakamura, None; V. Valim, None; R. Giacomelli, None; V. Devauchelle-Pensec, Roche-Chugai provided me tocilizumab
for the SEMAPHORER study, 2; B. Hofauer, None; M. Bombardieri, GSK, Amgen/MedImmune and UCB, 5; V.
Fernandes Moça Trevisani, None; D. S. Hammenfors, None; S. E. Carsons, None; S. G. Pasoto, None; J. Morel, None;
T. Gheita, None; F. Atzeni, None; C. F. Vollenweider, None; B. Kostov, None; X. Mariette, None; M. Ramos-Casals,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/epidemiologic-subsets-drive-a-

differentiated-clinical-and-immunological-presentation-of-primary-sjogren-syndrome-analysis-of-9302-patients-from-the-
big-data-international-sjogren-cohort
Modification of the Classification Criteria for Primary Sjögren Syndrome:

An International Vignette Survey
Sandrine Jousse-Joulin1, Florence Gatineau2, Chiara Baldini3, Alan N. Baer4, Francesca Barone5, Hendrika Bootsma6,
Simon Bowman7, Pilar Brito Zeron8, Divi Cornec9, Thomas Doerner10, Salvatore De Vita11, Benjamin Fisher12, Daniel S.
Hammenfors13, Malin V. Jonsson14, Xavier Mariette15, Vera Milic16, Hideki Nakamura17, Wan-Fai Ng18, Emmanuel
Nowak2, Manuel Ralos-Casals19, Astrid Rasmussen20, Raphaèle Seror21, Caroline Shiboski22, Takashi Nakamura23, Arjan
Vissink24, Alain Saraux25 and Valérie Devauchelle-Pensec1, 1Rheumatology, Brest university medical school, EA 2216,
UBO and CHU de la Cavale Blanche,, Brest, France, 2INSERM CIC 1412, Brest Medical University Hospital, Brest,
France, 3Internal Medicine, Rheumatology Unit, University of Pisa, Pisa, Italy, 4Medicine (Rheumatology), Johns Hopkins
University School of Medicine, Baltimore, MD, 5Institute of Inflammation and Ageing (IIA), University of Birmingham,
Birmingham, United Kingdom, 6Department of Rheumatology and Clinical Immunology, University of Groningen,
University Medical Centre Groningen, Groningen, Netherlands, 7Department of Rheumatology, University Hospitals
Birmingham NHS Foundation Trust, Birmingham, UK, Birmingham, United Kingdom, 8Autoimmune Diseases Unit,
Department of Internal Medicine, Hospital CIMA-Sanitas, Barcelona, Spain, 9CHU Brest, Brest, France, 10Charité
Universitätmedizin Berlin and DRFZ, Berlin, Germany, 11Rheumatology Clinic, Academic Hospital S. M. della
Misericordia, Medical Area Department, University of Udine, Italy, Udine, Italy, 12Rheumatology Research Group,
University of Birmingham, Birmingham, United Kingdom, 13Broegelmann Research Laboratory, Department of Clinical
Science, University of Bergen, Bergen, Norway, Bergen, Norway, 14Section for Oral and Maxillofacial Radiology,
Department of Clinical Dentistry, University of Bergen, Bergen, Norway, Bergen, Norway, 15Université Paris Sud, Paris,
France, 16Institute of Rheumatology, School of Medicine, University of Belgrade, Belgrade, Serbia, 17Department of
Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, 18Institute
of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom, 19Department of Medicine, University
of Barcelona, Barcelone, Spain, 20Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation,
Oklahoma City, OK, 21Assistance Publique-Hôpitaux de Paris (APHP), Hôpitaux universitaires Paris Sud, Université Paris
Sud, kremlin bicetre, France, 22Department of Orofacial Sciences, School of Dentistry, University of California, San
Francisco, CA, 23Department of Radiology and Cancer Biology, Nagasaki University School of Dentistry, Nagasaki, Japan,
24Department of Oral and Maxillofacial Surgery, University of Groningen, University Medical Center Groningen,
Groningen, Netherlands, 25Rheumatology Department, Rheumatology Department, CHU de la Cavale Blanche, Brest,
France, Brest Cedex, France
SESSION INFORMATION
Background/Purpose:
The common classification criteria sets of primary Sjogren syndrome, did not considered the ultrasonography (US) of the
major salivary glands as a useful item. However, it is well known that US can increase the performance of these two sets.
UTOPIA study (ultrasonography to diagnose and classify pSS) was an international vignette survey undertaken to determine
the accuracy of salivary gland ultrasonography (SGUS) and to add it as a new item in the AECG-2002 and new
ACR/EULAR-2017 classification criteria.
Methods: Twenty four experts in primary Sjogren, from 20 countries participated in the study (22 Europeans from 13
countries, two North Americans and two Japanese). They evaluated on an internet-secure relational database, 512 realistics
vignettes, randomly assigned, abstracted from 150 patients of an Italian cohort (CB). Each vignettes contained items of the
classification criteria and sections on ‘history’ (duration of the symptoms, gender, age), clinical symptoms (dry mouth or
eyes and systemic manifestations) and results of the SGUS evaluation. Each expert has to consider the diagnosis of pSS as
absent, unlikely, likely or present for 64 vignettes. Each vignette was evaluated by 3 experts. The diagnosis of pSS (the gold
standard) was obtained when 2/3 considered it as likely or present. Univariate and multivariate analysis were performed to
evaluate the association of US to the diagnosis of pSS. Data were secondly verified on an independent French cohort
(DiapSS cohort).
Results: The univariate and multivariate analysis confirmed that both classification criteria and SGUS were independently
associated with the diagnosis of pSS (p<0.001). Disease duration, OSS and ocular dryness were not associated with the
diagnosis of pSS. When adding US to the AECG-2002 criteria, the sensitivity (Se) and specificity (Sp) were respectively of
91 % and 83 % and of 98% and 80% if we add US. For the ACR/EULAR 2017 criteria, (with a global score of 4), the Se
and Sp were respectively of 90 % and 84 % and of 95% and 82% if we add US. Results were quite similar in the
independent French DiapSS. The SE and Sp of the ACR/EULAR 2017 were 87.5 and 84.5% and of 92.5 and 82 % with US.
If we considered each items of the vignettes separately to build a new weighted score, only 6 variables were selected by
logistic regression analysis: presence of anti-SSA (weight:4), focus score (weight:4), SGUS (weight:2), Schirmer’s test
(weight:1), dry eye (weight:1) and salivary fow rate (weight:1). According to ROC curve analysis, a score of ≥5 had 96% Se
and 84% Sp, compared with 90% Se and 84% Sp for the ACR/EULAR 2017 Criteria. The corrected C statistic (AUC) for
the new weighted score was 0.98.
Conclusion:
Adding US item to both AECG and ACR/EULAR 2017 classification criteria increased Se but did not change Sp. The
modified scores are easy to use especially the ACR/EULAR 2017.
Disclosure: S. Jousse-Joulin, None; F. Gatineau, None; C. Baldini, None; A. N. Baer, None; F. Barone, None; H.
Bootsma, None; S. Bowman, I have consulted in the field of Sjogren's for: AstraZeneca/Meddimmune, BMS, Celgene, Eli
Lilly, Glenmark, GSK, MTPharma, Novartis, Ono, Takeda, UCB, xtlbio). Roche provided Rituximab for the TRACTISS
Study, 5; P. Brito Zeron, None; D. Cornec, None; T. Doerner, None; S. De Vita, None; B. Fisher, Novartis, Roche,
Virtualscopics, 5; D. S. Hammenfors, None; M. V. Jonsson, None; X. Mariette, None; V. Milic, None; H. Nakamura,
None; W. F. Ng, None; E. Nowak, None; M. Ralos-Casals, None; A. Rasmussen, None; R. Seror, None; C. Shiboski,
None; T. Nakamura, None; A. Vissink, None; A. Saraux, None; V. Devauchelle-Pensec, Roche-Chugai provided me
tocilizumab for the SEMAPHORER study, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/modification-of-the-classification-

criteria-for-primary-sjogren-syndrome-an-international-vignette-survey
Diagnosis of Salivary Gland Lymphoma in Sjogren’s Syndrome Utilizing

Ultrasound-Guided Core Needle Biopsies
Alan N. Baer1, Thomas Grader-Beck1, Brendan Antiochos1, Julius Birnbaum1, Qing Kay Li2, Deborah Belchis2 and Joel
Fradin3, 1Medicine (Rheumatology), Johns Hopkins University School of Medicine, Baltimore, MD, 2Pathology, Johns
Hopkins University School of Medicine, Baltimore, MD, 3Radiology, Johns Hopkins University School of Medicine,
Baltimore, MD
SESSION INFORMATION
Background/Purpose:
Ultrasound (US)-guided core needle biopsy (CNB) with or without concomitant fine needle aspiration (FNA) is a standard
method for pre-operative evaluation of salivary gland tumors. Its application to the diagnosis of salivary gland lymphoma in
patients with Sjogren’s syndrome (SS) has not been evaluated extensively. We sought to review our experience with these
diagnostic techniques in SS patients with suspected salivary gland lymphoma.
Methods:
All patients of the Hopkins Sjogren’s Syndrome Center who underwent an US-guided CNB of a major salivary gland
between 7/1/2009 and 5/30/2017 were identified through a computer database search. Twenty-six such patients had
documented SS at the time of the biopsy and 25 underwent the procedure for evaluation of possible salivary gland
lymphoma. All US-guided procedures were performed by radiologists with extensive experience in these techniques. CNB
and FNA were done under real-time US guidance, using an 18 or 12 MHz linear transducer. The procedures included FNA
at the discretion of the radiologist. FNA was generally done first with cellular material assessed for adequacy by a
cytotechnologist present in the procedure room. The CNBs were obtained with an 18 gauge InRad needle. Patients were
contacted one day after the procedure to assess for complications.
Results:
The indications for CNB included bilateral parotid gland enlargement (n=15), unilateral parotid (n=1) or submandibular
gland (n=1) enlargement, discrete masses in the parotid (n=5) or submandibular (n=2) glands, and a sonographically
abnormal intraparotid lymph node (n=1). The US-guided procedures included CNB in all 25 patients [mean number of CNB
per gland = 2.15 (range, 1-4)], and FNA in 20 patients. Samples were sent for flow cytometry in 24 patients, using material
obtained from CNB alone in 4, CNB and FNA in 18, and FNA alone in 2. Immunohistochemistry (IHC) was performed on 9
CNB samples with a prominent lymphocytic infiltrate. Final pathologic diagnoses were marginal zone lymphoma of
mucosa-associated lymphoid tissue (MALT; n=8), benign lymphocytic infiltrate (n=10), salivary gland tissue without an
inflammatory infiltrate (n=6), and lymphoepithelial cyst (n=1). Flow cytometry revealed a clonally restricted cell population
in 10/24 patients (B cell in 9, plasma cell in 1), of whom 7 were diagnosed with MALT lymphoma based on histopathology,
IHC, and IgH gene rearrangement phenotyping of the B-cells. Flow cytometric samples were comprised of largely debris
and thus without diagnostic utility in 4 patients (despite inclusion of tissue cores in 3); none of these 4 had MALT lymphoma
on final diagnosis. No complications ensued from the procedures.
Conclusion:
US-guided CNB, coupled with flow cytometric analysis from one of the CNB samples and/or FNA, is a safe and effective
method for differentiating benign from malignant lymphoid proliferation of the salivary gland in patients with SS. A clonally
restricted B cell population on flow cytometry is not always indicative of lymphoma and must be corroborated by IHC and
routine histopathologic analysis of CNB samples.
Disclosure: A. N. Baer, None; T. Grader-Beck, None; B. Antiochos, None; J. Birnbaum, None; Q. K. Li, None; D.
Belchis, None; J. Fradin, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/diagnosis-of-salivary-gland-lymphoma-

in-sjogrens-syndrome-utilizing-ultrasound-guided-core-needle-biopsies
Association of Venous Thromboembolism with Spondyloarthopathies Among

Hospitalized Patients – Data from National Inpatient Sample
Dilli Poudel1, Rashmi Dhital2, Raju Khanal2, Pragya Shrestha3, Sijan Basnet2, Sushil Ghimire2 and Paras Karmacharya4,
1Internal Medicine, Reading Health System, WEST READING, PA, 2Internal Medicine, Reading Health System, West
Reading, PA, 3Internal medicine, Reading Health System, West Reading, PA, 4Division of Rheumatology, Mayo Clinic,
Rochester, MN
SESSION INFORMATION
Session Title: Spondyloarthropathies and Psoriatic Arthritis – Clinical Aspects and Treatment I
Background/Purpose: Venous thromboembolism (VTE) encompassing deep venous thrombosis (DVT) and pulmonary
embolism (PE) is the third most common cause of death related to cardiovascular disease following stroke and heart attack.
Studies in the past have shown an increased association with the common inflammatory rheumatological disorders, however
they still remain under-recognized as risk factors for VTE. We examined the risk of VTE among hospitalized
spondyloarthritis patients in a large inpatient US database.
Methods: Using the National Inpatient Sample (NIS) data from 2006-2011, we identified VTE related hospitalizations
(DVT or PE as primary diagnosis) and selected patients with spondyloarthritis, malignancy and osteoarthritis based ICD-9
codes. NIS is the largest publicly available all-payer inpatient care database in US. Discrete cohorts of patients with
spondyloarthropathies (SpA), osteoarthritis (OA), malignancy and control group were created after excluding all
hospitalizations with other common rheumatological diseases such as (RA, SLE, myositis, APS, vasculitis). Univariate and
multivariate logistic regressions (adjusted for age, sex, race, obesity, from nursing home, long bone fractures, prior
malignancy, post-surgery status, DM, CHF, respiratory failure, spinal cord injury, prior VTE, hypercoagulability, smoking,
length of stay ≥ 3 days, calendar year, venous catheterizations and infections) were used to derive odds ratio for measures of
association. SVY function was used in STATA version 13.0 to make weighted estimation for the whole US population.
Results:
Our study included 29,116 hospitalizations (weighted N= 143,650) with spondyloarthritis from 2006-2011. The rates of VTE
related hospitalizations was comparable between SpA and malignancy (1.50 % vs 1.54 %). Adjusted OR of VTE among
patients with SpA was close to that of malignancy ( 1.30 (1.17-1.4) vs 1.31 (1.29-1.33)), while that of osteoarthritis was 0.81
(0.79-0.83) (Table 1).
Conclusion:
It has been shown that inflammation drives thrombosis with imbalance between innate pro-coagulants, anti-coagulants and
fibrinolysis. Alarmingly elevated risk of VTE among inflammatory rheumatological diseases are reported and our study is in
line with the same. We found a relatively high risk of VTE among patients hospitalized with SpA, which was comparable
with that of malignancy (Table 1). This raises an argument as to whether an inflammatory rheumatological disease like SpA
should be considered as an independent risk factor for VTE among hospitalized patients. Given the large, rising burden of
rheumatological diseases and its proven associations with VTE, it appears prudent to include these in the pre-test probability
calculators such as Well’s or other validated scores for VTE. The weightage or score to be given should be guided by future
large, prospective trials.
Estimated weighted
counts and prevalence
Disease Groups Total Cases Cases Rate OR CI p- OR CI p-
without with VTE of Unadjusted value adjusted value
Vte VTE
(%)
Control 136028746 134542591 1,486,155 1.09
Spondyloarthritis 143,651 141,491 2,159 1.50 1.38 1.25 - <0.001 1.25 1.13 - <0.001
1.52 1.39
Psoriatic 82,145 80,856 1,289 1.57 1.44 1.27 - <0.001 1.30 1.14 - <0.001
1.64 1.49
Reactive 2,073 2,050 24 1.13 1.04 0.43 - 0.94 1.68 0.68 - 0.26
2.52 4.14
Enteropathic 3,674 3,637 38 1.02 0.93 0.44 - 0.86 0.71 0.34 - 0.38
1.98 1.5
AS 55,759 54,949 810 1.45 1.33 1.14 - <0.001 1.21 1.03 - 0.018
1.56 1.41
Osteoarthritis 15260121 15103916 156,205 1.02 0.94 0.92 - <0.001 0.78 0.76 - <0.001
0.96 0.8
Cancer 12059300 11873868 185,432 1.54 1.41 1.39 - <0.001 1.39 1.37 - <0.001
1.44 1.41
Total 166534017 164658376 1875641 1.13
Wald 87.3176 P <
Adjusted 0.0001
Chi-Square
Table 1: Proportion and odds of association of Spondyloarthritides with VTE
Disclosure: D. Poudel, None; R. Dhital, None; R. Khanal, None; P. Shrestha, None; S. Basnet, None; S. Ghimire, None;
P. Karmacharya, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/association-of-venous-

thromboembolism-with-spondyloarthopathies-among-hospitalized-patients-data-from-national-inpatient-sample
Tofacitinib Treatment in Patients with Psoriatic Arthritis and Rates of

Radiologic Progression According to Baseline CRP Levels: Results from a
Phase 3 Clinical Study
Désirée van der Heijde1, Dafna D Gladman2, Oliver FitzGerald3, Arthur Kavanaugh4, Daniela Graham5, Cunshan Wang5
and Lara Fallon6, 1Leiden University Medical Center, Leiden, Netherlands, 2Department of Medicine, University of
Toronto, Toronto Western Hospital, Toronto, ON, Canada, 3Department of Rheumatology, St Vincent's University Hospital,
Dublin, Ireland, 4University of California San Diego School of Medicine, La Jolla, San Diego, CA, 5Pfizer Inc, Groton, CT,
6Pfizer Canada, Montreal, QC, Canada
SESSION INFORMATION
Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor under investigation for the treatment of psoriatic arthritis
(PsA). Here, we evaluate radiographic progression in PsA patients (pts) treated with tofacitinib, using data from a global, 12-
month, placebo- and active-controlled, parallel-group Phase 3 study. Pts had an inadequate response to ≥1 conventional
synthetic disease-modifying antirheumatic drug, and were tumor necrosis factor inhibitor‑naïve (OPAL Broaden;
NCT01877668).
Methods: Pts were randomized to receive oral tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID, adalimumab
(ADA) 40 mg subcutaneous once every 2 weeks, or placebo (PBO). Pts who initially received PBO advanced to tofacitinib 5
or 10 mg BID at Month (M)3. Radiographs of the hands and feet at baseline (BL) and M12 were scored independently by 2
assessors using the van der Heijde-modified Total Sharp Score for PsA (mTSS; range 0–528);1 average scores were used.
For radiographs missing at M12, mTSS was calculated by linear extrapolation from an earlier mTSS. Change from BL in
mTSS, erosion and joint space narrowing (JSN) was reported for all pts and pts grouped by BL C‑reactive protein (CRP)
>2.87 mg/L or ≤2.87 mg/L. The proportion of pts with radiographic non-progression (defined as either an increase from BL
in mTSS ≤0.5 or ≤0 and less than the smallest detectable change [SDC; ≤0.66 derived from this trial]) at M12 are reported
for all pts.
Results: Treatment groups were comparable for demographics and BL characteristics (Table 1). Pts in all groups
demonstrated minimal changes from BL in mTSS, erosion, and JSN at M12 (Table 2). Change from BL was similar in pts
with CRP >2.87 mg/L or ≤2.87 mg/L. Radiographic non-progression at M12 using any threshold was observed in >90% of
pts in all groups. At M12, 95.9%, 94.9%, and 97.9% of pts receiving tofacitinib 5 mg BID, tofacitinib 10 mg BID, and ADA,
respectively, were non-progressors based on radiographic changes less than the SDC in mTSS.
Conclusion: Pts with PsA receiving tofacitinib showed minimal mean changes in mTSS at M12, regardless of whether BL
CRP level was >2.87 mg/L or ≤2.87 mg/L. At M12, >90% of pts who received tofacitinib or ADA met all radiographic non-
progression criteria.
1. van der Heijde et al. Ann Rheum Dis 2005;64 Suppl 2:ii61-4.
Disclosure: D. van der Heijde, AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim,
Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer Inc, Regeneron, Roche,
Sanofi, Takeda, UCB, 5,Imaging Rheumatology bv., 9; D. D. Gladman, AbbVie, Amgen, Bristol-Myers Squibb, Celgene,
Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, 2,AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen,
Novartis, Pfizer Inc, UCB, 5; O. FitzGerald, AbbVie, Bristol-Myers Squibb, Novartis, Pfizer Inc, 2,Amgen, Celgene,
Janssen, Lilly, 5; A. Kavanaugh, Pfizer Inc, 9; D. Graham, Pfizer Inc, 1,Pfizer Inc, 3; C. Wang, Pfizer Inc, 1,Pfizer Inc, 3;
L. Fallon, Pfizer Inc, 1,Pfizer Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/tofacitinib-treatment-in-patients-with-

psoriatic-arthritis-and-rates-of-radiologic-progression-according-to-baseline-crp-levels-results-from-a-phase-3-clinical-study

Ustekinumab Is Superior to TNF Inhibitor Treatment in Resolving Enthesitis
in Psa Patients with Active Enthesitis- Results from the Enthesial Clearance
in Psoriatic Arthritis Study
Elizabeth G. Araujo1, Matthias Englbrecht2, Sabrina Hoepken1, Stephanie Finzel3, Axel J. Hueber2, Juergen Rech4 and
Georg Schett1, 1Rheumatology and Immunology, Department of Internal Medicine 3, Universitätsklinikum Erlangen,
Erlangen, Germany, Erlangen, Germany, 2Department of Medicine 3, Rheumatology and Immunology, University of
Erlangen-Nuremberg, Erlangen, Germany, 3Rheumatology and Clinical Immunology, University Medical Center Freiburg,
Freiburg, Freiburg, Germany, 4Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Department of Internal Medicine
3 – Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen, Germany., Erlangen, Germany
SESSION INFORMATION
Background/Purpose: IL-23 is considered to play an important role in the development of enthesitis. Ustekinumab (UST),
a combined inhibitor of IL-12/IL-23 shows efficacy in psoriatic arthritis (PsA), while it has no therapeutic role in diseases
driven by synovitis only such as rheumatoid arthritis. We therefore speculated that inhibition of IL-23 is particularly
effective in enthesitis-driven PsA patients. To compare the efficacy of UST with tumor necrosis factor inhibitor (TNFi)
treatment in clearing enthesitis in PsA patients.
Methods: ECLIPSA is a prospective, observational, open study. Patients with PsA with active enthesitis (at least one painful
enthesis on SPARCC or MASES sites), were consecutively enrolled 1:1, receiving either standard doses of UST (arm 1) or
TNFi (arm 2). At baseline the following parameters were assessed: age, gender, BMI, disease duration, previous DMARDs,
use of corticosteroids, use of non-steroidal anti-inflammatories (NSAIDs), swollen and tender joint count, VAS-pain, VAS-
global, NAPSI, PASI, MASES, SPARCC, LDI, BASDAI, BASFI, HAQ-DI, SF-36, FACIT-F, ESR and CRP. Primary
endpoint was a SPARCC of 0 after 6 months. Patients were seen every 3 months and followed for a total of 6 months. In
order to investigate the effects of study treatment over time we used 2x3 mixed design ANOVA models for both physician’s
and patient’s reported outcomes. Furthermore, exploratory logistic regression was used to predict a SPARCC of 0 at month 6
from baseline PASI, tender joint count, swollen joint count, and FACIT while additionally accounting for age, gender, PsA
duration and study treatment.
Results: 51 patients (UST=25; TNFi= 26) were screened and 47 patients (UST=23; TNFi= 24) were enrolled with 4 patients
not presenting with active enthesitis at baseline. Mean ± SD age was 59.11 ± 12.16 years and mean ± SD disease duration
was 6.4 ± 7.79 years. Mean± SD SPARCC at baseline was 4.9±2.7 in the UST group and 3.8±2.5 in the TNFi group. Other
baseline characteristics were similar between both groups with exception of gender and mental component of the SF-36. In
regards to the effect of study treatment (TNFi vs. UST) and time, the corresponding ANOVAs suggested an important
interaction of both factors for measures of enthesitis (MASES and SPARCC), patient-reported disease activity (HAQ-DI),
and skin activity (PASI), all p≤0.03 with superiority of UST. After 6 months, 17 out of 24 UST patients (70.8%) and 10 out
of 26 TNFi patients (38.4%) reached the primary endpoint defined as clearence of enthesitis (SPARCC=0). Logistic
regression predicting enthesitis-free state of disease according to SPARCC was significantly related to study treatment, with
patients receiving UST being more likely to show no signs of enthesitis at month 6 (OR=0.034; p=0.005). Higher FACIT
scores at baseline were also predictive of an enthesitis free-state (OR=0.864; p=0.024).
Conclusion: These results show that UST is superior to TNFi in resolving the enthesitis component of disease in a
population of PsA patients characterized by active enthesial disease. Based on these data more stratified treatment
approaches can be designed in PsA patients, where enthesitis-driven patients are targeted by IL-23/IL-17 pathway inhibitors.
Disclosure: E. G. Araujo, None; M. Englbrecht, None; S. Hoepken, None; S. Finzel, None; A. J. Hueber, None; J.
Rech, None; G. Schett, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/ustekinumab-is-superior-to-tnf-inhibitor-
treatment-in-resolving-enthesitis-in-psa-patients-with-active-enthesitis-results-from-the-enthesial-clearance-in-psoriatic-
arthritis-study
A New Model of Care for Improving Early Rheumatology Access of Psoriatic

Arthritis Patients
Keith Colaco1,2, Dana Jerome3, Jensen Yeung4,5, Noah Ivers6,7,8, Carol Kitai7, Chandra Farrer3 and Lihi Eder1,9,
1Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada, 2Institute of Medical Science,
University of Toronto, Toronto, ON, Canada, 3Rheumatology, Women's College Hospital, Toronto, ON, Canada,
4Dermatology, Women's College Hospital, Toronto, ON, Canada, 5University of Toronto, Toronto, ON, Canada, 6Institute
for Clinical Evaluative Sciences, Toronto, ON, Canada, 7Women's College Hospital, Toronto, ON, Canada, 8Family and
Community Medicine, University of Toronto, Toronto, ON, Canada, 9Medicine, University of Toronto, Toronto, ON,
Canada
SESSION INFORMATION
Background/Purpose: The prevalence of undiagnosed psoriatic arthritis (PsA) in psoriasis patients is high, with delays in
diagnosis contributing to poor patient outcomes. We aimed to describe a novel model of care involving a self-referral system
and central triage clinic for psoriasis patients with musculoskeletal (MSK) symptoms and to compare the efficacy of several
triage methods for PsA.
Methods: Patients with psoriasis were identified by searching the institutional electronic medical records. These patients
received a letter inviting them to contact the research team if they were experiencing any MSK symptoms. Participants were
assessed in a central triage clinic to determine their likelihood of having PsA. The following triage methods were used: 1)
three PsA screening questionnaires (TOPAS-2, PEST, PASE); 2) MSK ultrasound assessment of symptomatic joints and
entheses; 3) clinical assessment by an advanced practice physiotherapist and 4) levels of CRP and ESR. Each patient was
then assessed by a rheumatologist to determine whether they have PsA. Patients were classified by the rheumatologist to
“Not PsA”, “Possible PsA” or “PsA”. The rheumatologist was blinded to the results of the triage methods. The performance
of each triage method to identify PsA was assessed by calculating its sensitivity, specificity, positive predictive value (PPV),
negative predictive value (NPV) and area under the ROC curve (AUC).
Results: Of the 1159 patients invited to participate, 300 responded (26%) and 152 (13%) agreed to participate. Of the 94
patients assessed thus far in the clinic, 69 (73%) did not have PsA, 17 (18%) had possible PsA, and 8 (9%) had PsA. The
performance of triage methods is presented in Table 1. The advanced practice physiotherapist’s assessment in detecting
clinical PsA was highly sensitive (100%) with good specificity (71%). The screening questionnaires varied by their
sensitivity and specificity with TOPAS-2 showing highest sensitivity (88%) and PASE with highest specificity (87%). The
prevalence of positive MSK inflammation by ultrasound (at least 1 joint or enthesis with positive power Doppler signal) was
39.4%. The sensitivity of positive MSK ultrasound was high (88%) but its specificity was moderate (65%). 22% of the study
participants who had positive MSK ultrasound findings were not classified by the rheumatologist as having PsA. The
performance of CRP and ESR as triage methods was poor.
Conclusion: MSK ultrasound, advanced practice physiotherapist and TOPAS-2 were highly sensitive in identifying patients
with PsA among psoriasis patients with MSK symptoms. A significant proportion of patients with positive MSK
inflammation by ultrasound were not identified as having PsA by the clinician.
Table 1 – Properties of various triage methods in detecting clinical
PsA among patients with psoriasis and musculoskeletal symptoms
Triage Method Sensitivity Specificity PPV NPV AUC

Positive MSK ultrasound 88% 65% 19% 98% 0.76
(Definition 1)
at least 1 joint or entheseal sites

with positive power Doppler
signal
Positive MSK ultrasound 75% 78% 24% 97% 0.77
(Definition 2)
at least 2 joint or entheseal sites

with positive power Doppler
signal
Advanced Practice 100% 71% 24.2% 100% 0.86
Physiotherapist: Positive
assessment
Positive TOPAS-2 88% 65% 19% 98% 0.76
questionnaire
Positive PEST questionnaire 75% 72% 21% 97% 0.74
Positive PASE questionnaire 63% 87% 31% 96% 0.75
Elevated CRP (>5 mg/dL) 43% 84% 19% 94% 0.63
Elevated ESR (Men: >15 43% 78% 15% 94% 0.61
mm/hr, Women: >20 mm/hr)
MSK – Musculoskeletal, TOPAS – Toronto Psoriatic Arthritis Screening,
PEST – Psoriasis Epidemiology Screening Tool, PASE – Psoriatic
Arthritis Screening and Evaluation, CRP – C-Reactive Protein, ESR –
Erythrocyte Sedimentation Rate
Disclosure: K. Colaco, None; D. Jerome, None; J. Yeung, None; N. Ivers, None; C. Kitai, None; C. Farrer, None; L.
Eder, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-new-model-of-care-for-improving-

early-rheumatology-access-of-psoriatic-arthritis-patients
The Risk of Deep Venous Thrombosis and Pulmonary Embolism in

Ankylosing Spondylitis: A General Population-Based Study
Jonathan Chan1, Anthony So2, Eric C. Sayre3 and J. Antonio Avina-Zubieta4, 1Rheumatology, University of British
Columbia, Vancouver, BC, Canada, 2University of British Columbia, Vancouver, BC, Canada, 3Arthritis Research Canada,
Richmond, BC, Canada, 4Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver,
BC, Canada
SESSION INFORMATION
Background/Purpose:
Venous thromboembolism (VTE)(pulmonary embolism [PE] and deep vein thrombosis[DVT]) is a potentially life
threatening disease. Previous hospital-based studies have shown an increased risk of VTE in patients with ankylosing
spondylitis (AS) but limited population-based data are available. We estimated the population-based risk of newly recorded
PE and DVT among incident cases with AS compared with controls from the general population using physician-billing
and hospitalization databases that cover the entire population of the province of British Columbia, Canada (~5 million)
Methods:
Our data includes all visits to health professionals and all hospital admissions from Jan 1, 1996 to Dec 31, 2012 and all
dispensed medications from Sept 1, 1996 to Dec 31, 2012 for all individuals. We conducted a retrospective matched cohort
study of all patients >18 years of age satisfying the following criteria: 1) two ICD-9 or 10 codes (720.0 or M45) for AS at
least two months apart and within a 2-year period by any physician or hospitalization; 2) all AS cases had at least a 7-year
run-in period before the 1st ICD code for AS in order to consider the case as incident. Each AS patient was matched with up
to 10 controls by birth year, sex, and entry cohort time. We excluded cases that were diagnosed with other inflammatory
conditions such as rheumatoid arthritis, vasculitis, myositis, and systemic lupus erythematosus on at least two visits. Ten
non-AS controls matched by birth year, sex, and calendar year of follow-up were selected from the general population for
each case.
Our outcomes were incident PE and DVT events that were recorded from outpatient visits, hospitalizations, or death
certificates. For non-fatal events, we required the use of anticoagulation medications within six-months as part of all
outcome definitions. We estimated relative risks (RRs) by comparing those with AS to age, sex, and entry time matched
comparison cohorts, adjusting for potential known risk factors for VTE.
Results:
Among 7,190 incident cases of AS (51% male, mean age of 46yrs [SD 15.6]), 35, 47, and 69 developed PE, DVT, or both,
respectively (incidence rates= 0.79, 1.06, and 1.56 per 1000 person years, respective) (see table). Compared with age, sex,
and entry time matched controls, the RRs were 1.95 (95% CI; 1.36-2.81), 2.19 (95% CI; 1.60-3.00), and 2.06 (95% CI; 1.59-
2.68) for PE, DVT, and both, respectively. After adjusting for covariates, the results remained similar (see table 1).
Conclusion:
This large population-based study indicates an increased risk of PE and DVT in patients with AS. Our results support the
increased need for awareness and potential monitoring of these complications in AS patients.
Table 1. Relative Risk of Incident PE and DVT according to AS Status

AS Non-AS
N=7,190 N=71,900
PE 7,165 71,775
Cases, N 35 177
Incidence Rate/1000 Person-Years 0.79 0.40
Age-, Sex-, Entry Time-Matched Cox HR (95% CI) 1.95 (1.36, 1.00
2.81)
Glucocorticoid-Adjusted Age-, Sex-, Entry Time- 1.60 (1.09, 1.00
Matched Cox HR (95% CI) 2.34)
Number of Outpatient Visit-Adjusted Age-, Sex-, 1.56 (1.08, 1.00
Entry Time-Matched Cox HR (95% CI) 2.26)
*Fully-Adjusted Age-, Sex-, Entry Time-Matched 1.36 (0.92, 1.00
Cox HR (95% CI) 1.99)
DVT 7,159 71,726
Cases, N 47 218
3.00)
*Fully-Adjusted Age-, Sex-, Entry Time-Matched 1.62 (1.16, 1.00
Cox HR (95% CI) 2.26)
VTE 7,143 71,638
Cases, N 69 336
2.68)
*Fully-Adjusted Age-, Sex-, Entry Time-Matched 1.53 (1.16. 1.00
Cox HR (95% CI) 2.01)
* Fully-adjusted models include the following selected covariates: Glucocorticoid use and number of outpatient visits.
Disclosure: J. Chan, None; A. So, None; E. C. Sayre, None; J. A. Avina-Zubieta, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-risk-of-deep-venous-thrombosis-and-

pulmonary-embolism-in-ankylosing-spondylitis-a-general-population-based-study
Changes in Lipid Levels and Incidence of Cardiovascular Events Following

Tofacitinib Treatment in Patients with Psoriatic Arthritis: An Integrated
Analysis across Phase 3 and Long-Term Extension Studies
Dafna D Gladman1, Christina Charles-Schoeman2, Iain B. McInnes3, Douglas J. Veale4, Bruce Thiers5, Daniela Graham6,
Cunshan Wang6, Thomas Jones7, Robert Wolk6 and Ryan DeMasi7, 1Department of Medicine, University of Toronto,
Toronto Western Hospital, Toronto, ON, Canada, 2University of California, Los Angeles, Los Angeles, CA, 3Glasgow
Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom, 4St. Vincent’s University Hospital and
University College Dublin, Dublin, Ireland, 5Medical University of South Carolina, Charleston, SC, 6Pfizer Inc, Groton, CT,
7Pfizer Inc, Collegeville, PA
SESSION INFORMATION
Background/Purpose: Cardiovascular (CV) disease and cardiometabolic syndrome are common comorbidities/causes of
mortality in patients (pts) with psoriatic arthritis (PsA). Tofacitinib is an oral Janus kinase inhibitor under investigation for
PsA. We investigated changes in lipid levels and incidence of CV events in pts with PsA treated with tofacitinib in Phase (P)
3 and long-term extension (LTE) studies.
Methods: Data were analyzed for pts who received ≥1 dose of tofacitinib 5 or 10 mg BID or placebo (PBO), integrated
across 2 P3 studies (OPAL Broaden [12 months (mo); NCT01877668, including adalimumab control]; OPAL Beyond [6 mo;
NCT01882439]) and 1 LTE study (OPAL Balance [data cut-off May 2016; ongoing, database not locked; NCT01976364]).
Lipid levels were assessed throughout P3 and LTE studies; this analysis included data from the PBO-controlled period (Mo
0–3) of P3 studies. Blood pressure, hypertension events (standardized MedDRA query [narrow]), and adjudicated
(independent/blinded to treatment) major adverse cardiovascular events (MACE) are reported for all pts who received ≥1
dose of tofacitinib, pooled across doses. Incidence rates (IR; pts with events/100 pt-years [PY]) and 95% CI are reported.
Results: Overall, 783 pts (776 PY of tofacitinib exposure) were included in P3 and LTE studies; treatment duration was 1–
927 days. After 3 mo of tofacitinib treatment in P3 studies, dose-dependent increases in lipid levels were observed with
tofacitinib; minimal changes were observed with PBO, except for triglycerides (Fig). Concurrent increases in high-density
and low-density lipoprotein (HDL/LDL) and no change in the total cholesterol/HDL ratio were shown. Across P3 and LTE
studies, no clinically significant changes in systolic or diastolic blood pressure were seen to 24 mo. Hypertension events
were reported in 38 (4.9%) pts: IR 4.93 (95% CI 3.49, 6.77). Of these events, 4 led to pt discontinuation, and 2 were serious
adverse events. MACE were reported for 3 (0.4%) pts receiving tofacitinib (IR 0.38; 95% CI 0.08, 1.11), and included
sudden cardiac death (57 days of exposure at time of event), myocardial infarction (197 days), and ischemic stroke (80
days). This is within the range reported in tofacitinib studies in pts with psoriasis (IR 0.24 [0.15, 0.37]; 8,759 PY of
exposure) and rheumatoid arthritis (RA) (IR 0.38 [0.30, 0.47]; 21,886 PY of exposure). No dose-dependent effects on blood
pressure, hypertension, or MACE were apparent.
Conclusion: In pts with PsA, the magnitude and dose dependency of increases in lipid levels to Mo 3 were consistent with
findings in tofacitinib studies in pts with psoriasis and RA. In P3 and LTE studies, no clinically significant changes were
seen in blood pressure or incidence of hypertension. Incidence of MACE was within the range reported in prior tofacitinib
studies in psoriasis and RA; however, the long latency of MACE requires longer-term observation.
Disclosure: D. D. Gladman, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB,
2,AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, 5; C. Charles-Schoeman,
AbbVie, Bristol-Myers Squibb, Pfizer Inc, 2,Amgen, Pfizer Inc, Regeneron-Sanofi, 3; I. B. McInnes, Celgene, Janssen,
Novartis, Pfizer Inc, Roche, UCB, 2,AbbVie, Celgene, Janssen, Novartis, UCB, 5; D. J. Veale, AbbVie, Actelion, Bristol-
Myers Squibb, Janssen, MSD, Novartis, Pfizer Inc, Roche, UCB, 2,AbbVie, Actelion, Bristol-Myers Squibb, Janssen, MSD,
Novartis, Pfizer Inc, Roche, UCB, 8; B. Thiers, Pfizer Inc, Valeant Pharmaceuticals, 5; D. Graham, Pfizer Inc, 1,Pfizer Inc,
3; C. Wang, Pfizer Inc, 1,Pfizer Inc, 3; T. Jones, Pfizer Inc, 1,Pfizer Inc, 3; R. Wolk, Pfizer Inc, 1,Pfizer Inc, 3; R. DeMasi,
Pfizer Inc, 1,Pfizer Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/changes-in-lipid-levels-and-incidence-

of-cardiovascular-events-following-tofacitinib-treatment-in-patients-with-psoriatic-arthritis-an-integrated-analysis-across-
phase-3-and-long-term-extension-studi
48-Week Complete Remission By Ethnic, Sex and Age Subgroups in Patients

with Active Lupus Nephritis Treated with Voclosporin
David Wofsy1, David A. Isenberg2, Frédéric A. Houssiau3, Mary Anne Dooley4, Neil Solomons5 and Simrat Randhawa6,
1Rheumatology, UCSF, San Francisco, CA, 2Centre for Rheumatology Research, Division of Medicine, University College
London, London, United Kingdom, 3Rheumatology, Pôle de Maladies Rhumatismales, Université catholique de Louvain,
Brussels, Belgium, 4UNC Kidney Centre, Chapel Hill, NC, 5Aurinia Pharmaceuticals Inc., Victoria, BC, Canada, 6Medical
Affairs, Aurinia Pharmaceuticals, Victoria, BC, Canada
SESSION INFORMATION
Session Title: Systemic Lupus Erythematosus – Clinical Aspects and Treatment I: Novel and Current Therapies
Background/Purpose:
Voclosporin (VCS) is a novel CNI with a favorable metabolic profile, no observed effect on electrolytes, and a predictable
dose response potentially eliminating the need for therapeutic drug monitoring.
VCS has completed testing in a global phase II trial, AURA, in patients with active lupus nephritis (LN). In AURA, two
doses of VCS (23.7mg BID, 39.5mg BID) were evaluated vs placebo in a double blind RCT when added on top of MMF
(2g/ day) and a stringent steroid taper.
Methods:
The primary endpoint was 24-week complete remission (CR). However, blinding and randomization were maintained
through 48 weeks permitting further efficacy assessments at 48 weeks. CR required a confirmed UPCR of <0.5 mg/mg,
eGFR >60 ml/min without a decrease of >20% from baseline, low-dose steroids for at least 8 weeks prior to the endpoint
assessment and no administration of rescue medications.
Results:
Previously reported 24-week data showed a statistically significant CR improvement in patients receiving low dose VCS vs
control (32.6% vs. 19.3%; OR: 2.03, p=0.045) and 27.3% in high dose VCS (p=NS). Furthermore, at 24 weeks both doses of
VCS demonstrated statistical superiority over control in partial response (PR, 50% reduction in proteinuria from baseline)
time to CR and time to PR. VCS treatment effect increased at 48 weeks with 49.4% low-dose (OR 3.21, p<.001) and 39.8 %
high dose (OR 2.1, p= .026) VCS patients achieving CR vs 29.6% of control patients. Additionally, all low dose VCS
patients in CR at 24 weeks remained in CR at 48 weeks. More AEs (84% control, 96% high, 91% low) and SAEs (19%
control, 25% high, 28% low) were observed in both VCS arms compared to control. There were 13 deaths (low dose 10,
high dose 2, control 1). All deaths were considered unrelated to VCS treatment by investigators and were consistent with
cause seen in other LN studies. Eleven of thirteen deaths were clustered in sites with compromised access to standard of
care and which disproportionately recruited to the low dose VCS arm. Following completion of study treatment, 3 control
arm patients died while one developed a malignancy. No additional deaths were reported in the low dose VCS arm
following 24 weeks.
We now present a 48-week CR subgroup analysis based on ethnicity, sex and age.
Table 1: 48-week complete remission ethnic, sex and age subgroups

Subgroup Low dose High dose Control CR N
CR%, (OR) CR% (OR) %
White 56.7 (3.64) 50 (2.82) 26.2 108
Asian Indian 59.1 (2.95) 40 (1.35) 33.3 60
subcontinent
Asian other 40 (2.43) 29.2 (1.47) 22.2 72
Other 28.6 (>99) 25 (>99) 0 25
Female 51.3 (3.87) 38.3 (2.2) 21.9 230

Male 38.5 (1.19) 57.1 (2.63) 33.3 35
Age ≤30 44.2 (2.17) 39.2 (1.7) 27 140
Age ≥30 56.8 (4.82) 40.5 (2.5) 21.6 125
Conclusion:
48-week subgroup analysis demonstrates sustained VCS treatment effect that was consistent across subgroups. AURA was
not powered to show statistical significance in these subgroups; however, odds ratios strongly favored low and high dose
VCS across these 8 subgroups. Further data regarding VCS treatment effect in subgroups of patients with active LN will is
currently being generated in the phase III AURORA trial.
Disclosure: D. Wofsy, None; D. A. Isenberg, EMD Serono, Inc, 5; F. A. Houssiau, None; M. A. Dooley, None; N.
Solomons, Aurinia Pharmaceutical, 3; S. Randhawa, Aurinia Pharmaceuticals, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/48-week-complete-remission-by-ethnic-
sex-and-age-subgroups-in-patients-with-active-lupus-nephritis-treated-with-voclosporin
CC-220 Decreases B-Cell Subsets and Plasmacytoid Dendritic Cells in

Systemic Lupus Erythematosus (SLE) Patients and Is Associated with Skin
Improvement: Pharmacodynamic Results from a Phase IIa Proof of Concept
Study
Victoria P Werth1, Richard Furie2, Allison Gaudy3, Ying Ye3, Shimon Korish3, Nikolay Delev3, Douglas Hough3, Michael
Weiswasser3, Suktae Choi3 and Peter Schafer3, 1University of Pennsylvania and the VA Medical Center, Philadelphia, PA,
2Northwell Health, Great Neck, NY, 3Celgene Corporation, Summit, NJ
SESSION INFORMATION
Background/Purpose:
CC-220 is a high affinity ligand for cereblon with immunomodulatory properties, currently in development for the treatment
of Systemic Lupus Erythematosus as well as other autoimmune conditions and multiple myeloma. CC-220 administration
results in significant reductions in ikaros (IKZF1) and aiolos (IKZF3), transcription factors which are genetically linked to
SLE risk, and are overexpressed in the peripheral blood of SLE patients compared to healthy controls.
Methods:
CC-220-SLE-001 is a randomized, double-blinded, placebo-controlled, phase 2a dose escalation study to investigate the
safety, PK, PD, and efficacy of CC-220 in patients with SLE. Forty-two (42) adult SLE subjects fulfilling SLE ACR criteria,
having a history of SLE for ≥6 months and a baseline Safety of Estrogens in Lupus Erythematosus National Assessment–
Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score ≥4. Subjects were randomized to placebo
or 1 of 4 escalating doses of CC-220 (0.3 mg QOD, 0.3 mg QD, 0.6/0.3 mg alternating QD, or 0.6 mg QD). Efficacy
endpoints were exploratory and included Cutaneous Lupus Area and Severity Index (CLASI) skin scores.
Results:
CC-220 significantly reduced total CD20+ B cells, immature B cells, unswitched memory B cells, switched memory B cells,
BAFFR+ B cells, and plasmacytoid dendritic cells (pDC) by as much as 96%, 91.2%, 59%, 81.4%, 67.5%, and 86.5% (Day
85 median percent change from baseline), respectively. CD4+ and CD8+ T cell counts were not significantly affected, but
trended upward, paralleling an increase in plasma cells in those subjects who received the highest dose (0.6 mg). Mean
CLASI activity score at baseline was 9.8 with mean reductions in the CLASI activity score at day 85 ranging from 4.3 to 7.8
in the CC-220 treatment groups compared to an increase of 0.4 in the placebo group. The reductions in CLASI activity score
were even more significant among subjects who had moderate-to-severe skin involvement (CLASI score ≥10 at baseline).
Strong correlations between CLASI improvement and pDC reductions, rather than B cell depletion, were observed in the
overall population and in subjects with a baseline CLASI score ≥10.
Conclusion:
CC-220 reduces B-Cell subset populations and pDCs in SLE subjects. Treatment with CC-220 resulted in improvement on
CLASI score in all treatment groups compared to placebo with strong correlation with pDC depletion. These results support
further development of CC-220 in SLE patient population with skin involvement.
References:
1. Klein R, et al. Arch Dermatol. 2011;147:203-208.
Disclosure: V. P. Werth, Celgene, 2; R. Furie, Celgene, 5; A. Gaudy, Celgene, 3; Y. Ye, Celgene, 3; S. Korish, Celgene, 3;
N. Delev, Celgene Corporation, 3; D. Hough, Celgene, 3; M. Weiswasser, Celgene, 3; S. Choi, Celgene, 3; P. Schafer,
Celgene, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/cc-220-decreases-b-cell-subsets-and-

plasmacytoid-dendritic-cells-in-systemic-lupus-erythematosus-sle-patients-and-is-associated-with-skin-improvement-
pharmacodynamic-results-from-a-phase-iia-proof
A Randomized, Placebo-Controlled, Double-Blind, Ascending-Dose, Safety,

and Pharmacokinetics Study of CC-220 in Subjects with Systemic LUPUS
Erythematosus
Richard Furie1, Victoria P. Werth2, Allison Gaudy3, Ying Ye3, Shimon Korish3, Ada Azaryan3, Nikolay Delev3, Douglas
Hough3, Michael Weiswasser3, Suktae Choi3 and Peter Schafer3, 1Northwell Health, Great Neck, NY, 2University of
Pennsylvania and the VA Medical Center, Philadelphia, PA, 3Celgene Corporation, Summit, NJ
SESSION INFORMATION
Background/Purpose: CC-220 is a CUL4CRBN E3 ubiquitin ligase modulator that binds to cereblon and leads to potent
and deep reduction of the transcription factors Ikaros(IKZF1) and Aiolos (IKZF3), which are overexpressed in the peripheral
blood of Systemic Lupus Erythematosus (SLE) subjects. CC-220 is currently in development for the treatment of SLE as
well as other autoimmune conditions and multiple myeloma. This study evaluated the safety, tolerability and
pharmacokinetics of CC-220 in subjects with SLE. Exploratory efficacy assessments were included.
Methods: Subjects with history of SLE ≥6 months and a baseline of hybrid SELENA-SLEDAI (hSS) score ≥4 were
randomized to 1 of 4 escalating doses of CC-220 or matching placebo (PBO). The 4 active treatments were CC-220 0.3 mg
QOD, 0.3 mg QD, 0.3 mg alternating with 0.6 mg QD, and 0.6 mg QD; subjects were randomized 4:1 active to PBO in each
group for 12 weeks of treatment, followed by 12 weeks of observational follow-up and/or long-term extension. Stable doses
of corticosteroids (≤10 mg prednisone or equivalent daily), non-steroidal anti-inflammatory drugs, and antimalarials were
permitted. Safety assessments included clinical evaluation of adverse events (AEs), laboratory parameters,
electrocardiograms, physical examinations, and overall tolerability. Exploratory efficacy assessments included hSS,
Cutaneous Lupus Area and Severity Index (CLASI) skin scores, Physician Global Assessment (PGA), swollen joint counts
(SJC), and tender joint counts (TJC).
Results: A total of 42 adult subjects were randomized; 39 subjects were female (93%); Mean age was 47.2 years; 64% were
White and 31% were Black or African-American. Mean SLE duration was 9.4 years, with a mean baseline hSS score of 6.6,
CLASI activity score of 9.8, and PGA score of 1.3. Seventy-nine percent of subjects completed the study; 9 of 42 subjects
discontinued, of which 6 subjects discontinued due to an adverse event (AE): 1 in the placebo group and 5 in the 2 highest
CC-220 groups combined. No discontinuations were due to lack of efficacy. Four subjects had serious AEs (highest CC-220
doses: n=2 [pneumonia]; PBO: n=2). Three subjects had neutropenia (grade 3: n=2; grade 1: n=1); 2 subjects in the highest
CC-220 dose group had dermatitis, and 1 subject in the 0.3 mg QD and 1 in the 0.6 mg QD dose groups had urticaria.
Pharmacokinetic evaluation demonstrated dose proportional exposure between cohorts, with moderate accumulation in the
non-alternating dose cohort. An exposure-response analysis demonstrated decreasing B cells, pDCs with increased exposure
to CC-220.
Conclusion: CC-220 was generally well tolerated in this SLE population over 12 weeks of treatment, with neutropenia and
dermatitis observed at the highest doses studied. Treatment with CC-220 resulted in a trend toward greater improvement in
multiple measures of SLE disease activity compared with PBO. These results support further development of CC-220 in
SLE patient population.
Disclosure: R. Furie, Celgene, 5; V. P. Werth, Celgene Corporation, 2; A. Gaudy, Celgene, 3; Y. Ye, Celgene, 3; S.
Korish, Celgene, 3; A. Azaryan, Celgene Corporation, 3; N. Delev, Celgene Corporation, 3; D. Hough, Celgene
Corporation, 3; M. Weiswasser, Celgene, 3; S. Choi, Celgene, 3; P. Schafer, Celgene, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-randomized-placebo-controlled-

double-blind-ascending-dose-safety-and-pharmacokinetics-study-of-cc-220-in-subjects-with-systemic-lupus-erythematosus
Phase 3 Trial Results with Blisibimod, a Selective Inhibitor of B-Cell

Activating Factor, in Subjects with Moderate-to-Severe Systemic Lupus
Erythematosus
Joan T. Merrill1, Renee S. Martin2, William Shanahan2, Morton Scheinberg3, Kenneth C. Kalunian4 and David Wofsy5,
1Oklahoma Medical Research Foundation, Oklahoma City, OK, 2Anthera, Hayward, CA, 3Department of Immunology,
Center for Clinical Immunology, Sao Paulo SP, Brazil, 4Division of Rheumatology, Allergy and Immunology, UCSD School
of Medicine, La Jolla, CA, 5Rheumatology, UCSF, San Francisco, CA
SESSION INFORMATION
Background/Purpose: The Phase 3 CHABLIS-SC1 trial (NCT01395745) evaluated blisibimod, an inhibitor of B-cell
activating factor (BAFF), in SLE. Prior SLE trials suggested that treatments are better distinguished from placebo in patients
with higher disease activity, greater corticosteroid use, anti-double-stranded DNA (dsDNA), low complement1. The
population in this study was enriched for these factors.
Methods: 442 SLE patients on corticosteroids (≤ 0.5 mg/kg or 40 mg) with anti-nuclear antibodies and/or anti-dsDNA and
SELENA-SLEDAI score ≥10 on standard of care medications were randomized to weekly subcutaneous blisibimod (200
mg) or placebo. Patients with renal activity were eligible unless proteinuria exceeded 6 g/24hour or disease severity required
escalation of immunosuppressive therapy. Corticosteroid taper was encouraged from Week 8 with the goal to reach ≤7.5 mg
prednisone/day. The primary endpoint was the Week 52 SLE Responder Index-6 (SRI-6) in the absence of new/increased
immunosuppressives or antimalarials: ≥6-point improvement in SELENA-SLEDAI, no new BILAG 1A or 2B domain
scores, and <0.3-point increase in Physician’s Global Assessment.
Results: At enrollment, the mean SELENA-SLEDAI score and corticosteroid dose was 13.5±4.2 and 15.6±9.1mg,
respectively. The SRI-6 primary endpoint at Week 52 was not met (Figure), and placebo response was greater than reported
in previous studies. More blisibimod-treated subjects achieved corticosteroid taper to prednisone ≤ 7.5 mg/day during Weeks
40-52 and better blisibimod effect was observed under the secondary endpoint which, in addition to meeting SRI-6 criteria at
Week 52, required corticosteroid dose in Weeks 40-52 to be lower than baseline (Figure). Reductions in anti-dsDNA,
significant reductions in peripheral B cell lineages, anti-phospholipid antibodies, and immunoglobulins, and significant
increases in complement C3 and C4 were observed with blisibimod.
In a subgroup of subjects with baseline urinary protein:creatinine ratio (UPCR) ≥0.5 mg/mg, greater decreases in UPCR
from baseline were observed in the blisibimod arm (Figure). At week 52, significantly more subjects who received
blisibimod achieved >50% reduction in UPCR from baseline (59.7 vs 30.8%, p=0.006), and/or UPCR <0.5 (53.2 vs 30.8%,
p=0.02).
Adverse events were balanced between treatment arms except injection/application site reactions which were more common
with blisibimod. None were serious or severe.
Conclusion: This study did not meet its primary endpoint. Blisibimod treatment was associated with successful steroid
reduction, decreased UPCR, and biomarker responses.
References: (1) van Vollenhoven Ann Rheum Dis 2012;71:1343
Disclosure: J. T. Merrill, Anthera, Amgen, EMD Serono, GSK, 5; R. S. Martin, Anthera, 1,Anthera, 3; W. Shanahan,
Anthera Pharmaceuticals Inc, 1,Anthera Pharmaceuticals Inc, 3; M. Scheinberg, Anthera, 5; K. C. Kalunian, Anthera
Pharmaceuticals, 5; D. Wofsy, Anthera, Celgene, GSK, Coherus, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/phase-3-trial-results-with-blisibimod-a-

selective-inhibitor-of-b-cell-activating-factor-in-subjects-with-moderate-to-severe-systemic-lupus-erythematosus
Attainment of Low Disease Activity By Patients with Systemic Lupus

Erythematosus Starting with High Disease Activity in a 24-Week,
Randomized, Placebo-Controlled, Phase IIb Study of Atacicept (ADDRESS
II)
Eric F Morand1, Joan T. Merrill2, Amy H. Kao3, Cristina Vazquez-Mateo3, Stephen Wax4, Peter Chang4, Kishore Pudota3
and David A. Isenberg5, 1Monash University, Melbourne, Australia, 2Arthritis and Clinical Immunology Research Program,
Oklahoma Medical Research Foundation, Oklahoma City, OK, 3EMD Serono Research & Development Institute, Inc. (a
business of Merck KGaA, Darmstadt, Germany), Billerica, MA, 4EMD Serono Research & Development Institute, Inc. (a
business of Merck KGaA, Darmstadt, Germany), BIllerica, MA, 5Centre for Rheumatology, Division of Medicine,
University College London, London, United Kingdom
SESSION INFORMATION
Background/Purpose: Low disease activity (LDA) in lupus patients is increasingly a goal of treatment. For instance,
Lupus Low Disease Activity State (LLDAS) attainment is associated with reduced damage accrual in patients with SLE
(Franklyn et al Ann Rheum Dis 2016). Atacicept targets the B-cell stimulating factors, BLyS and APRIL, and was
associated with reduction of disease activity in SLE patients (pts) starting with high disease activity (HDA; SLEDAI-2K ≥10
at Screening) in the Phase IIb ADDRESS II study. We present a post-hoc analysis of LDA attainment by ADDRESS II pts
who started with HDA.
Methods: In ADDRESS II (NCT01972568), pts received weekly atacicept (75 or 150 mg SC injection) or placebo (PBO)
for 24 weeks (1:1:1 randomization). 3 LDA definitions were used: LDA-1 (SLEDAI-2K ≤ 2); LDA-2 (SLEDAI-2K ≤ 2 and
prednisone-equivalent ≤7.5 mg/day); and LLDAS (SLEDAI–2K ≤ 4 without major organ activity, no new disease activity vs
previous visit, Physician’s Global Assessment ≤1, prednisone-equivalent ≤7.5 mg/day, and stable maintenance doses of
immunosuppressants). Each LDA definition was assessed at each post-baseline study visit. The association of LDA
attainment with SLE responder index (SRI)-6 was explored using descriptive statistics, and differences in LDA attainment
between HDA pts treated with atacicept vs PBO at Week 24 were analyzed using odds ratio (OR) of LDA attainment
estimated from logistic regression.
Results: Of the 306 pts in ADDRESS II, 158 (52%) had HDA at Screening (52 PBO; 55 atacicept 75 mg; 51 atacicept 150
mg). Fig 1 shows the attainment of LDA and SRI-6 response at Week 24: 37 pts (23.4%) achieved LDA-1, 19 (12.0%)
LDA-2, 25 (15.8%) LLDAS and 67 (42.4%) SRI-6 response, irrespective of treatment. Each LDA definition identified a
similar subset of pts, with LDA-2 the most stringent. Of the SRI-6 responders, 64.2% also attained LDA; all except 2 pts
who attained LDA were SRI-6 responders. LDA attainment increased with atacicept dose. Pts who received atacicept 150
mg were more likely to attain LDA at Week 24 vs those who received PBO (LDA-1: OR 3.82 [95% CI 1.44, 10.15],
p=0.007; LDA-2: OR 3.30 [95% CI 0.98, 11.17], p=0.055; LLDAS: OR 5.03 [95% CI 1.32, 19.06], p=0.018; Fig 2).
Conclusion: For pts in the ADDRESS II study starting with high disease activity, LDA attainment was associated with SRI-
6 response. Treatment with atacicept 150 mg vs PBO was associated with a 3- to 5-fold relative increase in the odds of LDA
attainment. These results warrant further evaluation of atacicept in SLE, and suggest that LDA endpoints, including LLDAS,
which has been validated against damage accrual, can be robust outcome measures in future SLE clinical trials.
Disclosure: E. F. Morand, None; J. T. Merrill, Anthera Pharmaceuticals, Lilly, EMD Serono, GlaxoSmithKline and
Biogen., 5; A. H. Kao, EMD Serono, Inc, 3; C. Vazquez-Mateo, EMD Serono, Inc, 3; S. Wax, EMD Serono, Inc., 3; P.
Chang, EMD Serono, Inc, 3; K. Pudota, EMD Serono Research & Development Institute, 3; D. A. Isenberg, EMD Serono,
Inc, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/attainment-of-low-disease-activity-by-

patients-with-systemic-lupus-erythematosus-starting-with-high-disease-activity-in-a-24-week-randomized-placebo-
controlled-phase-iib-study-of-atacicept-address
Synergetic B-Cell Immunomodulation with Rituximab and Belimumab

Combination Treatment in Severe, Refractory SLE
Tineke Kraaij1, Sylvia W.A. Kamerling1, Esther N.M. de Rooij1, Paul L. van Daele2, O.W. Bredewold1, Jaap A. Bakker3,
Ingeborg Bajema4, Hans U. Scherer5, Rene E.M. Toes5, Tom W.J. Huizinga5, Ton Rabelink1, Cees van Kooten1 and Y.K.
Onno Teng1, 1Nephrology, Leiden University Medical Center, Leiden, Netherlands, 2Immunology, Erasmus Medical Center,
Rotterdam, Netherlands, 3Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden,
Netherlands, 4Pathology, Leiden University Medical Center, Leiden, Netherlands, 5Rheumatology, Leiden University
Medical Center, Leiden, Netherlands
SESSION INFORMATION
Background/Purpose:
Neutrophil extracellular traps (NETs) are auto-antigenic DNA strands and potentially give rise to SLE-specific
autoantibodies that can deposit in glomeruli. It has been shown that autoantibodies can induce NETs, contributing to the
vicious circle of immune activation in SLE. We hypothesized that eliminating autoantibodies can lead to decreased NET
induction and thereby ameliorating disease in SLE. Therefore, we designed a proof-of-concept study to eliminate
autoantibodies and NET formation through synergetic B-cell immunomodulation (SynBiose) with rituximab and belimumab
(RTX+BLM) in severe, refractory SLE.
Methods:
We treated patients with severe, refractory SLE in a phase 2 study with RTX+BLM. The primary endpoint assessed
reduction of pathogenic autoantibodies and NET induction at 24 weeks. Anti-dsDNA autoantibodies were measured and
high sensitivity FACS was performed to assess B-cell subsets. NET induction was measured with 3D confocal
immunofluorescence microscopy.
Results:
We included 14 patients with severe, refractory SLE of whom 11 had a renal flare. At 24 weeks we observed significant
reductions in anti-dsDNA autoantibodies (p=0.0015). CD19+ B-cells were depleted throughout the study (p=0.0005) while
plasma cells (PCs) temporarily decreased but returned at week 24 despite persistent depletion of transitional B-cells. Taken
together with the observed reductions of autoantibodies and stable total IgG, there is no reconstitution of autoreactive PCs.
We also observed significant decrease in NET reduction (p=0.0017). In vitro studies elucidated this resulted in reduction of
immune complexes by RTX+BLM. Importantly, the beneficial immunological effects translated to amelioration of clinical
disease activity: SLEDAI decreased from a median of 18 to 2 (p=0.0002). Ten out of 11 LN patients showed a response (4
complete renal responders). The response was achieved while tapering immunosuppressive medication. Treatment was
generally well-tolerated.
Conclusion:
The SynBiose study is the first to demonstrate that RTX+BLM ameliorated disease in severe SLE in association with the
reduction of pathogenic autoantibodies and immune complex-mediated NET induction. Therefore, RTX+BLM represents a
novel treatment concept in SLE.
Disclosure: T. Kraaij, None; S. W. A. Kamerling, None; E. N. M. de Rooij, None; P. L. V. Daele, None; O. W.

Bredewold, None; J. A. Bakker, None; I. Bajema, None; H. U. Scherer, None; R. E. M. Toes, None; T. W. J. Huizinga,
None; T. Rabelink, None; C. van Kooten, None; Y. K. O. Teng, Aurinia Pharmaceuticals, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/synergetic-b-cell-immunomodulation-

with-rituximab-and-belimumab-combination-treatment-in-severe-refractory-sle
Long-Term Efficacy and Safety of Tocilizumab in Patients with Refractory

Takayasu Arteritis Treated Continuously over 52 Weeks: Results from Phase
3, Randomized, Double-Blind, Placebo-Controlled Trial and Open-Label
Extension in Japan
Yoshikazu Nakaoka1, Mitsuaki Isobe2, Syuji Takei3, Yoshiya Tanaka4, Tomonori Ishii5, Shumpei Yokota6, Akira Nomura7,
Seitaro Yoshida7 and Norihiro Nishimoto8, 1Department of Vascular Physiology, National Cerebral and Cardiovascular
Center Research Institute, Osaka, Japan, 2Sakakibara Heart Institute, Tokyo, Japan, 3Pediatrics of Developmental Medicine,
Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan, 4The First Department of
Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan, 5Clinical Research, Innovation
and Education Center, Tohoku University Hospital, Sendai, Japan, 6Laboratory of Pediatric Research, Institute of Medical
Science, Tokyo Medical University, Tokyo, Japan, 7Chugai Pharmaceutical Co., Ltd., Tokyo, Japan, 8Department of
Molecular Regulation for Intractable Disease, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan
SESSION INFORMATION
Session Title: Vasculitis I: Clinical Trials and Outcomes
Background/Purpose: Tocilizumab (TCZ), a humanized anti–IL-6 receptor antibody, showed a favorable trend toward
relapse suppression in patients (pts) with refractory Takayasu arteritis (TAK) in a randomized, double-blind (DB), placebo-
controlled, multicenter trial in Japan (TAKT Study; Arthritis Rheumatol. 2016;68:suppl 10). However, little is known about
the long-term efficacy and safety of TCZ in pts with TAK. Here we present the efficacy and safety of TCZ treatment over 52
weeks (wks) in the DB period and open-label extension (OLE) of the ongoing TAKT Study.
Methods: Pts ≥12 years old with TAK diagnosed according to the Japanese Circulation Society guideline (Circ J.
2011;75:474-503), who had relapsed while receiving oral glucocorticoid (GC; ≥0.2 mg/kg/day prednisolone equivalent)
within the prior 12 wks, were randomly assigned 1:1 to weekly subcutaneous TCZ 162 mg or placebo (PBO) after achieving
remission with oral GC therapy. During the DB period, background GC was tapered by 10%/wk from Wk 4 to a minimum
of 0.1 mg/kg/day. Pts who experienced protocol-defined relapse during the DB period could enter the OLE period to receive
weekly TCZ 162 mg. The DB period ended when relapse of TAK occurred in 19 pts and all pts were eligible to move on to
the OLE period. During the OLE period, background GC doses were adjusted at the investigator’s discretion. All pts were
evaluated for reduction of GC dose and protocol-defined relapse of TAK in long-term treatment of TCZ.
Results: Thirty-six pts were randomized to receive study treatment (18 pts received TCZ and 18 pts received PBO) in the
DB period and all pts entered the OLE period. As of the November 2016 data cut-off, 7 pts had withdrawn from the study
during the OLE period. The median (min–max) total duration of TCZ treatment was 70.4 (8.1–108.0) wks and 31 pts were
treated with TCZ over 52 wks. The median GC dose decreased from 0.22 mg/kg/day at relapse before participation in the
study to 0.13 mg/kg/day at Wk 52 (Figure). Twelve of the 31 pts achieved at least 50% reduction of GC dose and 2 pts were
weaned off GC at Wk 52. Protocol-defined relapse was observed in 8 pts during the OLE period. The exposure-adjusted
relapse rate was 23.6 events per 100 patient-years (PYs) in the OLE period while they were 203.1 events per 100 PYs in the
PBO group and 101.1 events per 100 PYs in the TCZ group in the DB period. In total, 34 (94.4%) pts experienced at least 1
adverse event (AE) while receiving TCZ. The exposure-adjusted AE rate did not increase after the DB period. Serious AEs
were reported in 6 pts (16.7%). Infections were the most frequent AEs (31 pts; 86.1%) and SAEs (2 pts; 5.6%). No new
safety concerns were observed with TCZ throughout the study. No pts died in this study.
Conclusion: Over 52 wks, TCZ exhibited sustained, clinically meaningful, steroid-sparing effects in pts with refractory
TAK. TCZ continued to show a safety profile consistent with that observed with RA/JIA.
Disclosure: Y. Nakaoka, Chugai, Takeda, 2,Chugai, Daiichi Sankyo, MSD, Kowa, 8,Chugai, 5; M. Isobe, None; S. Takei,
Chugai, Eisai, Takeda, Bristol-Myers Squibb, 2,Chugai, Mitsubishi-Tanabe, Pfizer, Ayumi, 8; Y. Tanaka, Mitsubishi-
Tanabe, Takeda, Daiichi-Sankyo, Chugai, Bristol-Myers, MSD, Astellas, Abbvie, Eisai, 2,Abbvie, Chugai, Daiichi-Sankyo,
Bristol-Myers, Mitsubishi-Tanabe, Astellas, Takeda, Pfizer, Teijin, Asahi-kasei, YL Biologics, Sanofi, Janssen, Eli Lilly,
GlaxoSmithKline, 8; T. Ishii, Chugai, Ono, Pfizer, Mitsubishi-Tanabe, Astellas, 8; S. Yokota, Chugai, 5,Chugai, 7; A.
Nomura, Chugai, 3; S. Yoshida, Chugai, 3; N. Nishimoto, Chugai, 2,Chugai, 5,Chugai, 7.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/long-term-efficacy-and-safety-of-

tocilizumab-in-patients-with-refractory-takayasu-arteritis-treated-continuously-over-52-weeks-results-from-phase-3-
randomized-double-blind-placebo-controlled-trial
Health-Related Quality of Life in Patients with Giant Cell Arteritis Treated

with Tocilizumab in a Randomized Controlled Phase 3 Trial
Vibeke Strand1, Sophie Dimonaco2, Katie Tuckwell2, Micki Klearman3, Neil Collinson2 and John H. Stone4, 1Division of
Immunology/Rheumatology, Stanford University, Stanford, CA, 2Roche Products, Ltd., Welwyn Garden City, United
Kingdom, 3Genentech, South San Francisco, CA, 4Massachusetts General Hospital Rheumatology Unit, Harvard Medical
School, Boston, MA
SESSION INFORMATION
Background/Purpose: Superior rates of sustained glucocorticoid (GC)–free remission were shown in patients with giant
cell arteritis (GCA) treated with weekly (QW) or every-other-week (Q2W) subcutaneous (SC) tocilizumab (TCZ) 162 mg +
26-week GC taper (TCZ+26) for 52 weeks compared with placebo + 26-week or 52-week GC taper (PBO+26 or PBO+52)
in a phase 3 randomized controlled trial (GiACTA). Improvements in patient-reported SF-36 Physical Component Summary
(PCS) score and Patient Global Assessment (PtGA) of disease activity were also reported for TCZ vs PBO+52 (Stone JH et
al, N Engl J Med, in press). QW TCZ was recently approved for the treatment of patients with GCA.
Methods: Exploratory analysis of patient-reported outcomes (PROs) was performed in patients treated with QW TCZ+26 (n
= 100) vs PBO+52 (n = 51) for 52 weeks based on observed data. Analyses included mean PROs based on a repeated-
measures model that included all patients and post-escape data. Post hoc exploratory analyses were based on proportions of
patients, and those who withdrew were classified as nonresponders at week 52.
Results: Improvements in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, 6
of 8 domains, and Functional Assessment of Chronic Illness Therapy (FACIT)–Fatigue at week 52 were statistically greater
with QW TCZ+26 than PBO+52 (descriptive p < 0.01; Table, Figure); similar trends were observed vs PBO+26 (not
shown). At week 52, mean scores exceeded age and gender (A/G)–matched normative scores with QW TCZ+26; higher
proportions of patients reported scores ≥A/G norms in SF-36, PCS, MCS, all domains, and FACIT-Fatigue scores (Table).
The median cumulative prednisone dose over 52 weeks was lower with QW TCZ+26 (1862.0 mg) than with PBO+52
(3817.5 mg) (p < 0.0001).
Conclusion: Patients with GCA treated with weekly TCZ 162 mg and a 26-week taper reported greater improvements in
health-related quality of life and fatigue than those treated with a 52-week prednisone taper alone, in part ascribed to lower
prednisone doses.
Disclosure: V. Strand, AbbVie, Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Celltrion, CORRONA,
Crescendo, EMD Serono, Genentech/Roche, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Protagen, Regeneron, Samsung,
Sandoz, Sanofi, UCB, 5; S. Dimonaco, Roche Products Ltd., 1,Roche Products Ltd., 3; K. Tuckwell, Roche, 1,Genentech,
3; M. Klearman, Genentech/Roche, 1,Genentech/Roche, 3; N. Collinson, Roche Products Ltd., 1,Roche Products Ltd., 3; J.
H. Stone, Roche, 2,Roche, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/health-related-quality-of-life-in-patients-

with-giant-cell-arteritis-treated-with-tocilizumab-in-a-randomized-controlled-phase-3-trial
Efficacy and Safety of Belimumab in Combination with Azathioprine for

Remission Maintenance in Granulomatosis with Polyangiitis and Microscopic
Polyangiitis: A Multicenter Randomized, Placebo-Controlled Study
David Jayne1, Daniel Blockmans2, Raashid Luqmani3, Beulah Ji4, Yulia Green5, Leanne Hall6, David Roth7 and Peter A.
Merkel8, 1Vasculitis and Lupus Clinic, Department of Medicine, University of Cambridge, Cambridge, United Kingdom,
2General Internal Medicine, University Hospital Gasthuisberg, Leuven, Belgium, 3Botnar Research Centre, University of
Oxford, Oxford, United Kingdom, 4GSK Stockley Park, Uxbridge, United Kingdom, 5GSK Stockley Park, Stockley Park,
United Kingdom, 6GSK Stevenage, Stevenage, United Kingdom, 7GSK Collegeville, Collegeville, PA, 8Division of
Rheumatology, University of Pennsylvania, Philadelphia, MN
SESSION INFORMATION
Background/Purpose: GPA (Wegener’s) and MPA are organ- and life-threatening systemic vasculitides characterized by
the presence of ANCA-associated vasculitis (AAV), implicating B cells in disease pathogenesis. This study investigated the
efficacy and safety of belimumab (BEL), a monoclonal antibody that inhibits B lymphocyte stimulator, in addition to
standard of care, for the maintenance of remission in AAV following a standard induction regimen.
Methods: This multicenter, double-blind study (BEL115466/NCT01663623) randomized (1:1) patients (≥18 years) with
GPA or MPA in remission (Birmingham Vasculitis Activity Score [BVASv3] = 0 plus prednisolone ≤10 mg/day or
equivalent) following prior induction with CYC or RTX for new or relapsing disease. Patients received azathioprine (AZA)
2 mg/kg/day, and oral glucocorticoids, plus either intravenous BEL 10 mg/kg or placebo (PBO) (Days 0, 14, 28, and every
28 days thereafter until study completion [12 months after last patient randomized]). The primary endpoint was time to first
relapse, defined as ≥1 major BVAS item, total BVAS score ≥6, or receipt of prohibited medications resulting in treatment
failure. Adverse events (AE) were monitored. The study was truncated from 300 to 105 patients due to changes in
conventional treatment practice.
Results: When the study stopped, of 105 patients in the intent-to-treat population, 76 continued for ≥1 year, 21 for ≥2 years,
and 2 for ≥3 years. Baseline data:
There was no significant difference in time to first relapse between treatment groups: adjusted hazard ratio (95% confidence
interval), 1.07 [0.44, 2.59]; p=0.884. Among patients who relapsed (BEL, 10 [19%]; PBO, 11 [21%]), median (range) time
to first relapse was 162 (1–371) days for BEL and 95 (15–789) days for PBO. For patients induced with RTX there were 0/1
relapses classified as vasculitis related in the BEL group versus 3/4 in the PBO group. In CYC-induced patients there were
6/9 versus 5/7 vasculitis relapses, respectively. At the final visit (double-blind) most patients were in remission (BEL, 40
[82%]; PBO, 40 [87%]).
AEs were reported in 49 (93%) BEL and 43 (83%) PBO patients post baseline. The most common AE category was
infection (BEL, 30 [57%]; PBO, 30 [58%]). Serious AEs (SAEs) occurred in 18 (34%) BEL and 16 (31%) PBO patients; the
most common category was infection (BEL, 4 [8%]; PBO, 4 [8%]).
Conclusion: In patients with AAV who were in remission, the addition of BEL to maintenance therapy with AZA and oral
glucocorticoids did not reduce risk of relapse. RTX-induced patients exhibited numerically fewer relapses of vasculitis with
treatment with belimumab compared with placebo, warranting further investigation. Overall relapse rate was low (21/105
[20%]). No new safety signals were identified for BEL in the overall population.
Study funded/conducted by GSK. Editorial assistance: Sam Halliwell, PhD, Fishawack Indicia Ltd, funded by GSK
Disclosure: D. Jayne, None; D. Blockmans, None; R. Luqmani, Arthritis Research UK, GSK, MRC, UCSF/OIF, Canadian
Institutes of Health Research, The Vasculitis Foundation, 2,Roche, GSK, Medpace, MedImmune, 5; B. Ji, GSK, 1,GSK, 3;
Y. Green, GSK, 1,GSK, 3; L. Hall, GSK, 1,GSK, 3; D. Roth, GSK, 1,GSK, 3; P. A. Merkel, Actelion, Alexion, Boston
Pharm., Bristol-Myers Squibb, ChemoCentryx, Genzyme/Sanofi, GlaxoSmithKline, Genentech/Roche, InflaRx,
PrincipioBio, Proteon, Seattle Genetics, 5,Actelion, Bristol-Myers Squibb, CaridianBCT, Celgene, ChemoCentryx,
Genentech/Roche, GlaxoSmithKline, Kypha, MedImmune/AstraZeneca, 2,American College of Rheumatology, European
League Against Rheumatism, National Institutes of Health: NHLBI, NIAMS, NIAID, NCATS, ORDR, US Food and Drug
Administration, The Patient-Centered Outcomes Research Institute, The Vasculitis Foundation, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/efficacy-and-safety-of-belimumab-in-

combination-with-azathioprine-for-remission-maintenance-in-granulomatosis-with-polyangiitis-and-microscopic-
polyangiitis-a-multicenter-randomized-placebo-controll
All Oral Interferon-Free Antivirals for Hepatitis C Virus Cryoglobulinemia

Vasculitis: A Long Term Follow up Multicenter International Study
Patrice Cacoub1, Si Nafa Si Ahmed2, Yasmina FerFar3, SN Pol4, Dominique Thabut5, Christophe Hezode6, Laurent
Albric7, Cloé Comarmond8,9,10, Gafaar Ragab11, Luca Quartuccio12, Mohamed Hegazy13, Thierry Poynard5, Mathieu
Resche-Rigon14 and David Saadoun15, 1Department of Internal Medicine and Clinical Immunology, Groupe Hospitalier
Pitié-Salpêtrière, Paris, France, 2Hôpital Orléans, Orléans, France, 3Internal Medicine, Hopital Pitié-Salpetrière, Paris,
France, 4Department of Hepatology, APHP, Hôpital Cochin, Paris, paris, France, 5Groupe Hospitalier Pitié-Salpétrière,
Paris, France, 6Hôpital Henri Mondor, Creteil, France, 7Centre hospitalier universitaire Purpan, Purpan, France, 8Internal
Medicine and Clinical Imunology, Referal Center for Autoimmune diseases, Internal Medicine and Clinical Imunology,
Hôpital Pitié Salpétrière, Paris, France, 9DHU 2iB Internal Medicine Referal Center for Autoimmune diseases Pitie
Hospital, Paris, France, 10Internal Medicine, Hôpital Pitié Salpétrière, Paris, France, 11Cairo University, Cairo, Egypt,
12University Hospital "Santa Maria della Misericordia, Udine, Italy, 13Faculty of Medicine – Cairo University, Cairo, El
Salvador, 14Hôpital Saint-Louis, Paris, France, 15Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and
Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75005, Paris, France; INSERM, UMR_S 959, F-
75013, Paris, France; CNRS, FRE3632, F-75005, Paris, France; AP-HP, Groupe Hospitalier, Paris, France
SESSION INFORMATION
Background/Purpose: Interferon (IFN) containing regimens used for hepatitis C virus (HCV)-cryoglobulinemia vasculitis
(CryoVas) are poorly effective and associated with important side effects. In small-size and short term studies, direct
antiviral agents (DAAs) have been reported to have a better response rate and tolerance. To evaluate effectiveness and
tolerance of all oral IFN-free regimen in a real life - long term follow up - large cohort of symptomatic HCV-CryoVas
patients.
Methods: 145 patients (57 years, 55% F) presenting symptomatic HCV-CryoVas who received DAAs, i.e. Sofosbuvir (SOF)
plus Ribavirin (n=50), SOF plus Daclatasvir (n=49), SOF plus Ledipasvir (n=23), SOF plus Simeprevir (n=18), or other
DAAs (n=5), for 12 or 24 weeks. Primary efficacy end point was a complete clinical response of CryoVas 12 weeks after
stopping antivirals. Secondary endpoints: (i) sustained virological response (SVR12), (ii) tolerance of antivirals, and (iii)
complete clinical response of CryoVas at the end of follow up.
Results: Baseline HCV-CryoVas features included arthralgia (64%), purpura (57%), neuropathy (58%), and
glomerulonephritis (17%). Forty six (36%) patients had cirrhosis and 70 (48.3%) were naïve of antivirals. At 12 weeks post-
DAAs, 103 (72%) showed a complete clinical response, 33 (23.1%) a partial response and 7 (4.9%) no response of CryoVas
symptoms. Cryoglobulinemia disappeared in 53.1%. SVR12 was obtained in 97.1%. Premature DAAs withdrawal due to
side effects was noted in 6 (4.1%). Main differences between patients with a complete response of the vasculitis (n=103) vs.
partial/no response (n=40) were a severe form of CryoVas (65.1% vs 85%), arterial hypertension (22.3% vs. 45%), type 3
mixed cryoglobulinemia (31.3% vs. 9.1%), and use of immunosuppressant/plasma exchange (36.1% vs. 13.7%). The only
factor that remained independently associated with a poor response was a severe form of CryoVas [OR 0.26, CI95% 0.07-
0.98; P=0.04]. After a median follow-up of 15.3 months, 4 (2.8%) patients died. The 12-months survival rate was 97%
[CI95% 94,100]. At the end of follow up, rates of CryoVas manifestations clearance were skin ulcers (98%), purpura (98%),
renal involvement (92%), arthralgia (87%), neuropathy (78%) and cryoglobulinemia (54%). Rates of CryoVas complete
remission at week12 post-treatment and at the end of follow up were for SOF plus Ribavirin 62% and 70%, SOF plus
Simeprevir 67% and 72%, SOF plus Daclatasvir 78% and 88%, and SOF plus Ledipasvir 87% and 87%, respectively.
Conclusion: Sofosbuvir-based IFN-free DAAs combinations are highly effective in HCV-CryoVas patients in short term and
long term, with a very good tolerance profile.
Disclosure: P. Cacoub, None; S. N. Si Ahmed, None; Y. FerFar, None; S. Pol, None; D. Thabut, None; C. Hezode,
None; L. Albric, None; C. Comarmond, None; G. Ragab, None; L. Quartuccio, None; M. Hegazy, None; T. Poynard,
None; M. Resche-Rigon, None; D. Saadoun, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/all-oral-interferon-free-antivirals-for-

hepatitis-c-virus-cryoglobulinemia-vasculitis-a-long-term-follow-up-multicenter-international-study
Temporal Trends in Incidence and Outcomes of End-Stage Renal Disease Due

to Granulomatosis with Polyangiitis in the US from 1995-2014
Zachary S. Wallace1, Yuqing Zhang2, Leo Lu3, John H. Stone4 and Hyon K. Choi5, 1Division of Rheumatology, Allergy
and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 2Department of Rheumatology,
Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 3Allergy, Immunology,
and Rheumatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 4Massachusetts General
Hospital Rheumatology Unit, Harvard Medical School, Boston, MA, 5Division of Rheumatology, Allergy, and Immunology,
Massachusetts General Hospital, Harvard Medical School, Boston, MA
SESSION INFORMATION
Temporal Trends in Incidence and Outcomes of End-Stage Renal Disease due to Granulomatosis with Polyangiitis in
the US from 1995-2014
Background/Purpose:
Granulomatosis with polyangiitis (GPA) often affects the kidneys, frequently leading to end-stage renal disease (ESRD). The
national trends in the frequency and outcomes of ESRD due to GPA are largely unknown, although these data would provide
important benchmarks in assessing GPA disease burden and care. Our objective was to examine temporal trends in the
incidence and outcomes of ESRD due to GPA.
Methods:
We identified ESRD due to GPA in the US Renal Data System (USRDS) between 1995 and 2014, using nephrologists’ ICD-
9 coding (446.4) for the ESRD etiology. The cohort was divided into four five-year subcohorts based on year of ESRD
onset. Overall and sociodemographic group trends in incidence rates (IRs) were assessed. Changes in rates for mortality,
waitlisting, and transplantation were assessed using Cox-proportional hazards models. We conducted analyses taking into
account the competing risk of death in analyses for the outcomes of waitlisting and transplantation
Results:
Between 1995 and 2014, there were 5,929 incident cases. The annual incidence rate increased over the study period (P-for-
trend <0.0001). The incidence rate of death (per 1,000 patient-years) declined from 19.0 (17.2-21.1) to 15.3 (14.0-16.7,
P<0.0001) with a corresponding adjusted HR of 0.77 (95% CI, 0.67-0.89). The log-rank test also showed significant
improvement in survival during the study period (P=0.03) (Figure 1). Adjusted HRs for death were 1.0, 0.90, 0.82, and 0.77
for the 1995-1999, 2000-2004, 2005-2009, and 2010-2014 sub-cohorts, respectively (P-for-trend = 0.005). Accounting for
competing risk, there was a 70% increase in the risk of being waitlisted for transplant (adjusted HR for 2010-2014, vs 1995-
1999 = 1.7, 95% CI, 1.38-2.11), whereas the risk for transplantation decreased by 30% (corresponding adjusted HR = 0.70,
95% CI, 0.53-0.93).
Conclusion:
The burden of ESRD due to GPA has increased in the US over the past two decades, which is likely related to overall
improvements in GPA survival. During the same period, survival of patients with GPA ESRD has improved, although the
likelihood for being waitlisted for a transplant is rising with access to renal transplantation becoming more limited. With
5,929 GPA ESRD patients included, this is the largest AAV study to date in the literature.
Figure 1: Kaplan-Meier Curve of Overall Survival in ESRD due to GPA (1995-2014)

Disclosure: Z. S. Wallace, None; Y. Zhang, None; L. Lu, None; J. H. Stone, Xencor, 2; H. K. Choi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/temporal-trends-in-incidence-and-

outcomes-of-end-stage-renal-disease-due-to-granulomatosis-with-polyangiitis-in-the-us-from-1995-2014
The Steroid Tapering in ANCA Vasculitis Evaluation Study (STAVE) 2: A

Systematic Review and Meta-Analysis
Jennifer Rodrigues1, David Collister1, Amy Archer2, Kim Cheema3, Paul Alexander4, Christian Pagnoux5, Lehana
Thabane4, Peter A. Merkel6, David Jayne7 and Michael Walsh1, 1Nephrology, McMaster University, Hamilton, ON,
Canada, 2Rheumatology, Northwestern University, Chicago, IL, 3Nephrology, University of Calgary, Calgary, AB, Canada,
4Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada, 5Division of
Rheumatology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada, 6Division of Rheumatology, University
of Pennsylvania; Perelman School of Medicine, Philadelphia, PA, 7Vasculitis and Lupus Clinic, Department of Medicine,
University of Cambridge, Cambridge, United Kingdom
SESSION INFORMATION
Background/Purpose: Relapses of ANCA-associated vasculitis (AAV) are associated with death, decreased renal function,
and end-stage renal disease. Whether longer-term treatment with glucocorticoids (GC) reduces the risk of relapse is
unclear. The objective of this study was to determine the association between dosages of GC and relapse in patients with
AAV and update a previous meta-analysis with long-term follow-up and trials with rituximab.
Methods: MEDLINE, EMBASE, Cochrane Clinical Trials, and the Grey Literature were searched from January 1, 2008
until May 26, 2016 without language restriction for studies with patients with AAV. Studies were included if duration of GC
use was specified a priori and patients were followed for a minimum of 18 months. Both randomized controlled trials
(RCT) and prospective cohort studies were included. Quality of evidence was assessed using modified Newcastle-Ottawa
criteria. Meta-analysis was completed using a random-effects model of DerSimonian and Laird.
Results: Twenty-four studies met inclusion criteria consisting of 2272 patients. Thirteen (54%) discontinued GC in less than
one year. All patients received additional non-GC immunotherapy for induction of remission and 3 studies (<10% of
patients) included patients receiving only GC as maintenance therapy. The pooled relapse rate was 14.3 per 100 patient
years (95% CI 4.5, 24.0). Relapse was more frequent when discontinuation of GC at any time was compared to long-term,
low-dose GC (20.7 per 100 patient years, 95% CI 6.8,34.5 as compared to 8.0 per 100 patient years, 95% CI 5.7,21.7).
Multivariable linear meta-regression confirmed that long-term, low-dose GC was associated with lower relapse rates (b =
-0.16, 95% CI -0.26,0.07, P = 0.001) and overall follow up time was associated with increased relapse rates (b = 0.003, 95%
CI 0.001,0.006, P = 0.002). Time to discontinuation of non-GC immunotherapy, time to GC discontinuation, study type,
renal function, presence of relapsing disease at baseline, and immunotherapy that included oral cyclophosphamide did not
demonstrate any significant association with relapse rates.
Conclusion: Long-term, low-dose GC is associated with decreased relapse rates in patients with AAV. The clinical severity
and consequences of the excess relapses are not well studied. Characterization and reporting of adverse events limited
analysis. These data have implications for both clinical care and trial design. RCTs are needed to determine optimal GC
administration in patients with AAV.
Figure Legend: Random effects meta-analysis of long-term, low dose GC as compared to GC discontinuation on relapse
per patient year. CYC = cyclophosphamide, MTX = methotrexate, IV = intravenous, PO = oral, MMF = mycophenolate
mofetil, AZA = azathioprine, LEF = leflunomide, RTX = rituximab, PLEX = plasma exchange, C = continuation arm, WD =
withdrawal arm.
Disclosure: J. Rodrigues, None; D. Collister, None; A. Archer, None; K. Cheema, None; P. Alexander, None; C.
Pagnoux, None; L. Thabane, None; P. A. Merkel, Actelion Pharmaceuticals US, Bristol-Myers Squibb, CaridianBCT,
Celgene, ChemoCentryx, Genentech/Roche, GlaxoSmithKline, Kypha, MedImmune/AZ, 2,American College of
Rheumatology, European League Against Rheumatism, Hational Institutes of Health, US Food and Drug Administration,
The Patient-Centered Outcomes Research Institute, The Vasulitis Foundation, 2,Actelion Pharmaceuticals US, Alexion,
Boston Pharm, Bristol-Myers Squibb, ChemoCentryx, Genzyme/Sanofi, GlaxoSmithKline, Genentech/Roche, InflRx,
PrincipioBio, Proteon, Seattle Genetics, 5; D. Jayne, None; M. Walsh, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-steroid-tapering-in-anca-vasculitis-

evaluation-study-stave-2-a-systematic-review-and-meta-analysis
Cutaneous Lupus Is Driven By an Exaggerated Interferon Kappa Loop

Which Primes for Interferon Alpha Responses
Johann Gudjonsson1, Mrinal Sarkar1, Alex Tsoi2, Celine C. Berthier3, Grace Hile4, Yun Liang4, Jianhua Liu5, Paul Harms6
and J. Michelle Kahlenberg7, 1Dermatology, University of Michigan, Ann Arbor, MI, 2Departments of Dermatology and
Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 3Nephrology, Division of
Nephrology, University of Michigan Medical Center, Ann Arbor, MI, 4University of Michigan, Ann Arbor, MI, 5Internal
Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI, 6Pathology, University of Michigan, Ann
Arbor, MI, 7Internal Medicine, Division of Rheumatology, University of Michigan Medical Center, Ann Arbor, MI
SESSION INFORMATION
Session Title: 2017 Rheumatology Research Foundation Edmond L. Dubois, MD Memorial Lecture
Background/Purpose: Cutaneous inflammation is a common and disfiguring manifestation for 70% of patients with
systemic lupus erythematosus, yet our understanding of the pathogenesis of cutaneous lupus erythematosus (CLE) has
lagged. Type I IFN signatures are elevated in CLE lesions and contribute to pathology. However, the source of type I IFN
production and the function of type I IFNs in CLE has not been examined. We thus investigated the sources of type I IFN in
CLE and examined the role of keratinocyte-produced IFN kappa to prime for type I IFN responses in keratinocytes.
Methods: 90 biopsy-proven CLE patients were examined for type I IFN expression using Affymetrix ST2.1 microarray.
Tissue expression of IFNs was confirmed with immunofluorescence microscopy. Primary keratinocytes were grown from
biopsies of non-lesional, non-sun exposed skin from healthy controls and patients meeting >4 ACR SLE criteria with a
history of documented CLE. IFN activation was examined using real-time PCR and Western blot. IFN kappa knockout
keratinocyte lines were made using CRISPR/cas9-mediated deletion.
Results: Analysis of CLE lesions confirmed heightened type I IFN responses and demonstrated IFNK as one of only two
increased type I IFN transcripts in CLE lesions vs. control skin. IFN kappa was expressed predominantly in the basal
keratinocyte layer in both healthy skin and lesional CLE, but its expression was increased in CLE lesions and in non-lesional
SLE keratinocytes. Importantly, IFN kappa was required for basal type I IFN responses in keratinocytes. Indeed, absence of
IFNK resulted in minimal type I IFN gene expression and a delayed response to exogenous type I IFN stimulation. In
contrast, IFN kappa overexpression accelerated and amplified responses to exogenous IFN alpha in a IFN kappa dependent
manner.
Conclusion: IFN kappa is a key regulator of IFN responses in keratinocytes. In SLE and CLE, keratinocytes are primed by
an abundance of IFN kappa to generate robust responses to exogenous type I IFNs, setting up a feed forward loop which
promotes exaggerated IFN responses and subsequent activation of the immune system. Thus, IFN kappa may serve as an
excellent and specific target for treatment and prevention of cutaneous inflammation in SLE patients.
Disclosure: J. Gudjonsson, None; M. Sarkar, None; A. Tsoi, None; C. C. Berthier, None; G. Hile, None; Y. Liang,
None; J. Liu, None; P. Harms, None; J. M. Kahlenberg, Idera Pharmaceuticals, Celgene, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/cutaneous-lupus-is-driven-by-an-
exaggerated-interferon-kappa-loop-which-primes-for-interferon-alpha-responses
B Cell Specific TLR9 Suppresses Disease in Murine Lupus

Jeremy Tilstra1, Rachael Gordon2, Shinu John3, Brady Marburger2, Sheldon Bastacky4, Kevin Nickerson2 and Mark
Shlomchik5, 1Rheumatology, Univ of Pittsburgh Medical Center, Pittsburgh, PA, 2University of Pittsburgh, Pittsburgh, PA,
3Moderna Therapeutics, Cambridge, MA, 4Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA,
5Immunology, University of Pittsburgh, Pittsburgh, PA
SESSION INFORMATION
Background/Purpose:
Toll-like receptor (TLR) signaling is a central to lupus pathogenesis. GWAS studies have repeatedly identified components
of TLR signaling pathway in SLE patients. Furthermore, the endosomal TLRs, 7 and 9, have been implicated in numerous
murine models of SLE. Despite being a “pro-inflammatory” innate immune receptor, TLR9 deficiency in lupus prone
MRL.Faslpr mice exacerbates clinical manifestations including reduced lifespan and more severe nephritis, despite lacking
anti-nucleosome (anti-DNA) antibodies; while TLR7 deficiency dominantly ameliorates disease. Similar regulatory roles for
TLR9 have been identified in multiple other lupus models. The mechanisms by which TLR9 suppresses rather than
promotes autoimmunity are unclear. We hypothesized that TLR9 has cell-specific functions.
Methods:
We created two novel murine strains: a conditional TLR9 knock-out (Tlr9flox) and a conditional TLR9 overexpression allele
(rosa26-flox-stop-Tlr9). These strains were both fully backcrossed onto lupus prone backgrounds MRL.Faslpr (MRL/lpr) and
B6.Yaa.FcgR2b-/-. The Tlr9flox allele was crossed several different cre allelles; including CD19-cre (B cell specific), CD11c-
cre (DC specific), MRP8-cre (neutrophil specific), and LysM-cre (macrophage and neutrophil targeting) to assess for cell
specific roles of TLR9. Cell specific deletion was assessed using cell sorting and qPCR of genomic DNA. These cohorts
were analyzed for disease pathology including proteinuria, renal histology, dermatitis, ANA, and immune cell activation.
Results:
Strikingly, of all the strains tested only B-cell specific deletion of TLR9 exacerbated disease, similar to what was observed
in the complete knockout, exhibiting increased proteinuria (p<0.05) and nephritis (p<0.05) with loss of anti-DNA antibodies
(p<0.001). DC, macrophage and neutrophil cell specific deletion of TLR9 did not result in alteration of pathology. Given the
positive results in the B cell specific deletion. We then performed the reciprocal experiment using the TLR9 overexpression
allele which results in a 2 fold overexpression of TLR9 in B cells with a concomitant increase in function. When TLR9 was
overexpressed only in B cells, we found that disease was ameliorated in two models of SLE, MRL.Faslpr and
B6.Fcgr2b-/-.Yaa,. In both models, there was reduced renal disease including proteinuria (p<0.05) and glomerulonephritis
(p<0.05); however, there were minimal alterations in tested anti-RNA and anti-DNA autoantibodies.
Conclusion:
These data, in which we manipulate TLR9 expression in both directions, indicate B cell expression of TLR9 accounts for a
substantial proportion of the known TLR9 regulatory effect. Additionally we have effectively ruled out a role for TLR9 in
numerous other hematopoietic cell types. The data further suggests that anti-DNA antibodies either play no role or are
protective in SLE pathogenesis in these murine models, thus going against the conventional wisdom in the field. To our
knowledge this is the first data to show that TLR9 overexpression can be protective, and given its significant ameliorative
effect, TLR9 overexpression in B cells alone may represent a potential therapeutic strategy.
Disclosure: J. Tilstra, None; R. Gordon, None; S. John, None; B. Marburger, None; S. Bastacky, None; K. Nickerson,
None; M. Shlomchik, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/b-cell-specific-tlr9-suppresses-disease-

in-murine-lupus
Neutrophil Gene Signature and Low Density Granulocyte Subsets Associate

with Coronary Plaque Burden and Vascular Inflammation in Systemic Lupus
Erythematosus
Philip Carlucci1, Monica Purmalek1, Simantini Sakhardande1, Yenealem Temesgen-Oyelakin1, Amit K. Dey2, Aditya A.
Joshi2, Joseph B. Lerman3, Alice Fike1, Michael Davis4, Hong-Wei Sun1, Jonathan H. Chung2, Martin P. Playford2,
Pragnesh Mistry1, Gustavo Gutierrez-Cruz1, Stefania Dell'Orso1, Faiza Naz1, Heather Teague2, Zerai G. Manna5, Peter C.
Grayson1, Mohammad Naqi1, Marcus Chen2, Sarfaraz A. Hasni1, Nehal N. Mehta2 and Mariana J. Kaplan1, 1NIH/NIAMS,
Bethesda, MD, 2NIH/NHLBI, Bethesda, MD, 3NIH/CC, Bethesda, MD, 4NIH/NIAMS, Bethesda, IA, 5NIH/NIAMS,
Bethesda, MD, Afghanistan
SESSION INFORMATION
Background/Purpose: Systemic lupus erythematosus (SLE) increases a young woman’s risk of myocardial infarction by up
to 50-fold. This marked increase in cardiovascular disease (CVD) risk is not explained by Framingham risk and is not well
understood. It has been suggested that innate immune responses associated with aberrant neutrophils, known as low density
granulocytes (LDGs), enhance CVD risk by promoting vascular damage due to their proinflammatory properties. LDGs may
represent a heterogeneous population of neutrophils and the pathogenicity of various LDG subsets has not been
characterized. In this study, we sought to explore the association of these cells with subclinical vascular disease.
Methods: SLE patients fulfilling ACR criteria and healthy controls underwent FDG-PET/CT scans to assess vascular
inflammation as target-to-background ratio (TBR) and coronary CT angiogram for coronary plaque characterization. Total
and non-calcified plaque burden were quantified using QAngio. Circulating LDGs and cholesterol efflux were measured by
previously validated methods. RNA sequencing of whole blood was used to analyze the transcriptional profile of both
patients and controls. A neutrophil gene signature was created by calculating a z-score for the most upregulated primary
granule neutrophil genes (AZU1, MPO, CTSG, PRTN3, ELANE, DEFA3) found in patients with cardiovascular involvement.
Results: Compared to controls, SLE patients had significantly elevated aortic TBR (1.68±0.16 vs.1.59±0.14, p=0.007) and
coronary non-calcified plaque burden (NCB) (0.86±0.33 vs. 0.76±0.19, p=0.022). We identified diverse subsets of LDGs
based on maturation. The percentage of an immature subset of LDGs was significantly elevated in peripheral blood
mononuclear cells in patients compared to controls (1.6 (3.2-0.47) vs. 0.35 (0.96-0.13), p<0.001). This immature subset
associated with the primary granule neutrophil gene signature (β=0.844, p<0.001), TBR (β=0.34 p=0.015), and with NCB
(β=0.31, p=0.001) in unadjusted analyses. The neutrophil gene signature also associated with NCB (β = 0.44, p<0.001). In
addition, a mature subset of LDGs was present in SLE, which associated with TBR (β=0.23, p=0.02), NCB (β=0.31,
p=0.002), and HDL efflux (β=-0.29, p=0.024), supporting previous work that suggests the enhanced neutrophil extracellular
trap formation in mature LDGs impairs HDL efflux. These associations persisted after adjusting for traditional risk factors in
multivariate analyses.
Conclusion: Patients with SLE have an increase in both aortic vascular inflammation and coronary plaque burden compared
to controls. The associations of aberrant neutrophil subsets with this atherosclerotic phenotype support studies suggesting a
pathogenic role for these cells in assaulting the vasculature and that targeting responses triggered by these cells may have
potential therapeutic benefits.
Disclosure: P. Carlucci, None; M. Purmalek, None; S. Sakhardande, None; Y. Temesgen-Oyelakin, None; A. K. Dey,
None; A. A. Joshi, None; J. B. Lerman, None; A. Fike, None; M. Davis, None; H. W. Sun, None; J. H. Chung, None; M.
P. Playford, None; P. Mistry, None; G. Gutierrez-Cruz, None; S. Dell'Orso, None; F. Naz, None; H. Teague, None; Z.
G. Manna, None; P. C. Grayson, None; M. Naqi, None; M. Chen, None; S. A. Hasni, None; N. N. Mehta, None; M. J.
Kaplan, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/neutrophil-gene-signature-and-low-

density-granulocyte-subsets-associate-with-coronary-plaque-burden-and-vascular-inflammation-in-systemic-lupus-
erythematosus
Choroid Plexus Tertiary Lymphoid Structures in Lupus: A Novel Neuro-

Immune Interface
Ariel Stock1, Evan Der2, Sivan Gelb3, Ayal Ben-Zvi3 and Chaim Putterman4, 1Microbiology and Immunology, Albert
Einstein College of Medicine, Bronx, NY, 2Albert Einstein College of Medicine, Bronx, NY, 3Hebrew University,
Jerusalem, Israel, 4Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY, USA, Bronx, NY
SESSION INFORMATION
Background/Purpose: The central nervous system (CNS) manifestations of SLE remain poorly understood. Although
potentially neuropathic autoantibodies have been identified in the serum, lupus patients show inconsistent correlations
between these and neuropsychiatric SLE (NPSLE). This is likely due to the highly restrictive nature of the blood brain
barrier and the variability between patients in barrier dysfunction and humoral immune transmission into the CNS.
Methods: We used the MRL/MpJ-Faslpr/lpr mouse, a well-established model of lupus associated neuropsychiatric deficits,
to evaluate the immune effectors responsible for CNS disease. We performed RNA sequencing, immunofluorescent
phenotyping, and light and electron microscopy of brain tissue to identify signaling pathways and cellular contributors to
NPSLE.
Results: We found extensive cellular infiltrates in the MRL/MpJ-Faslpr/lpr choroid plexus by 16 weeks of age, when these
mice display profound cognitive deficits and depression like behavior (Figure 1). Transcriptome analysis of the choroid
plexus revealed an expression signature driving tertiary lymphoid structure (TLS) formation, including elevated Cxcl13,
Lta/b (lymphotoxin α/β), Ccl19, and a host of other cytokines and chemokines related to lymphoid organization.
Additionally, gene ontology assessment revealed transcriptional profiles closely related to various stages of lymphocyte
activation and germinal center formation. Immunofluorescent evaluation of the choroid plexus defined the cellular infiltrate
in NPSLE mice to include locally proliferating B and T cells, extensive T-cell activation, and evidence of in-situ somatic
hypermutation and class switch recombination and IgG+ plasma cells. Finally, the choroid plexus was found to be important
in trafficking lymphocytes into the CNS, as evidenced by the routine presence of intra-epithelial lymphocytes on
transmission electron microscopy. Evaluation of human lupus choroid plexus tissue is in progress.
Conclusion: Collectively, we not only determined a potential new pathway underlying neuropsychiatric lupus, we identified
TLS formation in the choroid plexus as a novel mechanism through which the immune system may bypass the blood brain
barrier.
Disclosure: A. Stock, None; E. Der, None; S. Gelb, None; A. Ben-Zvi, None; C. Putterman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/choroid-plexus-tertiary-lymphoid-

structures-in-lupus-a-novel-neuro-immune-interface
Role of Epstein Barr Virus Serologic Reactivation in Transitioning to

Systemic Lupus Erythematosus in at Risk Individuals
Neelakshi R. Jog1, Kendra A. Young2, Melissa E. Munroe1, Michael T Harmon3, Joel M. Guthridge4, Diane L. Kamen5,
Gary S. Gilkeson6, Michael Weisman7, David Karp8, John B. Harley9,10, Daniel J. Wallace11, Jill M. Norris12 and Judith A.
James13,14, 1Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma
City, OK, 2Epidemiology, Colorado School of Public Health, Aurora, CO, 3Arthritis and Clinical Immunology Program,
Oklahoma Medical Research Foundation, Oklahoma City, OK, 4Arthritis and Clinical Immunology Program, Oklahoma
Medical Research Foundation, OKC, OK, 5Medicine/Rheumatology & Immunology, Medical University of South Carolina,
Charleston, SC, 6Department of Medicine, Medical University of South Carolina, Charleston, SC, 7Rheumatology, Cedars-
Sinai Medical Center, Los Angeles, CA, 8Rheumatology, UT Southwestern Med Ctr, Dallas, TX, 9US Department of
Veterans Affairs Medical Center, Cincinnati, OH, 10Cincinnati Children's Hospital Medical Center, Cincinnati, OH,
11Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, 12Department of Epidemiology, Colorado
School of Public Health, Aurora, CO, 13Arthritis & Clinical Immunology Program, Oklahoma Medical Research
Foundation, Oklahoma City, OK, 14Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma
City, OK
SESSION INFORMATION
Background/Purpose: Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease characterized by

autoantibody production and periods of elevated and suppressed disease activity. Various genetic and environmental factors
likely contribute to disease pathogenesis. Epstein Barr Virus (EBV) is an environmental factor consistently associated with
SLE. EBV maintains latency in B cells and shows frequent reactivation, which can be measured indirectly in terms of
antibodies to EBV antigens. In this study we determined whether antibody measures of viral reactivation and single
nucleotide polymorphisms (SNPs) in EBV associated genes were associated with transitioning to SLE in at risk individuals.
Methods: Blood relatives (n=436) of SLE patients who did not meet ACR SLE classification criteria at baseline were
evaluated an average of 6.3 (± 3.9) years later. At both baseline and follow-up, detailed demographic, environmental,
clinical information, and blood samples were obtained. 56 individuals (13%) transitioned to SLE (> 4 cumulative ACR
criteria) as verified by protocoled medical record review. Healthy, matched, unrelated individuals (n=122) were recruited at
local health fairs. To assess evidence of viral exposure/reactivation, antibody responses against the EBV antigens Viral
Capsid Antigen (VCA) and early antigen (EA) and Cytomegalovirus (CMV) were measured by ELISA. 5 SNPs in IL10, 1 in
complement receptor 2 (CR2) and 3 in CD40 gene were typed by Immunochip. Generalized estimating equations (GEE),
accounting for correlation within families, were used to test associations between the viral antibody variables and the
categorical outcome of transitioning to SLE. Associations between SNPs, seroconversion and disease transition were
examined in an additive model. Interactions between SNPs and antibody titers were examined.
Results: Higher proportion of individuals who transitioned to SLE were positive for anti EA IgG at baseline compared to
healthy controls (37.5% vs 12.7%, p=0.0005). Mean baseline anti VCA and EA IgG levels were significantly different
between those family members who transitioned to SLE and those who did not (4.88±1.80 vs 4.18±2.83; p=0.007; 1.19±1.11
vs 0.88±0.76; p=0.008 respectively). Increased levels of VCA IgG and EA IgG were associated with transitioning to SLE
when compared to healthy controls (OR 1.05, 95%CI 1.01-1.10; OR 1.18, 95%CI 1.09-1.26 respectively). VCA IgG, EA
IgG and CMV IgG positively correlated with number of autoantibody specificities and ACR scores at both baseline and
follow-up visits. Significant interaction was observed between SNPs in CD40 and VCA IgG and between SNPs in IL10 and
VCA IgA in transitioning to SLE.
Conclusion: Elevated EA IgG and VCA IgG were associated with transitioning to SLE in unaffected SLE relatives,
suggesting that viral reactivation may contribute to development or worsening of SLE autoimmune responses. To our
knowledge, this is the first prospective study examining the pre-clinical association between serologic measures of EBV
reactivation and SLE disease transition.
Disclosure: N. R. Jog, None; K. A. Young, None; M. E. Munroe, None; M. T. Harmon, None; J. M. Guthridge, None;
D. L. Kamen, None; G. S. Gilkeson, None; M. Weisman, None; D. Karp, None; J. B. Harley, None; D. J. Wallace,
None; J. M. Norris, None; J. A. James, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/role-of-epstein-barr-virus-serologic-

reactivation-in-transitioning-to-systemic-lupus-erythematosus-in-at-risk-individuals
Evidence for Inhibition of Osteoclastogenesis By Cytomegalovirus Infection:

Implication in RA Bone Erosion and Identification of a Cellular Protein As a
Therapeutic Target
Benjamin Rauwel1, Michel Baron1, Adeline Ruyssen-Witrand2, Delphine Nigon3, Yannick Degboé2, Jacques Izopet1,
Alain Cantagrel1 and Jean-Luc Davignon1, 1CPTP, INSERM UMR 1043, Toulouse, France, 2Rheumatology, Purpan
Hospital, Toulouse III University, Toulouse, France, 3Rheumatology, Purpan University Hospital, Toulouse Cedex 9, France
SESSION INFORMATION
Session Title: Biology and Pathology of Bone and Joint
Background/Purpose: Exacerbated differentiation of monocytes into osteoclasts (OC) contributes to the pathogenesis of
rheumatoid arthritis (RA) resulting in severe bone erosion and functional damage. Osteoclastogenesis is initiated by M-CSF
and RANKL signalization through their respective receptor CSF-1R and RANK. In vitro, it has been demonstrated that
Human Cytomegalovirus (HCMV) infection inhibits macrophage differentiation through a down regulation of numerous
receptor, including CSF-1R [Frascaroli et al., J. Immunol., (2009)]. As CSF-1R signaling is essential to induce RANK
expression, the key receptor for osteoclast differentiation, we studied the effect of HCMV infection on osteoclastogenesis
and evaluated the consequences of HCMV seropositivity on bone erosion evolution in a RA cohort.
Methods: Blood monocytes from healthy donors were purified by adherence selection and differentiated in osteoclast by
recombinant M-CSF and RANKL (both at 50 ng/mL) during 12 days. After 24 hours of differentiation, pre-osteoclasts were
infected with a HCMV clinical strain (VHL/E) at the m.o.i. of 3. Expression of cellular proteins CSF-1R, RANK, and “X-
protein” (patent being filed) and viral protein (IE) expressions were studied by RT-qPCR, Western Blot, Flow Cytometry and
fluorescence microscopy. OC differentiation was evaluated by manual counting after TRAP staining. Lentiviral transduction
and Amaxa transfections were performed to over-express or inhibit the expression of “X-protein” and confirm its role.
We then analyzed patients from the French « ESPOIR » cohort, fulfilling the 2010 ACR/EULAR criteria for RA. We
evaluated the correlation between HCMV serology status and structural involvement assessed by the modified Sharp score,
at baseline and 1 year.
Results: We demonstrated for the first time that HCMV infection inhibits osteoclastogenesis. No osteoclast was observed in
HCMV infected wells in vitro. We observed that HCMV infection inhibits CSF-1R and RANK mRNA and proteins
expression in a viral replication dependent manner. We found that viral IE protein expression was followed by an increase of
expression of the cellular “X-protein”. To confirm these observations, we over-expressed the “X protein” in monocytes and
observed that CSF-1R, RANK and, as a result, osteoclastogenesis were completely inhibited. Knock-down experiment of “X
protein” with shRNA lentiviral vectors blocked the inhibitory effect of HCMV on CSF-1R and RANK expression.
Analysis of the ESPOIR cohort, including 273 HCMV+ and 214 HCMV- RA patients, demonstrated that, although there was
no difference at inclusion, HCMV seropositive patients displayed less severe bone erosion score in comparison with HCMV
negative ones after one year (p=0.0151),thus providing a pathophysiological counterpart of our in vitro observations.
Conclusion: HCMV infection inhibits osteoclastogenesis through a mechanism involving “X-protein” and results in a
protective effect on bone erosion during RA. Over expression of this “X-protein” inhibited OC differentiation and could be a
new therapeutic target to limit bone erosion during chronic inflammatory disease such as RA and in osteoporosis.
Disclosure: B. Rauwel, None; M. Baron, None; A. Ruyssen-Witrand, None; D. Nigon, None; Y. Degboé, None; J.
Izopet, None; A. Cantagrel, None; J. L. Davignon, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/evidence-for-inhibition-of-

osteoclastogenesis-by-cytomegalovirus-infection-implication-in-ra-bone-erosion-and-identification-of-a-cellular-protein-as-
a-therapeutic-target

Increased Expression of CCN4/WISP1 in Osteoarthritic Articular Cartilage Is
Epigenetically Regulated and Disrupts Cartilage Homeostasis
Martijn H. van den Bosch1, Yolande F. Ramos2, Wouter den Hollander2, Nils Bömer2, Rob G. Nelissen3, Judith V.
Bovée4, Peter L. van Lent1, Arjen B. Blom1, Peter M. van der Kraan1 and Ingrid Meulenbelt2, 1Experimental
Rheumatology, Radboud university medical center, Nijmegen, Netherlands, 2Department of Molecular Epidemiology,
Leiden University Medical Center, Leiden, Netherlands, 3Department of Orthopedics, Leiden University Medical Center,
Leiden, Netherlands, 4Department of Pathology, Leiden University Medical Center, Leiden, Netherlands
SESSION INFORMATION
Background/Purpose: Previously, we described increased expression of Wnt-1-induced signaling protein 1 (Wisp1) in

murine synovium and cartilage after induction of experimental osteoarthritis (OA) models. WISP1 is a downstream target of
canonical Wnt signaling, which has been shown to play a pivotal role in the etiopathology of OA. In agreement with this, we
have observed increased breakdown of the articular cartilage after overexpression of Wisp1 in naïve mouse knee joints,
whereas Wisp1-/- mice revealed decreased cartilage degeneration in three independent experimental OA models compared to
wild type controls. Together, these data indicate a direct correlation between Wisp1 and OA in mice. In the current study we
set out to characterize the relation between expression of WISP1and human OA.
Methods: Articular cartilage from preserved and degenerated OA areas was collected from 39 Caucasian end-stage OA
patients. Cartilage from non-OA-diagnosed individuals was collected after femoral neck fractures. Cartilage degeneration
was classified according to the Mankin scoring system. DNA was isolated to determine correlation between WISP1
expression and methylation profiles using Generalized Linear Mixed Model (GLMM). RNA expression levels were
determined with microarray analysis and RNA sequencing. Immunohistochemical staining was used to determine WISP1
protein expression. Recombinant WISP1 was added to human chondrocyte microparticles, and cartilage extracellular matrix
deposition was determined by measuring cartilage microparticle size and Safranin O/Fast Green staining.
Results:
We observed increased WISP1 expression in cartilage of OA patients compared to non-OA-diagnosed controls. Moreover,
within OA patients, both WISP1 mRNA and protein expression were significantly increased in OA-affected cartilage
compared to preserved regions of the same joint, and WISP1 expression significantly correlated with Mankin score.
Interestingly, we found that positional CpG dinucleotides were hypomethylated in cartilage of OA-affected areas as
compared to unaffected areas from the same joint, which correlated with increased RNA expression as determined with both
microarray analysis and RNA sequencing analysis. Of note, methylation levels of a CpG affecting WISP1 transcription were
found to highly significantly correlate to a single nucleotide polymorphism (SNP) at the WISP1 locus. Next, to investigate
effects of increased WISP1 levels on chondrocyte microparticles, we added human recombinant WISP1. This resulted in a
significantly decreased deposition of cartilage extracellular matrix as reflected by decreased microparticle circumference,
and a strongly decreased proteoglycan content, suggesting that increased WISP1 levels are detrimental to cartilage.
Conclusion:
The expression of WISP1 is increased in OA-affected as compared to preserved articular cartilage. This increased expression
is inversely correlated with methylation levels of a positional CpG, which was found to be under the influence of a SNP at
the WISP1 locus. Together, our results suggest that tight regulation of WISP1 expression via methylation is essential to
maintain cartilage homeostasis.
Disclosure: M. H. van den Bosch, None; Y. F. Ramos, None; W. den Hollander, None; N. Bömer, None; R. G. Nelissen,
None; J. V. Bovée, None; P. L. van Lent, None; A. B. Blom, None; P. M. van der Kraan, Contract research UCB, 2; I.
Meulenbelt, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/increased-expression-of-ccn4wisp1-in-
osteoarthritic-articular-cartilage-is-epigenetically-regulated-and-disrupts-cartilage-homeostasis
Deficient Autophagy Induces Lamin a/C Accumulation in Aging and

Osteoarthritis
Paloma Lopez de Figueroa1, Uxia Nogueira-Recalde2, Fernando Osorio3, Martin Lotz4, Carlos Lopez-Otin3, Francisco J
Blanco2 and Beatriz Carames1, 1Cartilage Biology Group. Rheumatology Division, INIBIC-CHUAC, A Coruña, Spain, A
Coruña, Spain, 2Cartilage Biology Group. Rheumatology Division, INIBIC-CHUAC, A Coruña, A Coruña, Spain,
3Degradome Lab, Universidad de Oviedo, Oviedo, Spain, 4Department of Molecular & Experience Medicine, Scripps
Research Institute, LaJolla, CA
SESSION INFORMATION
Background/Purpose: Autophagy, an essential chondrocyte homeostasis mechanism, is defective in Aging and

Osteoarthritis (OA). However, the targets regulating this mechanism are still unknown. Here, we aimed to identify targets
regulating autophagy in human chondrocytes.
Methods: We performed quantitative proteomic analysis of Atg5 knockdown primary uman chondrocytes using iTRAQ
(isobaric tags for relative and absolute quantitation) labeling coupled with on-line 2D LC/MS/MS. Protein identification and
quantification were performed using Protein Pilot Software v 4.0. Each MS/MS spectrum was searched in the
Uniprot/Swissprot database for Homo sapiens. Human chondrocytes and human cartilage from healthy, aged and OA
patients were employed to confirm the role of the identified target by Western Blot (WB), Inmunofluorescence (IF) and
Inmunohistochemistry (IHC). Importanly, CRISPR/Cas9 genome editing technology and mutant mice were used for
mechanism of action studies.
Results: 24 out of 487 proteins were significantly altered (p<0.05) in response to defective autophagy. Cytoskeleton
organization, collagen catabolism, oxidative stress, and aging pathways were affected. Interestingly, Lamin A/C, a nuclear
protein implicated in cell senescence, was found upregulated under defective autophagy. Increased Lamin A/C expression
was found in human chondrocytes with reduced autophagy. Furthermore, aging and OA human cartilage showed increased
Lamin A/C expression. Induction of chondrocyte aging by genetic deletion of Zinc Metalloproteinase STE24 (Zmpste24) via
CRISPR-Cas9, lead to Lamin A/C accumulation, accompanied by a reduction of LC3 and increased chondrocyte death and
mitochondrial dysfunction. Importanly, Zmpste24 KO mice showed bone damage and intervertebral disc degeneration
(IDD), suggesting that deficient autophagy is correlated with aging and OA phenotype.
Conclusion: Lamin A/C, a nuclear protein contributing to structural integrity to the nucleus and matrix was identified as
candidate target for regulating cartilage function under defective autophagy, such as aging and OA. These results support the
hypothesis that autophagy is decreased with aging. Therefore, targeting autophagy might be a promising strategy to find
novel therapeutics for cartilage aging and OA.
Disclosure: P. Lopez de Figueroa, None; U. Nogueira-Recalde, None; F. Osorio, None; M. Lotz, None; C. Lopez-Otin,
None; F. J. Blanco, None; B. Carames, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/deficient-autophagy-induces-lamin-ac-

accumulation-in-aging-and-osteoarthritis
Regenerating Cartilage and Reversing Osteoarthritis (OA) Stimulation of

Adenosine A2A Receptors (A2AR) Increases Cartilage Volume and Matrix in
Vitro and In Vivo
Carmen Corciulo1, Cristina Castro2, Thomas Coughlin3, Tuere Wilder1, Oran Kennedy4 and Bruce Cronstein5,
1Department of Medicine, Division of Rheumatology, NYU School of Medicine, New York, NY, 2Medicine, NYU School of
Medicine, New York, NY, 3Orthopaedic Surgery, NYU School of Medicine, New York, NY, 4Department of Anatomy,
Royal College of Surgeons, Dublin, Ireland, 5Rheumatology, New York University School of Medicine, Division of
Rheumatology, New York, NY
SESSION INFORMATION
Background/Purpose: We have recently reported that endogenously produced adenosine, interacting with A2AR, is a
critical autocrine factor for maintenance of chondrocyte and cartilage homeostasis and intra-articular injections of liposomal
preparations of adenosine inhibit progression of OA in a post-traumatic OA (PTOA) model in rats. We therefore determined
whether intra-articular injection of a more selective A2AR agonist could also prevent progression and possibly reverse OA
in this model and in the obesity related OA model in mice.
Methods:
PTOA was induced in SD rats following rupture of the anterior cruciate ligament (ACL) by application of external force to
the knee. Starting 4 weeks after injury, when OA has already progressed, knees were injected with 100ul of saline, empty
liposomes (LIPO) or liposomes containing CGS21680 (LIPO-CGS) every 10 days (6 injections) before sacrifice. The
cartilage volume in OA and normal knees was measured by microCT after staining with hexabrix (40%). Chondrocytes were
isolated from neonatal mice and cultured, only first passage chondrocytes were studied.
For the obesity-OA model, C57Bl6 mice (3/group, 12 weeks old) were fed a 60% fat diet (HFF mice). After 3 months, when
OA was present, mice received intrarticular knee injection (10 µl) of LIPO, LIPO-CGS or liposomal adenosine (LIPO-Ado)
every 10 days for 4 injections before sacrifice.
Results: Injection of LIPO-CGS but not saline or LIPO, significantly reduced swelling of affected rat knees (p<0.001).
Surprisingly, there was an increase in tibial and femoral cartilage volume in normal knees treated with intra-articular
injections of LIPO-CGS but not LIPO or saline (47% increase in tibia and 22% in femur). More importantly, intra-articular
injections of LIPO-CGS, but not LIPO or saline, increased tibial and femoral cartilage volume in OA knees, as compared to
normal knees and completely abrogated the histologic evidence of OA as well (OARSI score for CGS21680 0.66±0.33 vs
4.55±0.82 in the vehicle group and 3.90±0.89 in the saline group). There was marked chondrocyte proliferation in the deep
cartilage of knees of rats treated with LIPO-CGS (Ki67 immunofluorescence).
Similarly, LIPO-CGS reversed the OA changes in the obesity related OA model. HFF mice had an OARSI score of 4.7±1.2.
Treatments with LIPO-Ado and lipo-CGS decreased OA severity (OARSI score 1.3±0.3 and 0.7±0.6, respectively, p<0.001
vs untreated). A2AR stimulation increased TGF-β immunostaining in LIPO-CGS-injected joints and increased TGF-b
production by cultured neonatal murine chondrocytes with increased SMAD2/3 phosphorylation and diminished RUNX2
expression.
Conclusion: These results demonstrate that intra-articular injection of a long-acting A2AR agonist stimulates chondrocyte
and cartilage regeneration, likely by a TGF-β-dependent mechanism. More importantly, these results indicate that treatment
with an A2AR agonist can reverse OA in both traumatic and obesity-related OA.
Disclosure: C. Corciulo, None; C. Castro, None; T. Coughlin, None; T. Wilder, None; O. Kennedy, None; B. Cronstein,
NIH grant, 2,Athritis foundation grant, 2,AstraZeneca, 2,Celgene, 2,Eli Lilly & Co., 5,AstraZeneca, 5,Canfite Biopharma, 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/regenerating-cartilage-and-reversing-

osteoarthritis-oa-stimulation-of-adenosine-a2a-receptors-a2ar-increases-cartilage-volume-and-matrix-in-vitro-and-in-vivo
Anp32a Is a Critical Regulator of Oxidative Stress in Cartilage and Protects

Against Osteoarthritis
Frederique Cornelis1, Silvia Monteagudo1, Wouter den Hollander2, Tine Peeters3, Laura-An Guns1, Lies Storms1, Ingrid
Meulenbelt2 and Rik Lories1, 1Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium,
2Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands, 3Skeletal Biology and
Engineering Research Center, KU Leuven, 3000, Belgium
SESSION INFORMATION
Background/Purpose: We described an association between polymorphisms in the ANP32a gene and osteoarthritis.
Osteoarthritis is one of the most common chronic musculoskeletal disorders and a cause of serious morbidity and
disablement, particularly in the elderly population. Progressive damage to the articular cartilage and bone leads to pain and
loss of joint function. The development of osteoarthritis is very complex and is influenced by both genetic and acquired or
environmental risk factors. Anp32a(acidic leucine‐rich nuclear phosphoprotein 32 family member a) functions as a tumor
suppressor gene and as a regulator of gene transcription, stabilization of RNA, intracellular transport and apoptosis.
Moreover, Anp32a associates with Axin-1 and Phosphatase 2A, molecules that exert a regulating role in the Wingless-type
signaling (Wnt) pathway, a signaling cascade with important roles in skeletal development, homeostasis and disease,
including in osteoarthritis. But it remains unknown how Anp32a affects cartilage health and osteoarthritis.
Methods: ANP32A expression levels were determined in preserved and damaged areas of articular cartilage of patients with
osteoarthritis (OA) by RNA sequencing. Different established mouse models for OA were induced in Anp32a-/- mice.
Genome-wide transcriptome analysis of the articular cartilage, comparing Anp32a-/- mice to C57Bl/6 wild-type (WT) mice,
was performed to understand how loss of Anp32a affects cartilage homeostasis at the molecular level. Chromatin
immunoprecipitation-quantitative PCR (CHIP-qPCR) and siRNA-mediated silencing were performed in primary human
articular chondrocytes. Detection of Atm and ROS was performed using immunohistochemical staining on mice knee
sections of Anp32a-/- and C57Bl/6 WT mice.
Results: We observed a significant decrease in ANP32A expression, in damaged areas of the cartilage of patients with OA,
compared to non-damaged areas in the same patients. In the different OA mouse models, absence of Anp32a resulted in
increased cartilage damage as compared to control animals. Transcriptome analysis identified Ataxia-telangiectasia-mutated
(Atm) as a potential Anp32a effector gene. Indeed, Atm was highly downregulated in Anp32-/- mice. Atm is a suppressor of
reactive oxygen species (ROS), which are known to induce chondrocyte hypertrophy during endochondral ossification and
in the onset of osteoarthritis. It is reported that the detrimental effects of Atm depletion on cartilage homeostasis can be
reversed by inhibiting ROS with N-acetyl-cysteine (NAC). We treated our Anp32a-/- mice in the DMM-induced OA model
with NAC, via the drinking water. Effectively, this treatment ameliorated the cartilage damage observed in our Anp32a-/-
mice. CHIP-qPCR demonstrated that Anp32a binds to the Atm gene promoter and influences the recruitment of the RNA
polymerase II transcription machinery.
Conclusion: We have demonstrated that Anp32a plays a relevant role in osteoarthritis, and identified Anp32a as an essential
regulator of Atm and oxidative stress in cartilage. Our insights have therapeutic implications, as pharmacological blockade of
ROS ameliorates osteoarthritis induced in Anp32a-/- mice.
Disclosure: F. Cornelis, None; S. Monteagudo, None; W. den Hollander, None; T. Peeters, None; L. A. Guns, None; L.
Storms, None; I. Meulenbelt, None; R. Lories, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/anp32a-is-a-critical-regulator-of-

oxidative-stress-in-cartilage-and-protects-against-osteoarthritis
Five-Year Evolution of the Center of Excellence in Musculoskeletal Care and

Education: A National Resource for the Continuum of Health Professions
Education and Scholarship
Andrea Barker1, J. Peter Beck2, Grant Cannon3, Marissa Grotzke4, Scott Swasey5,6, Curry L. Koening7, Dorota Lebiedz-
Odrobina6, Yasuharu Okuda8 and Michael J. Battistone1, 1Veterans Affairs Salt Lake City Health Care System and
University of Utah School of Medicine, Salt Lake City, UT, 2Orthopaedics, Salt Lake City VA Medical Center and
University of Utah, Salt Lake City, UT, 3Salt Lake City VA Medical Center and University of Utah, Salt Lake City, UT,
4Division of Endocrinology, Veterans Affairs Salt Lake City Health Care System and University of Utah School of
Medicine, Salt Lake City, UT, 5Salt Lake City VA Medical Center, Salt Lake City, UT, 6University of Utah, Salt Lake City,
UT, 7Rheumatology, University of Utah, Salt Lake City, UT, 8VHA SimLEARN National Center, Orlando, FL
SESSION INFORMATION
Session Title: Education
Background/Purpose: In 2011, the Veterans Affairs (VA) Office of Academic Affiliations funded the creation of the Center
of Excellence (COE) in Musculoskeletal (MSK) Care and Education at the Salt Lake City (SLC) VA. This report reviews the
growth of the COE from a local training program to a national resource supporting multicenter projects in health professions
education and scholarship.
Methods: Data was collected from program faculty on activities of the COE over the last five years.
Results: Four educational programs, two clinical experiences and 44 scholarly projects were identified.
Educational programs (offerings and participants listed in Figure 1):
1. MSK Education Week—an intensive week-long rotation for students and trainees
2. SLC Mini-Residency—a 3-day accredited continuing professional education (CPE) program for primary care providers
(PCPs)
3. National Mini-Residency—an accredited CPE program presented jointly as an educational partnership between faculty
from the SLC VA and 12 VA medical centers
4. National Simulation, Learning, Education, and Research Network (SimLEARN)—two programs: MSK Master
Educator (designed for educational leaders) and MSK Clinician (for PCPs seeking to expand their MSK skills)
Clinical experiences offering hands-on application of skills following educational programs (Figure 2):
1. A new-model MSK clinic embedded in primary care (PC MSK) and staffed by rheumatologists and a physician
assistant with orthopedic experience
2. A multidisciplinary MSK clinic (MD MSK), with rheumatology, endocrinology, orthopedics, physiatry and primary
care
Scholarship (summarized in Figure 3) has included published descriptions of educational programs, evidence of validity of
novel assessment tools, impact on learners’ clinical behaviors, and the durability of change.
Conclusion: The COE in MSK Care and Education has evolved from a local experience for students and trainees to a
national repository for a range of programs serving the continuum of health professions education that fulfils the three-fold
mission of academic health centers: clinical care, education, and scholarship. In addition to creating resources for educators,
the COE is now developing a shared database to support collaborative projects initiated by leaders at other sites participating
in this program through dissemination of their own innovations.
Disclosure: A. Barker, None; J. P. Beck, None; G. Cannon, Amgen, 2; M. Grotzke, None; S. Swasey, None; C. L.
Koening, None; D. Lebiedz-Odrobina, None; Y. Okuda, None; M. J. Battistone, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/five-year-evolution-of-the-center-of-

excellence-in-musculoskeletal-care-and-education-a-national-resource-for-the-continuum-of-health-professions-education-
and-scholarship
Impact of a National Training Program on Primary Care Providers

Utilization of Knee MRI
Erica Jaffe1, Andrea Barker2, J. Peter Beck3, Grant Cannon4 and Michael J. Battistone2, 1Internal Medicine, Veterans
Affairs Salt Lake City Health Care System and University of Utah School of Medicine, Salt Lake City, UT, 2Veterans
Affairs Salt Lake City Health Care System and University of Utah School of Medicine, Salt Lake City, UT, 3Orthopaedics,
Salt Lake City VA Medical Center and University of Utah, Salt Lake City, UT, 4Salt Lake City VA Medical Center and
University of Utah, Salt Lake City, UT
SESSION INFORMATION
Background/Purpose:
The US Department of Veterans Affairs (VA) has developed a national continuing professional development program to
train primary care providers (PCPs) in the care of patients with common musculoskeletal (MSK) conditions. Utilization of
advanced imaging technology (e.g., magnetic resonance imaging (MRI)) in evaluating knee pain is an important concern
because inappropriate ordering of MRI adds to costs in health care systems without increasing benefits, and limits access to
this technology for other patients who may have greater need. Several recent reports suggest that PCPs overuse MRI in
evaluating knee pain, and have called for the creation of educational programs and establishment of performance measures
to address this issue. The aim of this study was to investigate the impact of this educational program on providersÕ
utilization of MRI in the evaluation of knee pain.
Methods:
Two hundred twenty seven providers from 13 VA medical centers participated in the MSK ÒMini-ResidencyÓ between
April 2012 and October 2014. All orders for knee MRIs submitted by these providers over the 12-months prior to their
participation in the mini-residency (pre-training) were reviewed, as well as all orders submitted over the 12-months
following their participation (post-training). MRIs were categorized as follows:
ÒInappropriateÓ: No prior weight-bearing x-rays done within the 12 months preceding the MRI order
ÒProbably InappropriateÓ: Findings of osteoarthritis (OA) described on x-ray report
ÒPossibly AppropriateÓ: No findings of OA described on x-ray report.
The number of MRIs in each category was recorded for the pre-training and post-training period specific to each provider,
and the number of MRIs in each category was tallied. Differences in the numbers of MRIs that were ordered post-training as
compared to pre-training for each of the three categories were evaluated using paired StudentÕs t-test (2-tailed).
Results:
Numbers of MRIs ordered in the 12 months preceding training and following training for each of the categories described
above are presented in the Table:
Completed MRIs
n (% of total)
Change
12 12
n (% of
Months Months
change, p)
Pre- Post-
Category training training
255 180 -75 (-29%,
Inappropriate (76%) (73%) <0.005)
Probably -25 (-42%,
Inappropriate 59 (18%) 34 (14%) 0.09)
Possibly
Appropriate 22 (7%) 31 (13%) 9 (41%, 0.23)
336 245 -91 (-27%,
Total (100%) (100%) <0.005)
Conclusion:
Following the MSK Mini-Residency program, the total number of MRIs ordered by participants decreased by 27%. This
reduction was greatest in the number of studies classified as inappropriate. The total number of knee MRI orders that were
categorized as either inappropriate or probably inappropriate decreased by 100 (32%), while the number of those that were
possibly appropriate were not significantly changed. These findings provide further evidence that the VA MSK Mini-
Residency program is effective in changing provider behavior and improving access to appropriate care for patients, though
the high percentage of MRI scans classified as inappropriate indicate that additional work is needed in this area.
Disclosure: E. Jaffe, None; A. Barker, None; J. P. Beck, None; G. Cannon, Amgen, 2; M. J. Battistone, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/impact-of-a-national-training-program-

on-primary-care-providers-utilization-of-knee-mri
Two-Year Impact of a Continuing Professional Education Program to Train

Primary Care Providers to Perform Arthrocentesis
Michael J. Battistone1, Andrea Barker1, J. Peter Beck2, Phillip Lawrence3 and Grant Cannon4, 1Veterans Affairs Salt Lake
City Health Care System and University of Utah School of Medicine, Salt Lake City, UT, 2Orthopaedics, Salt Lake City VA
Medical Center and University of Utah, Salt Lake City, UT, 3Salt Lake City VA Medical Center and Roseman University of
Health Sciences, Salt Lake City, UT, 4Salt Lake City VA Medical Center and University of Utah, Salt Lake City, UT
SESSION INFORMATION
Background/Purpose: Initial reports of a local continuing professional education (CPE) program designed for primary care
providers (PCPs) described an increase in in the number of joint injections performed by those who had participated in the
training.(1) The aim of this study was to examine the magnitude and durability of this behavioral change in a larger,
geographically diverse impact of cohort of primary care providers. Methods: Thirty-eight primary care providers (PCPs)
from 28 VA clinics representing 15 states participated in the week-long MSK “Mini-Residency” which was held at the Salt
Lake City VA periodically between April 2012 and October 2013. The number of de-identified procedure codes performed
by participants over the 24-months prior to their matriculation in the mini-residency (pre-training) were reviewed, and
compared to those performed 24-months following their participation (post-training). Differences in the numbers of
procedure codes that were documented post-training as compared to pre-training were evaluated using paired Student’s t-test
(2-tailed). Results: Thirty-four PCPs (25 MDs/Dos, 9 PAs/NPs—89% of the total number of trainees) were clinically
active in primary care following the program. The mean number of injection codes per provider, as well as the ranges and
standard deviations for the physician and non-physician provider groups at 2-years and 1-year prior to the training, as well as
at 1- and 2-years post-training are presented in the Table below. Differences in these numbers, as well as the percent change
from the preceding period of observation, are also shown:
Mean Injections/yr (% 1-year change; p)
[Range, s.d]
N 2 Years Pre- 1 Year Pre- 1 Year Post- 2 Years Post-
Training Mean Training Training Training
Injections/yr
[Range, s.d.]
MD/DO 25 12 [0-75, 20] 12 (0%; 0.92) 34 (183%; 43 (26%; 0.26)
[0-75, 18] 0.02) [0-248, [0-309, 81]
54]
ARNP/PA 9 3 [0-12, 4] 3 (0%; 0.86) 16 (464%; 43 (40%; 0.18)
[0-12; 4] 0.07) [2-54, [2-74, 35]
16]
Overall 34 10 [0-75, 17] 10 (0%; 0.96) 29 (205%; 37 (28%; 0.17)
[0-75, 16] 0.004) [0-248, [0-309, 71]
48]
Conclusion: Results from the pilot program are confirmed at 2 years, showing sustained changes in clinical behavior, for
both physician and non-physician provider groups. Substantial variance in the number of joint injections was observed
across the participants, suggesting that after the training some providers expanded their clinical repertoire more than did
others. These findings should inform decisions made by clinic managers and clinical leadership in selecting participants for a
training opportunity designed to increase proficiency in joint injections. Additional investigation of the sources of variance
in provider behavior following the mini-residency program is needed to better understand these results.
Reference List
1. Battistone MJ, Barker AM, Lawrence P, Grotzke MP, Cannon GW. Mini-Residency in Musculoskeletal Care: An
Interprofessional, Mixed-Methods Educational Initiative for Primary Care Providers. Arthritis Care Res (Hoboken).
2016;68(2):275-9.
Disclosure: M. J. Battistone, None; A. Barker, None; J. P. Beck, None; P. Lawrence, None; G. Cannon, Amgen, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/two-year-impact-of-a-continuing-

professional-education-program-to-train-primary-care-providers-to-perform-arthrocentesis
Training Adult Rheumatology Fellows in Young Adult Transition and

Transfer Skills
Rebecca Sadun1, Gary Maslow2, Richard Chung3 and Lisa Criscione-Schreiber4, 1Rheumatology Adult and Pediatric,
Duke University Medical Center, Durham, NC, 2Psychiatry and Pediatrics, Duke University Medical Center, Durham, NC,
3Internal Medicine and Pediatrics, Duke University Medical Center, Durham, NC, 4Internal Medicine, Duke University
Medical Center, Durham, NC
SESSION INFORMATION
Background/Purpose: The transition from pediatric to adult healthcare is a vulnerable time for adolescents and young
adults (AYA) with chronic conditions. EULAR and the Pediatric Rheumatology European Society jointly published expert
opinions regarding transition care of AYA with juvenile-onset rheumatic diseases, and the ACR recently developed a
transition toolkit. However, there are no published curricula for teaching transition guidelines, skills, or utilization of
existing tools. We therefore designed and evaluated a workshop to help adult rheumatology fellows learn key skills for
providing effective transition care to transferring young adult patients.
Methods: A 1-hour skills-based workshop on transition and transfer best practices was developed alongside an objective
standardized clinical examination (OSCE) station in which trainees welcomed a young adult with lupus – and her parent – to
a first visit in an adult clinic. Adult rheumatology fellows (n=19) from 5 institutions were asked to self-asses their ability to
perform 10 transition/transfer skills pre- and post-workshop on a Likert scale from 1-4, with 1 being “not at all prepared”
and 5 being “completely prepared.” The OSCE evaluation rubric assessed 5 transition/transfer skills on a Likert scale of 1-5,
with 5 being the best performance. Twelve fellows were tested with the OSCE de novo, whereas 7 were tested with the
OSCE after participating in the workshop. Aggregated pre- and post-workshop survey responses were compared using
Fisher’s exact test, and OSCE scores were compared using an unpaired t-test.
Results: After participating in the workshop, fellows felt significantly more prepared with regards to 8 of the 10
transition/transfer skills (table 1). In addition, OSCE performance (table 2) was significantly better among the fellows who
participated in the OSCE after the workshop than among those who took the OSCE de novo (p=0.01).
Conclusion: This brief educational intervention successfully increased adult rheumatology fellows’ confidence with many
transition/transfer skills as well as increasing fellows’ ability to employ transition best practices in an OSCE setting. Making
this curriculum available to all rheumatologists-in-training would likely improve the care young adult rheumatology patients
receive when transferring from pediatric to adult rheumatology. Further exploration is needed to determine optimal teaching
strategies to enhance communication between pediatric and adult rheumatologist and to equip adult rheumatologists with
rapport-building skills for working with young adults.
Table 1
Self-Assessed Preparedness Increased Self-Assessed Preparedness Not

Increased
Orient young adult to adult rheumatology Establish rapport and trust with young
care (p<0.01) adult patients (p=0.13)
Provide expectations of the young adult Speak w/ pediatric providers re
patient (p<0.01) transferring patients (p=0.07)
Explain differences between pediatric &
adult care (p<0.01)
Assess young adult self-management
skills (p<0.0001)
Assure young adult of confidentiality
(p<0.001)
Ask parent to leave the room for social
history (p=0.01)
Take a transition-focused adolescent
social history (p<0.01)
Identify barriers to transition and
adherence (p<0.05)
Table 2
Explaining Placing the Assessing Performing Assessing Total
differences AYA patient self- a barriers to score /
between in the primary management confidential transition Average
pediatric role (parent skills adolescent & score
and adult for social adherence
care corroboration) history
Pre- 3.5 4.3 3.8 2.8 2.3 16.7/3.3
workshop
(n=12)
Post- 4.6 5.0 4.4 4.7 2.6 21.3/4.3
workshop
(n=7)
p-value <0.01 <0.05 0.18 0.01 0.86 0.01
Disclosure: R. Sadun, None; G. Maslow, None; R. Chung, None; L. Criscione-Schreiber, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/training-adult-rheumatology-fellows-in-

young-adult-transition-and-transfer-skills
How Well Do Rheumatology Fellows Manage Acute Infusion Reactions? a

Pilot Curricular Intervention
Jason Weiner1, Amanda M. Eudy2 and Lisa Criscione-Schreiber3, 1Department of Medicine, Division of Rheumatology
and Immunology, Duke University Medical Center, Durham, NC, 2Duke University Medical Center, Chapel Hill, NC,
3Internal Medicine, Duke University Medical Center, Durham, NC
SESSION INFORMATION
Background/Purpose:
Infusible DMARDs are commonly prescribed in rheumatology and other fields. There are no published formal educational
curricula rheumatology fellowship programs can use to teach infusion reaction management skills to fellows. We aimed to
better understand this educational gap, and implement and assess the effectiveness of an experiential curriculum on acute
infusion reaction management.
Methods:
We included current rheumatology fellows and recent graduates from five fellowship programs. Using a novel behavioral
checklist, we assessed fellowsÕ performance managing an infusion reaction in a simulation, followed by a didactic focused
on infusion reactions. Pre and post-surveys assessed experiences to determine relevance, as well as attitudes and knowledge.
Results:
Despite ubiquitous prescribing of infusible biologic DMARDs, >50% of fellows were uncomfortable managing infusion
reactions and 11% preferred prescribing injections because of these concerns. Only 11% of fellows reported infusion
reaction training during fellowship, but 56% reported managing actual patient infusion reactions. Graduates reported similar
experiences with 67% currently utilizing infusion services within their immediate clinic areas and 50% having managed
actual patient infusion reactions. Furthermore, all graduates reported no specific training requirements prior to prescribing
infusible DMARDs in their current practice. In the simulated infusion reaction, fellows managed grade 1 reactions
appropriately, but grade 4 reactions poorly, meeting <50% of objectives. All fellows discontinued the infusion in the setting
of anaphylaxis, but only 56% administered epinephrine. There was no difference in performance or written knowledge by
training year. All fellows felt more prepared to manage infusion reactions post-curriculum and were satisfied with the
experience. All graduates recommended fellows receive education on this topic.
Conclusion:
We confirmed an education gap in rheumatology fellowship training regarding infusion reactions, both in knowledge and
performance. We developed and implemented a brief experiential curriculum including simulation of a high-risk patient
care scenario. This curriculum was well received and is easily exportable to other programs and fields of medicine.
Disclosure: J. Weiner, None; A. M. Eudy, None; L. Criscione-Schreiber, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/how-well-do-rheumatology-fellows-

manage-acute-infusion-reactions-a-pilot-curricular-intervention
Has the Attractiveness of a Career in Rheumatology Changed for the Better?

Comparison of Trends in the Rheumatology Fellowship Match from 2014 to
2017 with 2008 to 2013
Huynh Tran1 and Richard Panush2, 1Special Project Manager, University of Southern California, Los Angeles, CA,
2Rheumatology, Program Director, University of Southern California, Los Angeles, CA
SESSION INFORMATION
Background/Purpose:
Rheumatology has been a less attractive career choice than most other medical subspecialties for many years. The
2015 American College of Rheumatology (ACR) workforce study, derived largely from rheumatology fellowship matching
data from 2008 to 2013, projected a shortage of up to 4,729 full-time equivalent rheumatologists by 2030. However the
attractiveness of rheumatology seems to have changed since 2014.
<>Goals/Objectives:
We therefore compared more recent trends in application and match rates in rheumatology with other popular
medical subspecialties.
Methods:
We reviewed data from the National Resident Matching Program from 2008 to 2017, the ACR Rheumatology
workforce study of 2015, and Medscape physician salaries from 2008 to 2017. We examined the numbers of applicants,
numbers of fellowship positions, ratios of applicants-to-fellowship positions, percentages of offered positions filled,
percentages of applicants who matched, percentages of US graduates in fellowships, and salary trends in rheumatology. We
compared data for rheumatology with that for non-procedure-oriented medical subspecialties (endocrinology,
hematology/oncology, infectious disease, and nephrology) and procedure-oriented medical subspecialties (cardiology,
gastroenterology, and pulmonology/critical care medicine) and trends for 2008-2013 with those from 2014-2017.
<>Results:
<>For rheumatology, the total number of applicants from 2008 to 2013 decreased from 251 to 230 (-8%) with an average
annual percentage change of -3.32 ± 2.8% (mean ± SEM) but from 2014 to 2017 increased from 230 to 332 (+44%) with an
average annual percentage change of 21 ± 10.5% (p = 0.02) (Figure). For non-procedural medical subspecialties the total
number of applicants from 2008 to 2013 decreased from 1,940 to 1,594 applicants (-18%) with an average annual percentage
change of -5.42 ± 3.4% but from 2014 to 2017 increased from 1,594 to 1,714, (+8%) with an average annual percentage
change of 0.9 ± 2.3%. For procedural medical subspecialties the total number of applicants from 2008 to 2013, increased
from 2,455 to 2,562 (+4%) with an average annual percentage change of 0.6 ± 1.4% while from 2014 to 2017 the number of
total applicants continued to increase from 2,562 to 2,631 (+3%) with an average annual percentage of 1 ± 1.1%. The
increase for rheumatology from 2014-2017 was significantly greater than changes in non-procedural specialties (p < 0.05)
(Figure). Trends for the other parameters examined generally supported the increased attractiveness and competitiveness of
rheumatology.
<>Conclusion:
<>Our observations complement and extend the 2015 ACR workforce report. While a few years and perhaps relatively
small quantitative changes may not constitute a lasting tendency, analysis of recent trends suggests that rheumatology has
become a more attractive career choice since 2014.
<>
Disclosure: H. Tran, None; R. Panush, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/has-the-attractiveness-of-a-career-in-

rheumatology-changed-for-the-better-comparison-of-trends-in-the-rheumatology-fellowship-match-from-2014-to-2017-
with-2008-to-2013
High Erythrocyte Levels of the n-6 Polyunsaturated Fatty Acid Linoleic Acid
Are Associated with Lower Risk of Subsequent Rheumatoid Arthritis in a
Southern European Nested Case-Control Study
Paola de Pablo1, Dora Romaguera2,3, Helena Fisk4, Philip Calder4, Anne-Marie Quirke5, Alison Cartwright5, Salvatore
Panico6, Amalia Mattiello6, Diana Gavrila7, Carmen Navarro7, Carlotta Sacerdote8, Paolo Vineis2,9, Rosario Tumino10,
William Ollier11, Dominique Michaud2,12, Elio Riboli2, Patrick Venables5 and Benjamin Fisher13, 1University of
Birmingham, Birmingham, United Kingdom, 2Imperial College London, London, United Kingdom, 3CIBER-OBN
(Fisiopatología de la Obesidad y Nutrición), University Hospital Son Espases, Palma, Spain, 4University of Southampton,
Southampton, United Kingdom, 5Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom,
6Federico II University of Naples, Naples, Italy, 7Murcia Regional Health Council, Murcia, Spain, 8Città della Salute e della
Scienza University-Hospital, Turin, Italy, 9Human Genetics Foundation, Turin, Italy, 10"Civic - M.P.Arezzo" Hospital,
Ragusa, Italy, 11Division of Population Health, Health Services Research and Primary Care, University of Manchester,
Manchester Academic Health Science Centre, Manchester, United Kingdom, 12Tufts University Medical School, Boston,
MA, 13Rheumatology Research Group, University of Birmingham, Birmingham, United Kingdom
SESSION INFORMATION
Session Title: Epidemiology and Public Health II: Non-Genetic Risk Factors for Incident Disease
Background/Purpose:
Long-chain n-3 (also known as omega-3) polyunsaturated fatty acids (PUFA), especially eicosapentaenoic acid (EPA; 20:5n-
3) and docosahexaenoic acid (DHA; 22:6n-3), have long-been considered to have anti-inflammatory and immunomodulatory
actions. Both n-3 and n-6 series PUFA (determined by the number of carbon atoms between the methyl end of the fatty acyl
chain and the first double-bond) cannot be synthesized de novo by animals. Findings relating to the dietary intake of n-3
PUFA and risk of rheumatoid arthritis (RA) are mixed. We compared erythrocyte membrane PUFA, as an accurate
biomarker of PUFA status, between pre-RA individuals and matched controls from a population-based sample.
Methods:
EPIC is a multicentre, pan-European prospective cohort study of apparently healthy populations. We undertook a nested
case-control study, by identifying RA cases with onset after enrolment (pre-RA) in four EPIC cohorts: Naples, Turin and
Ragusa in Italy, and Murcia in Spain. Identification and case validation has been previously described [1]. Confirmed pre-
RA cases were matched with controls by age, sex, centre, and date, time and fasting status at blood collection. Total
erythrocyte lipids were extracted and dissolved in toluene. Fatty acid methyl esters were synthesied and resolved in a BPX-
70 fused silica capillary column using an Agilent 6890 gas chromatograph equipped with flame ionisation detection. We also
measured the following serum cytokines: TNFα, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13 and IFNγ (Meso
Scale Diagnostics). Conditional logistic regression (CLR) analysis of data was adjusted for potential confounders including
body mass index (BMI), waist circumference, education level, physical activity, smoking status, and alcohol intake.
Negative binomial regression was used to test the relationship between PUFA and serum cytokine level, stratified by
incident RA, and adjusting for age, sex, country of origin, BMI, and smoking status.
Results:
The study analysed pre-symptomatic samples from 354 individuals of which 96 individuals went on to subsequently develop
RA. In this analysis, time to diagnosis (defined as time between date of blood sample and date of diagnosis), was 6.71 years
(SD 3.43).
No association was observed for any individual n-3 PUFA, or with total n-3 PUFA or total long chain n-3 PUFA, or with
total n-3/n-6 ratio, and risk of RA. However a significant inverse association was observed with the n-6 PUFA linoleic acid
(LA) level and pre-RA in the fully adjusted model (highest tertile : OR 0.29; 95% CI 0.12 to 0.75; p for trend 0.01).
Among the controls, LA was positively associated with serum levels of TNFα and IL-6 and negatively with IL-4, IL-5, IL-
10, IL-12, IL-13 and IFNγ in fully adjusted models. In the pre-RA population, LA was positively associated with TNFα and
IL-1, and negatively with IL-6, IL-5, IL-12 and IL-13 levels.
Conclusion:
In this nested case-control study within southern European prospective cohorts, high erythrocyte levels of the n-6 PUFA LA
are associated with lower levels of T cell related cytokines and with lower risk of subsequent RA.
[1] Fisher BA, et al. BMC Musculoskelet Disord. 2015;16:331.
Disclosure: P. de Pablo, None; D. Romaguera, None; H. Fisk, None; P. Calder, None; A. M. Quirke, None; A.
Cartwright, None; S. Panico, None; A. Mattiello, None; D. Gavrila, None; C. Navarro, None; C. Sacerdote, None; P.
Vineis, None; R. Tumino, None; W. Ollier, None; D. Michaud, None; E. Riboli, None; P. Venables, None; B. Fisher,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/high-erythrocyte-levels-of-the-n-6-

polyunsaturated-fatty-acid-linoleic-acid-are-associated-with-lower-risk-of-subsequent-rheumatoid-arthritis-in-a-southern-
european-nested-case-control-study

Occupational Exposure to Combustion Products and Risk of Developing
Anna Ilar1, Pernilla Wiebert1,2, Saedis Saevarsdottir3, Johan Askling4,5, Per Gustavsson1,2 and Lars Alfredsson1,2, 1The
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, 2Stockholm County Council, Centre for
Occupational and Environmental Medicine, Stockholm, Sweden, 3Rheumatology Unit, Department of Medicine, Karolinska
University Hospital and Karolinska Institutet, Stockholm, Sweden, 4Rheumatology unit, Department of Medicine,
Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden, 5Unit of Clinical Epidemiology, Department
of Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden
SESSION INFORMATION
Background/Purpose:
Studies have suggested a potential association between traffic pollutants and rheumatoid arthritis (RA), but findings have
been inconclusive. We therefore assessed the risk of RA from occupational exposure to combustion products in a large
population-based case-control study.
Methods:
We included participants living in Sweden from 2006 to 2013. Incident cases of RA were enrolled from the Swedish
Rheumatology Quality Register. Ten controls per case, matched on sex, age and county, were enrolled from the total
population register. Work histories were available through population and housing censuses. We estimated exposure to
asphalt fumes, diesel engine exhaust and polycyclic aromatic hydrocarbons from 1955 to 1995 with job-exposure matrices.
Conditional logistic regression was used to estimate the risks of two histological subtypes of RA (seropositive or
seronegative RA) from exposure to either of the combustion products taken separately or all of them combined. All main
exposures were adjusted for potential confounding from each other as well as from respirable crystalline silica dust and
household disposable income. The results are presented for men and women separately.
Results:
We analyzed 9 180 cases and 81 367 controls. Ever exposure to diesel engine exhaust in men was associated with a
marginally higher risk of seropositive RA (OR: 1.11, 95 % CI: 1.00-1.23), which was slightly higher among workers with at
least 20 years of exposure (OR: 1.22, 95 % CI: 1.00-1.49). More than 20 years of asphalt fumes exposure was also
associated with a higher risk estimate for seropositive RA among men (OR: 1.87, 95 % CI: 1.05-3.31). Being exposed to
asphalt fumes, diesel engine exhaust or polycyclic aromatic hydrocarbons combined for more than 20 years resulted in an
OR of 1.22 (95 % CI: 1.03-1.45) among men for seropositive RA and 0.98 (95 % CI: 0.77-1.23) for seronegative RA.
Women were less likely than men to have been exposed to combustion products during work and few female workers had
been exposed for a longer period of time. Ever exposure to polycyclic aromatic hydrocarbons in women was associated with
a potentially higher risk of seropositive RA (OR: 1.22, 95 % CI: 1.00-1.48). Women exposed to asphalt fumes, diesel engine
exhaust or polycyclic aromatic hydrocarbons combined for more than 20 years had an OR of 0.91 (95 % CI: 0.36-2.29) for
RA overall.
Conclusion:
Long-term exposure to combustion products may increase the risk of seropositive RA among men after adjustments for
potential confounders.
Disclosure: A. Ilar, None; P. Wiebert, None; S. Saevarsdottir, None; J. Askling, AbbVie, Eli Lilly, Janssen, Merck,
Pfizer, Roche, UCB, Samsung, 2; P. Gustavsson, None; L. Alfredsson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/occupational-exposure-to-combustion-

products-and-risk-of-developing-rheumatoid-arthritis
Pesticide Exposure and Risk of Systemic Lupus Erythematosus in an Urban

Population of Predominantly African-American Women
Jessica Williams1, Shun-Chiao Chang1, Corine Sinnette1, Susan Malspeis2, Christine G. Parks3, Elizabeth Karlson1,
Patricia Fraser1 and Karen H. Costenbader1, 1Brigham and Women's Hospital, Harvard Medical School, Boston, MA,
2Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School,
Boston, MA, 3Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Durham, NC
SESSION INFORMATION
Background/Purpose:
Several studies have reported an association between exposure to pesticides and the risk of systemic lupus erythematosus
(SLE). However, this association has not yet been examined in an urban population, where residential pesticide exposure is
more common than agricultural exposure. The purpose of this study was to assess the risk of SLE associated with residential
exposure to pesticides in an urban population of predominantly African-American females.
Methods:
Female patients with SLE were identified via 6 hospital databases and community screening in 3 predominantly African-
American neighborhoods in Boston, Massachusetts. Each SLE patient was reviewed by a rheumatologist and confirmed to
have ≥4 ACR criteria for SLE. Subjects without SLE were female volunteers from the same neighborhoods, screened for the
absence of connective tissue disease by questionnaire and finger stick anti-nuclear antibody. In-person interviews from April
2002 to August 2003 determined type and frequency of pesticide exposure prior to SLE diagnosis or corresponding
reference age in subjects without SLE. Subjects were considered exposed to pesticides if they had ever required an
exterminator for an ant, cockroach, or termite problem. The risks associated with exposure to pesticides were analyzed using
multivariable logistic regression models, adjusted for age, race, parity, employment status, educational attainment, smoking
status, and place of birth.
Results:
93 SLE patients and 170 subjects without SLE were matched by age and race, with similar baseline characteristics (see
table). Patients with SLE were more likely to have had exposure to pesticides than subjects without SLE (65% vs. 51%,
p=0.03). Pesticide exposure was associated with SLE, even after controlling for potential confounders (OR 2.24, 95% CI
1.28-3.93). A dose-response effect for increased frequency of exterminator service use was not statistically significant (p for
trend=0.21).
Conclusion:
Residential exposure to pesticides in an urban community of predominantly African-American women was associated with
an increased risk of SLE, even after controlling for potential confounders. Our findings demonstrate that previous reports of
an association between pesticide exposure and SLE may be applicable to urban African-American women, a population at
increased risk for SLE. As our results may be limited by recall bias and/or residual confounding, additional research is
needed to determine whether pesticide exposure is implicated in SLE pathogenesis, or is instead serving as a surrogate for a
related exposure such as pest burden or poor living conditions.
Table. Characteristics of subjects with and without SLE*

Characteristics SLE No SLE p-
value†
(n=93) (n=170)
Exposed to pesticides‡ 60 (65) 86 (51) 0.03
Age, mean ± SD years 44 ± 13 47 ±15 0.11
Race 0.10
African-American non-Hispanic 71 (76) 147 (86)
Hispanic 7 (8) 7 (4)
Caucasian non-Hispanic 6 (6) 3 (2)
Other 9 (10) 13 (8)
Parity, ever 71 (76) 134 (79) 0.64
Working full-time or part-time 44 (47) 90 (53) 0.38
Completed high school 71 (76) 122 (72) 0.42
Smoking status (≥100 cigarettes per 0.33
lifetime)‡
Current (past 30 days smoked ≥1 16 (17) 35 (21)
cigarette)
Past 20 (22) 47 (28)
Never 57 (61) 88 (52)
Born in Boston 36 (39) 81 (48) 0.16
*Unless indicated otherwise, values are the number (%).
†By chi-square test. Wilcoxon rank-sum test was used for age.
‡Before age at diagnosis or corresponding reference age.
Disclosure: J. Williams, None; S. C. Chang, None; C. Sinnette, None; S. Malspeis, None; C. G. Parks, None; E.
Karlson, None; P. Fraser, None; K. H. Costenbader, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/pesticide-exposure-and-risk-of-systemic-

lupus-erythematosus-in-an-urban-population-of-predominantly-african-american-women
Long Term Effects of Early Childhood Thymectomy: A Population-Based

Cohort Study of Association with Autoimmune Disease, Cancer, Infectious
and Atopic Diseases
Judith Gudmundsdottir1,2, Jonas Söderling3, Håkan Berggren4, Sólveig Óskarsdóttir5, Martin Neovius6, Olof Stephansson3
and Olov Ekwall7,8, 1Dept of Rheumatology and Inflammation Research, The Institute of Medicine, The Sahlgrenska
Academy, University of Gothenburg, Gothenburg, Sweden, 2Children's Medical Center, Landspítali University Hospital,
Reykjavík, Iceland, 3Clinical Epidemiology Unit, Dept of Medicine, Karolinska Institute, Stockholm, Sweden, 4Dept of
Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg,
Sweden, 5Dept of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg,
Gothenburg, Sweden, 6Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden,
7Dept. of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of
Gothenburg, Göteborg, Sweden, 8Dept of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of
Gothenburg, Göteborg, Sweden
SESSION INFORMATION
Background/Purpose:
The thymus is the site of T cell maturation and selection and thus of vital importance for the development of immunological
tolerance. Early thymectomy is routinely performed in infants undergoing surgical correction of congenital heart defects.
Various immunological changes have been described after early thymectomy but the long-term clinical consequences are
unknown. The aim of this study was to investigate the association between early thymectomy and risks of autoimmune
disease, cancer, infectious and atopic diseases.
Methods:
The study is a nationwide population-based cohort study using the Medical Birth, Cause of Death and National Patient
Registers in Sweden. We identified 5664 individuals born in 1973-2009 thymectomized before five years of age. For each
individual, ten age and sex matched general population controls as well as 2276 surgery controls who had undergone early
cardiac surgery, not involving thymectomy, were included. The main outcomes were incidence rates and hazard ratios for
selected autoimmune diseases, cancer, infectious and atopic diseases.
Results:
Compared to the surgery controls, thymectomized individuals were at increased risk for hypothyroidism (HR 3.03; 95%CI
1.17-7.83), type 1 diabetes (HR 3.16; 95%CI 1.08-9.21) and both viral (HR 1.40; 95%CI 1.30-1.50) and bacterial (HR 1.26;
95%CI 1.11-1.43) infections. The HR for asthma was reduced (HR 0.69; 95%CI 0.58-0.83). Compared to the general
population, increased risks were detected for hypothyroidism (HR 4.94; 95%CI 3.27-7.46), juvenile idiopathic arthritis (HR
1.85; 95%CI 1.11-3.09), rheumatic diseases (HR 1.89; 95%CI 1.00-3.57), celiac disease (HR 1.96; 95%CI 1.42-2.72),
cancer (HR 1.61; 95%CI 1.07-2.43), infections (HR 3.18; 95%CI 3.07-3.30) and asthma (HR 1.84; 95%CI 1.64-2.07) in
thymectomized individuals.
Conclusion:
In conclusion, early thymectomy is associated with increased risks of autoimmune disease, cancer as well as infectious
disease. The study implicates important roles for the post-natal human thymus for the preservation of immunological
tolerance as well as for immune effector functions. The results also indicate that avoidance of total thymectomy during early
cardiac surgery may be advisable.
Disclosure: J. Gudmundsdottir, None; J. Söderling, None; H. Berggren, None; S. Óskarsdóttir, None; M. Neovius,
Pfizer Inc, 2,AstraZeneca, 2,Pfizer Inc, 5; O. Stephansson, None; O. Ekwall, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/long-term-effects-of-early-childhood-

thymectomy-a-population-based-cohort-study-of-association-with-autoimmune-disease-cancer-infectious-and-atopic-
diseases
Prospective Association of Metabolic Syndrome with Incident Symptomatic

Interphalangeal Osteoarthritis but Not Thumb Based or Erosive Hand
Osteoarthritis
Charles Eaton1, Lena Franziska Schaefer2, Ida K. Haugen3, Mary Roberts4, Bing Lu5, Stacy Smith6, Jeffrey Duryea2,
Jeffrey B. Driban7 and Timothy E. McAlindon8, 1Family Medicine and Epidemiology, Warren Alpert Medical School,
School of Public Health, Brown University, Providence, RI, 2Radiology, Brigham & Women's Hospital/ Harvard Medical
School, Boston, MA, 3Diakonhjemmet Hospital, Oslo, Norway, 4Center for Primary Care and Prevention, Memorial
Hospital of Rhode Island, Pawtucket, RI, 5Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and
Harvard Medical School, Boston, MA, 6Radiology/Division of Musculoskeletal Imaging & Intervention, Brigham &
Women's Hospital/ Harvard Medical School, Boston, MA, 7Rheumatology, Tufts Medical Center, Boston, MA, 8Division of
Rheumatology, Tufts Medical Center, Boston, MA
SESSION INFORMATION
Background/Purpose: Symptomatic Hand Osteoarthritis (SxHOA) is a painful, destructive and deforming polyarticular
disorder that is highly prevalent. The epidemiology of incident SxHOA and its association with metabolic processes is
unclear with limited studies and conflicting results. We aimed to characterize individuals who develop symptomatic
interphalangel, thumb-based and erosive hand osteoarthritis and compare them to those who did not.
Methods: We evaluated 3604 participants in the Osteoarthritis Initiative (OAI) with complete data for baseline and 48-
month radiographic hand OA. We defined interphalangeal OA as a hand with at least two joints with KL grade ≥2 on at least
two fingers (digits 2 to 5), thumb-base OA using same KL criteria of either the CMC or STT joints, and erosive hand OA if
one erosion was also present on any interphalangel joint.
SxHOA required both presence of radiographic OA and symptoms (pain, aching, stiffness) on most days for the past 30
days. A metabolic syndrome score (MetS) was defined by summating presence of abdominal obesity (defined by gender-
specific waist circumference), hypertension, diabetes, and dyslipidemia (range 0-4). Logistic regression was performed
adjusting for age, sex and race for all models and other confounders (knee OA, smoking) depending on the outcome
examined using a backward selection process to define the most parsimonious model.
Results: The overall 4-year incidence of symptomatic interphalangeal OA (SxIPOA), thumb-based OA(SxTBOA) and
erosive hand OA(SxeHOA) were: SxIPOA n=536 (14.9%) ; SxTBOA n=551(15.3%); SxeHOA n=150 (4.2%). Older age,
female sex, and knee OA were associated with SxIPOA, SxTBOA, while SxeHOA was not associated with knee OA. Black
race compared to whites was inversely associated with all three symptomatic hand OA sub-types. (Table 1) A monotonically
increasing risk of SxIPOA was found related to MetS compared to no metabolic risk factors (1 component OR=1.36; 2
components OR=1.50; 3 or 4 components OR=1.59, P for trend <0.01). Of the MetS risk factors dyslipidemia was
significantly associated an increased risk of SxIPOA (OR=1.34, 95% CI 1.09,1.65 and SxTBOA(OR=1.34, 95% CI
1.09,1.64) while hypertension was associated with incident SeHOA(OR=1.52, 95% CI 1.06,2.18). MetS was not associated
with sxTBOA or SxeHOA nor with incident radiographic defined IPOA, TBOA and eHOA unrelated to symptoms.
Conclusion: Metabolic syndrome risk factors demonstrate a monotonically increased risk for SxIPOA but not with
radiographically defined IPOA. Further research into the metabolic pathways, sex and race differences in the progression of
symptomatic hand OA appear warranted.
Risk Factors SxIPOA SxTBOA SxeHOA
OR (95% CI) OR (95% CI) OR (95%CI)
Age (per SD) 1.81 (1.63, 2.00) 1.51 (1.37, 1.66) 1.86 (1.55, 2.24)
Sex
1.63 (1.34, 2.00) 1.68 (1.38, 2.05) 2.60 (1.78, 3.84)
Female vs Male
Race
0.67 (0.50, 0.89) 0.62 (0.46, 0.82) 0.23 (0.10, 0.54)
Black vs White
MetS
1.36 (1.05,1.77) 1.14 (0.89, 1.46) 1.34 (0.86, 1.55)
1 vs None
2 vs None 1.50 (1.13, 1.98) 1.31 (1.01, 1.71) 1.31 (0.80, 2.12)
3-4 vs None 1.59 (1.13, 2.22) 1.34 (0.96, 1.86) 1.24 (0.68, 2.28)
Knee OA 1.24 (1.02, 1.52) 1.29 (1.06, 1.57) N/A N/A
Smoking
N/A N/A N/A N/A 1.39 (0.99, 1.95)
Past vs Never
Current vs Never N/A N/A N/A N/A 0.42 (0.10, 1.75)
Disclosure: C. Eaton, None; L. F. Schaefer, None; I. K. Haugen, None; M. Roberts, None; B. Lu, None; S. Smith, None;
J. Duryea, None; J. B. Driban, None; T. E. McAlindon, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prospective-association-of-metabolic-

syndrome-with-incident-symptomatic-interphalangeal-osteoarthritis-but-not-thumb-based-or-erosive-hand-osteoarthritis
Development and Validation of a Clinical Rule to Facilitate Recognition of

Clinical Arthritis By General Practitioners
Robin M ten Brinck1, Bastiaan T van Dijk2, Hanna W van Steenbergen1, Saskia le Cessie3, Mattijs E Numans4 and
Annette H.M. van der Helm-van Mil1, 1Department of Rheumatology, Leiden University Medical Center, Leiden,
Netherlands, 2Rheumatology, Leiden University Medical Center, Leiden, Netherlands, 3Medical statistics and Epidemiology,
Department of Medical Statistics and Epidemiology, Leiden University Medical Center, Leiden, Netherlands, 4Public Health
and Primary Care, Leiden University Medical Center, Leiden, Netherlands
SESSION INFORMATION
Background/Purpose:
Early treatment of rheumatoid arthritis requires the early detection of arthritis. This is generally done by joint examination
and difficult for general practitioners (GPs). To promote early recognition of arthritis, the Leiden Early Arthritis Recognition
Clinic (EARC) was initiated, where GPs can send patients if in doubt about arthritis (instead of ‘wait-and-see’). Although
the EARC importantly improved the early identification, this approach may not be easily implemented at other places. This
study determined the discriminative value of a combination of symptoms and other signs for clinical arthritis.
Methods:
1,288 patients visited the EARC between 2010 and 2015. Symptoms and signs were studied with the presence of synovitis
(joint examination by experienced rheumatologist) as outcome. Parameters were identified using multivariable logistic
regression in 644 patients and validated in another 644 patients. A simplified rule was derived to facilitate application in
clinical practice.
Results:
41% had arthritis at examination. Male sex, age ≥60 years, a short symptom duration, morning stiffness >60 minutes, a low
number of tender joints, the presence patient-reported swollen swelling and difficulties with making a fist were significantly
associated with the presence of arthritis in the derivation cohort. A simplified rule, consisting of these 7 items, was generated
(Figure); it had an AUC of 0.74 (95%CI 0.78-0.70). When a sensitive rule is preferred, a cut-off of ≥4 yields a sensitivity of
94%; when a specific rule is preferred the cut-off ≥6 has a specificity of 92%. Risks of arthritis were determined, and also
estimated for a setting in which the prevalence of clinical arthritis in patients with suspected arthritis was half of that
observed here.
Conclusion:
A rule composed of clinical parameters had a reasonable discriminative ability for clinical arthritis. Ultimately this could
assist GPs in decision-making in patients with suspected inflammatory arthritis.
Figure. The Clinical Arthritis Rule (CARE) and corresponding risks of the presence of inflammatory arthritis per
score.
Disclosure: R. M. ten Brinck, None; B. T. van Dijk, None; H. W. van Steenbergen, None; S. le Cessie, None; M. E.
Numans, None; A. H. M. van der Helm-van Mil, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/development-and-validation-of-a-

clinical-rule-to-facilitate-recognition-of-clinical-arthritis-by-general-practitioners
HLA Type Imputation in the Genome Research in African American

Scleroderma Patients (GRASP) Cohort Reveals Strong Associations of
African Ancestry MHC Class II Types with Scleroderma and Lack of Class I
HLA Type Associations
Elaine F. Remmers1, Pravitt Gourh2, Steven Boyden3, Nadia D. Morgan4, Ami A. Shah4, Adebowale Adeyemo1, Amy
Bentley1, Mary A. Carns5, Settara C. Chandrasekharappa1, Lorinda Chung6, Lindsey A. Criswell7, Chris T. Derk8, Robyn T.
Domsic9, Ayo Doumatey1, Heather Gladue10, Avram Goldberg11, Jessica K. Gordon12, Vivien M Hsu13, Reem Jan14,
Dinesh Khanna15, Maureen D. Mayes16, Thomas A. Medsger Jr.17, Paula S. Ramos18, Marcin A. Trojanowski19, Lesley A.
Saketkoo20, Elena Schiopu15, Victoria K. Shanmugam21, Daniel Shriner1, Richard M. Silver22, Virginia D. Steen23, Antonia
Valenzuela24, John Varga25, Charles Rotimi1, Fredrick M. Wigley26, Francesco Boin27 and Daniel L. Kastner28, 1National
Institutes of Health (NIH), National Human Genome Research Institute, Bethesda, MD, 2NIAMS-Rheumatology, National
Institutes of Health (NIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, 3National
Institutes of Health (NIH), National Institute on Deafness and Other Communication Disorders, Bethesda, MD,
4Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, 5Northwestern University, Feinberg School
of Medicine Scleroderma Program, Chicago, IL, 6Rheumatology, Stanford University Medical Center, Palo Alto, CA,
7Medicine/Rheumatology, University of California, San Francisco, San Francisco, CA, 8Rheumatology, University of
Pennsylvania, Philadelphia, PA, 9Rheumatology, University of Pittsburgh, Pittsburgh, PA, 10Rheumatology, Arthritis and
Osteoporosis Consultants of the Carolinas, Charlotte, NC, 11NYU Langone Medical Center, New York, NY,
12Rheumatology, Hospital for Special Surgery, New York, NY, 13University of Medicine and Dentistry of New Jersey--
Robert Wood Johnson Medical School, New Brunswick, NJ, 14Medicine, Rheumatology, University of Chicago, Chicago,
IL, 15University of Michigan, Ann Arbor, MI, 16University of Texas McGovern Medical School, Houston, TX,
17Department of Medicine/Rheumatology, University of Pittsburgh, Pittsburgh, PA, 18Department of Public Health Sciences,
Medical University of South Carolina, Charleston, SC, 19Boston University School of Medicine, Boston, MA,
20Rheumatology, Tulane University School of Medicine, New Orleans, LA, 21Rheumatology, The George Washington
University, Washington, DC, 22Division of Rheumatology and Immunology, Department of Medicine, Medical University of
South Carolina, Charleston, SC, 23Rheumatology, MedStar Georgetown University Hospital, Washington, DC, 24Stanford
University School of Medicine, Stanford, CA, 25Rheumatology and Dermatology, Northwestern University, Feinberg School
of Medicine Scleroderma Program, Chicago, IL, 26Rheum Div/Mason F Lord, Johns Hopkins University, Baltimore, MD,
27Rheumatology, University California, San Francisco, San Francisco, CA, 28Inflammatory Disease Section, National
Human Genome Research Institute, National Institutes of Health, Bethesda, MD
SESSION INFORMATION
Session Title: Healthcare Disparities in Rheumatology
Background/Purpose: The Genome Research in African American Scleroderma Patients (GRASP) consortium was created
to obtain a collection of African American (AA) scleroderma patients to facilitate genomic studies to identify novel genetic
variants that could account for the increased scleroderma prevalence and severity in African Americans compared with
individuals of European ancestry. In a companion abstract we report a genome-wide association study establishing
significant genetic associations for AA scleroderma in the MHC and for TGFB3. Here we used MHC region genotypes to
impute classical HLA types and analyzed their associations with scleroderma in the GRASP cohort.
Methods: SNP genotyping of 934 scleroderma cases and 946 controls was performed on the Illumina Multi-Ethnic Global
array. We extracted the genotypes of 25,256 markers from 20 Mb encompassing the greater MHC region and used the
Michigan Imputation Server with 1000G Phase 3 v5 reference and Eagle phasing algorithm to obtain input data for
submission to the HLA*IMP:03 web server. HLA types were converted to presence or absence genotypes (PP/PA/AA) for
each typed allele and disease association was determined using a dominant model. Regression and conditional analyses
were performed after recoding the genotype data to 0 or 1 using a dominant model and the top 10 principal components were
included as covariates.
Results: The most significantly scleroderma-associated HLA type was a predominantly African allele, HLA-DRB1*08:04,
with odds ratio 2.95, 95%CI 2.26-3.85 (Figure 1). Regression analysis conditioning on the disease-associated alleles
identified another African DRB1 allele, *11:02, as well as HLA-DPB1*13:01, and HLA-DRB4*01:01 as independent
contributors to disease risk, but no association was found for MHC class I alleles (Figure 1). 34.6% of GRASP cases carry
either DRB1*08:04 or *11:02 compared with 16.3% of controls. Analysis of 246 anti-topoisomerase antibody positive cases
revealed a strong disease risk conferred by HLA-DPB1*13:01 (P=4.93x10-17, OR=4.10, 2.90-5.79). Remarkably, 30.49% of
anti-topoisomerase antibody-positive cases carry HLA-DPB1*13:01, compared with 9.7% of controls.
Conclusion: The scleroderma risk-associated HLA-DRB1 types identified in the GRASP cohort differ from those reported in
individuals of European ancestry. These HLA types are found at a higher population frequency than the European
scleroderma risk types and therefore could contribute to the increased disease incidence or severity observed in African
American patients.
Disclosure: E. F. Remmers, None; P. Gourh, None; S. Boyden, None; N. D. Morgan, None; A. A. Shah, None; A.
Adeyemo, None; A. Bentley, None; M. A. Carns, None; S. C. Chandrasekharappa, None; L. Chung, Cytori, Actelion,
Reata, 5; L. A. Criswell, None; C. T. Derk, None; R. T. Domsic, None; A. Doumatey, None; H. Gladue, None; A.
Goldberg, None; J. K. Gordon, Corbus Pharmaceuticals, 2,Cumberland Pharmaceuticals, 2,Bayer Pharmaceuticals, 2; V.
M. Hsu, None; R. Jan, None; D. Khanna, Actelion, Bayer, BoehringerIngelheim, Chemomab, Corbus, Covis, Cytori,Eicos,
EMD Serono, Genentech/Roche, Gilead, GSK, Sanofi-Aventis,UCB Pharma, 5,NIH/NIAMS, NIH/NIAID,Bayer, BMS,
Genentech/Roche, Pfizer, 2,Eicos, 4; M. D. Mayes, None; T. A. Medsger Jr., None; P. S. Ramos, None; M. A.
Trojanowski, None; L. A. Saketkoo, None; E. Schiopu, None; V. K. Shanmugam, Multiple, 9; D. Shriner, None; R. M.
Silver, None; V. D. Steen, None; A. Valenzuela, None; J. Varga, BMS, 2,Pfizer Inc, 2; C. Rotimi, None; F. M. Wigley,
None; F. Boin, None; D. L. Kastner, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/hla-type-imputation-in-the-genome-

research-in-african-american-scleroderma-patients-grasp-cohort-reveals-strong-associations-of-african-ancestry-mhc-class-
ii-types-with-scleroderma-and-lack-of-class
Area-Level Predictors of Medication Nonadherence Among U.S. Medicaid

Beneficiaries with Lupus: A Multilevel Study
Candace H. Feldman1, Karen H. Costenbader2, Daniel H. Solomon3, S.V. Subramanian4 and Ichiro Kawachi5, 1Division of
Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, 2Division of Rheumatology,
Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 3Brigham and
Women's Hospital and Harvard Medical School, Boston, MA, 4Social and Behavioral Sciences, Harvard T.H. Chan School
of Public Health, Boston, MA, 5Social and Behavioral Sciences, Harvard T. H. Chan School of Public Health, Boston, MA
SESSION INFORMATION
Background/Purpose: Among lupus patients, adherence to hydroxychloroquine (HCQ), the backbone of therapy, remains
suboptimal. Individual-level factors, including younger age, poverty, and black race, have been associated with HCQ
nonadherence. However contextual factors including neighborhood poverty and concentration of healthcare resources have
not been examined. We constructed multilevel models to investigate whether zip code, county and state-level characteristics
were associated with HCQ nonadherence.
Methods: We identified individuals with SLE enrolled in Medicaid (2000-2010) from 28 U.S. states using a previously
defined algorithm. We included new users of HCQ (no use in ≥6 months) with ≥12 months of continuous enrollment with
complete drug dispensing data following HCQ initiation. Adherence was measured over this 12-month period using the
proportion of days covered (PDC) and defined as ≥80%. We identified individual-level characteristics (demographics,
medications, comorbidities) from Medicaid data. We obtained zip code, county and state-level characteristics (percent of the
population below the Federal poverty level (FPL), educational attainment and percent black population) from the American
Community Survey. Health resource data (per capita hospitals, physicians, pharmacies and health professional shortage
areas) were obtained from Area Health Resources Files. We used four-level hierarchical multivariable logistic regression
models with Markov Chain Monte Carlo procedures to examine odds (OR [95% credible interval]) of adherence vs.
nonadherence.
Results: Among 10,268 HCQ initiators with SLE residing within 4,930 zip codes in 1,414 counties in 28 states, 15% were
adherent. After adjusting for individual-level characteristics, we observed lower odds of adherence across zip codes with
higher percentages of black residents (highest tertile OR 0.81 [0.68-0.96] vs. lowest) (Table). The association remained after
controlling for zip code percent below FPL and educational attainment. Odds of adherence were higher in counties with the
greatest number of hospitals vs. the fewest (OR 1.32 [1.08-1.60]), and lower in health professional shortage areas (OR 0.86
[0.75-1.00]). There was no association with county-level per capita number of physicians or pharmacists. There was minimal
variation in adherence by geographic area; the greatest was between states (1.4%).
Conclusion: Among Medicaid beneficiaries with lupus, after accounting for individual-level factors, we observed reduced
odds of HCQ adherence in areas with higher percentages of black residents, fewer hospitals, and shortages of health
professionals. Further studies are needed to assess whether racial residential segregation and poorer availability of high-
quality medical care may contribute to racial differences in HCQ nonadherence and in turn, to disparities in lupus outcomes.
Table: Multilevel hierarchical logistic regression models examining the odds (OR with 95% credible
interval) of adherence (PDC≥80%) vs. nonadherence among 10,268 individuals with lupus within 4,930 zip
codes in 1,414 counties in 28 states
Model 1 Model 2 Model 3 Model 4 Model 5
Zip code-level fixed effect variables
% Black Population
Tertile 2 0.84 (0.73- 0.85 (0.73- 0.87 (0.74- 0.84 (0.74- 0.85 (0.74-
0.98) 0.97) 1.02) 1.00) 0.98)
Tertile 3 0.81 (0.68- 0.79 (0.66- 0.83 (0.69- 0.81 (0.68- 0.82 (0.70-
0.96) 0.94) 1.00) 0.98) 0.96)
% Below Federal Poverty
Level
Tertile 2 1.02 (0.87-
1.19)
Tertile 3 1.09 (0.93-
1.28)
County-level fixed effect variables
Hospitals per capita
Tertile 2 1.14 (0.99-
1.31)
Tertile 3 1.32 (1.08-
1.60)
Health Professional
Shortage Area
Partial 0.82 (0.64-
1.03)
Whole 0.86 (0.75-
1.00)
State-level fixed effect variable
Rheumatologists per capita
Tertile 2 1.22 (0.91-
1.60)
Tertile 3 1.15 (0.87-
1.47)
In all models, tertile 1 is the reference. All models are adjusted for individual-level age, sex, race/ethnicity,
SLE risk-adjustment index, lupus nephritis, diabetes mellitus, antidepressant use, corticosteroid use,
immunosuppressive medication use, number of lupus-related lab tests, number of medications, healthcare
utilization, obesity, smoking and calendar year. All models account for zip code, county and state-level
random effects. County and state-level models are adjusted for all individual-level characteristics as well as
zip code-level percent black (Model 1). Model 1 was chosen from Models 1-2, and an additional model
including educational attainment, because it had the lowest deviance information criterion (DIC). Models 3-
5 included healthcare resource variables separately due to collinearity.
Disclosure: C. H. Feldman, None; K. H. Costenbader, None; D. H. Solomon, None; S. V. Subramanian, None; I.

Kawachi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/area-level-predictors-of-medication-

nonadherence-among-u-s-medicaid-beneficiaries-with-lupus-a-multilevel-study
Discordant Patient-Physician Assessments of Disease Activity and Its

Persistence Adversely Impact Quality of Life and Work Productivity in
United States Hispanics with Rheumatoid Arthritis
George Karpouzas1, Sera Ramadan2, Chelsie Cost3, Taylor Draper4, Elizabeth Hernandez3 and Sarah Ormseth3, 1Division
of Rheumatology, Harbor-UCLA Medical Center, Torrance, CA, 2Internal Medicine, Dignity Health St. Mary Medical
Center, Long Beach, CA, 3Rheumatology, Harbor-UCLA Medical Center, Torrance, CA, 4Psychology, Loma Linda
University, Loma Linda, CA
SESSION INFORMATION
Background/Purpose: The impact of discordant patient-physician assessments of rheumatoid arthritis (RA) activity on
quality of life is largely unknown. We examined the prevalence and stability of discordance on serial visits, over two years,
in a large cohort of Hispanics from a single center in the US; we further explored the influence of discordance -at any point-
and its persistence on health-related quality of life (HRQoL) and work productivity upon final visit.
Methods: We evaluated 308 patients with established RA. Patient (PGA) and physician/ evaluator (EGA) global
assessments were measured annually on 10-cm visual analogue scales; discordance was defined as a difference ³ 3 cm
between them. HRQoL was quantified using the SF-12 physical (PCS) and mental (MCS) component summary scores
(higher scores indicate better HRQoL). Activity impairment, work productivity loss, presenteeism and absenteeism were
calculated based on the Work Productivity and Activity Impairment Questionnaire. The impact of discordance and its
persistence on HRQoL, activity impairment and employment-related outcomes at two years was assessed using analysis of
covariance, adjusting for baseline values of those outcomes.
Results: Positive discordance (PD, or higher patient ratings) was more prevalent and stable over time (k range 0.32-0.36);
85 (27.6%) subjects had PD once, 49 (15.9%) twice, and 45 (14.6%) at all three time points. Negative discordance (ND, or
lower patient ratings) was less common and unstable; 45 (14.6%) patients had ND once, 10 (3.3%) twice, and 1 (0.3%) at all
three time points. Any PD throughout the study adversely impacted HRQoL upon last visit; persistence of PD yielded
progressively lower SF-12 PCS (Fig 1A, p<0.001), and SF-12 MCS was lower among patients with any PD compared to
those without (Fig 1B, p<0.001). Presence and persistence of PD yielded progressively greater activity impairment at final
visit (Fig 1C, p<0.001). PD was negatively associated with employment (p<0.025); moreover, higher presenteeism
(p=0.001) and work productivity loss (p=0.014) were seen with any PD (Fig 1D). PD appeared to be a patient-specific rather
than a visit-specific feature; those with baseline PD had higher prevalence of fibromyalgia and irreversible articular damage
(both p<0.01), and were 5-times more likely to have future PD.
Conclusion: Positive discordance is common and generally stable over time. Its presence Ð at any time- and persistence
adversely and incrementally impact clinical outcomes, including health related quality of life, work productivity, and activity
impairment upon final visit.
Disclosure: G. Karpouzas, None; S. Ramadan, None; C. Cost, None; T. Draper, None; E. Hernandez, None; S.
Ormseth, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/discordant-patient-physician-

assessments-of-disease-activity-and-its-persistence-adversely-impact-quality-of-life-and-work-productivity-in-united-states-
hispanics-with-rheumatoid-arthritis
Biologic DMARD Prescribing Patterns in Elderly Patients with Rheumatoid

Arthritis
Britney Jones1, Imran Hassan2, Walter P. Maksymowych3 and Elaine Yacyshyn4, 1University of Alberta, Edmonton, AB,
Canada, 2EPICORE Centre, University of Alberta, Edmonton, AB, Canada, 3Department of Rheumatology, University of
Alberta, Edmonton, AB, Canada, 4Medicine, University of Alberta, Edmonton, AB, Canada
SESSION INFORMATION
Background/Purpose:
Rheumatoid arthritis is a chronic inflammatory process involving progressive destruction of joints.
Currently, 30% of rheumatoid arthritis (RA) patients are over the age of 65. As the population ages, shifts in epidemiology
and disease patterns will require an appropriate response from the healthcare system. Elderly patients frequently have more
active disease; however, inequalities in prescribing patterns may favor more aggressive treatment in younger patients. There
are myriad different reasons why this may be the case; elderly patients tend to have a higher number of comorbidities, more
medications, and a greater degree of frailty.
Elderly patients with RA benefit from tight disease control and use of biologic Disease Modifying Anti-rheumatic Drugs
(boDMARDs) minimizes the need for other medications. There is a growing body of evidence suggesting that patient
outcomes do not significantly decline with age. The reluctance to use boDMARDs in the elderly from concerns around side
effects paradoxically means these patients may be exposed to much more deleterious drugs such as glucocorticoids,
narcotics, and NSAIDs that may be less desirable in the elderly population.
This study identified differences in biologic prescribing patterns between young (<65 years old) and elderly (> 65 years old)
patients with RA. Secondary outcomes examined demographic variation and disease activity between patient age groups.
Methods:
A retrospective cohort study of 1581 patients was conducted using information collected from the Rheumatoid Arthritis
Pharmacovigilance Program and Outcomes Research in Therapeutics (RAPPORT) Database. This database encompasses an
inception cohort of all RA patients in Northern Alberta starting treatment with biologics.
Fisher’s exact test was used to determine the age of RA patients at first boDMARD prescription using the cutoff of young
(<65 years old) and elderly (> 65 years old).
Wilcoxon-Mann-Whitney test was used to stratify disease activity in different age groups using the Health Assessment
Questionnaire (HAQ) and Disease Activity Score (DAS28).
Results:
A significantly larger proportion of young RA patients were prescribed boDMARDs compared with elderly RA patients
(96.8% vs 90.0%; p = 0.006). Elderly patients prescribed boDMARDs had significantly higher HAQ (mean 1.69 +/- 0.66; p
= 0.001) and DAS28 (mean 6.0 +/- 1.68; p = 0.002) scores compared to younger patients (mean 1.41 +/- 0.72 and mean 5.29
+/- 1.7, respectively)
There was no statistically significant difference in other demographic information including sex, ethnicity, and years of
schooling.
Conclusion:
Despite current guidelines recommending early, aggressive disease control including the timely introduction of boDMARDs,
this study suggests that a prescribing bias remains. Younger patients with lower levels of disease activity are more likely to
receive biologic therapies than their elderly counterparts. While there was no statistically significant difference between the
basic demographics of each cohort, patient’s level of frailty and comorbid conditions were not accounted for in this study.
Disclosure: B. Jones, None; I. Hassan, None; W. P. Maksymowych, None; E. Yacyshyn, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/biologic-dmard-prescribing-patterns-in-

elderly-patients-with-rheumatoid-arthritis
Can Education Mitigate the Effect of Poverty on Total Knee Replacement

(TKR) Outcomes?
Susan M. Goodman1, Bella Y. Mehta2, Meng Zhang3, Jackie Szymonifka4, Iris Navarro-Millán5, Joseph T. Nguyen3, Yuo-
Yu Lee3, Mark P. Figgie6, Michael L. Parks6, Shirin A. Dey4, Daisy Crego4, Linda A. Russell1, Lisa A. Mandl1 and Anne R.
Bass1, 1Rheumatology, Hospital for Special Surgery/Weill Cornell Medicine, New York, NY, 2Hospital for Special
Surgery/Columbia University Mailman School of Public Health, New York, NY, 3Epidemiology and Biostatistics, Hospital
for Special Surgery, New York, NY, 4Rheumatology, Hospital for Special Surgery, New York, NY, 5Hospital for Special
Surgery/Weill Cornell Medicine, New York, NY, 6Orthopaedic Surgery, Hospital for Special Surgery/Weill Cornell
Medicine, New York, NY
SESSION INFORMATION
Background/Purpose: Health outcomes after total knee replacement (TKR) are generally worse for patients from high
poverty neighborhoods. Whether education mitigates the effect of poverty is not known. We assessed the interaction
between education and poverty on pain and function 2 years after TKR.
Methods: Patient-level variables - demographics, baseline and 2-year WOMAC pain and function scores, and geocodable
US addresses - were obtained from an institutional TKR registry (5/07 - 2/11). Individual patient data were linked to US
Census Bureau data at the census tract level. Statistical models including both patient-level and census tract-level variables
were constructed within multilevel frameworks. Linear mixed effects models with separate random intercepts for each
census tract were used to assess the effect of the interaction between education at the individual and census tract level and
census tract poverty level on WOMAC scores at 2 years.
Results: Of 3970 TKR cases, 2438 (61%) were college-educated or above (Table 1, Figure 1). In the univariable analysis,
race, sex, BMI, baseline WOMAC, and Medicaid were significantly associated with worse WOMAC scores at 2 years. In a
linear mixed effects model, living in neighborhoods where <15% are college-educated and living in neighborhoods where
≥15% are below poverty were significantly associated with worse WOMAC pain (p=0.02) and function (p=0.006) at 2
years. There was little interaction between individual education and census tract education in our models, but when we
assessed the interaction between individual education and community poverty, we found a significant interaction between
them and WOMAC pain or function at 2 years. Comparing patients without college in high vs low poverty communities,
WOMAC pain at 2 years was predicted to be 10 points lower (83.36 versus 72.75) and decreased in a linear fashion as
community poverty increased, whereas patients with college had a difference in predicted WOMAC pain scores of only 1
point (87.10 vs. 86.09) (Figure 2); results for WOMAC function were similar.
Conclusion: In poorer communities, those without college education attain WOMAC scores 10 points lower than those with
college education, a clinically meaningful difference. Education has no effect in wealthier communities. The reason
education appears protective in poorer communities needs further study.
Table 1. Characteristics of the cohort
Characteristic Total College or above Non-college P-Value
Number of patients 3970 (100%) 2438 (61%) 1532 (39%)
Age at surgery (years), mean (SD) 67.13(9.58) 66.86 (9.35) 67.55 (9.92) 0.014
2437 (61.39%) 1397 (57.30%) 1040 (67.89%)
Female, n (%) <0.0001
BMI (kg/m2), mean (SD) 29.99 (5.92) 29.29 (5.53) 31.10 (6.34) <0.0001
81 (2.30%) 39 (1.78%) 42 (3.15%)
Hispanic, n (%) 0.008
One or more comorbidities, n (%) 1120 (28.21%) 634 (26.00%) 486 (31.72%) <0.0001
3780 (95.21%) 2352 (96.47%) 1428 (93.21%)
White, n (%) <0.0001
Insurance payer, n (%) 58 (1.46%) 13 (0.53%) 45 (2.94%)
Medicaid 2492 (62.77%) 1499 (61.48%) 993 (64.82%)

<0.0001
Medicare 1420 (35.77%) 926 (37.98%) 494 (32.25%)
Other insurance
ASA Class, n (%) 2 1 1
Missing 3162 (79.69%) 1963 (80.55%) 1199 (78.31%)

0.09
I-II 806 (20.31%) 474 (19.45%) 332 (21.69%)
III-IV
Hospital for Special Surgery 78.50 (17.99) 79.03 (17.56) 77.59 (18.68) 0.087
Expectations Score, mean (SD)
WOMAC pain at baseline, mean (SD) 54.32 (17.65) 57.23 (16.92) 49.63 (17.81) <0.0001
WOMAC pain at 2 Years, mean (SD) 87.42 (16.05) 89.21 (14.01) 84.54 (18.52) <0.0001
Delta WOMAC pain, mean (SD) 33.13 (20.30) 32.08 (19.36) 34.85 (21.65) <0.0001
WOMAC function at baseline, mean 53.45 (17.76) 56.95 (17.07) 47.85 (17.39) <0.0001
(SD)
WOMAC function at 2 Years, mean (SD) 85.08 (16.49) 86.94 (14.52) 82.09 (18.86) <0.0001
Delta WOMAC function, mean (SD) 31.58 (19.73) 30.00 (18.87) 34.11 (20.80) <0.0001
Census Tract Percent Below Poverty 3174 (79.97%) 2021 (82.93%) 1153 (75.26%)
Level, n (%)
594 (14.97%) 318 (13.05%) 276 (18.02%)
<10% <0.0001
201 (5.06%) 98 (4.02%) 103 (6.72%)
10%-20%
>20%
Census Tract Percent Below Poverty 3174 (79.97%) 2247 (92.20%) 1346 (87.86%)
Level, n (%)
594 (14.97%) 190 (7.80%) 186 (12.14%) <0.0001
Low poverty <15% Middle to
high poverty >=15%
Census Tract Percent of 25 or older with 81 (2.04%) 18 (0.74%) 63 (4.11%) <0.0001
Bachelor’s degree or above, n (%)
1194 (30.08%) 537 (22.03%) 657 (42.89%)
Low Education <15%
2695 (67.88%) 1883 (77.24%) 812 (53.00%)
Middle Education 15%-39.9%
High Education >=40%
Disclosure: S. M. Goodman, None; B. Y. Mehta, None; M. Zhang, None; J. Szymonifka, None; I. Navarro-Millán,
None; J. T. Nguyen, None; Y. Y. Lee, None; M. P. Figgie, Lima, 7,Mekanika, 1; M. L. Parks, Zimmer Biomet, Inc., 5; S.
A. Dey, None; D. Crego, None; L. A. Russell, None; L. A. Mandl, Boehringer Ingelheim, 2,American College of
Physicians, 3,Up To Date, 7; A. R. Bass, Pfizer, 9,Abbot, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/can-education-mitigate-the-effect-of-

poverty-on-total-knee-replacement-tkr-outcomes
Prevalence of Juvenile Idiopathic Arthritis in the Alaska Native Population

Beverly Khodra1, Anne Stevens2 and Elizabeth Ferucci3, 1Alaska WWAMI, University of Washington School of Medicine,
Anchorage, AK, 2Seattle Children's Res Inst, Seattle Children's Hospital, University of Washington, Seattle, WA, 3Division
of Community Health Services, Alaska Native Tribal Health Consortium, Anchorage, AK
SESSION INFORMATION
Background/Purpose: High rates of rheumatoid arthritis and systemic lupus erythematosus have been described in
indigenous North American (INA) populations. Few studies have investigated the prevalence or clinical patterns of juvenile
idiopathic arthritis (JIA) in INA populations, but two studies have suggested high rates in specific regions of the US and
Canada. The purpose of this project was to determine the prevalence of JIA overall and its subtypes in Alaska Native
children statewide and to describe the clinical characteristics and treatment patterns of JIA in this population.
Methods: Potential cases of JIA were identified by a query of administrative data from the electronic health record of the
Alaska Native Medical Center for codes possibly identifying JIA and from adult and pediatric rheumatology clinic
databases. Cases were required to be under age 18 as of 9/30/2015 and to have a diagnosis of JIA confirmed by medical
record abstraction. The denominator for prevalence was the 2015 Alaska Area Indian Health Service user population under
the age of 18. Medical record abstraction was used to confirm the criteria met for JIA, subtype diagnosed, demographic
features, other clinical characteristics, and medications ever used for treatment.
Results:
The unadjusted prevalence of JIA in Alaska Native children was 67.5 per 100,000 (age-adjusted 71.7 per 100,000). JIA was
more common in females than males (unadjusted prevalence 91.2 vs. 45.5 per 100,000). Oligoarthritis was the most
common subtype (32% of cases), but enthesitis-related arthritis was also common (26.3% of cases). The mean age at
diagnosis was 9 years and the prevalence was highest in children aged 16-18. During the one year study period, cases had a
mean of 2.2 visits to a rheumatologist. Of the combined cohort, 53% had a positive ANA, 26% had positive rheumatoid
factor, 24% had positive anti-CCP antibody, and 26% had the presence of HLA B27. Uveitis had been diagnosed in 26% of
cases. Methotrexate was the most commonly prescribed non-biologic DMARD (ever prescribed in 66% of cases) and
adalimumab was the most commonly prescribed biologic (in 32%).
Conclusion: The prevalence of JIA in Alaska Native children may be slightly higher than the general US population.
Enthesitis-related arthritis makes up a higher proportion of cases than in other populations described, likely because of the
high prevalence of HLA B27 in this population.
Disclosure: B. Khodra, None; A. Stevens, None; E. Ferucci, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prevalence-of-juvenile-idiopathic-

arthritis-in-the-alaska-native-population
Open-Source Conensus-Based Models to Improve the Cost-Effectiveness of

Rheumatology Care
Devin Incerti1, Jeffrey R. Curtis2, Maria Lorenzi1 and Jeroen Jansen1, 1Innovation and Value Initiative, Oakland, CA,
2Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL

SESSION INFORMATION
Session Title: ARHP Clinical Practice/Patient Care/Health Services Research
Background/Purpose: The treatment and prognosis of moderate to severe rheumatoid arthritis has improved considerably
due to the advent of biological therapies. But at the same time, the high costs of treatment are a threat to affordability and
access to patients, and highlight the need for cost-effectiveness models that can help align prices with value. Unfortunately,
there is no consensus in the literature on the proper mathematical structure for these models and estimates of value vary
widely. Moreover, new evidence on the efficacy of biologics is rapidly evolving, so estimates of value must be updated as
the evidence base evolves. Transparent, flexible, and accessible cost-effectiveness models that shed light on the implications
of different modeling approaches are needed.
Methods: We developed an open-source “family” of cost-effectiveness models that reflects a number of scientifically
defensible approaches and variation in the perspectives of decision makers. The code is publically available on GitHub, a
version control repository, and the model has been released as an R package. We also created a user-friendly web application
where users can modify parameter values or structural assumptions and run the model online. We used the models to
compare the cost-effectiveness of a standard sequence of 6 biologics treatments to conventional disease-modifying
antirheumatic drugs (cDMARDs) using a number of different modeling assumptions.
Results: Under various plausible assumptions, incremental cost-effectiveness ratios (ICERs) ranged from less than $100,000
to around $300,000. Biologics were predicted to be more cost-effective when they had a larger effect on the Health
Assessment Questionnaire (HAQ) Disability Index score at 6 months, increases in the HAQ score were assumed to lead to
larger increases in mortality, the drop in clinical efficacy after each treatment failure was smaller, the HAQ score on
cDMARDs progressed more quickly over time, biologics were assumed to be discounted more from their wholesale
acquisition cost, and productivity losses were larger. For example, under our baseline assumptions, the ICER was
approximately $120,000 when the effect of treatment on HAQ did not decline after the first treatment failure and over
$200,000 when we assumed no clinical efficacy after 1st line treatment. In addition, subgroup analyses conducted using our
baseline assumptions indicated that biologics were more cost-effectiveness in younger patients, with ICERs ranging from
$100,00 at age 35 to $165,000 at age 70.
Conclusion: Estimates of value vary considerably across different modeling assumptions, suggesting that steps must be
taken to shrink diversity in modeling approaches and evidence considered to the greatest extent possible. These include new
research studies and processes to encourage collaboration.
Disclosure: D. Incerti, Amgen, 5; J. R. Curtis, Crescendo Biosciences, 2,Crescendo Biosciences, 5; M. Lorenzi, None; J.
Jansen, Amgen, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/open-source-conensus-based-models-to-

improve-the-cost-effectiveness-of-rheumatology-care
Relationship of Traumatic Knee Injuries to Early-Onset Knee Osteoarthritis

in Young Military Officers
Yvonne M. Golightly1, Maryalice Nocera2, John Cantrell2, Jordan B. Renner3 and Stephen W. Marshall4, 1Epidemiology,
University of North Carolina at Chapel Hill, Chapel Hill, NC, 2Injury Prevention Research Center, University of North
Carolina at Chapel Hill, Chapel Hill, NC, 3UNC School of Medicine, University of North Carolina, Chapel Hill, NC,
4Epidemiology, University of North Carolina, Chapel Hill, NC
SESSION INFORMATION
Background/Purpose: Traumatic knee injuries, such as tears and ruptures of the anterior cruciate ligament (ACL) and/or
menisci, are associated with osteoarthritis (OA). Surprisingly little is known, however, about the etiology and pathology
underlying this association. Large epidemiologic studies of populations with high rates of knee injury are needed to enhance
our understanding of the onset and progression of injury-mediated OA. We investigated radiographic OA, symptoms, and
patient-reported outcomes in military officers with and without a history of traumatic knee injury.
Methods:
Participants were 439 military officers who either had a history of ACL and/or meniscal injuries (knee injury group) or were
injury-free (uninjured group). Participants were recruited from an existing cohort of 6452 military officers originally
enrolled between 2004 and 2008 as matriculating cadets at the U.S. Air Force Academy, U.S. Military Academy, or U.S.
Naval Academy. The knee injury group (n=167) experienced ACL/meniscal injuries prior to, during, or after their 4-year
academy career. The uninjured group (n=272) was site-matched from the same source cohort but had no history of
ACL/meniscal injuries. Injury status was established using a self-reported injury history questionnaire, confirmed by clinical
record review. Knee OA was assessed using 1) a single-item measure of knee pain, aching, or stiffness in the past 30 days, 2)
a patient-reported knee outcome measure (Knee injury and OA Outcome Score [KOOS]; 0 [extreme] - 100 [no problems]),
and 3) standardized weight-bearing posteroanterior radiographs of the tibiofemoral joint obtained using a fixed-flexion knee
positioning frame. Radiographic knee OA was defined as Kellgren-Lawrence grade ≥2. Knee-injured and non-injured
groups were compared using descriptive statistics and prevalence ratios (PR) with 95% confidence intervals (95%CI).
Results: Enrollment was completed on March 31, 2017, and collection of survey and radiographic data is on-going.
Currently available data are presented. Among 403 participants with survey data, mean age was 28 years and mean body
mass index was 25 kg/m2. Per the parent cohort, 40% were women. Mean time from first ACL/meniscal injury to follow-up
assessment was 8.6 years. Among participants with available knee radiographic data, 19.0% (16/84) of knee-injured had
radiographic knee OA, compared to 0% (0/104) of the uninjured (PR=40, p<0.001). Nearly 38% (51/136) of participants
with knee injury reported moderate-severe symptoms vs. 13% (20/156) of the uninjured (PR=2.9, 95%CI: 1.8, 4.7, p<0.001).
Among 292 participants with available KOOS data, the knee-injured had clinically-relevant deficits on KOOS symptoms,
sports/recreation, and quality of life scales (mean differences: -7.7, -8.1 and -11.0, respectively vs. non-injured, all p<0.001).
Conclusion: Traumatic knee injuries are strongly linked to early-onset knee OA, which greatly impacts quality of life and
knee function during physically-vigorous activities. At a mean age of <30 years, young officers with a history of knee
trauma experience substantial limitations from OA that impede their military performance.
Disclosure: Y. M. Golightly, None; M. Nocera, None; J. Cantrell, None; J. B. Renner, None; S. W. Marshall, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/relationship-of-traumatic-knee-injuries-

to-early-onset-knee-osteoarthritis-in-young-military-officers
Do Familiarity with Centers for Disease Control Guidelines, Continuing

Education, and Provider Characteristics Influence Adherence to Chronic Pain
Management Practices and Opioid Prescribing?
Kim Jones1, Ronald Friend2, Robert M. Bennett1 and Jean McCalmont3, 1Schools of Nursing and Medicine, Oregon Health
& Science University, Portland, OR, 2School of Nursing, Oregon Health & Science University, Portland, OR, 3Nursing,
Oregon Health & Science University, Portland, OR
SESSION INFORMATION
Background/Purpose: 1) To evaluate providers’ experience and knowledge with chronic pain management and opioid use
with actual utilization of the Centers for Disease Control’s 2016 Guidelines for Prescribing Opioids for Chronic Pain. 2) To
evaluate the specific influence of continuing education (CME), familiarity with CDC guidelines, and provider profession
and region on confidence and best practice adherence in chronic pain management.
Methods:
A cross-sectional, web-based survey conducted between January and April of 2017 with a convenience sample of 417
Oregon prescribing providers consisting of 210 MD and 207 NP participants (Urban/Rural= 64/36%; Age= 49.7 sd=12.2,
Female=32%, Years of Practice= 15.7, sd =12.3). Measures included CME hours in past 2 years (minimal, 0-3; moderate, 4-
10; high, 11 or more) and CDC familiarity (not read or read not applied vs. read and applied). Primary outcome variables
included provider confidence in pain management (0-9), opioid conversion confidence (0-9), and adherence to best practices
(opioid risk tool, urine drug screening, opioid treatment agreement, Oregon Prescription Drug Monitoring Program; all
Likert, 0-5). Multivariate analysis of variance (MANOVA) and Chi-Square were used to analyze the influence of CME,
CDC familiarity, provider profession and regional medical setting on provider best practices and confidence ratings.
Results: CME hours was significantly associated with increased use of opioid best practices (2.6, 3.2, 3.8; p <.001; scale 0-
5), opioid conversion confidence (5.5, 6.5, 7.4; p. <.001; scale 0-9) and confidence in pain management (5.5, 5.9, 6.9; p
<.001, scale 0-9). Providers familiar with CDC guidelines were only slightly more likely to apply best practices than were
not (57% vs 43%), while increases in CME were more strongly associated with CDC best practices use (42% vs 57% vs
72%; p <.001). Neither providers professional status (MD vs NP) nor regional setting (urban vs. rural) showed differences in
opioid best practices or general confidence in pain management with the exception of opioid conversion confidence where
NPs reported slightly less than MDs (5.9 vs. 6.9; p <. 001, scale 0-9) and rural slightly more than urban providers (6.8 vs
6.2; p<. 05; scale 0-9).
Conclusion: Results demonstrate that recent CME in chronic non-cancer pain positively benefits provider confidence in
pain management and application of best practices, as defined by the CDC guidelines. Nurse Practitioners and rural
providers were found to provide equivalent adherence to best practices and confidence levels to their MD and urban
counterparts, with minor exceptions.
Disclosure: K. Jones, None; R. Friend, None; R. M. Bennett, None; J. McCalmont, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/do-familiarity-with-centers-for-disease-

control-guidelines-continuing-education-and-provider-characteristics-influence-adherence-to-chronic-pain-management-
practices-and-opioid
Online Consultation for Chinese Patients with Rheumatic Diseases Based on

Smart System of Disease Management (SSDM) Mobile Tool: A Study of
Medical Economics
Fei Xiao1, Rui Wu2, Zhenchun Zhang3, Weiqi Min4, Yanchun Tang5, Xinwang Duan6, Lingfei Mo7, Zhaojun Guo8,
Yanping Zhao9, Henglian Wu10, Xia Xu11, Feng Jiang12, Jing Yu13, Jianhong Qiang14, Yan Wang9, Ruijie Wu15, Anbing
Zhang16, Limei Gu17, Hui Xiao1, Yuhua Jia1, Yuan Liu1, Bing Wu1, Chunhui Shi1 and Fengchun Zhang18, 1Gothic Internet
Technology Corporation, Shanghai, China, 2The First Affiliated Hospital of Nanchang University, Nanchang, China,
3People's Hospital of Linyi, Shandong, Linyi, China, 4Heze Municiple Hospital, Heze, China, 5Yantai YuHuangDing
Hospital, Yantai, China, 6Department of rheumatology, The Second Affiliated Hospital of Nanchang University, Nanchang,
China, 7The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China, 8The First People's Hospital of Huainan
City, Huainan, China, 9First Affiliated Hospital of Harbin Medical University, Harbin, China, 10Dongguan Donghua
Hospital, Dongguan, China, 11Changhai Hospital, Shanghai, China, 12Huzhou Third People's Hospital, Huzhou, China,
13The First Hospital Affiliated with the University of Traditional Chinese Medicine in Liaoning Province, Shenyang, China,
14Yan'an People's Hospital, Yan'an, China, 15The Second Affiliated Hospital of Shanxi Medical College, Taiyuan, China,
16Xiangyang Central Hospital, Xiangyang, China, 17Central People's Hospital of Siping, Siping, China, 18Peking Union
Medical College Hospital, Beijing, China
SESSION INFORMATION
Background/Purpose: China doesn’t have efficient primary medical care and referral system. Patients can choose any
hospitals or any doctors they like to seek medical care. As a result, most patients with rheumatic diseases rushed to a few
large cities. Surveys showed that more than 40% of the rheumatic disease patients were unnecessary to go to hospital and
they only need advices from specialist. Smart System of Disease Management (SSDM) is a series of applications for chronic
diseases management, which strengthens the interaction between doctors and patients based on valuable clinical data. Our
previous study showed that rheumatoid arthritis (RA) patients can master the SSDM and perform self-management after
training, including disease activity score with 28 joints (DAS28) and health assessment questionnaire (HAQ) evaluations, as
well as medication and lab test data entries. The purpose of this study is to evaluate the feasibility and benefit of the medical
economics of online consultation based on SSDM by rheumatologist.
Methods: The rheumatologists implemented the education and training programs on patients in using SSDM and assist the
patients in downloading SSDM mobile application. The SSDM includes doctors’ and patients’ interfaces. The patient’s
terminal system includes self-assessment (DAS28, HAQ), medication management, adverse events management and
laboratory records. After data entry, patients can synchronize data to the authorized doctor. On the basis of these data, the
rheumatologists can accept the request from their follow-up patients and practice consultation through SSDM in the form of
text or voice.
Results: From February 2015 to June 2017, 403 rheumatologists supplied 4,002 patients (RA 42%, systemic lupus
erythematosus 21%, ankylosing spondylitis 11%, gout 10%, osteoarthritis 5%, Sjogren syndrome 3% and other rheumatic
diseases 7%) with 293 free and 3,709 paid consultations. Paid consulting included 3,983 times text Q&A and 19 voice
consultations. The consulting fee ranged from RMB 10 to 500 yuan (UDS: RMB =1: 6.81) each in average of 96.06 ± 38.61
yuan, which match the registration fee in hospital. The total collection of fee for consultations was 477,960 yuan RMB.
35.3% patients receiving online consultation lived in different city with the rheumatologists. If patients seek medical care in
hospital, in addition to the registration fees and medical expenses, the mean cost of transportation, accommodation, meals
and lost wages was 565.17 ± 510.49 (200 - 2,800) yuan. The total of cost for all patients would have been 3,157,220 yuan
RMB, which is 6.61 times higher compared with the cost of online. Online consultations through the SSDM can save
84.86% of the cost for patients. Survey shows that all patients were satisfied and 66.35% of them were "very satisfied" with
the consultations.
Conclusion: Through online consultations using SSDM system, Chinese patients with rheumatic diseases can enjoy reduced
cost with high satisfaction. In the era lack of primary care system in China, SSDM may serve as a complimentary platform
to control medical care cost, as well as develop a new partnership between physicians and patients.
Disclosure: F. Xiao, None; R. Wu, None; Z. Zhang, None; W. Min, None; Y. Tang, None; X. Duan, None; L. Mo, None;
Z. Guo, None; Y. Zhao, None; H. Wu, None; X. Xu, None; F. Jiang, None; J. Yu, None; J. Qiang, None; Y. Wang, None;
R. Wu, None; A. Zhang, None; L. Gu, None; H. Xiao, None; Y. Jia, None; Y. Liu, None; B. Wu, None; C. Shi, None; F.
Zhang, Xian Janssen, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/online-consultation-for-chinese-patients-

with-rheumatic-diseases-based-on-smart-system-of-disease-management-ssdm-mobile-tool-a-study-of-medical-economics
Variation in SLE-Related Pain – a Seven Year Follow-up Study

Eva Waldheim1, Sofia Ajeganova2, Stefan Bergman3, Johan Frostegård4 and Elisabet Welin Henriksson5,6, 1Karolinska
Institutet, Stockholm, Sweden, 2Rheumatology unit, Department of Medicine,, Karolinska Institutet at Karolinska University
Hospital Huddinge, Stockholm, Sweden, 3University of Gothenburg, Gothenburg, Sweden, 4Institute of Environmental
Medicine, Karolinska Institutet, Stockholm, Sweden, 5Department of Medical and Health Sciences, Linkoping University,
Linköping, Sweden, 6Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
SESSION INFORMATION
Background/Purpose: We have previously shown that 24% of the patients in a SLE-cohort study (n=84) reported high
levels of SLE-related pain (VAS≥40 mm), and also impaired HRQoL, more fatigue, higher levels of symptoms regarding
anxiety and depression. In contrast, the patients reporting ≤39 mm on VAS did not differ from the controls regarding patient
reported outcomes. We have now investigated the variation in SLE-related pain and its association with chronic widespread
pain (CWP) and patient-related outcomes after seven years of follow-up.
Methods: 64 of 84 patients agreed to participate in the 7-year follow-up and answered questionnaires on pain (VAS/mm),
fatigue (MAF), HRQoL (SF-36), anxiety and depression (HADS) and, in case of remaining pain > three months, marked
painful body regions on a pain-drawing. Disease activity and damage (SLAM, SLEDAI, SLICC) were also captured.
Nonparametric statistics were used, and difference in measures (diff) between inclusion and follow-up was calculated.
Results: For the patients with low levels of SLE-related pain the previous week (≤39 mm on VAS) at inclusion, n=50, there
were no significant difference at 7 years follow-up in pain, fatigue, anxiety, depression and most dimensions of SF-36. Of
these patients with low level of pain, 26% indicated chronic widespread pain on the pain drawing.
Among patients with high degree of pain (≥40 mm VAS) at inclusion, n=14, half of the patients reported significantly
decreased pain, diff (IQR) 45 (35 to 65), p=0.021, fatigue, 8 (8 to 17), p=0.018, anxiety, 4 (1 to 4), p=0.035 and depression,
4 (2 to 5), p=0.018 and improvements in most dimensions of SF-36.
However, half of the patients with high degree of pain at inclusion reported no significant changes at follow up regarding
pain, median diff (IQR) -13 (-20 to 28), fatigue, 5 (-0.3 to 6), anxiety, 2 (-1 to 3) and depression, 0 (-3 to 2). These patients
reported significant deterioration in vitality in SF-36 but no significant changes in the other dimensions of SF-36. All
patients with high remaining pain indicated chronic widespread pain on the pain drawing. These patients with remaining
pain had significantly higher SLAM at follow-up compared to the patients with decreased pain at follow-up, p=0.017 and the
patients with low levels of pain at inclusion, p=0.006. No significant differences were found in SLEDAI and disease damage
Conclusion: For most patients, pain and other patient reported outcomes remained low or improved after seven years.
However, a minority of the patients reported remaining high levels of pain after seven years, and were characterized by a
heavy symptom burden with widespread pain more than three months, high levels of pain-related problems, impaired health-
related quality of life and remaining high levels of fatigue. The results highlight the heterogeneous nature of SLE and
stresses the needs of special attention to vulnerable sub-groups of patients with SLE.
Disclosure: E. Waldheim, None; S. Ajeganova, None; S. Bergman, None; J. Frostegård, None; E. Welin Henriksson,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/variation-in-sle-related-pain-a-seven-

year-follow-up-study
Efficacy and Safety of Modified-Release Prednisone in Managing Moderate

Activity SLE during Pregnancy: An Implemented Case-Control Study
Marianna Meroni1, Véronique Laure Ramoni2, Massimiliano Parodi3, Paolo Stobbione3 and Maurizio Cutolo4, 1Research
Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, IRCCS A.O.U. San
Martino-IST, University of Genova, Genoa, Italy, Genova, Italy, 2Division of Rheumatology, IRCCS San Matteo Hospital
Foundation, University of Pavia, Pavia, Italy, Pavia, Italy, 3Rheumatology Unit, Internal Medicine Department, A.O. S.S.
Antonio e Biagio e Cesare Arrigo, Alessandria, Italy, Alessandria, Italy, 4Research Laboratory and Academic Division of
Clinical Rheumatology, Department of Internal Medicine, IRCCS A.O.U. San Martino-IST, University of Genova, Genoa,
Italy, Genoa, Italy
SESSION INFORMATION
Background/Purpose: Systemic lupus erythematosus (SLE) can affect young women and pregnancy still represents a
challenge. Prednisone is safely used, at low doses (<7.5 mg daily), during pregnancy. Modified-release prednisone (MRP)
optimize corticosteroid treatment strategy in rheumatic diseases, thanks to its capability of respecting the physiological
cortisol circadian secretion. MRP has been approved from FDA in SLE treatment, but no data are available regarding its
administration during pregnancy.
We aimed to investigate whether this drug is safe and effective as the immediate release prednisone (IRP) in SLE pregnant
patients.
Methods: We retrospectively evaluated 9 female patients, fulfilling the ACR criteria for SLE, consulting our centers in a 4-
years observational range. All of them, thanks to a stable disease (not requiring treatment regimen modifications within 12
months), experienced a successful pregnancy during the observation. All the cases were taking low-dose MRP (5 to 7.5
mg/daily) as a baseline treatment, from at least 6 months. They were matched to 9 controls, defined as SLE patients with the
same age and duration of disease, taking the same prednisone dose, from at least 6 months, in the IR formulation. Age of
patients and disease duration (months); overall pregnancy outcome features; SLE disease activity (calculated at least once
during pregnancy, SLEPDAI) and at baseline/post-partum (SLEDAI) score; patient’s global assessment (VAS) at baseline,
during pregnancy and in postpartum (mm); need of treatment changes throughout pregnancy and at postpartum (%) were
assessed. Homogeneity tests, percentages and scores comparison were run out by non-parametric statistical analysis.
Results: Mean MRP age group was 312±52 months; disease duration, 48±96 months; IR one, respectively, 336±43 and
36±108 (both, p=ns). SLEDAI at baseline was 1±0.1 among MPR and 1±0.3 among IR women; SLEPDAI, 1±0.9 and 2±0.2
(both, p=ns). No major perinatal complications were detected. Preterm births, caesarean section rates, newborn’s weight and
APGAR scores, assessed 5 minutes after delivery, did not differ between the two subpopulations (all, p=ns). SLEDAI
assessed at postpartum was 2.8±0.6 in MRP subjects and 3.4±0.4 in IR (p<0.05). Patients VAS (MRP vs IR) was 3±0.4 and
2±09 at baseline (p=ns); 2±0.6 and 4±0.7 during pregnancy (p<0.05) and 3±0.3 and 4±0.9 at postpartum (p<0.05).
Regarding treatment regimen changes (add-on strategy), the observed rates involved 1/9 (MRP) and 5/9 (IR) women during
the observational gap (pregnancy+postpartum) (p<0.001).
Conclusion: Activity (SLEDAI) score was significantly higher at postpartum and treatment had to be increased in IR
patients, in comparison to the MRP, to manage SLE. VAS, conversely, was significantly higher among IR, both during
pregnancy and postpartum. No major perinatal side effects were observed during the study; minor and expected
complications rates did not differ between the two subpopulations. Despite the limited number of subjects, MRP treatment
seems to be as safe, but more effective, in comparison to the standard IR one, during pregnancy of SLE-affected women.
Disclosure: M. Meroni, None; V. L. Ramoni, None; M. Parodi, None; P. Stobbione, None; M. Cutolo, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/efficacy-and-safety-of-modified-release-
prednisone-in-managing-moderate-activity-sle-during-pregnancy-an-implemented-case-control-study
Dose-Response Effects of Tai Chi and Physical Therapy Exercise

Interventions in Symptomatic Knee Osteoarthritis
Augustine Lee1, William F. Harvey2, Lori Lyn Price3,4, Xingyi Han1, Jeffrey B. Driban1, Maura D. Iversen5,6,
Raveendhara R. Bannuru1 and Chenchen Wang2, 1Rheumatology, Tufts Medical Center, Boston, MA, 2Rheumatology,
Center of Integrative Medicine and Division of Rheumatology, Tufts Medical Center, Boston, MA, Boston, MA, 3Tufts
Clinical and Translational Science Institute, Tufts University, Boston, MA, 4Institute for Clinical Research and Health Policy
Studies, Tufts Medical Center, Boston, MA, 5Division of Rheumatology, Immunology and Allergy, Brigham and Women's
Hospital and Harvard Medical School, Boston, MA, 6Department of Physical Therapy, Movement & Rehabilitation
Sciences, Northeastern University, Boston, MA
SESSION INFORMATION
Session Title: Osteoarthritis – Clinical Aspects I: Pain and Functional Outcomes
Background/Purpose: Therapeutic exercise is the recommended non-pharmacological treatment for knee osteoarthritis
(OA). However, the optimal treatment dose and clinically meaningful treatment durations remain unclear. Our purpose was
to examine dose-response relationships, the minimum effective dose, and baseline factors associated with the timing of
response from two exercise interventions among adults with symptomatic knee OA.
Methods: Secondary analysis of a single-blind, randomized trial comparing 12-week Tai Chi and Physical Therapy exercise
programs among adults with symptomatic knee OA (ACR Criteria). WOMAC pain (0-500) and function (0-1700) scores
were completed each week of intervention. We defined dose as attendance-weeks (i.e. total treatment weeks attended), and
treatment response as ≥20% and ≥50% improvement in pain and function. Using log-rank tests, we compared time-to-
response between interventions, and used Cox regression to examine baseline factors associated with the timing of response
(≥50% improvement only).
Results: We examined 182 participants (mean age 61 years, BMI 32 kg/m2, 70% female, 55% white). Both interventions
had linear dose-response effect resulting in a 9 to 11-point reduction in WOMAC pain and a 32 to 41-point improvement in
function per week. There was no significant difference in overall time-to-response for pain and function between treatment
groups (Figure). Median time-to-response for ≥20% improvement in pain and function was 2 attendance-weeks and 4 to 5
attendance-weeks for ≥50% improvement. On unadjusted models, we found a general pattern wherein physical health
factors, self-efficacy, and outcome expectations tended to be significantly associated with treatment response rather than
psychosocial or biomechanical factors (Table). On multivariable models, outcome expectations were independently
associated with incident function response (Hazard Ratio: 1.47; 95% CI: 1.004 to 2.14).
Conclusion: Both interventions had linear dose-dependent effects on pain and function, their minimum effective doses
ranged from 2 (≥20% improvement) to 5 weeks (≥50% improvement), and patient-perceived benefits of exercise
independently influenced the timing of response among adults with symptomatic knee OA. These results may help clinicians
optimize patient-centered exercise treatments and better manage patient expectations.
Table. Unadjusted Hazard Ratios of Treatment Response (≥50%
improvement) in Pain and Physical Function by Baseline Factors (n=182)
Characteristic Hazard Ratio (95% Confidence
Interval)
Pain Function
Age, years 1.01 (0.99, 1.03) 1.02 (1.00, 1.04)
Female Sex, n (%) 1.32 (0.87, 2.01) 1.29 (0.85, 1.96)
Race, n (%)
White reference reference
Black 0.71 (0.47, 1.07) 0.59 (0.39, 0.91)
Asian/Other 0.94 (0.53, 1.67) 0.91 (0.52, 1.58)
Body Mass Index, kg/m 2 0.98 (0.96, 1.01) 0.98 (0.95, 1.00)
Duration of knee pain, years 1.01 (1.00, 1.03) 1.01 (1.00, 1.03)
Highest Level of Education, n (%)
High school graduate or less reference reference
Some college or more 1.69 (0.97, 2.94) 1.85 (1.02, 3.36)
WOMAC Pain n/a 0.86 (0.78, 0.95)
(Range: 0-500); (50-point units)

WOMAC Physical Function 0.96 (0.91, 1.004) n/a
(Range: 0-1700); (100-point units)

Patient Global Assessment 0.87 (0.80, 0.94) 0.88 (0.81, 0.96)
(Range: 0-10cm)
SF-36 Physical Component 1.35 (1.10, 1.65) 1.46 (1.18, 1.81)
Summary
(Range: 0-100)#; (10-point units)

PROMIS Sleep disturbance 0.88 (0.74, 1.05) 0.83 (0.69, 1.00)
(Range, T-Score: 28.9-76.5); (10-

point units)
SF-36 Energy and Vitality 1.06 (0.96, 1.17) 1.08 (0.97, 1.19)
(Range: 0-100)#; (10-point units)

CHAMPS Physical Activity 1.05 (1.003, 1.10) 1.06 (1.009, 1.11)
moderate-high calories/week#
(500-calories/week units)
6-Minute Walk Test 1.12 (1.01, 1.25) 1.14 (1.03, 1.27)
meters# (50-meter units)

Arthritis Self-Efficacy Scale-8 1.11 (1.01, 1.21) 1.14 (1.04, 1.25)
(Range: 0-10)#
Outcome Expectations 1.14 (0.82, 1.57) 1.43 (1.03, 1.97)
(Range: 1.0-5.0)#
CHAMPS= Community Healthy Activities Model Program for Seniors;
PROMIS= Patient-Reported Outcomes Measurement Information Systems; SF-
36= Short Form-36; WOMAC= Western Ontario and McMasters Osteoarthritis
Index. *Normal range reported for the general population. #Higher score
indicates greater health.
Disclosure: A. Lee, None; W. F. Harvey, None; L. L. Price, None; X. Han, None; J. B. Driban, None; M. D. Iversen,
NIAMS-NIH, PZifer, Fulbright, 2; R. R. Bannuru, None; C. Wang, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/dose-response-effects-of-tai-chi-and-

physical-therapy-exercise-interventions-in-symptomatic-knee-osteoarthritis
Association of Varus Knee Thrust during Walking to Worsening Knee Pain

over Two Years
Alexandra Wink1, K. Douglas Gross2, Carrie Brown3, Michael C. Nevitt4, Cora E. Lewis5, James Torner6, Leena Sharma7
and David T. Felson8, 1Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, 2Clinical Epidem
Rsrch, Boston University School Medicine, Boston, MA, 3Boston University School of Public Health, Boston, MA,
4Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, 5University of Alabama
Birmingham, Birmingham, AL, 6University of Iowa, Iowa City, IA, 7Division of Rheumatology, Northwestern University
Feinberg School of Medicine, Chicago, IL, 8Clinical Epidemiology Research and Training Unit, Boston University School
of Medicine, Boston, MA
SESSION INFORMATION
Background/Purpose: Varus knee thrust is an abrupt change in frontal plane tibiofemoral alignment observed during gait.
Thrust has been linked to radiographic knee OA progression and worsening cartilage and bone marrow lesions. In addition,
thrust has been cross-sectionally linked to knee pain presence during weight-bearing. Our objective was to determine the
longitudinal effect of knee thrust on worsening knee pain over 2 years in older adults with or at risk for OA.
Methods: The Multicenter Osteoarthritis Study (MOST) is a prospective cohort study of older Americans with or at risk for
knee OA. At the 60-month clinic exam, 60 Hz frontal plane videos recorded participants completing two self-paced walking
trials over a 4.9 meter walkway. A trained reader, blinded to disease status, assessed the presence of varus thrust on a
majority of steps (intra-rater κ = 0.73). Pain in each knee while walking, using stairs, standing upright, sitting, and in bed
was assessed using the WOMAC questionnaire at 60 and 84 months. Among knees with submaximal WOMAC scores at 60
months, worsening pain at 84 months was defined as any increase in WOMAC score, and clinically important worsening
was defined as an increase of ≥ 1.28 in WOMAC score. To assess the relation of thrust to worsening knee pain, we used
logistic regression with generalized estimating equations to account for non-independent limbs from a subject, adjusting for
age, sex, race, BMI, and gait speed. We repeated the analysis on a subset of knees with baseline WOMAC scores of 0 to
assess the relation of thrust to incident WOMAC knee pain. We also assessed the relation of thrust to worsening knee pain in
a subset of knees without baseline radiographic OA (Kellgren-Lawrence (KL) Grade < 2).
Results: 1623 participants (mean age 67.2 ± 7.6 years, mean BMI 30.4 ± 5.9, 59.9% female, 88.7% White) contributed 3204
knees. Varus thrust was observed in 31.5% of knees. At baseline, mean total WOMAC pain was 2.40, and 41% of knees had
radiographic knee OA (KL ≥ 2). Knees with a varus thrust had 1.45 (95% CI: 1.22, 1.72) and 1.46 (95% CI: 1.20, 1.77)
times the odds of any worsening and clinically important worsening total WOMAC pain, respectively, compared to knees
without thrust; this increased pain was consistent across all WOMAC listed activities (see Table) and among the subset of
knees without radiographic knee OA at baseline (OR = 1.39; 95% CI: 1.06, 1.82). Among knees with no WOMAC pain at
baseline, knees with thrust had 1.81 times the odds (95% CI: 1.35, 2.41) of incident pain at two years compared to knees
without thrust.
Conclusion: Varus knee thrust observed during walking is associated with increased odds of worsening knee pain during
both weight-bearing and non-weight-bearing activities in older adults with or at risk for OA. Given that thrust is potentially
modifiable using non-invasive therapies, detecting thrust provides an opportunity to prevent worsening knee pain in these
populations.
Table. Odds of Worsening WOMAC Pain in the Presence of Varus

Thrust
Varus
Adjusted** Odds
WOMAC Pain Thrust n/N* p-Value
Ratio (95% C.I.)
Status
Total WOMAC Pain Score
Present 355/1010 1.45 (1.22, 1.72) <0.0001
Any Worsening
Absent 625/2194 1.00 (ref)
Clinically
Present 221/1010 1.46 (1.20, 1.77) 0.0002
Important
Worsening (≥
Absent 375/2194 1.00 (ref)
1.28†)
Individual WOMAC Pain Questions
Present 185/1010 1.32 (1.08, 1.62) 0.008
Walking
Absent 325/2194 1.00 (ref)
Present 230/1010 1.38 (1.14, 1.67) 0.001

Using Stairs
Absent 412/2194 1.00 (ref)
Present 202/1010 1.44 (1.16, 1.79) 0.0009

Standing Upright
Absent 328/2194 1.00 (ref)
Present 163/1010 1.40 (1.12, 1.76) 0.003

Sitting
Absent 293/2194 1.00 (ref)
Present 145/1010 1.33 (1.06, 1.68) 0.01

In Bed
Absent 268/2194 1.00 (ref)
*Number of knees with worsening pain/Total knees
**Adjusted for age, sex, race, BMI, and gait speed

†Basedon the Minimum Clinically Important Difference for WOMAC Pain
from Angst et al. (2002)
Disclosure: A. Wink, None; K. D. Gross, None; C. Brown, None; M. C. Nevitt, None; C. E. Lewis, None; J. Torner,
None; L. Sharma, None; D. T. Felson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/association-of-varus-knee-thrust-during-

walking-to-worsening-knee-pain-over-two-years

Longitudinal Association between Sleep Quality and Knee Pain in the
Multicenter Osteoarthritis Study
Zhaoli (Joy) Dai1, Carrie Brown2, Tuhina Neogi3 and David T. Felson3, 1Boston University School of Medicine, Boston,
MA, 2Boston University School of Public Health, Boston, MA, 3Clinical Epidemiology Research and Training Unit, Boston
University School of Medicine, Boston, MA
SESSION INFORMATION
Background/Purpose: Sleep and pain have been shown to be reciprocally related. Studies have suggested a stronger effect
of sleep impairment on chronic pain such as fibromyalgia and widespread pain than pain effects on sleep quality. In this
study, we attempted to disentangle the longitudinal association of sleep quality with knee pain development and worsening
related to knee OA from chronic widespread pain.
Methods: In the Multicenter Osteoarthritis Study of participants with or at risk of knee OA, sleep quality was assessed at the
60-month study visit (baseline) using a single questionnaire item on a four-point Likert scale from the Pittsburgh Sleep
Quality Index, i.e. the overall quality of sleep in the past 7 days and 2) in the Center for Epidemiologic Studies Depression
Scale Revised (CESD) for frequency of restless sleep. We categorized sleep quality as ‘fairly good’ and ‘very good’ for the
upper two category responses, and ‘bad’ (referent group) for the lower two category responses combined together. Chronic
widespread pain (WSP) was defined as having pain above and below the waist, on both sides of the body, and in the axial
region. We defined our outcomes as follows: 1) knee pain worsening as relative change ≥ 14% or absolute change ≥ 2 in
WOMAC pain score; and 2) incident consistent frequent knee pain (CFKP, knee pain on most days in past month at both the
clinic visit and telephone screen ~30 days prior to the clinic visit and not present at baseline). We examined the relation of
sleep quality to each knee pain outcome over a 2-year period stratified by baseline WSP status using logistic regression with
Generalized Estimating Equations to account for correlations between two knees within an individual, and adjusted for
potential confounders (see Table).
Results: We included 2329 participants (4658 knees) with valid values for sleep quality [mean (SD) age: 62.1 (7.9), BMI:
30.9 (6.1), 60.5% female, 84.3% White, 41% with WSP]. The spearman correlation for sleep quality and restless sleep was
0.69 (p<0.001). There was a significant interaction between sleep quality and baseline WSP for both outcome measures
(p<0.01). In those who had knee pain at baseline, better sleep quality was associated with a lower risk of knee pain
worsening regardless of baseline WSP (p for trend <0.04), with an effect that appeared to be stronger among those with
WSP. No significant association was found for risk of incident CFKP in either stratum of WSP (see Table). Similar results
were observed using restless sleep in CESD.
Conclusion: Although better sleep quality was associated with a lower risk of worsening knee pain regardless of chronic
widespread pain, sleep quality did not affect the risk of developing new knee pain. Objective measures of sleep quality and
knee pain are warranted to study the role of sleep in knee pain in OA. Nonetheless, these data suggest that for those with
knee pain, sleep quality improvement should be considered for knee pain management.
Table Odds ratio (OR) [95% confidence interval (CI)] for relation of sleep quality from the
Pittsburgh Sleep Quality Index to knee pain worsening and joint pain stratified by baseline
widespread pain status in the Multicenter Osteoarthritis Study
Sleep quality
Knee pain outcomes 0,1=Bad (Referent
group) 2=Fairly good 3 =Very good p-trend
Knee pain worsening
Widespread pain absence
(N=2746)
Knee # (n/N)1 71/358 249/1476 159/912
OR (95% CI)2 1.0 0.86 (0.62, 0.70 (0.48, 0.04
1.21) 1.02)
Widespread pain presence
(N=1912)
Knee # (n/N) 176/470 359/1116 87/326
OR (95% CI) 1.0 0.73 (0.55, 0.54 (0.36, 0.002
0.98) 0.80)
Incident consistent frequent joint pain
Widespread pain absence
(N=2398)
knee # (n/N) 80/318 331/1296 149/784
OR (95% CI) 1.0 1.26 (0.86, 0.93 (0.61, 0.3
1.84) 1.43)
Widespread pain presence
(N=1656)
Knee # (n/N) 203/392 462/984 124/280
OR (95% CI) 1.0 0.93 (0.67, 0.92 (0.60, 0.7
1.28) 1.42)
1 Number of knees: n (knees with pain worsening or incident joint pain) / N (total number of knees)
2Model adjusted for age (years), sex (men vs. women), race (white vs. non-white), study site, BMI
(kg/m2), education level (college and above vs. below college), current work for pay (yes, no),
tobacco packyears, Charlson’s comorbidity index, fatigue (10-point scale), CESD (without the sleep
question), and use of NSAIDs.
Disclosure: Z. Dai, None; C. Brown, None; T. Neogi, None; D. T. Felson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/longitudinal-association-between-sleep-

quality-and-knee-pain-in-the-multicenter-osteoarthritis-study
Effectiveness of FX006 Intra-Articular Injection in Patients with Knee

Osteoarthritis Who Present with and without Clinical Inflammation at
Baseline: A Pooled Analysis of Data from 3 Double-Blind, Randomized,
Parallel-Group Clinical Trials
Herbert S. B. Baraf1, Christian Lattermann2, Deryk G. Jones3, Philip G. Conaghan4, Joelle Lufkin5, James Johnson6, Scott
Kelley5 and Neil Bodick5, 1Center for Rheumatology and Bone Research, Wheaton, MD, 2University of Kentucky,
Orthopaedic Surgery and Sports Medicine, Lexington, KY, 3Ochsner Sports Medicine Institute, New Orleans, LA, 4Leeds
Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom, 5Flexion Therapeutics,
Inc., Burlington, MA, 6Summit Analytical, Denver, CO
SESSION INFORMATION
Background/Purpose: Inflammation is a key contributor to osteoarthritis (OA).1 OA pain is mediated by interactions

between inflammatory cytokines and other features including local tissue damage, synovitis and cellular response
mechanisms.1 Synovitis is integral to OA, and is associated with symptom severity, joint dysfunction and cartilage loss.2
FX006, an extended-release formulation of triamcinolone acetonide (TA) for intra-articular (IA) injection, provided
statistically and clinically significant, sustained improvements in pain/stiffness/function of knee OA vs placebo in clinical
trials.3 We compared FX006 efficacy in patients with and without baseline inflammation determined by clinical assessment.
Methods: A pooled subgroup analysis of 3 double-blind, randomized, placebo-controlled trials

(NCT01487161/NCT02116972/NCT02357459) was conducted. Patients with Kellgren-Lawrence grade 2/3 knee OA and
Average Daily Pain (ADP)-intensity score ≥5–≤9 (0–10 Numerical Rating Scale) received a single IA injection of FX006 40
mg or saline-placebo. Investigators assessed index knees for clinical indicators of inflammation (effusion, Baker’s cyst,
tenderness, swelling, and/or redness/heat). ADP-intensity was assessed daily for 24 weeks. Western Ontario and McMaster
University Arthritis Index for OA (WOMAC; 0–4 Likert scale) pain (A), stiffness (B), and physical function (C) were
assessed at baseline and Weeks 4/8/12.
Results: 349/586 patients (60%) had baseline clinical inflammation (Table). Changes from baseline in weekly mean ADP-
intensity and WOMAC-A, B, C consistently favored FX006 vs saline-placebo (Figure). FX006 effect was enhanced,
generally >2-fold, in patients with vs without baseline clinical inflammation: least squares mean differences for ADP and
WOMAC-A, B, C, respectively, was -1.84 vs -0.74, -0.71 vs -0.27, -0.82 vs -0.41, and -0.69 vs -0.26 at Week 8, and -1.35 vs
-0.37, -0.44 vs -0.16, -0.50 vs -0.27, and -0.44 vs -0.16 at Week 12.
Conclusion: FX006 provided sustained clinical improvement in knee OA vs saline-placebo irrespective of baseline clinical
inflammation. Enhanced FX006 effect in patients with baseline clinical inflammation is consistent with the role of
inflammation in OA pathogenesis and known anti-inflammatory action of TA. A drawback of this study is the lack of
standardized measures of inflammation. Longer-term evaluations with objective inflammation measures (e.g., ultrasound,
biomarkers) are needed.
1Robinson WH, et al. Nat Rev Rheumatol. 2016;12:580-92.
2Sellam J. Nat Rev Rheumatol. 2010;6(11):625-35.
3Conaghan P, et al. Osteoarthr Cartil. 2017;25:S432-S433.
Disclosure: H. S. B. Baraf, Flexion Therapeutics, 2,Pfizer Inc, 2,Abbvie, 8,Horizon, 8; C. Lattermann, Cartiheal,
5,Cartilage, 9,J Sports Physiology, 9,The Knee, 9,Orthopaedic Journal of Sports Medicine, 9,Cocoon, 1,International
Cartilage Repair Society, 6,German-speaking Arthroscopy Society AGA, 6,Novartis Pharmaceutical Corporation,
5,Samumed, 5,Smith & Nephew, Inc., 2,Vericel, 5; D. G. Jones, Genzyme Corporation, 5,Mitek, 5,Musculoskeletal
Transplant Foundation, 5,Musculoskeletal Transplant Foundation, 6,Sanofi-Aventis Pharmaceutical, 2,Zimmer, 7; P. G.
Conaghan, Novartis Pharmaceutical Corporation, 5,Flexion Therapeutics, 5,AbbVie, 5,Infirst, 5,Medivir, 5,Merck Serono,
5,ONO Pharmaceutical Co., 5; J. Lufkin, Flexion Therapeutics, 3,Flexion Therapeutics, 1; J. Johnson, Flexion
Therapeutics, 1,Flexion Therapeutics, 3,Flexion Therapeutics, 5,Summit Analytical, LLC, 3,Acura Pharmaceuticals, 5,Iroko
Pharmaceuticals, 5,IX Biopharma, 5,Tolmar, Inc., 5; S. Kelley, Flexion Therapeutics, 1,Flexion Therapeutics, 3; N. Bodick,
Flexion Therapeutics, 1,Flexion Therapeutics, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effectiveness-of-fx006-intra-articular-

injection-in-patients-with-knee-osteoarthritis-who-present-with-and-without-clinical-inflammation-at-baseline-a-pooled-
analysis-of-data-from-3-double-blind-ran
Results from a 52 Week Randomized, Double-Blind, Placebo-Controlled,

Phase 2 Study of a Novel, Intra-Articular, Wnt Pathway Inhibitor (SM04690)
for the Treatment of Knee Osteoarthritis
Yusuf Yazici1, Timothy E. McAlindon2, Allan Gibofsky3, Nancy E. Lane4, Daniel J. Clauw5, Eddie Armas6, Nebojsa
Skrepnik7, Christopher J. Swearingen1, Anita DiFrancesco1, Jeymi Tambiah1 and Marc Hochberg8, 1Samumed, LLC, San
Diego, CA, 2Division of Rheumatology, Tufts Medical Center, Boston, MA, 3Rheumatology, Weill Cornell Medicine, and
Hospital for Special Surgery, New York, NY, 4Center for Musculoskeletal Health, University of California at Davis,
Hillsborough, CA, 5Chronic Pain & Fatigue Research Center, University of Michigan, Ann Arbor, MI, 6Well Pharma
Medical Research, Miami, FL, 7Tuscon Orthopedics Institute, Tuscon, AZ, 8Head, Division of Rheumatology & Clinical
Immunology; Vice Chair, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
SESSION INFORMATION
Background/Purpose: Knee osteoarthritis (OA) is characterized by pain, disability and joint deformity due to articular
cartilage degradation and bone remodeling. Wnt signaling is involved in these cellular processes and inflammation.
SM04690, a small molecule Wnt pathway inhibitor, is in development as a potential disease modifying drug for knee OA.
A phase 2, multicenter, 52-week, randomized, double-blind, placebo-controlled (PBO) trial was conducted to determine the
safety and efficacy of SM04690.
Methods: Knee OA subjects with Kellgren-Lawrence (KL) grades 2-3, received a single 2 mL injection of 0.03 mg, 0.07
mg, 0.23 mg SM04690 or PBO in target (most painful) knees. Western Ontario and McMaster Universities Arthritis Index
Outcome (WOMAC) Pain [0-50] and Function [0-170] were assessed at Weeks 0, 4, 13, 26, 39 and 52, and radiographs were
taken at Weeks 0, 26 and 52 for medial joint space width (mJSW). Analysis of covariance adjusted for baseline in the
intention-to-treat (ITT) population was conducted with multiple imputation. Two subgroups were explored: 1) unilateral
symptomatic knee OA subjects as determined by investigator through history and examination (pre-specified), and 2)
unilateral symptomatic knee OA subjects without widespread pain (Widespread Pain Index ≤4 and Symptom Severity ≤2
[WP], post-hoc).
Results: 455 subjects (mean age 60.3 [±8.7], BMI 29.9 [±4.6] kg/m2, female 58.9%, KL 3 [64.4%], unilateral symptomatic
OA [36.0%]) were enrolled. Serious adverse events, all deemed unrelated to SM04690, were reported in 17 (3.7%) subjects
(4.5% [0.03 mg], 3.5% [0.07 mg], 3.8% [0.23 mg], 2.8% [PBO]).
In the ITT population, clinically meaningful outcomes improvements (>10% full range) compared to baseline were seen in
all groups at all timepoints. Unilateral symptomatic subjects treated with 0.07 mg SM04690 had significant improvements in
WOMAC Pain with clinically meaningful and significant improvements in WOMAC Function compared to PBO at Week
52. Unilateral symptomatic subjects without WP treated with 0.07 mg SM04690 had clinically meaningful and significant
improvements in WOMAC Pain and Function compared to PBO at Weeks 26, 39, and 52 (Figure). At Week 52 in the ITT
population, mean changes in mJSW were -0.14 mm in PBO, 0.10 mm in 0.03 mg (NS), 0.06 mm in 0.07 mg (NS), and -0.02
mm 0.23 mg (NS).
Conclusion: In this phase 2 study, improvements compared to PBO in WOMAC Pain and Function were seen in study
subgroups of unilateral symptomatic and unilateral symptomatic without WP subjects. SM04690 maintained or improved
mJSW over 52 weeks. Radiographic and clinical outcomes suggested SM04690 has potential as a DMOAD for knee OA
treatment.
Disclosure: Y. Yazici, Samumed, LLC, 3,Samumed, LLC, 1; T. E. McAlindon, None; A. Gibofsky, Pfizer Inc, 1,AbbVie,
1,Amgen, 1,Bristol-Myers Squibb, 1,Johnson & Johnson, 1,Regeneron, 1,AbbVie, 5,AbbVie, 8,Pfizer Inc, 5,Pfizer Inc,
8,Celgene, 8,Novartis Pharmaceutical Corporation, 8,Takeda, 5,Horizon, 5,Relburn, 5,Samumed, 5; N. E. Lane, Pfizer Inc,
5,Eli Lilly and Company, 5,Regeneron, 5,Amgen, 5,Samumed, LLC, 5; D. J. Clauw, Abbott Pharmaceutical, 5,Aptinyx,
5,Astellas Phamaceutical, 5,Cerephex, 5,Daiichi Sankyo, 5,Pfizer Inc, 5,Pierre Fabre, 8,Samumed, 5,Theravance, 5,Tonix, 5;
E. Armas, Samumed, LLC, 2; N. Skrepnik, Orthofix, 5,Regeneron, 5,Sanofi-Aventis Pharmaceutical, 5; C. J. Swearingen,
Samumed, LLC, 3,Samumed, LLC, 1; A. DiFrancesco, Samumed, LLC, 3,Samumed, LLC, 1; J. Tambiah, Samumed,
LLC, 3,Samumed, LLC, 1; M. Hochberg, Bioiberica SA, 5,Bristol-Myers Squibb, 5,EMD Serono, 5,Galapagos, 5,IBSA
SA, 5,Novartis Pharmaceutical Corporation, 5,Pfizer Inc, 5,Plexxicon, 5,Samumed LLC, 5,Theralogix LLC, 5,TissueGene,
5,NIH, 2,Theralogix LLC, 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/results-from-a-52-week-randomized-

double-blind-placebo-controlled-phase-2-study-of-a-novel-intra-articular-wnt-pathway-inhibitor-sm04690-for-the-treatment-
of-knee-osteoarthritis
Knee Confidence Trajectories over 8 Years and Factors Associated with Poor
Trajectories: Data from the Osteoarthritis Initiative
Alison H. Chang, Julia (Jungwha) Lee, Orit Almagor, Joan S. Chmiel, Kirsten C. Moisio, Karen W. Hayes, Julie Szymaszek
and Leena Sharma, Northwestern University, Chicago, IL
SESSION INFORMATION
Background/Purpose: Lack of knee confidence, a frequent complaint, has been associated with function decline in knee
OA. Given its key role in weight-bearing activities, a better understanding of how confidence changes over time and
modifiable factors associated with poor trajectories will inform strategies to help to prevent function decline. Our objectives
were to identify, in persons with or at higher risk for knee OA, distinct trajectories of knee confidence over 8 years and
baseline factors associated with poor trajectories.
Methods: The OAI is a prospective longitudinal cohort study of persons with or at higher risk for knee OA aged 45-79 yrs.
Knee confidence was self-reported annually from baseline to 96m in the KOOS (Knee Injury and Osteoarthritis Score), as
how much an individual is troubled by lack of confidence in their knees: 0, not at all; 1, mildly, 2, moderately, 3, severely,
and 4, extremely. Confidence trajectories for % with score 2-4 were modeled using 4515 OAI participants who had ≥3 time
points for confidence. Latent class models identified groups with a similar underlying trajectory, and, in 4105 persons with
complete baseline data, logistic regression was used to model associations of baseline predictors with poor (vs. good)
trajectories.
Results: We identified 4 distinct knee confidence trajectories (Figure), persistently good, declining, improving, and
persistently poor, with estimated probabilities to each trajectory of 62.9%, 11.0%, 14.7%, and 11.3%, respectively. The
4105 persons had a mean age 61.4 years (SD 9.2), BMI 28.6 kg/m2 (4.8), and 2381 (58.0%) were women. As shown in the
Table, baseline factors associated with both persistently poor and declining confidence were BMI, depressive symptoms,
disease severity, and worse function; with persistently poor only were younger age, male sex, extensor weakness, injury, and
knee and ankle pain; with declining only were comorbidity, falls, and hip pain.
Conclusion: Four distinct 8-year knee confidence trajectories were identified in persons with or at higher risk for knee OA.
Targeting BMI, depressive symptoms, function, extensor weakness, and knee, ankle, and hip pain may help to prevent poor
or declining confidence trajectories.
Disclosure: A. H. Chang, None; J. Lee, None; O. Almagor, None; J. S. Chmiel, None; K. C. Moisio, None; K. W. Hayes,
None; J. Szymaszek, None; L. Sharma, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/knee-confidence-trajectories-over-8-

years-and-factors-associated-with-poor-trajectories-data-from-the-osteoarthritis-initiative
Treatment Response in Polyarticular JIA Is Associated with Transcriptional

Changes and Chromatin Reorganization in CD4+ T Cells
Evan Tarbell1, Kaiyu Jiang2, Yanmin Chen2, Tao Liu3 and James Jarvis4, 1Biochemistry, University at Buffalo, Buffalo,
NY, 2Pediatrics, University at Buffalo, Buffalo, NY, 3Biochemistry, University at Buffalo Jacobs School of Medicine,
Buffalo, NY, 4Department of Genetics, Genomics & Bioinformatics, University at Buffalo, Buffalo, NY
SESSION INFORMATION
Session Title: Pediatric Rheumatology – Pathogenesis and Genetics
Background/Purpose: To identify transcriptional changes in CD4+ T cells as children with polyarticular JIA transition
from active disease to remission, and to identify underlying changes in chromatin architecture that account for these
changes.
Methods: We isolated RNA from CD4+ T cells of children with 3 phenotypes: active, treated polyarticular JIA (ADT,
n=12), children on medication who fit criteria for clinical remission (CRM, n=10), and 10 healthy children (HC). RNA
sequencing was performed using the Illumina HiSeq 2500 platform. We used the assay for transposase-accessible chromatin-
sequencing (ATACseq) to survey open chromatin in a subset of these same patients (6 HC, and 5 ADT and CRM). We
investigated whether regions of open chromatin that were unique to any of the 3 phenotypes (ADT, CRM, or HC) might
show enrichment for specific transcriptional regulators, using standard computational approaches to determine whether
unique peaks were associated with up-regulated genes, as determined by phenotype-to-phenotype comparisons of RNAseq
data. We divided peaks into central and flanking regions then calculated the best match to each of 700+ motifs for each sub-
region within each peak, and calculated enrichment by comparing the score of the best central match to the score of the best
flanking matches.
Results: Each of the 3 phenotypes was associated with its own its own chromatin accessibility signature as identified by
ATACseq and its own transcriptional signature. We identified 16,039 accessible sites that were unique to HC, 38,451 that
were unique to ADT, and 58,289 sites that were unique to CRM. Further analyses of the open regions unique to the HC cells
showed that these regions were highly enriched (compared to genome background) for CCCTC-binding factor (CTCF)
binding sites. These CTCF binding sites were absent in JIA CD4+ T cells. Differential CTCF accessibility was identified
within 2 of the known JIA risk haplotypes, those identified by the SNPs rs147992 (upstream of the IL2 gene) and
rs2266959, an intronic region of the UBE2LR gene that also features H3K27ac+ enhancer marks in CD4+ T cells. This
finding suggests that aberrant 3D chromatin architecture (which is regulated by CTCF) may be a primary driver of the
transcriptional aberrations observed in JIA. Analysis of the combined RNAseq and ATACseq using BETA software
demonstrated that the differences in chromatin accessibility had high regulatory potential for the differentially expressed
genes, providing strong evidence that the chromatin changes and gene expression changes are causally linked. The CRM
state was not associated with normalization of either the chromatin or transcriptional signatures of CD4+ T cells in children
with JIA.
Conclusion: Treatment response in JIA is associated with significant re-organization of chromatin and is accompanied by
significant changes in transcription that can be attributed to the chromatin re-organization. Patterns of chromatin
accessibility suggest important roles for chromatin regulators (e.g., CTCF) in JIA and possible genetic determinants
governing CTCF accessibility. The achievement of CRM does not result in a normalization of either the transcriptome or the
epigenome of CD4+ T cells.
Disclosure: E. Tarbell, None; K. Jiang, None; Y. Chen, None; T. Liu, None; J. Jarvis, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/treatment-response-in-polyarticular-jia-

is-associated-with-transcriptional-changes-and-chromatin-reorganization-in-cd4-t-cells
A Germline Macrophage Activation Syndrome-Associated Nlrc4 Mutation

Causes Chronic, Systemic, Non-Hematopoietic IL-18 Elevation and Intestinal
MHC-II Upregulation
Eric Weiss1, Corinne Schneider2 and Scott Canna3, 1RK Mellon Institute, Children’s Hospital of Pittsburgh, Pittsburgh, PA,
2Pediatrics, Children's Hospital Pittsburgh, Pittsburgh, PA, 3NIAMS, National Institutes of Health, Bethesda, MD
SESSION INFORMATION
Background/Purpose: Patients prone to the development of Macrophage Activation Syndrome (MAS) can have extreme
and often chronic elevation in the pro-inflammatory cytokine interleukin-18 (IL-18). In particular, those with gain-of-
function mutations in the inflammasome-nucleating protein NLRC4 provided the first mechanistic link between the
inflammasome, IL-18, and MAS. Other inflammasome-associated disorders lack such extreme and persistent IL-18
elevation (Fig. 1). In order to dissect the mechanisms associated with NLRC4 hyperactivity, we generated a mouse with an
MAS-associated germline missense mutation (T337S) in Nlrc4 (N4-TS mice).
Methods: N4-TS mice were generated by Crispr-Cas9 genome engineering and bred to WT for at least four generations. IL-
18 was measured by bead-based immunoassay (Luminex or BD Cytometric Bead Array). RNA-sequencing was performed
on duodenal epithelial mucosal tissue scrapings placed into Trizol. MHC-II upregulation was assessed by flow cytometry.
Results: N4-TS mice overproduced IL-18 in an allele-dependent manner. We found that IL-18 elevation was present as early
as 3 weeks of age, and was unaffected by co-housing or antibiotic treatment. Using bone-marrow chimeras, we determined
that IL-18 elevation in N4-TS mice was non-hematopoietic. Upon review of publicly available transcriptional datasets, we
discovered that barrier epithelia, and in particular intestinal epithelial cells (IECs), are a rich source of colonization-
independent Il18 and expressed high levels of Nlrc4 compared to other inflammasome nucleators. RNA-seq of duodenal
epithelium showed upregulation of pathways associated with antigen presentation and epithelial turnover in N4-TS mice.
Though we saw no increase in Dextran Sodium Sulfate-Induced colitis in N4-TS mice, increased baseline IEC proliferation
was confirmed by EdU incorporation. MHC-II was upregulated in N4-TS intestinal epithelial cells as well intraepithelial and
αβ- and γd-T-cells, but not in splenic or liver lymphocytes. By contrast, mice with transgenic expression of Il18 (Il18tg) had
MHC-II upregulation in intestines, liver, and spleen. (Fig. 2)
Conclusion: Like NLRC4-MAS patients, N4-TS mice spontaneously overproduce IL-18. Barrier epithelia may be an
important site for NLRC4-dependent IL-18 maturation. MHC-II upregulation is tissue-specific in Nlrc4-T337S mice and
may be an anti-inflammatory response. These data suggest a role for barrier epithelial dysfunction as a contributor to
systemic inflammatory diseases, particularly those associated with chronic IL-18 elevation and MAS.
Disclosure: E. Weiss, None; C. Schneider, None; S. Canna, AB2Bio Ltd, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-germline-macrophage-activation-

syndrome-associated-nlrc4-mutation-causes-chronic-systemic-non-hematopoietic-il-18-elevation-and-intestinal-mhc-ii-
upregulation
Stimulator of Interferon Genes (STING)-Induced Endothelial-Mesenchymal

Transition (EndMT) Contributes to Interstitial Lung Disease in Sting-
Associated Vasculopathy with Onset in Infancy (SAVI) Patients
Louise Malle1, Dan Yang2, Adriana Almeida de Jesus1, Guibin Chen2, Bernadette Marrero1, Gina A. Montealegre
Sanchez1, Yin Liu3, Gregor Dueckers4, Suzanne Ramsey5, Joseph Fontana6, Rachel VanTries1, Yan Huang1, Laisa
Santiago7, Benito Gonzalez8, Paul Brogan9, Juergen Brunner10, Ebun Omoyinmi11, Athimalaipet V. Ramanan12, Amy
Paller13, Olcay Y. Jones14, Seza Ozen15, Stephen R. Brooks16, Manfred Boehm17 and Raphaela Goldbach-Mansky1,
1Translational Autoinflammatory Disease Studies (TADS), Laboratory of Clinical Investigation and Microbiology (LCIM),
NIAID/NIH, Bethesda, MD, 2Center for Molecular Medicine, NHLBI/NIH, Bethesda, MD, 3Scientific Review Branch,
NIAMS/NIH, Bethesda, MD, 4Helios Kliniken - Kinderklinik, HELIOS Klinikum Krefeld, Krefeld, Germany, 5Pediatric
Rheumatology, IWK Health Centre, Dalhousie University, Halifax, NS, Canada, 6Cardiovascular and Pulmonary Branch,
NHLBI/NIH, Bethesda, MD, 7Johns Hopkins All Children's Hospital Rheumatology, Saint Petersburg, FL, 8Luis Calvo
Mackenna Hospital, Santiago, Chile, 9Infection Inflammation and Rheumatology, UCL Institute of Child Health, and Great
Ormond Street Hospital NHS Foundation Trust, London, United Kingdom, 10Division of Pediatric Rheumatology, Medical
University Innsbruck, Innsbruck, Austria, 11University College London Institute of Child Health, London, United Kingdom,
12Bristol Royal Hospital for Children, Bristol, United Kingdom, 13Department of Dermatology, Northwestern University
Feinberg School of Medicine, Chicago, IN, 14Department of Pediatrics, Walter Reed National Military Medical Center,
Bethesda, MD, 15Department of Pediatrics, Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara,
Turkey, 16Biodata Mining and Discovery Section, Office of Science and Technology, NIAMS/NIH, Bethesda, MD, 17Center
for Molecular Medicine, NHLBI/ NIH, Bethesda, MD
SESSION INFORMATION
Background/Purpose: Pulmonary fibrosis, is a life-threatening complication of the monogenic autoinflammatory

interferonopathy, STING-Associated Vasculopathy with onset in Infancy (SAVI) that is caused by gain-of-function mutations
in the viral sensor/adaptor TMEM173/STING. Pathogenic mechanisms causing fibrosis and factors modifying the onset and
severity of lung fibrosis in SAVI patients (pts.) are unknown. Here we show that STING-mediated endothelial cell activation
induces an endothelial-mesenchymal transition (EndMT)-like differentiation program that causes lung fibrosis in SAVI pts.
Methods: To understand the role of STING signaling in pulmonary fibrosis, we assessed chest computed tomography (CT),
pulmonary function tests (PFTs) in 13 SAVI patients (pts.), and lung histopathology was available from 4 pts. We conducted
pts. and control fibroblast, human lung and umbilical vein endothelial cell (EC) lines (HMVEC-L and HUVECs,
respectively) and pts. and control induced pluripotent stem cell (iPSC)-derived EC stimulations with endogenous and
microbial cGAMP plus/minus IFNb. Gene expression (q-RT-PCR, RNA-seq), cytokine production, and EndMT (by cell
morphology and gene expression studies), were assessed. Pts. were genotyped for a common STING SNP (R232H,
rs1131769) and the modifying effect of the variant was examined in transfection studies in HEK293T cells.
Results: Of 13 SAVI pts., 10 had severe lung disease, 4 succumbed to pulmonary complications. Pulmonary findings
included hilar lymphadenopathy, diffuse ground glass opacities and cystic emphysematous changes on chest CT, and
reduced diffusing lung capacity for carbon monoxide (DLCO) and abnormal 6-minute walk test on PFTs. In contrast to
control lung biopsies (n=5), pts.’ biopsies (n=4) displayed perivascular fibrosis on Masson’s trichrome-stain around
medium-sized and small alveolar vessels. In pts., endothelial lining co-expressed mesenchymal (α-SMA) and stromal
fibroblast (FSP-1) markers within the subendothelial compartment. cGAMP stimulation in pt. and control fibroblasts showed
no expression of myofibroblast and extracellular matrix (ECM) markers by RNA-seq and q-RT-PCR. Endogenous cGAMP
stimulation on HMVEC-L induced morphologic transition to fibroblasts with a decreased expression of EC markers CDH5
(V-cadherin), VWF and PECAM1 (CD31), and an increased expression of the mesenchymal markers ACTA2 (α-SMA) and
FAP and of the stromal fibroblast marker S100A4 (FSP-1). IFNβ and cGAMP stimulation synergize and addition of a JAK
inhibitor attenuated the mesenchymal transformation. IPSC-derived EC (iEC) from 4 SAVI pts. but not HCs spontaneously
differentiated into myofibroblasts in culture. Differentiation was attenuated by JAK inhibition and in shRNA STING knock
down iEC. Homozygosity for R232/R232, a STING SNP associated with increased IFNβ production, in addition to the SAVI
STING mutation led to a more severe clinical lung phenotype in SAVI patients.
Conclusion: We suggest a novel pathway of STING-mediated ECs activation to induce EndMT-like mesenchymal
transformation as cause for lung fibrosis in SAVI pts.
Disclosure: L. Malle, None; D. Yang, None; A. Almeida de Jesus, None; G. Chen, None; B. Marrero, None; G. A.
Montealegre Sanchez, Eli Lilly and Company, 9; Y. Liu, None; G. Dueckers, None; S. Ramsey, None; J. Fontana, None;
R. VanTries, None; Y. Huang, None; L. Santiago, None; B. Gonzalez, None; P. Brogan, None; J. Brunner, None; E.
Omoyinmi, None; A. V. Ramanan, None; A. Paller, None; O. Y. Jones, None; S. Ozen, None; S. R. Brooks, None; M.
Boehm, None; R. Goldbach-Mansky, Eli Lilly and Company, 9,SOBI, 9,Regeneron, 9,Novartis Pharmaceutical
Corporation, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/stimulator-of-interferon-genes-sting-

induced-endothelial-mesenchymal-transition-endmt-contributes-to-interstitial-lung-disease-in-sting-associated-
vasculopathy-with-onset-in-infancy-savi-patient
IL1RN Variation Is Associated with Systemic Juvenile Idiopathic Arthritis

and Predicts Non-Response to Anakinra Treatment
Emily Shuldiner1, Victoria Arthur1, Anne Hinks2, Patricia Woo3, Wendy Thomson2, Elaine F. Remmers4 and Michael J.
Ombrello1, 1Translational Genetics and Genomics Unit, NIAMS, NIH, Bethesda, MD, 2Arthritis Research UK Centre for
Genetics and Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Sciences Centre, The
University of Manchester, Manchester, United Kingdom, 3University College London, London, United Kingdom, 4Genetics
and Genomics Branch, NIH, NIAMS, Bethesda, MD
SESSION INFORMATION
Background/Purpose: Systemic juvenile idiopathic arthritis (sJIA) is a childhood inflammatory disease whose
pathophysiology is poorly understood. sJIA is phenotypically heterogeneous with variable manifestations and responses to
treatment. Until recently genetic investigations of sJIA have consisted of candidate gene studies in small patient collections.
These studies found only modest associations, yet these associations are regularly included in discussions of sJIA
pathophysiology. Therefore, we examined the 11 reported sJIA candidate susceptibility loci (IL1A/B, GLI2, IL1RN/PSD4,
IL1R2, IL10/20, IL6, MVK, CCR5, MIF, SLC26A2 and TAPBP) in the largest sJIA study population assembled to date.
Methods: Single nucleotide polymorphism (SNP) genotypes were extracted from the INCHARGE dataset, (771 sJIA, 6947
controls). Logistic regression was performed in each case-control stratum and association results were meta-analyzed. The
effect of sJIA associated SNPs on gene expression was evaluated in silico in paired whole genome (WGS) and RNA
sequencing (RNAseq) data from lymphoblastoid cell lines (LCL) of 373 European 1000 Genomes Project subjects. The
relationship between sJIA associated SNPs and response to recombinant interleukin-1 (IL-1) receptor antagonist (anakinra)
treatment was evaluated in 38 US patients for whom treatment response data were available.
Results: None of the 26 SNPs with previously reported sJIA associations demonstrated even nominal (p<0.05) association
with sJIA in our study. We expanded the analysis to determine whether the 11 loci containing the 26 SNPs harbored any
sJIA risk SNPs. We examined 5479 SNPs from the 11 candidate regions, among which 500 SNPs were independent
(r2<0.5), defining the study’s significance threshold as p<1E-4. Association meta-analysis revealed only one significant
association among the 11 candidate loci, the promoter region of IL1RN, where 3 SNPs in strong linkage disequilibrium
showed a significant association with sJIA. Analysis of LCL data showed that the sJIA associated SNPs correlated with
IL1RN expression, with an inverse correlation between sJIA risk and IL1RN expression. Importantly, the presence of
homozygous IL1RN high expression alleles correlated strongly with non-response to anakinra (p=9.8E-4, OR 17.3 [2.8,
108.1]).
Conclusion: IL1RN was the only candidate locus associated with sJIA in our study. The sJIA associated SNPs are among
the strongest known determinants of IL1RN and IL1RA levels, linking low expression with increased sJIA risk. Although
high expression alleles were protective against sJIA, patients with 2 high expression alleles were significantly less likely to
respond to anakinra treatment than those with 1 or 2 low expression alleles. Even though anakinra is well known to
ameliorate or reduce inflammation in some sJIA patients, this is the first report to link sJIA risk and response to anakinra
treatment with genetically determined capacity to produce IL1RN or IL1RA. These SNPs are the first potential biomarker(s)
capable of prospectively guiding therapeutic decision making in sJIA.
Disclosure: E. Shuldiner, None; V. Arthur, None; A. Hinks, None; P. Woo, None; W. Thomson, None; E. F. Remmers,
None; M. J. Ombrello, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/il1rn-variation-is-associated-with-

systemic-juvenile-idiopathic-arthritis-and-predicts-non-response-to-anakinra-treatment
Ro/SSA Autoantibody Exposed Neonates Have an Expansion of NK Cells and

a Discernible Type II IFN Signature with High IFNγ in Peripheral Blood
Margarita Ivanchenko1, Malin Hedlund1, Gudny Ella Thorlacius1, Vijole Ottosson1, Karine Chemin2, Sven-Erik
Sonesson3 and Marie Wahren-Herlenius1, 1Unit of Experimental Rheumatology, Department of Medicine, Karolinska
Institutet, Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden, 2Department of Medicine, Center for
Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden,
3Pediatric Cardiology Unit, Department of Women´s and Children´s Health, Karolinska Institutet, Karolinska University
Hospital, Stockholm, Sweden, Stockholm, Sweden
SESSION INFORMATION
Background/Purpose: Congenital heart block (CHB) may develop in the fetus of women with Ro/SSA autoantibodies. The
mothers are commonly diagnosed with Sjögren’s syndrome or SLE. During pregnancy, the antibodies are transported across
placenta and bind to the fetal heart where inflammation develops, leading to the fibrosis and calcification that cause the
permanent disruption of impulse propagation. The mechanism by which the antibodies initiate inflammation is however not
understood. In the mother, Ro/SSA antibodies may induce type I IFN production, and we recently described an upregulation
of type I IFN-regulated genes in PBMC as well as an increase in circulating IFN-alpha also in the Ro/SSA exposed
newborns. IFN-alpha is known to influence leukocytes, expand and activate NK cells, and in this study, we, therefore,
analyzed the immune cell populations in cord blood of anti-Ro/SSA exposed neonates and evaluated the influence of IFN-
alpha on fetal cardiac cells.
Methods: Maternal and cord blood was sampled at birth from healthy controls (HC) (n=9) and Ro/SSA positive pregnancies
(n=13). PMBC were prepared and used for microarray analysis and for flow cytometry to define CD19+ B cell (CD27-IgD+
naïve, CD27+IgD- memory, CD27+IgD+ marginal zone), CD3+ T cell (CD8+, CD4+) subpopulations and CD16+CD56+ NK
cells. Cardiomyocyte cultures were established from human fetal tissues (n=5) and stimulated by medium with or without
IFN-alpha for 6 hours before mRNA preparation and microarray analysis.
Results: In the Ro/SSA positive mothers, an increase in naïve B cells, but decrease in memory and marginal zone cells was
observed, confirming previous reports for non-pregnant Sjögren’s syndrome and SLE. Surprisingly, Ro/SSA exposed
neonates presented an expanded population of NK cells (p=0.02), the presence of which was influenced by
immunomodulatory treatment of the mother (neonates of non-treated mothers p=0.002, neonates of treated mothers p=ns
compared to HC). No other differences in the T or B cell subsets analyzed were observed. Microarray analysis of PBMC
revealed a type II IFN signature with high IFNγ, the prototype cytokine produced by activated NK cells, in Ro/SSA exposed
neonates compared to HC. Finally, stimulation of fetal cardiomyocytes with IFN-alpha induced upregulation of MICA and
MICB (major histocompatibility complex (MHC) class I chain related sequence A and B), which are ligands for activating
NK cell receptors.
Conclusion: Our data demonstrate an expansion of NK cells and their activity markers in Ro/SSA exposed neonates, as well
as an upregulation of activating NK cell receptors in fetal cardiac cells after IFN-alpha exposure, indicating that NK cell
related effector mechanisms such as antibody-dependent cell cytotoxicity (ADCC) may be a central mechanism by which
the inflammation is initiated in CHB. The expansion of NK cells in neonates at risk for CHB is a novel observation, and
implicates fetal innate immune mechanisms in the pathogenesis.
Disclosure: M. Ivanchenko, None; M. Hedlund, None; G. E. Thorlacius, None; V. Ottosson, None; K. Chemin, None; S.
E. Sonesson, None; M. Wahren-Herlenius, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rossa-autoantibody-exposed-neonates-

have-an-expansion-of-nk-cells-and-a-discernible-type-ii-ifn-signature-with-high-ifn%ce%b3-in-peripheral-blood
Role of the Pyrin Inflammasome in Resistance to Yersinia Pestis: A Possible

Selective Advantage for Carriers of MEFV Mutations
Yong Hwan Park1, Wonyong Lee1, Lawton Chung2, James Bliska2, Daniel L. Kastner1 and Jae Jin Chae3, 1Inflammatory
Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 2Department of
Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, NY, 3Inflammatory
disease section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
SESSION INFORMATION
Background/Purpose: Mutations in MEFV, encoding pyrin, cause the prototypic autoinflammatory disease, familial
Mediterranean fever (FMF). The carrier frequency of FMF-associated MEFV mutations is extraordinarily high in
Mediterranean and Middle Eastern populations, suggesting that heterozygous FMF mutations may confer a selective
advantage against some pathogenic microbes. Inactivation of the RhoA GTPase is a common bacterial virulence mechanism,
because RhoA activation is required for actin polymerization and leukocyte migration, phagocytosis, and degranulation. The
pyrin inflammasome senses RhoA inactivation and activates IL-1β as part of the host defense against these bacteria.
Pathogenic Yersinia, including Y. pestis, the agent of plague in humans, deliver virulence effectors, termed Yersinia outer
proteins (Yops), into host cells; some of these Yops are known to inactivate RhoA. In the current study, we utilized pyrin
knockin (KI) and knockout (KO) mice to examine the role of pyrin in host defense against Yersinia infection.
Methods: Pyrin-KO and FMF-KI mice harboring the FMF-associated M680I or V726A mutations were examined for
susceptibility to Y. pestis by infection studies. We measured IL-1β production by ELISA in immune cells from wild type and
from FMF-KI mouse strains, in response to wild type (WT) Y. pseudotuberculosis or Y. pestis, or to mutant Yersinia strains
with deletions of specific Yops. Protein interactions were studied by immunoprecipitation.
Results: In Yersinia-infected macrophages, the pyrin inflammasome was activated by the RhoA-inactivating enzymatic
activities of YopE and YopT. On the other hand, YopM specifically inhibited pyrin to promote virulence by activating the
host protein kinases (PKN1 and PKN2) that phosphorylate pyrin to block pyrin inflammasome activation. Pyrin-KO mice
were highly susceptible to Yersinia yopM mutant infection, while WT mice were not susceptible. However, bone marrow-
derived macrophages (BMDMs) from both homozygous and heterozygous FMF-KI mice released significantly higher levels
of IL-1β in comparison with WT BMDMs in response to Yersinia infection. These results suggest that the FMF-associated
mutant pyrin is not suppressed by YopM, thereby providing survival advantage of FMF-KI mice against Yersinia infection.
Indeed, FMF-KI mice, both homozygotes and heterozygotes, showed significant resistance to Y. pestis infection in
comparison with WT mice.
Conclusion: These findings, taken together with the historical record of high-mortality epidemics throughout human history,
suggest that Yersinia pestis played an important role in selecting for the high frequency of FMF-associated MEFV mutations
in Mediterranean and Middle Eastern populations.
Disclosure: Y. H. Park, None; W. Lee, None; L. Chung, None; J. Bliska, None; D. L. Kastner, None; J. J. Chae, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/role-of-the-pyrin-inflammasome-in-

resistance-to-yersinia-pestis-a-possible-selective-advantage-for-carriers-of-mefv-mutations
The Course of the Forced Vital Capacity during Treatment for Systemic
Sclerosis-Related Interstitial Lung Disease Predicts Long-Term Survival in 2
Independent Cohorts
Elizabeth R. Volkmann1, Donald P. Tashkin1, Myung Sim1, Dinesh Khanna2, Michael Roth3, Philip J. Clements3, Daniel
E. Furst1, Lynette Keyes-Elstein4, Ashley Pinckney4, Ellen Goldmuntz5, Robert Elashoff6 and Keith Sullivan7, 1University
of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, 2University of Michigan, Ann Arbor, MI,
3Medicine, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, 4Rho Federal
Systems, Inc., Chapel Hill, NC, 5NIAID, NIH, Bethesda, MD, 6University of California, Los Angeles, Los Angeles, CA,
7Duke University, Durham, NC
SESSION INFORMATION
Session Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's – Clinical Aspects and Therapeutics I
Background/Purpose: While prior observational studies have identified predictors of mortality in systemic sclerosis-
interstitial lung disease (SSc-ILD), no studies have evaluated predictors of long-term mortality in a clinical trial, in which all
patients receive standard care. The objective of this study was to identify predictors of mortality in patients who participated
in the Scleroderma Lung Study (SLS) I1 and II2.
Methods: SLS I randomized 158 SSc-ILD patients to 1 year of oral cyclophosphamide (CYC) versus placebo. SLS II
randomized 142 patients to 1 year of oral CYC followed by 1 year of placebo versus 2 years of mycophenolate (MMF). The
FVC%-predicted and DLCO%-predicted were measured every 3 months for 2 years in both trials. 12 years after SLS I
commenced, each study center contacted enrolled patients/designated surrogates to assess morbidity and mortality outcomes.
Counting process cox proportional hazard modeling identified variables associated with mortality. A joint model of
longitudinal FVC and survival data was used to internally validate the model. We externally validated the model using long-
term mortality data from SLS II (up to 5 years of follow-up).
Results: Among SLS I patients, 43% died during the follow-up period (median follow-up: 8 years), and only 24% remained
alive without organ failure. Where known, the cause of death was attributable most often to SSc. The most common type of
organ failure was respiratory failure (N=31 of 33 organ failures) defined as the need for supplemental oxygen therapy
(N=29) and/or lung transplantation (N=3). There was no significant difference in the time to death between patients
randomized to CYC versus placebo (Figure 1). The Cox model identified the following mortality predictor variables:
baseline skin score (HR 1.03; P=0.004), age (HR 1.06; P<0.0001), and the course of the FVC from baseline to 24 months
(HR 0.98; P=0.022). The course of the FVC was a better predictor than the baseline FVC. The joint model identified the
same variables associated with mortality. Using the SLS II data, the Cox model identified the same mortality predictor
variables: baseline skin score (HR 2.08; P=0.021), age at randomization (HR 1.08; P=0.011), and the course of the FVC
from baseline to 24 months (HR 0.79; P=0.020).
Conclusion: Treatment with 1-year of oral CYC for SSc-ILD did not significantly decrease long-term mortality compared
with placebo. In addition to identifying traditional mortality risk factors in SSc (i.e. increased skin score and advanced age),
this study found that a decline in FVC over 2 years was a better predictor of mortality than the baseline FVC. These findings
suggest that early changes in surrogate measures of SSc-ILD progression may have important effects on long-term
outcomes.
1Tashkin et al. NEJM 2006.
2Tashkin et al. Lancet Resp Med 2016.
Figure 1. Time to death in patients randomized to CYC (solid line) and placebo (dotted line).
Disclosure: E. R. Volkmann, None; D. P. Tashkin, None; M. Sim, None; D. Khanna, Actelion, Bayer,
BoehringerIngelheim, Chemomab, Corbus, Covis, Cytori,Eicos, EMD Serono, Genentech/Roche, Gilead, GSK, Sanofi-
Aventis,UCB Pharma, 5,NIH/NIAMS, NIH/NIAID,Bayer, BMS, Genentech/Roche, Pfizer, 2,Eicos, 4; M. Roth, None; P. J.
Clements, None; D. E. Furst, None; L. Keyes-Elstein, None; A. Pinckney, None; E. Goldmuntz, None; R. Elashoff,
None; K. Sullivan, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-course-of-the-forced-vital-capacity-

during-treatment-for-systemic-sclerosis-related-interstitial-lung-disease-predicts-long-term-survival-in-2-independent-
cohorts
Long-Term Survival and Follow-up of Anti-Th/to Antibody Positive Systemic

Sclerosis Patients
Devon Charlton1, Maureen Laffoon2, Thomas A. Medsger Jr.3 and Robyn T. Domsic4, 1Division of Rheumatology and
Clinical Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, 2Rheumatology, University of Pittsburgh
Medical Center, Pittsburgh, PA, 3Department of Medicine/Rheumatology, University of Pittsburgh, Pittsburgh, PA,
4Medicine - Rheumatology, University of Pittsburgh, Pittsburgh, PA
SESSION INFORMATION
Background/Purpose:
Anti-Th/To antibody is an autoantibody associated with systemic sclerosis (SSc), occurring in 5-10% of patients. To date,
only relatively small case series have described the clinical associations of this autoantibody, as commercial testing has not
been readily available. Thus, the long-term clinical features and outcomes of patients with anti-Th/To antibody is not known.
The objective of this study was to further characterize the clinical associations and mortality risk of SSc patients who are
anti-Th/To positive.
Methods:
We performed a case-control study. Eligible patients were identified from consecutive new SSc patietns seen at a large US
SSc Center between 1980-2015. Cases were found to be anti-Th/To antibody positive by immunoprecipitation. Each case
was matched to the next two consecutive SSc patients seen in clinic (2:1 match). Descriptive statistics, Kaplan-Meier and
Cox proportional hazards was performed using SAS 9.4.
Results:
199 Th/To-positive SSc patients were identified and matched to 398 controls. The mean age of the entire population was
51.6 ± 14.1 years, 78% female and 92% Caucasian. Th/To positive patients were more frequently Caucasian, had long
disease duration at evaluation and more often presented with SSC sine scleroderma (see Table 1). At baseline Th/To patients
were more frequently found to have pulmonary hypertension, but less frequent joint involvement. There was no difference in
rate of interstitial lung disease (ILD) found on radiographic imaging (Table 1).
As of last follow-up 41 (21%) of Th/To positive patients had developed PAH compared to 43 (11%; p=0.001). Twenty-five
(13%) Th/To positive patients had developed PH secondary to ILD compared to 33 (8%) controls (p= 0.10), with no
difference in frequency of ILD. Despite the greater frequency of PH in cases, 5-year cumulative survival was not any
different between Th/To positive patients (29%) and controls (28%; p=0.90), even after adjustment for age and gender.
Conclusion:
This is the largest cohort of Th/To antibody positive SSc patients for which there is long-term follow-up for clinical features
and survival data available. Compared to other SSc patients, anti-Th/To patients develop higher rates of PAH. Cumulative 5-
year survival is not reduced in Th/To patients, likely reflecting advances in PAH management. SSc patients should be
routinely screened for the Th/To antibody, with consideration of appropriate screening for PAH.
Table 1: Characteristics of Anti-Th/To Positive Patients and Controls at First SSc Center Visit
Anti-Th/To Controls
n=199 n=398 p-value

Demographics 52.4 (12.2) 51.2 (15.0) NS
Mean age in years at first visit* (SD)

Female 156 (78%) 312 (78%) NS
Caucasian 189 (95%) 356 (90%) 0.04
SSc Disease Characteristics 7.8 (2.5, 15.0) 5.4 (1.8, 13.0) 0.01
Median disease duration in years (IQR)

Median modified Rodnan skin score† (IQR) 2 (1,4) 4 (2,14) <0.0001
Limited skin thickening 197 (99%) < 0.0001
Systemic sclerosis sine scleroderma 45 (23%) 62 (16%) 0.03
Overlap 0 (0%) 7 (3.5%) NS
SSc Internal Organ Involvement at 1st Visit 35 (19%) 29 (8%) 0.0002
Pulmonary Arterial Hypertension

Fibrosis by imaging 36 (18%) 74 (19%) NS
Cardiac 24 (12%) 41 (10%) NS
Gastrointestinal 26 (14%) 77 (19%) NS
Joint 62 (32%) 223 (58%) < 0.0001
Renal Crisis 3 (2%) 15 (4%) NS
WHO Group Pulmonary Hypertension 35 29 0.02
Pulmonary arterial hypertension (Group 1) 1 3
Related to cardiac disease (Group 2) 14 20
Related to lung disease (Group 3)

*Disease onset defined as first symptom attributable to SSc; SD = standard deviation; IQR =
interquartile range
Disclosure: D. Charlton, None; M. Laffoon, None; T. A. Medsger Jr., None; R. T. Domsic, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/long-term-survival-and-follow-up-of-

anti-thto-antibody-positive-systemic-sclerosis-patients

Autoantibodies to the hPOP1 and Rpp25/38 Components of the Th/to
Complex Identify a Subgroup of Systemic Sclerosis (SSc) Associated
Interstitial Lung Disease (ILD) and Antibodies to hPOP1 Are Associated with
Reduced Survival
Jennifer G Walker1, Mandana Nikpour2, Molla Huq3, Karen Patterson1, Peter Roberts-Thomson4, Susanna Proudman5,
Wendy Stevens6, Susan Lester7, Maureen Rischmueller8, Jane Zochling9, Joanne Sahhar10, Peter Nash11, Janet Roddy12,
Catherine Hill13, Marie Hudson14, Murray Baron15, Janet E. Pope16, Maureen D. Mayes17, Shervin Assassi18, Michael
Mahler19 and Marvin J. Fritzler20, 1Flinders University of South Australia, Adelaide, Australia, 2Melbourne University,
Melbourne, Australia, 3Department of Medicine (Rheumatology), Melbourne University, Melbourne, Australia,
4Immunology, Flinders University of South Australia, Adelaide, Australia, 5University of Adelaide, Adelaide, Australia,
6Rheumatology, St. Vincent’s Hospital, Melbourne, Australia, 7Queen Elizabeth Hospital, Adelaide, Australia, 8Medicine,
University of Adelaide, Adelaide, Australia, 9Menzies Institute for Medical Research, Tasmania, Hobart, Australia,
10Department of Rheumatology, Monash Medical Centre, Melbourne, Australia, 11University of Queensland, Brisbane,
Australia, 12Royal Perth Hospital, Perth, Australia, 13Medicine, The University of Adelaide, Adelaide, Australia, 14Division
of Rheumatology, Jewish General Hospital, Lady David Institute for Medical Research, Montreal, QC, Canada, 15Medicine,
McGill University, Quebec, Montreal, QC, Canada, 16Department of Medicine, Division of Rheumatology, University of
Western Ontario, St Joseph's Health Care, London, ON, Canada, 17Internal Medicine/Rheumatology, University of Texas
Health Science Center at Houston, Houston, TX, 18University of Texas McGovern Medical School, Houston, TX,
19Research and Development, Inova Diagnostics, San Diego, CA, 20Medicine, University of Calgary, Calgary, AB, Canada
SESSION INFORMATION
Background/Purpose: The clinical associations of anti-Th/To antibodies (Abs) are not fully established, and until recently
immunoprecipitation (IP) was the only reliable assay. Using IP, anti-Th/To Abs are mostly detected in SSc but other reported
associations include ILD. Our objective was to examine clinical correlates of anti-Th/To Abs targeted against three different
proteins associated with the Th/To autoantigen complex in SSc. We used a commercially available hPOP1 immunoblot and a
recently described Rpp25 and Rpp38 chemiluminescence assay in a multinational cohort of SSc.
Methods: Cross sectional retrospective study including 1312 patients from the Australian Scleroderma Cohort study
(ASCS), Canadian Scleroderma Research Group (CSRG) and the Genetics versus Environment in Scleroderma Outcome
Study (GENISOS). Demographic and clinical variables were harmonized and sera tested for anti-Th/To Abs using hPOP1
(EUROLINE, Eurimmun, Lubeck, Germany) and Rpp25/38 (QUANTA Flash Assay, Inova Diagnostics Inc, San Diego,
CA). Rpp25/38 was defined as positive if either one or both autoantibodies were present. ILD was determined by high
resolution CT chest (HRCT) or a published algorithm [1] which allows diagnosis of ILD by chest X-ray showing increased
interstitial markings or fibrosis and/or physician reported “velcro-like crackles” when HRCT is not available. Descriptive
statistics summarise baseline demographic and clinical variables and Kaplan Meier analyses were used to assess survival
Results:
Patients had median (interquartile range) age at disease onset 46.3y (18.6) and disease duration 5.1y (11.4) at recruitment.
hPOP1 was positive in 2.4% and Rpp25/38 was positive in 4.5% patients. Notably hPOP1 and Rpp25/38 identified
overlapping patient populations (p<0.001). Median age of disease onset for hPOP1 patients was 48.9y (23.3) and for
Rpp25/38 patients was 48.8y (17.3).
hPOP1 was associated with ILD on HRCT chest (OR:5.16; p=0.02) but not ILD by algorithm (OR:1.19; p= 0.642). hPOP1
was negatively associated with centromere Abs (CENP) (OR:0.24, p=0.018) and positively associated with PM75/100 (OR:
3.07, p=0.01) ,and Ro52/TRIM21 (OR: 3.18, p=0.002). hPOP1 was not associated with Scl-70 (p=0.089).
Fifty patients (4.0%) were Rpp25 positive and 14 patients (1.1%) Rpp38 positive with strong correlation between the two (p
<0.001; rho=0.72). Rpp25/38 was associated with ILD detected by HRCT (OR:3.04; p=0.009) and by algorithm (OR: 2.01
p=0.01). Rpp25/38 was negatively associated with CENP (OR: 0.08, p<0.001) and Scl-70 (OR: 0.19, p=0.020).
Survival was reduced in hPOP1 positive patients (p<0.001), especially when ILD was present. Rpp25/38 and hPOP1
positivity was not associated with pulmonary hypertension nor other disease manifestations.
Conclusion:
In a large multinational SSc cohort autoantibodies to the hPOP1 and Rpp25/38 components of Th/To were found
infrequently and appeared to identify two ILD populations. hPOP1 positivity was associated with ILD on HRCT chest and
reduced survival while Rpp25/38 positivity was associated with ILD on HRCT and by clinical algorithm and testing may
therefore identify those with differing lung involvement.
1. Arthritis Care Res (Hoboken), 2012. 64(4): p. 519-24.
Disclosure: J. G. Walker, None; M. Nikpour, I have received, either directly, or indirectly through close research
collaborations, research support from the following companies: Actelion, GSK, Pfizer, BMS, UCB, Astra Zeneca, Janssen.,
2,I have presented for UCB as a speaker. I have consulted for Eli Lilly., 5; M. Huq, None; K. Patterson, None; P. Roberts-
Thomson, None; S. Proudman, Actelion Pharmaceuticals US, 2,GlaxoSmithKline, 2; W. Stevens, None; S. Lester, None;
M. Rischmueller, None; J. Zochling, None; J. Sahhar, None; P. Nash, AbbVie, Amgen, Bristol-Myers Squibb, Celgene,
Eli Lilly and Company, Hospira, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, 5,AbbVie, Amgen, Bristol-
Myers Squibb, Celgene, Eli Lilly and Company, Hospira, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB,
8,AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Hospira, Janssen, MSD, Novartis, Pfizer, Roche,
Sanofi, and UCB, 2; J. Roddy, None; C. Hill, None; M. Hudson, None; M. Baron, None; J. E. Pope, AbbVie, Amgen,
Bayer, BMS, Celtrion, Eli Lilly and Company, Merck, Novartis, Pfizer, Roche, UCB, 5,Amgen, Bayer, BMS, GSK, Merck,
Novartis, Pfizer, Roche, UCB, 2; M. D. Mayes, None; S. Assassi, Bayer Healthcare, 2,Biogen Idec, 2,Reata, 5,Boehringer
Ingelheim, 5; M. Mahler, Inova Diagnostics, Inc., 3; M. J. Fritzler, Inova Diagnostics, Inc., 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/autoantibodies-to-the-hpop1-and-

rpp2538-components-of-the-thto-complex-identify-a-subgroup-of-systemic-sclerosis-ssc-associated-interstitial-lung-disease-
ild-and-antibodies-to-hpop1-are-associat
Clinical and Serological Features of Systemic Sclerosis in a Multicenter

African American Cohort: Analysis of the Genome Research in African
American Scleroderma Patients Clinical Database
Nadia D. Morgan1, Ami A. Shah1, Maureen D. Mayes2, Robyn T. Domsic3, Thomas A. Medsger Jr.4, Virginia D. Steen5,
John Varga6, Mary A. Carns7, Paula S. Ramos8, Richard M. Silver9, Elena Schiopu10, Dinesh Khanna10, Vivien Hsu11,
Jessica K. Gordon12, Heather Gladue13, Lesley A. Saketkoo14, Lindsey A. Criswell15, Chris T. Derk16, Marcin A.
Trojanowski17, Victoria K. Shanmugam18, Lorinda Chung19, Antonia Valenzuela20, Reem Jan21, Avram Goldberg22, Elaine
F. Remmers23, Daniel L. Kastner23, Fredrick M. Wigley24, Pravitt Gourh25 and Francesco Boin26, 1Rheumatology, Johns
Hopkins University School of Medicine, Baltimore, MD, 2Rheumatology, University of Texas Health Science Center at
Houston, Houston, TX, 3Medicine - Rheumatology, University of Pittsburgh, Pittsburgh, PA, 4Department of
Medicine/Rheumatology, University of Pittsburgh, Pittsburgh, PA, 5Division of Rheumatology, Department of Medicine,
MedStar Georgetown University Hospital, Washington, DC, 6Rheumatology and Dermatology, Northwestern University,
Feinberg School of Medicine Scleroderma Program, Chicago, IL, 7Northwestern University, Feinberg School of Medicine
Scleroderma Program, Chicago, IL, 8Division of Rheumatology and Immunology, Medical University of South Carolina,
Charleston, SC, 9Division of Rheumatology and Immunology, Department of Medicine, Medical University of South
Carolina, Charleston, SC, 10University of Michigan, Ann Arbor, MI, 11Rheumatology, Robert Wood Johnson University
Scleroderma Program, New Brunswick, NJ, 12Rheumatology, Hospital for Special Surgery, New York, NY,
13Rheumatology, Arthritis and Osteoporosis Consultants of the Carolinas, Charlotte, NC, 14Rheumatology, Tulane
University School of Medicine, New Orleans, LA, 15Medicine/Rheumatology, University of California, San Francisco, San
Francisco, CA, 16Rheumatology, University of Pennsylvania, Philadelphia, PA, 17Boston University School of Medicine,
Boston, MA, 18Rheumatology, The George Washington University, Washington, DC, 19Division of Immunology and
Rheumatology, Stanford University School of Medicine, Stanford, CA, 20Stanford University School of Medicine, Stanford,
CA, 21Medicine, Rheumatology, University of Chicago, Chicago, IL, 22NYU Langone Medical Center, New York, NY,
23National Institutes of Health (NIH), National Human Genome Research Institute, Bethesda, MD, 24Rheum Div/Mason F
Lord, Johns Hopkins University, Baltimore, MD, 25NIAMS-Rheumatology, National Institutes of Health (NIH), National
Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, 26Rheumatology, University of California, San
Francisco, San Francisco, CA
SESSION INFORMATION
Background/Purpose:
Racial differences exist in the severity of systemic sclerosis (SSc). To enhance our knowledge about SSc in African
Americans, we established a comprehensive clinical database from the largest multicenter cohort of African American SSc
patients assembled to date (the Genome Research in African American Scleroderma Patients (GRASP) cohort). We
compared the phenotypic manifestations of SSc in the GRASP cohort to that reported in the European League Against
Rheumatism Scleroderma Trials and Research (EUSTAR) cohort1.
Methods:
African American SSc patients were enrolled retrospectively and prospectively over a 30-year period (1987 to 2016), from
18 academic centers throughout the United States. 945 (94%) patients met the 2013 ACR/EULAR classification criteria for
SSc, with the remaining 64 (6%) meeting the 1980 ACR or CREST criteria. The cross-sectional prevalence of
sociodemographic, clinical and serological features was evaluated using data obtained at the time of study enrollment.
Factors associated with clinically significant manifestations of SSc were assessed using multivariate logistic regression
analyses.
Results:
The study population included a total of 1009 African American SSc patients comprised of 84% women. While 43% were
actively employed, 33% required disability support. The majority (57%) had the more severe diffuse subtype and a young
age at symptom onset (39.1±13.7 years), in marked contrast to that reported in the EUSTAR cohort. 11% of patients had a
severe Medsger cardiac score2 of 4 (Figure 1). Pulmonary fibrosis evident on computed tomography (CT) chest was present
in 43% of patients, and was significantly associated with anti-topoisomerase I positivity (Table 1). 38% of patients with CT
evidence of pulmonary fibrosis had a severe restrictive ventilator defect with forced vital capacity (FVC) £50% predicted.
16% of patients in the GRASP cohort required oxygen therapy compared to 3% in the EUSTAR cohort. A significant
association was noted between longer disease duration and higher odds of pulmonary hypertension (Table 1). The
prevalence of potentially fatal scleroderma renal crisis was 7%, 3.5 times higher than that reported in the EUSTAR cohort.
Conclusion:
Our study emphasizes the unique and severe disease burden of SSc in African Americans compared to those of European
ancestry.
1. Meier FM, et al. Update on the profile of the EUSTAR cohort: an analysis of the EULAR Scleroderma Trials and
Research group database. Ann Rheum Dis. 2012;71:1355-60.
2. Medsger TA, Jr., et al. Assessment of disease severity and prognosis. Clin Exp Rheumatol. 2003;21:S42-6.
Disclosure: N. D. Morgan, None; A. A. Shah, None; M. D. Mayes, None; R. T. Domsic, None; T. A. Medsger Jr., None;
V. D. Steen, None; J. Varga, BMS, 2,Pfizer Inc, 2; M. A. Carns, None; P. S. Ramos, None; R. M. Silver, None; E.
Schiopu, None; D. Khanna, Actelion, Bayer, BoehringerIngelheim, Chemomab, Corbus, Covis, Cytori,Eicos, EMD
Serono, Genentech/Roche, Gilead, GSK, Sanofi-Aventis,UCB Pharma, 5,NIH/NIAMS, NIH/NIAID,Bayer, BMS,
Genentech/Roche, Pfizer, 2,Eicos, 4; V. Hsu, None; J. K. Gordon, None; H. Gladue, None; L. A. Saketkoo, None; L. A.
Criswell, None; C. T. Derk, None; M. A. Trojanowski, None; V. K. Shanmugam, Multiple, 9; L. Chung, Cytori,
Actelion, Reata, 5; A. Valenzuela, None; R. Jan, None; A. Goldberg, None; E. F. Remmers, None; D. L. Kastner, None;
F. M. Wigley, None; P. Gourh, None; F. Boin, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/clinical-and-serological-features-of-

systemic-sclerosis-in-a-multicenter-african-american-cohort-analysis-of-the-genome-research-in-african-american-
scleroderma-patients-clinical-database
Norway As a National Reference Population for Systemic Sclerosis;

Preliminary Results from a Complete, Nationwide Cohort
Anna-Maria Hoffmann-Vold1, Håvard Fretheim1, Anne Kristine Halse2, Marit Seip3, Marianne Wallenius4, Helle Bitter5,
Torhild Garen1, Oyvind Midtvedt1 and Øyvind Molberg1, 1Oslo University Hospital, Oslo, Norway, 2Haukeland University
Hospital, Bergen, Norway, 3University Hospital of North Norway, Tromso, Norway, 4St. Olav's University Hospital,
Trondheim, Norway, 5Hospital of Southern Norway, Kristiansand, Norway
SESSION INFORMATION
Background/Purpose: To fully understand the impact of Systemic sclerosis (SSc) there is a need to complement existing
multi-center registry data with novel, unbiased, high resolution results from large population based cohorts, such as
complete, nationwide cohorts. The Norwegian health system is organized so that all SSc patients are followed by specialists
at public hospitals; making it possible to identify every single patient resident in the country within a defined time period.
Here, we took advantage of this possibility; and aimed to determine incidence, prevalence, mortality and organ involvement
of SSc in Norway (denominator population 5.0 million).
Methods: The Norwegian, nationwide SSc (Nor-SSc) study cohort included all adult patients in Norway who were; (A)
resident in Norway from 2000-12, (B) first time registered with an ICD-10 code M34 (SSc) in a public hospital database, (C)
had a clinical SSc diagnosis verified by rheumatologist and (D) met the 1980 ACR and/or 2013 ACR/EULAR classification
criteria for SSc. Detailed electronic patient journal review was performed in all cohort patients to assess disease features
from SSc onset and to the end of the defined observation period (January 2013).
Results: The Nor-SSc cohort included 885 patients, of whom 666 (75.3%) were alive by January 2013. Point prevalence of
SSc in Norway was estimated to 13/100.000. Number of new SSc cases per year is shown in Figure 1. Mean age at onset
was 49 years, 70% were female and 70% had limited cutaneous SSc (Figure 2). Preliminary analyses of echocardiography
data (available in 705 patients; 80%), lung HRCT (from 637 pts; 72%) and right heart catheterization (performed in 290 pts;
33%) indicate frequencies of cardiopulmonary involvement that are comparable to multi-centre registry data (Figure 3).
Upper GI involvement appears to be highly prevalent (Figure 3).
Conclusion: In this population based, nationwide study, we found a comparable SSc prevalence to regional studies from
other northern European countries. We found that a large proportion of the patients had severe organ involvement;
reinforcing the view that SSc truly has a very high burden of disease.
Figure 1:
Figure 2:
Figure 3:
Disclosure: A. M. Hoffmann-Vold, None; H. Fretheim, None; A. K. Halse, None; M. Seip, None; M. Wallenius, None;
H. Bitter, None; T. Garen, None; O. Midtvedt, None; Ø. Molberg, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/norway-as-a-national-reference-

population-for-systemic-sclerosis-preliminary-results-from-a-complete-nationwide-cohort
Application of a Diagnostic Algorithm to Identify Inflammatory Myopathy in

Systemic Sclerosis
Vandana Bhushan1,2, Adam Maundrell1, Charlotte Proudman1,2, Leah McWilliams1, Llew Spargo1, Robert Metcalf1,
Jennifer Walker3, Mandana Nikpour4,5, Wendy Stevens4, Vidya Limaye1,2 and Susanna Proudman1,2, 1Rheumatology Unit,
Royal Adelaide Hospital, South Australia, Adelaide, Australia, 2Discipline of Medicine, University of Adelaide, South
Australia, Adelaide, Australia, 3Flinders University of South Australia, Adelaide, Australia, 4St Vincent's Hospital,
Melbourne, Victoria, Melbourne, Australia, 5Department of Medicine, University of Melbourne, Victoria, Melbourne,
Australia
SESSION INFORMATION
Background/Purpose:
Muscle involvement in systemic sclerosis (SSc) is under-recognised and poorly understood. Reported prevalence varies up
to 15%, reflecting lack of consistent definition, the heterogeneous spectrum of muscle involvement, ranging from non-
specific myopathic changes to idiopathic inflammatory myopathies such as polymyositis, but also lack of a standardised
approach to detection. Early diagnosis of inflammatory myopathy by muscle biopsy is important to guide
immunosuppressive therapy to minimise irreversible loss of muscle power and function. We sought to determine the
prevalence of inflammatory myopathy in patients with SSc assessed annually for features of muscle involvement according
to a standardised algorithm.
Methods:
Consecutive patients with SSc, according to the 1980 ACR or LeRoy and Medsger criteria, enrolled in the Australian
Scleroderma Cohort Study (ASCS) since 2007, are assessed annually for features of myopathy: proximal muscle weakness
based on the Medical Research Centre scale and elevated creatine kinase (CK) > 150 U/L. No specific guidelines for further
investigation are followed. In a subset of patients from a single ASCS centre, if proximal weakness and/or elevated CK were
present, myositis immunoblot for myositis specific antibodies (MSA) and/or MRI of upper or lower limbs for increased T2
signal or fatty infiltration and atrophy were performed; positive findings prompted a muscle biopsy. Features of patients with
and without histopathological features of inflammation on biopsy were compared.
Results:
Among 1197 patients enrolled in the ASCS, 176 (14.7%) had elevated CK with or without weakness at any time during
follow up, 128 (10.7%) had weakness with a normal CK, and 18 (1.5%) patients had biopsy-proven inflammatory myopathy.
In a separate ASCS cohort of 333 patients in South Australia, 89 of 323 (27.6%) had elevated CK, 83 of 326 (25.5%) had
proximal weakness and 34 (10.2%) were selected for muscle biopsy. Abnormalities were present in all 34 biopsies, with
inflammatory myopathy (polymyositis, 10; dermatomyositis, 4; inclusion body myositis, 3; necrotising, 1; other, 2)
confirmed in 20 (58.8%) and nonspecific features of myopathy reported in 14.
Among the biopsied patients, incidence of diffuse cutaneous subtype and levels of CK were significantly higher in those
with inflammatory compared with non-inflammatory myopathy (Table 1). Immunosuppressive use at time of biopsy was
similar in the two groups.
Table 1: Characteristics of SSc patients selected for muscle biopsy

Inflammatory Non-inflammatory P value1
myopathy myopathy
n = 20 n = 14
Diffuse SSc 6 0 0.031
SSc antibodies: 10/20 9/14 0.500
ACA 3 2
Scl70 2 2
RNA polymerase III 1 3
RNP 4 2
Immunosuppressive 9 9 0.147
therapy at time of
biopsy
Elevated CK 14 7 0.238
CK level U/L (median, 436 (243-571) 132 (63-383) 0.0232
IQR)
Proximal weakness 15 11 1.000
Myositis immunoblot 10/17 4/10 0.440
+ve:
7 2
Ro52
1 0
Mi-2
1 1
Ku
2 1
PM-Scl75
1 1
Jo-1
1 0
SRP
1 0
PL7
1 0
PL12
Increased T2 signal on 6/7 2/7 0.103
MRI muscle
IQR, interquartile range

1Fisher’s exact test except where indicated. 2Mann Whitney U.
Conclusion:
A diagnostic algorithm including MSA and MRI, detected biopsy-proven muscle involvement in 10.2% of patients with SSc
and increased the detection of inflammatory myopathy to 6% of patients compared with 1.5% in the whole ASCS cohort.
Disclosure: V. Bhushan, None; A. Maundrell, None; C. Proudman, None; L. McWilliams, None; L. Spargo, None; R.
Metcalf, None; J. Walker, Actelion Australia, Bayer, CSL Biotherapies, GlaxoSmithKline Australia and Pfizer, 2; M.
Nikpour, Actelion Australia, Bayer, CSL Biotherapies, GlaxoSmithKline Australia and Pfizer, 2; W. Stevens, Actelion
Australia, Bayer, CSL Biotherapies, GlaxoSmithKline Australia and Pfizer, 2; V. Limaye, None; S. Proudman, Actelion
Australia, Bayer, CSL Biotherapies, GlaxoSmithKline Australia and Pfizer, 2,Actelion Australia, 8.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/application-of-a-diagnostic-algorithm-to-
identify-inflammatory-myopathy-in-systemic-sclerosis
Sequence Homology and Immune Reactivity between T Cell Epitopes

of Related Gut Microbes and Two Novel Autoantigens Provide a Link
between Microbial and Host Immunity in Patients with Rheumatoid Arthritis
Annalisa Pianta1, Sheila Arvikar2, Klemen Strle3, Elise E. Drouin1, Qi Wang4, Catherine E. Costello4 and Allen C.
Steere5, 1Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School,
Boston, MA, 2Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, BOSTON, MA,
3Department of Immunology and Inflammatory Diseases, Massachusetts General Hospital, BOSTON, MA, 4Center for
Biomedical Mass Spectrometry, Boston University School of Medicine, Boston, MA, 5Center for Immunolgy and
Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA
SESSION INFORMATION
Session Title: T Cell Biology and Targets in Autoimmune Disease
Background/Purpose: It has been proposed that immunological triggers at mucosal sites, such as the gut microbiota, may
promote autoimmunity affecting joints in patients with rheumatoid arthritis (RA). We recently reported evidence for immune
relevance of Prevotella copri, a gut microbe, in a subgroup of new-onset and chronic RA patients. However, it has been
unclear how immune responses to gut microbes may be linked to autoimmune joint pathology.
Methods: To identify disease-relevant microbial and self antigens involved in the pathogenesis of RA, we used a novel
proteomic approach to identify HLA-DR-presented peptides (T cell epitopes) in patients’ samples by tandem mass
spectrometry. Immunoreactive peptides or their source proteins were then tested for T cell reactivity by IFN-γ ELISpot assay
and for antibody responses by ELISA in our large cohort of RA patients or control subjects. Serum samples were also
analyzed for innate, Th1, and Th17 mediators by Luminex. Immunoreactive epitopes were searched for microbial sequence
homology using BLASTp, and homologous peptides were tested for T cell reactivity. All RA patients met the 2010
ACR/EULAR criteria for RA.
Results: From proteomic analyses, we identified two novel autoantigens, N-acetylglucosamine-6-sulfatase (GNS) and
filamin A (FLNA), as targets of T and B cell responses in about half of RA patients. These autoantibody responses were
found primarily in patients with antibodies to P. copri, and both IgG and IgA responses to P. copri correlated with the
autoantibody levels. These microbial and self immune responses occurred specifically in RA patients, and not in those with
other rheumatic diseases or in healthy subjects. Both self proteins were highly expressed in synovia. GNS (but not FLNA)
appeared to be citrullinated, and antibody to the citrullinated GNS correlated with anti-citrullinated-protein antibody levels.
Anti-GNS and anti-FLNA autoantibodies also correlated with inflammatory cytokines IFN-γ, IL-12, IL17-F, and IL-22,
indicative of Th1 and Th17 adaptive immune responses. In a search for T cell epitope mimicry, the HLA-DR-presented GNS
peptide was found to have marked sequence homology with epitopes from sulfatase proteins of the gut microbes of the
Prevotella and Parabacteroides sp., whereas the HLA-DR-presented FLNA peptide had homology with epitopes from
proteins of of Prevotella and Butyricimonas sp., another gut commensal. Patients with T cell reactivity with each self-
peptide had responses to the corresponding microbial peptides, and the levels correlated directly. These responses were more
common in patients with shared-epitope alleles.
Conclusion: These findings provide evidence for immune relevance of a related order of gut commensals in a subgroup of
RA patients, and suggest that gut dysbiosis may compromise the mucosal barrier resulting in leakage of microbes.
Moreover, the identification of T cell epitope mimicry between microbial and self epitopes as well as significant correlations
in patients’ immune responses to these antigens provide a mechanism linking mucosal immunity and joint autoimmunity in
these patients. Finally, the specificity of these responses may advance diagnostic testing in RA.
Disclosure: A. Pianta, None; S. Arvikar, None; K. Strle, None; E. E. Drouin, None; Q. Wang, None; C. E. Costello,
None; A. C. Steere, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/sequence-homology-and-immune-

reactivity-between-t-cell-epitopes-of-related-gut-microbes-and-two-novel-autoantigens-provide-a-link-between-microbial-
and-host-immunity-in-patients-with-rheumat
Identification of Naturally Processed Immunodominant Topoisomerase I

Epitopes in Patients with Systemic Sclerosis
Eleni Tiniakou1, Andrea Fava2, Tara Guhr3, Francesco Boin4 and Erika Darrah5, 1Division of Rheumatology, Johns
Hopkins University School of Medicine, Baltimore, MD, 2Johns Hopkins University, Baltimore, MD, 3University of North
Carolina, Chapel Hill, NC, 4Rheumatology, University California, San Francisco, San Francisco, CA, 5Department of
Medicine/Division of Rheumatology, The Johns Hopkins University School of Medicine, Baltimore, MD
SESSION INFORMATION
Background/Purpose:
Identification of immunodominant T cell epitopes of autoantigens is crucial to understanding the pathogenesis of

autoimmune diseases and developing disease-specific diagnostic and therapeutic tools. A subset of patients with systemic
sclerosis (SSc) exhibit autoantibodies and CD4+ T cells specific for topoisomerase-I (Topo-I), which are quantitatively
associated with the presence and severity of lung fibrosis. Mapping of immunodominant Topo-I T cell epitopes has been
difficult due to poor sensitivity, high cost of current protocols, and has mainly been based on in silico prediction or
overlapping peptide libraries. Existing data are limited by the low precision of these approaches and the poor sensitivity of
detection assays. We present a new method for mapping immunodominant Topo-I T cell epitopes using the natural
processing and presentation of HLA-DR-restricted Topo-I peptides by monocyte derived dendritic cells (MoDCs) from SSc
patients.
Methods:
MoDCs from 6 anti-Topo-I positive SSc patients were pulsed with whole Topo-I protein. Following overnight exposure,
immunoprecipitation was performed to isolate HLA-DR/peptide complexes. Peptides were identified by mass spectrometry,
and matched to the Topo-I sequence. The peptides were then synthesized and used to stimulate peripheral blood
mononuclear cells (PBMCs) from these patients in the presence of anti-CD40 antibody. Topo-I-reactive CD4+ T cells were
identified by flow cytometry based on activation status (CD40L/CD154 upregulation). PBMCs from 8 additional randomly
selected anti-Topo-I + patients and 6 anti-Topo-I negative controls (anti-centromere or anti-RNA-Polymerase-III) were
stimulated using the same protocol.
Results:
Ten different naturally processed Topo-I peptides were identified. The peptides detected were located mainly in the core
region of the molecule. The median number of distinct peptides presented by each individual patient was 4 (range 1-8).
Peptide overlap among patients existed despite differences in their HLA-DR haplotype, with 8 out of 10 epitopes being
presented by two or more subjects. All Topo-I peptides were able to stimulate CD154 upregulation by CD4+ T cells from at
least one of the 14 anti-Topo-I positive patients tested. These T cell responses were significantly higher than that of 6
randomly selected anti-Topo-I negative SSc controls (p<0.001).
Conclusion:
Through characterization of naturally processed peptides, we have identified immunodominant Topo-I epitopes capable of
stimulating CD4+ T cells from anti-Topo-I positive patients with SSc. Additionally, our approach showed that a restricted
set of immunodominant Topo-I epitopes is presented by SSc patients carrying diverse HLA-DR alleles. This method
represents a cost-effective and dependable way to identify immunodominant epitopes and can provide novel targets for
disease monitoring and eventually, designing peptide-targeted immunotherapy.
Disclosure: E. Tiniakou, None; A. Fava, None; T. Guhr, None; F. Boin, None; E. Darrah, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/identification-of-naturally-processed-

immunodominant-topoisomerase-i-epitopes-in-patients-with-systemic-sclerosis
Cross Sectional Analysis of Citrullinated-Synovial Antigen-Specific CD4+ T

Cells in an RA Cohort Demonstrates Antigen Based Differences in T Cell
Frequency, Phenotype and the Influence of Immunotherapy
Cliff Rims1, Sylvia Posso1, Bernard Ng2, Jeffrey Carlin3, Eddie James4 and Jane H. Buckner4, 1Translational Research,
Benaroya Research Institute at Virginia Mason, Seattle, WA, 2Rheumatology, VA Puget Sound Healthcare System, Seattle,
WA, 3Rheumatology, Virginia Mason Medical Center, Seattle, WA, 4Benaroya Research Institute at Virginia Mason, Seattle,
WA
SESSION INFORMATION
Background/Purpose:
The presence of ACPA in RA indicates that an immune response directed toward citrullinated synovial antigens participates
in disease development or persistence. Research from our group have identified T cell targets derived from the auto-antigens
aggrecan, vimentin, fibrinogen, alpha-enolase, and cartilage intermediate layer protein (CILP). In this study, we visualized
peripheral antigen-specific CD4+ T cells using a multiplexed flow-cytometry based HLA class II tetramer assay in a cross-
sectional cohort of 80 RA and 30 matched healthy control subjects to understand their relevance to RA disease progression
and response to therapy.
Methods:
All subjects were DRB1*04:01. RA subjects were CCP positive and represented a range of characteristics including time
from diagnosis, disease activity and treatment at the time of blood draw. Antigen-specific T cells were visualized by directly
staining peripheral blood mononuclear cells (PBMC) with multiple tetramers corresponding to different antigens.
Frequencies and phenotypic features of antigen-specific CD4+ T cells were assessed for correlation with clinical
characteristics.
Results:
Ex-vivo analysis of PBMC revealed an increase in synovial targeted CD4 T cells when compared to matched healthy
DRB1*04:01 subjects. When analyzed by individual antigen CD4 T cells, aggrecan, vimentin and fibrinogen were increased
in RA, and by contrast cartilage-intermediate-layer-protein (CILP) and enolase specific T cells were reduced in comparison
to healthy subjects, suggesting that the characteristics of the CD4+ T cells response to synovial epitopes may be unique to
antigen specificity.
Within this patient cohort we found a lower frequency of synovial specific T cells in individuals on TNF therapies sampled
within 5 years of diagnosis. These differences were most pronounced in the CD4 T cells specific for aggrecan, vimentin and
fibrinogen, and showed alterations in chemokine receptor and activation marker expression in the treated group.
Ongoing studies will determine if frequency, phenotype and specificity of synovial specific CD4 T cells correlate directly
with disease duration, therapeutic duration, and clinical diagnostic values such as level of RF, CCP, CRP, and disease
severity.
Conclusion:
We have shown that a multiplexed tetramer assay can define the breadth and character of the T cell response to synovial
antigens. Characterizing a relatively large cohort of subjects, we demonstrate differences in the phenotype and frequency of
the T cells that respond to a diverse set of synovial antigens thought to be important targets in RA. In particular, we show
that synovial specific T cell frequency is influenced by therapeutic interventions. Better understanding the interplay of
antigen specificities and phenotypes in RA is vital to understanding disease pathogenesis, response to therapy and ultimately
developing antigen specific therapies.
Disclosure: C. Rims, None; S. Posso, None; B. Ng, None; J. Carlin, None; E. James, None; J. H. Buckner, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/cross-sectional-analysis-of-citrullinated-

synovial-antigen-specific-cd4-t-cells-in-an-ra-cohort-demonstrates-antigen-based-differences-in-t-cell-frequency-phenotype-
and-the-influence-of-immunotherap
Serine Arginine-Rich Splicing Factor 1 (SRSF1) Is a Novel Regulator of T

Lymphocyte Homeostasis In Vivo and Its Deficiency Associates with
Lymphopenia in SLE Patients
Takayuki Katsuyama1, Michael W. Mosho1, Andrew R. Gillooly2, George C. Tsokos1 and Vaishali R. Moulton3, 1Division
of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA,
2Medicine/ Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 3Rheumatology,
Beth Israel Deaconess Medical Center, Boston, MA
SESSION INFORMATION
Background/Purpose: Lymphopenia is a common clinical feature in patients with systemic lupus erythematosus (SLE), and
associates with high disease activity and comorbidities including infections. However, the mechanisms of lymphopenia in
SLE patients are not fully understood. SLE T cells exhibit increased susceptibility to apoptosis and display altered
expression of apoptosis/survival related genes such as the Bcl-2 family genes, many of which have pro- and anti-apoptotic
isoforms. Using discovery approaches we previously identified the serine arginine-rich splicing factor 1 (SRSF1) in human
T cells, and showed that it regulates normal expression of the CD3zeta chain and is required for IL-2 production. We showed
that SRSF1 expression levels are decreased in T cells from SLE patients, and this decrease associates with severe disease.
Because it is reported that SRSF1 regulates alternative splicing of the apoptosis-related gene BcL-x to promote the anti-
apoptotic long (L) isoform over the pro-apoptotic short (s) isoform, we hypothesized that SRSF1 is important for T
lymphocyte homeostasis, and its deficiency leads to apoptosis and lymphopenia in mice and in SLE patients.
Methods: 42 SLE patients, and age-, race- and gender-matched healthy individuals were enrolled, and clinical and
laboratory parameters recorded. Peripheral blood T cells were isolated by negative selection and SRSF1 protein levels
assessed by western blot. SLE patients were divided into lymphopenic (<1000/μL) and non-lymphopenic groups, and
correlations were assessed with relative SRSF1 expression levels, and compared to gender- and age-matched healthy
controls. To generate T cell-specific Srsf1 conditional knockout (Srsf1-cko) mice, Srsf1-flox mice were crossed with
d.Lck.Cre transgenic mice. Mice were euthanized at 10-20 weeks of age or aged to >1 year, and lymphoid tissues (spleen
and lymph nodes) were analyzed. Immune cell phenotype was assessed by flow cytometry. Apoptosis was assessed in
splenocytes ex vivo or after induction by anti-CD95 (Fas) crosslinking, by flow cytometry staining for 7AAD and Annexin
V.
Results: SLE patients with lymphopenia presented significantly lower expression levels of SRSF1 (0.65 vs. 1.05,
p=0.0074), whereas there was no correlation of SRSF1 with hemoglobin, platelet counts, or serum complement levels. In
parallel, peripheral T cell lymphopenia was observed in Srsf1-cko mice. Lymphopenia was more evident in younger mice,
and was more profound in the CD8 than CD4 T cells. Crosslinking with anti-CD95 (Fas) antibody led to increased apoptosis
in T cells from Srsf1-cko mice. The expression levels of anti-apoptotic gene Bcl-xL were decreased in spleen cells from the
Srsf1-cko mice both ex vivo and after anti-CD95 (Fas) crosslinking. These results indicate that a deficiency of SRSF1
induces apoptosis in T cells through decreased expression of Bcl-xL.
Conclusion: SRSF1 controls the expression of the anti-apoptotic gene Bcl-xL and is an important regulator of T lymphocyte
homeostasis in vivo and its reduced expression levels associate with lymphopenia in SLE patients. Therefore, deficiency of
SRSF1 may represent a molecular defect that contributes to the pathophysiology of systemic autoimmune disease.
Disclosure: T. Katsuyama, None; M. W. Mosho, None; A. R. Gillooly, None; G. C. Tsokos, GSK, 5; V. R. Moulton,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/serine-arginine-rich-splicing-factor-1-

srsf1-is-a-novel-regulator-of-t-lymphocyte-homeostasis-in-vivo-and-its-deficiency-associates-with-lymphopenia-in-sle-
patients
Persistence of Pathogenic CD4 Memory T Cells Revealed through Cytometry

Time of Flight in Juvenile Idiopathic Arthritic Patients with Disease
Resurgence upon Withdrawal of Anti-TNFA Biologics
Jing Yao Leong1, Joo Guan Yeo2, Phyllis Chen3, Liyun Lai4, Fauziah Ally5, Loshinidevi D/O Thana Bathi3, Justin Hung
Tiong Tan2, Thaschawee Arkachaisri2, Femke van Wijk6, Salvatore Albani4, Daniel J Lovell7 and Gerdien Mijnheer8,
1SingHealth Translational Immunology and Inflammation Centre, Singapore Health Services Pte Ltd, Singapore, Singapore,
2Rheumatology and Immunology Service, KK Women's and Children's Hospital, Singapore, Singapore, 3Singhealth
Translational Immunology and Inflammation Centre (STIIC), Duke-NUS Medical School, Singapore, Singapore,
4SingHealth Translational Immunology and Inflammation Centre (STIIC), Duke-NUS Medical School, Singapore,
Singapore, 5STIIC, SingHealth Translational Immunology and Inflammation Centre, Singapore, Singapore, 6University
Medical Center Utrecht, Utrecht, Netherlands, 7Rheumatology, PRCSG - Cincinnati Children's Hospital Medical Center,
Cinncinnati, OH, 81Laboratory of Translational Immunology, Department of Paediatric Immunology, , The Netherlands,
University Medical Centre Utrecht, Wilhelmina Children’s Hospital, Utrecht, Netherlands
SESSION INFORMATION
Background/Purpose: Treatment of polyarticular JIA with anti-TNFA biologics has experienced significant success, with
up to 80% of patients demonstrating clinically meaningful efficacy. Yet concerns regarding medium/long term toxicities and
costs, have driven the clinical need to locate predictors for successful drug discontinuation. Compelling evidence indicate
that T cells play a paramount role in disease progression. Identification of these pathogenic subsets within the T cell
immunome will likely help stratify patients in terms of clinical fate. JIA patients previously treated with anti-TNFA were
recruited through the Understanding TNFA trial and segregated into flare, active and inactive arms after drug
discontinuation. Utilising a high dimensional platform, CyToF, that is capable of phenotyping up to 41 markers at single cell
resolution, we aim to identify the pathogenic subsets responsible for clinical relapse and signatures capable of distinguishing
therapeutic outcomes.
Methods: Patients treated with anti-TNF-alpha were recruited into the study (Improved Understanding of the Biology and
Use of TNF inhibition in Children with JIA Trial) with clinically inactive disease on treatment (Wallace criteria) and
initiated with therapy discontinuation. The patients were followed and evaluated as flare, inactive and active based on 6 JIA
core set parameters; number of joints with active arthritis and/or loss of motion, MD global assessment of current disease
activity, patient/parent global assessment of overall disease severity in prior week, a validated measure of physical function
and ESR.
Results: PBMCs from 47 JIA patients (Flare= 18, Active= 11, Inactive= 18) and 10 healthy controls were stained and
interrogated with CyToF. Patients destined to flare (vs inactive/healthy) prior to therapy withdrawal, displayed significant
dysregulation in the CD4 Memory compartment (p< 0.05), enriched particularly in (a) CD4 CD45RA- TNFA+ , (b) CD4
CD45RA- CXCR5+, and were skewed towards (c) CD152- / PD1-. When contrasting against healthy controls, patients
destined to flare additionally upregulated CD4 CD45RA- TNFA+ IL-6+, possibly a sub-clinical disease subset. Intriguingly
we noted a migratory subset, CD4 CD45RA- CXCR3+ CCR6+ that was present in patients destined to develop active disease
(vs inactive/healthy). Upon flaring, the sub-clinical subset CD4 CD45RA- TNFA+ IL-6+ surfaces and CD4 memory subsets
are now upregulating expression of CD152/PD1 (vs inactive) in response to ongoing inflammation, but when compared to
healthy controls are still inadequate. Parallel pathogenic subsets were also detected in the synovial microenvironment,
reflecting targeting towards the joints.
Conclusion: For some patients (Flare), anti-TNFA therapy is merely suppressing disease activity and not curative. The
persistence of CD4 memory cells are likely to play a pivotal role in disease relapse, that may be partially explained by a
weaker control through immune checkpoints (CD152/PD1). These results suggest that clinical fate is immunologically
predetermined and patients who will develop different clinical fates can be identified from prior biologic sampling.
Disclosure: J. Y. Leong, None; J. G. Yeo, None; P. Chen, None; L. Lai, None; F. Ally, None; L. D. T. Bathi, None; J. H.
T. Tan, None; T. Arkachaisri, None; F. van Wijk, None; S. Albani, None; D. J. Lovell, None; G. Mijnheer, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/persistence-of-pathogenic-cd4-memory-

t-cells-revealed-through-cytometry-time-of-flight-in-juvenile-idiopathic-arthritic-patients-with-disease-resurgence-upon-
withdrawal-of-anti-tnfa-biologics
Microrna-21 Is a Critical Regulator of Autoimmunity through Promoting

Effector and Metabolic Function of Pathogenic TH17 Cells
Xiang Yu1 and Nan Shen1,2,3, 1Shanghai Institute of Rheumatology, Renji Hospital, School of Medicine, and Shanghai Jiao
Tong University, Shanghai, China, 2Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and
Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences,
Shanghai, China, 3Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center,
Cincinnati, OH
SESSION INFORMATION
Background/Purpose:
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease that causes mortality and morbidity worldwide.
Recent studies suggest proinflammatory TH17 cells are key pathogenic factors that contribute to lupus nephritis. Our group
previously demonstrate that microRNA-21 was highly upregulated in effector CD4+ T cells from both lupus patients and
lupus-prone mice. However, the role of microRNA-21 in pathogenic TH17 cells and TH17 cell-mediated autoimmune
diseases is still unclear. In this study, we systemically dissect the role of microRNA-21 in the differentiation and effector
function of pathogenic TH17 cells and they-mediated autoimmune diseases.
Methods:
MicroRNA-21 knockout and conditional knockout mice (CD11c-cre, Lyz2-cre, and CD4-cre) were generated for studying
the role of microRNA-21 in the differentiation and effector function of TH17 cells. Experimental autoimmune
encephalomyelitis (EAE) was induced to study the role of microRNA-21 in pathogenic TH17 cell-mediated autoimmune
diseases. RNA-seq and DAVID bioinformatic analysis were conducted to find key microRNA-21 regulated pathway and
molecular targets in pathogenic TH17 cells. Metabolomics study and metabolic assays were done to study the glycolytic
activity of microRNA-21-deficent pathogenic TH17 cells.
Results:
In this study, we demonstrate that microRNA-21 induced by IL-6-STAT3 signaling targets the E3 ubiquitin ligase Peli1-c-
Rel axis to promote effector and metabolic function of pathogenic TH17 cells. We demonstrate that microRNA-21 is not
required for the development of intestinal homeostatic TH17 cells, but is essential for the maintenance of pathogenic TH17
cells in vivo. MicroRNA-21-deficient TH17 cells express less pathogenic TH17 signature genes and show less glycolytic
activity. Many of the genes involved in glycolytic and related metabolic pathways are significantly downregulated in
microRNA-21-deficient pathogenic TH17 cells, which include key transporters for glucose intake, Slc2a1/3 (Glut1/3), and
rate-limiting enzymes, Hk1/2, Pfkl, Pgm2, Ldha and Pdk1. Interestingly, we find that non-pathogenic and pathogenic TH17
cells have greatly distinct metabolic states, with pathogenic TH17 cells highly glycolytic. We further show that conditional
deletion of microRNA-21 in CD4+ T cells protects mice from EAE while loss of microRNA-21 expression by dendritic cells
and myeloid cells do not.
Conclusion:
To our knowledge, our study identifies the first evidence that by targeting the E3 ubiquitin ligase Peli1 microRNA-21
promotes the effector and metabolic function of pathogenic TH17 cells. Furthermore, the selective dependence of pathogenic
TH17 cells on microRNA-21-mediated metabolic reprogramming has provided novel targets for therapeutic intervention of
autoimmune and inflammatory diseases elicited by pathogenic TH17 cells.
Disclosure: X. Yu, None; N. Shen, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/microrna-21-is-a-critical-regulator-of-

autoimmunity-through-promoting-effector-and-metabolic-function-of-pathogenic-th17-cells
In Vitro Effects of CR6086, a Potent ProstaglandinE2 Subtype 4

Receptor Antagonist, on Bone Erosive Pathways
Tiziana Piepoli1, Mario Montagna1, Daniele Maggioni1, Silvia Zerbi1, Laura Mennuni1, Marco Lanza1, Gianfranco
Caselli1 and Lucio C. Rovati2, 1Rottapharm Biotech, Monza, Italy, 2Clinical Research Department, Rottapharm Biotech,
Monza, Italy
SESSION INFORMATION
Session Date: Monday, November 6, 2017
Session Title: Cytokines, Mediators, Cell-Cell Adhesion, Cell Trafficking and Angiogenesis Poster II: Mesenchymal Cells
Do React - But How?
Session Type: ACR Poster Session B
Background/Purpose: CR6086 is a selective EP4 receptor antagonist immunomodulator in clinical development for
rheumatoid arthritis (RA). In animal models of RA, it demonstrated a superior efficacy vs. conventional, biologic, or
targeted synthetic DMARDs in both early and late disease paradigms. In vitro on human immunocompetent cells, we
previously showed that CR6086 counteracts the immunological unbalance characteristic of RA. This partly explains its
efficacy in vivo, but does not completely account for its superior efficacy vs. DMARDs. Bone erosion contributes even to
very early phases of RA and EP4 receptors have a key role in bone resorption. Acting on this receptor, PGE2 stimulates
different cell types (including macrophages, chondrocytes, and osteoblasts) to release mediators causing bone erosion.
Among them, IL-6, RANK ligand (RANKL), the major inducer of osteoclastogenesis, and VEGF that has angiogenic, pro-
inflammatory and bone destructive roles in RA. Aim of this study was to assess the effects of CR6086 on the expression and
release of these mediators by human macrophagic cells, chondrocytes and osteoblasts.
Methods: Human THP-1 cells were differentiated to macrophages with PMA. Chondrocytes and osteoblasts were purified
from material obtained from patients undergoing knee replacement. Gene expression and release of IL-6, RANKL with its
endogenous inhibitor osteoprotegerin (OPG), and VEGF were analysed by Real Time PCR and ELISA assay.
Results: CR6086 dose-dependently inhibited gene expression of IL-6, RANKL and VEGF in human macrophages and/or
chondrocytes. Conversely, it had no effect on gene expression of OPG, maintaining the balance RANKL/OPG in favor of a
reduction of bone erosion. In particular, in macrophages stimulated with LPS 10ng/ml + PGE2 10nM, CR6086 dose
dependently inhibited gene expression of VEGF (fig. 1), reduced IL-6 gene expression (up to 44%) and IL-6 release (up to
53%).
In chondrocytes stimulated with PGE2 or IL-1β + PGE2, CR6086 dose-dependently suppressed RANKL and IL-6 gene
expression (Table 1). Similar results were obtained in osteoblasts.
Conclusion: The new potent EP4 receptor antagonist immunomodulator CR6086 directly affects bone resorption by
inhibiting the expression of different mediators that induce bone erosions in RA (RANKL, IL-6 and VEGF). These results
support the in vivo findings and confirm that CR6086 may potentially act as a novel DMARD. CR6086 is in Phase II
clinical development in DMARD-naïve early RA patients.
Disclosure: T. Piepoli, Rottapharm Biotech, 3; M. Montagna, Rottapharm Biotech, 3; D. Maggioni, Rottapharm Biotech,
3; S. Zerbi, Rettapharm Biotech, 3; L. Mennuni, Rottapharm Biotech, 3; M. Lanza, Rottapharm Biotech, 3; G. Caselli,
Rottapharm Biotech, 3; L. C. Rovati, Rottapharm Biotech, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/in-vitro-effects-of-cr6086-a-potent-

prostaglandine2-subtype-4-receptor-antagonist-on-bone-erosive-pathways
Inhibition of Fucosylation in Endothelial Cells Reduces Rheumatoid Arthritis

Angiogenesis
Takeo Isozaki, Airi Nishimi, Shinichiro Nishimi, Sho Ishii, Takahiro Tokunaga, Hidekazu Furuya, Kuninobu Wakabayashi
and Tsuyoshi Kasama, Div of Rheumatology, Showa University School of Med, Shinagawa-ku Tokyo, Japan
SESSION INFORMATION
Do React - But How?
Background/Purpose: Glycosylation has been reported to associate with tumor invasion and metastasis. Fucosylation is
involved the biological functions of adhesion molecules and growth factor receptors. In regards to arthritis, we have
previously reported that fucosylated proteins were expressed on rheumatoid arthritis (RA) synovial tissues. Here, we
examined the expression of fucosylated proteins in RA and mediates angiogenesis.
Methods: Total glycans were determined in serum from normal (NL) subjects and RA patients using mass spectrometry. To
determine whether fcosylated proteins involved with RA inflammation, the correlation with disease activity score (DAS) 28
(ESR) was measured. 2-deoxy-D-galactose (2-dGal) is an analog of hexose that inhibits fucosylation. In order to confirm the
role of fucosylation in RA angiogenesis, we did Matrigel assays in vitro. To block the expression of fcosylated proteins,
human umbilical vein endothelial cells (HUVECs) were treated with 2-dGal (15 mM) for 5 days. After treatment with 2-
dGal, HUVECs were plated on Matrigel and were incubated with phosphate buffered saline (PBS) or RA synovial fluids.
Finally, expression of proangiogenic cytokines such as fractalkine/CX3CL1, CXCL16, interleukin (IL)-8/CXCL8, monocyte
chemotactic protein 1 (MCP-1)/CCL2, epithelial neutrophil-activating protein 78 (ENA-78)/CXCL5 and vascular
endothelial growth factor (VEGF) in 2-dGal treated HUVEC conditioned medium were measured by ELISA.
Results: Total glycans in RA serum were significantly higher than in NL serum [mean ± SEM; 477 ± 24 pmol/μl (n=10) and
339 ± 14 pmol/μl (n=10), p<0.05, respectively]. In addition, total glycans in RA serum were significantly decreased with
tocilizumab treatment at 24 weeks. Total glycans in RA serum were also correlated with DAS28 (ESR). Percent of
fucosylated proteins in total glycans were decreased with TCZ treatment at 24 weeks. 2-d Gal treated HUVEC tube formed
towards RA synovial fluids (n=6 patients) were decreased compared with nontreated HUVEC tube formed (number of tube
formed; 7 ± 1 and 25 ± 2, p<0.05, respectively). Fractalkine/CX3CL1, CXCL16, or IL-8/CXCL8 in 2-d Gal treated HUVEC
conditioned medium were decreased compared with in non-treated HUVEC conditioned medium but not MCP-1/CCL2,
ENA-78, or VEGF.
Conclusion: These data indicate that glycoproteins are involved with RA, and play a role in angiogenesis in RA and suggest
that targeting glycosylation especially fucosylation may provide a method by which to decrease inflammation and
potentially treat other inflammatory diseases.
Disclosure: T. Isozaki, None; A. Nishimi, None; S. Nishimi, None; S. Ishii, None; T. Tokunaga, None; H. Furuya, None;
K. Wakabayashi, None; T. Kasama, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/inhibition-of-fucosylation-in-endothelial-

cells-reduces-rheumatoid-arthritis-angiogenesis
A Disintegrin and Metalloprotease 15 Is Expressed on Rheumatoid Arthritis

Synovial Tissue Endothelial Cells and Mediates Angiogenesis
Shinichiro Nishimi, Takeo Isozaki, Airi Nishimi, Sho Ishii, Takahiro Tokunaga, Hidekazu Furuya, Kuninobu Wakabayashi
SESSION INFORMATION
Do React - But How?
Background/Purpose: A disintegrin and metalloproteases (ADAMs) are reported that membrane-anchored glycoproteins
composed of multiple distinct protein modules. ADAM-15 is one of them and is reported in several malignancies such as
breast cancer and prostate cancer. However, the role of ADAM-15 in autoimmune diseases is unclear. Here, we have shown
the role of ADAM-15 in rheumatoid arthritis (RA) angiogenesis.
Methods: RA and osteoarthritis (OA) synovial fluids (SFs) were obtained from patients. RA and normal (NL) serum were
also obtained. ADAM-15 expression was measured in serum and SFs using enzyme-linked immuno sorbent assay (ELISA).
To clarify the differences of ADAM-15 in RA treatment, the level of ADAM-15 at pre, 12, 24 and 54 weeks with
tocilizumab treatment was measured. To determine ADAM-15 expression on RA synovial tissues, immunohistochemistry
was performed. In order to examine the role of ADAM-15 in RA angiogenesis, we used human umbilical vein endothelial
cells (HUVECs). To examine whether ADAM-15 was expressed on HUVECs, immunohistochemistry was also performed.
To block the expression of ADAM-15, HUVECs were transfected with small interfering (si) RNA against ADAM-15. In
order to confirm the role of angiogenesis, we did Matrigel assays in vitro. Finally, proangiogenic cytokines in ADAM-15
siRNA transfected HUVEC conditioned medium were measured.
Results: ADAM-15 in RA serum was significantly higher compared with NL (500 ± 21 pg/ml and 390 ± 29 pg/ml,
respectively, p<0.05). The levels of ADAM-15 in RA SFs were also higher compared with OA SFs (619 ± 53 pg/ml and 328
± 39 pg/ml, respectively, p<0.05). After treatment with tocilizumab, ADAM-15 in serum was significantly decreased
between pre and 24 weeks (500 ± 21 pg/ml and 432 ± 21 pg/ml, respectively, p<0.05), pre and 54weeks (500 ± 21 pg/ml and
434 ± 22 pg/ml, respectively, p<0.05). We found that ADAM-15 was expressed on RA synovial tissue ECs and HUVECs.
ADAM-15 siRNA treated HUVECs had decreased EC line and tube formed in Matrigel in response to RA SFs compared
with non-treated HUVECs (number of EC lines 14 ± 2 and 7 ± 1, respectively, p<0.05) (number of EC tube formed 4 ± 1
and 1 ± 0, respectively, p<0.05). Epithelial neutrophil-activating protein 78 (ENA-78)/CXCL5 and intercellular adhesion
molecule (ICAM) -1 in tumor necrosis factor (TNF) -α stimulated ADAM-15 siRNA transfected HUVEC conditioned
medium were decreased compared with in TNF-α stimulated control siRNA transfected HUVEC conditioned medium.
Conclusion: These data show that ADAM-15 is expressed on RA synovial tissue ECs and may play a role in RA
angiogenesis. ADAM-15 may be a potential target in inflammatory disease such as RA.
Disclosure: S. Nishimi, None; T. Isozaki, None; A. Nishimi, None; S. Ishii, None; T. Tokunaga, None; H. Furuya, None;
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-disintegrin-and-metalloprotease-15-is-

expressed-on-rheumatoid-arthritis-synovial-tissue-endothelial-cells-and-mediates-angiogenesis
Tumor Necrosis Factor-α Induces Production of Eotaxin-1/CCL11 from

Fibroblast-like Synoviocyte in Rheumatoid Arthritis
Kuninobu Wakabayashi, Takeo Isozaki, Airi Nishimi, Shinichiro Nishimi, Sho Ishii, Takahiro Tokunaga, Hidekazu Furuya
SESSION INFORMATION
Do React - But How?
Background/Purpose: Chemokine C-C motif ligand 11 (CCL11) also known as eotaxin-1 is a member of the CC
chemokine family, which acts as a major chemoattractant of eosinophils and a stimulator of basophils. Eotaxin-1/CCL11 is
produced by lymphocytes, eosinophils and monocytes/macrophages and interacts with C-C chemokine receptor 3 (CCR3).
CCR3 is associated with numerous inflammatory conditions and a recent study has also suggested expression of CCR3 on
fibroblast-like synoviocyte (FLS) in rheumatoid arthritis (RA). In this study, we investigate the expression and the role of
eotaxin-1/CCL11 and CCR3 in RA.
Methods: The levels of eotaxin-1/CCL11 were determined in serum from healthy control (HC) and the patients with RA
using enzyme-linked immunosorbent assay (ELISA). We also measured the levels of eotaxin-1/CCL11 and tumor necrosis
factor α (TNF-α) in synovial fluids (SFs) from the patients with RA and osteoarthritis (OA) using ELISA. To investigate the
expression of eotaxin-1/CCL11 on RA FLS, cells were left unstimulated or were stimulated for 12-, 24- and 48-hours with
50 ng/mL of TNF-α. After stimulation, the protein expression levels of eotaxin-1/CCL11 in TNF-α treated RA FLS
conditioned medium were measured by ELISA and the messenger RNA (mRNA) expression of eotaxin-1/CCL11 and CCR3
in RA FLS were measured by quantitative polymerase chain reaction (qPCR) analysis. The expression of eotaxin-1/CCL11
on RA FLS was demonstrated by immunohistochemistry.
Results: The levels of eotaxin-1/CCL11 in the serum from RA were higher than those in the serum from HC [mean ± SEM;
76 ± 6 pg/mL (n=48) and 52 ± 9 pg/mL (n=31), p<0.05, respectively]. The levels of eotaxin-1/CCL11 in SFs from the
patients with RA were higher than those in SFs from the patients with OA [mean ± SEM; 61 ± 24 pg/mL (n=43) and 9 ± 2
pg/mL (n=20), p<0.05, respectively] and were positively correlated with the levels of TNF-α (r=0.35, p<0.05). The
expression of eotaxin-1/CCL11 mRNA and the secretion of eotaxin-1/CCL11 in RA FLS were time-dependently increased
by TNF-α stimulation following 12-, 24- and 48-hours (p<0.05). The expression of CCR3 mRNA was also induced time-
dependently by TNF-α stimulation (p<0.05). Furthermore, it was observed that the eotaxin-1/CCL11 mRNA expression was
positively correlated with the CCR3 mRNA expression (r=0.89, p <0.01). In addition, we confirmed that the expression of
eotaxin-1/CCL11 on RA FLS was increased with TNF-α stimulation using immunohistochemistry.
Conclusion: These data indicate that TNF-α induced production of eotaxin-1/CCL11 from RA FLS, suggesting that eotaxin-
1/CCL11 and CCR3 may play an important role of inflammation in RA.
Disclosure: K. Wakabayashi, None; T. Isozaki, None; A. Nishimi, None; S. Nishimi, None; S. Ishii, None; T. Tokunaga,
None; H. Furuya, None; T. Kasama, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/tumor-necrosis-factor-%ce%b1-induces-

production-of-eotaxin-1ccl11-from-fibroblast-like-synoviocyte-in-rheumatoid-arthritis
A Disintegrin and Metalloprotease -17 Is Overexpressed on Rheumatoid

Arthritis Osteoblasts and Is Regulated with TNF-α Stimulation
Hidekazu Furuya, Takeo Isozaki, Shinichiro Nishimi, Airi Nishimi, Takahiro Tokunaga, Kuninobu Wakabayashi and
Tsuyoshi Kasama, Div of Rheumatology, Showa University School of Med, Shinagawa-ku Tokyo, Japan
SESSION INFORMATION
Do React - But How?
Background/Purpose: A disintegrin and metalloprotease family proteins (ADAMs) have been reported to be involved in a
number of inflammatory conditions. We have previously reported a disintegrin and metalloprotease- 17 (ADAM-17) is
expressed in rheumatoid arthritis (RA) synovial fluids and synovial tissues, and is increased compared to osteoarthritis (OA)
synovial fluids. Cells involved in bone formation express a variety of cytokines and osteoblasts appear to be major
regulators of bone remodeling in RA. The association between ADAM-17 expression and osteoblasts is unclear. Here, we
examine the expression of ADAM-17 in RA osteoblasts.
Methods: RA human osteoblasts (HOB) isolated from femora of RA patients were incubated. RA-HOB were stimulated
with 25ng/ml tumor necrosis factor (TNF)-α at 4 hours, and messanger RNA (mRNA) was collected. ADAM-17 mRNA
expression was examined using quantitative polymerase chain reaction (qPCR). To examine the expression of ADAM-17 in
TNF-α stimulated RA-HOB conditioned medium, RA-HOB were stimulated with 0.25 ng/ml, 2.5 ng/ml and 25 ng/ml TNF-
α at 24 hours and measured using enzyme linked immunosorbent assay (ELISA). To determine ADAM-17 expression in
RA-HOB lysate, western brotting (WB) was also performed. Finally, to confirm the presence of ADAM-17 on RA
osteoblasts, immunostaining was performed.
Results: ADAM-17 was expressed in TNF-α stimulated RA-HOBconditioned medium which was significantly higher
compared to non-stimulated (NS) RA-HOB conditioned medium (mean ± SEM; 171 ± 4 pg/ml and 310 ± 21 pg/ml ,
respectively , p<0.05). Furthermore TNF-α was induced dose-dependent secretion of ADAM-17 levels from RA-HOB
(mean±SEM; NS: 171 ± 4 pg/ml , TNF-α 0.25 ng/ml: 255 ± 15 pg/ml, TNF-α 2.5ng/ml: 234 ± 7 pg/ml, TNF-α 25 ng/ml:
310 ± 21 pg/ml, p<0.05). We found that ADAM-17 mRNA in TNF-α stimulated RA-HOB was 70 times elevated compared
with in non-stimulated RA-HOB (p<0.05). Additionally, we also found that ADAM-17 expression on RA-HOB was
inducible by TNF-α by using immunostaining and WB.
Conclusion: We have reported that ADAM-17 is involved in angiogenesis in synovial tissue of RA. In this study, we
showed the expression of ADAM-17 in RA osteoblasts, suggesting the possibility that it plays an important role in bone
destruction in inflammatory desease such as RA.
Disclosure: H. Furuya, None; T. Isozaki, None; S. Nishimi, None; A. Nishimi, None; T. Tokunaga, None; K.
Wakabayashi, None; T. Kasama, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-disintegrin-and-metalloprotease-17-is-
overexpressed-on-rheumatoid-arthritis-osteoblasts-and-is-regulated-with-tnf-%ce%b1-stimulation
ADAM-17 Is Expressed on Rheumatoid Arthritis Synovial Fibroblasts and

Mediates Monocyte Migration and Adhesion
Sho Ishii, Takeo Isozaki, Airi Nishimi, Shinichiro Nishimi, Takahiro Tokunaga, Hidekazu Furuya, Kuninobu Wakabayashi
SESSION INFORMATION
Do React - But How?
Background/Purpose: A disintegrin and metalloproteinase 17 (ADAM-17), also known as tumor necrosis factor-α
converting enzyme (TACE), have been reported to be involved in a number of inflammatory conditions. We examined the
expression of ADAM-17 in rheumatoid arthritis (RA) biological fluids and the role it plays in monocyte migration and
adhesion to RA synovial fibroblasts.
Methods: ADAM-17 expression was measured by enzyme-linked immunosorbent assay in serum and synovial fluids from
normal (NL) subjects, osteoarthritis (OA) patients and RA patients. We also analyzed relativity with ADAM-17 and disease
activity score 28 (DAS28) in RA. To determine expression of ADAM-17 on RA synovial tissues (STs) and RA fibroblast
like synoviocite (FLS), immunofluorescence was performed. To determine the role of ADAM-17 in RA, RA FLSs or THP-
1(human acute monocytic leukemia cell line) were transfected with small interfering RNA (siRNA) against of ADAM-17.
THP-1 adhesion to ADAM-17 siRNA transfected RA FLSs was measured. THP-1 chemotaxis assay was performed towards
RA synovial fluids or monocyte chemotactic protein-1 (MCP-1)/CCL2.
Results: The levels of ADAM-17 in RA serum was significantly higher compared with NL serum [mean ± SE; 2093 ± 539
pg/ml (n=23) and 0 ± 0 pg/ml (n=7), respectively, p<0.05] . ADAM-17 in RA synovial fluids was higher compared with OA
synovial fluids [1644 ± 952 pg/ml (n=10) and 4.6 ± 4.3 pg/ml (n=7), respectively, p<0.05] .The level of ADAM-17 in RA
serum was also correlated with DAS28 (n=58, r=0.64, p<0.05). ADAM-17 was expesssed on RA ST lining cells. On the
other hand, ADAM-17 was not expressed on OA STs. ADAM-17 was also expressed on RA FLS. THP-1 adhesion to
ADAM-17 siRNA transfected RA FLS had decreased compared with that to control siRNA transfected RA FLS [adhesion
index; 0.61 ± 0.10 (n=12) and 0.93 ± 0.05 (n=12), respectively, p<0.05]. We found ADAM-17 siRNA transfected THP-1
cells had decreased migration compared with control siRNA transfected THP-1 cells towards RA synovial fluids [number of
THP-1 migrated 6 ± 2 (n=6) and 33 ± 12 (n=6), respectively, p<0.05]. Furthermore, ADAM-17 siRNA transfected THP-1
cells also had decreased migration compared with control siRNA transfected THP-1 cells towards MCP-1/CCL2 [number of
THP-1 migrated 27 ± 4 (n=3) and 146 ± 18 (n=3), respectively, p<0.05].
Conclusion: These data indicate that ADAM-17 may play a role in RA inflammation by regulating monocyte migration and
adhesion to RA synovial fibroblasts. ADAM-17 may be a potential target in inflammatory disease like RA.
Disclosure: S. Ishii, None; T. Isozaki, None; A. Nishimi, None; S. Nishimi, None; T. Tokunaga, None; H. Furuya, None;
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/adam-17-is-expressed-on-rheumatoid-

arthritis-synovial-fibroblasts-and-mediates-monocyte-migration-and-adhesion
Adalimumab Reduces CXCR4 Expression during Inflammatory Arthritis and

in Fibroblast-like Synoviocytes and Osteoclasts Under Chronic TNF Exposure
Bohdan P. Harvey1, Li Li1, Mark Konrad1, Heather Knight1, Susan Westmoreland2, Melanie Ruzek1 and Zehra
Kaymakcalan1, 1AbbVie Bioresearch Center, Worcester, MA, 2AbbVie Inc, AbbVie Bioresearch Center, Worcester, MA
SESSION INFORMATION
Do React - But How?
Background/Purpose: The CXCL12/CXCR4 chemokine axis has been implicated in the pathogenesis of RA. The
expression of this chemokine and receptor has been shown to be increased in RA synovium, and moreover, CXCR4 levels in
synovium have been correlated with joint destruction in RA patients. Given that high levels of CXCR4 are associated with
RA pathogenesis, we sought to determine whether CXCR4 levels are altered by adalimumab (ADA) both in vivo in RA
patients and in the human TNF transgenic mouse model (huTNF Tg197) of arthritis, as well as in vitro with RA fibroblast-
like synoviocytes (RA-FLS) and human osteoclast precursors (OCP) following TNF exposure. In addition, we investigated
the role of CXCR4 in human osteoclastogenesis (OCgenesis) under chronic TNF exposure.
Methods: Public DNA microarray data of synovial tissue from ADA treated RA patients was analyzed for changes in the
expression level of various chemokines and their cognate receptors. PBMC populations from ADA treated RA patients taken
at baseline, wks. 4 & 12 were assessed by CyTOF for CXCR4. IHC staining was performed on formalin paw sections from
wk. 13 placebo control and ADA treated (1 mg/kg i.p.) huTNF Tg197 mice to evaluate CXCR4 expression in various
pannus-associated cells. To assess the role of TNF and concomitant ADA treatment on human cultures in vitro, CXCR4
RNA expression was evaluated in RA-FLS treated with conditioned media from PBMCs +/-ADA for 6 hrs., and CXCR4
protein on OCP by flow cytometry in response to 72 hr. M-CSF+RANKL+/-TNF+/-ADA. To demonstrate the role of
CXCR4 in OCgenesis, OCP were cultured for 6 d. in M-CSF+RANKL+/-TNF following 30 min. pretreatment with CXCR4
neutralizing antibody. OC maturation and activity were assessed by measuring TRAcP 5b activity and CTX-I release,
respectively.
Results: Preliminary microarray data analysis of RA synovial tissue demonstrated that active RA patients over-expressed
CXCR4 while CXCR4 was significantly normalized (two-fold reduction) in the responders to Ada therapy. In addition,
CyTOF analysis of PBMC from ADA treated RA patients indicated a significant reduction from baseline in CXCR4
expression on B cells and CD4+ T cells by wk. 4. In huTNF Tg197 mice, CXCR4 expression in the inflamed pannus (most
notably in FLS, lymphocytes and OC) was also decreased by ADA therapy. In vitro human cultures of similar cell types
including RA-FLS and OCP were subjected to conditioned media or TNF, respectively, and found to express higher levels of
CXCR4 that was reduced with concomitant ADA treatment. Finally, antibody-mediated blockade of CXCR4 on human OCP
decreased both TNF-enhanced OC maturation and activity.
Conclusion: Our findings demonstrate that ADA therapy reduces CXCR4 expression in vivo both in RA patient PBMCs and
in the pannus of huTNF Tg mice with inflammatory arthritis especially in lymphocytes, FLS and OC. Similar results were
also observed with our in vitro human cultures of equivalent cell types. More importantly, we’ve shown that inhibition of
CXCR4 can reduce TNF-enhanced OCgenesis in vitro, suggesting that CXCR4 may be a contributing factor to TNF-
mediated osteolysis in RA.
Disclosure: B. P. Harvey, AbbVie, Inc., 3,AbbVie, Inc., 1; L. Li, AbbVie, Inc., 3,AbbVie, Inc., 1; M. Konrad, AbbVie,
Inc., 3,AbbVie, Inc., 1; H. Knight, AbbVie, Inc., 3,AbbVie, Inc., 1; S. Westmoreland, AbbVie, Inc., 3,AbbVie, Inc., 1; M.
Ruzek, AbbVie, Inc., 3,AbbVie, Inc., 1; Z. Kaymakcalan, AbbVie, Inc., 3,AbbVie, Inc., 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/adalimumab-reduces-cxcr4-expression-
during-inflammatory-arthritis-and-in-fibroblast-like-synoviocytes-and-osteoclasts-under-chronic-tnf-exposure
Role of Syndecans in Cytokine Mediated Inflammation in Rheumatoid

Arthritis Synovial Fibroblasts
Solomon Agere1, Nahid Akhtar1, David Fox2 and Salahuddin Ahmed1, 1Department of Pharmaceutical Sciences,
Washington State University, College of Pharmacy, Spokane, WA, 2Department of Medicine [Division of Rheumatology],
University of Michigan Medical System, Ann Arbor, MI
SESSION INFORMATION
Do React - But How?
Background/Purpose: Syndecans (SDCs) are type-I transmembrane proteoglycans that prominently interact with heparan
sulfate, extracellular matrix (ECM) components and glycoproteins. The present study was carried out to determine the role
of syndecans in promoting tissue destruction mediated using human rheumatoid arthritis synovial fibroblasts (RASFs) and a
rat adjuvant-induced arthritis (AIA) model of RA
Methods: Human RASFs and healthy (NL) SFs were isolated from de-identified RA and NL synovial tissues, respectively,
under an IRB approved protocol. RASF and NLSF lysates were prepared to study the expression of SDC-1, SDC-2, SDC-3,
and SDC-4 using qRT-PCR and Western immunoblotting. Knockdown of SDCs using siRNA approach was conducted to
study its effect on IL-1β (10 ng/ml) or TNF-α (20 ng/ml) induced signaling pathways and downstream inflammatory
mediators in RASFs. Ankle, heart, spleen and liver homogenates from naïve and AIA rats were analyzed for differences in
the expression levels of SDCs. Serum levels of SDC-2 and SDC-4 were also analyzed in RA patients and in AIA rats.
p<0.05 was considered significant.
Results: Our qRT-PCR results showed that the expression of SDC-2 (~320%) and SDC-4 (~80%) was significantly higher
in RASFs when compared to NLSFs, which was also confirmed in protein levels using Western blotting method. No
significant changes were observed in SDC-1 and SDC-3 expression in RASFs compared to NLSFs. Stimulation of RASFs
with IL-1β or TNF-αinduced SDC-2 and SDC-4, but not SDC-1 or SDC-3, expression compared to the un-stimulated
controls. Knockdown of SDC-2 and SDC-4 significantly inhibited IL-1β-induced matrix metalloproteinase-1 (MMP-1) and
MMP-13 production, which could partly be due to the decrease in ERK and PKCδ activation in RASFs. In addition, we also
observed a statistically significant decrease in IL-1β-induced IL-6 production with the knockdown of SDC-2 or SDC-4.
Evaluation of the tissue homogenates from naïve and early (day 8) and established (day 18) AIA in rats for SDC expression
showed a marked increase in SDC-2 and -4 expression in serum, ankles, liver, and spleen in AIA group at day 8 and at day
18 compared with naïve group. Treatment of methotrexate (MTX) significantly decreased both SDC-2 and -4 expression
compared to the AIA alone group. However, human RA serum samples showed a consistent increase only in SDC-4
expression compared to the serum from healthy donors.
Conclusion: These findings suggest SDC-4 may be a potential therapeutic target in regulating the role of cytokines and
MMPs in mediating tissue destruction in RA.
Disclosure: S. Agere, None; N. Akhtar, None; D. Fox, None; S. Ahmed, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/role-of-syndecans-in-cytokine-mediated-

inflammation-in-rheumatoid-arthritis-synovial-fibroblasts
Artesunate Inhabits Migration and Invasion of Fibroblast-like Synoviocytes

and Matrix Metalloproteinases Expression Via Suppression of PI3K/Akt
Pathway in Rheumatoid Arthritis
Jian-Da Ma1, Jun Jing1, Tao Yan2, Ying-Qian Mo1 and Lie Dai1, 1Department of Rheumatology, Sun Yat-Sen Memorial
Hospital, Sun Yat-Sen University, Guangzhou, China, 2Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou,
China
SESSION INFORMATION
Do React - But How?
Background/Purpose: Fibroblast-like synoviocytes (FLS) play major roles on joint destruction in rheumatoid arthritis (RA)
through migrating and invasing cartilage and bone by secreting proteases such as matrix metalloproteinases (MMPs).Recent
studies show that artesunate, an important artemisinin derivative, may inhibit proinflammatory cytokines secretion of RA-
FLS. We aim to investigate the effect of artesunate on migration and invasion of RA-FLS and itsunderlying mechanism
Methods: FLS isolated from knee synovium of active RA patients were cultured in vitro. The effects of artesunate,
methotrexate (MTX) or hydroxychloroquine (HCQ) on cell viability and anti-proliferation were measured by CCK-8 assay.
Effects on migration and invasion capacity were detected by wound healing and transwell assays. Differential expression of
MMPs were analyzed by Proteome profiler human protease array (R&D Systems) and furtherly verifiedby quantitative real-
time PCR, western blot (WB) and ELISA. The expression of PI3K, PIP2, PIP3, PDK1 and Akt in PI3K/Akt signal pathway
was measured by WB.
Results: The IC50 value of artesunate, MTX and HCQ on RA-FLS were 6891μM, 181.4nM and 5433μM respectively.
Compared with untreated group, IC1-20μM, IC3-40μM, IC5-60μM of artesunate, IC5-10nM of MTX and IC5-20μM of HCQ
showed no significant change in proliferation even after 72h. Wound healing and migration assays for 12h and invasion
assay for 24h showed artesunate inhabits the migration and invasion of RA-FLS in a dose-dependent manner. MTX also has
inhibition effect on the migration and invasion of RA-FLS, but HCQ not (Fig. A). Proteome profiler human protease array of
culture supernatant showed that 60μM artesunate markedly inhibited MMP-2/9 expression (Fig. B). Further verification
showed that RA-FLS pretreated with 60μM artesunate attenuated MMP-2/9 mRNA and protein expression, and ELISA
results showed 60μM artesunate decreased MMP-2 and MMP-9 concentration of 5.82±0.45 and 11.74±1.30ng/mL
respectively (Fig. C). Further pre-treatment with recombination human MMP-2 (6 ng/ml) or MMP-9 (12 ng/ml) for 24h
could reverse inhibitory effect of 60μM artesunate on invasion, but not migration (Fig. D). Quantitative real-time PCR and
WB analysis showed that PDK1 expression and Akt activity (phophso-Akt/Akt) in 60μM artesunate treatment group was
significantly lower than that in untreated group which indicated that artesunate suppressed generation of PDK1-induced
activation of Akt (Fig. E).
Conclusion: Artesunate could inhibit migration and invasion of RA-FLS and MMP-2/9 expression through suppressing
PDK1-induced activation of Akt.
Disclosure: J. D. Ma, National Natural Science Foundation of China (no. 81471597 and 81671612), 2,Guangdong Natural
Science Foundation (no.2014A030313074), 2,Scientific Program of Traditional Chinese Medicine Bureau of Guangdong
Province (no. 20161058), 2,Medical Science Research Grant of Guangdong Province, China (no. A2017109), 2; J. Jing,
National Natural Science Foundation of China (no. 81471597 and 81671612), 2,Guangdong Natural Science Foundation
(no.2014A030313074), 2,Scientific Program of Traditional Chinese Medicine Bureau of Guangdong Province (no.
20161058), 2; T. Yan, National Natural Science Foundation of China (no. 81471597 and 81671612), 2,Guangdong Natural
Science Foundation (no.2014A030313074), 2,Scientific Program of Traditional Chinese Medicine Bureau of Guangdong
Province (no. 20161058), 2; Y. Q. Mo, National Natural Science Foundation of China (no. 81471597 and 81671612),
2,Guangdong Natural Science Foundation (no.2014A030313074), 2,Scientific Program of Traditional Chinese Medicine
Bureau of Guangdong Province (no. 20161058), 2; L. Dai, National Natural Science Foundation of China (no. 81471597
and 81671612), 2,Guangdong Natural Science Foundation (no.2014A030313074), 2,Scientific Program of Traditional
Chinese Medicine Bureau of Guangdong Province (no. 20161058), 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/artesunate-inhabits-migration-and-

invasion-of-fibroblast-like-synoviocytes-and-matrix-metalloproteinases-expression-via-suppression-of-pi3kakt-pathway-in-
Atherogenic Potency of Plasma from Persons with Autoimmune Rheumatic

Disorders: Comparative Effects on Cholesterol Flux in Human Macrophages
Andrew Maidhof1, Allison B. Reiss1,2, Lora J. Kasselman2, Elise Belilos1, Kristina Belostocki1, Gary Rosenblum1, Lois
Bonnetti1, Melissa Fazzari2, Joshua DeLeon1 and Steven E. Carsons1,2, 1NYU Winthrop University Hospital, Department of
Medicine, Mineola, NY, 2NYU Winthrop University Hospital, Winthrop Research Institute, Mineola, NY
SESSION INFORMATION
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Background/Purpose:
Although the risk of atherosclerotic cardiovascular disease and abnormalities in cholesterol transport have been
demonstrated in rheumatoid arthritis (RA), lupus (SLE) and, to a lesser extent, in psoriatic arthritis (PsA), the degree of
cholesterol transport abnormalities is not known. This study examines the effect of RA, PsA, and SLE versus healthy control
(HC) plasma on cholesterol transport genes. Particular genes affect atherosclerotic processes by modulating cholesterol
influx, catabolism, and efflux. Dysfunctional cholesterol handling underlies mechanisms that promote atherosclerosis.
Methods:
THP-1 human macrophages (106/ml) were incubated (18h-24h, RPMI1640 media) in the presence of 10% plasma from
patients diagnosed as follows: 8 RA females; 12 SLE (9 female, 3 male), 22 PsA (7 female, 15 male); 21 HC (21 female).
Cholesterol transport mRNA was quantified by real-time RT-PCR using specific primers for each gene. Statistical analysis
was performed using Graphpad Prism. All data were analyzed by one-way analysis of variance, and pairwise multiple
comparisons were made between control and treatment conditions using Bonferroni correction. RA patients fulfilled the
2010 revised criteria of the American College of Rheumatology for classification of RA. SLE patients fulfilled the Systemic
Lupus International Collaborating Clinics Classification Criteria of 2012. PsA patients fulfilled the Classification Criteria for
Psoriatic Arthritis of 2006. Patients with previous documentation of a diagnosis of a connective tissue disorder other than
RA, PsA or SLE were excluded.
Results:
SLE: 10% SLE plasma increased cholesterol influx gene expression. CD36 mRNA increased by 220±56% (P<0.001), LOX-
1 by 202±22% (P<0.001), and SR-A1 increased to 122.0±45.0% versus HC plasma (set at 100%). Efflux genes were
suppressed. ABCA1 mRNA decreased to 77.0±47.0%, ABCG1 to 89.0±33.0%, and 27-hydroxylase (27-OH) mRNA to
20.0±48.0% versus HC.
RA: 10% RA plasma increased CD36 by 157.4±111.0%, SR-A1 to 124±19.0%, and LOX-1 to 102.0±53.0% versus HC.
Mean ABCA1 mRNA decreased to 65.7±28.4 (P<0.001), ABCG1 to 65.0±47.0% (P<0.05), and 27-OH to 32.5±14.2%
(P<0.01) in RA treated plasma versus HC plasma.
PsA: 10 % PsA plasma didn’t alter message level of influx nor efflux genes. However, levels of SR-A1 decreased to
80.0±30.0%.
Conclusion:
Consistent with clinic evidence, cholesterol transport abnormalities are most deranged in SLE. RA and SLE plasma induced
a consistent pro-atherogenic profile of cholesterol flux genes. PsA plasma was less atherogenic, reflecting their lesser
disease-related cardiovascular risk. These results identify cholesterol transport genes as a potential new therapeutic target for
atherosclerosis prevention in the setting of autoimmunity.
Disclosure: A. Maidhof, None; A. B. Reiss, None; L. J. Kasselman, None; E. Belilos, None; K. Belostocki, None; G.
Rosenblum, None; L. Bonnetti, None; M. Fazzari, None; J. DeLeon, None; S. E. Carsons, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/atherogenic-potency-of-plasma-from-

persons-with-autoimmune-rheumatic-disorders-comparative-effects-on-cholesterol-flux-in-human-macrophages
Decoy Receptor 3 up-Regulates Cadherin 2 in Rheumatoid Synovial

Fibroblasts
Koji Fukuda1, Yasushi Miura2,3, Shinya Hayashi2, Toshihisa Maeda1,4 and Ryosuke Kuroda1, 1Department of Orthopaedic
Surgery, Kobe University Graduate School of Medicine, Kobe, Japan, 2Orthpaedic Surgery, Kobe University Graduate
School of Medicine, Kobe, Japan, 3Department of Rehabilitation Science, Kobe University Graduate School of Health
Sciences, Kobe, Japan, 4Department of Immunology and Rheumatology, Stanford University, Stanford, CA
SESSION INFORMATION
Do React - But How?
Background/Purpose: Decoy receptor 3 (DcR3) is a secreted decoy tumor necrosis factor receptor and competitively binds
and inhibits the TNF family including Fas-ligand, LIGHT, and TL1A. We previously reported that DcR3 overexpressed in
rheumatoid synovial fibroblasts (RA-FLS) stimulated by TNFα protects the cells from Fas-induced apoptosis [1]. We
recently reported that DcR3 binds to TL1A expressed on RA-FLS resulting in the negative regulation of cell proliferation
induced by inflammatory cytokines [2]. Further, we newly revealed the gene expression profiles in RA-FLS regulated by
DcR3 by using microarray data analysis [3] and the possible involvement of tryptophan hydroxylase 1 down-regulated [4],
interleukin 12B up-regulated by DcR3 [5] and centrosomal protein 70kDa [6] in the pathogenesis of RA. The profiles
indicated that Cadherin 2/type 1/N-cadherin (CDH2) was up-regulated by DcR3 (fold change 1.93) [3]. CDH2 has been
reported to be associated with cell attachment and migration [7], osteoblast differentiation [8], and the proliferation of RA-
FLS [9]. The hemophilic interaction of CDH2 suppresses the proliferation of RA-FLS through increasing the P27Kip1 that
inhibit cell-cycle progression [9]. In this study, we investigated the significance of DcR3 regulation of CDH2 for RA-FLS.
Methods: Before the quantification of relative expression levels of CDH2 mRNA by real-time polymerase chain reaction
(real-time PCR), RA-FLS were stimulated with various concentration of DcR3-Fc or 1,000 ng/ml IgG1 as a control, or left
untreated in serum-free Opti-MEM® for 12 h. Anti-CDH2 antibody was applied to frozen sections of synovial tissues from
patients with RA or OA for overnight. After that, the expression of CDH2 protein was evaluated by immunohistochemical
analysis.
Results: Real-time PCR demonstrated that DcR3-Fc significantly increased the expression of CDH2 mRNA in RA-FLS.
Immunohistochemistry revealed that CDH2 was expressed more in the sublining layer of rheumatoid synovium than OA
synovium.
Conclusion: In the gene expression profiles, we focused on CDH2 as the gene was highly up-regulated and belonged to
major functional clustering categories; protein complex assembly, cell motility, regulation of transcription, cell membrane
and glycosylation. In this study, we showed that the expression of CDH2 mRNA in RA-FLS was induced by DcR3 and that
CDH2 was increased in the sublining layer of rheumatoid synovium. Considering the fact that CDH2 inhibits RA-FLS
proliferation, the induction in CDH2 expression by DcR3 signaling may control the hyperplasia of RA synovium.
References: 1. Hayashi S. et al., Arthritis Rheum. 2007;56:1067-1074,
2. Takahashi M. et al., Int J Mol Med. 2011;28:423-427,
3. Fukuda K. et al., Int J Mol Med. 2013;32:910-916,
4. Maeda T. et al., Mol Med Rep. 2015;12:5191-5196,
5. Fukuda K. et al., Mol Med Rep. 2016;13:3647-3652,
6. Fukuda K. et al., Mod Rheumatol. in press
7. Akitaya T. et al., Dev Dyn. 1992;194:12-20.
8. Marie P, J Cell Physiol 2002;190:297-305.
9. Nonomura Y. et al., J Rheumatol. 2009;36:698-705.
Disclosure: K. Fukuda, None; Y. Miura, None; S. Hayashi, None; T. Maeda, None; R. Kuroda, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/decoy-receptor-3-up-regulates-cadherin-
2-in-rheumatoid-synovial-fibroblasts
In Search of Mechanisms Underlying Fibroblast-like Synoviocyte Cell-to-Cell

Cargo Transfer
Ruth Byrne1, Isabel Olmos Calvo2, Felix Kartnig3, Uwe Hansen4, Denise Beckmann4, Adelheid Korb-Pap4, Bernhard
Brandstätter1, Thomas Karonitsch1, Günter Steiner1, Johannes Holinka5, Peter Ertl6, Thomas Pap4, Josef S. Smolen7 and
Hans Peter Kiener1, 1Rheumatology, Medical University of Vienna, Vienna, Austria, 2Department of Chemical Technologies
and Analytics, Vienna University of Technology, Vienna, Austria, 3CeMM, Research Center for Molecular Medicine of the
Austrian Academy of Sciences, Vienna, Austria, 4Institute of Musculoskeletal Medicine, University Hospital Muenster,
Muenster, Germany, 5Orthopaedics, Medical University of Vienna, Vienna, Austria, 6Vienna University of Technology,
Vienna, Austria, 7Medical University Vienna, Division of Rheumatology, Department of Internal Medicine III, Vienna,
Austria
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Background/Purpose: The synovium is primarily built by fibroblast-like-synoviocytes (FLS). These cells form a complex
tissue network via long-distance connections (nanotubes) and wide intercellular matrix spaces. FLS coordinate and transfer
information between each other to carry out tissue functions that are critical to joint homeostasis. For this, they exchange
cargo, i.e. organelles like mitochondria either via transfer through interconnecting nanotubes or vesicles. Here we search for
the underlying mechanisms of cell-to-cell cargo transfer. As targets, we selected actin and tubulin, both part of the
cytoskeleton of nanotube structures, as well as the clathrin pathway for endocytosis.
Methods: Human FLS were taken from joint synovectomies. Passaged FLS were used to generate micromass cell cultures
using Matrigel (BD®). Within just a few days these cells build a 3D structure that strongly resembles the in-vivo situation of
the synovium. Cells were dyed with Celltracker and Mitotracker dyes (TF®) and challenged with various blocking agents.
Analyses of the 3D confocal and multiphoton imaging data were done with Imaris Bitplane® software.
Results: By extracting the actin skeleton from the cells body, we show the triangular arrangement of actin filaments
connected by the Arp2/3 complex at the basis of nanotubes as well as their linear arrangement in building nanotubes using
electron microscopy. To block actin filament construction via the Arp2/3 complex we used CK666. This not only changed
the architecture of the tissue but also significantly lowered the mitochondrial transfer rate between cells.
While thin nanotubes only consist of actin filaments, thick nanotubes may also contain microtubules. Additionally, kinesins
use microtubules to shuttle cargo through the cytoplasm. To block tubulin synthesis, we used nocodazole. This treatment
changed the structure of FLS micromasses, however, did not significantly lower the mitochondrial transfer rate. Moreover,
we determined the mitochondrial travelling speed through nanotubes at 45,4 μm/h. This contrasts kinesin-mediated shuttling
which amounts to 0,005 μm/h.
Clathrin mediated endocytosis, and thus the transfer of vesicles between cells, can be blocked by sucrose. Intriguingly, this
treatment does not only affect vesicle transfer but also the formation of nanotubes, as it hinders the cell to build curvatures
into its membrane. Sucrose treatment resulted in both a change in tissue architecture and significantly lowered the
mitochondrial transfer rate.
Conclusion: Since the mitochondrial transfer rate was not affected by blocking the synthesis of microtubules and the
traveling speed of mitochondria in our experiments was very different from that of kinesin shuttling, we conclude that
microtubules are not involved in cell-to-cell cargo transfer. However, by blocking actin synthesis as well as clathrin
mediated endocytosis, mitochondrial transfer was significantly lowered. Thus, cell-to-cell cargo transfer is likely an
important feature of synovial tissue function that operates using distinct cellular pathways. Further studies will demonstrate
its significance in the normal as well as the diseased synovium.
Disclosure: R. Byrne, None; I. Olmos Calvo, None; F. Kartnig, None; U. Hansen, None; D. Beckmann, None; A. Korb-
Pap, None; B. Brandstätter, None; T. Karonitsch, None; G. Steiner, None; J. Holinka, None; P. Ertl, None; T. Pap,
Orthogen, 5; J. S. Smolen, AbbVie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, Glaxo, ILTOO,
Janssen, Eli Lilly and Company, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, UCB,
5,AbbVie, Janssen, Eli Lilly and Company, MSD, Pfizer, Roche, 2,AbbVie, Amgen, Astra-Zeneca, Astro, BMS, Celgene,
Celltrion, Chugai, Gilead, Glaxo, ILTOO, Janssen, Eli Lilly and Company, Medimmune, MSD, Novartis-Sandoz, Pfizer,
Roche, Samsung, Sanofi-Aventis, UCB, 8; H. P. Kiener, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/in-search-of-mechanisms-underlying-

fibroblast-like-synoviocyte-cell-to-cell-cargo-transfer
NF-κb-Inducing Kinase Regulates LTβR-Driven NF-κb Signaling and

Inflammatory Activation of Endothelium
Paulina Kucharzewska1, Chrissta Maracle2, Jan Piet van Hamburg2, Kim Jeucken2, Henric Olsson1 and Sander W. Tas3,
1Bioscience, AstraZeneca, Göteborg, Sweden, 22Department of Clinical Immunology & Rheumatology and Laboratory for
Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands, 3Department of
Clinical Immunology & Rheumatology and Laboratory for Experimental Immunology, ARC | Academic Medical
Center/University of Amsterdam, Amsterdam, Netherlands
SESSION INFORMATION
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Background/Purpose: Sites of chronic inflammation, such as rheumatoid arthritis synovial tissue, are characterized by
neovascularization and often contain tertiary lymphoid structures with characteristic features of lymphoid organs such as
endothelial venules (HEV), and sometimes true germinal centers. Ligation of the lymphotoxin-β receptor (LTβR) results in
activation of both canonical and NF-κB-Inducing Kinase (NIK)-dependent non-canonical NF-κB signaling in endothelial
cells (ECs) and plays a crucial role in lymphoid neogenesis. Non-canonical NF-κB signaling in ECs promotes inflammation-
induced angiogenesis and triggers the development of the cuboidal HEV appearance. However, the relative contribution of
the individual pathways to the acquisition of leukocyte traffic-regulating properties by ECs is less well understood.
Goal of the current study is to identify molecular pathways by which LTβR drives inflammatory activation of ECs to
promote interactions with leukocytes.
Methods: Primary human ECs were treated with LTβ or LIGHT to activate LTβR. Induction of downstream signaling
pathways was assessed by western blot and NF-κB transcription factor ELISA. The expression of adhesion molecules,
inflammatory cytokines and chemokines in ECs was measured by RT-qPCR and cytokine antibody arrays. EC interactions
with leukocytes were determined by adhesion assay, and EC barrier integrity was assessed by permeability assay. To repress
canonical NF-κB signaling pathway, a small molecule inhibitor of IKKβ was used, and inactivation of non-canonical NF-κB
signaling was achieved with siRNAs targeting NFκB2. The role of NIK in LTβR signaling was investigated using small
molecule inhibitors of NIK, siRNAs targeting NIK and adenoviral vectors encoding wild type and kinase-deficient NIK.
Results: LTβR triggering in ECs resulted in activation of both canonical and non-canonical NF-κB signaling pathways and
induced the expression of inflammatory cytokines and chemokines (CXCL1, CXCL5, CXCL8, MCP-1, GM-CSF, CCL5).
Consistent with inflammatory activation of ECs, LTβR ligation also induced adhesion of immune cells to activated
endothelium and increased permeability across EC monolayers. IKKβ inhibition completely repressed LTβR-induced
inflammatory activation of ECs, indicating that this process was mediated through canonical NF-κB signaling. Interestingly,
inactivation of NIK with small molecule inhibitors and siRNAs significantly decreased LTβR-induced expression of
inflammatory cytokines and adhesion of immune cells to endothelium, whereas silencing of NFκB2 had no effect. This
suggests that the non-canonical pathway is dispensable for NIK-dependent activation of endothelial cells through the
canonical NF-kB pathway. Further analyses, including silencing of NIK and NIK overexpression, demonstrated a role for
NIK in activation of the canonical NF-kB pathway by amplifying IKK complex activity.
Conclusion: These findings suggest that in addition to its pivotal role in the non-canonical pathway, NIK can serve as an
amplifier of the canonical NF-κB pathway and associated inflammatory responses in ECs mediated by LTβR ligation, which
may play a role in development and maintenance of chronic inflammation.
Disclosure: P. Kucharzewska, AstraZeneca, 3; C. Maracle, None; J. P. van Hamburg, None; K. Jeucken, None; H.
Olsson, AstraZeneca, 3; S. W. Tas, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/nf-%ce%bab-inducing-kinase-regulates-

lt%ce%b2r-driven-nf-%ce%bab-signaling-and-inflammatory-activation-of-endothelium
Mononuclear Phagocytes Mediate Systemic Autoimmune Disease-Related

Valvular Heart Disease Via Inflammatory Cytokine Production and
Recruitment of Tissue-Reparative macrophages
Lee Meier1, Jennifer L. Auger2, Brianna J. Engelson3, Hannah Cowan3, Elise Breed4, Mayra Gonzalez-Torres5, Joshua
Boyer6 and Bryce A. Binstadt7, 1Peadiatrics, University of Minnesota, Minneapols, MN, 2Center for Immunology and
Department of Pediatrics, University of Minnesota, Minneapolis, MN, 3Pediatrics, University of Minnesota, Minneapolis,
MN, 4University of Minnesota Medical School, Minneapolis, MN, 5University of Puerto Rico, Ponce, Puerto Rico,
6University of California, San Diego, San Diego, CA, 7remove this, remove this, remove this, MN
SESSION INFORMATION
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Background/Purpose:
Cardiovascular comorbidity is significant in patients with systemic autoimmune diseases including rheumatoid arthritis and
systemic lupus erythematosus . T cell receptor transgenic K/B.g7 mice develop autoimmune arthritis and concomitant
inflammatory and fibrotic valvular heart disease (VHD) with complete penetrance. This model allows dissection of the
molecular and cellular pathways that drive accelerated cardiovascular disease in the setting of systemic autoimmunity. We
have previously demonstrated that VHD in K/B.g7 mice is orchestrated by discrete mononuclear phagocyte populations with
CD301b+ tissue-reparative macrophages comprising the dominant valve-infiltrating population. We have also demonstrated
that a TNF/IL6-VCAM1-VLA4 axis drives disease. Here we sought to assess the specific contribution of mononuclear
phagocytes (MNPs) in this disease process, using a conditional gene knockout approach.
Methods:
To test the hypothesis that MNPs responding to circulating autoantibodies provide the source of TNF and IL6 during mitral
valve disease (MVD) initiation, we first generated a Cx3cr1-Cre:Sykfl/fl K/B.g7 line to prevent FcγR-mediated MNP
activation. Histological assessment of valve disease severity and flow-cytometric assessment of TNF and IL6 production
from valve-infiltrating and lymphoid MNPs were employed. Secondly, to test the hypothesis that recruitment of circulating
MNPs drives MVD progression through VLA4-VCAM1 interactions, we generated a Cx3cr1-Cre:Itga4fl/fl K/B.g7 line to
disrupt this interaction. Valve inflammation and fibrosis were quantified histologically. Cre-negative littermates were
employed as controls in all cases.
Results:
Deletion of Syk in from MNPs ameliorated MVD severity and was accompanied by impaired TNF and IL6 production by
valve infiltrating macrophages. Interestingly, lymphoid-resident MNP cytokine production was unaffected. Impairing MNP
recruitment through deletion of VLA4 (Itga4) significantly attenuated the severity of K/B.g7 cardiac valve inflammation and
fibrosis.
Conclusion:
These studies define the critical molecular pathways used by MNPs to promote cardiovascular pathology in the setting of
systemic autoimmunity. We have defined multiple therapeutic targets (TNF, IL6, Syk, VLA4, VCAM1) that could be
exploited for the treatment of the cardiovascular comorbidity that accompanies human rheumatic diseases. Ongoing studies
are aimed at clarifying the molecular pathways governing MNP-mediated matrix production following their infiltration to
the valve stroma.
Disclosure: L. Meier, None; J. L. Auger, None; B. J. Engelson, None; H. Cowan, None; E. Breed, None; M. Gonzalez-
Torres, None; J. Boyer, None; B. A. Binstadt, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/mononuclear-phagocytes-mediate-

systemic-autoimmune-disease-related-valvular-heart-disease-via-inflammatory-cytokine-production-and-recruitment-of-
tissue-reparative-macrophages
Modulation of Cartilage Degradation Biomarkers Reflect the Activation and

Inhibition of Pro-Inflammatory Cytokine Signaling in an Ex Vivo Model of
Bovine Cartilage
Cecilie F. Kjelgaard-Petersen1,2, Neha Sharma1,3, Ashref Kayed4,5, Britt Christensen1, Morten Karsdal6, Anne-C. Bay-
Jensen7 and Christian S. Thudium1, 1Biomarkers and Research, Nordic Bioscience, Herlev, Denmark, 2Bioengineering,
Technical University of Denmark, Kgs. Lyngby, Denmark, 3Biomedical Sciences, University of Copenhagen, Copenhagen,
Denmark, 4Research and Biomarkers, Nordic Bioscience, Herlev, Denmark, 5Biomolecular Sciences, University of
Copenhagen, Copenhagen, Denmark, 6Biomarkers and Reseacrh, Nordic Bioscience, Herlev, Denmark, 7Biomarkers and
Reseach, Nordic Bioscience, Herlev, Denmark
SESSION INFORMATION
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Background/Purpose:
Several inflammatory cytokines and intracellular signaling pathways have been targeted in drug development with varying
clinical results. Improved understanding of the intracellular signaling’s modulation of the extracellular matrix turnover could
aid in selecting novel anti-inflammatory treatments for inflammatory arthritis. The aim of this study was to investigate the
effect of small molecule inhibitors targeting 4 main pro-inflammatory signaling pathways (p38, Syk, IκBα, and STAT) on
Oncostatin M (OSM) and Tumor Necrosis Factor α (TNFα) stimulated cartilage.
Methods:
Full depth cartilage explants (FDC) were isolated from bovine knees. The FDCs were cultured for 21 days without (WO)
treatment, OSM [10ng/mL]+TNFα [2ng/mL] or OSM+TNFα together with SB203580, R406, TPCA-1 or Tofacitinib (Tofa)
at 3 µM, 1 µM, 0.3 µM, or 0.1µM. DMSO was included in WO and OSM+TNFα. The inhibitors were given at start of the
experiment (preventive) or after 10 days of OSM+TNFα stimuli (interventive). Activation of the p38, JNK, ERK, IκBα, and
STAT3 signaling pathways were assessed at time 0, 15’, 30’, 1h, 2h, 4h, 8h, and 24h of OSM+TNFα stimuli by western blot.
The effect of the OSM+TNFα induced cartilage turnover was assessed by the biomarkers AGNx1, C2M, and FFGV by
ELISA in the conditioned medium.
Results:
Western blot verified activation of p38, JNK, ERK, IκBα, and STAT3 signaling within 24h of OSM+TNFα stimuli.
OSM+TNFα significantly increased the biomarkers AGNx1 (P<0.001), FFGV (P<0.001) (Fig. 1), and C2M (P<0.001).
Preventive SB203580 treatment had no effect on OSM+TNFα induced AGNx1 release, while R406 (3µM: P=0.034),
TPCA-1 (3µM: P<0.001) and Tofa (3µM: P<0.001) significantly decreased AGNx1 in a dose-dependent manner. All
inhibitors given preventive inhibited the release of C2M and FFGV (Fig.1a-d). SB203508 in a dose-dependent manner
(3µM: P=0.001), while all concentrations of R406, TPCA-1, and Tofa significantly inhibited the release (P<0.05).
Interventive treatment with SB203580 tended to decrease C2M and FFGV (Fig. 1e) release 4 days after addition. R406,
TPCA-1, and Tofa had no effect on C2M or FFGV after 4 days of interventive treatment, but tended to decrease C2M and
significantly decreased FFGV (Fig. 1f-h) release after seven days of treatment in a dose-dependent manner (C2M: 3 µM,
P≤0.055, FFGV).
Conclusion:
In summary, we verified that OSM+TNFα stimulation activates a series of signaling pathways in our FDC culture. Using
small molecule inhibitors targeting these individual pathways we found that they modulate the release of extracellular matrix
degradation fragments in a spatial and temporal manner. This is both dependent on the target signaling pathway and whether
the treatment is preventive or interventive.
Disclosure: C. F. Kjelgaard-Petersen, None; N. Sharma, None; A. Kayed, None; B. Christensen, Nordic Bioscience A/S,
3; M. Karsdal, Nordic Bioscience Diagnostic, 1,Symic Bio, 1,Nordic Bioscience A/S, 3; A. C. Bay-Jensen, Nordic
Bioscience A/S, 1,Nordic Bioscience A/S, 3; C. S. Thudium, Nordic Bioscience Diagnostic, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/modulation-of-cartilage-degradation-

biomarkers-reflect-the-activation-and-inhibition-of-pro-inflammatory-cytokine-signaling-in-an-ex-vivo-model-of-bovine-
cartilage
ACPA Activate Challenged Synovial Fibroblasts through a PAD Dependent

Mechanism: A Potential Explanation of the “Second Hit Model” in RA
Meng Sun1, Vijay Joshua1, Akilan Krishnamurthy1, Aase Hensvold1, Yanying Liu2, Sergiu-Bogdan Catrina3, Caroline
Ospelt4, Vivianne Malmström1, Johanna Steen1, Marianne Engström1, Heidi Wähämaa1, Bence Rethi1 and Anca I. Catrina1,
1Rheumatology Unit, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden,
2Rheumatology Unit, Department of Medicine, Peking University People's Hospital, Beijing, China, 3Molecular Medicine
and Surgery, Molecular Medicine and Surgery, Stockholm, Sweden, 4Center of Experimental Rheumatology, University
Hospital Zürich, Zurich, Switzerland
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Background/Purpose:
Anti-citrullinated proteins antibodies (ACPAs) injected in mice induce IL-8 dependent bone loss and arthralgia, but no
synovial changes. We hypothesized that additional stimulus, sensitizing the synovial compartment to ACPA effects, is
needed for the transition from bone to synovial pathology.
Methods:
Synovial biopsies were obtained from healthy volunteers and RA patients by arthroscopy. Synovial fibroblasts (SFs) were
isolated from synovial tissue of RA patients by enzymatic digestion. Polyclonal ACPA and other non-ACPA IgGs were
separated from peripheral blood of RA patients by affinity purification on a cyclic citrullinated peptide (CCP)-2 column.
Monoclonal ACPAs were generated from synovial fluid single B-cells. SFs migration capacity was tested by scratch-assays
in starved and non-starved cultures treated with ACPAs, with or without presence of IL-8. The results were evaluated by
NIH ImageJ software. SF adhesion was analyzed by xCELLigence System Real-Time Cell Analyzer (ACEA bioscience).
Peptidylarginine deiminases (PAD) expression and protein citrullination were evaluated by immunohistochemistry and
immunofluorescence on SFs. Citrullination level of synovial biopsies were evaluated by biotinylated monoclonal ACPAs.
The role of signaling pathways in the ACPA-mediated SF modulation was analyzed by using specific signal inhibitors and
by monitoring protein phosphorylation using western blot.
Results:
Serum starvation of SFs increased citrullinated proteins and PAD expression. Starved but not non-starved SFs showed an
increased mobility index following polyclonal ACPA stimulation to a mean±SD fold increase of 2.6±0.5. Similar effects
were observed with monoclonal B09 but not C03, with a fold increase of the migration index of 1.8±0.4 for B09 antibody
and 1.0±0.5 for C03 antibody. This effect was abolished by PAD inhibition as well as ACPA blocking with citrullinated but
not native fibrinogen. Exogenous pro-inflammatory cytokines IL-8 and TNF induced PAD expression in SF and
synergistically increased their mobility when added together with ACPA. Phosphorylation and inhibition studies of
intracellular signaling pathways in starved SFs indicated an important role for PI3K-mediated signals in the ACPA-induced
increase of SF mobility. Neither B09 nor C03 were binding to the non-inflammed healthy synovial tissues, while both B09
and C03 showed various degrees of binding to the inflammed RA synovial biopsies, with only B09 bidning the fibroblast
cell population.
Conclusion:
We demonstrated that some but not all ACPAs fail to activate SFs in basal conditions but have a pronounce effect on cellular
stressed SF. Our findings offer a novel scenario on how a synovial insult (in this case the in vitro induced cellular stress) that
will normally resolve unobserved, might be essential for the transition towards chronic synovial changes in the presence of
ACPA.
Disclosure: M. Sun, None; V. Joshua, None; A. Krishnamurthy, None; A. Hensvold, None; Y. Liu, None; S. B. Catrina,
None; C. Ospelt, None; V. Malmström, None; J. Steen, None; M. Engström, None; H. Wähämaa, None; B. Rethi, None;
A. I. Catrina, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/acpa-activate-challenged-synovial-

fibroblasts-through-a-pad-dependent-mechanism-a-potential-explanation-of-the-second-hit-model-in-ra
Synovial Fibroblast CD318 Expression Mediates T Cell Adhesion and

Migration in Rheumatoid Arthritis
Ray A. Ohara1, Stephanie M. Rasmussen1, W. Alexander Stinson1, Huadong Cui1, Yuxuan Du1, Daniel P. Weber1, M. Asif
Amin1, Phillip L. Campbell2, Nora Singer3, Feng Lin4, David A. Fox1 and Jeffrey H. Ruth5, 1Division of Rheumatology
and Clinical Autoimmune Center of Excellence, University of Michigan, Ann Arbor, MI, Ann Arbor, MI, 2Ann Arbor, MI,
3Division of Rheumatology, MetroHealth Medical Center, Cleveland, OH, Cleveland, OH, 4Department of Immunology,
Lerner Research Institute, Cleveland Clinic, Cleveland, OH, Cleveland, OH, 5Internal Medicine, Division of Rheumatology
and Clinical Autoimmune Center of Excellence, University of Michigan, Ann Arbor, MI, Ann Arbor, MI
SESSION INFORMATION
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Background/Purpose: CD6 is an important marker and regulator of T cells and interacts with its known ligand, CD166.
Our group has previously shown that interferon gamma (IFNγ)-inducible antigen recognized by monoclonal antibody 3A11
is a new CD6 ligand distinct from CD166. And, it has recently been discovered that CD318 is the new CD6 ligand
recognized by 3A11. CD318 is a cell surface protein widely expressed on epithelial tissues and tumor cells as an important
regulator of cell adhesion through phosphorylation of its intracellular tyrosine domain. We currently examined CD318
expression on synovial tissues (STs) and soluble CD318 concentrations in synovial fluids (SFs) of rheumatoid arthritis (RA)
patients. In addition, we investigated its potential roles in recruitment and retention of T cells in the RA joints. We
hypothesize that CD6 on T cells interacts with CD318 on synovial fibroblasts and may lead to activation of either or both
cellular subsets to induce proinflammatory responses in RA.
Methods: To determine the localization of CD318 in the RA joints, normal (NL), RA, and osteoarthritis (OA) ST sections
were stained via both chromogenic and fluorescent immunohistochemistry using 3A11. To quantify the CD318 levels, STs
were homogenized and measured for CD318 using ELISA. Additionally, to examine whether CD318 is shed in a soluble
form, NL and RA peripheral blood sera and RA, OA, and juvenile idiopathic arthritis (JIA) SFs were measured for CD318
using ELISA. To confirm the expression of CD318 in vitro, synovial fibroblasts were treated with or without IFNγ and
stained for CD318 for flow cytometric analysis. To investigate the role of CD318 in the interaction between synovial
fibroblasts and T cells, adhesion assays were performed on synovial fibroblasts stimulated with or without IFNγ in the
presence or absence of neutralizing antibodies to CD318 and/or CD166. To further characterize the function of CD318, T
cell migration assay was performed in a modified 48-well Boyden chamber system.
Results: Immunohistochemistry revealed robust staining in the RA STs, specifically on the synovial fibroblasts and
endothelial cells, greater in RA than in NL and OA STs. ELISA showed elevated levels of CD318 in the RA ST
homogenates compared to that of NL and OA ST homogenates. ELISA for SFs also showed that soluble CD318 is
selectively and significantly elevated in the SF from patients with RA and JIA. Flow cytometry showed upregulation of
CD318 on synovial fibroblast lines upon IFNγ treatment. In adhesion assays, without IFNγ treatment, only CD166 was
functionally involved, consistent with low expression of CD318 on these cells. In contrast, with IFNγ treatment, both CD318
and CD166 were functionally involved, and adhesion was substantially diminished only by antibodies to both CD166 and
CD318. T cell migration assay confirmed CD318 as a chemoattractant at concentrations corresponding to the levels seen in
RA sera and SFs.
Conclusion: CD318 is highly elevated in the RA joints and involved in T cell adhesion to synovial fibroblasts. Soluble
CD318 is a T cell chemoattractant and its levels are similarly elevated in the SFs of RA and JIA patients. CD318 is a
potential new biomarker or target for the diagnosis and treatment of RA and other inflammatory arthritides.
Disclosure: R. A. Ohara, None; S. M. Rasmussen, None; W. A. Stinson, None; H. Cui, None; Y. Du, None; D. P. Weber,
None; M. A. Amin, None; P. L. Campbell, None; N. Singer, None; F. Lin, None; D. A. Fox, None; J. H. Ruth, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/synovial-fibroblast-cd318-expression-

mediates-t-cell-adhesion-and-migration-in-rheumatoid-arthritis
JAK/STAT Mediated Inhibition of Mir-23a~24-2~27a Cluster Potentiates

Activation of CD14+ Monocytes in Treatment-Resistant RA
Marina Frleta-Gilchrist, Donna McIntyre, Aziza Elmesmari, Lynn Stewart, Derek Baxter, Mariola Kurowska-Stolarska,
Derek Gilchrist and Iain B. McInnes, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow,
United Kingdom
SESSION INFORMATION
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Background/Purpose:
While emerging and existing treatments of RA allow better options and clinical outcomes for patients, studies informing
drug resistant states and further clinical therapeutic choices are lagging. We sought herein to compare a cross-sectional
cohort of patients with maintained low disease activity on conventional DMARDs (cDMARDs) and patients failing multiple
modes of both conventional or biologic treatments. A broad insight into the treatment resistant state was obtained by
selecting blood derived CD14+ cells as precursors of many pathogenic cell types in RA. From these, we profiled the
expression of microRNAs (miR), which as post-transcriptional regulators have the ability to control entire pathways giving
an informative ‘snapshot’ of cell state. The resulting data identified regulatory miRs and associated pro-inflammatory
pathways underpinning treatment resistance in RA, highlighting how they could be utilized to inform future treatment
choices.
Methods:
RA patients meeting ACR 2010 diagnostic criteria were selected for this study. Two control groups included 21 healthy
matched controls and 16 patients with established disease, well controlled by conventional DMARDs (cDMARDs); while
treatment resistant groups contained 22 patients with high disease activity with cDMARDs and 41 patients with active
disease after multiple biologic agents. Peripheral blood CD14+ cells were isolated using Miltenyi isolation kit. MiR
expression was determined using the Affymetrix 3.0 miR Array. Predicted miR targets were identified using TargetScan.
Direct miR-target interactions were confirmed by luciferase reporter assay. CD14+ cells isolated from buffy coats were
stimulated with IL-6, IFNγ or GM-CSF. THP-1 cell lines lacking the activities of miR-23a, miR-27a singly or together were
created by the stable introduction of miR sponge transgenes.
Results:
Microarray profiling of CD14+ cells from patient cohort showed that the expression of miR-23a~24-2~27a cluster was
significantly repressed in both treatment resistant RA groups. Specifically, miR-23a and miR-27a were found to mediate a
novel regulatory feedback loop of the IL-6 pathway. IL-6 stimulation of primary monocytes suppressed the expression of
these miRs. In turn, this alleviated the repression of their direct targets, both soluble and membrane bound IL-6R, further
sensitizing the cells to IL-6 signaling. Additionally, miR-23a and miR-27a expression was repressed by other cytokines
utilizing JAK/STAT signaling cascade, such as viral mediator IFNγ, but also monocyte maturation factor GM-CSF,
suggesting a potential mechanism for their activation upon migration into tissues. Moreover, cells lacking miR-23a and miR-
27a expressed higher levels of the pro-inflammatory cytokines TNFα and IL-6 upon LPS stimulation.
Conclusion:
Collectively, these data provide evidence of how the multifactorial induction of intracellular JAK/STAT signaling inhibits
miR-23a cluster expression leading to increased production of IL-6R, further potentiating the role of this novel pro-
inflammatory circuit in treatment resistant RA.
Disclosure: M. Frleta-Gilchrist, None; D. McIntyre, None; A. Elmesmari, None; L. Stewart, None; D. Baxter, None;
M. Kurowska-Stolarska, None; D. Gilchrist, None; I. B. McInnes, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/jakstat-mediated-inhibition-of-mir-

23a24-227a-cluster-potentiates-activation-of-cd14-monocytes-in-treatment-resistant-ra
IL-6 and TNF-a Cooperate to Modulate the Cell Cycle of RA-Fibroblast-like

Synoviocytes Via Cyclin Dependent Kinase Inhibitors
Kenta Kaneshiro1, Kohsuke Yoshida1, Ayako Nakai1, Kohjin Suzuki1, Koto Uchida1, Teppei Hashimoto2, Yoshiko
Kawasaki3, Natsuko Nakagawa4, Koji Tateishi5, Nao Shibanuma6, Yoshitada Sakai7 and Akira Hashiramoto1, 1Department
of Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan, 2Department of Rheumatology, Kobe
Kaisei Hospital, Kobe, Japan, 3The Center of Rheumatic Diseases, Department of Rheumatology, Kobe Kaisei Hospital,
Kobe, Japan, 4Department of Orthopaedic Surgery, Konan-Kakogawa Hospital, Kakogawa, Japan, 5Orthpaedic Surgery,
Kobe University Graduate School of Medicine, Kobe, Japan, 6Departmant of Orthopaedic Surgery, Kobe Kaisei Hospital,
Kobe, Japan, 7Division of Rehabilitation Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
SESSION INFORMATION
Do React - But How?
Background/Purpose:
IL-6 and TNF-α play an important role in the pathogenesis of RA, and the proliferation of RA-synoviocytes (FLS) is
controlled by cell cycle regulators including Cyclins, Cyclin dependent kinases (CDK), CDK inhibitors (CKDIs) and
retinoblastoma protein (RB). To reveal actions of proinflammatory cytokines on the cell cycle of RA-FLS, we examined the
expressions of the cell cycle regulators and the cellular viability under stimulations of IL-6 and TNF-α.
Methods:
RA-FLS were cultured with or without IL-6/soluble IL-6 receptor (sIL-6R) (100ng/ml) or TNF-α (10ng/ml). The
expressions of CDKIs (p16INK4a, p21Cip1, p27Kip1) and Cyclin E1/2 mRNA were measured by Real-time PCR, CYCLIN D
and CYCLIN E protein were measured by Western blot, the expression of CYCLIN D and the phosphorylation of RB were
observed by immunofluorescence, and the cellular viabilities were measured by WST-8. In addition, siRNA/p27Kip1 was
introduced into RA-FLS to analyze the expression of Cyclin E1 mRNA by Real-time PCR, under stimulations with or
without IL-6/sIL-6R or TNF-α.
Results:
IL-6/sIL-6R decreased the expression of p16INK4a, whereas increased CYCLIN D and the phosphorylation of RB. TNF-α
increased the expressions of p27Kip1, Cyclin E1/2 mRNA, CYCLIN D, and the phosphorylation of RB. The expression of
CYCLIN D and the phosphorylation of RB were synergistically increased by IL-6 and TNF-α. The expression of Cyclin E1
mRNA was decreased by siRNA/p27Kip1.
Conclusion:
Results clearly indicate that IL-6 and TNF-α interact with each other in regulating the cell cycle of RA-FLS.
Disclosure: K. Kaneshiro, None; K. Yoshida, None; A. Nakai, None; K. Suzuki, None; K. Uchida, None; T. Hashimoto,
None; Y. Kawasaki, None; N. Nakagawa, None; K. Tateishi, None; N. Shibanuma, None; Y. Sakai, None; A.
Hashiramoto, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/il-6-and-tnf-a-cooperate-to-modulate-

the-cell-cycle-of-ra-fibroblast-like-synoviocytes-via-cyclin-dependent-kinase-inhibitors
Leucine-Rich α-2 Glycoprotein Promotes Lung Fibrosis By Modulating TGF-

β Signaling in Fibroblasts
Hiromi Honda, Minoru Fujimoto, Satoshi Serada, Hyun Lee, Tomoharu Ohkawara and Tetsuji Naka, Center for Intractable
Immune Disease, Kochi University, Nankoku, Japan
SESSION INFORMATION
Do React - But How?
Background/Purpose: Interstitial lung disease (ILD) is one of the most common extraarticular manifestation of rheumatoid
arthritis. ILD is characterized by progressive fibrosis of the lung parenchyma and is associated with increased morbidity and
mortality. Since TGF-β is thought to play an important role in tissue fibrosis, understanding the molecular details of TGF-β
signaling will provide us a novel therapeutic target for fibrotic disorders. Recently, leucine-rich α-2 glycoprotein (LRG) was
reported to function as a modulator of TGF-β signaling in angiogenesis in retinal disease and cardiac remodeling. However,
the role of LRG in fibrotic diseases including lung fibrosis has not yet been investigated. In this study, we aimed to
investigate the involvement of LRG in lung fibrosis using an animal model of lung fibrosis.
Methods: Bleomycin was intratracheally administered to C57BL/6 (WT) mice and LRG knockout (KO) mice, and lung
fibrosis was evaluated by Masson’s trichrome staining and hydroxyproline quantification in the lung. TGF-β signaling in the
lung was examined by analyzing phosphorylation of Smad proteins and expression of TGF-β downstream genes.
Furthermore, in vitro analysis using L929 mouse fibroblast cell line was performed to assess the effect of LRG on TGF-β
signaling in fibroblasts.
Results: The amount of LRG in BALF of WT mice was increased after bleomycin treatment. Immunohistochemistry of the
lung section showed that LRG was expressed in alveolar epithelial cells, bronchial epithelial cells and infiltrated immune
cells in bleomycin-treated WT mouse lung. In LRG KO mice, fibrosis in the lung was less severe as indicated by attenuated
Masson’s trichrome staining and lower collagen content in the lung compared with WT mice. In addition, expression of α-
SMA was decreased and phosphorylation of Smad2 was reduced in the lung of LRG KO mice compared with WT mice,
suggesting that fibroblast activation was inhibited in the absence of LRG. In vitro experiments indicated that LRG enhanced
TGF-β-induced phosphorylation of Smad2 and expression of PAI-1 and α-SMA in fibroblasts. On the other hand, Smad1/5/8
signaling was not enhanced by LRG. Although endoglin, an accessory TGF-β receptor, is known to be essential for LRG to
modulate TGF-β signaling in endothelial cells, we found that endoglin was not involved in the process of enhancing Smad2
phosphorylation in fibroblasts.
Conclusion: LRG promotes lung fibrosis by enhancing TGF-β-induced phosphorylation of Smad2 in fibroblasts and by
accelerating fibroblast differentiation into myofibroblasts.
Disclosure: H. Honda, None; M. Fujimoto, None; S. Serada, None; H. Lee, None; T. Ohkawara, None; T. Naka,
Practical Project for Rare/Intractable Diseases from Japan Agency for Medical Research and development
(15ek0109045h0003), 2,Research collaboration with SEKISUI MEDICAL, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/leucine-rich-%ce%b1-2-glycoprotein-

promotes-lung-fibrosis-by-modulating-tgf-%ce%b2-signaling-in-fibroblasts
IL-17A Induced Autophagy That the Proliferation of Rheumatoid Arthritis

Fibroblast-like Synoviocytes through Down-Regulation of PI3K/AKT/mTOR
Signaling Pathway
Sang-Hyon Kim1, Jihye Bang2, Ji-Min Kim1, Chang-Nam Son1, Jin-Nyeong Chae1 and Hye-Jin Jeong3, 1Division of
Rheumatology, Department of Internal Medicine, Keimyung University Dongsan Medical Center, Keimyung University
School of Medicine, Daegu, Republic of Korea, Daegu, Korea, Republic of (South), 2Division of Rheumatology,
Department of Internal Medicine, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea,
Republic of (South), 3Department of Rheumatology, Keimyung University Dongsan Medical Center, Daegu, Korea,
Republic of (South)
SESSION INFORMATION
Do React - But How?
Background/Purpose: Autophagy is generally thought of as a survival mechanism, although its deregulation has been
linked to non-apoptotic cell death. Fibroblast-like synoviocytes (FLS) resistance to apoptosis is a major characteristic of
rheumatoid arthritis (RA). We hypothesized that interleukin (IL)-17A might have an impact on autophagic flux and that
modulation of autophagy might be involved in migration and proliferation of synovial fibroblasts in the patients with RA
under inflammatory condition.
Methods: Synovial tissue was obtained from clinically involved knee joints of patients with RA or osteoarthritis (OA)
patients. The autophagosome of FLS isolated from RA and OA patients displayed different morphological and physiological
features by using transmission electron microscopy. The effects of IL-17 on the relationship between autophagy and cell
migration were evaluated with co-treatment of autophagy inhibitor using bafilomycin A1 and transfection of si-Atg5.
Results: IL-17 induced autophagosome formation and autolysosome accumulation in RA FLS, suggesting that they were
resistant to apoptosis. IL-17A increased autophagy of RA FLS by causing up-regulation of LC3II, Atg5 and Beclin1.
Migration and proliferation of FLS stimulated by IL-17A was suppressed by bafilomycin A1 and si-Atg5 which knocked
down of autophagy. And, autophagy inhibitor regulated signaling pathway which decreased IL-17A-induced expression of
phosphorylation-Akt and increased mTOR signaling pathway.
Conclusion: Taken together, our findings demonstrated that IL-17A could induce activate autophagy, induce inflammatory
response, and eventually lead to proliferation of synoviocytes. We suggest that autophagy can be one of the therapeutic
target for the RA management.
Disclosure: S. H. Kim, None; J. Bang, None; J. M. Kim, None; C. N. Son, None; J. N. Chae, None; H. J. Jeong, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/il-17a-induced-autophagy-that-the-

proliferation-of-rheumatoid-arthritis-fibroblast-like-synoviocytes-through-down-regulation-of-pi3kaktmtor-signaling-
pathway
Cannabinoid Receptor 2 Agonist (JWH-015) Inhibits Interleukin-1β-Induced

Inflammation in Rheumatoid Arthritis Synovial Fibroblasts
Sabrina Fechtner and Salahuddin Ahmed, Department of Pharmaceutical Sciences, Washington State University, College
of Pharmacy, Spokane, WA
SESSION INFORMATION
Do React - But How?
Background/Purpose: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by activated synovial
fibroblasts in which pro-inflammatory cytokine interleukin-1β (IL-1β) mediates inflammation. The endocannabinoid system
(ECS) is comprised of two evolutionarily conserved cannabinoid receptors 1 and 2 (CB1 and CB2) which elicit their effects
through Gαi/o mediated signaling. However, the mechanism through which ECS activation can modulate inflammatory
signaling in RA is poorly understood.
Methods: Human RASFs were obtained from patients diagnosed with RA according to the ACR guidelines (7 female, 2
male, average age 50 ± 43 years). RASFs were pre-treated with 10 or 20 µM of JWH-015 for 10 minutes prior to the
addition of IL-1β (10 ng/mL). Stimulation duration was for 30 minutes for signaling studies or 24 hours to evaluate the
production of IL-6, IL-8, PGE2, and cyclooxygenase (Cox) enzymes. Conditioned media was used for the quantification of
IL-6, IL-8, and PGE2 by ELISA and cell lysates were prepared for the analysis of IL-1β signaling proteins like p-P38, p-
JNK, p-ERK, and p-TAK-1Thr184/187 using Western immunoblotting. To understand the role of CB2, knockdown studies
were performed using CB2 siRNA for 48 hours prior to the addition of JWH-015 and IL-1β.
Results: Pretreatment of JWH-015 inhibited IL-1β-induced IL-6 (39 and 50% at 10 and 20 µM, respectively) and IL-8 (20
and 47% at 10 and 20 µM, respectively) production in human RASFs (p<0.05; n=3). Evaluation of the signaling pathways
using Western immunoblotting showed JWH-015 reduced the expression of phosphorylated TAK-1Thr184/187 by 12% and
27% at 10 and 20 µM concentration, respectively. Phosphorylated JNK1 was also inhibited by 11% and 22% at 10 and 20
µM and JNK2 by 18% and 64% at 10 and 20 µM, respectively (p<0.05; n=3). Knockdown of CB2 expression using siRNA
approach showed almost 40% reduction in the production of IL-β-induced IL-6 and IL-8 and also abrogated the protective
effect of JWH-015 (p< 0.05; n=3), suggesting CB2 as a receptor central to JWH-015’s anti-inflammatory action. We also
observed CB2 knockdown resulted in a significant decrease of IL-1β-induced Cox-2 expression by ~58%, which resulted in
a marked inhibition of PGE2 production by ~80% (p<0.05; n=3).
Conclusion: Our study provides novel evidence that CB2 activation is anti-inflammatory in response to IL-1β stimulation in
RASFs, and JWH-015 elicits anti-inflammatory effects through CB2, not CB1, in human RASFs. These findings suggest
that JWH-015 may be tested as an adjunct therapy option to reduce inflammation and the perception of local pain through
the ECS.
Disclosure: S. Fechtner, None; S. Ahmed, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/cannabinoid-receptor-2-agonist-jwh-015-

inhibits-interleukin-1%ce%b2-induced-inflammation-in-rheumatoid-arthritis-synovial-fibroblasts
Association of Leisure-Time Physical Activity with Late-Life Mobility

Limitation Among Women with Total Joint Replacement for Hip or Knee
Osteoarthritis
Aladdin Shadyab1, Wenjun Li2, Charles Eaton3 and Andrea LaCroix4, 1Family Medicine and Public Health, University of
California, San Diego, La Jolla, CA, 2Medicine, University of Massachusetts Medical School, Worcester, MA, 3Family
Medicine and Epidemiology, Warren Alpert Medical School, School of Public Health, Brown University, Providence, RI,
4Family Medicine and Public Health, University of California, San Diego School of Medicine, La Jolla, CA
SESSION INFORMATION
Session Title: Epidemiology and Public Health Poster II: Rheumatic Diseases Other than Rheumatoid Arthritis
Background/Purpose: Maintaining mobility in old age is an important public health goal for patients with hip or knee
osteoarthritis (OA), who are vulnerable to functional decline and disability. Previous studies have observed that physical
activity (PA) may improve physical function among OA patients and before undergoing total joint replacement (TJR)
surgery for hip or knee OA. However, the association of PA with long-term functional outcomes after total hip (THR) or
total knee (TKR) replacement for OA is less clear. We examined associations of leisure-time PA with late-life mobility
limitation and death among women who underwent THR or TKR for OA.
Methods: The Women’s Health Initiative recruited women aged 65-79 years from 1993-1998 and followed them through
2012. Medicare claims data were used to determine THR (n=904) and TKR (n=1867) for OA. Women were followed for up
to 18 years after receiving a TJR to determine mobility status at age 85. If women reported that their health limited their
ability to walk one block or climb one flight of stairs in annual follow-up, they were classified as having mobility limitation.
Women completed a questionnaire at baseline to determine engagement in activities of light, moderate, and vigorous
intensities. PA variables were analyzed in metabolic equivalent-hours/week (MET-h/wk). Multinomial logistic regression
analyses were performed to determine associations of PA variables with mobility limitation at age 85 and death before age
85 (reference category=mobility intact at age 85). Total PA, moderate-to-vigorous physical activity (MVPA), walking, and
walking speed were analyzed in separate regression models adjusted for demographic, lifestyle, and health-related
characteristics.
Results: Relative to women with the highest level of total PA (>17.42 MET-h/wk), women with THR (odds ratio
[OR]=2.41; 95% confidence interval [CI]=1.29-4.51) or TKR (OR=1.56; 95% CI=1.04-2.34) who reported no PA had the
highest risk of developing mobility limitation at age 85. Compared with women with the highest amount of MVPA (≥15
MET-h/wk), women with THR (OR=1.96; 95% CI=1.18-3.24) or TKR (OR=1.48; 95% CI=1.05-2.07) who reported no
MVPA had increased risk of mobility limitation; the risk was also increased among women who did not meet federal
guidelines of ≥7.5 MET-h/wk of MVPA. Women with THR (OR=2.03; 95% CI=1.16-3.58) or TKR (OR=1.54; 95%
CI=1.05-2.27) who reported casual compared with fast walking speed were more likely to experience mobility limitation.
Among women with THR, there were significant dose-response associations of total PA, MVPA, walking, and walking
speed with mobility limitation and death. Among women with TKR, there were significant dose-response associations of
total PA, MVPA, and walking speed with mobility limitation and death.
Conclusion: Among older women with hip or knee OA, higher levels of total PA and MVPA, as well as faster walking
speed, before TJR were associated with better mobility in late life and decreased risk of death. Further studies are needed to
determine whether physical activity before TJR is associated with better mobility later in life among women with hip or
knee OA.
Disclosure: A. Shadyab, None; W. Li, None; C. Eaton, None; A. LaCroix, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/association-of-leisure-time-physical-

activity-with-late-life-mobility-limitation-among-women-with-total-joint-replacement-for-hip-or-knee-osteoarthritis
Dietary Patterns and Risk of Developing Knee Osteoarthritis: Data from the
Osteoarthritis Initiative
Bing Lu1, Jeffrey B. Driban2, Timothy E. McAlindon3 and Charles Eaton4, 1Rheumatoloy, Immunology and Allergy,
Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 2Rheumatology, Tufts Medical Center, Boston,
MA, 3Division of Rheumatology, Tufts Medical Center, Boston, MA, 4Family Medicine and Epidemiology, Warren Alpert
Medical School, School of Public Health, Brown University, Providence, RI
SESSION INFORMATION
Background/Purpose: Few studies have examined the effect of diet on future risk of knee OA development. The
association between overall dietary patterns and risk of OA is unknown. We aimed to examine the prospective association of
major dietary patterns by principal component analysis (PCA) with risk of developing radiographic knee OA.
Methods: In the Osteoarthritis Initiative (OAI), 2835 participants (4570 knees) without knee OA in at least one knee
[Kellgren and Lawrence (KL) grade of 0 or 1] who had dietary data at baseline were followed up to 48 months. We defined
knee OA incidence as KL grade ≥ 2. Dietary intake was assessed with a Block Brief Food Frequency Questionnaire
completed at baseline. We identified two major underlying patterns of food consumption by PCA: “Western” pattern,
characterized by high intakes of red / processed meats, refined grains, french fries, desserts, and sweets, and the “Prudent”
pattern characterized by high intakes of fruit/ vegetables, legumes, poultry, and fish. Each subject receives a score for each
dietary pattern, with a higher score indicating a higher adherence to the respective pattern. The derived patterns are
statistically uncorrelated with each other. We grouped the dietary pattern scores using quartiles. We developed a Cox
proportional hazards model (with discrete time) to assess the association between dietary patterns and incident knee OA. The
robust covariance estimates were used to account for intra-subject correction.
Results: Among our sample, 414 knees developed knee OA within 48 months. In multivariable models after controlling for
age, sex, race, injury/surgery, and other covariates, adherence to the Western pattern was associated with an increased risk of
knee OA (HRQ4 vs Q1: 1.60, 95% CI: 1.03 to 2.51, p trend: 0.03), while adherence to the Prudent pattern tended to be
associated with a reduced risk of knee OA (HRQ4 vs Q1: 0.72, 95% CI: 0.52 to 1.00, p trend: 0.11) (Table). The observed
associations were attenuated after additionally adjusting for body mass index (BMI).
Conclusion: Following a Western diet may increase the future risk of knee OA, whereas following a Prudent pattern may be
associated with a reduced risk of knee OA. The associations may be partially mediated through BMI. Replication of these
novel findings in other prospective studies demonstrating that improvement of dietary quality leads to delay in knee OA
development are needed.
Key words: Western dietary pattern, Prudent dietary pattern, osteoarthritis.
Table. Dietary patterns and risk of knee OA (Hazard ratio, 95% CI)
Quartiles HR (95% CI) * P trend HR (95% CI) ┼ P trend
Western Q1 1.00 (Ref) 0.03 1.00 (Ref) 0.14
pattern Q2 1.60(1.19,2.16) 1.50(1.11,2.04)
Q3 1.55(1.11,2.17) 1.42(1.01,1.99)
Q4 1.60(1.03,2.51) 1.38(0.88,2.19)
Prudent Q1 1.00 (Ref) 0.11 1.00 (Ref) 0.22
pattern Q2 0.85(0.63,1.15) 0.87(0.65,1.17)
Q3 0.93(0.69,1.24) 0.97(0.72,1.30)
Q4 0.72(0.52,1.00) 0.76(0.55,1.07)
* Cox proportional hazards model with the discrete likelihood method
handling ties in failure times, adjusting for age, sex, race, physical activity,
NSAIDs use, injury/surgery, and total energy intake.
┼ Additionally adjusting for BMI.
Disclosure: B. Lu, None; J. B. Driban, NIAMS-NIH, 2,AXSOME Therapeutics, Inc., 5; T. E. McAlindon, None; C.
Eaton, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/dietary-patterns-and-risk-of-developing-

knee-osteoarthritis-data-from-the-osteoarthritis-initiative
What Have We Learned from Trajectory Analysis of Clinical Outcomes in

Osteoarthritis?
Maud Wieczorek1, Anne-Christine Rat1,2,3, Francis Guillemin1,2 and Christine Rotonda1, 1Université de Lorraine,
EA4360, APEMAC, Nancy, France, 2Inserm, CIC-1433 Epidémiologie Clinique, Vandoeuvre-lès-Nancy, France,
3Rheumatology Department, CHRU Nancy, Vandoeuvre-lès-Nancy, France
SESSION INFORMATION
Background/Purpose: The aims of this review were to summarize the literature on the trajectories of clinical outcomes in
knee and hip OA, to describe the distinct trajectories for each outcome and to collect the predictive factors associated with
these trajectories.
Methods: The Medline database was searched for relevant studies. Selection criteria were: i) patients >= 18 years old, ii)
patients at high risk of, or diagnosed with, knee or hip OA, iii) studies aiming to identify homogeneous subgroups with
distinct trajectories of clinical outcomes, iv) methodology and analysis designed to identify trajectories (longitudinal design
and repeated measures). Articles selection was made independently and in duplicate by two reviewers while the final
selection was made independently by three reviewers based on the full text.
Results: Of the 3867 abstracts retrieved, 37 studies met inclusion criteria among which 15 other studies analyzed trajectories
before surgery. The other 22 studies focused specifically on the course of clinical outcomes after hip or knee arthroplasty.
The most frequent outcome reported in the papers was pain (28 studies) while 19 studies reported results on function, 5 on
mental health, 1 on stiffness, 3 on social participation and 1 on activity limitation. In the cohort studies without surgery, hip
pain trajectories were divided in stable mild, moderate and severe pain. 3 additional subgroups included patients who
underwent a moderate pain regression, oscillated between moderate and severe pain levels or highly progressed over time
(Fig). A low educational level, high body mass index (BMI), an impaired physical function WOMAC score, high Kellgren
(KL) grade for the hip, a limited flexion and internal rotation of the hip and concurrent back and trochanteric pain were
associated with the membership in the severe pain trajectory. For the knee joint, the number of trajectories identified in the
literature was between 1 and 6. A “no pain”, a mild pain, a moderate pain and a severe pain trajectories were identified as
well as pain progression (moderate or severe worsening) or regression (major or moderate improvement) trajectories.
Patients belonging to the severe pain trajectory were more likely to be male, have a younger age , a low educational level, a
low social class, a high BMI, a high number of comorbidities, a high WOMAC physical function score, a high KL grade,
higher levels of anxiety and depression, and a poorer general health.
Conclusion: This review highlighted the high heterogeneity across studies in terms of numbers of trajectories retrieved,
especially for the pain outcomes. Nonetheless, some predictive factors of membership in a severe pain trajectory have been
identified and these findings could be an aid to an early identification of patients with a high risk of clinical worsening.
Disclosure: M. Wieczorek, None; A. C. Rat, None; F. Guillemin, None; C. Rotonda, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/what-have-we-learned-from-trajectory-

analysis-of-clinical-outcomes-in-osteoarthritis
Is Intra-Articular Injection of Synvisc Associated with a Delay to Knee

Arthroplasty in Knee OA Patients?
Kevin Ong1, Maria Runa1, Edmund Lau2 and Roy Altman3, 1Exponent, Inc., Philadelphia, PA, 2Exponent, Inc., Menlo
Park, CA, 3UCLA Medical Center, Los Angeles, CA
SESSION INFORMATION
Background/Purpose: Knee OA patients may undergo intra-articular (IA) hyaluronic acid (HA) injection treatment, but
there is debate about its effectiveness. We asked: (1) What is the epidemiology of IA HA use in knee arthroplasty (KA)
patients? (2) Is hylan G-F 20 associated with a delay to KA? (3) Is there a difference in the delay to KA with the number of
HA courses?
Methods: A retrospective, observational dataset (Optum Clinformatics; 2006 to June 2016) was used to identify knee OA
patients. Three different cohorts were identified: (1) No HA cohort who did not receive any IA HA; (2) Non-hylan G-F 20
cohort who received multiple HA types or only one type of non-hylan G-F 20 HA; and (3) hylan G-F 20 cohort who
received only hylan G-F 20. Patients who subsequently received a KA were further identified. A quantile regression model
was used, adjusting for clinical confounding factors and with propensity score weighting, to evaluate the effect of the
covariates on the median duration from knee OA to KA. The trend in time to KA with each additional course of HA was
also evaluated.
Results: From the initial cohort of 4,027,848 knee OA patients, 141,305 KA patients were identified. Overall median time
from knee OA diagnosis to KA was 1.2 years (average: 1.9 ± 1.9 years) with a corresponding interquartile range of 0.4 to
2.8 years. After propensity score adjustment, HA patients had significantly longer median time to KA by at least 5 months
(p<0.001; Table 1). When the HA cohort was compared after adjusting for the time to HA and number of injections, no
significant differences in the time to KA between multiple-shot hylan G-F 20 and non-hylan G-F 20 HA patients were
observed (p≥0.620), but a longer time was observed for one-shot hylan G-F 20 patients by about 3 months and patients who
received both one- and multiple- shot hylan G-F 20 (“One+multiple-shot hylan G-F 20”) by about 15 to 16 months. There
was a trend toward longer time to KA the more HA courses the patient underwent (Figure 1). For example, the average time
to KA increased from 2.3 years to 5.1 years as the hylan G-F 20 patients increased their treatment courses from one to five
or more. There was disparity between states in terms of KA patients who used HA. The three states with the lowest percent
of KA patients who used HA were HI (14.5%), IN (16.3%), and AK (16.7%), while the three states with the highest percent
of KA patients who used HA were NJ (39.1%), LA (33.9%), and MS (31.8%).
Conclusion: Most KA patients did not use HA (73.7%) and the ones who received it were associated with a longer median
time to KA by 5 to 22 months, depending on the HA cohort. The time to KA was shown to increase with more HA courses.
Disclosure: K. Ong, Sanofi-Aventis Pharmaceutical, 5,Stryker, 5,Zimmer Biomet, 5,Ethicon, 5,Ferring Pharmaceuticals,
5,Medtronic, 5,Paradigm Spine, 5,Pacira Pharmaceuticals, 5,DJO, 5; M. Runa, Sanofi-Aventis Pharmaceutical, 5; E. Lau,
Sanofi-Aventis Pharmaceutical, 5; R. Altman, Ferring Pharmaceuticals, 5,Novartis Pharmaceutical Corporation, 5,Pfizer
Inc, 5,Sanofi-Aventis Pharmaceutical, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/is-intra-articular-injection-of-synvisc-

associated-with-a-delay-to-knee-arthroplasty-in-knee-oa-patients
The Common Risk Factors for Hyperuricemia and Gout Do Not Predict
Incident Gout Once Hyperuricemia Is Established
Richard J. Reynolds1 and Jasvinder A. Singh2, 1Medicine, University of Alabama at Birmingham, Birmingham, AL,
2Rheumatology, University of Alabama at Birmingham, Birmingham, AL
SESSION INFORMATION
Background/Purpose: Metabolic syndrome, chronic kidney disease and hypertension are known to be associated with
hyperuricemia and gout. Hypertension is associated with incident gout. The Normative Aging Study indicates five times the
number of people with gout have asymptomatic hyperuricemia, and it is not understood what factors can explain this
difference. Using data from two prospective cohorts, the Framingham Heart Study (FHS) and the Atherosclerosis Risk in
Communities Study (ARIC), we tested the hypothesis that traits representing the comorbid conditions of hyperuricemia and
gout, given hyperuricemia at baseline, could discriminate those that subsequently develop gout from those that do not during
the follow-up period.
Methods: A total of 3,415 and 1,040 participants from ARIC and FHS, respectively met the inclusion criterion in which
serum urate concentration was greater than 7.0 mg/dL at the 1st exam in ARIC or exam 1, 2, or 8 of the offspring cohort in
FHS. Prevalent gout cases were excluded. With ARIC, incident gout was defined only if self report gout was reported at the
fourth exam (ARIC). With FHS, incident gout was defined only if clinical diagnostic impression of gout was reported at any
exam subsequent to the exam with serum urate concentration greater than 7.0. We extracted the following variables at the
exam where hyperuricemia was recorded: Age, sex, race (ARIC), systolic blood pressure, glomerular filtration rate (ARIC),
BMI, triglycerides, low-density lipoprotein-LDL, WaistHipRatio (ARIC), glucose and serum urate level (7-8, > 8 mg/dL).
Logistic regression was used to model incident gout with a linear predictor comprising the explanatory variables.
Results: A total (proportion) of 167 (0.05) and 99 (0.095) incident gout cases occurred during follow-up. The mean (SD)
age at baseline was 55 (5.8) and 39.5 (11.5) with 10 and 16 years of follow-up for ARIC and FHS, respectively. Age at first
exam (P-value=0.047-ARIC; 0.033-FHS), with odds ratio-OR (95% confidence interval [CI]), 0.97 (0.94, 1.0)-ARIC, 0.98
(0.96, 0.999)-FHS, and serum urate level (P-value=<0.0001-ARIC, 0.056-FHS), with OR 3.42 (2.38, 4.93)-ARIC, 1.53
(0.985, 2.38)-FHS, were the only consistent explanatory variables for incident gout between the two data sets. Increased
LDL was associated with incident gout in FHS (P-value=0.02, mean (SD) in gout vs no gout 145.2 (33.9) vs 138.2 (36.1),
with OR = 1.01 (1.001,1.014)). The model R2 was 6.3% and 2.8% for the ARIC and FHS datasets respectively.
Conclusion: The traditional risk factors for hyperuricemia and gout do not differentiate people with hyperuricemia that
develop incident gout from those that do not during the follow-up period. A possible explanation is that most of the risk
factors predict the development of hyperuricemia but not gout. Individuals presenting with serum urate levels > 8 mg/dL had
the highest risk for developing gout in the future. The low explanatory ability of these models indicates that additional
features, possibly molecular (e.g., genomic, metabolomic), behavioral (e.g. exercise, smoking, alcohol use) and use of
medications (diuretics, aspirin, ACE inhibitors), may be important predictors of gout given the state of hyperuricemia.
Disclosure: R. J. Reynolds, None; J. A. Singh, Takeda, Savient, 2,consultant fees from Savient, Takeda, Regeneron, Merz,
Iroko, Bioiberica, Crealta and Allergan pharmaceuticals, WebMD, UBM LLC and the American College of Rheumatology,
5,. JAS serves as the principal investigator for an investigator-initiated study funded by Horizon pharmaceuticals through a
grant to DINORA, Inc., a 501 (c)(3) entity. JAS is a member of the executive of OMERACT, an organization that develops
outcome mea, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-common-risk-factors-for-

hyperuricemia-and-gout-do-not-predict-incident-gout-once-hyperuricemia-is-established
Epidemiology and Mortality in Systemic Sclerosis in South Korea: A

Nationwide Population-Based Study
Kyong-Hee Jung1, Seong-Ryul Kwon1, Joo-Hyun Lee2, Hyeong Sik Ahn3, Hyun Jung Kim3 and Gil Won Kang4,
1Rheumatology, Inha University, Incheon, Korea, Republic of (South), 2Rheumatology, Inje University Ilsan Paik Hospital,
Goyang, Korea, Republic of (South), 3Korea University, Seoul, Korea, Republic of (South), 4Chungbuk University,
Cheongju, Korea, Republic of (South)
SESSION INFORMATION
Background/Purpose:
Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by small vessel vasculopathy,
autoantibody production, and excessive collagen deposition in the skin and internal organs. Its clinical manifestations and
progressions are chronic and diverse. Studies on epidemiology and mortality of systemic sclerosis (SSc) at the national level
are scarce. To investigate incidence, prevalence, mortality, and causes of death in SSc patients using nationwide population
based data in Korea.
Methods:
We used data from the Rare Intractable Disease (RID) registry and Health Insurance Review and Assessment (HIRA)
service, which include information on all SSc patients diagnosed based on uniform criteria between 2008 and 2013. The
RID¡¯s diagnostic criteria for SSc adopt the 1980 criteria of American College of Rheumatology. We linked the data from
Statistics Korea to the HIRA-RID database to confirm the causes of death.
Results:
The mean annual incidence of SSc in Korea was 8.0 per 106 population, with a female-to-male ratio of 3.9:1. The prevalence
in 2013 was 77.7 per 106 population. The average annual mortality was 1.40 per 106 people, and the standardized mortality
ratio was 4.34. The 5-year survival rates were 88.5%, which was significantly lower than the age-gender matched general
population. SSc was the most common cause of death (36.5% of total death), followed by malignancy (18.2%),
cardiovascular diseases and respiratory diseases (10.7%, each).
Conclusion:
Incidence and prevalence of SSc in East Asian countries is considered to be lower than in North America and Australia, but
higher than in Northern European countries. The higher mortality of SSc patients compared to the general population is
attributable to SSc related diseases, lung cancer and respiratory diseases. Post-diagnosis survival of SSc patients was better
than previous studies, which may represents a recent improvement in patient management.
Figure 1. Incidence of Systemic sclerosis by sex and age in Korea, 2008–2013. The vertical axis shows incidence rates
per 105 population; the horizontal axis shows age in 5-year increments until the age of 80.
Disclosure: K. H. Jung, None; S. R. Kwon, None; J. H. Lee, None; H. S. Ahn, None; H. J. Kim, None; G. W. Kang,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/epidemiology-and-mortality-in-systemic-

sclerosis-in-south-korea-a-nationwide-population-based-study
Identifying Exposures to Chemicals in Patients with SLE – a Non-Targeted

Exposome Approach Reveals Enrichment for Phthalates
Cristina Lanata1, Thomas Lin2, Maria Dall'Era1, Jinoos Yazdany3, Patricia P. Katz1, Laura Trupin3, Charles G. Helmick4,
Roy Gerona5 and Lindsey A. Criswell1, 1Medicine/Rheumatology, University of California, San Francisco, San Francisco,
CA, 2Univeristy of California, San Francisco, SAN FRANCISCO, CA, 3Medicine/Rheumatology, University of California
San Francisco, San Francisco, CA, 4Centers for Disease Control and Prevention, Atlanta, GA, 5Obstetrics and Gynecology,
University of California, San Francisco, SAN FRANCISCO, CA
SESSION INFORMATION
Background/Purpose:
Environmental exposures may play a substantial role in the pathogenesis of SLE. The goal of this study is to characterize the
serum levels of multiple chemicals in a cohort of SLE patients and controls.
Methods:
Patients from the California Lupus Epidemiology Study and healthy controls were studied. Banked serum was analyzed by
Liquid Chromatography Quadruple Time-of-Flight Mass Spectrometry (LC-QTOF/MS). The results of the LC-QTOF/MS
analysis were matched into a database of 740 potentially detected environmental organic chemicals. Detection frequencies of
chemicals were calculated. Univariate and multivariate analyses were performed, adjusting for potential confounders.
Association testing between chemical classes, chemicals and specific lupus phenotypes and disease activity was performed.
Results:
58 females with SLE and 78 healthy females were studied. The number of unique chemicals detected was 309, with an
average of 60 chemical-hit matches per subject (range 32-150). SLE patients had a higher detection frequency of phthalates
whereas healthy controls had a higher detection frequency of pesticides and phenols (table 1). A higher phthalate detection
frequency was associated lupus nephritis, but did not correlate with disease activity (SLEDAI score), hypocomplementemia
or anti ds-DNA status. In patients with SLE, a per count increase in detection frequency of a phthalate was associated with
an OR of 1.4 for history of lupus nephritis, adjusting for age, disease duration, race, education and income (p=0.002, CI[1.1-
1.7]). Chemicals detected at a higher frequency in SLE were enriched for specific phthalates such as metabolites of DHEP
(table 2). Among SLE patients, 2 specific phthalates, mono2ethyl5oxohexylphthalate (p=0.00002) and
mono2ethyl5oxohexylphthalate (p=0.00015) were associated with lupus nephritis.
Conclusion:
LC-QTOF/MS can identify a wider range of potential chemical exposures in SLE, and may aid in prioritizing chemicals for
further research and intervention. We found that patients with SLE had significantly increased exposure to phthalates
compared to healthy controls, with further enrichment among patients with lupus nephritis. Exposure to Mono-(2-
carboxymethylhexyl) phthalate has been associated with dsDNA production and lupus nephritis in NZB/W F1 mice.
Disclosure: C. Lanata, None; T. Lin, None; M. Dall'Era, None; J. Yazdany, None; P. P. Katz, Bristol-Myers Squibb, 2;
L. Trupin, None; C. G. Helmick, None; R. Gerona, None; L. A. Criswell, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/identifying-exposures-to-chemicals-in-

patients-with-sle-a-non-targeted-exposome-approach-reveals-enrichment-for-phthalates
Identification of Key Screening Characteristics for Systemic Lupus

Erythematosus Natural History
Kendra A. Young1, Melissa E. Munroe2, Joel M. Guthridge3, Diane L. Kamen4, Gary S. Gilkeson5, Michael Weisman6,
David Karp7, John B. Harley8, Daniel J. Wallace6, Judith A. James9 and Jill M. Norris10, 1Epidemiology, University of
Colorado Denver, Aurora, CO, 2Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma
City, OK, 3Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, OKC, OK,
4Medicine/Rheumatology & Immunology, Medical University of South Carolina, Charleston, SC, 5Department of Medicine,
Medical University of South Carolina, Charleston, SC, 6Cedars-Sinai Medical Center Division of Rheumatology, Los
Angeles, CA, 7Rheumatology, UT Southwestern Med Ctr, Dallas, TX, 8Center for Autoimmune Genomics and Etiology
(CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 9Arthritis and Clinical Immunology Program,
Oklahoma Medical Research Foundation, Oklahoma City, OK, 10Department of Epidemiology, Colorado School of Public
Health, Aurora, CO
SESSION INFORMATION
Background/Purpose: A prospective study of preclinical SLE disease evolution is needed to help elucidate critical aspects
of disease etiology and early pathogenesis, and to identify early directed therapeutic targets. However, designing the most
informative study of this complex heterogeneous disease is unclear without better definition of high-risk populations. Our
objective was to determine screening characteristics to identify individuals for follow-up in a prospective study.
Methods: We sent letters to 3823 individuals who reported having a family member with SLE and who did not meet ≥ 4
ACR criteria for SLE at their baseline visit to enroll in a follow-up study to gather information regarding interim
development of signs and symptoms consistent with SLE; 436 enrolled. Fifty-six individuals had transitioned to SLE (> 4
cumulative ACR criteria, verified by medical record review) by the time of follow-up. Generalized estimating equations,
accounting for correlation within families, assessed associations between our dichotomous outcome of transitioning to SLE
with baseline characteristics, including age, sex, race, ANA positivity (ANA+), Connective Tissue Disease Screening
Questionnaire (CSQ) SLE score, and number of ACR criteria. Predictive accuracy of characteristics on transitioning were
analyzed using positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity. Characteristics
were separated by the amount of effort required to collect the data: questionnaire alone; questionnaire and a blood test; and a
blood draw and medical records for ACR criteria confirmation.
Results: Age (47.2 vs 47.2 years), sex (87.5% vs 83.2%), and race (76.8% vs 73.4% European American (EA)) were similar
between those who transitioned and those who did not transition. Sisters of a SLE proband were just as likely to transition as
other first-degree relatives (OR=1.5, 95% CI 0.8-2.8), as were those <30 years of versus those ≥ 30 years old (OR=1.3, 95%
Ci 0.5-3.2), and non-EAs versus EA (OR=1.3, 95% 0.5-3.5). ANA+, CSQ classification of possible or probable SLE (CSQ-
SLE+), and greater number of ACR criteria were each associated with transitioning to SLE. Being ANA+ and having
photosensitivity by confirmed ACR criteria had the highest PPV and specificity for transitioning to SLE (Table 1). CSQ-
SLE+ had a better PPV, NPV, sensitivity and specificity than ANA+ alone. Combining ANA+ and CSQ-SLE+ increased the
PPV and specificity of transitioning to SLE; additionally limiting to females did not increase the predictive accuracy.
Conclusion: Limiting follow-up to females or to a specific race/ethnic group does not appear to be needed. Confirmed ACR
criteria provided the best predictive accuracy. Given limited resources, identifying subjects based on the SLE portion of the
CSQ questionnaire could be most efficient for follow-up.
Table 1. Predictive Accuracy of Baseline Characteristics for Transitioning to SLE.

Baseline N (%) with Positive Negative Sensitivity Specificity
Characteristics Characteristic(s) Predictive Predictive
Value Value
Using Questionnaire Data alone
CSQ-SLE+* 183 (42.0%) 27.9% 98.0% 91.1% 65.3%
Female 365 (83.7%) 13.4% 90.1% 87.5% 16.8%
CSQ-SLE+* and 166 (38.1%) 27.7% 96.3% 82.1% 68.4%
Female
Using Questionnaire Data and Blood Draw for Measurement of ANA
ANA+ 226 (51.8%) 19.0% 93.8% 76.8% 51.8%
ANA+ and CSQ- 122 (28.0%) 32.8% 94.9% 71.4% 78.4%
SLE+*
ANA+ and 200 (45.9%) 19.5% 92.8% 69.6% 57.6%
Female
ANA+, CSQ- 113 (25.9%) 32.7% 94.1% 66.1% 80.0%
SLE+*, and
Female
ANA+ and 80 (18.4%) 33.8% 91.9% 48.2% 86.1%
Positive
Photosensitivity
from CSQ
ANA+ and 112 (25.7%) 28.6% 92.6% 57.1% 78.9%
Positive Raynaud
from CSQ
Using Blood Draw for Measurement of ANA and Medical Records to confirm ACR
Criteria
ANA+ and 21 (4.8%) 52.4% 89.2% 19.6% 97.4%
Immunologic
Disorder by
Confirmed ACR
Criteria
ANA+ and 24 (5.5%) 62.5% 90.0% 26.8% 97.6%
Positive
Photosensitivity
by Confirmed
ACR Criteria
ANA+ and 60 (13.8%) 58.3% 94.4% 62.5% 93.4%
Positive Clinical†
ACR Criteria
Disclosure: K. A. Young, None; M. E. Munroe, None; J. M. Guthridge, None; D. L. Kamen, None; G. S. Gilkeson,
None; M. Weisman, None; D. Karp, None; J. B. Harley, None; D. J. Wallace, None; J. A. James, None; J. M. Norris,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/identification-of-key-screening-

characteristics-for-systemic-lupus-erythematosus-natural-history
Heart Failure Hospitalizations Among SLE and Diabetes Mellitus Patients

Compared to the General U.S. Medicaid Population
Sarah Chen1, Medha Barbhaiya2, Michael A. Fischer3, Hongshu Guan4, Candace H. Feldman5, Brendan M. Everett6 and
Karen H. Costenbader7, 1Brigham and Women's Hospital, Boston, MA, 2Rheumatology, Immunology and Allergy, Brigham
and Women's Hospital and Harvard Medical School, Boston, MA, 3Division of Pharmacoepidemiology and
Pharmacoeconomics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 4Rheumatology, Brigham
and Women's Hospital and Harvard Medical School, Boston, MA, 5Rheumatology, Brigham & Women's Hospital, Boston,
MA, 6Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA,
7Brigham and Women's Hospital, Harvard Medical School, Boston, MA
SESSION INFORMATION
Background/Purpose: Cardiovascular disease (CVD) risk is increased in SLE patients, compared to the general population
and age- and sex-matched diabetes mellitus (DM) patients. Heart failure (HF) is the leading cause of hospitalizations in the
U.S., and HF risk is elevated among DM patients compared to those without DM. Given the elevated CVD risk in SLE
patients, we investigated rates and risks of HF hospitalization among SLE patients and age- and sex-matched DM and
general Medicaid patients.
Methods: We used Medicaid Analytic eXtract (MAX) data, containing billing claims for Medicaid patients from the 29
most populated US states, 2007-2010. We identified both SLE and DM patients, ages 18-65, using >3 ICD-9 codes for SLE
or DM, each separated by >30 days. Index date was the date of the 3rd diagnosis code. We matched each SLE patient at
index date to 2 DM patients and 4 general Medicaid patients without SLE or DM, by age at index date and sex. (The general
Medicaid cohort had non-SLE, non-DM ICD-9 codes on date of SLE index date.) We required a baseline period of 6 months
of continuous Medicaid enrollment prior to the index date for all patients. Subjects were followed from index date until
death, disenrollment or end of follow-up. We used ICD-9 codes to identify HF as primary or secondary hospital discharge
diagnosis and calculated rates of first HF hospitalization event per 1,000 person-years for each cohort. We used Cox
proportional hazard models to calculate hazard ratios (HR) for first HF hospitalization events. In a secondary analysis, we
excluded those with baseline HF.
Results: 40,212 SLE patients were matched to 80,424 DM and 160,848 general patients. In all cohorts, 92% were female,
and mean age was 40.3 (+12.1) years. Mean follow up was 1.8 (+1.1) years for SLE, 1.8 (+1.1) years for DM, and 1.6 (+1.2)
years for general patients. Baseline CVD was prevalent in 18% of SLE, 13% of DM and 1% of non-SLE, non-DM cohorts,
and baseline HF was prevalent in 6% of SLE, 5% of DM and <1% of non-SLE, non-DM patients. HF hospitalization rates
per 1,000-person years were similar in SLE and DM, but lower in the general population (Table). Adjusted HRs for first HF
hospitalizations were higher among DM (HR 4.0, 95% CI 3.6-4.3) and SLE (HR 2.4, 95% CI 2.2-2.7) patients compared to
non-SLE, non-DM patients. When patients with baseline HF were excluded, the HR for first HF hospitalizations were
similar between SLE (HR 2.5, 95% CI 2.3-2.8) and DM (HR 2.7, 95% CI 2.4-2.9).
Conclusion: SLE and age- and sex-matched DM patients had significantly higher rates of HF hospitalization than age- and
sex-matched general (non-SLE, non-DM) Medicaid patients. The adjusted risk of first HF hospitalization was also over
twice as high in both SLE and DM patients than in patients without either condition, which has important implications for
improving clinical care for SLE patients.
Table. Rates and Multivariable Hazard Ratios for Hospitalizations for HF* among
SLE Patients and Age- and Sex-Matched DM Patients, compared to the General
(non-SLE, non-DM) Medicaid population, 2007-2010
HR§ (95% CI)
Person- Rate‡ Including all Excluding patients
Cohort† Events years (95% CI) patients with baseline HF
General 2.5 (2.3-
Medicaid 620 250,281 2.7) 1.0 (ref) 1.0 (ref)
11.4 (10.7-
SLE 837 73,299 12.2) 2.4 (2.2-2.7) 2.5 (2.3-2.8)
Diabetes 11.5 (11.0-
Mellitus 1,675 145,692 12.1) 4.0 (3.6-4.3) 2.7 (2.4-2.9)
*HF: Heart failure events by hospitalization ICD-9 diagnosis codes 402.01, 402.11,
402.91, 404.01, 404.11, 404.91, 404.03, 404.13, 404.93, and 428.xx, but excluding
398.91 rheumatic heart disease (Chen J, Circulation, 2013).
†Cohort: SLE cohort defined as >3 SLE ICD-9 codes (710.0), each separated by >30
days; DM cohort defined as >3 ICD-9 codes (249.XX, 250.XX, 357.2, 362.01-362.06,
366.41), 1:2 matched by age, sex to SLE cohort; General Medicaid cohort defined as
any non-SLE, non-DM ICD-9 code on same date as SLE index date, 1:4 matched by
age, and sex to SLE cohort
‡Rate: Rate of first HF hospitalization events per 1000 person-years of follow up
§HR: Hazard ratio for first HF hospitalization event adjusted for age, sex,
race/ethnicity, US region of residence, zip-code level socioeconomic status, Charlson
comorbidity index; Two separate Cox proportional hazard models: 1) including all
patients, 2) excluding patients who had baseline HF diagnosis
Disclosure: S. Chen, None; M. Barbhaiya, None; M. A. Fischer, None; H. Guan, None; C. H. Feldman, None; B. M.
Everett, None; K. H. Costenbader, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/heart-failure-hospitalizations-among-sle-

and-diabetes-mellitus-patients-compared-to-the-general-u-s-medicaid-population
Do Death Certificates Underestimate the Burden of Rare Diseases: The

Example of Systemic Lupus Erythematosus Mortality in Sweden
Titilola Falasinnu1, Marios Rossides2, Yashaar Chaichian3 and Julia F Simard4, 1Health Research and Policy, Stanford
University, Stanford, CA, 2Medicine Solna, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden,
3Medicine, Immunology & Rheumatology Division, Stanford School of Medicine, Stanford, CA, 4Division of
Epidemiology, Health Research and Policy Department, Stanford School of Medicine, Stanford, CA
SESSION INFORMATION
Background/Purpose: Routine data sources such as death certificates are used to estimate the burden or cost of disease in a
population. However, mortality due to rare diseases, e.g., systemic lupus erythematosus (SLE), that are significant sources of
premature mortality, is often ignored in mortality reports. The objective of this study was to determine the completeness of
SLE mention in the death register in Sweden and patterns of completeness by demographic factors.
Methods: A Swedish population-based cohort of individuals with prevalent SLE (the Swedish Lupus Linkage [SLINK];
2001-2013) was linked to the Cause of Death Register. All death records from subjects known to be deceased in the cohort
were reviewed and information regarding patient demographics (i.e., sex, age, region, place, and year of death) and causes of
death were extracted. Odds ratios (OR) and 95% confidence intervals (95% CI) for the absence of SLE on death certificates
were estimated using a multivariable-adjusted logistic model. We also estimated the degree of over- or underestimated SLE
mortality using the comparability ratio.
Results: Approximately 59% of decedents with SLE had SLE absent from their death certificates (n=1,802). The majority of
deceased individuals were aged 60-79 years at death (52%), female (81%), and born in Nordic countries (96%). In the
adjusted model, increasing age was associated with SLE being absent from death certificates among those in the established
cohort. Decedents 60-79 years old at death were approximately 2.5 times as likely to have SLE missing from their death
certificates compared with those <40 years (OR: 2.48, 95% CI: 1.34-4.58). Having renal failure listed on the death certificate
decreased the likelihood of SLE being absent (OR: 0.55, 95% CI: 0.41-0.73), while cancer increased this likelihood (OR:
2.35, 95% CI: 1.83-3.02). Death certificate data underestimated SLE mortality by 59% (comparability ratio 0.41 [95% 0.38-
0.43]).
Conclusion: SLE is greatly underreported as a cause of death on death certificates thereby underestimating the burden of
this disease. This may be due to ambiguity and disparate practices concerning the recording of comorbidities in death
certificates. Inadequate attention may be devoted to the contribution of lupus to cancer secondary to systemic inflammation
compared to lupus mortality related to direct organ involvement.
Disclosure: T. Falasinnu, None; M. Rossides, None; Y. Chaichian, None; J. F. Simard, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/do-death-certificates-underestimate-the-

burden-of-rare-diseases-the-example-of-systemic-lupus-erythematosus-mortality-in-sweden
Death Certificates Do Not Accurately Identify SLE Patients

Kelly Kaysen, Cristina Drenkard, Gaobin Bao and S. Sam Lim, Division of Rheumatology, Emory University School of
Medicine, Atlanta, GA
SESSION INFORMATION
Background/Purpose: Mortality rates are higher in SLE patients compared to the general population, and research on SLE
mortality is ongoing. The majority of mortality studies have relied on death certificates to identify SLE patients. However,
this approach may misclassify cases and include both false positives and negatives. The rate of misclassification on death
certificates is unclear. Using a large population-based registry of validated SLE patients, we sought to ascertain the accuracy
of death certificates in identifying SLE patients.
Methods: The Georgia Lupus Registry (GLR) is a population-based registry of validated SLE patients living in Atlanta,
GA from 2002-04. The state HIPAA exemption for surveillance allowed health care providers and facilities to provide
access to protected health information without written patient consent. Patients were validated by meeting ≥4 ACR criteria
or 3 ACR criteria with a final diagnosis of SLE by a board-certified rheumatologist. These patients were matched to the
Georgia Office of Vital Records death certificates through 2013. The primary, secondary, tertiary, and contributing causes of
death were identified on the death certificates using ICD-10 codes.
Results: State death certificates matched with 321 SLE patients from the GLR through 2013. Only 24.6% (79/321) of
patients had SLE listed on the death certificate. Characteristics of the deceased SLE patients are listed in the below table.
While there were no significant differences with race and sex, SLE patients captured in death certificates were much
younger at SLE diagnosis and died at a younger age.
Conclusion: In a population-based registry with many high-risk black SLE patients, SLE was recorded on the death
certificates of only 24.6% of deaths. SLE was listed more often on the death certificates of those who were younger at SLE
diagnosis and death, perhaps indicating more severe disease or increased awareness by the caring providers. Death
certificates do not accurately capture the full spectrum of SLE patients. Reliance on death certificates to obtain SLE
mortality data will underestimate the burden of the disease.
Characteristics of deceased SLE patients and identification of SLE on death

certificates
Characteristic Category Overall SLE captured in death certificate
(n=321) No (n=242) Yes (n=79) P Value

Sex, n (%) Male 44 (13.7) 37 (84.1) 7 (15.9)
0.15
Female 277 (86.3) 205 (74.0) 72 (26.0)
Race, n (%) White 58 (18.1) 47 (81.0) 11 (19.0)
0.27
Black 263 (81.9) 195 (74.1) 68 (25.9)
Age at diagnosis Mean ± SD
39.1 ± 17.6 41.0 ± 17.5 33.4 ± 16.6 0.0008
(years)
Age at death Mean ± SD
52.7 ± 17.3 55.5 ± 16.4 44.4 ± 17.6 <0.0001
(years)
Disclosure: K. Kaysen, None; C. Drenkard, None; G. Bao, None; S. S. Lim, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/death-certificates-do-not-accurately-

identify-sle-patients
Association of Ultraviolet-B Radiation and Risk of SLE Among Women in the

Nurses’ Health Studies
Medha Barbhaiya1, Jaime Hart2,3, Susan Malspeis4, Sara K. Tedeschi5, David J. Kreps5, Trang VoPham6, Jeffrey A.
Sparks7, Elizabeth Karlson5, Francine Laden2,3,8 and Karen H. Costenbader5, 1Rheumatology, Immunology and Allergy,
Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 2Department of Environmental Health, Harvard
T.H. Chan School of Public Health, Boston, MA, 3Department of Medicine, Brigham and Women's Hospital and Harvard
Medical School, Boston, MA, 4Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and
Harvard Medical School, Boston, MA, 5Division of Rheumatology, Immunology and Allergy, Brigham and Women's
Hospital and Harvard Medical School, Boston, MA, 6Department of Epidemiology, Harvard T. H. Chan School of Public
Health, Boston, MA, 7Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical
School, Boston, MA, 8Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
SESSION INFORMATION
Background/Purpose: Ultraviolet-B radiation (UV-B) exposure may lead to worsened photosensitivity, rashes, and
systemic flares among SLE patients. Although UV-B radiation damages keratinocytes and may result in production of novel
forms of autoantigens, it remains unknown whether UV-B exposure increases the risk of developing SLE. We aimed to
examine the association of UV-B exposure with risk of incident SLE in a large prospective cohort of women, examining
SLE risk overall and by subtypes defined by presence of anti-Ro/La antibodies (+anti-Ro/La) and/or cutaneous
manifestations most associated with UV exposure in SLE patients.
Methods: The Nurses’ Health Study (NHS) enrolled 121,701 U.S. female nurses in 1976; NHSII enrolled 116,430 in 1989.
Biennial questionnaires collected lifestyle, environmental, and medical data. Residential addresses were geocoded. Incident
SLE was confirmed by medical record review. National Aeronautics and Space Administration Total Ozone Mapping
Spectrometer and Ozone Monitoring Instrument gridded remote sensing images scaled to a 1 km spatial resolution predicted
average July noon-time erythemal UV-B (mW/m2) annually starting in 1980. Participants without UV-B data at baseline
were excluded. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression models across
tertiles of cohort-specific, time-varying cumulative average UV-B through one cycle prior to SLE onset. We examined SLE
risk overall and stratified by presence of anti-Ro/La or cutaneous manifestations (malar rash and/or photosensitivity) at
diagnosis through 2014 (NHS) or 2013 (NHSII), controlling for potential confounders. We also conducted a ‘lagged’
analysis by ending the exposure window two cycles prior to SLE diagnosis, as SLE symptoms may develop insidiously pre-
diagnosis.
Results: Mean age at SLE diagnosis was 49.3 (10.4) years among 286 SLE cases in NHS/NHSII. At SLE diagnosis, 13% of
women had +anti-Ro/La whereas 80% had either +anti-Ro/La or at least one cutaneous manifestation. Compared to the
lowest tertile of UV-B exposure, risk of overall SLE, SLE with +anti-Ro/La, or SLE with photosensitivity in the highest UV-
B tertile were increased, but not statistically significant in the main analysis (Table) or in lagged analyses. However, women
in the highest UV-B tertile had statistically significantly increased risks of SLE with malar rash (HR 1.68 [95% CI 1.08-
2.62]) (Table), but this was no longer significant in the lagged analysis (HR 1.41 [95% CI 0.88-2.25]).
Conclusion: Increasing cumulative UV-B exposure was not associated with risk of developing overall SLE. However,
among women at risk for SLE, living in areas with higher UV-B exposure was associated with increased risk of developing
SLE presenting with malar rash. Further studies are warranted to determine whether high UV-B exposure may play a role in
triggering SLE onset with malar rash.
Disclosure: M. Barbhaiya, None; J. Hart, None; S. Malspeis, None; S. K. Tedeschi, None; D. J. Kreps, None; T.
VoPham, None; J. A. Sparks, None; E. Karlson, None; F. Laden, None; K. H. Costenbader, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/association-of-ultraviolet-b-radiation-

and-risk-of-sle-among-women-in-the-nurses-health-studies
Impact of DMARD Treatment on Risk of Repeat Cardiovascular Events

Among Patients with Rheumatoid Arthritis, Psoriatic Arthritis, or Psoriasis
Jeffrey A. Sparks1, Tamara Lesperance2, Neil A. Accortt3 and Daniel H. Solomon4, 1Rheumatology, Immunology, and
Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 2DOCS Global, Inc., North Wales, PA,
3Center for Observational Research, Amgen, Inc., Thousand Oaks, CA, 4Brigham and Women's Hospital and Harvard
SESSION INFORMATION
Background/Purpose: Chronic inflammatory diseases such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), and
psoriasis (PsO) increase the risk of cardiovascular (CV) disease. However, it is unclear what factors, including DMARD
treatment, after a first CV event may affect risk of subsequent CV events. We estimated and compared the incidence of
subsequent CV events among patients with RA, PsA, or PsO who were being treated with DMARDs prior to the initial CV
event.
Methods: Patients with RA, PsA, or PsO, who experienced a major non-fatal CV event (acute myocardial infarction, stroke,
or cardiac revascularization) between 1/1/2006 and 6/30/2015 were identified in an administrative claims database. Index
date was defined as the hospital discharge date for the first non-fatal CV event during the study period. Eligible patients
were: continuously enrolled for 12 months prior to index date; had ≥1 DMARD claim (categorized as TNF inhibitor (TNFi),
conventional synthetic [csDMARD], or a non-TNFi biologic DMARD including tofacitinib) within 12 months prior to the
index date; and had ≥30 days of follow-up after index date. The primary outcome was the occurrence of any CV event
during the follow-up period. Incidence rates (IR) per 1,000 person-years with 95% confidence intervals (CI) were calculated
and age and sex standardized to the general population. The hazard ratio (HR) and 95% CI for a subsequent CV event was
estimated using Cox proportional hazard models. Patients who were not treated with any DMARD after initial CV event
were not included in the analyses.
Results: We identified 8,610 patients with RA, PsA, or PsO eligible for study. After the index date, 2,924 (34.0%) patients
used a TNFi, 4,813 (55.9%) used a csDMARD as monotherapy or combination, and 873 (10.1%) used a non-TNFi biologic
DMARD. Median follow-up time after initial CV event was 1.6 years. Patients using non-TNFi biologic DMARDs had
higher crude incidence rates of repeat CV events than those who used TNFi or csDMARDs (Table 1). The multivariate
adjusted hazard ratios for subsequent CV events were 0.98 (95% CI, 0.82-1.17) for csDMARDs, and 1.16 (0.86-1.57) for
other biologic DMARDs compared to TNFi (Table 2). RA diagnosis (as compared to PsO diagnosis) and heart failure
diagnosis in baseline were risk factors independently associated with increased risk of subsequent CV event.
Conclusion: In this large nationwide database reflecting typical clinical care, we found that type of DMARD use after initial
non-fatal CV event was not associated with risk for subsequent CV event among RA, PsA, and PsO patients. Predictors of
subsequent CV event included having RA and heart failure prior to initial CV event.
Table 1. Incidence of Subsequent CV Events among RA, PsA, PsO Patients

(n=9,529)
Other (non-
TNFi)
TNF Inhibitors csDMARDs Biologics
(n=2,924) (n=4,813) (n=873)
Subsequent CV events (stroke,
230 288 53
AMI, revascularization), n
Follow-up, person-years 2744.4 2984.7 482.0
Median follow-up per patient,
1.8 (0.8-3.5) 1.6 (0.7-3.1) 1.4 (0.6-2.6)
years (IQR)
Age- and sex-standardized
83.6 (53.3- 122.4 (60.6-
Incidence Rate (95% CI) per 1,000 75.2 (54.4-96.0)
113.9) 184.3)
person-years
Table 2. Hazard Ratios for Risk of Subsequent CV Events
among RA, PsA, PsO Patients (n=9,529)
Covariate Adjusted HR (95% CI)
Model 1 a
csDMARD vs. TNFi 1.03 (0.86-1.23)
Non-TNFi biologics vs. TNFi 1.23 (0.91-1.66)
Model 2 b
csDMARD vs. TNFi 0.97 (0.80-1.18)
Model 3 c
csDMARD vs. TNFi 0.98 (0.82-1.17)
Age, per 10 years 1.02 (0.94-1.10)
Male sex 1.13 (0.96-1.34)
RA vs. PsO 1.55 (1.00-2.39)
PsA vs. PsO 1.43 (0.85-2.40)
Heart failure 1.39 (1.13-1.72)
Diabetes mellitus 1.16 (0.97-1.39)
Renal disease 1.27 (0.96-1.67)
Pre-index oral glucocorticoid 1.14 (0.96-1.35)
use¥
aModel 1 was adjusted for age and sex.
bModel 2 was adjusted as model 1 plus disease indication, index

CV event, pre-index comorbidities (heart failure, chronic
pulmonary disease, diabetes mellitus, hyperlipidemia,
hypertension, obesity, unstable angina, renal disease), number of
pre-index unique DMARDs used, and baseline medication
exposures (statins, oral glucocorticoids, ACE inhibitors, beta
blockers).
cModel 3 adjusted model 2 via backwards elimination and the
following covariates were retained: age, sex, disease indication,
pre-index comorbidities (heart failure, diabetes mellitus, renal
disease), and pre-index oral glucocorticoid use.
¥Defined as use in the 12 months prior to index CV event.
Disclosure: J. A. Sparks, Amgen, 2; T. Lesperance, Amgen, 5; N. A. Accortt, Amgen, 3,Amgen, 1; D. H. Solomon,

Amgen, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/impact-of-dmard-treatment-on-risk-of-

repeat-cardiovascular-events-among-patients-with-rheumatoid-arthritis-psoriatic-arthritis-or-psoriasis
Higher Omega-6 to Omega-3 Fatty Acid Ratio Is Associated with Increased

Odds of Inflammatory Arthritis in a Health Fair Population Positive for Anti-
Citrullinated Protein Antibodies (ACPA)
Kristen J. Polinski1, Ryan W. Gan2, Elizabeth A. Bemis1, M. Kristen Demoruelle3, Michael J. Clare-Salzler4, V. Michael
Holers5, Kevin D. Deane6 and Jill M. Norris7, 1Epidemiology, Colorado School of Public Health, Aurora, CO, 2Colorado
School of Public Health, University of Colorado Denver, Aurora, CO, 31775 Aurora Ct, 1775 Aurora Ct, Aurora, CO,
4Experimental Pathology, University of Florida, College of Medicine, Gainesville, FL, 5Rheumatology Division, University
of Colorado School of Medicine, Aurora, CO, 6Division of Rheumatology, University of Colorado School of Medicine,
Aurora, CO, 7Department of Epidemiology, Colorado School of Public Health, Aurora, CO
SESSION INFORMATION
Background/Purpose: We previously found that lower levels of omega-3 fatty acids (n-3 FA) were associated with the
presence of inflammatory arthritis (IA) as well as risk of developing incident IA in ACPA+ individuals without IA at
baseline. Omega-6 fatty acids (n-6 FA) compete with n-3 FA for elongation and desaturation enzymes in the body that help
determine the pro- and anti-inflammatory potential of these FA and their derivatives. Western diets tend to have a high n-6 to
n-3 ratio that may promote the pathogenesis of inflammatory and autoimmune diseases. We examined the association
between n-6 FA levels and the presence of IA/rheumatoid arthritis (RA) in ACPA+ individuals.
Methods: At Colorado-based health fairs from 2008-2014, 47 subjects without a previous diagnosis of RA tested positive
for the ACPA, anti-cyclic citrullinated peptide (CCP3, Inova), and were recruited into a follow-up research study. At their
immediate post-health fair research visit (baseline), 10 of these ACPA+ subjects were identified as having disease-modifying
anti-rheumatic drug (DMARD)-naive IA. Of the 10 ACPA+ subjects with prevalent IA at baseline, 8 were classified as RA
by 2010 ACR/EULAR Criteria. Findings in those subjects with IA were compared to those without IA. Specifically, n-3 and
n-6 as percent of total lipids in red blood cell membranes (RBC) were measured. Logistic regression assessed the
associations between baseline IA and RBC n-6 FA%, as well as the n-6 to n-3 ratio.
Results: Subjects with IA at baseline were more likely to be ever smokers and test positive for rheumatoid factor and C-
reactive protein than those without IA (Table 1). In addition, we found that subjects with higher n-6 FA and linoleic acid
levels had higher odds of IA (Table 2). Furthermore, analysis of the n-6 to n-3 ratio demonstrated that higher total n-6 FA %
relative to total n-3 FA % in RBCs significantly increased the odds of IA by almost 3-fold (Table 2).
Conclusion: We found that a higher n-6 to n-3 ratio was associated with prevalent IA in this ACPA+ population. Building
off our previous work, this suggests a potential beneficial role of n-3 FAs in decreasing the risk of transitioning from ACPA
positivity to IA. Specifically, our findings herein suggest that decreasing the n-6 to n-3 FA ratio in the body, perhaps either
via n-3 FA supplementation or diet may play a role in decreasing the transition from an ACPA+ state to IA, findings that
warrant further investigation.
Table 1: Descriptive Characteristics by IA status at Baseline, Colorado Health Fair Population, 2008-2014
Variable Prevalent IA at Baseline No IA at Baseline p-value
(n=10) (n=37)
Age, yrs (mean ± SD) 55.9 (10.3) 55.9 (10.4) 0.996
Age ≥ 50 yrs 8 (80.0) 26 (70.3) 0.703
Sex: Female 8 (80.0) 21 (56.8) 0.277
Race/Ethnicity: non-Hispanic White 7 (70.0) 29 (78.4) 0.679
Education: > High school 8 (80.0) 32 (86.5) 0.630
Income: > $40,000 7 (77.8) 25 (71.4) 1
Smoking: Ever 9 (90.0) 16 (43.2) 0.012
Shared Epitope (SE)+ 7 (70.0) 16 (43.2) 0.168
Omega 3 supplement use 8 (80.0) 19 (51.3) 0.154
Rheumatoid Factor (RF)+ 6 (60.0) 5 (13.5) 0.006
C-Reactive Protein (CRP)+ 6 (60.0) 7 (18.9) 0.017
n-6 : n-3 ratio (mean ± SD) 4.00 (1.41) 3.14 (0.81) 0.093
All values reported as n(%) unless otherwise stated. Fisher Exact p-values presented for categorical variables. Satterthwaite
p-values reported for continuous variables.
Table 2: Adjusted analyses evaluating the relationship between omega-6 fatty acid % and IA at Baseline (N=47)
FA% in RBC OR (95% CI) p-value
n-6 : n-3 FA ratio 2.99 (1.11, 8.05) 0.030
Total n-6 FA 2.96 (1.12, 7.79) 0.028
Linoleic acid 2.63 (1.10, 6.29) 0.030
Gamma linolenic acid 4.91 (0.85, 28.35) 0.075
Arachidonic acid 0.81 (0.21, 3.22) 0.768
The n-6:n-3 FA ratio model adjusted for ever smoking status, SE, RF+, and CRP+; and the OR represents the odds of IA
for each unit difference in the n-6:n-3 ratio. The n-6 models adjusted for ever smoking status, n-3 FA supplement use, SE+,
RF+, and CRP+; and the ORs represent the odds of IA for a one standard deviation (SD) difference in the n-6 FA% in
RBC. The SD for these variables are as follows: Linoleic acid: 1.72, Gamma linolenic acid: 0.06, Arachidonic acid: 1.37,
Total n-6: 1.97.
Disclosure: K. J. Polinski, None; R. W. Gan, None; E. A. Bemis, None; M. K. Demoruelle, None; M. J. Clare-Salzler,
None; V. M. Holers, None; K. D. Deane, Inova Diagnostics, Inc., 5; J. M. Norris, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/higher-omega-6-to-omega-3-fatty-acid-

ratio-is-associated-with-increased-odds-of-inflammatory-arthritis-in-a-health-fair-population-positive-for-anti-citrullinated-
protein-antibodies-acpa
Publication Timeliness of the Randomized Controlled Trials of Drug Therapy

for Inflammatory Arthritis
Vyjayanthi Ganga1, Mohan Edupuganti2 and Nasim A. Khan3, 1St. Vincent Healthcare System, Little Rock, AR, 2Internal
Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 3Rheumatology, University of Arkansas for
Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR
SESSION INFORMATION
Background/Purpose: Timely publication of randomized controlled trials (RCTs) is crucial for their potential impact on
patient care. We assessed the publication timeliness of drug therapy RCTs of inflammatory arthritis.
Methods: The print issues (or online issues for online-only journal) of the 10 highest impact factor (IF) rheumatology
journals publishing original research and 5 highest IF internal medicine journals for the years 2013-2014 were searched
using Medline. Original parallel-design, non-phase-1 RCTs reports of drug therapy for inflammatory arthritis with clinical
primary outcome(s) were eligible. RCT completion dates were retrieved either from the manuscript or the respective trial
registry information in the manuscript. The dates of manuscript submission, acceptance, first online publication, and
publication in a print issue were used to calculate the intervals in the publication process of study RCTs. RCT characteristics
associated of with the time from trial completion to first (online or print) and final (typically print) available version were
assessed.
Results: Eligibility criteria were met by 67 RCTs. The study conditions were rheumatoid arthritis (68.7%),
spondyloarthropathy (20.9%), gout (6%) and others (4.5%). Experimental drug manufacturer fully or partially funded 56
(83.6%) RCTs. All RCTs had trial registry information (ClinicalTrials.gov for (58[86.6%]) RCTs). The experimental
interventions included biologics (73.1%), small molecule (14.9%), traditional disease modifying agent ([10.4%), and other
(1.5%). Most trials were multicenter (92.5%) and multinational (56.7%). RCT completion date was obtained from the
manuscript for 16 (23.8%) and trial registry record for 49 (73.1%) RCTs. Some dates such as manuscript submission and
acceptance were unreported for nearly 45% RCTs. Table shows the different time intervals in the publication process. The
first available version was published within a year of completion for 8 (12%) and within 2 years for 39 (58%) RCTs. Final
available version of RCTs with positive results (statistically significant result favoring the experimental intervention) was
available earlier [median (IQR): 25.5 (21.7-35) months for positive vs 32.5 (26.6-44.5) months, p = 0.04]. No significant
differences were noted in the time from RCT completion to first or final publication according to study condition, funding
source, experimental intervention type, and whether the RCT was multicenter or multinational.
Conclusion: There is a considerable time lag between the completion and publication of RCTs. Several crucial dates needed
to assess the publication timeliness were unavailable in the manuscripts. Clinical trial registries enabled publication
timeliness assessment. Advance online publication helps in early availability of trial results.
Table. Different intervals from RCT completion to final publication.

Time interval N* Median Range**
(IQR)**
RCT completion to manuscript 35 20 (13-30) 14-100
submission
Manuscript submission to acceptance 36 4 (3.5-6) 1.5-12
Manuscript acceptance to first 56 1 (0.7-1.4) 0-3.5
published version
First version to final published 67 4.6 (1.5-9) 0-15
version
RCT completion to first version 65 21.7 (18- 4.6-98.5
32.9)
RCT completion to final version 65 27.5 (22.5- 13.8-99.5
39.6)
*RCTs with available data, **months
Disclosure: V. Ganga, None; M. Edupuganti, None; N. A. Khan, None.

View Abstract and Citation Information Online - http://acrabstracts.org/abstract/publication-timeliness-of-the-
randomized-controlled-trials-of-drug-therapy-for-inflammatory-arthritis
The Effect of Anti-TNF Therapy on Work Productivity and Activity

Impairment in Patients with Rheumatoid Arthritis, Ankylosing Spondylitis
and Psoriatic Arthritis over One Year – Real Life Data from the Czech
Biologics Registry Attra
Jakub Zavada1, Lenka Szczukova2, Karel Pavelka3 and Jiri Vencovsky3, 1Institute of Rheumatology, Prague, Czech
Republic, 2Institute of Biostatistics and Analyses. Faculty of Medicine, Masaryk University, Brno, Czech Republic,
3Institute of Rheumatology and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech
Republic
SESSION INFORMATION
Background/Purpose: The ATTRA registry captures more than 95% of patients with RA, PSA or AS treated with
biologics in the Czech Republic (CZ). In CZ, anti-TNF-therapy is reimbursed for RA if DAS28>5.1 despite therapy with
csDMARDs, for PSA if disease is not Òadequately controlledÓ with csDMARDs and for AS if BASDAI>4 and CRP/ESR
elevated above normal. To assess the effect of anti-TNF therapy on work productivity using the Work Productivity and
Activity Impairment-Specific Health Problem (WPAI-SHP) questionnaire in patients with RA, PSA and AS in the real life
setting using the data from ATTRA.
Methods: WPAI-SHP scores were collected for all patients enrolled in ATTRA since 2012 at baseline and after 12 months
of anti-TNF exposure. BionŠive patients with RA (n=352), AS (n=442) and PSA (n=133) starting anti-TNF therapy with
available baseline data on demography, disease duration and physical function, and WPAI-SHP at baseline and at 12 months
were included in this analysis. Patients older than 60 years, on maternity leave or students were excluded. Only patients
working for pay at baseline were assessed for WPAI-SHP summary scores: absenteeism (mean % work time missed),
presenteeism (mean % productivity loss at work), overall work impairment (mean % overall work productivity loss), and
activity impairment (mean % productivity loss in regular activities). Regression analyses were performed to analyse the
predictors of improvement in WD overall work impairment one year.
Results: Baseline characteristics were significantly different between diagnoses (Table 1). Working status changed
significantly only in patients with RA (employed 69→64%, p=0.013), but not in AS (77→78%) or PSA (77→73%). In
patients employed for pay both at baseline and after 12 months, all WPAI-SHP scores improved significantly over one year
of anti-TNF therapy (Table 2). Patients with AS, younger age and more pronounced functional impairement (HAQ) at start
of anti-TNF therapy had most profit in terms of improvement in overall work impairment over one year (table 3).
Conclusion: In the real life setting of the CZ, anti-TNF therapy effectively reduced absenteeism, presenteeism, activity
impairment and work impairment over one year in employed patients with RA, AS and PSA.
Acknowledgements: Supported by project 00023728 of Ministry of Health, CZ.

Table 1. Baseline characteristics
RA (n = AS (n= PSA (n=
p-value*
352) 442) 133)
257 (73.0 104 (23.5 < 0.001
Female %) %) 58 (43.6 %) ABC
Disease
7.1 ± 5.7 7.0 ± 6.7 7.5 ± 7.2 0.245
duration
Age at start of < 0.001
anti-TNF 47.2 ± 8.9 39.5 ± 8.6 44.4 ± 9.1 ABC
therapy
HAQ 1.5 ± 0.5 1.2 ± 0.5 1.2 ± 0.6 < 0.001 AB
Post-hoc analysis (with Bonferroni correction): statistically
significant difference btw groups A) RA vs. AS, B) RA vs.
PSA, C) AS vs. PSA. Values or N (%) or mean (SD)
Table 2. The effect of one year of anti-TNF therapy on WPAI-SHP components

across diagnoses.
Mean Number
12 change of
Dg. WPAI –SHP component Baseline P-value*
months after 12 assessed
months patients
12.8
Absenteeism 5.1 (18.5) 7.7 (30.3) 203 < 0.001
(27.9)
52.1 27.6 24.5
Presenteeism 183 < 0.001
(21.9) (20.9) (26.3)
RA
53.9 28.7 25.2
Overall work impairment 183 < 0.001
(22.8) (22.0) (26.9)
62.4 36.0 26.4
Activity impairment 352 < 0.001
(21.4) (23.0) (27.7)
10.6
Absenteeism 3.5 (15.8) 7.1 (28.0) 307 < 0.001
(25.6)
53.1 21.1 32.0
(22.2) (18.0) (24.9)
AS
54.8 21.8 33.0
(22.6) (18.8) (25.5)
60.7 27.3 33.5
(22.1) (21.4) (26.4)
Absenteeism 5.7 (17.3) 4.2 (18.4) 1.5 (24.6) 90 0.135
43.9 15.3 28.6
(24.0) (16.2) (24.5)
PSA 45.2 15.9 29.3
(25.0) (16.8) (25.1)
57.4 26.2 31.2
(24.6) (21.3) (26.5)
Values are mean %(SD). * Wilcoxon paired test for difference between baseline and 12
months within each WPAI score.
Table 3 Prediction of improvement in overall work
impairment
Univariate analysis Multivariate analysis
β(95% CI) p-value β (95% CI) p-
Predictor value
Diagnosis: RA reference reference
Diagnosis: AS 7.83 (3.01; 0.001 6.67 (1.12; 0.019
12.65) 12.23)
Diagnosis: 4.128 (-2.555; 0.226 5.85 (-0.79; 0.084
PSA 10.812) 12.50)
Gender (male) reference reference
Gender -5.10 (-9.52; 0.024 -2.87 (-7.65; 0.238
(female) -0.67) 1.90)
Age at start of -0.41 (-0.65; 0.001 -0.35 (-0.61; 0.006
anti-TNF -0.17) -0.10)
therapy
Disease -0.25 (-0.59; 0.151 -0.19 (-0.52; 0.252
duration 0.09) 0.14)
Ln (CRP) 3.64 (1.62; < 0.001 1.90 (-0.10; 0.062
5.67) 3.90)
HAQ 11.49 (7.33; < 0.001 14. 21 (9.99; < 0.001
15.64) 18.43)
Disclosure: J. Zavada, None; L. Szczukova, None; K. Pavelka, None; J. Vencovsky, Samsung Bioepis Co., Ltd., Biogen,
5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-effect-of-anti-tnf-therapy-on-work-

productivity-and-activity-impairment-in-patients-with-rheumatoid-arthritis-ankylosing-spondylitis-and-psoriatic-arthritis-
over-one-year-real-lif
Increase in Prevalence of Psoriasis Arthritis over Time: Analysis of Claims

Data from 65 Million People in Germany from 2009 to 2012
Philipp Sewerin1, Matthias Schneider2, Benedikt Ostendorf1 and Ralph Brinks3, 1Department and Hiller-Research-Unit for
Rheumatology, Heinrich-Heine University, Düsseldorf, Germany, 2Policlinic for Rheumatology & Hiller Research Centre
for Rheumatology, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany, 3Department and Hiller-Research-Unit
for Rheumatology, Heinrich-Heine University, Duesseldorf, Germany
SESSION INFORMATION
Background/Purpose: Epidemiological studies are important contributors for our understanding of psoriatic arthritis (PsA).
Currently, there are no data about temporal trends of prevalence of PsA on the population level. The aim of this study is to
estimate the annual age- and sex-specific prevalence of diagnosed PsA in Germany during 2009 to 2012.
Methods: Complete diagnosis data from about 80% of the overall German population from 2009 to 2012 were screened for
physician diagnosed and ascertained PsA. Diagnoses are based on claims data from all insurances of the German statutory
health insurance (SHI) system. Quality checked claims data were provided by a governmental data trustee. After
determining the age- and sex-specific prevalence of PsA for each of the years from 2009 to 2012, trend tests for age-
standardized and age-specific prevalence in men and women were applied.
Results: In 2009, a total of 127 thousand patients with diagnosed and ascertained PsA were identified in 64.6 million people
from the German SHI. In the following years 2010 to 2012, 138, 146, and 156 thousand people with diagnosed PsA have
been observed, respectively. The age-standardized prevalence increases from 1.8 to 2.1 per mil in men (p-trend = 0.009), and
from 2.1 to 2.5 per mil in women (p-trend = 0.01). The age-specific prevalence of PsA for men and women increases
linearly from age group <20 to a peak of about 60 years of age. After age 60, the age-specific prevalence is steeply
decreasing. In virtually all age groups, there is evidence for an increase of the age-specific prevalence with time in men and
women. The highest increases are in the age groups 60+.
Conclusion: These data from about 65 million people insured in the German SHI for the first time indicate that there is an
increasing prevalence of PsA on the population level. A selection bias is likely to be present, because the roughly 20% of the
overall German population not included in our analysis is known to have other health risks (mainly privately insured
people). However, our results refer to the vast majority of the German population and the 127 to 156 thousand people with
diagnosed PsA. The analysis cannot be adjusted for potential confounders other than age and sex (e.g., socio-economic
position or presence of co-morbidities).
Disclosure: P. Sewerin, None; M. Schneider, None; B. Ostendorf, None; R. Brinks, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/increase-in-prevalence-of-psoriasis-

arthritis-over-time-analysis-of-claims-data-from-65-million-people-in-germany-from-2009-to-2012
Increasing Population Burden of Psoriatic Disease in Ontario, Canada – a

Longitudinal Cohort Study
Lihi Eder1,2, Jessica Widdifield3, Cheryl F. Rosen4, Dafna D Gladman2,5, Raed Alhusayen6, Michael Paterson7, Stephanie
Cheng7, Shirin Jabbari7, Willemina Campbell8, Sasha Bernatsky9 and Karen Tu7, 1Women's College Research Institute,
Women's College Hospital, Toronto, ON, Canada, 2Medicine, University of Toronto, Toronto, ON, Canada, 3University
Health Network, Toronto, ON, Canada, 4Dermatology, Toronto Western Hospital, University of Toronto, Toronto, ON,
Canada, 5Rheumatology, University Health Network, Toronto, ON, Canada, 6Sunnybrook Research Institute, Sunnybrook
Health Sciences Centre, Toronto, ON, Canada, 7Institute for Clinical Evaluative Sciences, Toronto, ON, Canada,
8Rheumatology, Toronto Western Hospital, Toronto, ON, Canada, 9Divisions of Rheumatology and Clinical Epidemiology,
Research Institute of the McGill University Health Centre, Montreal, QC, Canada
SESSION INFORMATION
Background/Purpose: There is limited information on the epidemiology of psoriasis and psoriatic arthritis (PsA) in North
America. The aims of this study were to estimate the prevalence and incidence rates of psoriasis and PsA and their temporal
trends in Ontario, Canada.
Methods: A retrospective cohort analysis was performed in Ontario health administrative databases. The following
validated algorithms were used for case definition: 1) Psoriasis: diagnosis in hospitalization records or at least 2 psoriasis
diagnostic codes assigned by any physician (specificity 99%, sensitivity 52%, PPV 62%); 2) PsA: diagnosis in
hospitalization records or a combination of: [1 psoriasis code by any physician or 1 prescription of topical anti-psoriatic
treatment] and 2 diagnostic codes of spondyloarthritis at least 1 by a rheumatologist (specificity 100%, sensitivity 52%, PPV
66%). The crude and age and sex-standardized prevalence and incidence rates of psoriasis were calculated from 2000 to
2015 in the general population. For PsA, results are reported from 2008 onwards due to a change in billing code in 2006.
Results: Among the 10,757,627 individuals aged 20 years and older living in Ontario in 2015, we identified 263,586 and
16,144 patients with psoriasis, and PsA, respectively, resulting in overall crude psoriasis and PsA cumulative prevalence of
2.25% and 0.14%, respectively. For psoriasis, the age and sex-standardized prevalence increased from 1.43% in 2000 to
2.24% in 2015 (Figure 1). For PsA, the age and sex-standardized prevalence increased from 0.07% in 2008 to 0.13% in 2015
(Figure 2). In contrast, the incidence rates of both diseases remained relatively stable.
Conclusion: These findings enhance our understanding of the Canadian epidemiology of psoriatic disease and burden for
healthcare resources planning. Although our previous validation work showed that administrative data under captures
psoriatic disease the prevalence and incidence rates of psoriasis and PsA in Ontario were comparable to European
populations. The steady increase in the prevalence of psoriasis and PsA over the past decade may be attributable to
population growth, an aging demographic, and increase in patients seeking medical care.
Disclosure: L. Eder, None; J. Widdifield, None; C. F. Rosen, None; D. D. Gladman, None; R. Alhusayen, None; M.
Paterson, None; S. Cheng, None; S. Jabbari, None; W. Campbell, None; S. Bernatsky, None; K. Tu, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/increasing-population-burden-of-

psoriatic-disease-in-ontario-canada-a-longitudinal-cohort-study

The Epidemiology of Psoriatic Arthritis in Israel – a Population-Based Study
Lihi Eder1,2, Arnon Dov Cohen3, Ilan Feldhamer4, Sari Greenberg-Dotan4, Eraz Batat4 and Devy Zisman5, 1Women's
College Research Institute, Women's College Hospital, Toronto, ON, Canada, 2Medicine, University of Toronto, Toronto,
ON, Canada, 33Chief Physician’s Office, Central Headquarters, Clalit Health Services, Tel Aviv, Israel, 4Chief Physician’s
Office, Central Headquarters, Clalit Health Services, Tel Aviv, Israel, 5The Ruth and Bruce Rappaport Faculty of Medicine,
Technion, Haifa, Israel
SESSION INFORMATION
Background/Purpose: There is limited information on the epidemiology of Psoriatic Arthritis (PsA) in general and in
Middle Eastern populations in particular. The aims of this study were to estimate the prevalence and incidence rates of PsA
and their temporal trends in the general population in Israel.
Methods: In this study, we derived a cohort of adult patients with PsA from the database of Clalit Health Services (CHS),
Israel’s largest health fund, with over 4.4 million members (52% of Israel’s population). PsA cases were identified if they
fulfilled one of the following conditions: 1) PsA diagnosis assigned at least once by a rheumatologist; 2) permanent
diagnosis code assigned by a family physician combined with use of synthetic or biologic disease modifying antirheumatic
drugs; 3) PsA code listed in a hospitalization discharge summary. This algorithm had positive predictive value, sensitivity
and specificity of 90.5%, 88.7% and 88.1%, respectively.
We calculated crude and age- and sex-standardized prevalence and incidence rates of PsA from 2006 to 2015 in the general
population. The variation in PsA prevalence was assessed in relation to several demographic factors.
Results: Among the 2,931,199 individuals aged 18 years and older registered in the CHS database in 2015, 4490 patients
had a diagnosis of PsA (322 incident cases), resulting in overall crude prevalence and incidence rates of 0.153% (95% CI
0.149%, 0.158%) and 10.9 (95% CI% 9.8, 12.3) per 100,000 population, respectively. The prevalence of PsA in Israel
doubled between 2006 and 2015 (0.073% to 0.153%). In contrast, the global incidence rate remained stable, with a gradual
increase in the incidence among individuals aged 51 to 70 years (Figure 1). PsA is associated with Jewish ethnicity, high
socioeconomic status, rural residency and higher body mass index (Table 1).
Conclusion: The prevalence and incidence of PsA in Israel are within the range of previous estimates from Southern
European populations. An increase in the prevalence of PsA was observed over the past decade in the general population in
Israel.
Table 1 – Prevalence of PsA by demographic characteristics
Prevalence OR 95% CI
(%)
Sex
Male 0.147 0.93 0.87, 0.98
Female 0.159
Socioeconomic status
High 0.204 1.76 1.63, 1.90
Middle 0.167 1.44 1.35, 1.55
Low 0.116
Ethnicity
Jewish 0.175 2.13 1.95, 2.33
Arab 0.082
Residential Area
Urban 0.151 0.82 0.73, 0.92
Rural 0.184
BMI
>30 0.266 2.57 2.37, 2.80
25-30 0.200 1.94 1.78, 2.10
Disclosure: L. Eder, None; A. D. Cohen, None; I. Feldhamer, None; S. Greenberg-Dotan, None; E. Batat, None; D.
Zisman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-epidemiology-of-psoriatic-arthritis-

in-israel-a-population-based-study
Accuracy of Canadian Administrative Health Data in Identifying Patients

with Psoriasis and Psoriatic Arthritis Using Primary Care Medical Records
As the Reference Standard
Lihi Eder1,2, Jessica Widdifield3, Cheryl F. Rosen4, Dafna D Gladman2, Raed Alhusayen5, Michael Paterson6, Stephanie
Cheng6, Shirin Jabbari6, Willemina Campbell7, Sasha Bernatsky8 and Karen Tu6, 1Women's College Research Institute,
Women's College Hospital, Toronto, ON, Canada, 2Medicine, University of Toronto, Toronto, ON, Canada, 3University
Health Network, Toronto, ON, Canada, 4Dermatology, Toronto Western Hospital, University of Toronto, Toronto, ON,
Canada, 5Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, 6Institute for Clinical
Evaluative Sciences, Toronto, ON, Canada, 7Rheumatology, Toronto Western Hospital, Toronto, ON, Canada, 8Divisions of
Rheumatology and Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, QC,
Canada
SESSION INFORMATION
Background/Purpose: We assessed the accuracy of algorithms to identify patients with psoriasis and psoriatic arthritis
(PsA) in administrative health data in a validation set derived from primary care electronic medical records (EMRs), and
contrasted the effect of different algorithms on the population-based prevalence of psoriasis and PsA in Ontario, Canada.
Methods: We developed a validation set using a sample of 2210 adult patients with suspected psoriasis and PsA. This
sample was identified through a targeted search for psoriatic disease-related terms in the EMRs of a random sample of
30,424 patients in the primary care Electronic Administrative data Linked Database (EMRALD) in Ontario, Canada. The
reference standard for classifying patients with physician-recorded psoriasis or PsA, was confirmed using a retrospective
chart abstraction. All patients were then linked to health administrative data to assess the performance of the different
algorithms combining physician billing and hospitalization diagnostic codes, medications and procedures for identification
of patients with psoriatic disease. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value
(NPV) of each algorithm were computed. Estimated population prevalence of psoriasis and PsA were then calculated for
each algorithm.
Results: Based on our reference standard we identified 1028 patients with psoriasis and 90 patients with PsA which resulted
in overall psoriasis and PsA prevalence of 3.4% and 0.29%, respectively. The majority of the patients with PsA (67%) had a
documented diagnosis by a rheumatologist, while only 29% of the psoriasis patients had a documented diagnosis by a
dermatologist. The accuracy of selected psoriasis and PsA case definition algorithms are presented in Table 1. All algorithms
had excellent specificity (97-100%). However, the sensitivity and PPV of the algorithms were low to modest, ranging from
28% to 72% for sensitivity and 43% to 72% for PPV. The population prevalence of psoriasis (1.07-2.4%) and PsA (0.12-
0.14%) ranged depending on the algorithm used for case definition.
Conclusion: The accuracy of identifying patients with psoriasis and PsA in Ontario health administrative databases varies
widely, however when we applied these algorithms to the entire Ontario population, we observed similar patterns and a
steady increase in prevalence, irrespective of the algorithm used. We recommend that PsA receives a distinct outpatient
diagnostic code to improve case ascertainment.
Table 1 – The accuracy of selected psoriasis case definition algorithms
Prevalence
SensitivitySpecificity PPV NPV (per 100

Algorithm (%) (%) (%) (%) population)
1 H or 1 P ever 71% 97% 43% 99% 2.40%
1 H or 1 P ever by a specialist 50% 98% 48% 98% 1.69%
1 H or 2 P ever 52% 99% 62% 98% 1.76%
1 H or 2 P ever at least 1 by a 43% 99% 63% 98% 1.46%
specialist
1 H or 2 P in 1 years 44% 99% 63% 98% 1.49%
1 H or 2 P in 2 years 47% 99% 63% 98% 1.58%
1 H or 2 P in 3 years 48% 99% 63% 98% 1.61%
1 H or 3 P ever 41% 99% 71% 98% 1.38%
1 H or 3 P in 2 years 28% 100% 72% 98% 1.07%
1 H or 3 P in 3 years 32% 100% 72% 98% 1.14%
1 H or 1 P ever or 1 72% 97% 42% 99% 2.42%
prescription of anti-psoriatic
treatment
1 H or 2 P ever or 1 55% 99% 60% 98% 1.86%
treatment
1 H or 2 P ever or 2 54% 99% 61% 98% 1.82%
treatment
H: Hospitalization psoriasis code; P=physician psoriasis diagnostic code; Specialist
= dermatologist; anti-psoriatic medications=tar, topical or oral retinoids, topical
vitamin D derivate, IL-17 inhibitor, PDE4 inhibitor, IL-12/23 inhibitor
Table 2 – The accuracy of selected PsA case definition algorithms

Prevalence
SensitivitySpecificity
PPV NPV (per 100
Algorithm (%) (%) (%) (%) population)
1 H or (1 P(Ps) and 1 P(SpA)) ever 53% 100% 53% 100% 0.13%
1 H or ((1 P(Ps) ever or 1 prescription 55% 100% 54% 100% 0.14%
of topical anti-psoriatic treatment) and
1 P(SpA) ever)
2 P(SpA) ever)
2 P(SpA) ever at least 1 by a
specialist)
3 P(SpA) ever at least 1 by a
specialist)
H: Hospitalization PsA code; P(Ps)=physician psoriasis diagnostic code;
P(SpA)=physician spondyloarthritis diagnostic code; Specialist = rheumatologist;
topical anti-psoriatic treatment=tar, retinoids or vitamin D derivate
Disclosure: L. Eder, None; J. Widdifield, None; C. F. Rosen, None; D. D. Gladman, None; R. Alhusayen, None; M.
Paterson, None; S. Cheng, None; S. Jabbari, None; W. Campbell, None; S. Bernatsky, None; K. Tu, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/accuracy-of-canadian-administrative-

health-data-in-identifying-patients-with-psoriasis-and-psoriatic-arthritis-using-primary-care-medical-records-as-the-
reference-standard
Incidence and Clinical Characteristics of Active Tuberculosis in a Cohort of

Patients with Inflammatory Arthritis Treated with TNF-Inhibitors
Ana Maria Gheorghiu1, Alexandru Garaiman2, Alexandra Radu2, Alina Soare3, Victoria Arama4, Dragos Bumbacea5,
Rucsandra Dobrota6, Raida Oneata7, Simona Pintilie2, Mihaela Milicescu7, Ioan Ancuta7, Andrei Martin2, Mariana Sasu1,
Claudia Ciofu1, Liviu Macovei1, Victor Stoica7, Mihai Bojinca7 and Carina Mihai8, 1Carol Davila University of Medicine
and Pharmacy,Internal Medicine and Rheumatology Department ,,Dr.I.Cantacuzino'' Clinical Hospital, Bucharest, Romania,
2Internal Medicine and Rheumatology, CANTACUZINO HOSPITAL, Carol Davila University of Medicine and Pharmacy,
Bucharest, Romania, 3Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen,
Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany, 4Infectious Diseases 1 Department, Matei
Bals National Institute for Infectious Diseases, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania,
5Department of Pneumology, Elias Emergency University Hospital, Carol Davila University of Medicine and Pharmacy,
Bucharest, Romania, 6Department of Rheumatology, Center of Experimental Rheumatology, University Hospital Zurich,
Zurich, Switzerland, 7Carol Davila University of Medicine and Pharmacy, Internal Medicine and Rheumatology
Department, Cantacuzino Clinical Hospital, Bucharest, Romania, 8Internal Medicine and Rheumatology Dept., Cantacuzino
Clinical Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
SESSION INFORMATION
Background/Purpose:
Tuberculosis (TB) is a major concern in patients receiving TNF inhibitors (TNFi).
Objectives: To assess the incidence of active TB and the efficacy of TB prevention measures in a large, single-center cohort
of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) receiving TNFi.
Methods:
Data of all patients in whom treatment with TNFi was initiated in our rheumatology clinic from January 1st 2002 until
December 31st 2015 have been retrospectively analysed. The cohort was divided into 2 groups per the mandatory latent TB
infection (LTBI) screening method at baseline: tuberculin skin test (group TST), and QuantiFERON®-TB Gold test (group
QFT). The incidence of active TB was analysed for each group and compared to TB incidence data in general population.
Results:
653 patients were included (344 RA, 52 PsA, 257 AS); 324 patients belonged to the TST and 329 to the QFT group. The
number of active TB cases/ time of exposure to TNFi (person-years, PY) was 17/2002.6 and 7/1041.2 respectively,
accounting for an incidence of 848.9 and 672.3 cases per 105 PY, about 8 times higher (8.3 and 8.8 for TST, respectively
QFT group) than the average TB during the period of exposure to TNFi. LTBI reactivations per total TB cases were only
4/17 and 2/7, respectively, too few to identify statistically significant differences between the 2 LTBI screening protocols.
Only 10 patients had pulmonary TB, whereas the rest were disseminated TB (8 cases), TB pleurisy and/or pericarditis (4
cases), one mediastinal lymph node TB and one isolated hepatic TB. Using Pearson chi-square test, we found no significant
differences between LTBI group and active TB (Table 1).
Conclusion:
In our cohort, new infection TB exceeds reactivation TB, suggesting the necessity of periodical LTBI re-screening.
Table 1. LTBI screening results and TB occurrence in the 653 TNFi-treated patients. (Pearson χ2 test)
TST QFT All p value
(n=324) (n=329) (n=653)

Positive
immuno- 52 63 115
<0.001*
diagnostic test at (16.0%) (19.1%) (17.6%)
baseline
Active TB 17 7 (2.1%) 24 0.185*
(5.2%) (3.7%)
Reactivation TB 4 (1.2%) 2 (0.6%) 6 **
(0.9%)
New infection 13 5 (1.5%) 18 0.052*
TB (4.0%) (2.8%)
Total TB 848.9 672.3 788.5 -
incidence
(per 105 PY)

Maximal period 2002- 2011- 2002- -
of TNFi 2016 2016 2016
exposure in
group
Mean TB 102.3 76.7 102.3 -
incidence in
Romania in the
respective time
period (per 105
PY)
TB incidence 8.3 8.8 7.7 0.88†
patients/general
population
*Pearson χ2 test comparing TST and QFT. **Reactivation TB cases were too few to perform statistical testing †Pearson χ2
test comparing total TB incidence in the TST and QFT groups to the average TB incidence in our region in the respective
period of exposure.
Disclosure: A. M. Gheorghiu, None; A. Garaiman, None; A. Radu, None; A. Soare, None; V. Arama, None; D.
Bumbacea, None; R. Dobrota, None; R. Oneata, None; S. Pintilie, None; M. Milicescu, None; I. Ancuta, None; A.
Martin, None; M. Sasu, None; C. Ciofu, None; L. Macovei, None; V. Stoica, None; M. Bojinca, None; C. Mihai, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/incidence-and-clinical-characteristics-of-

active-tuberculosis-in-a-cohort-of-patients-with-inflammatory-arthritis-treated-with-tnf-inhibitors

Mental Health in Patients with Axial Spondyloarthritis: Increasing Our
Understanding of the Disease. Results from the Spanish Atlas
Marco Garrido-Cumbrera1, Victoria Navarro-Compán2, David Galvez-Ruiz1, Carlos Jesus Delgado Dominguez1, Pilar
Font-Ugalde3, Olta Brace1, Pedro Zarco4, Jorge Chacon-Garcia1 and Pedro Plazuelo-Ramos5, 1Universidad de Sevilla,
Seville, Spain, 2Rheumatology, Hospital Universitario La Paz, Madrid, Spain, 3Rheumatology service, IMIBIC/Reina Sofia
Hospital/University of Cordoba, Cordoba, Spain, 4H Fundación Alcorcón, Alcorcón, Spain, 5CEADE, Madrid, Spain
SESSION INFORMATION
Background/Purpose: This study’s aim was to assess the association between sociodemographic characteristics, disease
progression, and mental health comorbidity with risk of mental disorders (RMD).
Methods: In 2016 a sample of 680 axSpA patients was interviewed as part of the Spanish Atlas. To quantify the RMD,
Goldberg’s General Health Questionnaire (GHQ-12) scale was employed. Possible RMD predictors analysed were:
sociodemographic characteristics (age, gender, being part of a couple, patient association membership, job status); disease
characteristics (BASDAI, spinal stiffness ranging from 0-3, functional limitation in 18 daily activities ranging from 0-3); and
mental health comorbidities (depression and anxiety). All clinical variables showed a Cronbach’s alpha coefficient
guaranteeing the reliability of the scales used. First, a descriptive analysis was employed to describe the sample and study
variables. Second, we performed univariate correlation and homogeneity analyses between each predictor (independent
variable) and RMD (GHQ-12). Third, selection of variables that showed statistical significance in the univariate analyses in
order to conduct a multiple hierarchical and stepwise regression analysis.
Results: All variables except educational level and thoracic stiffness showed significant univariant correlation with RMD.
BASDAI, functional limitation and age showed higher coefficient (R = 0.543, R = 0.378, R = -0.174, respectively). Multiple
Hierarchical regression analysis showed as sociodemographic variables explained in great detail the RMD (R2 = 83.2%). By
contrast, having established sociodemographic as a control variable, the inclusion of depression and anxiety to the model
increase the R2 value to just 0.6% (p = 0.001), while the inclusion of variables related to the disease characteristics add 5.5%
(p = 0.000) to the GHQ-12 punctuation variability. The only variables presenting a significant coefficient different from 0
were BASDAI (0.52, p = 0.000) and functional limitation (0.14, p = 0.004). This suggests that once the sociodemographic
and mental commorbidity variables are established, a change to BASDAI levels or functional limitation impacts the GHQ-
12 score. In the stepwise regression analysis, four variables (BASDAI, functional limitation, association membership,
cervical stiffness) showed a significant relation to GHQ-12 and explained the majority of RMD variability. BASDAI
displayed the highest explanatory degree (R2 = 0.875).
Table 1. Sample characteristics (n = 474, unless other specified).

Variables Values (means ± SD or percentage)
Age, mean ± SD 45.43 ± 10.78
Sex, No. of men 233 (49.16%)
Having a couple, No. of participants (N=444) 386 (86.94%)
Education level, No. of university studies 185 (39.30%)
Job status, No. of unemployed 68 (14.35%)
Association Membership 227 (47.89%)
BASDAI, mean ± SD (N=442) 5.49 ± 2.17
Cervical stiffness, No. (N=447) 201 (44.97%)
Thoracic stiffness No. (N=435) 186 (42.76%)
Lumbar stiffness No. (N=458) 288 (62.88%)
Functional Limitation, mean ± SD (N=473) 27.54 ± 12.78
Depression, No. (%) (N=474) 99 (20.89)
Anxiety, No. (%) (N=474) 134 (28.27)
GHQ-12, mean ± SD 18.30 ± 8.01
Conclusion: Patients at certain sociodemographic levels are more prone to present a higher BASDAI. Taking these
conditions for granted, the degree of disease progression measured by BASDAI is a good indicator of RMD. Therefore, in
those with higher disease activity, psychiatric evaluation and intervention should be considered within the medical treatment.
Disclosure: M. Garrido-Cumbrera, None; V. Navarro-Compán, None; D. Galvez-Ruiz, None; C. J. Delgado

Dominguez, None; P. Font-Ugalde, None; O. Brace, None; P. Zarco, None; J. Chacon-Garcia, None; P. Plazuelo-
Ramos, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/mental-health-in-patients-with-axial-

spondyloarthritis-increasing-our-understanding-of-the-disease-results-from-the-spanish-atlas
Association between Smoking with Spinal Level of Stiffness and Functional

Limitation in Patients with Axial Spondyloarthritis: Results from the Spanish
Atlas
Marco Garrido-Cumbrera1, Victoria Navarro-Compán2, Jorge Chacon-Garcia1, Jordi Gratacos-Masmitja3, David Galvez-
Ruiz1, Eduardo Collantes Estevez4, Pedro Zarco5 and Olta Brace1, 1Universidad de Sevilla, Seville, Spain, 2Rheumatology,
Hospital Universitario La Paz, Madrid, Spain, 3Rheumatology, Hospital Parc Taulí, Sabadell - Barcelona, Spain,
4Universidad de Cordoba, Cordova, Spain, 5H Fundación Alcorcón, Alcorcón, Spain
SESSION INFORMATION
Background/Purpose: Smoking has been associated with greater disease activity and radiographic progression in patients
with Axial Spondyloarthritis (ax-SpA). In addition, radiographic damage has been linked to greater functional limitation.
However, clarification is still being sought as to whether or not this association exists. To investigate the association between
smoking and both the area of spinal stiffness and functional limitation in patients with ax-SpA.
Methods: A sample of 680 patients diagnosed with ax-SpA was interviewed during 2016 as part of the Spanish Atlas, which
aims to promote early referral and improve healthcare and the use of effective treatments in patients with ax-SpA. Tobacco
consumption was recorded as: Smoker (62.4%), Occasional Smoker (8.9%) and Non-Smoker (28.7%). Spinal stiffness was
assessed in the three different vertebral areas: cervical, dorsal and lumbar.To determine de degree of functional limitation we
used a composed index which includes the sum of the degree of limitation in the 18 daily activities well established
(dressing, grooming, bathing, tying shoelaces, moving around the home, stairs, getting to/out of bed, toilet, shopping,
preparing meals, eating, cleaning, walking, using public transportation, going to the doctor, driving, physical exercise, sexual
relations) using an ordinal variable (0=none, 1=little, 2=some and 3=moderate). A descriptive analysis was used to compare
the level of stiffness (chi-squared test) and the mean degree of limitation (Kruskal-Wallis test) in the different groups of
smokers consumptions. Regression analysis was also used to assess the relation between smoking and degree of limitation
(0-54).
Results: 53% were females, mean age 46 years and 77.1% were HLA-B27+. The percentage of patients with stiffness in the
lumbar region was significantly higher in habitual/occasional smokers than in non-smokers (89.0%, 93.8%, 83.5%
respectively; p<0.01) (Table). The mean degree of functional limitation increased with tobacco consumption, although this
difference was not statistically significant (47.9 ± 12.1 vs. 45.1 ± 11.5 vs. 44.8 ± 13.7 respectively; p=0.2). However,
regression analysis showed a statistically significant correlation between smoking and functional limitation (r=0.096;
p=0.02).
Table 1. Relationship between tobacco consumption and spinal stiffness levels in patients with ax-SpA
Occasional Non
Smoker
smoker smoker
P X2
Cervical
84.2% 77.1% 73.1% 0.171 9.044
stiffness
Thoracic
76.0% 76.6% 72.4% 0.408 6.141
stiffness
Lumbar
89.0% 93.8% 83.5% 0.002 20.518
stiffness
Conclusion: Smoking in patients with ax SpA is associated to greater stiffness in the lumbar region, but is not related to
stiffness in the cervical or dorsal regions. Additionally, smoking is associated to the degree of functional limitation in these
patients.
Disclosure: M. Garrido-Cumbrera, None; V. Navarro-Compán, None; J. Chacon-Garcia, None; J. Gratacos-

Masmitja, None; D. Galvez-Ruiz, None; E. Collantes Estevez, None; P. Zarco, None; O. Brace, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/association-between-smoking-with-

spinal-level-of-stiffness-and-functional-limitation-in-patients-with-axial-spondyloarthritis-results-from-the-spanish-atlas
Use of Mutual Information Theory in Development and Refinement of a

Predictive Model for Early Identification of Ankylosing Spondylitis
Atul A. Deodhar1, Cody Garges2, Oodaye Shukla2, Theresa Arndt2, Tara Grabowsky2 and Yujin Park3, 1Oregon Health &
Science University, Portland, OR, 2HVH Precision Analytics, LLC, King of Prussia, PA, 3Novartis Pharmaceuticals
Corporation, East Hanover, NJ
SESSION INFORMATION
Background/Purpose: Delayed diagnosis and treatment of ankylosing spondylitis (AS) contribute to the economic, physical
and psychological burden on patients and their caregivers. The objective of this analysis was to refine a previously
developed predictive mathematical model for AS1 based on features observed in the medical histories of patients with and
without a diagnosis of AS to aid in the earlier identification of AS.
Methods: This retrospective cohort study used administrative claims data from > 182 million patients in the Truven Health
MarketScan® Commercial and Medicare Supplemental Databases from January 2006 to September 2015 (Segment 1) and
October 2015 to November 2016 (Segment 2). The AS population in Segment 1 included all patients with ≥ 2 diagnoses of
AS (ICD-9-CM 720.0) by rheumatologists ≥ 30 days apart who had ≥ 12 months of continuous enrollment prior to first AS
diagnosis. Control patients were matched by age, sex, enrollment period and geographic location and were randomly
selected from the same database. Mutual information was used to identify features that differentiated AS from the control
population; select features were then used as inputs in development of a suite of predictive models using data from Segment
1.1 The optimized predictive model was then tested by observing whether patients predicted to have AS in Segment 1
subsequently received an ICD-10-CM AS diagnosis code (M45.x or M08.1) in Segment 2.
Results: In the initial study, 3 iterations of the predictive risk model (Models 1, 2 and 3a/3b) were developed using data
from patients with ≥ 1 ICD-9-CM AS diagnosis during Segment 1, with each subsequent model iteration using additional
AS-specific queries to reflect a more real-world situation.1 A 2-stage model (Models 4 and 5) was built using patients with ≥
2 ICD-9-CM AS diagnoses during Segment 1 to improve performance. Model 4 identified patients with AS from the general
control population in the database (Figure 1A). To further improve precision, Model 5 was built using 50,000 random
patients in Segment 1 who scored above a 0.5 in Model 4 (i.e., were more like patients with AS) as a new control population
(Figure 1B). Models 4 and 5 were then combined to identify new patients with AS in Segment 2; of the ≈ 20 million
patients who tracked across Segment 1 and Segment 2, 742 patients had an ICD-10-CM AS diagnosis in Segment 2 who did
not have an ICD-9-CM diagnosis in Segment 1.
Conclusion: Predictive models for AS diagnosis were developed and refined in this US administrative claims database.
Work is ongoing to compare the sensitivity and positive predictive value of these predictive models versus more traditional
linear regression models, and future research will validate the model in a separate, commercially insured population
database.
Reference:
1.) Garges C, et al. Presented at the ISPOR 22nd Annual International Meeting; May 20-24, 2017; Boston, MA; [Poster
PRM85].
Disclosure: A. A. Deodhar, Eli Lilly, GSK, Janssen, Novartis, Pfizer, Sun Pharma and UCB, 2,AbbVie, Eli Lilly, Janssen,
Novartis, Pfizer and UCB, 9; C. Garges, HVH Precision Analytics, LLC, 3; O. Shukla, HVH Precision Analytics, LLC, 3;
T. Arndt, HVH Precision Analytics, LLC, 3; T. Grabowsky, HVH Precision Analytics, LLC, 3; Y. Park, Novartis
Pharmaceuticals Corporation, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/use-of-mutual-information-theory-in-

development-and-refinement-of-a-predictive-model-for-early-identification-of-ankylosing-spondylitis
Persistence, Discontinuation, and Switching Patterns Among Ankylosing

Spondylitis Patients Newly Initiating Biologic Therapy
Theresa Hunter1, Krista Schroeder2, Sarah Al Sawah2 and David Sandoval Calderon2, 1Global Patient Outcomes and Real
World Evidence, Eli Lilly and Company, Indianapolis, IN, 2Eli Lilly and Company, Indianapolis, IN
SESSION INFORMATION
Background/Purpose: The primary goals of treating Ankylosing Spondylitis (AS) patients are to maximize long-term
health-related quality of life through control of symptoms and inflammation, prevention of progressive structural damage,
and preservation of function. With two classes of biologic disease modifying agent (bDMARD) currently available,
providers have more options to offer to their patients, especially after failing a first biologic. The objective of this study was
to describe treatment patterns (persistence, discontinuations, and switch to a 2nd or 3rd line biologic) in the 2 years
following the initiation of biologic therapy in AS patients.
Methods: Adult patients with ≥ 2 AS diagnoses were included in this retrospective analysis of medical and pharmacy claims
data from the Truven MarketScan Commercial Claims database. AS patients who newly initiated a biologic agent
(etanercept, adalimumab, golimumab, infliximab, or certolizumab pegol) during the period from January 1, 2009, to
December 31, 2013 were selected and indexed on their first biologic during the time period. All patients were required to
have a 1-year pre-index clean period of all biologic therapy and continuous enrollment (medical and prescription) 1-year
pre-index and 2-years post-index. Patients were excluded if they had ≥2 diagnostic codes for any of the following
conditions: Rheumatoid Arthritis, Juvenile Idiopathic Arthritis, Psoriatic Arthritis, Crohn’s Disease, Ulcerative Colitis,
Plaque Psoriasis, Hidradenitis Suppurarativa, or Uveitis. Demographic, clinical, and treatment patterns were analyzed.
Treatment patterns included switching to a new biologic (2 and 3+ lines), discontinuation (≥90-day gap in therapy), or
persistence (no gaps in therapy ≥90-days) during the 2-year follow-up period.
Results: A total of 1,372 AS patients met the inclusion criteria for this study. The majority of patients (61.7%) were male
and the overall mean age of patients was 43.8 years. Adalimumab was the index biologic for 44.1% of patients, followed by
etanercept (40.9%), infliximab (10.6%), golimumab (4.3%), and certolizumab pegol (0.1%). During the follow-up period,
33.1% of patients (n=454) were persistent on their index biologic, while 66.9% (n=918) either discontinued their index
biologic therapy or switched to a 2nd line biologic. Among the patients who discontinued their first index biologic, 39.1%
(n=359) switched to a 2nd line biologic. Of those with a 2nd line biologic, 20.1% (n=72) had 3 or more different biologics
prescribed during the follow-up period. From 2009 to 2013, the proportion of new biologic users initiating 2nd line biologic
increased over time from 25.2% to 28.8% (average for all four years = 26.2%).
Conclusion: This study suggests that approximately two-thirds of AS patients newly initiating on a biologic do not remain
on the index therapy 2 years post initiation. More work is needed to understand the reasons for non-persistence and the
increasing trend of second line biologic use in this population.
Disclosure: T. Hunter, Eli Lilly and Company, 3; K. Schroeder, Eli Lilly and Company, 3; S. Al Sawah, Eli Lilly and
Company, 1,Eli Lilly and Company, 3; D. S. Calderon, Eli Lilly and Company, 1,Eli Lilly and Company, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/persistence-discontinuation-and-

switching-patterns-among-ankylosing-spondylitis-patients-newly-initiating-biologic-therapy
Survival and Years of Potential Life Lost in Connective Tissue Disease and Vasculitis;
Data from the Norwegian Connective Tissue Diseases and Vasculitis Registry
(NOSVAR)
Torhild Garen1, Karoline Lerang1, Anna Maria Hoffmann-Vold2, Helena Andersson1, Øyvind Midtvedt1, Karin Kilian1, Ragnar
Gunnarsson1, Birgir Gudbrandsson1, Gudrun Norby1, Oyvind Molberg2 and Øyvind Palm1, 1Department of Rheumatology, Oslo
University Hospital, Oslo, Norway, OSLO, Norway, 2Department of Rheumatology, Oslo University Hospital, Oslo, Norway, Oslo,
Norway
SESSION INFORMATION
Background/Purpose:
Survival is decreased in patients with connective tissue diseases (CTDs) and vasculitis, however few studies have compared the
mortality between the specific diseases prospectively by similar methods for patient’s selection. Here, we aimed to compare survival,
standard mortality rates (SMR) and premature mortality between diagnoses of CTDs and vasculitis .
Methods:
All patients included in NOSVAR diagnosed from January 1, 1999 to December 31, 2016, in total 2148 patients were followed up until
death or study end. Fifteen controls matched for each individual patient for year of birth, sex and residence area was randomly selected
from the Norwegian Central Public Population Register. All controls were alive at time of patients diagnosis. Kaplan-Meier survival
probabilities and curves were used to determine survival, and the difference between patients and controls was estimated by the log-rank
test (Mantel Cox). In the Standardized mortality ratio (SMR) the number of deaths was divided by number of years of observation for
each diagnosis and calculated as the ratio between the observed and expected numbers of death. The years of potential life lost (YPLL)
was defined as the years a person would have lived if he or she had not died prematurely (here defined as 60 years of age). The YPLL
for each death in patients are summed to represent the total years of potential life lost for all patients in each patient-group. The YPLL
(60) rate is found by dividing YPLL by years of observation under the age of 60 in each group.
Results:
During a mean (SD) follow-up time of 9,2 years (4,7), 280/2148 (13%) patients deceased compared to 2885/32186 (9%) of the controls
(p<0.001). Patient’s characteristics and demographics are shown in Table 1. Compared to controls, the lowest 5-and 10 years survival
was seen in diffuse cutaneous systemic sclerosis (dcSSc) (79 % and 60%), (p<0.001), Antisynthetase syndrome (86% and 73%),
(p<0.001), and limited systemic sclerosis, (89% and 75%), (p<0.001) Figure 1). For ANCA vasculitis and controls 5 years survival was
91% vs 95% and 10 years survival was 80 % vs 87%., (p=0.030). Highest SMR was observed for dSSc (5,8) and Antisynthetase
syndrome (4,1)(Figure 2) The sum of YPLL60 among patients was 493 years and in matched controls 115 years, indicating a four-fold
increase in premature deaths among the patients. The mean YPLL60 was highest in SLE and Takayasu with 19 and 15 years lost,
respectively. Both lcSSc and dcSSc had a mean of 7 years lost YPLL60. The ranking of annual rate of YPLL60 for each disease is
shown in (Figure 3)
Conclusion:
We show that there is a difference in survival, mortality and YPLL60 among the different CTDs and vasculitis. Methods used
supplement each other and highlights the different aspects of outcome among the diagnoses. Systemic sclerosis and Antisynthetase
syndrome had the lowest 5 and 10 years survival and the highest rate of premature mortality, but the mean loss of years before 60 years
of age were higher in individuals with Takayasus and SLE.
Disclosure: T. Garen, None; K. Lerang, None; A. M. Hoffmann-Vold, None; H. Andersson, None; Ø. Midtvedt, None; K. Kilian,
None; R. Gunnarsson, None; B. Gudbrandsson, None; G. Norby, None; O. Molberg, None; Ø. Palm, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/survival-and-years-of-potential-life-lost-in-

connective-tissue-disease-and-vasculitis-data-from-the-norwegian-connective-tissue-diseases-and-vasculitis-registry-nosvar
Hair Treatments and the Risk of Systemic Lupus Erythematosus: the Michigan
Lupus Epidemiology & Surveillance (MILES) Program
Emily C. Somers1, Christina Mrukowicz2, Wendy Marder1, W. Joseph McCune3, Afton L. Hassett4, Suzanna Zick5, Siobán Harlow6
and Caroline Gordon7, 1Internal Medicine-Rheumatology, University of Michigan, Ann Arbor, MI, 2University of Michigan, Ann
Arbor, MI, 3Int Med/ Rheum, University of Michigan, Ann Arbor, MI, 4Rheumatology, Emory University, Atlanta, GA, 5Department of
Family Medicine, University of Michigan, Ann Arbor, MI, 6Epidemiology Department- School of Public Health, Obstetrics and
Gynecology- Medical School, University of Michigan, Ann Arbor, MI, 7School of Immunity and Infection, College of Medical and
Dental Sciences, University of Birmingham, Birmingham, United Kingdom
SESSION INFORMATION
Session Title: ARHP Epidemiology and Public Health Poster
Background/Purpose:
Hair dye exposure has been reported as a risk factor for systemic lupus erythematosus (SLE) and connective tissue diseases, though
conflicting results exist. We performed a population-based case-control study based on the MILES Program to determine whether hair
dyes, rinses and permanents were associated with SLE risk.
Methods:
The MILES Program includes a population-based cohort of SLE cases and controls from southeast Michigan. Detailed data on history
of hair treatment exposures prior to SLE diagnosis (i.e., hair dyes, rinses and permanents to curl/straighten hair) were collected,
including details regarding frequency, duration, colors used and timing in relation to SLE diagnosis. For controls, we generated a
reference date in lieu of a diagnosis date using multiple imputation (SAS PROC MI). Multivariable logistic regression, adjusted for
covariates (race, ethnicity, age, county of residence, family income, and history of beauty salon occupation), was used to assess
association between hair product use and case/control status.
Results:
In this study population of 654 participants (462 SLE cases, 192 controls), 584 (89.3%) were female, 288 (44%) black, and mean age at
baseline visit was 53 years. Primary analyses were restricted to females, due to small numbers in males. In female cases vs controls, hair
dye use was reported in 35.1% of cases/38.8% of controls; hair permanents in 55.8%/56.7%; hair rinses in 19.7%/19.6%; and history of
beauty salon occupation in 9.1%/6.5%. Odds ratios (95% CIs) adjusted for covariates were: hair dye [0.94 (0.63, 1.40)]; hair rinse [0.91
(0.57, 1.46)]; hair permanent [0.86 (0.57, 1.30)]. Likewise, duration of use, dark color hair dyes, and history of beauty salon occupation
were not found to be associated with SLE. Results from analyses stratified by race were similar.
Conclusion:
This population-based case-control study is one of the largest studies to examine the relationship between hair product use and lupus.
We found no evidence of an association between any of the treatment types – hair dye, hair rinse, or hair permanents – and risk of lupus.
Disclosure: E. C. Somers, None; C. Mrukowicz, None; W. Marder, None; W. J. McCune, None; A. L. Hassett, None; S. Zick,
None; S. Harlow, None; C. Gordon, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/hair-treatments-and-the-risk-of-systemic-lupus-

erythematosus-the-michigan-lupus-epidemiology-surveillance-miles-program
Arthritis Impact at the State and County Level — United States, 2015
Kamil E. Barbour1, Suson Moss2, Janet Croft2, Jennifer M. Hootman3, Louise Murphy4, Kristina Theis2, Yan Wang2, Hua Lu2, Teresa
J. Brady1 and Charles G. Helmick2, 1Arthritis Program, Centers for Disease Control and Prevention, Atlanta, GA, 2Centers for Disease
Control and Prevention, Atlanta, GA, 3Centers for Disease Control and Prevention, Kennesaw, GA, 4Division of Population Health,
Centers for Disease Control and Prevention, Atlanta, GA
SESSION INFORMATION
Background/Purpose: Arthritis, a leading cause of disability, affects 54.4 million US adults. By knowing the state and county level
arthritis impact, state-level public health professionals can determine appropriate resource allocation, understand existing disparities,
and target dissemination of evidence-based interventions that can reduce arthritis impact.
Methods: To summarize the arthritis burden at the state and county-level, we used data from the 2015 Behavioral Risk Factor
Surveillance System, an annual, random-digit–dialed landline and cellphone survey that is representative of the noninstitutionalized
adult population aged ≥18 years in the 50 states and territories. Arthritis was defined as a "yes" to "Has a doctor or other health
professional ever told you that have some form of arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia?” For each state, we
calculated arthritis prevalence overall and among those with specific comorbidities; among adults with arthritis, we estimated the
prevalence of arthritis-attributable activity limitation (AAAL), social participation restriction (SPR), severe joint pain (SJP), physical
inactivity (PIA), leisure walking (LW), and arthritis management behaviors; the latter category on management was calculated for the
13 states that collected this information. Age-adjusted (standardized to the projected 2000 U.S. population) percentages were calculated
for all prevalence estimates shown below.
Results: For the 50 states and DC in 2015, the median prevalence of arthritis was 23.0% (range: 17.2-33.6%). For arthritis-attributable
impact measures among adults with arthritis, median (range) prevalence for AAAL was 49.7% (40.4-59.4%); SPR was 19.7% (12.6-
30.4%); and SJP was 29.7% (20.3-46.0%). Median (range) prevalence of arthritis among adults with obesity, heart disease, and diabetes
was 30.9% (24.6-41.2%), 44.5% (25.6-72.6%), and 37.3% (27.1-53.7%), respectively. Median (range) prevalence of PIA and LW
among adults with arthritis was 35.0% (23.1-47.9%) and 48.0% (38.5-59.5%), respectively. For arthritis management, median (range)
prevalence of being told to exercise for their arthritis and lose weight if overweight/obese to manage arthritis symptoms was 58.5%
(52.3-61.9%) and 44.5% (35.1-53.2%), respectively; median prevalence of attending a self-management education (SME) course was
14.5% (range=9.1-19.0%). Arthritis prevalence varied considerably by county (range: 13.5%-34.8%).
Conclusion: Arthritis was common -- particularly among those with comorbid conditions -- and varied substantially at both the state
and county level. Adults with arthritis have a high prevalence of characteristics that impact quality of life (e.g., AAAL, SPR, and SJP),
and a large percentage are PIA and do not participate in LW. Participation in a SME course among adults with arthritis remains low;
approximately half of health care providers recommended self-management behaviors. Greater use of evidence-based physical activity
and SME interventions could reduce pain and improve function and quality of life for all adults with arthritis including those with
comorbidities.
Disclosure: K. E. Barbour, None; S. Moss, None; J. Croft, None; J. M. Hootman, None; L. Murphy, None; K. Theis, None; Y.
Wang, None; H. Lu, None; T. J. Brady, None; C. G. Helmick, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/arthritis-impact-at-the-state-and-county-level-

united-states-2015
The Prevalence of Patellofemoral Osteoarthritis in China: A Multi-Center

Population-Based Cross-Sectional Study
Zhanglai Li1, Qiang Liu1, Changsheng Zhao2, Yuqing Zhang3, Xiaowei Li1 and Jianhao Lin1, 1Arthritis Clinic and Research Center,
Peking University People's Hospital,Peking University, Beijing, China, 2Peking University International Hospital, Peking University
International Hospital, Beijing, China, 3School Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital,
SESSION INFORMATION
Background/Purpose: To describe the prevalence and risk factors of patellofemoral osteoarthritis (OA) in a Chinese population.
Methods: A multi-center population-based cross-sectional survey was conducted in 2015 in Beijing, Henan and Ningxia, China. 4138
residents aged &ge50 years were recruited using a cluster sampling method. Subjects completed a home interview (including socio-
demographic factors, history of knee injury, joint symptoms, job-related physical activity and work history) and had weight-bearing
posterior-anterior semi-flexed view of radiographs at tibiofemoral joints and skyline view of radiographs at patellofemoral joints (PF).
Height was measured twice for each subject, using a wall-mounted studio meter and weight was assessed using a balance beam scale
with a precision to 0.1 kg. BMI was calculated as weight in kilograms divided by height in meters squared. Radiographs were read by
two orthopedic surgeons. Each knee was evaluated for the presence of osteophytes (OST), joint space narrowing (JSN) on a 0-3 scale
based on OARSI atlas. If two readers disagreed on a patient's OA status, adjudication session was held with third orthopedic surgeon
present. Radiographic OA (ROA) at PF joint was defined if OST score was &ge2 or if JSN score was &ge2 with concurrent grade 1
OST in the PF joint. The kappa for inter-rater reliability was 0.71-0.85 and the intra-rater reliability was 0.85-0.91 prior to adjudication.
Knee pain symptoms were asked for each participant using the following questions &Prime Did knee pain occur when going up and
down stairs on most days in the past month? &Prime PF symptomatic OA (SxOA) was recorded if both pain and ROA were present at
the same knee. We examined the relations of a set of risk factors to the prevalence of PF ROA and SxOA using logistic regression
model.
Results: Of 4138 subjects recruited, 533 (12.9%) subjects were excluded from the analysis due to missing knee radiographs. Of the
remaining (n=3605) 35.6% (n=1283) were men, mean age was 62.89&plusmn7.58 years, and mean BMI was 25.05&plusmn3.60
kg/m2; 64.4% (n=2322) were women, mean age was 60.86&plusmn7.50 years, and mean BMI was 26.26&plusmn3.81 kg/m2. The
prevalence of PF ROA and SxOA was 23.7% and 14.1%, respectively. As shown in Table 1, women, older age, higher BMI, history of
knee injury and bicycling &ge2 hours per day lasted less than 30 years were significantly associated with both PF ROA and SxOA. Few
years of education was associated with high prevalence of PF ROA, whereas standing &ge2 hours per day lasted less than 30 years was
associated with PF SxOA. No statistical significant difference was observed between job-related physical activity and PF ROA/SxOA.
Conclusion: Our study suggests that prevalence of PF ROA and SxOA was high in China. Several potential risk factors for prevalent
PF OA were identified and need to be verified in the future prospective cohort studies.
Table 1. Association between risk factor with PF ROA/SxOA

Potential risk factors Level Radiographic patellofemoral OA Symptomatic patellofemoral OA
OR (95% CI) P-value OR (95% CI) P-value
Sex 1.23 (1.01,1.49) 0.034 1.33 (1.06,1.67) 0.015
Education 0.80 (0.66,0.97) 0.026 0.82 (0.65,1.05) 0.113
Age 1.06 (1.04,1.07) &lt0.001 1.06 (1.05,1.08) &lt0.001
BMI 1.12 (1.10,1.15) &lt0.001 1.12 (1.09,1.15) &lt0.001
History of knee injury No
Yes 1.38 (1.04, 1.83) 0.026 1.74 (1.28, 2.39) 0.001
Duration of physical activity at work, year
Standing &ge2 hours 0 1.0 1.0
per day 1-29 1.12 (0.87,1.44) 0.396 1.33 (1.00,1.77) 0.048
30+ 0.86 (0.61,1.21) 0.387 0.99 (0.71,1.37) 0.942
Walking &ge2 hours per 0 1.0 1.0
day 1-29 1.05 (0.81,1.35) 0.131 0.94 (0.69,1.29) 0.712
30+ 0.91 (0.64,1.30) 0.298 0.79 (0.52,1.21) 0.284
Bicycling &ge2 hours 0 1.0 1.0
per day 1-29 1.33 (1.01,1.74) 0.042 1.43 (1.04,1.97) 0.027
30+ 1.16 (0.84,1.61) 0.358 1.38 (0.71,1.37) 0.915
Bending &ge2 hours per 0 1.0 1.0
day 1-29 1.06 (0.81,1.40) 0.651 1.26 (0.81,1.94) 0.309
30+ 1.04 (0.71,1.53) 0.825 1.04 (0.71,1.52) 0.837
Squatting &ge30 0 1.0 1.0
minutes per day 1-29 1.17 (0.74,1.56) 0.699 1.17 (0.87,1.57) 0.308
30+ 1.08 (0.40,1.10) 0.113 1.28 (0.85,1.94) 0.232
Lifting &ge10kg object 0 1.0 1.0
per day 1-29 1.20 (0.95,1.53) 0.133 1.23 (0.92,1.65) 0.169
30+ 1.17 (0.74,1.84) 0.497 1.36 (0.82,2.23) 0.230
Climbing &ge2 hours 0 1.0 1.0
per day 1-29 1.39 (0.75,2.60) 0.300 1.21 (0.56,2.58) 0.630
30+ 0.83 (0.37,1.86) 0.826 1.29 (0.52,3.20) 0.582
Disclosure: Z. Li, None; Q. Liu, None; C. Zhao, None; Y. Zhang, None; X. Li, None; J. Lin, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-prevalence-of-patellofemoral-osteoarthritis-in-

china-a-multi-center-population-based-cross-sectional-study
Sex Differences in Depressive Symptom Subtypes in Knee Osteoarthritis

Alan Rathbun1, Megan Schuler2, Elizabeth Stuart3, Michelle Shardell4, Michelle S. Yau5 and Marc Hochberg6, 1Epidemiology and
Public Health, University of Maryland School of Medicine, Baltimore, MD, 2Rand Coportation, Boston, MA, 3Mental Health,
Biostatistics, and Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 4Translational
Gerontology Branch, National Institute on Aging, Baltimore, MD, 5Institute for Aging Research, Hebrew SeniorLife, Harvard Medical
School, Boston, MA, 6Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
SESSION INFORMATION
Background/Purpose: Knee osteoarthritis (OA) is characterized by structural changes in subchondral bone and degradation of articular
cartilage, but the pathology does not necessarily lead to pain and functional limitations. Latent and modifiable factors, such as
depression, may contribute to or worsen knee OA symptoms. However, depression is clinically heterogeneous and presentation may
manifest differently by subtypes and by sex. The objectives were to identify depressive symptom subtypes, examine sex differences
across subtypes, and evaluate clinical correlates. Methods: Eligible participants (n=4490) were enrolled in the Osteoarthritis Initiative
(OAI) and had or were at risk for symptomatic knee OA. Latent class analysis was applied to symptomology measured by the 20-Item
Center for Epidemiological Studies Depression Scale to identify homogenous subtypes with similar patterns of depressive symptoms at
study enrollment. Subtype prevalence and item-response probabilities, an indicator of severity within subtype, were estimated separately
in men and women. Posterior probability estimates were used to assign each participant to the subgroup for which he or she had the
highest probability of membership. Clinical characteristics, including body mass index (BMI), Charlson comorbidity, gait speed,
analgesic use, pain severity, and radiographic evidence of knee OA (Kellgren-Lawrence grade ≥ 2), were compared across subtypes by
sex. Results: Four depressive symptom subtypes were identified: “No Symptoms,” “Moderate,” “Moderate-Melancholic,” and
“Severe.” Item-response probabilities and prevalence estimates significantly differed by sex (P = <0.001). “No Symptoms” was more
common in men (79.8%) than women (77.5%) and had low item-response probabilities across all symptoms. “Moderate” was
characterized by sadness and anhedonia and occurred more frequently in men (12.2%) than women (11.2%); however, item-response
probabilities were higher in women, indicating greater severity. “Moderate-Melancholic” and “Severe” were differentiated from other
subtypes by fatigue, loss of appetite, and insomnia and were more common in women (7.0% and 4.2%, respectively) than men (6.4%
and 1.7%, respectively); yet, item-response probabilities were higher in men, suggesting greater severity. Comorbidity scores, gait
speed, pain scores, and analgesic use were significantly associated with subtype membership among both sexes; radiographic evidence
of knee OA was only significant in men, while BMI was only significant in women (Table 1). Conclusion: Study findings indicate the
presence of four distinct depressive symptom subtypes that differ in prevalence and clinical presentation by sex among persons who
have or are at risk for symptomatic knee OA. Understanding variation in concurrent depressive symptoms among knee OA patients will
help inform tailored treatment strategies.
Table 1. Baseline clinical characteristics among men and women enrolled in the Osteoarthritis
Initiative by depressive symptom subtype (N=4490).
Men (n=1881)
Variable No Symptoms Moderate Moderate-Melancholic Severe
(n % or mean sd) (n=1540) (n=208) (n=103) (n=30) P Value
BMI 28.75 4.07 28.93 4.26 29.38 4.00 28.46 5.24 0.429
Charlson Comorbidity 0.39 0.89 0.52 1.03 0.47 0.85 0.79 1.35 0.025
Gait Speed 1.37 0.20 1.31 0.22 1.31 0.24 1.3 0.22 <0.001
Analgesic Use 406 26.50 58 27.90 44 42.70 57 57.10 <0.001
WOMAC Pain 1.86 2.70 2.62 3.70 3.99 3.77 3.6 3.92 <0.001
K-L Grade ≥ 2 613 39.80 98 47.10 58 56.30 15 50.00 0.002
Women (n=2609)
Variable No Symptoms Moderate Moderate-Melancholic Severe
(n % or mean sd) (n=2086) (n=268) (n=145) (n=110) P Value
BMI 28.14 5.07 29.37 5.63 29.57 6.04 30.39 6.15 <0.001
Charlson Comorbidity 0.31 0.68 0.55 1.07 0.60 1.13 0.68 0.94 <0.001
Gait Speed 1.32 0.21 1.25 0.21 1.21 0.26 1.18 0.22 <0.001
Analgesic Use 667 32.00 96.00 36.00 64 44.40 58 52.70 <0.001
WOMAC Pain 2.16 2.99 3.25 3.88 3.87 4.51 4.43 4.63 <0.001
K-L Grade ≥ 2 897 43.00 132 49.30 73 50.30 51 46.40 0.093
BMI, body mass index; K-L, Kellgren-Lawrence; SD, standard deviation; WOMAC, Western
Ontario & McMaster Universities Osteoarthritis Index.
Disclosure: A. Rathbun, None; M. Schuler, RAND, 3; E. Stuart, None; M. Shardell, None; M. S. Yau, None; M. Hochberg, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/sex-differences-in-depressive-symptom-subtypes-in-

knee-osteoarthritis
Smoking Signicantly Reduces Effectiveness and Long-Term Survival of Biologic

Treatment in Patients with Rheumatoid Arthritis
Roger Rolon Campuzano1, Andrea Lujan Coronel Ale1, Osvaldo Luis Cerda1, Fernando Dal Pra1, Emilce E Schneeberger1, María de
los Angeles Correa2, Marcos Rosemffet1, Emilio Buschiazzo3, Rodrigo Garcia Salinas4, Silvia Papasidero5, Belén Barrios5, Hernán
Maldonado Ficco6 and Gustavo Citera7, 1Section of Rheumatology, Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina,
Buenos Aires, Argentina, 2Section Rheumatology, Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina, Buenos Aires,
Argentina, 3Section of Rheumatology, Hospital Señor del Milagro, Salta, Argentina, Salta, Argentina, 4Section of Rheumatology,
Hospital Italiano de La Plata, Buenos Aires, Argentina, La Plata, Argentina, 5Section of Rheumatology, Hospital General de Agudos
“Dr. E. Tornú”, Buenos Aires, Argentina, Buenos Aires, Argentina, 6section of Rheumatology, Clinica Regional del Sud, Córdoba,
Argentina, Córdoba, Argentina, 7Section of Rheumatology, Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina, Buenos
Aires, Argentina
SESSION INFORMATION
Background/Purpose: The introduction of biological agents has been an important advance in the
treatment of RA. However, they are not exempt from adverse events and their high cost limits ac-
cess and maintenance of treatment in many circumstances. Our aim was to evaluate the biological
treatment patterns in RA patients and their accumulated survival and long-term efficacy using the
LUNDEX index.
Methods: Patients ≥ 18 years of age who met ACR/EULAR 2010 criteria for RA and who had
started their first biological disease modifying drugs (b-DMARD) between 01/2006 and 12/2017
were included. Socio-demographic variables such as age, sex, employment status, marital status,
health coverage, education and number of cohabitants, as well as comorbidities, smoking status
(current, past), date of onset of symptoms, disease characteristics and previous DMARDs treatment
were recorded. Disease activity and functional capacity were assessed before and after biologic
treatment using CDAI and HAQ, respectively. Cumulative drug survival was assessed by Kaplan
Meier curves and comparisons using log Rank. LUNDEX was calculated as the product of efficacy
(CDAI remission or low disease activity) and percentage of patients who continued to receive bio-
logical treatment at different cut-off times
Results: 347 patients were included, 89.6% were female, median age was 57.80 years (IQR 48-65),
96.5% had positive rheumatoid factor and 60.8% had positive anti-CCP. 70.6% of patients had
health insurance, 79,8% were smokers and 47% of them had comorbilities. The first bDMARD
was etarnecept in 46.8%, adalimumab (ADA) 28.9, certolizumab 7.2%, abatacept 6.4%, golimumab
4.3, tocilizumab 2.6%, rituximab 2.3% and infliximab 1.4%. Only 5.6% of patients received mono-
therapy, 53.9% of patients discontinued treatment with bDMARD, and the causes of discontinua-
tion were: lack of provision (33.5%), inefficacy (33%), adverse events (20.3%). Out of the available
data the most frequent adverse event was infection. The median survival of the first biological was
31 months (95%CI: 21.8-40.1), without differences between different drugs. CDAI significantly im-
proved over time. Lundex was 45.5% at 6 months and 41.1% at one year. CDAI at 6 months was
significantly lower in non smokers vs smokers (11.37±9.6 vs 17.71±14, p=0.03). In Cox regression
analysis, smoking status (HR 1.8, 95%CI:1.2-2.8) and younger age (HR: 0.98, 95%CI: 0.96-0.99)
were independently associated with lower bDMARD survival rates.
Conclusion: Socioeconomic factors impact on biological survival in our region. Smoking signifi-
cantly reduces the effectiveness of biological treatment, as well as it reduces drug survival.
Disclosure: R. Rolon Campuzano, None; A. L. Coronel Ale, None; O. L. Cerda, None; F. Dal Pra, None; E. E. Schneeberger,
None; M. D. L. A. Correa, None; M. Rosemffet, None; E. Buschiazzo, None; R. Garcia Salinas, None; S. Papasidero, None; B.
Barrios, None; H. Maldonado Ficco, None; G. Citera, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/smoking-signicantly-reduces-effectiveness-and-

long-term-survival-of-biologic-treatment-in-patients-with-rheumatoid-arthritis
mtDNA Cybrids from OA Patients Are Less Efficient Using Glycolysis and Are More
Susceptible to Apoptosis Under Stress Conditions
Mercedes Fernandez Moreno1,2, Tamara Hermida-Gómez3, Andrea Dalamao-Fernandez4, M. Eugenia Vazquez Mosquera4, Estefanía
Cortés-Pereira1, Morena Scotece4, Sara Relaño-Fernandez5, Ignacio Rego-Pérez1 and Francisco J Blanco6, 1Servicio de Reumatología.
Area Genomica. Instituto de Investigación Biomédica de A Coruña (INIBIC). Complexo Hospitalario Universitario de A Coruña
(CHUAC), Sergas. Universidade da Coruña (UDC), A Coruña, Spain, 2CIBER-BBM, Madrid, Spain, 3Rheumatology, INIBIC.
Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. CIBER-BBN., A Coruña, Spain, 4Servicio de Reumatología.
Area Genomica. Instituto de Investigación Biomédica de A Coruña (INIBIC). Complexo Hospitalario Universitario de A Coruña
(CHUAC), Sergas. Universidade da Coruña (UDC), A CORUÑA, Spain, 5Plataforma de Genómica. Instituto de Investigación
Biomédica de A Coruña (INIBIC). Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidade da Coruña
(UDC), A Coruña, Spain, 6Servicio de Reumatología. Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo
Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidade da Coruña (UDC). As Xubias, 15006. A Coruña. España, A
Coruña, Spain
SESSION INFORMATION
Session Title: Genetics, Genomics and Proteomics Poster II
Background/Purpose: Previous studies have showed that chondrocytes from OA patients had mitochondrial alteration in comparison
with healthy. However the role of mitochondria in the biological dysfunction of chondrocytes is not totally know. Cybrids are optimal
cellular models to study mitochondrial biology and function implications in the cellular behavior, since they carry different
mitochondrial variants with the same nuclear background, excluding the variations because of nuclear genome. Purppose: To test the
real role of mitochondrial function in OA pathogenesis using mtDNA cybrids.
Methods: mtDNA Cybrids were developed using the cell line 143B.TK- Rho-0 as the nuclear donor, and platelets from patients without
and with knee osteoarthritis respectively as mitochondrial donors (N vs OA). The stress response was evaluated analyzed O2-
production; percentage of cell survival in presence of H2O2 and the level of apoptotic cells were studied using flow cytometry. The
OXPHOS function and glycolytic activity was evaluated by SeaHorse XFp. The metabolic status was evaluated by glucose consumption
and lactic acid production.
Results: Cybrids carrying the platelets from OA patients showed significant higher levels O2- than N (36.61% vs 17.79%). Percentage
of not viable cell in presence of H2O2 was higher in OA than in N cybrids (40.1 % vs 27.15 %,). The percentage of cell in inducing
apoptosis condition was higher in OA than in N cybrids (15.68% vs 6.41%). OA cybrids had lower basal respiration (92.07 and 155.5),
and maximal respiratory capacity (114.7 and 160.6) than N. The analysis of ATP production was lower in OA than in N cybrids (66.69
vs 101.5). The % spare respiratory capacity for the N was significantly lower than in OA cybrids (107 vs 124.7). Cybrids carrying the
mtDNA from OA patients showed higher glucose consumption than N cybrids (43.77 mg/ml vs 31.91 mg/ml) however in the lactic acid
production did not exit differences. The glycolytic showed that OA cybrids had lower glycolysis (71.05 vs 85.43) but higher glycolytic
reserve than N cybrids (56.60 vs 39.73).
Conclusion: These results showed that the mitochondria obtained from healthy and OA donors had a different behaviour and offer a
real rationale for why mitochondria alterations play an important role in OA pathogenesis.
Disclosure: M. Fernandez Moreno, None; T. Hermida-Gómez, None; A. Dalamao-Fernandez, None; M. E. Vazquez Mosquera,
None; E. Cortés-Pereira, None; M. Scotece, None; S. Relaño-Fernandez, None; I. Rego-Pérez, None; F. J. Blanco, Pfizer Inc, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/mtdna-cybrids-from-oa-patients-are-less-efficient-
using-glycolysis-and-are-more-susceptible-to-apoptosis-under-stress-conditions
Novel Non-Coding RNAs Associated with Rheumatoid Arthritis in Asians By Gene-

Based Testing
Aleksander Lenert1 and David W. Fardo2, 1Internal Medicine, Div. of Rheumatology, University of Kentucky, Lexington, KY,
2Biostatistics, College of Public Health, University of Kentucky, Lexington, KY
SESSION INFORMATION
Background/Purpose:
Rheumatoid arthritis (RA) is a complex genetics disease driven by multiple genetic contributors as evidenced by association with over
100 risk SNPs by GWAS. However, the majority of risk SNPs are not causal and explain only a small proportion of heritability in RA.
Novel approaches for the analysis and interpretation of large-scale genomics data are needed to detect the missing heritability of and
gain further insight into RA. Additionally, risk gene and SNP associations differ in European and Asian RA populations (1). Regulatory
genetic elements, such as non-coding micro RNAs (miRNA), are thought to play an important role in RA and have been identified by
gene-based testing in Europeans with RA (2). Our aim was to identify non-coding genetic elements in Asians with RA with gene-based
association testing.
Methods:
Our dataset consisted of 4,873 RA cases and 17,642 controls from GWAS meta-analysis in Asians (1). All RA cases fulfilled the 1987
ACR criteria or were diagnosed by a rheumatologist. We used the Knowledge-based mining system for Genome-wide Genetic studies
(KGG v.4) for gene-based association testing using extended Simes procedure (GATES) with SNPs outside the extended MHC [Chr. 6,
25.7-33.3 Mb] (3). Genes were defined as ± 5kb. Genomic control was calculated by median of Chi-square statistic. We accounted for
linkage disequilibrium (LD) between SNPs with 1000 Genomes Phase 1 for Asians. Benjamini & Hochberg false discovery rate (FDR)
was used to correct for multiple testing. UCSC Genome Browser was used for visualization of findings.
Results:
Our genome analysis build used 6,581,301 million SNPs and a total of 25,550 genes (including 5189 non-coding RNAs); 51.66% of
SNPs were located inside genes. A total of 108 genes were found to be significant by GATES (FDR <0.05). Amongst the top genes by
GATES, we identified several non-coding RNAs associated with RA in Asians. The significant long non-coding RNAs were
TNFRSF14-AS1 (Chr.1 at RA risk locus TNFRSF14-MMEL1), LINC01843 (Chr. 5 near JADE2), LINC00336 (Chr.6 near GGNBP1-
BAK1) and LINC01016 (Chr.6 near MLN). The significant miRNAs were MIR3934 (Chr.6 near UQCC2-ITPR3), MIR7159 (Chr. 6 near
MLN), MIR4647 (Chr.6 at RA risk locus NFKBIE), MIR3939 (Chr.6 at RA risk locus CCR6), MIR4658 (Chr.7 near C7orf43) and
MIR4308 (Chr. 14 near GCH1). There was no overlap of these non-coding RNAs identified in Asians with RA compared with RA in
Europeans.
Conclusion:
Through large-scale gene-based association testing, we identified novel non-coding RNA associations specific for RA in Asians. These
novel regulatory genetic elements, in addition to established RA risk loci, may improve our understanding of the complex genetics of
RA. Non-coding RNAs could also play a role as potential biomarkers and novel drug targets in RA.
References:
1. Okada Y, et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature. 2014 Feb 20;506(7488):376-81.
2. Lenert A, Fardo DW. Detecting novel micro RNAs in rheumatoid arthritis with gene-based association testing. Clin Exp Rheumatol.
2017 Jan 27. PMID: 28134081.
3. Li MX, et al. GATES: a rapid and powerful gene-based association test using extended Simes procedure. Am J Hum Genet. 2011 Mar
11;88(3):283-93.
Disclosure: A. Lenert, None; D. W. Fardo, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/novel-non-coding-rnas-associated-with-rheumatoid-

arthritis-in-asians-by-gene-based-testing
Identification of Circulating Biomarkers of Disease Activity and Organ Involvement

in ANCA-Associated Vasculitis By Targeted Proteomics
Jun Ishizaki1, Ayako Takemori2, Koichiro Suemori1, Takuya Matsumoto1, Yoko Akita1, Masaki Yasukawa1, Nobuaki Takemori2 and
Hitoshi Hasegawa1, 1Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of
Medicine, Ehime, Japan, 2Division of Proteomics Research, Proteo-Science Center, Ehime University, Ehime, Japan
SESSION INFORMATION
Background/Purpose: Targeted proteomics, which involves quantitative analysis of targeted proteins using selected reaction
monitoring (SRM) mass spectrometry, has emerged as a new methodology for discovery of clinical biomarkers. The aim of this study
was to identify circulating biomarkers for prediction of disease activity and organ involvement in antineutrophil cytoplasmic antibody
(ANCA)-associated vasculitis (AAV) by using targeted serum proteomics.
Methods: We selected the targeted candidates by an experiment-based approach in which we conducted MS-based serum proteomic
profiling of AAV patients before and after treatment. We further selected 87 endothelium-related proteins, which were expected to be
present in blood, based on information from publicly available databases. A large-scale SRM assay targeting 135 biomarker candidates
was established using a triple quadrupole mass spectrometer coupled with nano-flow liquid chromatography. Target proteins in serum
samples from patients in the active and remission (6 months after treatment) stages were quantified using the established assays.
Identified marker candidates were further validated by ELISA using serum samples (n=169) collected in a large-cohort Japanese study
(RemIT-JAV-RPGN study).
Results: The following proteins were identified as biomarkers for discriminating patients with highly active AAV from those in
remission or healthy controls: tenascin C (TNC), C-reactive protein (CRP), tissue inhibitor of metalloproteinase 1 (TIMP1), leucine-rich
alpha-2-glycoprotein 1, S100A8/A9, CD93, matrix metalloproteinase 9, and transketolase (TKT). Of these, TIMP1 was the best-
performing marker of disease activity, allowing distinction between non-remission (mildly active AAV) and remission. The serum levels
of TKT and CD93 were higher in patients with renal involvement than in those without, and predicted renal outcome. The serum level
of TNC was elevated significantly in patients with lung infiltration. AAV severity was associated with markers reflecting organ
involvement (TKT, CD93 and TNC) rather than inflammation.
Conclusion: We have identified promising biomarkers of disease activity and severity and organ involvement in AAV with targeted
proteomics approach using serum samples collected in a large-cohort Japanese study. Especially, our analysis demonstrated the
effectiveness of TIMP1 as a marker of AAV activity. In addition, we identified TKT and CD93 as novel markers for evaluation of renal
involvement and renal outcome in AAV.
Disclosure: J. Ishizaki, None; A. Takemori, None; K. Suemori, None; T. Matsumoto, None; Y. Akita, None; M. Yasukawa, None;
N. Takemori, None; H. Hasegawa, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/identification-of-circulating-biomarkers-of-disease-

activity-and-organ-involvement-in-anca-associated-vasculitis-by-targeted-proteomics

Mitochondrial Haplogroups-Mediated Methylation Regulates Apoptosis in
Osteoathritis Cartilage
Ignacio Rego-Pérez1, Estefanía Cortés-Pereira1, Juan Fernández-Tajes Sr.2, Mercedes Fernandez Moreno1, Maria Eugenia Vazquez
Mosquera1, Sara Relaño-Fernandez3, Natividad Oreiro4, Carlos Fernandez-Lopez1 and Francisco J Blanco1, 1Servicio de
Reumatología. Area Genomica. Instituto de Investigación Biomédica de A Coruña (INIBIC). Complexo Hospitalario Universitario de A
Coruña (CHUAC), Sergas. Universidade da Coruña (UDC), A Coruña, Spain, 2The Wellcome Trust Center for Human Genetics.
McCarthy´s Group. University of Oxford, Oxford, United Kingdom, 3Plataforma de Genómica. Instituto de Investigación Biomédica de
A Coruña (INIBIC). Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidade da Coruña (UDC), A Coruña,
Spain, 41) Servicio de Reumatología. Instituto de Investigación Biomédica de A Coruña (INIBIC). Complexo Hospitalario Universitario
de A Coruña (CHUAC), Sergas. Universidade da Coruña (UDC). As Xubias, 15006. A Coruña, España, A Coruna, Spain
SESSION INFORMATION
Background/Purpose:
Recent studies revealed that haplogroup J associates with a decreased rate of incident knee Osteoarthritis. Among the functional
characteristics of this haplogroup, lower rates of apoptosis stand out. In this study we aimed to evaluate if this process is epigenetically
regulated.
Methods:
DNA methylation profiling from a previous study performed in knee articular cartilage was obtained from Gene Expression Omnibus
database (accession GSE-43191). In that study, cartilage DNA was isolated from 13 samples carrying the haplogroup J and 20 samples
carrying the haplogroup H. The differential methylome between J and H haplogroups was obtained using Lumi and Methylumi packages
(R bioconductor).
A subsequent validation by RNA-seq was performed in 7 haplogroup J cartilage samples and 9 haplogroup H cartilage samples.
Differential expression data between haplogroups were analyzed using Kallisto package (R bioconductor). Gene ontology analyses from
methylation and expression approaches were performed using DAVID (https://david.ncifcrf.gov/).
Results:
Gene ontology analysis of the 538 differentially methylated regions between haplogroups J and H revealed that genes involved in the
negative regulation of apoptosis (p=0,021) and catalytic activity (p=0,036) were hypomethylated in haplogroup J cartilages. On the
contrary, haplogroup H cartilages showed a enrichment of hypomethylated genes involved in the positive regulation of apoptosis
(p=0,008); an enrichment of hypomethylated genes involved in the negative regulation of the metabolic processes of nitrogen
compounds (p=0,03) and macromolecules (p=0,026) was detected in haplogroup H cartilages.
Subsequent validation by RNA-seq revealed 416 differentially expressed genes between haplogroups H and J, considering an adjusted
p-value≤0,005 as well as a logFc≥±4 (Figure 1). Of these genes, 362 were up-regulated in haplogroup J cartilages and 54 up-regulated
in haplogroup H. Among the most differentially altered biological processes, a enrichment of over-expressed genes involved in the
positive regulation of apoptosis (p=0,047) and cellular adhesion (p=0,0018) was detected in haplogroup H cartilages. On the contrary,
an enrichment of up-regulated genes involved in lipid synthesis (p=0,044), Calcium homeostasis (p=0,047), cell signaling (p=0,00031)
and immune system development (p=0,0092) was detected in haplogroup J cartilages.
Conclusion:
Mitochondrial haplogroups J and H induce specific methylation and expression profiles in cartilage samples that lead to an epigenetic
regulation of apoptosis, being more repressed in cartilages with J haplogroup and more active in cartilages with H haplogroup.
Disclosure: I. Rego-Pérez, None; E. Cortés-Pereira, None; J. Fernández-Tajes Sr., None; M. Fernandez Moreno, None; M. E.
Vazquez Mosquera, None; S. Relaño-Fernandez, None; N. Oreiro, None; C. Fernandez-Lopez, None; F. J. Blanco, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/mitochondrial-haplogroups-mediated-methylation-

regulates-apoptosis-in-osteoathritis-cartilage
Analysis of microRNAs in Familial Mediterranean Fever

Gil Amarilyo1, Nir Pillar2, Ilan Ben-Zvi3, Daphna Weissglas-Volkov2, Jonatan Zalcman2, Liora Harel4, Avi Livneh3 and Noam
Shomron2, 1Schneider Children's Medical Center of Israel, Sackler School of Medicine, Tel Aviv University, Petach Tikva, Israel,
2Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel, 3Chaim Sheba Medical Center, Tel Hashomer, Sackler School of
Medicine, Tel Aviv University, Tel Aviv, Israel, 4Schneider Children's Medical Center of Israel, Sackler School of Medicine, Tel Aviv
University, Tel Aviv, Israel
SESSION INFORMATION
Background/Purpose: Familial Mediterranean fever (FMF) is thought to be inherited as an autosomal recessive trait. However, there
are frequent deviations from this model. The aim of this study was to explore epigenetic modifications in patients with FMF.
Methods: Ten patients diagnosed with FMF according to the Tel-Hashomer criteria were recruited from the rheumatology outpatient
clinic of Sheba Medical Center, Tel Hashomer, Israel. All patients were homozygous for the M694V mutation, the most common
mutation in FMF, and all had the most severe phenotype of the disease. All were in the quiescent phase at the time of the study. Total
RNA was drawn from peripheral blood and profiled for microRNA expression using NanoString nCounter technology. Findings were
compared to 10 healthy age- and sex-matched control subjects. Statistical analyses were conducted using R software, version 3.2. Data
preprocessing and normalization followed by differential expression analysis were performed using the R package DESeq2 (25516281)
and in house scripts. A priori P values were adjusted for false discovery rate (FDR).
Results: Of the 798 mature human miRNAs probed, 103 exhibited reasonable expression levels in these cells. Seven were found to be
significantly deregulated in the patients with FMF: three were significantly downregulated compared to control samples (miR-107,
let−7d−5p, and miR-148b-3p), and four were significantly upregulated (miR-144-3p, miR-21−5p, miR−4454 and miR-451a), all with an
adjusted P value of <0.01 (Figure 1).
To ensure that the observed changes were true biological effects and not technical artifacts, we performed Taqman quantitative real time
polymerase chain reaction (qRT-PCR) analysis of two of the differentially expressed miRNAs between the patients and controls. Each
miRNA was quantified in each sample, and its expression level was normalized to the reference RNA, U6-snRNA. In both groups, the
direction of effect and the miRNA expression patterns in the NanoString analysis were consistent with the Taqman measurements
(R2=0.93)
Conclusion: We identified significant epigenetic changes in patients with clinically quiescent FMF. Further research is warranted in
order to elucidate critical FMF manifestation such as susceptibility to early disease, disease severity, risk of the development of
amyloidosis, and resistance to colchicine. All these factors might be ultimately explained, at least in part, by epigenetic modifications.
Figure 1
Disclosure: G. Amarilyo, None; N. Pillar, None; I. Ben-Zvi, None; D. Weissglas-Volkov, None; J. Zalcman, None; L. Harel, None;
A. Livneh, None; N. Shomron, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/analysis-of-micrornas-in-familial-mediterranean-

fever
HLA-Class II Associations with ANCA-Associated Vasculitis in the Japanese

Population: Different Features from European Populations
Aya Kawasaki1, Fumio Hirano2, Ken-ei Sada3, Shigeto Kobayashi4, Hidehiro Yamada5, Hiroshi Furukawa1, Kenji Nagasaka6,
Takahiko Sugihara7, Kunihiro Yamagata8, Takayuki Sumida9, Shigeto Tohma10, Shoichi Ozaki5, Seiichi Matsuo11, Hiroshi
Hashimoto12, Hirofumi Makino13, Yoshihiro Arimura14, Masayoshi Harigai15 and Naoyuki Tsuchiya1, 1Molecular and Genetic
Epidemiology Laboratory, University of Tsukuba, Faculty of Medicine, Tsukuba, Japan, 2Departments of Rheumatology, Graduate
School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan, 3Department of Nephrology,
Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical
Sciences, Okayama, Japan, 4Department of Internal Medicine, Juntendo University Koshigaya Hospital, Koshigaya, Japan, 5Department
of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan, 6Department of Rheumatology, Ome Municipal
General Hospital, Ome, Japan, 7Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan,
8Department of Nephrology, University of Tsukuba, Faculty of Medicine, Tsukuba, Japan, 9Department of Internal Medicine, University
of Tsukuba, Faculty of Medicine, Tsukuba, Japan, 10Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital,
National Hospital Organization, Sagamihara, Japan, 11Department of Nephrology, Nagoya University Graduate School of Medicine,
Nagoya, Japan, 12Juntendo University School of Medicine, Tokyo, Japan, 13Okayama University Hospital, Okayama, Japan, 14First
Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan, 15Division of Epidemiology and
Pharmacoepidemiology of Rheumatic Diseases, Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
SESSION INFORMATION
Background/Purpose: HLA-class II region harbors the strongest genetic factors for ANCA-associated vasculitis (AAV), and
differences in the genetic background of HLA-class II may partly explain the epidemiologic differences in AAV between European and
Asian populations. HLA-DPB1*04:01, highly prevalent in the European populations, is associated with granulomatosis with polyangiitis
(GPA)/PR3-AAV prevalent in the European populations, whereas DRB1*09:01, almost exclusively distributed in Asian populations, is
associated with microscopic polyangiitis (MPA)/MPO-AAV, which account for the majority of AAV in Japan. Of interest, although
DRB1*09:01 is very rare in the European populations, genome-wide association study (GWAS) detected significant association of a
single nucleotide polymorphism (SNP) rs5000634 between DQB1 and DQA2 loci with MPA/MPO-AAV. Whether this association is
independent from HLA alleles has not been reported. Another unique feature in Japanese AAV is that only half of the patients with GPA
are positive for PR3-ANCA, and the other half are positive for MPO-ANCA. This provides a valuable opportunity to distinguish
whether the genetic factors are associated with clinical classification of GPA or ANCA specificity. In the present study, we addressed
these two issues in Japanese patients with AAV.
Methods: HLA-DRB1 and DPB1 were genotyped using high-resolution allele typing, and rs5000634 using TaqMan SNP assay.
Association was tested in 467 Japanese AAV patients (clinical classification: MPA [285], GPA [92], eosinophilic GPA [56],
unclassifiable [34], ANCA specificity: MPO-AAV [376], PR3-AAV [62]) and 596 healthy controls. Among GPA, 36 were single
positive for PR3-ANCA (PR3-GPA) and 35 were single positive for MPO-ANCA (MPO-GPA).
Results: As shown in Table 1, rs5000634A was slightly decreased in MPO-AAV and MPA. However, when conditioned on
DRB1*09:01 or DRB1*13:02, the association was no longer significant, while the association of DRB1 alleles remained significant after
conditioned on rs5000634. When the associations of DRB1 and DPB1 were examined in MPO-GPA and PR3-GPA (Table 2),
DPB1*04:01 was associated with PR3-GPA, but slightly decreased in MPO-GPA. In contrast, association of DRB1*08:02 was observed
in MPO-GPA, but not in PR3-GPA.
Conclusion: In Japanese AAV, the genetic contribution of HLA-DQ region GWAS SNP was the secondary one caused by linkage
disequilibrium with HLA-DRB1 alleles. Striking differences in HLA-DRB1 and DPB1 associations were observed between MPO-GPA
and PR3-GPA, suggesting that HLA may be more strongly associated with ANCA specificity than with clinical classification of GPA.
Table 1. The association of European GWAS SNP rs5000634 with
MPA/MPO-AAV was secondary to DRB1 association in the Japanese
population.
unconditioned Conditioned Conditioned Conditioned on
on on rs5000634
DRB1*09:01 DRB1*13:02
P OR P OR P OR P OR
(95%CI) (95%CI) (95%CI) (95%CI)

MPO-AAV
DRB1*09:01 1.6E- 1.58 - - - - 1.6E- 1.53
04 03
(1.25- (1.18-
2.00) 1.99)
DRB1*13:02 7.0E- 0.43 - - - - 3.9E- 0.46
05 04
(0.28- (0.30-
0.65) 0.70)
rs5000634 0.044 0.82 0.64 0.95 0.33 0.91 - -
(0.68- (0.77- (0.75-

1.00) 1.17) 1.10)
MPA
DRB1*09:01 6.4E- 1.56 - - - - 4.2E- 1.52
04 03
(1.21- (1.14-
2.02) 2.01)
DRB1*13:02 1.1E- 0.47 - - - - 3.9E- 0.50
03 03
(0.30- (0.32-
0.74) 0.80)
rs5000634 0.074 0.83 0.67 0.95 0.35 0.90 - -
(0.68- (0.76- (0.73-

1.02) 1.19) 1.11)
Conditional logistic regression analysis was performed under the additive
model. OR: odds ratio, CI: confidence interval.
Table 2. Differential association of DRB1*08:02, DRB1*13:02 and

DPB1*04:01 with PR3-ANCA single positive GPA and MPO-ANCA single
positive GPA.
PR3-GPA MPO-GPA Controls
AF P OR(95%CI) AF P OR(95%CI) AF (%)
(%) (%)
DRB1*08:02 1.4 0.72 0.49 11.4 1.3E-03 4.53 2.8
(0.07-3.67) (2.01-10.22)
DRB1*13:02 8.3 1.0 0.93 1.4 0.025 0.15 8.9
(0.39-2.20) (0.02-1.08)
DPB1*04:01 13.9 0.025 2.39 1.4 0.12 0.21 6.3
(1.18-4.85) (0.03-1.57)
AF: allele frequency, PR3-GPA: PR3-ANCA positive, MPO-ANCA negative
GPA, MPO-GPA: MPO-ANCA positive, PR3-ANCA negative GPA, OR:
odds ratio, CI: confidence interval. P values were calculated by Fishers exact
test.
Disclosure: A. Kawasaki, None; F. Hirano, Chugai Pharmaceutical Co., Ltd.; Ono Pharmaceuticals; Mitsubishi Tanabe Pharma Co.;
UCB Japan; CSL Behring; Towa Pharmaceutical Co., Ltd.; Abbvie Japan Co., Ltd.; Japan Blood Products Organization; Ayumi
Pharmaceutical Co.; and Nippon Kayaku Co., Ltd, 3,Astellas Pharma Inc, 5; K. E. Sada, None; S. Kobayashi, None; H. Yamada,
None; H. Furukawa, Bristol-Myers Squibb Co., 2,Ayumi Pharmaceutical Corporation, 5; K. Nagasaka, Chugai Pharmaceutical Co.,
Ltd., Bristol Myers Squibb K.K., Teijin Pharma Ltd., Actelion Pharmaceuticals Ltd., Ayumi Pharmaceutical Co., Ltd.., 5; T. Sugihara,
Takeda Pharmaceutical Co. Ltd., Mitsubishi-Tanabe Pharma Co., Chugai Pharmaceutical Co., Ltd., Ayumi Pharmaceutical Co., Ltd.,
UCB Japan Co. Ltd, Astellas Pharma Inc., Janssen Pharmaceutical K.K., Pfizer Japan Inc., and Bristol Myers Squibb K.K, 5; K.
Yamagata, None; T. Sumida, None; S. Tohma, None; S. Ozaki, None; S. Matsuo, None; H. Hashimoto, None; H. Makino, None; Y.
Arimura, None; M. Harigai, Eisai Ltd, Takeda Ltd, Teijin, 2,Eli Lilly and Company, BMS, Chugai, Janssen, 5; N. Tsuchiya, Novartis
Pharmaceutical Corporation, 2,Ayumi Pharmaceutical Co, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/hla-class-ii-associations-with-anca-associated-

vasculitis-in-the-japanese-population-different-features-from-european-populations
The Rheumatic Disease Data Refinery: A Case Study in Integrative Genomics

Reveals Complex IFN Signatures in Therapeutic Studies in SLE
Jaclyn N Taroni and Casey S. Greene, Systems Pharmacology and Translational Therapeutics, University of Pennsylvania,
Philadelphia, PA
SESSION INFORMATION
Background/Purpose: Over the past 15 years, more than 10,000 whole tissue biopsies from patients with rheumatic diseases have been
deposited into publicly available gene expression databases. Often rheumatic diseases are studied in isolation, but these data can be
harnessed to characterize the full catalog of shared molecular patterns perturbed in these disease states. We present plans for a rheumatic
disease transcriptomic compendium (Fig 1) and demonstrate feasibility through a case study in SLE whole blood gene expression data.
Methods: We curated experiments from studies of rheumatic diseases from ArrayExpress. For our SLE whole blood case study, we
selected 8 experiments from multiple platforms, including data from 2 clinical trials examining the effects of treatments modulating IFN
(Lauwerys, et al. Arthritis Rheumatol. 2013; Welcher, et al. Arthritis Rheumatol. 2015.). Cross-platform normalization using quantile
normalization was performed. Interferon module gene sets from Chiche, et al. Arthritis Rheumatol. 2014. and unsupervised machine
learning algorithms were used to examine the change in IFN signatures during treatment and the overall data structure during the
integration process. This is, to our knowledge, the first application of the Chiche, et al. whole blood modular framework to these trials.
Results: We demonstrate that it is possible to integrate SLE whole blood data from multiple platforms and studies and retain underlying
biology. We find that expression of Type I IFN module genes are altered following the treatment with the therapeutic vaccine IFN-
alpha-kinoid in patients with high baseline Type I signatures, consistent with the therapeutics mechanism of action and the original
study (Fig 2). We also find that only putative Type II modules are altered during blockade of IFN-gamma.
Conclusion: We have established the feasibility of a rheumatic disease gene expression compendium that is an order of magnitude
larger than any single publicly available experiment. Our results further support the utility of data-driven cross-disease modules and
suggest that unsupervised approaches can yield insight into complex molecular patterns altered in rheumatic diseases (Fig 1).
Fig 1. Overview of the Rheumatic Disease Data Refinery.
Fig 2. Summarized expression values (change from baseline) of IFN
modules during treatment with IFN-_-kinoid (data from Lauwerys, et al. Arthritis Rheumatol. 2013.). Patients were stratified into the
following groups: placebo, those with a low Type I (M1.2) signature at base (IFN-negative), and those with a high M1.2 signature at
baseline.
Disclosure: J. N. Taroni, None; C. S. Greene, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-rheumatic-disease-data-refinery-a-case-study-in-

integrative-genomics-reveals-complex-ifn-signatures-in-therapeutic-studies-in-sle

Key Genes and Pathways between Rheumatoid Arthritis and Osteoarthritis By
Integrative Genome-Wide Gene Expression Profiling Analysis
Rongqiang Zhang1,2, Aimin Yang3, Xiaomei Ren2, Jie Zhang3, Xiaoli Yang4, Qiling Liu2, Na Sun2, Puwei Yuan5 and Yongmin
Xiong4, 1School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic
Diseases of the National Health and Family Planning Commission, Xi'an 710061, China, Xi'an, China, 2Shaanxi University of Chinese
Medicine, Xianyang 712046, China, Xianyang, China, 3School of Public Health, Brown University, Providence, RI 02906, US,
Providence, RI, 4School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and
Endemic Diseases of the National Health and Family Planning Commission, Xi'an 710061, China, Xian, China, 5Shaanxi University of
Chinese Medicine, Xianyang 712046, China, XianYang, China
SESSION INFORMATION
Background/Purpose: Rheumatoid arthritis (RA) and Osteoarthritis (OA) are two most common types of joint diseases with lots of
similar symptoms, and their pathological mechanisms remain largely unknown. Although some key genes and diagnostic markers have
been identified by microarray, these biomarkers still cannot reveal the complicated pathogenesis of RA and OA entirely. We conducted
a novel integrative analysis of identification the key biomarkers of synovial tissue from RA and OA patients to better understand their
difference.
Methods: After screening NCBI GEO database, 3 new expression profiling datasets (GSE 55235, GSE 55584, GSE 55457) met the
eligibility criteria (from synovial tissue of RA and OA patients diagnosed according to American Rheumatism Association 1987 revised
criteria, detected by the same platform, and sample size >15). A global normalization was performed to minimize the data inconsistency
and heterogeneity. Differentially expressed genes (DEGs, p<0.05, FDR<0.05, Fold Change >2) between RA and OA from the 3 datasets
were explored by R v3.4.0 software. Gene Ontology and KEGG pathway analysis of the DEGs were conducted by Cytoscape 3.4.0.
Protein-protein interaction (PPI) network of the DEGs was obtained from STRING database v9.05.
Results: 375, 242 and 264 DEGs from GSE 55235, GSE 55584 and GSE 55457 datasets were obtained, respectively. Among them, 81
DEGs presented identical expression trends in the 3 datasets, including 50 up-regulated genes (IGHG1, GUSBP11, STAT1, et al) and 31
down-regulated genes (SCRG1, MAB21L2, GHR, et al). The DEGs mainly involved in negative regulation of I-kappa B kinase/NF-
kappa B signaling, cellular response to vitamin D pathway, et al(Fig. 1). STAT1 and GHR were the cores of PPI networks of 50 up-
regulated proteins and 31 down-regulated proteins, respectively (Fig. 2).
Conclusion: Several apoptosis and vitamin D related pathways were more closely related to RA than OA, which suggested that anti-
oxidative stress therapy and vitamin D might be more effective for RA. STAT1 and GHR (both relate to bone metabolism) are the key
genes presenting statistical significant difference between RA and OA. This study provides novel insights into the molecular
mechanisms underlying RA and OA, thereby aiding the diagnosis and treatment of the diseases. Well-designed, well-controlled and
dependent experiments are needed in future to validate the findings of the present study.
Fig. 1. Networks of key pathways related to RA

(A: up-regulated DEGs; B: down-regulated DEGs; Names in dark color: P<0.05)
Fig. 2. PPI networks of up-regulated (A) and down-regulated DEGs (B)
Disclosure: R. Zhang, None; A. Yang, None; X. Ren, None; J. Zhang, None; X. Yang, None; Q. Liu, None; N. Sun, None; P. Yuan,
None; Y. Xiong, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/key-genes-and-pathways-between-rheumatoid-

arthritis-and-osteoarthritis-by-integrative-genome-wide-gene-expression-profiling-analysis
The Genetic Biomarkers to Predicting Response of TNF Inhibitors Treatment in

So-Young Bang1, Youngho Park2, Kwangwoo Kim3, Young Bin Joo4, Soo-Kyung Cho5, Chan-Bum Choi1, Yoon-Kyoung Sung2, Tae-
Hwan Kim2, Jae-Bum Jun1, Dae-Hyun Yoo1, Hye-Soon Lee6 and Sang-Cheol Bae7, 1Department of Rheumatology, Hanyang
University Hospital for Rheumatic Diseases, Seoul, Korea, Republic of (South), 2Hanyang University Hospital for Rheumatic Diseases,
Seoul, Korea, Republic of (South), 34Department of Biology, Kyung Hee University, Seoul, Korea, Republic of (South), 4Internal
Medicine, Department of Rheumatology, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Gyeonggido, Korea,
Republic of (South), 5Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea, Republic of (South),
6Hanyang University Guri Hospital, Gyeonggi-do, Korea, Republic of (South), 7Department of Rhematology, Hanyang University
Hospital for Rheumatic Diseases, Seoul, Korea, Republic of (South)
SESSION INFORMATION
Background/Purpose: Although pharmacogenetic studies of TNF inhibitors (TNFi) response presented the estimates of high
heritability, only few loci with suggestive weak association as biomarkers for TNFi response have been identified. We aimed to identify
optimal phenotype for drug response using heritability estimates (h2) and new predictive biomarkers of response to TNFi using genome-
wide association studies (GWAS) in the Korean population.
Methods: Disease Activity Scores based on 28 joint counts (DAS28) and Clinical Disease Activity Index (CDAI) were assessed at
baseline, and after 6 months in 370 Korean RA patients who started TNFi due to moderate or high disease activity from Hanyang
university hospital. Genotypes were generated on the Illumina HumanOmni2.5Exome array (2.5 million variants). Quality control (QC)
procedures were applied using the PLINK 1.9 and R 3.2.2 software. We estimated heritability by a linear mixed effect modeling
approach (GCTA) for TNFi response using changes (Δ) in DAS28 and CDAI. To identify clinical and genetic variables that influence
response to TNFi, a multivariate generalized linear model (GLM) analysis was performed. We also conducted a gene-based analysis
[optimal sequence kernel association test (SKAT-O)] of rare variants.
Results: We identified that clinical factors seem to influence the therapeutic good response of TNFi including male, high disease
activity score at baseline, BMI. The heritability estimates were found for ΔDAS28 h2=0.44, ΔCDAI h2=0.62, Δprovider global
assessment of disease activity (PrGA) h2=0.66, Δswollen joint count (SJC) h2=0.66, Δtender joint count (TJC) h2=0.59, Δpatient global
assessment of disease activity (PtGA) h2=0.58, and ΔESR h2=0.49. We identified two novel significant functional SNPs [rs117811759
(UTR3 of SAP18), rs17279819 (exon of SKA3)] associated with response to TNFi, surpassing genome-wide significant threshold (P <
5.0×10−8). Using a gene-based approach, we also identified two genes (SAP18 and SKA3) with significant burden signals after
correction for multiple comparisons.
Conclusion: The optimal phenotype based on heritability suggests the use of changes in clinical disease activity index (CDAI)
including provider global assessment than DAS28 in pharmacogenetic study. Our study suggests that SAP18 and SKA3 associated with
response to TNFi therapy may serve as the useful genetic biomarker in RA patients of Koreans.
Disclosure: S. Y. Bang, None; Y. Park, None; K. Kim, None; Y. B. Joo, None; S. K. Cho, None; C. B. Choi, None; Y. K. Sung,
None; T. H. Kim, None; J. B. Jun, None; D. H. Yoo, Celltrion Inc., 5; H. S. Lee, None; S. C. Bae, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-genetic-biomarkers-to-predicting-response-of-

tnf-inhibitors-treatment-in-rheumatoid-arthritis
Investigation of Differential Methylation As a Potential Biomarker of Methotrexate

Response in Patients with Rheumatoid Arthritis
Nisha Nair1, Darren Plant2,3, Suzanne M Verstappen1, John D Isaacs4, Ann W. Morgan5, Kimme L. Hyrich6, Anne Barton7 and
Anthony G. Wilson8, 1Arthritis Research UK Centre of Genetics and Genomics and Centre of Epidemiology, Manchester, United
Kingdom, 2Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester, United Kingdom,
3NIHR Manchester Musculoskeletal BRU, Central Manchester Foundation Trust and University of Manchester, Manchester Academic
Health Science Centre, Manchester, United Kingdom, 4Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne,
United Kingdom, 5NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds, United Kingdom, 6National Institute of Health
Research Manchester Musculoskeletal Biomedical Research Centre, Central Manchester NHS Foundation Trust, Manchester Academic
Health Science Centre, Manchester, United Kingdom, 7Arthritis Research UK, Centre for Genetics and Genomics, Centre for
Musculoskeletal Research, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, United Kingdom,
8UCD School of Medicine and Medical Science, Conway Institute, University College Dublin, Dublin, Ireland
SESSION INFORMATION
Background/Purpose: Methotrexate (MTX) is the first-line disease modifying anti-rheumatic drug for the treatment of rheumatoid
arthritis (RA). However, many patients do not respond adequately or experience adverse effects, therefore identifying blood-based
biomarkers that predict treatment response is a clinical priority. DNA methylation is an epigenetic marker that modifies, but does not
alter, DNA sequence, and it is thought that MTX may act, at least in part, by inhibiting intracellular methyl donor status leading to DNA
hypomethylation. We aimed to identify differential DNA methylation signatures in whole blood, which may be predictive of response to
MTX in patients with RA.
Methods: DNA methylation was measured using the HumanMethylation450 BeadChip in DNA samples from individuals recruited to
the Rheumatoid Arthritis Medication Study (RAMS), a one year observational study in the UK including patients with RA starting
MTX for the first time. In RAMS, demographic and clinical data are collected prior MTX start (baseline) and at 6 months after
commencing MTX. DNA was extracted from whole blood samples collected baseline and at 4 weeks from patients who, at 6 months,
had a EULAR good response (n=36) or EULAR poor response (n=36) to MTX (test cohort). Differentially methylated positions
(DMPs) between the baseline and 4 weeks, and between good and poor response were identified using linear regression, adjusting for
gender, age, cell composition, baseline disease activity score (DAS28), and smoking status. Analyses also compared methylation with
changes in DAS28 and the individual DAS28 components over 6 months. DMPs that showed significant differences in the test cohort
were selected for replication by pyrosequencing in an independent group of 100 patients with both baseline and 4 week samples
(replication cohort).
Results: In the test cohort, differential methylation at 2 CpG sites in samples taken at 4 weeks was associated with response status
determined at 6 months (p-value <10-5). Three additional DMPs were associated with change in tender joint count, whilst three other
DMPs were associated with change in swollen joint count, and a further four DMPs associated with change in C-reactive protein. One
of the 4 DMPs associated with change in CRP, cg04334751, showed a trend to association in the independent replication cohort
(Spearmans Rho p-value =0.058). This CpG site is located close to microRNA, mir182.
Conclusion: These preliminary results suggest DNA methylation may provide a biomarker of MTX response but requires additional
replication in other cohorts and testing in a prospective study of patients starting MTX for the first time.
Disclosure: N. Nair, None; D. Plant, None; S. M. Verstappen, None; J. D. Isaacs, None; A. W. Morgan, None; K. L. Hyrich, None;
A. Barton, None; A. G. Wilson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/investigation-of-differential-methylation-as-a-

potential-biomarker-of-methotrexate-response-in-patients-with-rheumatoid-arthritis
Comprehensive Identification of Differentially Methylated Regions Associated with

Systemic Sclerosis in Dermal Fibroblasts from African-American Patients
Paula S. Ramos1,2, Willian da Silveira3, E. Starr Hazard3, Ilia Atanelishvili4, Robert C. Wilson5, Jim C. Oates1, Galina S.
Bogatkevich4 and Gary Hardiman1,2,3, 1Department of Medicine, Medical University of South Carolina, Charleston, SC, 2Department
of Public Health Sciences, Medical University of South Carolina, Charleston, SC, 3Center for Genomic Medicine, Medical University
of South Carolina, Charleston, SC, 4Division of Rheumatology and Immunology, Department of Medicine, Medical University of South
Carolina, Charleston, SC, 5Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC
SESSION INFORMATION
Background/Purpose: The etiology and reasons underlying the ethnic disparities in systemic sclerosis (SSc) remain unknown. African-
Americans are disproportionally affected by SSc, yet dramatically underrepresented in research. The role of DNA methylation in
disease risk remains unclear. This analysis was conducted to comprehensive identify differentially methylated loci associated with SSc
in AA.
Methods: Genomic DNA was isolated from cultured dermal fibroblasts isolated from 15 AA SSc cases and 15 AA controls. All patients
met the 2013 ACR/EULAR classification criteria for SSc, most (93%) presenting with diffuse cutaneous SSc. DNA methylation
patterns were profiled through reduced representation bisulfite sequencing (RRBS). Alignment and methylation calling were performed
using Bismarck v0.16.3 and the GRCh37/hg19 reference genome. Data was filtered, normalized, and analyzed with RnBeads v1.6.1.
Differential methylation analysis was conducted on CpG, promoter, gene and system level.
Results: We generated DNA methylation data for over 5 million CpGs in each sample with at least 40x coverage in promoter and CpG
islands. Using the Combined Score approach implemented in RnBeads, a total of 97 CpG islands, 197 genes and 112 promoters showed
significant differential enrichment in methylation levels between cases and controls. The top differentially methylated loci include,
among others, the promoter of SERPINA1 (a protease inhibitor of elastase, plasmin, thrombin and trypsin) and SERPINA3,
SERPINA4, SERPINA5, SERPINA11 and SERPINA13P. The SERPIN superfamily is characterized by its function as chaperone
proteins and its roles in inflammation and immune function. Enrichment analysis revealed that both hypo- and hypermethylated genes
and their promoter regions were enriched for differentiation and immune-related gene ontology terms (hypomethylated regions: IL2-
mediated signaling pathway, P=5E-3; and mesenchymal cell differentiation, P=3E-4; hypermethylated regions: type I IFN signaling
pathway, P=8E-4; and positive regulation of cell differentiation, P=1E-3).
Conclusion: We observed dramatic DNA methylation differences between cases and controls. Interestingly, most of the dysregulated
genes can be placed in immune pathways, supporting the role of immune dysregulation in triggering the fibrosis characteristic of SSc.
These add to previous reports of mostly European-Americans that report an enrichment of extracellular matrix-receptor interaction and
focal adhesion genes. These data support a role for DNA methylation differences in mediating susceptibility to SSc in AA, and a
potentially stronger immune-driven etiology in AA.
Disclosure: P. S. Ramos, None; W. da Silveira, None; E. S. Hazard, None; I. Atanelishvili, None; R. C. Wilson, None; J. C. Oates,
None; G. S. Bogatkevich, NIH/NIAMS P60 AR062755, 2,Scleroderma Foundation, 2; G. Hardiman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/comprehensive-identification-of-differentially-

methylated-regions-associated-with-systemic-sclerosis-in-dermal-fibroblasts-from-african-american-patients
Molecular Profiling of RA Patients Suggests a Differential Involvement of Adaptive

and Innate Cell Populations in Response to Anti-TNF Treatment
Victor Farutin1, Thomas Prod'homme1, Kevin McConnell1, Nathaniel Washburn1, Patrick Halvey1, Jamey Guess1, Nur Sibel Gunay1,
Jan Hillson2, Carol J. Etzel3, Katherine C. Saunders3, Dimitrios A. Pappas3,4, Anthony Manning1, Leona Ling1 and Ishan Capila1,
1Research, Momenta Pharmaceuticals, Inc., Cambridge, MA, 2Clinical Research, Momenta Pharmaceuticals, Inc., Cambridge, MA,
3Corrona, LLC, Southborough, MA, 4Columbia University, New York, NY
SESSION INFORMATION
Background/Purpose:
Despite the success of anti-TNF therapies in RA, ~ 30 % of patients are non-responders. Several studies have focused on understanding
the biology underlying non-response in these patients, and this remains an area of active investigation. We conducted a comprehensive
molecular profiling of biologic naïve RA patients being treated with anti-TNF therapy in combination with MTX, prior to initiating
(baseline) and following 3 months of treatment. The aim of the study was to understand the molecular mechanisms (other than drug
neutralization), that affect clinical response to anti-TNF and to identify potential predictive markers that could allow us to differentiate
responders and non-responders at baseline.
Methods:
Two independent cohorts of 52 and 41 RA patients were selected from the Corrona CERTAIN registry. Clinical response at three
months was defined according to EULAR criteria. Patients were included in each cohort only if a minimum level of anti-TNF was
detected in the 3 month plasma sample to assure drug exposure.
Whole-blood RNA (PAXgene) and plasma samples from baseline and after 3 months of treatment were profiled using a broad array of
technologies including RNAseq (Illumina HiSeq2500), shotgun and targeted proteomics, and glycan / glycopeptide analysis. A cell-
specific transcriptional data analysis methodology was developed and applied to results of RNAseq analysis to enable characterization
of the most common immune cell sub-populations.
Results:
Results from each cohort show a strong treatment-related molecular signature between 3 months and baseline, and also a high level of
correlation (ρ=0.7; permutation p<10-3), between cohorts. Interestingly, no significant difference could be established between
responders and non-responders in terms of treatment signature. Cell-specific transcriptional profiling analysis indicated a decrease in
neutrophil markers at 3 months (permutation p<0.01), which is concordant with observed changes in neutrophil counts. Shotgun
proteomics in plasma showed a significant reduction of acute phase proteins, including CRP. Results at baseline, comparing responders
to non-responders, demonstrated a lower concordance across the two cohorts, however, cell-specific analysis indicated increased
representation of innate cell type signatures in responders and, conversely, increased expression of adaptive cell type signatures in non-
responders. These results were not only conserved between the two cohorts, but were also observed when this analysis was applied to
other independent publicly available RA datasets assessing response to anti-TNF treatment.
Conclusion:
Results from this comprehensive molecular profiling study identified that differences in innate / adaptive immune cell signatures at
baseline may be a major contributor to response to anti-TNF treatment within the first 3 months of therapy. These observations were
supported by analysis of independent, publicly available RA datasets, and could potentially lead to an approach to patient selection,
resulting in improved treatment outcomes.
Disclosure: V. Farutin, Momenta Pharmaceuticals, Inc, 1,Momenta Pharmaceuticals, Inc, 3; T. Prod'homme, Momenta
Pharmaceuticals, Inc, 1,Momenta Pharmaceuticals, Inc, 3; K. McConnell, Momenta Pharmaceuticals, Inc., 1,Momenta
Pharmaceuticals, Inc., 3; N. Washburn, Momenta Pharmaceuticals, Inc., 1,Momenta Pharmaceuticals, Inc, 3; P. Halvey, Momenta
Pharmaceuticals, Inc, 1,Momenta Pharmaceuticals, Inc, 3; J. Guess, Momenta Pharmaceuticals, Inc, 1,Momenta Pharmaceuticals, Inc,
3; N. S. Gunay, Momenta Pharmaceuticals, Inc., 1,Momenta Pharmaceuticals, Inc., 3; J. Hillson, Momenta Pharmaceuticals, Inc,
1,Momenta Pharmaceuticals, Inc, 5,Chemocentryx, 1,Chemocentryx, 3; C. J. Etzel, Corrona, LLC, 3,Merck Human Health, 9; K. C.
Saunders, Corrona, LLC, 3; D. A. Pappas, Corrona, LLC., 3,Abbvie, 5,Abbvie, 2,Novartis Pharmaceutical Corporation, 9,Corrona,
LLC., 1; A. Manning, Momenta Pharmaceuticals, Inc., 1,Momenta Pharmaceuticals, Inc., 3; L. Ling, Momenta Pharmaceuticals, Inc,
1,Momenta Pharmaceuticals, Inc, 3; I. Capila, Momenta Pharmaceuticals Inc, 3,Momenta Pharmaceuticals Inc, 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/molecular-profiling-of-ra-patients-suggests-a-

differential-involvement-of-adaptive-and-innate-cell-populations-in-response-to-anti-tnf-treatment
The Inflammatory and Proliferative Synovial Lesion in Post-Infectious Lyme

Arthritis Results from Impaired Wound Healing
Robert Lochhead1,2, David Ordonez-Del Valle1,2, Klemen Strle2,3, Sheila Arvikar1,2, John Aversa4 and Allen Steere1,2, 1Center for
Immunology and Inflammatory Diseases, Massachusetts General Hospital, BOSTON, MA, 2Department of Medicine, Harvard Medical
School, BOSTON, MA, 3Department of Immunology and Inflammatory Diseases, Massachusetts General Hospital, BOSTON, MA,
4School of Medicine, Yale University, New Haven, CT
SESSION INFORMATION
Background/Purpose: Lyme arthritis (LA) is initially triggered by Borrelia burgdorferi infection, but in some patients, the synovitis
persists despite 2-3 months of antibiotic therapy and spirochetal killing, called post-infectious LA. As in rheumatoid arthritis (RA), post-
infectious LA is characterized by autoimmune inflammation and synovial hyperplasia. Our recent microRNA analysis revealed that
antibacterial responses characterized the infectious phase of LA, and impaired wound healing may contribute to inflammatory and
proliferative synovitis following resolution of infection. In mice, impaired wound repair and elevated interferon (IFN) responses during
B. burgdorferiinfection are associated with severe murine LA, but the role of impaired wound healing has not been explored in post-
infectious LA or RA.
Methods: High-throughput RNA sequencing was performed using synovial tissue from patients with post-infectious LA (n=14), RA
(n=5), and osteoarthritis (OA, n=5), and analyzed using in-house and online bioinformatics tools. Cells expressing IFNγ were identified
by intracellular cytokine staining and flow cytometry of cells collected from fresh synovial tissue and synovial fluid.
Immunofluorescent (IF) microscopy was used to identify IFNγ-responsive cells from patient synovial biopsies.
Results: 1001 genes were differentially expressed (DE) in post-infectious LA synovial tissue compared with OA tissue, of which 517
(43%) were interferon-regulated genes. In addition, 85/190 (45%) of genes in the response to wounding gene ontology (GO) set were
DE in post-infectious LA patients compared with OA patients. Of these, ~1/3 were involved in coagulation, cell
proliferation/differentiation, and extracellular matrix (ECM) formation, and were down-regulated in post-infectious LA, but less
consistently in RA, compared with OA; whereas ~2/3 were involved in immune activation, IFN responses, and ECM degradation, and
were up-regulated in both post-infectious LA and RA, compared with OA. Cytotoxic CD8+ T cells were a major source IFNγ in post-
infectious LA and RA synovial tissue, and fibroblasts within foci of active synovitis expressed high levels of IFNγ-inducible HLA-DR
molecules.
Conclusion: These data show that impaired wound healing is a previously unrecognized component of the inflammatory-proliferative
synovial pathology of post-infectious LA and RA. We propose that dysregulated wound healing in inflamed tissue may potentiate break
in immune tolerance during the early stages of autoimmune development. Thus, post-infectious LA provides a natural human model of
infection-induced autoimmunity, in which impaired wound healing leads to autoimmune synovial pathology of the chronic
inflammatory arthritides, including RA.
Disclosure: R. Lochhead, None; D. Ordonez-Del Valle, None; K. Strle, None; S. Arvikar, None; J. Aversa, None; A. Steere, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-inflammatory-and-proliferative-synovial-lesion-

in-post-infectious-lyme-arthritis-results-from-impaired-wound-healing
GWAS of Gout in Patients with Hyperuricemia Identified Many Possible New

Candidate Risk Alleles
Jing Cui1, Zhi Zhang1, Elizabeth Karlson2 and Daniel H. Solomon2, 1Division of Rheumatology, Immunology and Allergy, Brigham
and Women's Hospital, Harvard Medical School, Boston, MA, 2Brigham and Women's Hospital and Harvard Medical School, Boston,
MA
SESSION INFORMATION
Background/Purpose: Virtually all gout patients have high levels of uric acid in the blood (hyperurincemia, HU), but approximately
80% of patients with HU will never develop gout. There are a numbers of GWAS that identified risk alleles for hyperuricemia and/or
gout using general population as comparison. This study examines genes that might influence the risk of gout among subjects with HU.
Methods: Subjects with HU (uric acid ≥6.5 mg/dl from lab data) and available GWAS data were requested from Partners HealthCare
Biobank, a collaborative database that contains linked electronic medical records (EMR), survey data and genomic data for 15,000+
subjects. Gout was defined using a validated EMR algorithm with positive predict value of 0.95. Samples were genotyped from three
Illumina MEGA chips. We performed standard quality control (QC) procedures for each file, merged them into one analysis dataset,
and applied standard QC again. We restricted our genome-wide association study (GWAS) analysis to the Caucasian population.
Principal component analysis (PCA) was performed. Among subjects with HU, association between SNPs and gout was tested using
logistic regression assuming a genetic additive model. The first 10 PCAs were utilized as covariates to control for any potential
population stratification. We also looked at potential gout and HU SNPs with genome-wide significance among European ancestry from
the GWAS Catalog (https://www.ebi.ac.uk/gwas/) .
Results: 3146 self-reported Caucasian subjects with HU were identified from the Biobank, with 467 (14.8%) were identified as having
gout. The gout group was slightly older (mean ±SD, 72±11 vs 66±14, p<0.0001), more likely to be male (79% vs 56%, p<0.0001)
compared to non-gout HU group. 793,514 SNPs passed QC and were utilized in the GWAS. The most significant SNP was rs1481012
in ABCG2 gene with p value of 1.8 x 10-6, which is a known risk factor for gout. We identified 14 SNPs at p ~10-6 (see Table); 12 were
new SNPs and 2 had been previously identified as gout/HU risk SNPs from the GWAS catalog. 53 SNPs were identified at p~10-5; only
1 is a previously identified gout/HU risk SNP. 623 SNPs were identified at p~10-4; with only 1 as a known gout/HU SNP.
Conclusion: We carried out a GWAS of gout in patients with HU, and found that some of the risk alleles for gout in the general
population are also associated with gout in a population with HU. But, we found many possible new SNPs and some previously
identified SNPS were null in the HU population. The null findings may be because of limited power, confounding, or true non
associations.
Table Top 20 SNPs associated with gout compared to hyperuricemia

SNP Chr BP Allele Gene OR P
Known gout/HU risk SNPs from previous GWAS with genome-wide
significance
rs1481012 4 89039082 G ABCG2 0.61 1.8E-06
kgp2887248 4 89052323 T ABCG2 0.61 1.8E-06
rs4148155 4 89054667 G ABCG2 0.61 1.8E-06
Not found in previous GWAS (new SNPs identified)
JHU_2.206047717 2 206047718 A PARD3B 0.20 1.9E-06
rs7020787 9 12340300 C - 1.42 1.9E-06
rs73235131 21 23989516 T - 0.60 2.9E-06
rs2367897 12 72492104 G TRHDE 0.67 2.9E-06
rs1928873 9 12350564 C - 0.72 4.4E-06
rs4760822 12 72479611 T TRHDE 0.67 5.5E-06
JHU_9.12340636 9 12340637 T - 1.39 6.1E-06
rs7222347 17 72027224 T - 0.52 6.2E-06
rs7040701 9 12318093 C - 1.38 8.0E-06
rs143936778 5 34594023 A - 0.41 8.3E-06
rs113854545 10 53981733 G PRKG1 0.37 8.3E-06
JHU_12.72507970 12 72507971 T TPH2 0.68 1.0E-05
rs7721690 5 85185350 A - 1.68 1.1E-05
rs59996437 3 30845824 T GADL1 0.20 1.2E-05
JHU_10.102775026 10 102775027 G PDZD7 0.65 1.2E-05
rs10756369 9 12401666 A - 0.73 1.5E-05
JHU_12.128023894 12 128023895 G - 1.38 1.8E-05
Disclosure: J. Cui, None; Z. Zhang, None; E. Karlson, None; D. H. Solomon, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/gwas-of-gout-in-patients-with-hyperuricemia-

identified-many-possible-new-candidate-risk-alleles
A Personalized Medicine Approach to Improve the Prediction of Azathioprine-

Induced Pancreatic Injury: Preliminary Results
Tyler Reese1, Savannah Hurt2, Rany Octaria2, Alyson Dickson2, Prathima Anandi2, Vivian Kawai2, Kelly Birdwell2, Adriana Hung2,
C. Michael Stein3, QiPing Feng2 and Cecilia P. Chung3, 1Department of Medicine, Vanderbilt University Medical Center, Nashville,
TN, 2Vanderbilt University Medical Center, Nashville, TN, 3Medicine, Vanderbilt University Medical Center, Nashville, TN
SESSION INFORMATION
Background/Purpose: Azathioprine (AZA) is used to treat rheumatic diseases and to prevent transplant rejection. There is marked
variability in toxicity to azathioprine; one such toxicity is thiopurine-induced acute pancreatitis (TIAP). The cause of TIAP is not
known, but a HLA-DRB1*07:01-HLA-DQA1*02:01 haplotype was recently identified as a risk factor, suggesting that pancreatic injury
may be immunologically mediated and modified by genetic factors. We aimed to build a cohort of patients who had pancreatic injury
while taking AZA to perform pharmacogenetic studies. Here we present preliminary data.
Methods: We used the Vanderbilt University Medical Center BioVU resource that contains de-identified medical records linked to a
biobank containing DNA samples from 225,000 patients. A validated bioinformatic algorithm was used to assemble a cohort of
European American patients taking AZA. Those AZA users with amylase or lipase values that exceeded twice the upper limit of normal
or with ICD-9/ICD-10 codes for acute pancreatitis were identified. Each record was reviewed to confirm AZA use at the time and to
further classify patients into three not mutually exclusive categories: pancreatic injury (enzyme abnormalities alone), acute pancreatitis
(defined by American College of Gastroenterology Guidelines), or TIAP (Figure 1). The remaining patients served as controls. Age,
sex, race, and BMI were compared between groups. All available genotypes from Infinium MEGAEX, a platform for genome wide
analysis (GWA), were retrieved. After standard quality control measures with removal of variants with minor allele frequency <0.01, we
performed an exploratory GWA with 849,934 variants adjusted for age and sex.
Results: We identified 3,212 AZA users. Evidence of pancreatic injury based on enzyme abnormalities occurred in 109 patients, of
whom 22 and 7 met criteria for pancreatitis and TIAP, respectively. The remaining 3,103 were controls (Figure 1). Patients with
pancreatic injury were more likely to be male (p=0.002). MEGAEX genotypes were available in 34 cases and 449 controls. Although the
results did not reach GWAS statistical significance, variants in two snps, rs4859716 (p=3.01x10-6) and rs4843192 (p=7.13x10-6),
differed in patients with pancreatic injury.
Conclusion: These preliminary findings suggest that AZA users with pancreatic injury are more likely to be male and that variants in
rs4859716 or rs4843192 may be associated with pancreatic injury. The rs4859716 variant is an intergenic variant near the SHROOM3
gene, necessary for epithelial morphogenesis of the gut, and rs4843192 is an intergenic variant near the FOXL1 gene, a tumor
suppressor gene whose activity predicts tumor aggressiveness in pancreatic cancer. Further investigation is warranted into clinical and
genetic determinants of pancreatic toxicity with azathioprine.
ADDIN EN.REFLIST
Disclosure: T. Reese, None; S. Hurt, None; R. Octaria, None; A. Dickson, None; P. Anandi, None; V. Kawai, None; K. Birdwell,
None; A. Hung, None; C. M. Stein, None; Q. Feng, None; C. P. Chung, NIH/NIAMS and Rheumatology Research Foundation, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-personalized-medicine-approach-to-improve-the-

prediction-of-azathioprine-induced-pancreatic-injury-preliminary-results

The Autoimmune Discovery Ichip Distinguishes Healthy Individuals (HC) from
Those with SLE, Rheumatoid Arthritis (RA), Scleroderma (SSc), Sjogren’s
Syndrome (SS), and the Anti-Phospholipid Syndrome (APS)
Chaim Putterman1, Armando Gabrielli2, Alexandra Balbir-Gurman3, Pennina Safer4, Keren Jakobi-Brook4, Rachel Sorek4, Ilana
Gluzman4, Steve Wallace5 and Irun R. Cohen4,6, 1Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY, USA,
Bronx, NY, 2Istituto di Clinica Medica dell'Università di Ancona, Ancona, Italy, Ancona, Italy, 3Rheumatology Unit, Rambam Health
Care Campus, Rappaport Faculty of Medicine, Technion, Haifa, Israel, Haifa, Israel, 4ImmunArray Ltd., Rehovot, Israel, Rehovot,
Israel, 5ImmunArray Inc., VA, USA, Richmond, VA, 6Weizmann Institute of Science, Rehovot, Israel, Rehovot, Israel
SESSION INFORMATION
Background/Purpose:
Current serological tests are not sufficiently accurate in differentiating between HC and those with autoimmune rheumatic diseases. We
developed the iCHIP antigen microarray to provide extensive autoantibody profiling in human serum. We previously described the SLE-
Key Rule-Out test, which distinguishes SLE patients from HC with 94% sensitivity, 75% specificity, and a negative predictive value
(NPV) of 93%1,2,3. Here, we report the use of the autoimmune discovery iCHIP to distinguish between HC and subjects with SLE, RA,
SSc, SS, and the APS.
Methods:
We examined IgM and IgG autoantibodies binding to 519 antigens (1038 features) in the sera of HC subjects (N=136), and in patients
with SLE (N=30), RA (N=30), SSc (N=40), SS (N=20), and APS (N=16). FDR-adjusted p-values were calculated for each univariate
test. Three independent multivariate classification methods were applied: Support Vector Machine (SVM), Quadratic Discriminant
Analysis (QDA) and Naive Bayesian classifier (NB). Classifier training and testing were performed based on 10-fold cross validation on
all samples, and the performance of each classifier was determined.
Results:
Univariate analysis revealed multiple statistically significant separating reactivities. We found that IgG autoantibody reactivity to the
connective tissue antigen receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) differentiated HC subjects with all of
the 5 diseases with a p value of 2.8E-63. Other highly significant autoantigen reactivities included connective tissue proteins such as
collagen III (p = 6.5E-26 (IgM)) and collagen II (p = 5E-22 (IgG)). Figure 1 shows anti-LAIR-1 data comparing HC subjects to each of
the 5 diseases; each of the three classification methods differentiated between HC and subjects with autoimmune diseases. The typical
mean classifier performance was 93% sensitivity, 96% specificity, and 95% accuracy. Interestingly, LAIR-1 appears to function as a
“checkpoint” down-regulator of immune reactivity4 ; thus, it is possible that anti- LAIR-1 represent a target for therapeutic discovery
and also may be pathogenic, and predispose to a variety of autoimmune conditions.
Conclusion:
Autoantibody specificities detected by the autoimmune discovery iCHIP successfully distinguished between HC individuals and
individuals with several autoimmune rheumatic diseases, including SLE, RA, SSc, SS, and APS. These preliminary results are based on
relatively small numbers of serum samples, but are very promising and warrant additional validation in larger cohorts of autoimmune
and HC subjects.
References: 1Putterman et al; J Immunol Methods 2016 2Cohen IR, LOA 2016 3Massenburg et al; LOA 2017 4Tang et al; J Immunol
2012
Acknowledgements: Authors wish to acknowledge Cohen-Gindi O, Lerner M, Tarnapolski O, Blumenstein Y, Javaherian A, Pitts J,
Barton M and Wong E
Disclosure: C. Putterman, Consultant, 5; A. Gabrielli, None; A. Balbir-Gurman, None; P. Safer, None; K. Jakobi-Brook, None; R.
Sorek, None; I. Gluzman, None; S. Wallace, None; I. R. Cohen, Consultant, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-autoimmune-discovery-ichip-distinguishes-

healthy-individuals-hc-from-those-with-sle-rheumatoid-arthritis-ra-scleroderma-ssc-sjogrens-syndrome-ss-and-the-anti-phospholipid-
synd
High-Throughput Proteomic Profiling Identifies Dysregulated Proteins in Neonatal-

Onset Multisystem Inflammatory Disease (NOMID) That Respond to IL-1blocking
Treatment
Megha Garg1,2, Brian Sellers3, Adriana Almeida de Jesus4, Angélique Biancotto5, Foo Cheung6 and Raphaela Goldbach-Mansky4,
1National Institutes of Arthritis, Musculoskletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 2Translational
Autoinflammatory Disease Studies, NIH/NIAID, Bethesda, MD, 3Center for Human Immunology, Autoimmunity and Inflammation,
NIH/NHLBI, Bethesda, MD, 4Translational Autoinflammatory Disease Studies (TADS), Laboratory of Clinical Investigation and
Microbiology (LCIM), NIAID/NIH, Bethesda, MD, 5Center for Human Immunology, Autoimmunity and Inflammation (CHI), NHLBI,
NIH, Bethesda, MD, 6Center for Human Immunology Autoimmunity and Inflammation (CHI), NHLBI, NIH, Bethesda, MD
SESSION INFORMATION
Background/Purpose: Neonatal-onset multisystem inflammatory disease (NOMID) is an IL- 1 mediated autoinflammatory disease
caused by a gain-of-function mutations in NLRP3that results in constitutive activation of IL-1b and specific organ/tissue inflammation
and damage. To date no reliable serum biomarkers that identify IL-1 mediated systemic inflammation or inflammatory organ damage
particulary CNS inflammation exist. We explore high-throughput proteomic profiling to screen for potential biomarkers.
Methods: Serum samples were obtained from healthy age-matched children (HC), n=8 and 12 NOMID patients(pts.) before and after a
median of 42 months (range 3-96mo) after starting IL-1 blocking treatment with anakinra. All patients were in inflammatory remission
at the time of blood draw. Using an aptamer-based proteomic assay (SOMAscan) we screened 1129 proteins. To identify biomarkers of
exaggerated systemic and tissue specific IL-1-mediated inflammation, we selected proteins that significantly changed with anakinra
treatment many were significantly increased or decreased in untreated NOMID vs HC. Mann-Whitney U test and Wilcoxon rank-sum
analyses with FDR correction were used for statistical comparison. We determined RNA transcripton levels (RNAseq) of the protein
targets in whole blood. RPKMs< 1 characterized low expression in blood cells and suggested that the protein origin might be from non-
hematopoietic cells. We also determined protein function.
Results: In the SOMAscan Assay we identified 70 proteins that changed in the serum of NOMID pts. before and after treatment (n=12;
q<0.05). Of these 15 (21%) were also significantly increased or decreased compared to controls at baseline. Protein levels of 30 proteins
decreased and protein levels of 40 increased with treatment. Of these, 63% and 82% respectively had low or no gene expression in
whole blood. Protein targets of the IL-1 pathway (IL-1β, soluble IL-1RI, IL-1 RAcP) significantly decreased. Of markers that decreased
were those indicating systemic inflammation including complements (i.e CRP, SAA1, C3, C9, CFI) and markers that have been
associated with tissue damage including CNS manifestaions (CFI TNFSD11A) and hypercoagualabitly (F9) as well as vascular
endothelial markers associated with atherosclerosis (PLAUR, CST3). Of the markers that increase, most are associated with growth and
tissue regeneration (including growth hormone receptor: GHR, IGFBP3 and -5, NOTCH3, TGFβ), p<0.05 for all.
Conclusion: Protein changes with anakinra treatment reveal markers of IL-1 pathway that are not reliabley detectable in ELISA assays
and transcription assays. These markers need to be validated in other presumed IL-1 mediated diseases. Furthermore, markers of tissue
inflammation particulary of CNS inflammation need to be validated in treatment studies to determine their utility in assessing
appropriate treatment with IL-1 blocking therapies.
Disclosure: M. Garg, None; B. Sellers, SomaLogic, 1; A. Almeida de Jesus, None; A. Biancotto, None; F. Cheung, None; R.
Goldbach-Mansky, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/high-throughput-proteomic-profiling-identifies-

dysregulated-proteins-in-neonatal-onset-multisystem-inflammatory-disease-nomid-that-respond-to-il-1blocking-treatment
Submetabolome Profiling with Differential Chemical Isotope Labeling Liquid

Chromatography Mass Spectrometry and a Universal Metabolome Standard Reveals
a Metabolite Profile with 99% Accuracy for Rheumatoid Arthritis
Walter P. Maksymowych1, Derrick Blackmore2, Roman Eisner3, Liang Li4 and Zaeem Siddiqi2, 1Department of Medicine, University
of Alberta, Edmonton, AB, Canada, 2Medicine, University of Alberta, Edmonton, AB, Canada, 3City of Edmonton, Edmonton, AB,
Canada, 4Chemistry, University of Alberta, Edmonton, AB, Canada
SESSION INFORMATION
Background/Purpose: Early diagnosis of rheumatoid arthritis (RA) is hampered by suboptimal accuracy of currently available
serological biomarkers. Recent advancements in metabolomic profiling include dansylation liquid chromatography mass spectrometry
(LC-MS), resulting in 1000-fold increase in detection sensitivity of amine/phenol-containing metabolites, and universal metabolome-
standard (UMS) methodology in conjunction with differential chemical isotope labeling (CIL LC−MS), to provide long-term analytical
reproducibility and facilitate metabolome comparisons among different data sets. CIL LC-MS uses different labeling reagents to target
chemical group-based submetabolomes to provide in-depth metabolomic analysis. We aimed to identify a metabolite signature with high
accuracy for RA.
Methods: 12C-dansylation and acid labeling of individual serological samples and 13C-dansylation and acid labeling of pooled samples
from 47 age/gender matched healthy control subjects, 52 age/gender matched RA patients, and 46 patients with seropositive myasthenia
gravis was undertaken. A total of 7,458 amine/phenol and 9954 organic acid metabolites were combined into a single data set for
analysis. Metabolite concentrations were natural-log transformed. Model accuracy estimation was performed using 5-fold cross-
validation, and metabolites were selected using within-fold feature selection. Metabolites were ranked using Spearman correlation
coefficient, and the top n were selected, with a varying n. Training of the predictive model was done using a linear Support Vector
Machine (SVM). After cross-validation, the final model formula was calculated on the entire data set using the same methodology as
was evaluated using cross-validation. Cross-validation accuracy was further analyzed using randomly selected metabolites. Data
processing and analysis was performed entirely in R (version 3.2.3). SVM was trained using the e1071 package (version 1.6-7) and
cross-validation was done using the caret package (version 6.0-64).
Results: A total of 5711 metabolites were identified in all samples with orthogonal partial least squares discriminant analysis showing a
clear separation of the 3 groups (R2=0.98, Q2=0.80). 34 serum metabolites were identified as potential RA biomarkers with correlation
coefficients ≥0.80. Cross-validation accuracy of top-ranked metabolites, according to Spearman’s correlation, and using a varying
number of metabolites shows that 99.1% accuracy for RA versus controls is achieved using only 4 metabolites.
Conclusion: CIL LC-MS metabolomic profiling and UMS methodology reveals that serum metabolomes of RA patients differ
considerably from healthy and autoimmune disease.
Disclosure: W. P. Maksymowych, None; D. Blackmore, None; R. Eisner, None; L. Li, None; Z. Siddiqi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/submetabolome-profiling-with-differential-

chemical-isotope-labeling-liquid-chromatography-mass-spectrometry-and-a-universal-metabolome-standard-reveals-a-metabolite-
profile-with-99-accuracy-for-rheuma
Gene Expression Analysis Reveals Common Pathways of Tissue Pathogenesis in

Lupus Organ Involvement
Amrie Grammer1, Sarah Heuer1, Robert Robl1, Adam Labonte1, Prathyusha Bachali1, Sushma Madamanchi1 and Peter E. Lipsky2,
1AMPEL BioSolutions and RILITE Research Institute, Charlottesville, VA, 2AMPEL BioSolutions, LLC, Charlottesville, VA
SESSION INFORMATION
Background/Purpose:
Lupus is a prototypic autoimmune disease characterized by B cell hyperactivity, autoantibody formation and resultant tissue damage.
The mechanisms underlying tissue pathology in lupus are not completely understood. Analysis of gene expression in various tissues has
been employed in an attempt to develop a better understanding of disease pathogenesis and tissue injury. The current experiments were
undertaken to develop a more comprehensive understanding of molecular pathways involved in lupus organ pathogenesis by assessing
gene expression profiles so that novel treatment candidates targeting commonly dysregulated cellular functions could be identified.
Methods:
Publicly available gene expression profiles were identified in GEO from lupus affected skin, synovium, and kidney. The raw data were
downloaded, normalized, curated and assessed for differentially expressed (DE) genes. Correlation with clinical or histologic features
was carried out by Weighted Gene Correlation Network Analysis (WGCNA) and variation in pathway activity was determined in
individual samples and groups of samples by Gene Set Variation Analysis (GSVA).
Results:
More than 300 gene expression profiles from lupus patients and controls were analyzed to determine DE genes (8279 discoid lupus skin,
5465 synovium, 6381 kidney glomerulus WHO class 3/4, 5587 kidney tubulointerstitum WHO class 3/4). Notably, 45% of lupus tissue
DE genes were detected in more than one tissue and 439 were differentially expressed in all tissues. Curated STRING-based protein-
protein interaction analysis carried out using MCODE in Cytoscape of these 439 DE genes identified a number of gene clusters that
were functionally characterized by both Biologically Informed Gene Cluster Analysis (BIG-C) and IPA. BIG-C identified 13 pathways
that were abnormally expressed in all lupus tissues, whereas IPA identified 65 dysregulated pathways shared among these tissues. Using
the the 45 BIG-C functional categories, GSVA separated lupus tissues from control tissues, identified commonly dysregulated functional
pathways, documented individual tissue variation and also largely identified the same functional pathways that emerged from pathway
construction generated from DE genes. WGCA identified a number of gene modules that correlated with clinical of histologic features.
These modules contained nearly 85% of the DE genes. A number of approaches were employed to connect the dysregulated lupus organ
pathways to potential drug candidates, including cross referencing to the Library of Integrated Network Based Cellular Signatures
(LINCS). More than 75 potential drug candidates were identified.
Conclusion:
These results indicate that common cellular and molecular pathways can be identified in all of the affected lupus tissues, implying that
related processes might be involved in the pathology of multiple organs in this autoimmune disease. Connectivity between lupus organ
gene expression abnormalities and candidate drug induced changes in gene expression identified a number of potential novel treatments
that could target the commonly dyregulated molecular pathways underlying lupus organ pathology.
Disclosure: A. Grammer, None; S. Heuer, None; R. Robl, None; A. Labonte, None; P. Bachali, None; S. Madamanchi, None; P. E.
Lipsky, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/gene-expression-analysis-reveals-common-

pathways-of-tissue-pathogenesis-in-lupus-organ-involvement
Quantification of Leukocytes’ Secretome to Guide Diagnosis and Treatment Options

in Patients with Suspected Chronic Auto-Inflammatory Syndromes
Philippe A. Tessier1, Marie-Pier Longchamps1, Nathalie Amiable1, Nathalie Pagé1, Laetitia Michou2, Louis Bessette2, Paul R. Fortin1,
Alexandra Albert2, Anne-Laure Chetaille2 and Martin Pelletier1, 1Infectious Diseases and Immunity Research Division, CHU de
Québec-Université Laval Research Center, Québec, QC, Canada, 2Division of Rheumatology, Department of Medicine, CHU de
Québec-Université Laval, Québec, QC, Canada
SESSION INFORMATION
Background/Purpose: Auto-inflammatory syndromes are inherited conditions characterized by recurrent inflammation (fever,
abdominal pain, dermatitis, arthritis). Diagnosis and treatments are challenging as detection rate of mutations in patients with high
suspicions for auto-inflammatory syndromes is low, symptoms are reminiscent of other autoimmune diseases, especially Systemic
Autoimmune Rheumatic Diseases (SARD), and the cytokines abnormally secreted are unknown. As a consequence, patients can be
misdiagnosed, leading to inappropriate treatment, severe complications and substantial socio-economic costs. We hypothesized that the
secretion of cytokines by peripheral blood mononuclear cells (PBMC) is an indicator of the disease and could guide the treatment to the
most suitable anti-cytokine.
Methods: Plasma and peripheral blood mononuclear cells (PBMCs) were obtained from healthy controls, suspected auto-inflammatory
patients, and rheumatoid arthritis and systemic lupus erythematosus patients from the CHU de Québec SARD Biobank Repository
Database (SBRD). PBMC were stimulated with inflammatory and immune stimuli, and cytokines in the supernatant were analyzed by
multiplex assays.
Results: The cytokines found in the plasma were similar between healthy donors, SARD patients and suspected auto-inflammatory
patients. In contrast, PBMC had a distinct profile of cytokine secretion. Stimulation of PBMCs with IL-15 or anti-Ig (Figure 1) led to
differential secretion of members of IL-1 cytokine family, IL-12 and IFNγ in autoimmune, but not auto-inflammatory patients. In
contrast, stimulation with inflammasome activators or pro-inflammatory cytokines led to selective secretion of IL-1α, IL-1β, IL-1RA,
IL-18 (Figure 2), IFNγ or IL-12 in suspected auto-inflammatory patients, but not in autoimmune patients.
Conclusion: This study demonstrates that analysis of leukocytes’ secretome is reliably more sensitive than serum to reveal cytokine
signatures and to predict treatment options in patients with suspected chronic auto-inflammatory syndromes.
Acknowledgement: This work was partly funded by the Fondation du Grand défi Pierre Lavoie. We thank Pfizer, Amgen, BMS,
Abbvie, Roche, Sanofi-Genzyme and Merck & Co. for their unrestricted financial support of the SBRD.
Figure 1: Stimulation of PBMCs with anti-immunoglobulins to activate B cells reveals different cytokine signatures between
autoimmune and auto-inflammatory patients
Figure 2: Stimulation of PBMCs with inflammasome activators or pro-inflammatory cytokines uncovers abnormal over-
secretion of the IL-1 cytokine family member IL-18 by auto-inflammatory patients
Disclosure: P. A. Tessier, None; M. P. Longchamps, None; N. Amiable, None; N. Pagé, None; L. Michou, None; L. Bessette,
Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Lilly, Novartis, Sanofi, 8,Amgen, BMS, Janssen, Roche, UCB,
AbbVie, Pfizer, Merck, Celgene, Lilly, Novartis, Sanofi, 5,Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Lilly,
Novartis, Sanofi, 2; P. R. Fortin, None; A. Albert, None; A. L. Chetaille, None; M. Pelletier, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/quantification-of-leukocytes-secretome-to-guide-

diagnosis-and-treatment-options-in-patients-with-suspected-chronic-auto-inflammatory-syndromes
Association of a Non-Synonymous, Loss-of-Function, Variant in NOD2 with Reduced

Tissue Damage in ACPA +Ve RA
Ricardo Segurado1, Denis Shields1, Rachel Knevel2, Annette H.M. van der Helm-van Mil3, Tom W.J. Huizinga4 and Anthony G.
Wilson5, 1University College Dublin, Dublin, Ireland, 2Medical and Population Genetics Program, Broad Institute of MIT and Harvard,
Cambridge, MA, 3Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands, 4Department of
Rheumatology, LUMC, Leiden, Netherlands, Leiden, Netherlands, 5UCD School of Medicine and Medical Science, Conway Institute,
University College Dublin, Dublin, Ireland
SESSION INFORMATION
Background/Purpose:
The functional capacity of individuals with rheumatoid arthritis (RA) is related to the severity of damage to bone and cartilage within
joints. This is a highly variable trait that is known to have a significant genetic component. A loss-of-function non-synonymous variant
(rs2066844, Arg702Trp) in nucleotide-binding oligomerization domain containing 2 (NOD2) gene, results in lower activation of NF-
kB-mediated inflammation and tissue damage in RA. Our hypothesis was that the 702Trp variant is, as a result of reduced inflammatory
load, be associated with lower radiological damage in RA.
Methods:
The initial study was performed in the British Genetics of RA (GORA) cross-sectional population (N=914), radiological damage was
assessed by the Modified Larsen Score (MLS). Genotyping was performed using either the Illumina HumanCoreExome array (N=568)
or the Illumina HumanCNV370 Quad v3 array (N=346). Genotypes for rs2066844 were imputed for individuals typed on latter platform
using IMPUTE v2. Replication was performed in the Leiden EAC (N=597), with damage assessed at baseline and yearly thereafter
using the Sharp-van der Heijde score (SHS) and samples were genotyped on the Illumina iScan platform (Immunochip). RF and ACPA
status was available for both populations. Analyses were conducted in R v3.4.0 and SPSS v20. For the combined meta-analysis, we used
the most recent measurement on each patient in a zero-inflated negative binomial model adjusted for sex and age at assessment,
followed by a fixed-effects meta-analysis of the two summary statistics.
Results:
In the discovery GORA population the minor rs2066844 (702Trp) frequency was 5%, similar to the 1000 genomes European frequency
(5.1%), genotypes fitted Hardy-Weinberg equilibrium. The minor allele carriage was associated with lower MLS: incidence ratio risk
0.75 (95% CI: 0.60-0.93), p=0.009. The association was only significant in RF+ (p=0.008) or ACPA+ (p=0.013) subgroups. The
proportion of variance explained by rs2066844 was 0.007. In the replication Leiden cohort we observed a similar lower yearly
progression of SHS score for each minor allele, by 0.95 SHS (95% CI: 0.92-0.99, p=0.006) in all patient and in ACPA positive patients
(0.92, 95% CI: 0.87-0.97, p=0.004). Meta-analysis of the two cohorts revealed a significant pooled effect with an IRR of 0.76 (95% CI:
0.64-0.91 , p=0.003).
Conclusion: These data reveal a protective effect of rs2066844 minor allele with severity of sero-positive RA that is likely a
consequence of the lower inflammatory activity associated with this genotype. Although the overall influence on the variance of tissue
damage is modest, in combination with established prognostic biomarkers, it may contribute to the development of prognostic algorithm
for RA.
Disclosure: R. Segurado, None; D. Shields, None; R. Knevel, None; A. H. M. van der Helm-van Mil, None; T. W. J. Huizinga,
None; A. G. Wilson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/association-of-a-non-synonymous-loss-of-function-

variant-in-nod2-with-reduced-tissue-damage-in-acpa-ve-ra

What to Measure after Arthroplasty? Confirmation of a Core Domain Set
Anh Hoang1, Susan M. Goodman2, Mark P. Figgie3, Mathias Bostrom4, Douglas Padgett4, Lisa A. Mandl5,6,7, Peter Sculco8,
Alexander McLawhorn9 and Jasvinder A. Singh10, 1Rheumatology, Hospital for Special Surgery, New York, NY, 2Medicine, Hospital
for Special Surgery/Weill Cornell Medicine, New York, NY, 3Orthopaedic Surgery, Hospital for Special Surgery/Weill Cornell
Medicine, New York, NY, 4Orthopaedic Surgery, Hospital for Special Surgery, New York, NY, 5Department of Medicine, Hospital for
Special Surgery, New York, NY, 6Rheumatology, Hospital for Special Surgery/Weill Cornell Medicine, New York, NY, 7Department of
Rheumatology, Hospital for Special Surgery, New York, NY, 8Orthopaedic Surgery, Hospital for Special Surgey, New York, NY,
9Hospital for Special Surgey, New York, NY, 10Rheumatology, University of Alabama at Birmingham, Birmingham, AL
SESSION INFORMATION
Session Title: Health Services Research Poster II: Osteoarthritis and Rheumatoid Arthritis
Background/Purpose: The Outcomes Measures in Rheumatology Trials (OMERACT) TJR Working Group has proposed six core
domains that would constitute a standardized measurement set that can be used as a tool to compare outcomes among TJR clinical trials.
The specific aim was to query two different groups of stakeholders, patients and surgeons, to establish a consensus regarding the
domains.
Methods: We e-mailed a survey to 3810 hip/knee TJR patients and 49 hip/knee arthroplasty surgeons at a high-volume orthopedic
center of excellence to rate the importance of the six core domains and two additional domains for consideration. Ratings were on a 1 to
9 scale: 1-3 indicating limited or no importance for patients, 4-6 being important, but not critical, and 7-9 being critical. Scores were
summarized with median [interquartile range]. Comparisons between the sexes, age groups (< 55 years vs. ≥ 55 years), and participant
types (surgeons vs. patients) were made using the Wilcoxon rank-sum test.
Results: 1295 patients (34%) and 21 (43%) surgeons completed the questionnaire. Patient non-responders were similar in age (≥ 55
years, 86%) and gender (57.5% female) to responders. All core domains were confirmed as “critical” by both patients and surgeons.
This consensus rating persisted even when compared between the sexes as well as the age groups. The only exception was cost, while
“critical” overall, when compared to patients and females respectively, which both surgeons and males scored cost as only “important”,
not “critical”. Cost was also rated differently between those < 55 years vs. participants ≥ 55 years: 6 [5, 8] vs. 7 [5, 8], p=0.015.
Conclusion: Our study confirmed that both orthopedic surgeons and TJR patients agree that the OMERACT TJR core domains were
critical for patients. These results support a broad endorsement and encourage the identification of candidate outcome instruments to
further develop a TJR standardized measurement set.
Table 1. Demographic Characteristics (n=1316) N (%)

Sex Female 743 (56.5%)
Age Groups < 55 years 157 (12%)
≥ 55 years 1159 (88%)
Participant Type Hip/Knee TJR Patient 1295 (98.5%)
Orthopedic Surgeon 21 (1.5%)
Arthritis Conditions (TJR Patients only) Osteoarthritis only 1071 (82.7%)
Rheumatoid Arthritis 34 (2.6%)
Another type of arthritis 44 (3.4%)
Joints aches and pains 66 (5.1%)
No arthritis or joint aches or pains 80 (6.2%)
Table 2. Ratings of Domains for TJR Clinical Trials Between Patients & Surgeons
Patients Surgeons
Core Domains Overall p-value
(N=1316) (n=1295) (n=21)
Joint Pain 9 [8, 9] 9 [8, 9] 9 [7, 9] 0.75
Function or functional ability 9 [8, 9] 9 [8, 9] 8 [7, 9] 0.01
Patient Satisfaction 9 [8, 9] 9 [8, 9] 8 [8, 9] 0.02
Revision surgery 8 [5, 9] 8 [5, 9] 8 [7, 8] 0.41
Adverse events 8 [7, 9] 8 [7, 9] 7 [6, 9] 0.23
Death 9 [6, 9] 9 [6, 9] 9 [7, 9] 0.47
Patients Surgeons
Additional Domains for Consideration Overall p-value
(N=1316) (n=1295) (n=21)
Cost 7 [5, 8] 7 [5, 8] 6 [5, 6] 0.01
Patient participation in work and social activities 8 [6, 9] 8 [6, 9] 8 [6, 8] 0.26
Table 3. Ratings of Domains for TJR Clinical Trials Between Males & Females
Female Male
Core Domains Overall p-value
(N=1316) (n=743) (n=573)
Joint Pain 9 [8, 9] 9 [8, 9] 8 [7, 9] <0.001
Function or functional ability 9 [8, 9] 9 [8, 9] 9 [8, 9] <0.001
Patient Satisfaction 9 [8, 9] 9 [8, 9] 8 [8, 9] <0.001
Revision surgery 8 [5, 9] 8 [5, 9] 7 [5, 9] <0.001
Adverse events 8 [7, 9] 9 [7, 9] 8 [6, 9] <0.001
Death 9 [6, 9] 9 [7, 9] 9 [5, 9] 0.002
Female Male
Additional Domains for Consideration Overall p-value
(N=1316) (n=743) (n=573)
Cost 7 [5, 8] 7 [5, 9] 6 [5, 8] <0.001
Patient participation in work and social activities 8 [6, 9] 8 [7, 9] 7 [6, 8] <0.001
Disclosure: A. Hoang, None; S. M. Goodman, None; M. P. Figgie, Lima, 7,Mekanika, 1; M. Bostrom, None; D. Padgett, Pixar Bio,
1,DJO Global, 5,Hip Society, American Joint Registry, 9; L. A. Mandl, Boehringer Ingelheim, 2,American College of Physicians, 3,Up
To Date, 7; P. Sculco, None; A. McLawhorn, None; J. A. Singh, Takeda and Savient, 2,Savient, Takeda, Regeneron, Merz, Iroko,
Bioiberica, Crealta/Horizon and Allergan pharmaceuticals, WebMD, UBM LLC and the American College of Rheumatology., 5,JAS
serves as the principal investigator for an investigator-initiated study funded by Horizon pharmaceuticals through a grant to DINORA,
Inc., a 501 (c)(3) entity., 9,JAS is a member of the executive of OMERACT, an organization that develops outcome measures in
rheumatology and receives arms-length funding from 36 companies., 9,JAS is the editor and the Director of the UAB Cochrane
Musculoskeletal Group Satellite Center on Network Meta-analysis., 9,Jas is a member of the American College of Rheumatology's
(ACR) Annual Meeting Planning Committee (AMPC); Chair of the ACR Meet-the-Professor, Workshop and Study Group
Subcommittee., 9,a member of the Veterans Affairs Rheumatology Field Advisory Committee, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/what-to-measure-after-arthroplasty-confirmation-of-

a-core-domain-set
Healthcare Service Utilization and Costs of Certolizumab Pegol Versus Infliximab

Treatment in Patients with Rheumatoid Arthritis
Joseph Tkacz1, Edward Lee2, Robert Low2, Jeffrey Stark2, Mohamed Yassine2 and Brenna Brady1, 1Health Analytics LLC, Columbia,
MD, 2UCB Pharma, Smyrna, GA
SESSION INFORMATION
Background/Purpose: Prior retrospective claims analyses examining rheumatoid arthritis (RA) treatment costs have shown infliximab
(IFX) to be costlier than certolizumab pegol (CZP) across all sites of care (physician office, home, outpatient [OP]), primarily due to
lower CZP drug costs.1 The present study assessed one-year (yr) healthcare resource utilization (HRU) and costs incurred by RA
patients (pts) treated with CZP vs IFX.
Methods: Medical and pharmacy claims data (2008–2015) were derived from the Truven MarketScan® database of insured pts
matching the inclusion criteria: RA diagnosis, treatment initiation (index date) with CZP or IFX (July/1/2008–December/31/2014),
continuous eligibility ±12 months around index date, and age ≥18 yrs. Mean, unadjusted one-yr visits (OP, inpatient [IP], emergency
room [ER], and physician office) and costs (pharmacy, medical, and total healthcare) were calculated and compared between groups via
Mann-Whitney U tests. These were also assessed using multivariate (MV) regression models and adjusted for treatment (CZP/IFX),
prior biologic use (yes/no), gender, age, baseline health, and baseline HRU and costs.
Results: 1,398 RA pts were treated with CZP and 3,592 with IFX. CZP pts were more likely to have prior biologic use than IFX pts
(74.0% vs 40.8%, p<0.001; Table 1). In the unadjusted analyses, CZP pts demonstrated increased pharmacy usage (68.7 vs 56.1 fills per
pt per yr, p<0.001), but reduced physician office visits (19.8 vs 21.9, p<0.001) and OP hospital-based services (4.4 vs 4.9, p=0.221)
compared to IFX pts, resulting in greater overall pharmacy costs but lower medical expenditure than IFX patients (p values <0.001;
Figure 1A). In adjusted analyses, MV models controlling for patient and treatment characteristics revealed that prior biologic use was
associated with more office visits (p<0.001), OP visits (p<0.001), ER utilization (p<0.001), and elevated total medical costs (p<0.001).
Despite the CZP cohort having more biologic-experienced pts, CZP treatment was associated with fewer physician office (p<0.001;
Table 2) and OP (p<0.001; Table 2) services compared to IFX pts, but a greater pharmacy spend (p<0.001; Figure 1B). However, CZP
treatment was associated with reduced total healthcare costs (p<0.001), with IFX pts incurring over $4,000 per pt per yr more than CZP
pts ($46,908 vs $42,867, p<0.001; Figure 1B).
Conclusion: Despite the CZP-treated RA population having a higher rate of prior biologic use, which has been correlated with more
severe disease,2 annual total healthcare costs were higher for IFX-treated RA pts. MV models controlling for demographics and baseline
HRU revealed that treatment with CZP was associated with a $4,000 saving per pt per yr compared to treatment with IFX.
References:
1. Tkacz J. J Manag Care Spec Pharm 2016;22(Suppl10):S106(Abstract M12)
2. Harrold L. Arthritis Rheumatol 2016;68(Suppl10):3489–91

Disclosure: J. Tkacz, Health Analytics LLC, 3; E. Lee, UCB Pharma, 3; R. Low, UCB Pharma, 3; J. Stark, UCB Pharma, 3; M.
Yassine, UCB Pharma, 3; B. Brady, Health Analytics LLC, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/healthcare-service-utilization-and-costs-of-

certolizumab-pegol-versus-infliximab-treatment-in-patients-with-rheumatoid-arthritis
Developing a Multi-Phase Claims-Based Algorithm to Facilitate the Study of Drug

Exposure during Pregnancy
S Phillips1, KE Johnson1, SW Shen2, KJ Woodcroft3, SA Oliveria4 and TA Simon5, 1QuintilesIMS, Seattle, WA, 2Bristol-Myers
Squibb, Hopewell, NJ, 3Henry Ford Health System, Detroit, MI, 4QuintilesIMS, New York, NY, 5Bristol-Myers Squibb, Princeton, NJ
SESSION INFORMATION
Background/Purpose: The use of antirheumatic medications during pregnancy may lead to birth defects or other complications. Safety
studies are critical, with registries being common but often yielding a small number of cases after years of follow-up. Medical
administrative claims data can be used to study large numbers of women and infants more quickly and efficiently, if these claims data
accurately identify: pregnancy outcomes, gestational age, drug exposure by trimester and mother/infant links. No single existing
algorithm uses only administrative claims data to measure all of these variables. The objective is to develop a multi-phase algorithm for
use in administrative medical claims data to identify live/non-live pregnancy outcomes (phase 1), estimate gestational age (phase 2),
estimate drug exposure by trimester (phase 3) and link claims data for mothers and infants (phase 4).
Methods: A multi-phase algorithm is being developed in a phased manner among women aged ≥15 and ≤50 years with ≥1 International
Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) end of pregnancy code. Women were enrolled and had
prescription coverage 340 days prior to the end of pregnancy in the Henry Ford Health System between 1/1/2013 and 9/30/2015. In all
phases, algorithms will be developed, applied to claims data and compared to electronic medical records for validation. Positive
predictive value (PPV), sensitivity and 95% CI will be calculated. The best performing algorithm developed in each phase will be used
to move to the next phase.
Results: A total of 698 women met inclusion criteria. Three algorithms were developed and tested for phase 1. Algorithm 1 (≥1
definitive ICD-9-CM end of pregnancy code) performed best (Table 1). Two algorithms for phase 2 were developed and tested.
Algorithm 2 (adjusted delivery date based on selected procedure codes and assigned 245 days to preterm, 273 days to term, and 294
days to post-term) performed best for preterm and term births (Table 2).
Conclusion: End of pregnancy outcomes can be identified in claims data with high PPV and sensitivity. Gestational age can be
estimated with reasonable PPV and sensitivity for preterm and term live births. Further analyses are underway for phases 3 and 4.
Disclosure: S. Phillips, Bristol-Myers Squibb, 2,QuintilesIMS, 3; K. Johnson, None; S. Shen, Bristol-Myers Squibb, 3,Bristol-Myers
Squibb, 1; K. Woodcroft, None; S. Oliveria, QuintilesIMS, 3; T. Simon, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/developing-a-multi-phase-claims-based-algorithm-

to-facilitate-the-study-of-drug-exposure-during-pregnancy
Trends in Hospitalizations Following Heart Failure Diagnosis in Rheumatoid

Arthritis
Elena Myasoedova1, Eric L. Matteson2, Sara J. Achenbach3, John M. Davis III4, Soko Setoguchi5, Sherine E. Gabriel6 and Cynthia S.
Crowson7, 1Rheumatology, Mayo Clinic, Rochester, MN, 2Rheumatology, Mayo Clinic College of Medicine and Science, Rochester,
MN, 3Mayo Clinic, Rochester, MN, 4Division of Rheumatology, Mayo Clinic, Rochester, MN, 5Rutgers School of Public Health, New
Brunswick, NJ, 6Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, 7Health Sciences Research, Mayo Clinic College
of Medicine and Science, Rochester, MN
SESSION INFORMATION
Background/Purpose: The rising prevalence of heart failure (HF) in the general population and associated increased hospitalization
costs is a major public health problem. There is a 2-fold increased risk of HF in rheumatoid arthritis (RA) compared to the general
population. Little is known about hospitalization rates in patients with RA and HF. We aimed to compare the frequency of and trends in
hospitalizations following HF diagnosis in patients with and without RA during 1987-2015.
Methods: The study included a retrospectively identified population-based cohort of patients with incident HF and prior RA (age≥18
years, 1987 ACR criteria) and a comparison cohort of incident HF patients without RA matched 3:1 on age, sex, and year of HF
diagnosis. Hospitalizations at the time of HF diagnosis were excluded from analyses. All subjects were followed until death, migration,
or 1/1/2015. Person-years methods and rate ratios (RR) from Poisson regression models were used to compare hospitalization rates
between the groups. Generalized linear models were used to analyze the length of stay (LOS).
Results: The study included 212 patients with RA (mean age at HF diagnosis 78.3 years; 68% female) and 636 non-RA patients (mean
age at HF diagnosis 78.6 years; 68% female). The hospitalization rate following HF diagnosis was higher in RA vs non-RA patients
(RR 1.16; 95%CI 1.08-1.25). This difference may be decreasing after 2010 (Figure). The magnitude of the increase was similar in both
sexes and across all ages. In patients with available echocardiography, HF with preserved ejection fraction (HFpEF) was not different in
RA (57%) vs non-RA (51%; p=0.3). Patients with RA and HF with reduced ejection fraction (HFrEF, RR 1.65; 95%CI 1.29-2.09) but
not those with HFpEF (RR 0.80; 95%CI 0.63-1.01) had significantly more hospitalizations than non-RA patients. Following HF
diagnosis, RA patients were more likely to be hospitalized for non-cardiovascular causes (RR 1.26; 95%CI 1.14-1.39), but not for HF
(RR 0.96; 95%CI 0.76-1.21) or other cardiovascular causes (RR 0.99; 95%CI 0.81-1.20) compared to the non-RA patients. There was
no overall difference in hospital LOS in RA vs non-RA patients after HF diagnosis (mean of 5.6 vs 5.3 days, respectively, p=0.31). LOS
was higher in earlier years in RA than non-RA and declined faster in RA than non-RA over time, with similar LOS in both groups in
recent years (interaction p=0.019). Readmission rates within 30 days of prior discharge were similar in RA and non-RA (p=0.14).
Conclusion: Hospitalization rate following HF diagnosis was 16% higher in RA than in non-RA patients regardless of sex and age. This
increased hospitalization risk was mostly among patients with RA who had HFrEF rather than HFpEF, and was predominantly due to
non-cardiovascular causes. Increased complexity of management of patients with comorbid RA may play a role in more frequent
hospitalizations in the RA cohort.
Disclosure: E. Myasoedova, None; E. L. Matteson, None; S. J. Achenbach, None; J. M. Davis III, None; S. Setoguchi, None; S. E.
Gabriel, None; C. S. Crowson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/trends-in-hospitalizations-following-heart-failure-

diagnosis-in-rheumatoid-arthritis
Burden of Illness in Patients with RA and Anti-Cyclic Citrullinated Peptide Positivity

ML Paudel1, JP Swindle1, J McPheeters1, R Szymialis2 and K Price2, 1Optum, Inc., Eden Prairie, MN, 2Bristol-Myers Squibb,
Princeton, NJ
SESSION INFORMATION
Background/Purpose: RA is often treated with a biologic DMARD (bDMARD), such as abatacept (ABA) or a TNF inhibitor (TNFi).
Real-world data on how economic outcomes vary by bDMARD therapy in patients (pts) with seropositivity to anti-cyclic citrullinated
peptide (anti-CCP) are sparse. The objective of this study was to compare healthcare resource utilization (HCRU) and costs among pts
with RA and anti-CCP positivity who initiated a new bDMARD therapy. Methods: A retrospective study was conducted using claims
data from a large US health plan, linked with laboratory results. Pts were aged ≥18 years with ≥1 diagnosis code for RA (ICD-9-CM
714.x) and ≥1 claim for ABA (identified first) or a TNFi (adalimumab, certolizumab pegol, etanercept, golimumab or infliximab) during
Jan 1, 2007–Jul 31, 2015. Cohort assignment was based on index therapy (ABA or first observed TNFi). Pts were required to have ≥18
months of continuous health plan enrollment (≥6 months pre-index [pre-initiation], 12 months post-index [post-initiation]), no pre-index
claims for index therapy and anti-CCP positivity (≥20 IU/mL). Per-pt-per-month HCRU and costs (total and RA-related) were
calculated separately for the pre- and post-index periods. Independent sample t-tests were used to examine differences by cohort.
Results: Analyses included 203 ABA users and 1066 TNFi users (etanercept=487, adalimumab=331, infliximab=144, certolizumab=60,
golimumab=44) with anti-CCP positivity (median age 55 & 52 years, female 88 & 75%, Medicare Advantage 17 & 15%; mean
Charlson Comorbidity Index score 1.6 & 1.4, pre-index bDMARD use 48 & <1%). Compared with TNFi users, ABA users experienced
greater mean ambulatory visits in pre-index (2.6 vs 2.0, p<0.01) and post-index periods (2.6 vs 1.7, p<0.01). No statistically significant
differences (p<0.05) in mean emergency room visits or inpatient days for the pre- or post-index periods were observed between cohorts.
Compared with TNFi users, ABA users experienced higher mean costs in pre-index ($2543 vs $932, p<0.01) and post-index periods
($3632 vs $2957, p<0.01). Analyses of RA-related costs and utilization were similar, with the exception that a statistically significant
difference was not observed in post-index RA-related costs between ABA and TNFi users ($2660 vs $2306, p=0.06).
Conclusion: Among pts with RA and anti-CCP positivity, unadjusted differences in pre-index ambulatory care and healthcare costs
were observed between abatacept and TNFi users, which carried over to post-index cost and HCRU comparisons. These differences
appeared to be driven, in part, by greater ambulatory care among abatacept users. Further research is needed to understand additional
factors driving pre-index costs among pts initiating bDMARDs to treat RA, to inform multivariable adjusted analyses and ensure
comparability of cohorts, as abatacept is likely to be their second line of therapy due to formulary availability.
Table 1. Per-Patient-Per-Month Costs and Healthcare Resource Utilization
by Biologic DMARD Group
6 months pre-index 12 months post-index
Abatacept TNFi Abatacept TNFi
Healthcare costs, USD,
mean (SD)
Total healthcare costs 2543 (3283) 932 (1668)* 3632 (3480) 2957
(2457)*
RA-related healthcare costs 1379 (1660) 310 (1168)* 2660 (2567) 2306 (1785)
Healthcare resource
utilization, mean (SD)
Total ambulatory visits 2.62 (1.86) 1.96 (1.42)* 2.56 (1.73) 1.68 (1.35)*
Total ER visits 0.11 (0.29) 0.07 (0.28) 0.10 (0.29) 0.06 (0.19)
Total inpatient days 0.12 (0.72) 0.06 (0.67) 0.12 (0.58) 0.09 (0.47)
RA-related ambulatory 1.15 (0.66) 0.61 (0.46)*
1.02 (0.75) 0.74 (0.48)*
visits
RA-related ER visits 0.03 (0.09) 0.01 (0.07) 0.02 (0.04) 0.01 (0.06)
RA-related inpatient days 0.10 (0.69) 0.05 (0.66) 0.11 (0.54) 0.08 (0.43)
Costs and healthcare resource utilization were reported as per-patient-per-month
*p<0.05; statistically significant differences were computed between abatacept
and TNFi groups ER=emergency room; TNFi=TNF inhibitor; USD=United
States dollars, adjusted to 2016 dollars
Disclosure: M. Paudel, None; J. Swindle, None; J. McPheeters, None; R. Szymialis, Bristol-Myers Squibb, 1,Bristol-Myers Squibb,
3; K. Price, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/burden-of-illness-in-patients-with-ra-and-anti-

cyclic-citrullinated-peptide-positivity
Presence of Anti-Cyclic Citrullinated Peptide Antibodies Is Associated with Better

Treatment Response to Abatacept but Not to TNF Inhibitors in Patients with RA: A
Meta-Analysis
E Alemao1, R Postema2, Y Elbez3, C Mamane4 and Axel Finckh5, 1Bristol-Myers Squibb, Princeton, NJ, 2Bristol-Myers Squibb,
Uxbridge, United Kingdom, 3Excelya, Boulogne-Billancourt, France, 4Mapi, London, United Kingdom, 5University Hospital of
Geneva, Geneva, Switzerland
SESSION INFORMATION
Background/Purpose: The association between anti-citrullinated protein antibody (ACPA) status and erosions, as well as response to
TNF inhibitor (TNFi) treatment, has been explored.1,2 Results based on a large US RA registry study have suggested that anti-cyclic
citrullinated peptide (anti-CPP; a surrogate for ACPA) positivity predicts better clinical responses to abatacept, but not to TNFi.3 The
objective of this study was to investigate whether ACPA status is associated with clinical responses to abatacept or to TNFi in RA, in
the published literature Methods: A systematic literature review (SLR) was performed to identify published studies and conference
abstracts estimating biologic DMARD response according to ACPA status. The SLR was supplemented by additional studies that were
identified through expert input. Mantel–Haenszel meta-analysis methods were used to pool risk ratios (RRs) based on ACPA status. In
the base-case, response to therapy was assessed using the EULAR response as the primary outcome, while a scenario analysis assessed
response by combining various definitions including ACR20 and EULAR for abatacept, and ACR20, DAS28 and EULAR for TNFi
therapy. Results: Nineteen studies were included in the meta-analysis: 4 for abatacept, 14 for TNFi and 1 for both treatments. The base-
case analysis included 4 of the abatacept and 6 of the TNFi studies and showed a statistically significant positive association between
ACPA positivity and EULAR response for patients treated with abatacept (RR 1.13 [95% CI 1.00, 1.26]; Figure 1), while ACPA
positivity was associated with lower EULAR responses to TNFi therapy (RR 0.92 [95% CI 0.86, 0.98]; Figure 2). For the scenario
analyses, in which all definitions of response were pooled, the results were consistent with base-case for abatacept (RR 1.18 [95% CI
1.30, 1.35]), while for TNFi therapy, no significant difference by ACPA status was observed (RR 0.97 [95% CI 0.86, 1.10]).
Conclusion: This meta-analysis confirms that ACPA-positive RA patients are more likely to achieve response to abatacept treatment
compared to ACPA-negative patients. Additionally, the analysis demonstrates that there is no association between ACPA status and
response to TNFi therapy, consistent with the findings of previously published studies.1,3 1. Lv Q, et al. PLoS One 2014;9:e89442.
2. Jilani AA and Mackworth-Young CG. Int J Rheumatol 2015;2015:72810. 3. Harrold LR, et al. J Rheum 2017 [Epub ahead of
print].
Disclosure: E. Alemao, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; R. Postema, Bristol-Myers Squibb, 1,Bristol-Myers Squibb,
3; Y. Elbez, None; C. Mamane, Mapi, 3,Bristol-Myers Squibb, 5; A. Finckh, AbbVie, A2BIO, BMS, MSD, Pfizer, and Roche, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/presence-of-anti-cyclic-citrullinated-peptide-

antibodies-is-associated-with-better-treatment-response-to-abatacept-but-not-to-tnf-inhibitors-in-patients-with-ra-a-meta-analysis
Risk of Hospitalization Among RA Patients with Multiple Autoimmune Co-

Morbidities Differs By DMARD Treatment
E Alemao, Z Guo and L Burns, Bristol-Myers Squibb, Princeton, NJ
SESSION INFORMATION
Background/Purpose: Patients (pts) with autoimmune (AI) disorders are at higher risk of developing another AI disorder; co-
occurrence of some AI conditions is reported more frequently than others in RA pts.1 The objective was to evaluate 6- and 12-month
(mo) hospitalization rates in RA pts with multiple AI co-morbidities, treated with abatacept, biologic (b) or conventional (c)DMARDs.
Methods: Administrative claims data from Optum Clinformatics Data Mart (database A) and QuintilesIMSTM PharMetrics Plus
(database B) from 2006 to 2015 were used. Inclusion was based on the presence of 2 diagnosis codes for RA plus 1 DMARD
prescription, age ≥18 yrs, ≥1 of the 5 most prevalent AI conditions: ankylosing spondylitis (AS), Crohn’s disease, lupus, psoriasis or
ulcerative colitis at or before index, ≥3 mo baseline (pre-index date) and 3 mo of follow-up (post-index date). Mutually exclusive
treatment groups were classified based on the index prescription using hierarchy of abatacept, other bDMARD and cDMARD. Also, an
RA group without record of DMARD (NoDMARD) was identified. Date of first DMARD was index date (for NoDMARD, index date
was first diagnosis date). Primary outcome was 6- and 12-mo hospitalizations. Treatment groups were compared using descriptive
statistics (Wilcoxon rank-sum test for continuous variables or Pearson's chi-square test for categorical variables) and using multivariate
Cox regression analyses for hospitalization risk. Covariates included in the multivariate analysis were age, sex, region, past
hospitalization, physician office visits during past 3 mo, an indicator variable for 714.0x, medication use (steroids, NSAIDs, salicylates,
antidyslipidemics), the 5 AI and 18 co-morbidity conditions. Results: A total of 18,964 and 47,105 RA pts with multiple AI co-
morbidities from databases A and B, respectively, were included. The mean (SD) age of study population was 55.4 (15.1) yrs in
database A and 50.0 (13.0) in database B. Respectively, 4.4%, 20.7%, 41.6% and 33.3% were prescribed abatacept, bDMARD,
cDMARD and NoDMARD in database A; and 3.7%, 25.9%, 40.5% and 29.8% in database B. The most common AI co-morbidities in
databases A vs B were AS (29 vs 27%), lupus (32 vs 32%) and psoriasis (32 vs 34%). Abatacept-treated pts had higher past
hospitalization rates vs bDMARD and cDMARD groups. 6- and 12-mo pooled adjusted hazard ratios for hospitalization were higher for
bDMARDs (and cDMARDs) vs abatacept (Table). Results were consistent in both databases.
Conclusion: Among RA pts with multiple AI co-morbidities, adjusted risk of hospitalization in both bDMARD- and cDMARD-treated
pts was significantly higher compared with abatacept-treated pts. Though the NoDMARD group had an even higher risk of
hospitalization, this should be interpreted with caution as it comprises a heterogeneous pt population
1. Cooper GS, et al. J Autoimmunity 2009;3:197–207.
Disclosure: E. Alemao, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; Z. Guo, Bristol-Myers Squibb, 3; L. Burns, Bristol-Myers
Squibb, 1,Bristol-Myers Squibb, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/risk-of-hospitalization-among-ra-patients-with-

multiple-autoimmune-co-morbidities-differs-by-dmard-treatment
Blood Glucose Changes Surrounding Initiation of Tumor-Necrosis Factor Inhibitors

and Conventional Disease-Modifying Anti-Rheumatic Drugs in Veterans with
Patrick R. Wood1, Evan Manning2, Joshua Baker3, Grant Cannon4, Lisa Davis5, Bryant R. England6, Ted R. Mikuls7 and Liron
Caplan8, 1Rheumatology, University of Colorado School of Medicine, Aurora, CO, 2University of Colorado School of Medicine,
Aurora, CO, 3Rheumatology, University of Pennsylvania, Philadelphia, PA, 4Salt Lake City VA Medical Center and University of Utah,
Salt Lake City, UT, 5Div of Rheumatology, Denver Health, Denver, CO, 6Division of Rheumatology & Immunology, Department of
Internal Medicine, Nebraska-Western IA VA Health Care System & University of Nebraska Medical Center, Omaha, NE, 7Internal
Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, 8Division of Rheumatology, University of
Colorado School of Medicine, Aurora, CO
SESSION INFORMATION
Background/Purpose: There is evidence linking activation of the innate immune system and insulin resistance. Perturbations in
glucose homeostasis upon initiation of tumor-necrosis factor inhibitors (TNFis) and conventional DMARDs have been described in
small studies, perhaps due to suppression of inflammation. To evaluate this association, we measured glucose before and after initiation
of TNFis and DMARDS in a large registry of patients with rheumatoid arthritis (RA).
Methods: Patients enrolled in the Veterans Affairs RA (VARA) registry were retrospectively examined. Subjects were selected who,
during study follow-up, initiated treatment with TNFis, prednisone, or DMARDs, and for whom proximate random blood glucose
(RBG) or hemoglobin A1C (A1C) values were available. Proximate values were the closest RBG within 2 weeks prior to, and 6 months
following, medication initiation. A1C values were the closest A1C within 2 months prior to, and 12 months following, medication
initiation. Measurements were compared before and after medication initiations using paired t-tests and multivariate regression,
adjusting for demographics and comorbid conditions.
Results: 2111 patients contributed at least one proximate measurement surrounding initiation of any agent. Significant decreases in
RBG were associated with 653 hydroxychloroquine-initiation events (-3.68mg/dL, p =0.04), and increases were noted in RBG
surrounding 665 prednisone-initiation events (+5.85mg/dL, p <0.01). A significant decrease in A1C was noted surrounding 49
sulfasalazine-initiation events (-0.70%, p <0.01). Multivariate regression analyses suggest sulfasalazine and hydroxychloroquine use as
predictors of lower post-medication-initiation blood glucose values; congestive heart failure was also a predictor for higher RBG values
after all medication-initiation events. We found no association of TNFi initiation with changes in glucose.
Conclusion: This study quantifies hyperglycemic effects of prednisone initiation. We also observed hypoglycemic effects of
sulfasalazine and hydroxychloroquine initiation. TNFi initiation was not observed to impact measured blood glucose. Further large-
scale and prospective investigation of DMARD and TNFi blood glucose effects in other populations is warranted.
Disclosure: P. R. Wood, None; E. Manning, None; J. Baker, None; G. Cannon, Amgen, 2; L. Davis, None; B. R. England, None; T.
R. Mikuls, BMS, 2,Ironwood Pharm, 2,Pfizer Inc, 5,NIH, VA, 2; L. Caplan, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/blood-glucose-changes-surrounding-initiation-of-

tumor-necrosis-factor-inhibitors-and-conventional-disease-modifying-anti-rheumatic-drugs-in-veterans-with-rheumatoid-arthritis
Biosimilar Knowledge Among US Rheumatologists – a Survey

Allan Gibofsky1,2 and Sam Badawi3, 1Medicine and Public Health, Hospital for Special Surgery, New York, NY, 2Rheumatology, Weill
Cornell Medicine, and Hospital for Special Surgery, New York, NY, 3Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT
SESSION INFORMATION
Background/Purpose:
Four biosimilar tumor necrosis factor α (TNFα) inhibitors have been approved by the FDA in the United States as of April 2017. This
survey was developed to evaluate US rheumatologists’ familiarity with biosimilars, the concept of biosimilarity, and the approval
process for biosimilars in the treatment of immune-mediated chronic diseases.
Methods:
A 20-question survey was administered by WebMD between December 9 and 14, 2016. Physicians (n=958) who were medscape.com
members were invited to participate in an online survey via email. Most survey items used a 5-point Likert scale. Results were
summarized descriptively.
Results:
Overall, 131 physicians responded, a response rate of 13.67%. Data were collected from 102 participants who were self-identified
rheumatologists, practicing in the US for ≥1 year. All but 1 respondent had prescribed a TNFα monoclonal antibody (mAB) for the
treatment of an autoimmune disease. When asked to choose the status of biosimilar development (as of December 2016), the majority
(84%) of respondents were aware that an infliximab biosimilar was approved in the US, but only 47% and 34% were aware of the recent
approvals of the adalimumab and etanercept biosimilars, respectively. Most physicians were extremely (38%) or moderately (36%)
familiar with the FDA’s definition of a biosimilar. Most respondents (71%) were aware that an approved biosimilar was not
automatically deemed interchangeable by the FDA. When asked to rate their expectations of biosimilar products, 74% indicated that an
interchangeable designation was very or moderately important. Regarding other characteristics of the biosimilar compared with the
originator, the majority indicated that effectiveness (96%), safety (96%), and durability of response (95%) were very or moderately
important. Regarding treatment initiation, 66% of physicians were extremely likely or likely to initiate biosimilar treatment for a
biologic treatment-naïve patient with RA if the approval included efficacy and safety studies in the same indication, whereas 5% and
29% were extremely likely or likely, respectively, to initiate biosimilar treatment for a biologic treatment-naïve patient with a different
rheumatologic condition than the one on which the approval was based. Approximately 60% of survey respondents were unlikely to
switch therapy from an originator to its biosimilar TNFα mAB in patients who were doing well, regardless of whether the patient had
the same or a different rheumatologic indication than the one on which the biosimilar approval was based. Also, 21% of respondents
were extremely likely or likely to switch to a biosimilar if the patient was failing on the originator.
Conclusion:
This survey supports a need to further educate US rheumatologists about biosimilars, extrapolation, and interchangeability. Knowledge
gaps include a lack of understanding of biosimilarity based on switching, and the availability of currently approved biosimilars.
Disclosure: A. Gibofsky, Pfizer Inc, 1,AbbVie, 1,Amgen, 1,Bristol-Myers Squibb, 1,Johnson & Johnson, 1,Regeneron, 1,AbbVie,
5,AbbVie, 8,Pfizer Inc, 5,Pfizer Inc, 8,Celgene, 8,Novartis Pharmaceutical Corporation, 8,Takeda, 5,Horizon, 5,Relburn, 5,Samumed, 5;
S. Badawi, Boehringer Ingelheim, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/biosimilar-knowledge-among-us-rheumatologists-a-

survey
Impact of Patient Support Program Utilization on Patient Activation Measure Scores

Among Patients with Rheumatoid Arthritis
Filip van Den Bosch1,2, Siegfried Wassenberg3, Andrew Östör4, Chen Wang5, Vishvas Garg5 and Jasmina Kalabic6, 1Ghent University
Hospital, Ghent, Belgium, 2Rheumatology, Ghent University Hospital, Gent, Belgium, 3Rheumazentrum Ratingen, Ratingen, Germany,
4Addenbrooke's Hospital, Cambridge, United Kingdom, 5AbbVie Inc., North Chicago, IL, 6AbbVie Deutschland GmbH & Co. KG,
Ludwigshafen, Germany
SESSION INFORMATION
Background/Purpose : AbbVie’s Patient (pt) Support Program (PSP) is offered to pts who are prescribed adalimumab (ADA) for their
Rheumatoid arthritis (RA). The purpose of this analysis was to assess the association of Patient Activation Measure (PAM)-13 scores
with PSP utilization among pts with moderate to severe RA initiating ADA who had option to enroll in the PSP.
Methods : PASSION (NCT01383421) was a 78-week post-marketing observational study of pts with RA receiving ADA in routine
clinical care. Pts from the EU, Israel, Mexico, Puerto Rico, and Australia with an insufficient response to ≥1 disease-modifying
antirheumatic drug (DMARD) newly initiating ADA (1 prior biologic DMARD was allowed) were enrolled. Pts were offered a panel of
“Core elements” (starter pack, call center/hotline, nursing services, educational material, and injection guide; offered in all participating
countries) and “Other elements” (e.g, refill reminders, email communications, newsletters, support groups, home medication delivery,
and financial assistance; vary by country) of PSP. Pts were divided in 2 groups based on their participation in the PSP: ever (PSP users)
vs never (PSP non-users). The PAM-13 scores were collected at baseline (BL) and at week 78. PAM-13 scores evaluate knowledge,
skills, and confidence essential to a pt managing his/her own health. PAM-13 scores were classified a priori into 4 levels (higher level =
greater pt involvement in disease management). Multivariate inferential analysis was used to examine the associations between PSP
utilization (yes/no) and PAM-13 scores after adjusting for the following BL characteristics: age, gender, race, RA disease duration, prior
use of biologic DMARD, BL Health Assessment Questionnaire Disease Index (HAQ-DI), and BL PAM-13 score. The response variable
of the model was PAM-13 scores change from BL.
Results : PSP users had significantly larger increase in the PAM-13 scores (2.33, 95% CI 0.05 – 4.61, P=0.045) compared to the BL
than the PSP non-users after adjusting for relevant BL characteristics (Figure 1A). Percentage of pts that demonstrated improvement in
PAM-13 levels were significantly higher among PSP users vs PSP non-users at week 78 compared to BL (35.7% vs 28.1%, P=0.01)
(Figure 1B). Additionally, lower PAM-13 and HAQ-DI BL scores were statistically significantly associated with increases in the PAM-
13 scores at week 78 compared to BL.
Conclusion : Among pts with moderate to severe RA that initiated ADA treatment, PSP users reported significantly larger improvement
from BL to week 78 in PAM-13 scores compared to the PSP non-users. Greater increase in PAM-13 scores among PSP users (vs. non-
users) from baseline to week-78 indicate towards their increased ability in managing their health, gaining confidence and knowledge
about their health, and taking action to maintain and improve their health.
Disclosure: F. van Den Bosch, AbbVie, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, and UCB., 5,AbbVie, Celgene, Eli
Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, and UCB., 9; S. Wassenberg, AbbVie, Celgene, Novartis, Pfizer, MSD, Lilly, Janssen
and UCB, 9,AbbVie, Pfizer, Novartis, Janssen, Roche-Chugai, Celltrion, BMS and Fuji., 9; A. Östör, Roche, Chugai, MSD, AbbVie,
Pfizer, Novartis, Napp, Janssen, Lilly and BMS., 5,Roche, Chugai, MSD, AbbVie, Pfizer, Novartis, Napp, Janssen, Lilly and BMS.,
9,Roche, Chugai, MSD, AbbVie, Pfizer, Novartis, Napp, Janssen, Lilly and BMS, 9; C. Wang, Abbvie, 1,Abbvie, 3; V. Garg, Abbvie,
1,Abbvie, 3; J. Kalabic, AbbVie Inc, 1,AbbVie Inc, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/impact-of-patient-support-program-utilization-on-

patient-activation-measure-scores-among-patients-with-rheumatoid-arthritis
Influences for Therapeutic Changes in Rheumatoid Arthritis Patients from the

Veterans Affairs Rheumatology Arthritis Registry Who Have Moderate to High
Disease Activity
Brian Sauer1, Jacob R. Stever1, Chia-Chen Teng, MS1, Neil Accortt2, David Collier2 and Grant Cannon1, 1Salt Lake City VA Medical
Center and University of Utah, Salt Lake City, UT, 2Amgen Inc., Thousand Oaks, CA
SESSION INFORMATION
Background/Purpose: Current guidelines encourage the measurement of rheumatoid arthritis (RA) disease activity to achieve a low
disease state (treat-to-target). Many RA patients with documented moderate to high disease activity, however, remain on their current
regimen. This study used clinical and administrative data of US Veterans, identified as having moderate/high disease activity
(DAS28≥3.2), to identify patient and treatment characteristics associated with a major change in therapy.
Methods: Patients in the Veterans Affairs (VA) RA registry were included if they had: 1) moderate/high disease activity on the index
date, 2) 18-months of VA activity prior to the index and 3) two or more prior DAS28 measures during the preceding 18-months (≥ three
months apart). Patients were defined as having a major change in therapy if any of the following occurred within 7 days prior to 30 days
after the index date: 1) initiation or escalation of DMARDs, 2) initiation or increase dose of prednisone and/or 3) ≥ 2 joint injections.
Disease stability was determined during the observation period prior to the index date using an area under the curve calculation and
compared to the index DAS28. Patients were categorized as improving (index DAS28 was ≥ 0.6 points lower), worsening (≥ 0.6 higher)
or stable. Poisson multivariable regression was used to explore how demographic, clinical and treatment patterns influenced the initial
finding that stability of disease activity was a strong predictor of a major treatment change.
Results: Of the 941 patients who met enrollment criteria only 41% had a major therapeutic change. Major therapeutic changes occurred
in 50%, 37% and 30% with worsening, stable and improved DAS28, respectively. In multivariable models, patient demographics and
individual components of the DAS28 score were not independently associated with a major therapeutic change. In the full model, the
current DAS28, and oral steroids and non-biologic DMARDs in the past year increased the likelihood of a major change. Non-biologic
DMARDs in the past 90-days decreased the likelihood of a major change. Table 1 displays the RR with “stable DAS28” as the
comparison group after adjustment for demographic, demographic + DAS28 and clinical components and the full model, which added
indicators of medication use, surgery, radiographs and comorbidity scores.
Conclusion: More than half the patients did not experience a major change in therapy despite moderate/high disease activity even
among those patients with worsening disease. In crude analysis, the likelihood that RA patients with moderate/high RA disease received
a change in therapy was highly associated with worsening disease activity, but this effect was diminished when accounting for current
DAS28, indicators of non-biologic DMARDs and steroid use in the previous year. The decision to modify therapy is complex and we
are conducting chart-review to better understand why providers are not modifying therapy.
Disclosure: B. Sauer, Amgen, 2; J. R. Stever, None; C. C. Teng, MS, Amgen, 2; N. Accortt, Amgen, 1,Amgen, 3; D. Collier,
Amgen, 1,Amgen, 3; G. Cannon, Amgen, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/influences-for-therapeutic-changes-in-rheumatoid-

arthritis-patients-from-the-veterans-affairs-rheumatology-arthritis-registry-who-have-moderate-to-high-disease-activity
Perceptions of US Community Rheumatologists on Biosimilars

Janna Radtchenko, Yolaine Smith, Jonathan Kish and Bruce Feinberg, Specialty Solutions, Cardinal Health, Dallas, TX
SESSION INFORMATION
Background/Purpose: Biosimilars contain a highly similar version of the active substance of an already approved biologic or
“reference product.”1 Regulatory agencies mandate that safety, efficacy, dosing, route of administration, and immunogenicity are
established. The FDA allows extrapolation of safety and efficacy data from one biosimilar indication to another significantly lowering
drug development cost. Biosimilars are thereby expected to have a lower price point than their reference product and result in reduced
healthcare spending, but that will largely depend on how providers perceive and prescribe them. As of May 2017, four biosimilars have
been FDA approved for rheumatologic conditions. We have evaluated the perceptions of U.S. community rheumatologists to identify
areas of opportunity to support biosimilar adoption
Methods: Using audience response technology, we surveyed 24 community rheumatologists and 20 rheumatology practice managers
(PMs) during a live meeting in April 2017. Participating physicians and PMs represented various practice sizes and geographic locations
throughout the U.S.
Results: Regarding the legal and regulatory aspect of biosimilars and their reference biologics: only 51% of the respondents understood
the concept of interchangeability between biosimilars and reference biologic; 76% were unaware of compatibility requirements for
reference biologics following a manufacturing change; while only 40% believed biosimilars match the safety and efficacy of their
reference biologics. When asked if they or their practice would prescribe a biosimilar approved for anti-rheumatic treatment: 20%
would not prescribe at all, only 23% would switch a patient from the reference biologic, and 57% responded that they would prescribe it
to patients initiating biologic therapy. The responses to the query, “Which issues are most concerning?” in descending order are:
Regulations related to substitutions, understanding when to prescribe a biosimilar versus a reference biologic, and coordinating with
pharmacists on substitutions. Information about safety and efficacy, guidelines on when to prescribe a reference biologic versus a
biosimilar, and reimbursement information were named as tools for achieving a greater understanding of biosimilars.
Conclusion: Significant barriers to biosimilar adoption for rheumatologic conditions exist due to physicians’ perceptions. Education
around biosimilar efficacy, safety, appropriate use, and reimbursement may improve perceptions and facilitate usage.
Disclosure: J. Radtchenko, None; Y. Smith, None; J. Kish, None; B. Feinberg, None.

View Abstract and Citation Information Online - http://acrabstracts.org/abstract/perceptions-of-us-community-rheumatologists-on-
biosimilars
Real-World Utilization of Biosimilars for Management of Rheumatoid Arthritis (RA)

in the US
Janna Radtchenko, Yolaine Smith, Jonathan Kish and Bruce Feinberg, Specialty Solutions, Cardinal Health, Dallas, TX
SESSION INFORMATION
Background/Purpose: A biosimilar product is a biological product highly similar to another FDA-approved biological product,
reference product, and has no clinically meaningful differences in safety and effectiveness from the reference product. While four
biosimilars have been approved by the FDA in rheumatology in 2016-2017, only one biosimilar infliximab-dyyb (IFX-b) has launched.
We have evaluated early uptake of IFX-b in RA following its approval in April 2016 and launch in November 2016.
Methods: Symphony Health longitudinal prescription and medical claims data was used to evaluate the uptake of IFX-b relative to its
reference product infliximab (IFX) from biosimilar approval through Q1 2017. The database contains claims records for 279 million
unique patients representing an estimated 63% of specialty prescriptions, 58% of medical claims, and 25% of hospital claims in the US.
Duration of therapy was defined as days from biologic initiation to the last administration. Time to treatment discontinuation (TTD) was
defined as months from biologic initiation to switch or last administration + 90 days if no other biologic was administered. Duration of
therapy was described with a Kaplan-Meier curves. Patient characteristics were evaluated using frequencies for categorical and mean
and standard deviation (SD) for continuous variables.
Results: Of the 78,481 patients who initiated a biologic/biosimilar therapy for RA since IFX-b approval, 90 (0.1%) were treated with
IFX-b and 5,178 (6.6%) were treated with IFX. The first patient started IFX-b in May 2016 and 78 IFX-b patients (86.7%) started in Q1
2017. Of the patients treated with IFX-b, 66 (73.3%) were female, 58 (64.4%) were 65 or older, 1 patient was commercially insured, the
rest were with unknown insurance status, 31 (34.4%) were previously treated with IFX, 56 (62.2%) received IFX-b as their first
biologic. Mean (SD) age for IFX-b patients was 65.9 (12.4) compared to 55.0 (16.7) for infliximab patients (p<0.0001). Mean (SD)
number of prior biologics was 0.5 (0.8) for IFX-b and 0.5 (0.9) for IFX patients. Median (mean) duration was 1.0 (4.5) days for IFX-b
and 60.0 (101.2) for IFX (Log Rank P<0.001) due to late IFX-b adoption.
Conclusion: Adoption of IFX-b in the US so far has been low and has not yet significantly impacted the reference biologic. The
majority of IFX-b patients received it as first biologic, however a third of them switched from IFX. Duration of therapy on IFX-b is
relatively short due to delayed launch. Future monitoring of IFX-b uptake is warranted especially as other approved biosimilars prepare
for launch.
Disclosure: J. Radtchenko, None; Y. Smith, None; J. Kish, None; B. Feinberg, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/real-world-utilization-of-biosimilars-for-

management-of-rheumatoid-arthritis-ra-in-the-us
Remote Management of Osteoporosis Screening and Treatment in US Veterans Using

a Bone Health Team: A Cost-Effectiveness Analysis
Karla L. Miller1, Jordan King2, Phillip Lawrence3, Richard Nelson4, Joanne Lafleur5, Grant Cannon6 and Scott Nelson7, 1Internal
Medicine, Veterans Affairs Salt Lake City Health Care System and University of Utah School of Medicine, Salt Lake City, UT, 2Clinical
Pharmacy Specialist, Research, Kaiser Permanente Colorado, Aurora, CO, 3Salt Lake City VA Medical Center and Roseman University
of Health Sciences, Salt Lake City, UT, 4Epidemiology, Veterans Affairs Salt Lake City Health Care System and University of Utah
School of Medicine, Salt Lake City, UT, 5University of Utah Department of Pharmacotherapy and Salt Lake City VA Medical Center,
Salt Lake City, UT, 6Salt Lake City VA Medical Center and University of Utah, Salt Lake City, UT, 7Biomedical Informatics, Vanderbilt
University Medical Center, Nashville, TN
SESSION INFORMATION
Remote Management of Osteoporosis Screening and Treatment in US Veterans using a Bone Health Team: A Cost-effectiveness
Analysis
Background/Purpose: To evaluate the cost effectiveness of a bone health team (BHT) as a primary prevention service to screen,
monitor, and treat Veterans at risk for fragility fractures compared to current clinical practice from the Veteran’s Administration (VA)
perspective over a life-time.
Methods: We conducted this analysis by adapting a previously validated Markov microsimulation model of osteoporosis incidence and
outcomes in the VA. The model was used to estimate fracture events, quality-adjusted life years (QALYs), and direct healthcare costs of
using a BHT vs current clinical practice. Model inputs were derived from national sources, published literature, and program estimates
from the BHT. Uncertainty in model parameters was assessed by conducting one-way and probabilistic sensitivity analyses.
Results: In the base-case, the BHT was associated with a substantially higher proportion of patients with underlying osteoporosis or
osteopenia diagnosed and treated with bisphosphonates (osteoporosis: 38.0% vs 6.9%, osteopenia: 25.5% vs 0.2%). This resulted in the
BHT strategy being associated with a modestly lower fracture rate than current clinical practice. In probabilistic sensitivity analysis, the
BHT was the dominant option; however, in all analyses, no meaningful differences were observed in life-time estimated costs,
unadjusted survival, and QALYs between the prevention strategies.
Table 1. Base-case Results (per patient average)

Bone Health Team No Bone Health Team Difference
Costs (mean) $58,250 $59,617 -$1,367
Unadjusted life years (mean) 11.937 12.059 -0.122
QALYs (mean) 8.379 8.446 -0.068
ICER
Costs/life year $20,190
Costs/QALY $11,174
Treated
Percent with osteoporosis 38.0% 6.9% 31.1%
Percent with osteopenia 25.5% 0.2% 25.3%
# AEs/1000 treatment years 1.92 5.05 -3.122
Years of treatment (mean) 9.93 5.42 4.518
Fracture Incidence (per 1,000 patient years
Clinical Vertebral 15.399 16.587 -1.188
Hip 3.797 4.073 -0.276
Subclinical Vertebral 5.062 5.494 -0.432
Wrist 0.808 0.977 -0.169
Death 70.548 70.089 0.459
Other (#/1000 patients)
Dependence 27.336 27.084 0.252
Nursing home placement 13.907 13.857 0.050
Conclusion: A BHT appears to be a potentially cost-effective method for screening and treating US Veterans for osteoporosis compared
to no intervention. Quality improvement programs addressing primary prevention of osteoporotic fractures provide a feasible, team-
based, approach to this important problem, while unburdening the increasingly limited time and availability of primary care providers.
Disclosure: K. L. Miller, None; J. King, None; P. Lawrence, None; R. Nelson, None; J. Lafleur, None; G. Cannon, Amgen, 2; S.
Nelson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/remote-management-of-osteoporosis-screening-and-
treatment-in-us-veterans-using-a-bone-health-team-a-cost-effectiveness-analysis
Comparison of the Costs for Hyaluronic Acid and Total Knee Arthroplasty in the
Treatment of OA for the Blue Cross/Blue Shield Patient Population
Kevin Ong1, Faizan Niazi2, Edmund Lau3, Peter Shaw2 and Steven Kurtz1, 1Exponent, Inc., Philadelphia, PA, 2Ferring
Pharmaceuticals, Inc., Parsippany, NJ, 3Exponent, Inc., Menlo Park, CA
SESSION INFORMATION
Background/Purpose: Previous HA studies have focused on the Medicare population, but less is known of the treatment patterns and
cost of HA relative to knee arthroplasty (KA) and other therapies for younger privately insured patients. We evaluated the overall cost of
treating knee OA in a large group of Blue Cross/Blue Shield (BCBS) patients, including those from KA and non-arthroplasty therapies,
such as HA, corticosteroid injections, and physical therapy. We hypothesized that non-arthroplasty interventions would account for the
majority of knee OA costs in the younger patient population.
Methods: Knee OA-related claims were identified from Blue Health Intelligence claims data (2011-2015). The dataset contains claims
for 140+ million unique BCBS members nationwide in the U.S. Cumulative costs (adjusted to November 2016$) were evaluated from a
payor perspective and grouped into various categories, such as physical therapy, corticosteroid injections, HA, and KA.
Results: The overall cost of treating knee OA for 1,567,024 knee OA patients over the five-year period was $5.7B (average
$3,600/patient). HA accounted for $196.9M (3.5%) of the overall cost, based on 216,523 HA patients (13.8% of knee OA cohort). KA
accounted for $3.6B (63.5%) of the overall costs, while office visits, arthroscopy, anesthesia for knee surgery, arthrocentesis, knee
imaging, and physical therapy accounted for $229.3M (4.0%), $141.8M (2.5%), $140.8M (2.5%), $124.6M (2.2%), $115.0M (2.0%),
and $51.9M (0.91%), respectively. 16.5% of the HA patients subsequently underwent knee arthroplasty during the study period, but HA
contributed to 2.8% of their overall knee OA treatment costs compared to KA, which contributed 82.9%. For those who received KA,
the median costs for the HA cohort were lower at 1 and 2 years compared to the no-HA cohort, but similar at 3 years and marginally
higher at 4 years (Table 1). If the 180,862 HA patients who avoided KA during the study period had, instead, undergone arthroplasty,
the cost of KA would be estimated to total $4.8B. Instead, there was a cost savings of $4.3B (90.1%) by utilizing non-arthroplasty
therapies.
Conclusion: Non-arthroplasty therapies accounted for about a third of the costs (36.5%) in treating knee OA in our cohort of younger
patients. Interventions that were not recommended or determined to have inconclusive evidence by AAOS accounted for 3.5% (HA),
0.12% (corticosteroid), and 0.54% (knee brace) of the overall costs. Although questions have been raised about the effectiveness of HA,
the majority of HA patients avoided knee arthroplasty during the study period; they saved an estimated 90.1% by utilizing non-
arthroplasty therapies. With the wide spectrum of therapies to treat knee OA, efforts to identify the most appropriate candidates for
arthroplasty and non-arthroplasty therapies, such as HA or other non-HA therapies, can help reduce costs to the healthcare system.
Disclosure: K. Ong, Ferring Pharmaceuticals, 5,Stryker, 5,Zimmer Biomet, 5,Ethicon, 5,Paradigm Spine, 5,Medtronic, 5,Pacira
Pharmaceuticals, 5,DJO, 5,Ossur Generation II, 5; F. Niazi, Ferring Pharmaceuticals, 3; E. Lau, Ferring Pharmaceuticals, 5; P. Shaw,
Ferring Pharmaceuticals, 3; S. Kurtz, Ferring Pharmaceuticals, 5,Elsevier, 7,Active Implants, 2,Aesculap/B. Braun, 2,Celanese,
2,Ceramtec, 2,DePuy Synthes, 2,DJO, 2,Formae, 2,Invibio, 5,Kyocera Medical, 5,Medtronic, 5,Simplify Medical, 9,Smith & Nephew,
Inc., 9,Stelkast, 9,Stryker, 9,Wright Medical, 9,Zimmer Biomet, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/comparison-of-the-costs-for-hyaluronic-acid-and-
total-knee-arthroplasty-in-the-treatment-of-oa-for-the-blue-crossblue-shield-patient-population
Medical Care Costs Associated with Rheumatoid Arthritis in the US: A Meta-
Analysis
Andrew Hresko1, Tzu-Chieh Lin2 and Daniel H. Solomon3, 1Tufts Medical School, Boston, MA, 2Health Outcomes, Amgen,
Thousand Oaks, CA, 3Brigham and Women's Hospital and Harvard Medical School, Boston, MA
SESSION INFORMATION
Background/Purpose: Rheumatoid arthritis (RA) is a morbid, mortal, and costly condition without a cure. Treatments for RA have
expanded over the last two decades with the introduction of biologic disease modifying anti-rheumatic drugs (bDMARDs). Biologic
DMARDs offer alternatives for patients unresponsive to traditional synthetic DMARDs, but carry an increased financial burden.
Detailed understanding of the cost of care for RA patients since the advent of bDMARDs is of importance to policy makers,
administrators, and physicians, as the high cost of RA treatments impacts the use of limited medical resources.
Methods: We conducted a systematic literature review and meta-analysis to assess direct annual medical cost for RA patients in the US
receiving any treatment regimen for RA since the marketing of the first bDMARD in 1999. Studies were identified through a search of
Medline using MeSH search terms related to cost of care and RA. Data were extracted independently by two reviewers (AH and DHS).
Total direct medical costs as well as RA-specific costs were calculated using random effects meta-analysis. A subgroup analysis
addressed costs for RA patients using bDMARDs.
Results: We found 541 potentially relevant studies and 11 papers met the selection criteria for meta-analysis. Total direct annual
medical costs were estimated at $12,509 (95% CI $7,451-21,001) for all RA patients using any treatment regimen (see Figure 1) and
$36,053 (95% CI $32,138-40,445) for bDMARD users (see Figure 2). RA-specific annual costs were $3,723 (95% CI $2,408-5,762)
for all RA patients using any treatment regimen, representing 30% of total costs for all care. RA-specific annual costs were $20,262
(95% CI $17,480-23,487) for bDMARD users, representing 56% of total costs for all care.
Conclusion: The total and disease-specific direct annual medical cost of patients with RA is substantial. Among bDMARD users, cost
of RA care is over half of all direct medical costs. These findings indicate that the burden of RA patients on the US health care system
may become outsized compared to the disease’s relatively small prevalence as more patients use bDMARDs in the future. While
patients that use bDMARD's have increased annual cost over typical RA patients, the increment is below the total cost of bDMARDs
themselves. This discrepancy suggests that either the use of bDMARD's is associated with lower total non-drug direct medical costs or
that there are crucial underlying demographic differences between bDMARD and traditional DMARD users.
Disclosure: A. Hresko, None; T. C. Lin, Amgen, 3; D. H. Solomon, Amgen, Lilly, Pfizer, BMS, Genentech, AstraZeneca, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/medical-care-costs-associated-with-rheumatoid-

arthritis-in-the-us-a-meta-analysis
The Potential Value of a Shared Decision-Making Intervention for Choices

Regarding Triple Therapy in Rheumatoid Arthritis
Nick Bansback1, Tima Mohammadi2, Aslam Anis3, James R. O'Dell4 and Glen Hazlewood5, 1School of Population and Public Health,
University of British Columbia, Vancouver, BC, Canada, 2Centre for Health Evaluation and Outcome Sciences, Vancouver, BC,
Canada, 3University of British Columbia, School of Population and Public Health, Vancouver, BC, Canada, 4Department of Internal
Medicine, University of Nebraska Medical Center, Omaha, NE, 5Division of Rheumatology, University of Calgary, Calgary, AB,
Canada
SESSION INFORMATION
Background/Purpose: Previous studies have shown that using Triple Therapy (a combination of 3 generic drugs) prior to a biologic, is
the most cost-effective strategy for patients with rheumatoid arthritis. While studies also find that many patients would prefer to trial
Triple Therapy prior to a biologic, fewer than 5% of patients do so in the US. We determined the potential value of an intervention that
promotes informed shared decision-making between patients and clinicians around triple therapy use after failure of methotrexate.
Methods: We developed an economic model that compared a strategy where patient preferences for triple therapy use were integrated
into treatment decisions, versus usual care. A previous study suggests that 59% of patients would choose triple therapy first if provided
the comparative evidence of benefits, potential adverse events and dosing schedule. We assumed a cost of $50 for a shared decision
making intervention such as a patient decision aid. Patient’s trialling triple therapy first were assumed to switch to a sequence of
biologics upon withdrawal. We extrapolated the influence of the initial treatment decision on subsequent disease progression, resource
use such as hospitalizations, quality of life, mortality and Quality Adjusted Life Years (QALYs). Various sensitivity analyses were
performed. A scenario that incorporated the value patients assign to the process of shared decision-making was also considered.
Results: Incorporating patient preferences into the decision was estimated to reduce average costs for a patient by $40,000 over a
lifetime through delaying the introduction of biologic therapy. Even under the most pessimistic assumptions regarding the potential for
earlier biologic use delaying joint erosions, only 0.08 QALYs (28 days of full health) over a lifetime were estimated to be lost. The
consequent incremental cost-effectiveness ratio for usual care vs the patient preference strategy is over $500,000/QALY. Sensitivity
analysis supported this finding. Incorporating the process of shared decision-making offsets the negative QALYs, implying the patient
preference strategy saves costs and increases QALYs.
Conclusion: This study demonstrates that systematically giving patients with rheumatoid arthritis who fail methotrexate an informed
choice between triple therapy and a biologic as the initial treatment is cost-saving and can even provide more 'benefits' to the patient.
This strategy allows patients who prefer biologic therapy to choose it, but saves costs by delaying the biologic initiation in patients who
choose triple therapy first. The results suggest that strategies used elsewhere for increasing shared decision-making such as building
infrastructure for implementing patients decision aids, or introducing fee codes for shared decision-making, could be cost-effective and
should be explored to promote value based prescribing in rheumatology.
Disclosure: N. Bansback, None; T. Mohammadi, None; A. Anis, None; J. R. O'Dell, Medac, 5,Coherus, 5; G. Hazlewood, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-potential-value-of-a-shared-decision-making-

intervention-for-choices-regarding-triple-therapy-in-rheumatoid-arthritis
Biological and Targeted Synthetic Dmards’ Prior Authorization Time Is Significantly

Reduced with Pharmacy Presence in the Rheumatology Clinic
Wendy Ramey1, Kristine M. Lohr2, Matt Zeltner1, Haley Herrell Postonl1, Andrew Johannemann1, Aric D. Schadler1 and Aleksander
Lenert3, 1University of Kentucky, Lexington, KY, 2Rheumatology, University of Kentucky, Lexington, KY, 3Internal Medicine, Div. of
Rheumatology, University of Kentucky, Lexington, KY
SESSION INFORMATION
Background/Purpose: Treatment with biological DMARDs (bDMARD) and targeted synthetic DMARDs (tsDMARD) has led to
improved outcomes for chronic rheumatic diseases. Current treat-to-target (T2T) strategy relies on quick escalation in therapy to achieve
disease control. A delay in escalation of therapy may impact clinical outcomes adversely. Insurance prior authorization, required for
specialty DMARD approval, represents a significant bottleneck to care. Clinical pharmacists embedded in a collaborative clinical team
could optimize rheumatologic care by shortening time to specialty medication authorization. Our aim was to assess the impact of
pharmacy support on specialty DMARD approval in an academic rheumatology clinic.
Methods: We performed a retrospective review of patient records followed in the Rheumatology Clinics at the University of Kentucky
who were prescribed specialty medications for RA, PsA and AS. All patients were diagnosed by clinical rheumatologists and met ACR,
CASPAR or ASAS criteria respectively. We included 8 bDMARDs and 2 tsDMARDs currently prescribed. We collected data during
two 6 month periods from prescriptions written pre-pharmacy (1/2014-6/2014) and post-pharmacy establishment (1/2016-6/2016). We
excluded the transition to pharmacist period of 7/2014-12/2015. Our primary outcome was the time to authorization defined as time (in
days) between rheumatologist's prescribing and pharmacist's completion of authorization for a given specialty DMARD. We compared
the mean time to authorization pre- and post-pharmacist establishment in the rheumatology clinic. Statistical analysis was performed
with IBM SPSS Statistics 23; continuous variables were analyzed utilizing an independent samples t-test and categorical variables with
Pearson's chi-square test.
Results: We screened 423 specialty prescriptions; 112 were eligible for study inclusion. Thirty-one specialty prescriptions from 28
patients were completed pre-pharmacist (Group 1) and 81 specialty prescriptions from 71 patients were completed post-pharmacist
(Group 2) (Table 1). There were no significant differences between the groups in baseline characteristics that were tested including age,
gender, diagnosis, and type of insurance. The majority of patients were women with RA; most patients had commercial insurance or
Medicaid. The mean time to authorization was significantly shorter post-pharmacist compared to pre-pharmacist routine care
(6.43±15.48 vs. 52.03±58.64 days, p=0.002).
Conclusion: In a large tertiary academic rheumatology practice, the mean time to authorization of specialty DMARDs was significantly
reduced to <7 days with establishment of a clinical pharmacist in a collaborative clinical team, facilitating implementation of T2T
strategy.
Disclosure: W. Ramey, None; K. M. Lohr, None; M. Zeltner, None; H. Herrell Postonl, None; A. Johannemann, None; A. D.
Schadler, None; A. Lenert, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/biological-and-targeted-synthetic-dmards-prior-

authorization-time-is-significantly-reduced-with-pharmacy-presence-in-the-rheumatology-clinic
Cost-Effectiveness of Drug-Level Guided Adalimumab Dosing

Zara Izadi1, Gabriela Schmajuk2, Milena Gianfrancesco3, Laura Trupin4, Kashif Jafri5, Jinoos Yazdany4 and Dhruv Kazi6,
1Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, 2San Francisco VA Medical Center,
University of California San Francisco, San Francisco, CA, 3Medicine/Rheumatology, University of California, San Francisco, San
Francisco, CA, 4Medicine/Rheumatology, University of California San Francisco, San Francisco, CA, 5University of California, San
Francisco, San Francisco, CA, 6Department of Medicine, University of California, San Francisco, Zuckerberg San Francisco General
Hospital, San Francisco, CA
SESSION INFORMATION
Background/Purpose: Adalimumab (ADA) induces and maintains clinical remission in patients with rheumatoid arthritis (RA) and
Crohn’s disease (CD) but is an expensive drug. Drug-level and antidrug antibody testing has the potential to facilitate personalization of
dosing, particularly the use of less frequent dosing of ADA (de-escalation). The cost-effectiveness of drug-level guided dose de-
escalation of therapy is unknown.
Methods: We evaluated the effectiveness (in quality adjusted life years [QALYs]) and cost-effectiveness of a drug-level guided dose-
reduction strategy for ADA compared with standard dosing in patients with CD who are in clinical remission, from a health system
perspective using a 4-year horizon. We chose CD rather than RA because drug-level guided dose de-escalation studies have not been
conducted in RA. We developed a discrete-time Markov simulation model for the analysis, using inputs from published randomized
controlled trials and observational studies. The intervention studied was reduction in frequency of ADA dosing from 40mg every other
week (EOW) to 40mg every three weeks (ETW) among patients with sustained clinical remission and therapeutic ADA trough levels.
Patients who lost clinical remission would undergo drug-level testing. A switch to an alternate biologic was indicated with positive
antidrug antibodies or drug resistance (adequate levels despite active symptoms); otherwise the dose was re-escalated back to 40mg
EOW. Standard dosing (control arm) involved continuation of 40mg EOW dosing and switch to an alternate biologic on loss of clinical
remission.
Results: Among patients with CD in remission on standard dose ADA, reductions in dose yielded similar QALYs but lower costs
compared with continuing standard dosing strategy. The difference between the standard and dose-reduction strategies ranged from 0.00
to 0.06 QALYs across the range of probabilities tested (with standard strategy being marginally more effective), but the intervention
resulted in cost-savings in every circumstance. In sensitivity analyses, the dose-reduction strategy was the dominant option (less costly
and more effective) when ≥87% of patients who were controlled on standard dosing continued to be in remission under the dose-
reduction strategy. The findings were most sensitive to the probability of formation of antidrug antibodies after dose reduction and the
cost of ADA.
Conclusion: Based on lower costs and similar overall efficacy, dose reduction may be a cost-saving alternative among patients with CD
who are in sustained remission with therapeutic ADA levels. These findings suggest that further research to explore drug-level guided
tapering in RA may also be warranted. Given the small difference we observed in incremental effectiveness, our proposed strategy may
prove to be dominating if future studies also demonstrate that reduced dosing improves the safety of ADA.
Disclosure: Z. Izadi, None; G. Schmajuk, None; M. Gianfrancesco, None; L. Trupin, None; K. Jafri, None; J. Yazdany, None; D.
Kazi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/cost-effectiveness-of-drug-level-guided-

adalimumab-dosing
Efficacy of Educating Visiting Pharmacists Regarding Drug Administration for

Patients with Rheumatoid Arthritis Who Poorly Adhere to Treatment Regimens
Masatoshi Hayashi1, Hiroyuki Matsubara2, Kei Funamura1, Masataka Maeda1 and Toshihisa Kanamono1, 1Rheumatology, Nagano
Red Cross Hospital, Nagano, Japan, 2Orthopaedics, Hekinan municipal hospital, Hekinann, Japan
SESSION INFORMATION
Background/Purpose: Patients with rheumatoid arthritis (RA) need to take lifelong oral or injectable medication to alleviate their
symptoms and prevent disease progression. However, some patients may not adhere or poorly adhere to treatment and have poor
understanding of biological agents. Poor or no adherence may be attributed to the following factors: complex regimen for medications,
such as methotrexate (MTX), difficulty in self-administration of injectables due to hand deformities, and forgetfulness due to dementia.
This study aimed at determining the effect of educating visiting pharmacists regarding administration of oral medication and injectables
for patients with RA who poorly adhere to treatment regimens.
Methods: A prospective analysis was performed by enrolling 21 patients with RA who were treated with different types of medication,
including self-injectable biological agents. Two cases were excluded because one had been added on subcutaneous tocilizumab and the
other on MTX with increased dosage. The remaining 19 cases did not have any change in their treatment, including dosage or intervals
between drug administration, just before and after the pharmacist visit. Baseline characteristics, such as age, Steinblocker Stage and
Class, disease duration, use of biological agents, use of MTX and its dosage, use of prednisolone (PSL) and its dosage, presence of
dementia, and living or not living alone, were assessed. DAS28-ESR, SDAI and CDAI as markers of RA disease activity were
evaluated just before and after the pharmacist visit.
Results: Mean ± SD were as follows: age (years), 74.4 ± 6.1; Stage I, 1; II, 4; III, 6; IV, 8; Class 1, 0; 2, 7; 3, 8; 4, 4; disease duration
(months), 144.2 ± 114.5; use of biological agents; 36.8%; use of MTX and its dosage (mg/week), 84.2% and 6.6 ± 2.7; use of PSL and
its dosage (mg/day), 47.4% and 4.4 ± 1.2; presence of dementia, 10.5%; living alone, 42.1%. The mean values of DAS28-ESR, SDAI,
and CDAI just before and after the pharmacist visit showed improvements; they were 3.56 ± 1.46 and 3.12 ± 1.16 (p = 0.084), 7.99 ±
6.88 and 4.39 ± 3.47 (p = 0.0176), and 6.85 ± 5.74 and 3.90 ± 3.18 (p = 0.0148), respectively. All patients reported satisfaction with the
overall effectiveness of the care.
Conclusion: Adherence to treatment in patients with RA may decline with increasing age. For such patients, education regarding oral
and injectable medication may be useful in controlling RA activity and avoiding any adverse effects due to consumption of wrong
medication. This finding is important for better and safer management of patients with RA in the ageing communities in Japan and other
developed countries.
Disclosure: M. Hayashi, None; H. Matsubara, None; K. Funamura, None; M. Maeda, None; T. Kanamono, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/efficacy-of-educating-visiting-pharmacists-

regarding-drug-administration-for-patients-with-rheumatoid-arthritis-who-poorly-adhere-to-treatment-regimens
Heart Rate Variability Testing with Autonomic Nervous System Optimization: Could
It Change the Course of Spending for Rheumatoid Arthritis Patients in the U.S.? an
Exploratory Minimal Model Analysis
Marita Zimmermann1, Elisabeth Vodicka2, Andrew J Holman3,4,5 and Louis P Garrison2, 1Constants in Global Health, University of
Washington, Seattle, WA, 2Consultants in Global Health, University of Washington, Seattle, WA, 3Rheumatology, Pacific
Rheumatology Associates Inc PS, Seattle, WA, 4Inmedix, Normandy Park, WA, 5Pacific Rheumatology Reseach, Seattle, WA
SESSION INFORMATION
Background/Purpose:
Autonomic nervous system (ANS) testing with heart rate variability (HRV) has been shown to predict 52-week anti-TNF therapeutic
outcomes in rheumatoid arthritis (RA).1 HRV testing could be combined with the three currently available putative ANS biologic
pathways (vagal nerve stimulation,2 obstructive sleep apnea,3 and restless leg [RLS] medications4) to improve treatment response for
RA patients. We explored the potential costs and health outcomes of introducing HRV testing into RA treatment, both without vs. with
ANS optimization.
Methods:
A decision tree exploratory economic model compared HRV testing to standard care in moderate-to-severe biologic-eligible patients
over a 10-year time horizon. Patients were stratified by HRV test scores into “low probability of response” and “moderate to high
probability of response” (parasympathetic HRV<=vs. >0.12) with positive predictive value (PPV)=33% and negative predictive value
(NPV)=100%.5 We then explored adding ANS optimization (RLS method4) based on HRV score, with patients stratified into
parasympathetic <=vs. >0.19, PPV=0.63, NPV=0.88.5 Finally we explored a hypothetical scenario expanding the eligible population to
all RA patients using hypothetically analogous ANS-prediction and ANS-enhancement of non-biologic treatment (no study yet done)
over a range of potential PPV values (10-25%). We also evaluated model outcomes when biologic utilization was assumed to increase
from current 26%6 of eligible patients to 35-55%. Costs and quality-adjusted life-years (QALYs) per patient and for the US population
were estimated. Cost-effectiveness was defined as an incremental cost-effectiveness ratio (ICER) below $150,000/QALY.
Results:
HRV testing in biologic-eligible patients decreased non-effective biologic use, reducing US costs by $9.8B over 10 years with QALYs
unchanged. When combined with ANS optimization in biologic-eligible patients, HRV testing could increase costs by $1.5 billion over
10 years and save 102,000 QALYs (ICER $14,000/QALY). Our hypothetical analysis estimated that, among all RA patients, HRV
testing with ANS optimization could save $15-20 billion and 780,000 QALYs over 10 years, depending on PPV of the HRV test. In this
scenario, if biologic use increased from current uptake, costs could increase from $13 to 98 billion, ICER maintained <$150,000/QALY.
Incremental Incremental Incremental
Standard of Standard Standard
Change with Change with Change with
Care of Care of Care
HRV Testing HRV Testing HRV Testing
HRV testing vs. no testing (10 year total)
Biologics utilization 26%
Biologics utilization 35% Biologics utilization 45%
(current)
Total
$57.33 bil -$9.30 bil -- -- -- --
costs
Biologics $36.07 bil -$9.84 bil -- -- -- --
QALYs 2,228,036 0 -- -- -- --
ICER -- -- -- -- -- --
HRV testing + ANS optimization vs. no testing or optimization, biologic eligible patients
(10 year total)
(current)
Total
$57.33 bil $1.45 bil $57.33 bil $14.20 bil $57.33 bil $28.39 bil
costs
Biologics $36.07 bil $0.03 bil $36.07 bil $12.55 bil $36.07 bil $26.48 bil
QALYs 2,228,036 101,765 2,228,036 163,444 2,228,036 232,054
ICER -- $14,244/QALY -- $86,894/QALY -- $122,330/QALY
HRV testing + ANS optimization vs. no testing or optimization, all patients (10 year total), hypothetical
analysis
(current)
Total $207.38 $207.38
$207.38 bil -$15.36 bil $19.66 bil $58.58 bil
costs bil bil
PPV Biologics $122.27 bil -$23.08 bil $122.27 $122.27
$11.28 bil $49.47 bil
10% bil bil
QALYs 9,348,102 780,335 9,348,102 852,805 9,348,102 933,359
ICER -- -- -- $23,049/QALY -- $62,759/QALY
Total $207.38 $207.38
$207.38 bil -$19.98 bil $13.30 bil $50.29 bil
costs bil bil
PPV Biologics $122.27 bil -$27.99 bil $122.27 $122.27
$4.66 bil $40.96 bil
25% bil bil
QALYs 9,348,102 946,503 9,348,102 1,015,410 9,348,102 1,092,002
ICER -- -- -- $13,100/QALY -- $46,055/QALY
Conclusion:
The potential US health economic impact of introducing HRV testing and ANS optimization into RA treatment appears substantial and
is possibly cost-effective. Additional rigorous studies are warranted in larger patient samples, particularly investigation into non-
biologic therapeutic applications.
1. Holman, Arthritis Rheum. 2015;67 (suppl 10) #1571
2. Koopman, Proc Natl Acad Sci. 2016;113(29)
3. Shimizu, Arthritis Rheum. 2003
4. Holman, Arthritis Rheum. 2015;67 (suppl 10) #422
5. Holman, Auton Neurosci. 2008;143(1-2)
6. Yazici, Bull NYU Hosp Jt Dis. 2008;66(2)
Disclosure: M. Zimmermann, None; E. Vodicka, None; A. J. Holman, Inmedix, 4; L. P. Garrison, None.

View Abstract and Citation Information Online - http://acrabstracts.org/abstract/heart-rate-variability-testing-with-autonomic-
nervous-system-optimization-could-it-change-the-course-of-spending-for-rheumatoid-arthritis-patients-in-the-u-s-an-exploratory-
minimal-model-analysis
Prevalence and Predictors of Knee Replacement Overuse and Underuse in the US

Hassan Ghomrawi1, Alvin Mushlin2, Raymond Kang3, Samprit Banerjee2, Jasvinder A. Singh4, Leena Sharma5, Tuhina Neogi6,
Michael C. Nevitt7 and Daniel Riddle8, 1Surgery and Pediatrics/Center for Healthcare Studies, Feinberg School of Medicine of
Northwestern University, Chicago, IL, 2Healthcare Policy and Research, Weill Cornell Medical College, New York, NY, 3Center for
Healthcare Studies, Feinberg School of Medicine of Northwestern University, Chicago, IL, 4Rheumatology, University of Alabama at
Birmingham, Birmingham, AL, 5Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL,
6Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, MA, 7Epidemiology and
Biostatistics, University of California, San Francisco, San Francisco, CA, 8Virginia Commonwealth University, Richmond, VA
SESSION INFORMATION
Background/Purpose: The elective nature of knee replacement (KR) creates difficult decisions and the potential for both overuse and
underuse. We examined the temporal relationship between needing a KR and actually undergoing one to determine the rates and
investigate predicotrs of overuse and underuse.
Methods: We pooled longitudinal data from the Osteoarthritis Initiative (OAI) and the Multicenter Osteoarthritis (MOST) Study to
estimate KR overuse and underuse. These cohorts closely followed 8,002 participants with or at risk of knee OA over multiple years
and collected demographic, patient-reported, radiographic, and clinical exam information. To determine need for KR, we longitudinally
applied the modified and validated Escobar KR appropriateness criteria (AC) to classify participants as either appropriate or
inappropriate for KR (Table 1). Examining the temporal relationship between appropriateness status and KR utilization, we classified
participants into: 1) appropriate and had KR (appropriate use), 2) appropriate but did not have KR (potential underuse), and 3)
inappropriate but had KR (potential overuse). We used multinomial logistic regression to estimate the association between overuse and
underuse and age, sex, race, educational status, obesity categories, CESD depression score>16, SF-12 PCS, Charlson comorbidity score,
and living alone. We repeated our analyses by dividing potential underusers into those with and without extreme pain (an indicator of
necessity and a likely substantial benefit from KR).
Table 1: Elements of the modified Escobar appropriateness criteria for KR*

Factor Levels
Age 1-<55 years
2-55-65 years
3->65 years
Knee Stability 1-Preserved mobility and stable joint (<5
degrees flexion contracture and normal
or minor medial or lateral gapping in the
20 degrees flexed knee)
2-Limited mobility and/or unstable joint

(>=5 degrees flexion contracture and/or
moderate or severe medial or lateral
gapping in the 20 degrees flexed knee)
Compartments 1-Uni-compartmental
involved
2-Bi/ tri-compartmental
Radiographic 1-Slight (KL grade <=3)
findings
2-Moderate or severe (KL grade = 4)
Symptomatology 1-Slight (mild overall functional loss and
function-related pain [e.g. up to half of
WOMAC pain and physical scale items
scored from 0 to 11])
2-Moderate (moderate overall functional

loss and function-related pain [e.g. up to
half of WOMAC pain and physical scale
items scored from 12 to 22])
3-Intense (intense overall functional loss

and function-related pain [e.g. up to half
of WOMAC pain and physical scale
items scored from 23 to 33]) or
4-Severe (severe overall functional loss

and function-related pain [e.g. up to half
of WOMAC pain and physical scale
items scored from >=34])
*16 combination of factors, depending on levels involved,
determined whether person was appropriate or
inappropriate for surgery. Example: for a 54-year-old
patient with KL=4 and moderate symptoms TKR is
inappropriate; however, if the symptoms are intense or
severe TKR becomes appropriate
Results: 3,449 of 8,002 participants fell into one of the 3 groups, with 843 (24.4%) classified as appropriate users, 2256 (65.4%) as
potential underusers, and 350 (10.1%) as potential overusers. Of potential underusers, 988 (43.8%) were deemed likely to receive
substantial benefit. Compared to appropriate use, the odds of underuse were greater in blacks (OR=2.9, 95% CI [2.3, 3.8]). The odds of
overuse increased with postgraduate degree, higher SF-12 PCS score, living alone, and decreased with being overweight or obese,
having depressive symptoms, and having comorbidities. Distinguishing necessary from not necessary but appropriate in the underuser
group increased racial disparities in KR underuse (blacks OR=4.9, 95% CI[3.8, 6.5]), without significantly affecting findings related to
the other predictors.
Conclusion: We found a substantial proportion of patients either overuse or underuse KR. For the underusers, almost 50% would likely
receive substantial benefit if they underwent KR and of these, African Americans are at greatest risk for underuse. Overuse appears to
be less of a issue but still occurs approximately 10% of the time. Future work needs to focus on ways of reducing rates of overuse and
underuse of KR given the substantial costs and consequences of the procedure.
Disclosure: H. Ghomrawi, NIH, QNRF, 2,Haman Medical Corporation, NIH, 5; A. Mushlin, None; R. Kang, None; S. Banerjee,
None; J. A. Singh, Takeda and Savient, 2,Savient, Takeda, Regeneron, Merz, Iroko, Bioiberica, Crealta/Horizon and Allergan
pharmaceuticals, WebMD, UBM LLC and the American College of Rheumatology, 5,JAS serves as the principal investigator for an
investigator-initiated study funded by Horizon pharmaceuticals through a grant to DINORA, Inc., a 501 (c)(3) entity., 9,JAS is a
member of the executive of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length
funding from 36 companies., 9,JAS is the editor and the Director of the UAB Cochrane Musculoskeletal Group Satellite Center on
Network Meta-analysis., 9,JAS is a member of the American College of Rheumatology's (ACR) Annual Meeting Planning Committee
(AMPC); Chair of the ACR Meet-the-Professor, Workshop and Study Group Subcommittee., 9,JAS is a member of the Veterans Affairs
Rheumatology Field Advisory Committee., 9; L. Sharma, None; T. Neogi, None; M. C. Nevitt, None; D. Riddle, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/prevalence-and-predictors-of-knee-replacement-

overuse-and-underuse-in-the-us
Telemedicine for Rheumatoid Arthritis in the Alaska Native Population

Elizabeth Ferucci1, Tammy Choromanski1, Gretchen Day2 and Sarah Freeman3, 1Division of Community Health Services, Alaska
Native Tribal Health Consortium, Anchorage, AK, 2Clinical and Research Services, Alaska Native Tribal Health Consortium,
Anchorage, AK, 3Alaska Native Tribal Health Consortium, Anchorage, AK
SESSION INFORMATION
Background/Purpose:
Access to a rheumatologist and frequent monitoring of disease activity in rheumatoid arthritis (RA) are associated with higher quality of
care and improved outcomes. With the current rheumatology workforce shortage in the US and concentration of rheumatologists in
urban areas, there is a need for strategies addressing barriers to access. Telemedicine video consultation has been implemented within
the Alaska Tribal Health System specialty clinics, including rheumatology. The purpose of this study is to evaluate the impact of
telemedicine follow-up for RA on disease activity, quality of care, and access to care and to investigate patient perceptions of
telemedicine. This analysis describes the baseline characteristics and perceptions of enrolled study participants.
Methods: Study participants with a diagnosis of RA were recruited when seeing a rheumatologist, either in-person or by telemedicine.
At the study visit, participants completed the RAPID3 and a telemedicine survey and agreed to medical record review for demographics,
disease characteristics, and measures of quality and access to care. Participants also agreed to telephone contact at 6 and 12 months for
follow-up surveys and RAPID3. For data analysis, participants are categorized as being in the telemedicine group if they have had at
least one telemedicine visit with a rheumatologist and in the in-person group otherwise.
Results: To date, 65 participants have enrolled in the study (25 telemedicine and 40 in-person). Age, sex, disease duration, and baseline
RAPID3 score were similar across groups. The telemedicine group had a higher mean number of rheumatologist visits in the past year
(3.3 vs. 2.3, p=0.002). Both groups expressed a preference of seeing a specialist in-person rather than by video and the opinion that it is
important for the specialist to physically examine them. However, those seen by telemedicine were more likely to consider telemedicine
an acceptable way to receive health services (p=0.008) and to have favorable opinions about other aspects of telemedicine, including
respect for culture (p=0.002), patient involvement in decision-making (p<0.001), ability to talk easily and openly to provider (p<0.001),
and trusting the equipment to work (p=0.04). Finally, those seen by telemedicine were more likely to consider the care given in video
visits to be as good as in-person visits (p<0.001).
Conclusion:
Telemedicine can improve access to care in patients with RA. Although patients in both groups expressed a preference for in-person
visits, those seen by telemedicine were more likely to have favorable opinions of it. Whether telemedicine can improve quality of care
and disease activity is not yet known.
Disclosure: E. Ferucci, None; T. Choromanski, None; G. Day, None; S. Freeman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/telemedicine-for-rheumatoid-arthritis-in-the-alaska-

native-population
Systematic Review of Modelling Approaches and Quality for the Cost Effectiveness
of sequential Targeted Therapy in Patients with Rheumatoid Arthritis That Show an
Inadequate Response to at Least One Tumor Necrosis Factor Alpha Inhibitor
Aliza Matusevich1, Maria Suarez-Almazor1, Scott B. Cantor2 and Maria A. Lopez-Olivo1, 1Section of Rheumatology and Clinical
Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA,
Houston, TX, 2Department of Health Services Research, Division of Cancer Prevention and Population Sciences, The University of
Texas MD Anderson Cancer Center, Houston, TX, USA, Houston, TX
SESSION INFORMATION
Background/Purpose: Results from cost-effectiveness analysis (CEAs) comparing treatment options for patients with rheumatoid
arthritis (RA) who have an inadequate response to an initial tumor necrosis factor inhibitor (TNFi) have been inconclusive. Our
objective was to systematically review the modelling approaches and quality of economic evaluations comparing the cost-effectiveness,
cost-utility, or cost-minimization of subsequent TNFi (cycling) versus a therapy with a different mode of action (swapping) in order to
understand their discrepant results.
Methods: We searched seven electronic databases until 2016, sources of gray literature and the references of relevant publications. Two
independent reviewers screened retrieved citations, including studies published in English-language and economic evaluations
comparing second line biological treatments in RA patients. We excluded reviews, conference abstracts and poster presentations. Data
extraction was done by one reviewer and crosschecked by another. Reporting quality was evaluated based on the Consolidated Health
Economic Evaluation Reporting Standards (CHEERS) statement. Reported incremental cost-effectiveness ratios (ICERs) were
synthetized and adjusted to 2016 US dollars according to rules specified by the Panel on Cost-Effectiveness in Health and Medicine.
Results: Of 4,563 citations, ten economic evaluations comprising 21 comparisons and representing six European countries, Canada and
the United States were included. Most studies (8 of 10) were funded by the pharmaceutical industry. There were two discrete event
simulations, three microsimulations, two Markov cohort models, two decision trees and one single study-based evaluation. The most
common time horizons were lifetime (6/10) and one year (2/10). Seven studies were from a payer perspective. The cohorts were
predominantly female (78%), on average aged 53.4 years, disease duration of 10.2 years and baseline health assessment questionnaire
(HAQ) of 2.3. Adherence to reporting standards was good with seven studies scoring ≥26 out of 36. The most common failing point was
justification of modelling choices. One study did not report any sensitivity analysis, but most performed probabilistic as well as one-way
sensitivity analysis. Common influential parameters include rituximab dosing schedule as well as assumptions regarding HAQ
progression and conversion to utilities. In the cost-utility analyses, the median ICER was US$25,617 for the swapping strategy,
rituximab dominated in half of the comparisons. Of the CEA comparisons, tofacitinib dominated adalimumab while the ICER for
abatacept versus infliximab was $20,803 and $27,976 per case of low disease activity and remission respectively. The single cost-
minimization study found in favor of rituximab.
Conclusion: Despite disparate modelling approaches it appears that swapping to a targeted agents with an alternative mechanism of
action is cost-effective at the $50,000/QALY threshold as ICER’s ranged between $9,323 to 41,467/QALY, dominating in 8 of 20
comparisons.
Disclosure: A. Matusevich, None; M. Suarez-Almazor, Pfizer Inc, 5; S. B. Cantor, None; M. A. Lopez-Olivo, Rheumatology
Research Foundation, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/systematic-review-of-modelling-approaches-and-

quality-for-the-cost-effectiveness-of-sequential-targeted-therapy-in-patients-with-rheumatoid-arthritis-that-show-an-inadequate-
response-to-at-least-one-t

Impact of Step Therapy Protocols on North Carolina Rheumatologists’ Job
Satisfaction and the Quality of Care Received By Their Patients with Rheumatoid
Arthritis
Victoria Hamby1, Amanda Nelson2, Antonia Bennett1, Leigh F. Callahan3 and Stacie Dusetzina4, 1Gillings School of Global Public
Health, Department of Health Policy and Management, University of North Carolina at Chapel Hill, Chapel Hill, NC, 2Division of
Rheumatology, Allergy, and Immunology and Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel
Hill, NC, 3Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 4Eshelman School of
Pharmacy and Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC
SESSION INFORMATION
Background/Purpose: Early diagnosis and treatment of rheumatoid arthritis (RA) is crucial in minimizing disease damage. Step-
therapy, a form of prior authorization used by payers to manage costs, determines which medications will be covered and thus
affordable. Expansion of the Institute for Healthcare Improvements Triple Aim initiative to the Quadruple Aim initiative added the aim
to promote workplace happiness for providers. We examined provider beliefs regarding the role of step-therapy in managing health care
costs, quality of care delivered, and on clinical autonomy and job satisfaction in North Carolina. We also evaluated provider awareness
and agreement with proposed state policies aimed at streamlining step-therapy exceptions processes.
Methods: In this cross-sectional survey study, a web-based questionnaire was emailed on March 7 and March 16, 2017 to all members
of the North Carolina Rheumatology Association. We summarized the data through frequency counts to determine knowledge, beliefs
and perception of step-therapy, and chi-square tests were used to compare respondent knowledge of state legislation, NC HB 1048, to
their beliefs about autonomy and job satisfaction.
Results: The survey was sent to 118 providers, and the final analysis included 38 completed surveys (effective response rate of 32.2%).
Respondents were more likely to be male (58%), report 20+ years in practice (53%), work in a private practice (87%), and see patients
with Medicare (34%) or private insurance (38%). Providers disagreed that step-therapy reduced costs for society overall (52%) or
patients (57%). Instead, 82% agreed that step-therapy reduced costs for insurance companies. With respect to quality, 92% of providers
believed step-therapy negatively impacted the quality of care provided to patients (50% somewhat reduced quality, 42% greatly reduced
quality) and 82% of providers agreed that step-therapy delayed beginning proper treatment (50% agree, 31% strongly agree). Nearly
90% of providers reported step-therapy negatively affects their autonomy and 87% reported step-therapy negatively impacting their job
satisfaction. When considering the burden of step-therapy on providers, 79% of providers reported step-therapy as being common when
prescribing for RA. Most respondents (76%) were directly involved in processing step-therapy paperwork. In addition, half of
respondents reported spending >60 minutes on step-therapy paperwork in an average clinic day. Despite the burden of step-therapy, only
47% of providers were aware of proposed NC state legislation to reduce the burden of step-therapy. Notably nearly all surveyed
providers agreed with the exceptions proposed within the state legislation.
Conclusion: Providers view step-therapy as a burden without justifiable results for cost and quality. This unjustified burden coupled
with provider agreement with state proposed legislation suggests that providers should engage with policy makers to support legislative
action on this topic. Additionally, provider groups such as the ACR should create advocacy groups to increase awareness of state and
federal legislation.
Disclosure: V. Hamby, None; A. Nelson, QuantiaMD, 9,NIAMS-NIH, 2,RRF, 2; A. Bennett, None; L. F. Callahan, None; S.
Dusetzina, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/impact-of-step-therapy-protocols-on-north-carolina-

rheumatologists-job-satisfaction-and-the-quality-of-care-received-by-their-patients-with-rheumatoid-arthritis
Healthcare Utilization Profiles in Rheumatoid Arthritis – a Cluster Analysis

Nina Mars1,2, Anne M Kerola2,3, Markku J Kauppi4,5, Matti Pirinen1, Outi Elonheimo6 and Tuulikki Sokka-Isler7, 1Institute for
Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, 2University of Helsinki, Helsinki, Finland,
3Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland, 4School of Medicine, University of Tampere, Tampere,
Finland, 5Department of Rheumatology, Päijät-Häme Central Hospital, Lahti, Finland, 6FCG Finnish Consulting Group Ltd., Helsinki,
Finland, 7Rheumatology, Jyvaskyla Central Hospital, Jyvaskyla, Finland
SESSION INFORMATION
Background/Purpose: Utilization patterns in rheumatoid arthritis (RA) are complex. For targeted interventions, patients with special
healthcare needs should be recognized. Our aim was to explore healthcare utilization profiles in RA by cluster analysis.
Methods: The RA patients attending Jyväskylä Central Hospital rheumatology unit, Finland, are as of 2007 enrolled prospectively in a
structured digital database, from which we identified patients with rheumatology clinic visits in 2012-2014. We combined this clinical
data with well-recorded administrative data on fiscal year 2014 on all public healthcare visits, both in primary and specialty care. For
each patient, we considered the median of time dependent clinical variables. Clustering variables were disease activity score (DAS28-
3), health assessment questionnaire index (HAQ index, 0-3), pain on visual analogue scale (VAS, 0-100) and total annual health services
related direct costs (€), excluding out of pocket medication costs. The number of clusters was set based on dendrogram examination. We
applied hierarchical clustering with Ward's minimum variance method with Euclidean distance.
Results: Of 844 patients with RA, complete-case analysis (n = 827) derived four clusters. Descriptive statistics are in Table 1 and
distributions for DAS28-3 and HAQ index are in Figure 1. Cluster 1 was the largest cluster constituting relatively young patients with
low costs, low disease activity, and minimal disability. Cluster 2 was characterized by high pain levels and disability, despite fairly low
average DAS28-3. Compared with cluster 2, patients in cluster 3 had high average disease activity and rheumatic disease -related costs,
and biologics were more frequently used. Still, they presented with less pain and disability compared with cluster 2. Cluster 4 was small,
heterogeneous and characterized by exceptionally high average costs. These patients had costly and severe comorbidities in addition to
RA.
Conclusion: Over half of patients had low costs and favorable outcome measures, whereas a fifth was characterized by high disease
activity and active treatment of RA, yielding higher costs. Pain and disability did not necessarily relate to high rheumatic disease -
related costs. In all clusters, over half of costs were attributable to comorbidities.
Cluster Cluster Cluster Cluster

1 2 3 4
n 467 147 180 33
58.2 ± 66.5 ± 63.3 ± 71.1 ±
Age (mean ± SD) 15.3 11.8 13.9 10.8
11.8 ± 16.3 ± 16.0 ± 18.6 ±
Disease duration (median) 8.5 12.6 12.5 12.9
15.9 ± 55.2 ± 37.2 ± 47.0 ±
Pain (mean ± SD) 12.2 18.3 15.8 20.9
RF+ (%) 65 71 77 90
Ever biologics (%) 23.3 24.5 43.3 45.5
Number of comorbidities 2.1 ± 2.13.7 ± 2.83.4 ± 2.55.7 ± 3.5
Mean total costs/patient
(€) 2367 3785 6772 36206
Mean rheumatic disease 1054 1455 3076 4323
costs/patient (%*) (48.5) (44.8) (48.5) (13.0)
*Of recorded healthcare contacs
Table 1. Descriptive statistics.

Figure 1. Distributions for DAS28-3 and HAQ index based on individual time dependent medians.
Disclosure: N. Mars, None; A. M. Kerola, None; M. J. Kauppi, None; M. Pirinen, None; O. Elonheimo, Finnish Consulting Group
Ltd, 3; T. Sokka-Isler, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/healthcare-utilization-profiles-in-rheumatoid-

arthritis-a-cluster-analysis
A Combination of Self-Reported Symptoms and ACPA Testing Can Identify

Individuals with Previously Undiagnosed Inflammatory Arthritis in a Health-Fair
Setting
Elizabeth A. Bemis1, Nicholas Ellinwood2, Kaylynn Aiona3, Christopher C. Striebich4 and Kevin D. Deane5, 1Epidemiology,
Colorado School of Public Health, Aurora, CO, 2Pharmacology and Toxicology Graduate Group, University of California Davis, Davis,
CA, 3Denver Health and Hospitals and Colorado School of Public Health, Denver, CO, 4Division of Rhuematology, University of
Colorado School of Medicine, Aurora, CO, 5Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO
SESSION INFORMATION
Background/Purpose:
Early identification and treatment of inflammatory arthritis (IA) and in particular rheumatoid arthritis (RA) can lead to improved
outcomes. However, there are often delays in diagnosis. We hypothesized that evaluation of individuals in a health-fair setting could
identify those with previously undiagnosed IA/RA. In addition, because performing physical examinations is difficult to perform on a
large scale, we sought to evaluate the diagnostic characteristics of self-reported symptoms and antibody testing to identify IA.
Methods:
Subjects who self-reported no prior diagnosis of RA were evaluated from 2012 to 2015 at a Colorado based health-fair. Each subject
reported presence/absence and location of joint symptoms in the wrists and hands on a cartoon picture of these joints. All subjects
additionally underwent ACPA testing (CCP3, Inova) and a joint examination of the wrists and hands (excluding DIPs) by a
rheumatologist who recorded presence/absence of IA. The diagnostic accuracy of symptoms and ACPA as single variables or an overall
score were evaluated using regression techniques.
Results:
1703 subjects were evaluated, and 98 (5.8%) were found to have IA (Table 1). Of single joint areas, self-reported symptoms of joint
pain, stiffness or swelling in the MCPs had the strongest association with the presence of IA on examination (OR 4.8). CCP3(+) was
also significantly associated with IA (OR 3.1) but was present in only 8% of all subjects with IA, and 45 subjects were CCP3(+) without
hand/wrist IA. In multivariate analyses, four variables including symptoms in wrists, MCPs, PIPs, and CCP3(+) were significantly
associated with IA. When these 4 variables were evaluated as counts, the highest positive predictive value (PPV) for IA was 22% (³3
items present), and the highest negative PV was ~98% (0 items present) (Table 2).
Conclusion:
Health-fair evaluations can be used to identify individuals with IA, some of whom likely have RA due to CCP3(+), and others with
potentially other forms of IA. A scoring system using a combination of self-reported joint symptoms and CCP3 testing can be used to
identify those with IA in the hands, with varying predictive values depending on the score used. Further evaluations including
determining what specific forms of arthritis are identified and cost-effectiveness need to be performed, but overall these findings
support a health-fair based approach using questionnaires and ACPA testing as a way to improve identification of IA. Additionally,
N=46 CCP3(+) subjects did not have IA, indicating this method could be used to identify individuals at future risk for RA.
Table 1. Univariate analyses of differences in

demographics, CCP positivity and joint symptoms
between subjects with/without IA
OR (95%
IA No IA P-value
CI)
N 98 1605
Mean Age at
56.43 56.07 0.7835
Visit (Years)
0.51 (0.47,
Percent Female 64.29 69.84 0.2458
1.19)
46 3.08 (1.41,
N, (%) CCP+ 8 (8.16%) 0.003
(2.90%) 6.73)
Self-Reported
symptoms of
pain, stiffness
or swelling on
the day of the
health-fair
evaluation
2.37 (1.44,
22.45 10.9 0.0005
Wrist 3.90)
4.80 (3.16,
57.14 21.74 <0.0001
MCP 7.28)
4.60 (3.03,
PIP 48.98 17.26 <0.0001
6.98)
Table 2. Counts of symptoms in wrists, MCPs, PIPs,
and CCP3 positivity and diagnostic accuracy for
inflammatory arthritis
Number of
Items Positive
(joint
Positive Negative
symptoms in
Predictive Predictive
wrists, MCPs, Sensitivity Specificity
Value Value
PIPs and
(PPV) (NPV)
positive for
CCP3 each get
1 point)
1 or more* 80.61 63.36 11.84 98.17*
2 or more 42.86 86.29 16.03 96.11
3 or more 11.22 97.63 22.45 94.74
All 4 items 2.04 100.00 100.00 94.36
*Of note, the 1036 subjects who reported no symptoms in
their wrists, MCPS and PIPs or had CCP3 positivity, 19
were found to have IA on examination
Disclosure: E. A. Bemis, None; N. Ellinwood, None; K. Aiona, None; C. C. Striebich, None; K. D. Deane, Inova Diagnostics, Inc.,
5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-combination-of-self-reported-symptoms-and-acpa-

testing-can-identify-individuals-with-previously-undiagnosed-inflammatory-arthritis-in-a-health-fair-setting
Evolution of Health Care Consumption in the Knee and Hip Osteoarthritis Long
Term Assessment Cohort, a French Population Based Cohort of Symptomatic Knee
and/or Hip OA Patients
Anne-Christine Rat1,2,3, Jean-Hugues Salmon4, Willy Ngueyon Sime5, Maud Wieczorek6, Alain Saraux7, Claudine Gard8, Francis
Guillemin9 and Bruno Fautrel10, 1Inserm, CIC-1433 Epidémiologie Clinique, Vandoeuvre-lès-Nancy, France, 2Rheumatology
Department, CHRU Nancy, Vandoeuvre-lès-Nancy, France, 3Université de Lorraine, EA4360, APEMAC, Nancy, France,
4Rheumatology, Rheumatology Department CHU Teaching Hospital Reims, Reims, France, 5CIC 1433 Epidémiologie clinique, Inserm,
Nancy, France, 6Université de Lorraine EA 4360 APEMAC, Nancy, France, 7Rheumatology Department, Rheumatology Department,
CHU de la Cavale Blanche, Brest, France, Brest Cedex, France, 8Pitié Salpetrière hospital, Paris, France, 9CHRU Nancy, Clinical
Epidemiology and Evaluation, Université de Lorraine, Paris Descartes University, APEMAC, EA 4360, Nancy, France, 10UPMC
University Paris 06, Pitié-Salpétrière Hospital, Paris, France
SESSION INFORMATION
- Background/Purpose: in hip and knee OA, one of the leading causes of global disability, recent population-based data of health
care practices and utilization are scarce. Describing trajectories of patients’ patterns of care and their predictive factors is important to
adapt health care practices and guide interventions to optimize patients’ use of health care services. The aim of the study was to describe
health care utilization trajectories and associated factors of a representative sample of patients with knee or hip symptomatic OA.
- Methods: the KHOALA cohort is a French population-based multicenter cohort of 878 patients with symptomatic knee and/or hip
OA, aged between 40 and 75 years old recruited between 2007 and 2009. Patients are followed annually by self-report questionnaires.
Analyses used the data from the 5 first years of the follow up. We used Latent Class Growth Analyses (LCGA) to define homogeneous
subgroups of trajectories based on the individual health care consumptions over time, and logistic regressions to explain the differences
between the identified trajectories with baseline characteristics.
- Results: Among the 878 patients, 609 (69%) were women, 222 (25%) have hip OA, 607 (69%) knee OA and 49 (6%) both hip and
knee OA. Groll comorbidity index (0-18) was 3.1 (1.6). The most optimal and clinically relevant models retrieved by LCGA were two
group models for consultations with the different health care professionals (primary care physician (PCP), rheumatologist, orthopedic
surgeon, physiotherapist), hospitalizations, use of assisting devices and acid hyaluronic (AH) injections, and 3 group models for
corticoids injections and use of complementary and alternative medicine (CAM). In multivariate analyses, increasing age was
independently associated with the trajectory of high number of consultations with PCP and rheumatologist, and with a high use of
corticoids injections or complementary medicine. Impaired mental health was associated with the groups of frequent consultations with
PCP, rheumatologists and physiotherapists and with corticoid injections. Pain was only associated with increasing number of orthopedic
surgeons consultations and high use of assisting devices. Impaired function abilities were only associated with frequent hospitalizations.
Comorbidities are associated with PCP consultations and hospitalizations (frequent use).
- Conclusion: In multivariate analyses, mental health impairment is the only symptom associated with trajectories of frequent use of
medical care while pain is only associated with orthopedic surgeon consultations.
Disclosure: A. C. Rat, None; J. H. Salmon, None; W. Ngueyon Sime, None; M. Wieczorek, None; A. Saraux, None; C. Gard,
None; F. Guillemin, None; B. Fautrel, AbbVIe, Biogen, BMS, Celgene, Hospira, Janssen, Eli Lilly and Company, Novartis, Pfizer,
Roche, SOBI Pharma, UCB, 5.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/evolution-of-health-care-consumption-in-the-knee-

and-hip-osteoarthritis-long-term-assessment-cohort-a-french-population-based-cohort-of-symptomatic-knee-andor-hip-oa-patients
Budgetary Impact Analysis of Real-World Dosing Patterns in Matched Cohorts of

Rheumatoid Arthritis Patients Treated with Infliximab or Golimumab Intravenous
Anti-TNF Medications
Lorie A. Ellis1, Elisabetta Malangone-Monaco2, Helen Varker2, Diana Stetsovsky3, Maureen Kubacki4, Raphael J. DeHoratius5 and
Shelly Kafka4, 1Janssen HECOR Immunology, Horsham, PA, 2Truven Health Analytics, Bethesda, MD, 3Truven Health Analytics,
Philadelphia, PA, 4Janssen Scientific Affairs, LLC, Horsham, PA, 5Janssen Scientific Affairs, LLC/Sidney Kimmel School of Medicine,
Thomas Jefferson University, Horsham/Philadelphia, PA
SESSION INFORMATION
Background/Purpose: Infliximab (IFX) is more frequently selected than golimumab for intravenous use (GLM-IV) in patients with
Rheumatoid Arthritis (RA) but differences in dosing and administration recommendations for these products may have budgetary
consequences. This study aimed to determine the budgetary impact of IFX and GLM-IV based upon real-world treatment patterns and
commercial reimbursement in a matched sample of RA patients.
Methods: Truven Commercial Claims and Encounters and Medicare Supplemental data were used to evaluate maintenance infusion
interval, frequency of first or subsequent hour billing code and cost of infusions for adult RA patients starting a new episode of IFX
(J1745) or GLM-IV (J1604). Adult patients with ≥12 months continuous enrollment before and after the 1st IFX or GLM-IV claim
(index) between 1/1/2014 and 3/31/2016 and no evidence of index medication use 12 months before index were studied. IFX and GLM-
IV patients were matched 1:1 on index medication treatment duration, gender, payer type, prior-biologic use and post-index
methotrexate (MTX). The payer paid drug plus administration cost was used applied to population treatment patterns. Descriptive
statistics summarized key variables (mean, SD, median, n, %). Chi-squared tests determined differences between categorical variables
and t-test was used for continuous variables.
Results: A total of 1,094 matched patients were identified (n=547 GLM-IV; n=547 IFX). In both groups, median age was 56 years;
82% were female and 38% had no prior biologic use. Mean (SD) follow-up was 609 (161) days (d) for GLM-IV and 613 (163) days for
IFX. Mean (SD) duration of GLM-IV use was 396 (240) d and 397 (239) d for IFX. A total of 3,961 GLM-IV infusions and 4,716 IFX
infusions were administered. The proportion of maintenance infusions given every 8 wk was 80% for GLM-IV vs 39% for IFX; 6% of
GLM-IV vs 53% of IFX infusions occurred more frequently than every 8 wk (P<0.0001). Mean drug plus administration cost per
infusion was $5,846.10 (GLM-IV) and $5,443.66(IFX). Mean GLM-IV administration cost was $224.26 with <1% of infusions having
a second hour billing code vs IFX with mean administration cost of $360.36 and 96% of IFX infusions requiring a second hour billing
code (P<0.0001). Based upon the average maintenance infusion interval, GLM-IV patients cost approximately $10,507 less than IFX
patients in the first year and approximately $6,774 less than IFX patients in subsequent years.
Conclusion: From the commercial health plan perspective, annual GLM-IV drug plus administration cost was less than IFX in RA
patients due to differences in real-world dosing and administration. These findings have important implications for population health
decision makers.
Disclosure: L. A. Ellis, Janssen, 3,Johnson & Johnson, LLC, 1; E. Malangone-Monaco, Janssen Scientific Affairs, LLC, 5; H.
Varker, Janssen Scientific Affairs, LLC, 5; D. Stetsovsky, Janssen Scientific Affairs, LLC, 5; M. Kubacki, Janssen Scientific Affairs,
LLC, 3; R. J. DeHoratius, Johnson & Johnson, 3; S. Kafka, Janssen Pharmaceuticals, 3,Johnson & Johnson, 1.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/budgetary-impact-analysis-of-real-world-dosing-

patterns-in-matched-cohorts-of-rheumatoid-arthritis-patients-treated-with-infliximab-or-golimumab-intravenous-anti-tnf-medications
Variation in DMARD Therapy Following Methotrexate Failure for Newly-Identified

Rheumatoid Arthritis in a National Veterans Health Administration Cohort
John McDougall Jr.1,2, Cynthia Brandt3,4, Melissa Skanderson3, Joseph Goulet3 and Liana Fraenkel5, 1National Clinican Scholars
Program, Yale School of Medicine, New Haven, CT, 2Dep't. of Rheumatology, Yale School of Medicine, New Haven, CT, 3Veterans
Affairs Connecticut Healthcare System, West Haven, CT, 4Emergency Medicine, Yale School of Medicine, New Haven, CT,
5Rheumatology, Rheumatology, Yale University School of Medicine, New Haven, CT, New Haven, CT
SESSION INFORMATION
Background/Purpose:
Absent contraindications to conventional DMARD (cDMARD) use, the Veterans Administration (VA) requires a 3-month trial of 2
cDMARDs prior to the use of biologic DMARD (bDMARD), for active rheumatoid arthritis (RA). In this national VA study, we used a
time-to-event analysis in cases of newly-identified RA to examine variation between VA Integrated Service Network (VISN) areas in
prescriptions following MTX monotherapy.
Methods:
A previously validated, 3-part definition was used to identify patients with RA within the VA Musculoskeletal Disorder (MSD) cohort
(N > 5 million, Jan 1, 2000-Dec 31, 2013). The date of the first VA DMARD prescription was used to define both RA diagnosis and RA
cohort entry. To limit our analysis to newly-identified RA, we included patients with >1 year in the MSD cohort prior to RA diagnosis.
To make our RA cohort as uniform as possible, we included only patients who first received a >90-day period of VA-prescribed MTX
monotherapy. Kaplan Meier survival analysis and bivariate logistic regression were used to assess patient demographic and clinical data.
After adjusting for significant predictor variables, we used a multivariate logistic regression to examine initial, non-MTX DMARD
prescription by VISN.
Results:
A total of 4,823 patients (91% male, median age 64yrs, median observation time 3.91 yrs) met our inclusion criteria. All 21 VISN areas
were represented (mean number of RA patients per VISN = 230 pts; range 88-488). Overall, 1,911 patients (40%) were prescribed only
MTX monotherapy while observed in the RA cohort. Of the remaining patients who did receive a non-MTX DMARD, 748 (15%) went
on to receive a bDMARD, whereas 2,164 (45%) received a cDMARD, as their initial, non-MTX DMARD prescription. The median
interval between the first MTX prescription and initial, all non-MTX DMARD prescription was 1.13 years (IQR 0.56-2.25); a Kaplan
Meier survival analysis did not show a significant difference between bDMARD and cDMARD interval prescription times (Kaplan
Meier log rank p=0.94). Examining regional variation, 8 VISN areas were at statistically higher odds of receiving an initial bDMARD
prescription, when compared to the VISN with lowest percentage bDMARD prescriptions (OR range 1.0-3.29, reference cDMARD
prescription in VISN 23, see Figure 1).
Conclusion:
Following MTX monotherapy for newly-identified RA, we found a 3-fold variation by VISN in the prescription of biologic versus
conventional DMARDs (see Figure 1; base 1.0 [VISN 23] in blue, highest 3.29 [VISN 22] in red). Further work is needed to assess the
causes of these differences.
Disclosure: J. McDougall Jr., None; C. Brandt, None; M. Skanderson, None; J. Goulet, None; L. Fraenkel, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/variation-in-dmard-therapy-following-methotrexate-

failure-for-newly-identified-rheumatoid-arthritis-in-a-national-veterans-health-administration-cohort
Cost-Effectiveness of Tai Chi Versus Physical Therapy for Knee Osteoarthritis

John B. Wong1, Mei Chung2, Lori Lyn Price3 and Chenchen Wang4,5, 1Tufts Medical Center, Boston, MA, 2Department of Public
Health and Community Medicine, Tufts University School of Medicine, Boston, MA, 3Biostatistics Research Center, Institute for
Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, 4Rheumatology, Center of Integrative Medicine and
Division of Rheumatology, Tufts Medical Center, Boston, MA, Boston, MA, 5Division of Rheumatology, Tufts Medical Center, Boston,
MA
SESSION INFORMATION
Background/Purpose: A single-blind randomized comparative effectiveness trial showed that Tai Chi yielded beneficial effects similar
to those of a standard course of physical therapy in the treatment of knee osteoarthritis, so we aimed to examine the cost-effectiveness of
Tai Chi vs. physical therapy for knee osteoarthritis.
Methods: Using standard microeconomic methods, we developed a simulation model to estimate healthcare resource utilization
(hospitalizations, inpatient, outpatient, testing, medications and nutraceutical use) and cumulative effectiveness outcomes (WOMAC
pain, WOMAC function, Global Visual Analog Scale and SF36 pain component score) over 12 weeks, 24 weeks, and a year. Based on
available data, we fit longitudinal models for each patient. To account for uncertainty in the results and estimates, we performed Monte
Carlo simulations incorporating the uncertainty surrounding all estimates. We estimated physical therapy costs at $100 per session for 6
weeks twice a week and group Tai Chi classes at $25 per session at twice a week for 12 weeks and accounted for the adherence
observed in the study.
Results: In the 1000 simulations for 12, 24 and 52 weeks, Tai Chi was always less expensive than Physical Therapy, with mean (SD)
savings of $289 (47) at 12 weeks, $648 (60) at 24 weeks and $1668 (112) after 52 weeks. The analysis was most sensitive to the cost of
PT or Tai Chi. At $25 per session for PT, PT was cost-saving at 12 and 24 weeks but Tai Chi was cost saving at 52 weeks. At $60 per
session for Tai Chi, Physical Therapy was cost-saving at 12 weeks, but Tai Chi became cost-effective at 24 and 52 weeks.
In terms of effectiveness for 100 patients with knee OA, Tai Chi improved WOMAC pain (0-500) by 50,925 points over 12 weeks,
220,159 points over 24 weeks and 368,642 points over 52 weeks. Similarly, Tai Chi improved WOMAC function (0-1700) by 93,339
points over 12 weeks, 279,460 points over 24 weeks and 439,979 points over 52 weeks. Tai Chi improved Global Visual Analog Scale
(0-10) by 1899 over 12 weeks, 5770 over 24 weeks and 12,724 over 52 weeks. Lastly, Tai Chi improved SF36 Physical Component
Score (0-100) by 13,589 over 12 weeks, 44,197 over 24 weeks and 84,294 over 52 weeks.
Conclusion: Our analysis suggests that Tai Chi is cost-saving relative to physical therapy because it on average both reduces costs and
improves outcomes. The results are relatively robust (consistent) when varying the cost of physical therapy and Tai Chi until extreme
values were considered. The results suggest that reimbursement for Tai Chi as a treatment for knee osteoarthritis should be considered
by health payers.
Disclosure: J. B. Wong, None; M. Chung, None; L. L. Price, None; C. Wang, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/cost-effectiveness-of-tai-chi-versus-physical-

therapy-for-knee-osteoarthritis
Assessing Interferon Regulatory Factor 5 (IRF5) Function in Human Primary

Immune Cells with Cell-Penetrating Peptides
Jaspreet Banga1, Dinesh Srinivasan2, Chia Chi Sun3, Francesca Milletti4, Kuo-Sen Huang5, Shannon Hamilton6, Ann F. Hoffman5,
Yajuan G. Qin2, Sandip Panicker2, Gang Lu2, Dan Li7, Hong Qian5, David R. Bolin5, Lena Liang5, Charles Wartchow5, Nader
Fotouhi5, Julie A. DeMartino3, Seng-Lai Tan2, Gang Chen3 and Betsy J. Barnes7, 1The Feinstein Institute for Medical Research,
Manhasset, NY, 2Inflammation Discovery, Hoffmann-La Roche, Inc., Nutley, NJ, 3TIP Immunology, EMD Serono Research and
Development Institute, Inc., Billerica, MA, 4Roche Innovation Center New York, New York, NY, 5Hoffmann-La Roche, Inc., Nutley,
NJ, 6Hoffmann-La Roche, Inc., Nutley, NJ, Afghanistan, 7Center for Autoimmune and Musculoskeletal Diseases, The Feinstein
Institute for Medical Research, Manhasset, NY
SESSION INFORMATION
Session Title: Innate Immunity and Rheumatic Disease Poster II
Background/Purpose: Interferon regulatory factor 5 (IRF5) is a key mediator of pathogen-induced immune responses that acts
downstream of Toll-like receptors (TLRs), NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs). IRF5 polymorphisms leading
to its elevated expression and activation have been detected in patients with autoimmune diseases; yet, the contribution of IRF5 to
disease onset and/or severity remains to be fully elucidated. IRF5 typically remains inactive in the cytoplasm of a cell but upon
stimulation by external signals, IRF5 undergoes post-translational modification(s), homo-dimerization, and nuclear translocation, where
the dimeric protein induces transcription of antiviral and pro-inflammatory genes. Here, we report the evaluation of novel cell-
penetrating peptides (CPPs) designed to disrupt IRF5 dimerization which is considered critical for nuclear translocation and function in
immune cells.
Methods: We designed CPPs targeting IRF5 Helix 2 or Helix 5 regions based on a modelled structure of the IRF5 dimer. CPPs binding
to the IRF5 monomer were measured in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. Potencies of IRF5-
CPPs were assessed in an IRF5 dimerization assay using recombinant biotin- and his-tagged IRF5 (222-467, S430D). Cell penetration
was first tested in Hela cells with FITC-conjugated CPPs followed by confocal microscopy. The effects of IRF5-CPPs on nuclear
localization and phosphorylation of IRF5 in CD14+ monocytes, CD123+BDCA2+ plasmacytoid dendritic cells (pDC) and CD19+ B
cells were analyzed on an ImageStream Mark II cytometer following stimulation of peripheral blood mononuclear cells (PBMCs) with
CpGA, R848 or SLE serum. Levels of inflammatory cytokines (IL-6, TNFα), IgG and IFNα in PBMCs were measured by AlphaLISA.
Results: Biochemical and imaging analyzes showed that IRF5-CPPs are cell permeable, non-cytotoxic at concentrations <50 µM, and
directly bind to IRF5 (KD = 0.5-0.93 µM). FRET assays revealed that IRF5-CPPs disrupt IRF5 homo-dimerization (IC50 = 8.5-10.9
µM). Stimulation of PBMCs with TLR ligands revealed that IRF5-CPPs blocked pro-inflammatory cytokine production (IL-12, TNFα,
and IL-6), IgG production in B cells, and IFNα production in pDCs. Inhibition of cytokine and IgG production from primary immune
cells correlated with a significant, concentration-dependent reduction in the nuclear localization of phosphorylated IRF5. Similar
findings were made in PBMCs derived from patients with systemic lupus erythematosus (SLE) or lupus nephritis (LN).
Conclusion: Rational design of novel cell-penetrating peptide inhibitors that target IRF5 dimerization not only provides new tools for
the functional interrogation of IRF5 in healthy and disease-relevant cells, but also facilitates the development of new therapeutics to
treat inflammatory and autoimmune disorders such as SLE.
Disclosure: J. Banga, None; D. Srinivasan, Anthera Pharmaceuticals Inc., LQT Therapeutics, 1,Anthera Pharmaceuticals Inc., 3,LQT
Therapeutics, 5,Hoffmann-La Roche Inc., 9; C. C. Sun, EMD Serono Research and Development Institute, Inc., 3; F. Milletti, Roche
Pharmaceuticals, 1,Roche Pharmaceuticals, 3; K. S. Huang, None; S. Hamilton, None; A. F. Hoffman, None; Y. G. Qin, None; S.
Panicker, None; G. Lu, None; D. Li, None; H. Qian, None; D. R. Bolin, None; L. Liang, None; C. Wartchow, None; N. Fotouhi,
None; J. A. DeMartino, EMD Serono, Merck and Co., 1,EMD Serono, 3; S. L. Tan, None; G. Chen, EMD Serono, 1,EMR Serono, 3;
B. J. Barnes, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/assessing-interferon-regulatory-factor-5-irf5-

function-in-human-primary-immune-cells-with-cell-penetrating-peptides
Cardiac Endothelial Cell Transcriptome Analyses Support a Pathological Role of

Metabolic and Inflammasome Genes in Anti-SSA/Ro-Associated Congenital Heart
Block
Sara Rasmussen1, Robert M. Clancy2 and Jill P. Buyon2, 1Department of Medicine, Division of Rheumatology, NYU School of
Medicine, New York, NY, 2NYU School of Medicine, New York, NY
SESSION INFORMATION
Background/Purpose:
The role of Type I IFN in anti-SSA/Ro-associated Congenital Heart Block (CHB) may include an adverse consequence to the cardiac
vasculature. One scenario consistent with injury is that the phenotype of cardiac endothelial cells contributes to Caspase-1/Interleukin-1
converting enzyme (inflammasome) to account for chronic levels of inflammatory cytokines and oxidative stress. This study sought to
test the hypothesis that anti-SSA/Ro-mediated injury to the vasculature occurs via a Type 1 IFN-enriched environment, which acts on
the endothelial cells to upregulate the inflammasome along with metabolical changes contributing to damage by decreasing oxygen to
the tissue.
Methods:
Two sources of endothelial cells were studied. In an in vitro approach, cultured HUVECs were evaluated in the presence and absence of
supernatants generated from macrophages treated with ssRNA (hY3) since previous studies have identified macrophages as a potential
source of IFN in CHB. Both transcriptomic analyses and cellular metabolism as reflected in the extracellular acidification rate (ECAR)
and mitochondrial oxygen consumption (OCR) were analyzed using the Seahorse platform. A second in vivo approach used freshly
obtained endothelial cells (DAPI negative cells isolated by flow using antibodies to CD31) from a 19 week fetus dying with CHB and
an otherwise healthy 22 week heart.
Results:
For the in vitro experiments, IFIT1 (IFN response gene) was significantly increased by 163-fold in HUVECs incubated with hY3
macrophage supernatants compared to HUVECS treated with macrophage supernatants alone (p=0.023, qPCR). The inflammasome
components NLRP3 and CASP1 were also significantly increased by 2.8 fold and 2.1 fold in HUVECS treated with hY3 macrophage
supernatants vs macrophage supernatants alone (p=0.025, p=0.05, respectively). Reflecting oxidant stress, significant increases in
ECAR were observed in the HUVECS treated with hY3 macrophage supernatants compared to macrophage supernatants alone (15±4
mpH/min vs 5±3 mpH/min, p=0.05, N = 3). For bioenergetic health index (BHI), a composite of spare capacity, coupling efficiency,
Proton leak and non mitochondrial respiration, there was a trend to be lower EC + hY3 macrophage supernatants vs EC + macrophage
supernatants (2.0 vs 3.3, p=0.2, respectively) .
Transcriptomes of the two hearts for each isolated endothelial cell fraction were compared. Based on DAVID annotation, data were
organized into clusters of closely related genes. The top GO category was the type I IFN signaling pathway with 5 IFN inducible genes
in the top 10. Regarding targeted genes with greater than two-fold upregulation (CHB vs control), there were genes within the
inflammasome pathway, including IFN inducible NLRC5, which serves to interact with NLRP3, along with well characterized
multiprotein oligomer of the inflammasome such as NLRP3, IRF7, IRF9 & CASP1. Inflammasome precursors including IL18, IL1B, &
IL1A were also upregulated.
Conclusion:
Anti-SSA/Ro-induced cardiac injury may include a previously unappreciated effect on the vasculature mediated by IFN. This vascular
effect is reflected in the upregulation of metabolic and inflammasome genes.
Disclosure: S. Rasmussen, None; R. M. Clancy, None; J. P. Buyon, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/cardiac-endothelial-cell-transcriptome-analyses-

support-a-pathological-role-of-metabolic-and-inflammasome-genes-in-anti-ssaro-associated-congenital-heart-block
Ptpn22 Regulates Synovial Slam Family Receptor Expression during Toll-like

Receptor-Driven Suppression of Inflammatory Arthritis
David Ewart1, Juan Abrahante Lloréns2 and Erik J. Peterson3, 1Rheumatology, University of Minnesota, Minneapolis, MN,
2Informatics Institute (UMII), University of Minnesota, Minneapolis, MN, 3Center for Immunology/Department of Medicine,
University of Minnesota, Minneapolis, MN
SESSION INFORMATION
Background/Purpose:
Genetic factors contribute strongly to Rheumatoid arthritis (RA) risk. Protein tyrosine phosphatase non-receptor 22 [PTPN22] encodes
the hematopoietic-specific Lymphoid Phosphatase [“Lyp”]. A PTPN22 coding variant “LypW” is the most potent non-HLA genetic risk
factor for RA. TLR agonists potently suppress inflammatory arthritis in murine models of RA. Our previous work revealed that Lyp
promotes induction of type 1 interferon [IFN1] and IFN1-dependent genes during TLR3 agonist treatment of serum transfer arthritis
(STA). RA-associated variant LypW shows loss of function behavior in arthritis suppression. The molecular and cellular mechanism(s)
by which Lyp promotes IFN1-dependent inflammatory arthritis amelioration are not known. The goal of this study was to analyze the
PTPn22-dependent transcriptome within arthritic synovium of animals receiving TLR agonist treatment.
Methods:
Wild-type (WT) or Lyp-deficient (Lyp-/-) mice (n = 6 per genotype) were injected with K/BxN serum on days 0 and 2. On days 4 and 6,
half of the mice were given 150 μg poly I:C [pIC], a TLR 3 agonist and arthritis-suppressing agent, by intraperitoneal injection. 12
hours after the second dose of pIC, mice were sacrificed. Total RNA was extracted from ankle synovial aspirates. RNA-Seq mapping,
gene quantification and differential expression were done in Bowtie2, Feature Counts and edgeR.
Results:
15 genes were differentially-regulated by pIC in Lyp-/- arthritic synovium. Among the genes with known immune-modulating function,
Signaling lymphocytic activation molecular family member 7 [Slamf7] and family member 4 [Slamf4] had the highest fold-change
differences between genotypes. pIC treatment robustly upregulated expression of Slamf7 in synovium from arthritic WT mice, but
upregulation was markedly attenuated in Lyp-/- animals (figure 1). In contrast, Slamf4 transcripts were reduced after pIC treatment in
both genotypes; Slamf4 suppression was greater in Lyp-/- mice. Because SLAM family members are important for innate
immunoregulation, we examined TLR-signaled SLAM expression within candidate SLAM-expressing innate immune cells. Preliminary
results from studies of TLR3 or TLR4-treated bone marrow-derived macrophages or dendritic cells, or of splenic macrophages after in
vivo pIC exposure revealed minimal upregulation of Slamf7, regardless of Lyp genotype. NK cells from pIC-treated animals showed
upregulation of surface SLAMf7, and suppression of SLAMf4, but not in a Lyp-dependent manner.
Conclusion:
TLR agonist treatment induced modulation of SLAMf4 and 7 and is differentially regulated by Lyp during serum transfer arthritis.
Preliminary studies do not support the hypothesis that Lyp modulates TLR-stimulated SLAM family receptor expression in key
inflammation-regulating innate immune cell types, including dendritic cells, macrophages, or NK cells.
Disclosure: D. Ewart, None; J. Abrahante Lloréns, None; E. J. Peterson, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/ptpn22-regulates-synovial-slam-family-receptor-

expression-during-toll-like-receptor-driven-suppression-of-inflammatory-arthritis
Activation of Toll-like Receptor 2 in Human Synovium Explants Increase Tissue

Turnover and Secretion of Interleukin-6
Neha Sharma1,2, Ashref Kayed3,4, Cecilie F. Kjelgaard-Petersen2,5, Thorbjørn G. Christiansen6, Morten Karsdal7, Christian S.
Thudium2 and Anne-C. Bay-Jensen8, 1Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark, 2Biomarkers and
Research, Nordic Bioscience, Herlev, Denmark, 3Biomolecular Sciences, University of Copenhagen, Copenhagen, Denmark, 4Research
and Biomarkers, Nordic Bioscience, Herlev, Denmark, 5Bioengineering, Technical University of Denmark, Kgs. Lyngby, Denmark,
6Gentofte University Hospital, Orthopaedicsurgery unit, Gentofte, Denmark, 7Biomarkers and Reseacrh, Nordic Bioscience, Herlev,
Denmark, 8Biomarkers and Reseach, Nordic Bioscience, Herlev, Denmark

SESSION INFORMATION
Background/Purpose:
The innate immune system is important for initiation and development of OA. Increased degradation of the cartilage release fragments
into the synovial fluid, which can then bind to innate immune receptors in the synovium. The aim of this study was to investigate the
effect of Toll like receptor 2 (TLR2) activation by synthetic agonists and a synthetic aggrecan 32 amino acid fragment (32-mer) on the
tissue turnover and IL-6 secretion, in a human synovial membrane explant model.
Methods:
Human synovial membrane biopsies retrieved from OA patients undergoing total knee replacement were lysed and the presence of
TLR2 were investigated by western blotting. Human synovial membrane explants (SME) were prepared from the synovial biopsies:
Excess fat was removed and the biopsies were cut into explants of 30±5 mg. The SMEs were cultured for 14 days without treatment
(WO), OSM [10ng/mL] + TNFα [20ng/mL] (positive control), Pam2CSK4 in three doses (100 ng/mL, 10 ng/mL, or 1 ng/mL), or
Pam3CSK4 in three doses (300 ng/mL, 30 ng/mL, or 3 ng/mL). Furthermore, stimulation with a synthetic aggrecan 32-mer (100000
ng/mL, 10000 ng/ml, 1000 ng/ml, 100 ng/ml and 10 ng/ml, respectively) was evaluated. Release of the neo-epitope biomarkers
acMMP3 and C3M were measured by ELISA and secretion of IL-6 was evaluated by western blotting at day 5 and 10 in the conditioned
media.
Results:
Western blotting confirmed the presence of TLR2 in untreated OA synovial biopsies (Fig. 1a). Activation of the SMEs were assessed by
acMMP3, C3M, and IL-6 release. OSM+TNFα significantly increased the release of IL-6 secretion, acMMP3 (P<0.05), and C3M
(P<0.01) (Fig. 1). The TLR2 agonists, Pam2CSK4 and Pam3CSK3, significantly increased the release of acMMP3 at day 10 compared
to WO (PAM2CSK4: 100 ng/mL P <0.001, 10 ng/mL P=0.016, Pam3CSK4: 30 ng/mL P<0.001) (Fig. 1c). The overall C3M release
was significantly increased by Pam2CSK compared to WO (100 ng/mL P=0.007 and 10 ng/mL: P=0.008) (Fig. 1d). Pam3CSK tended
to increase the overall C3M and significantly increased C3M release at day 10 compared to WO (100 ng/mL: P=0.035, 10 ng/mL:
P=0.008). The western blotting confirmed increased secretion of IL-6 from SMEs stimulated with Pam2CSK4 (Fig. 1b) and
Pam3CSK4 compared to WO. Synthetic aggrecan 32-mer did not show any significant increase of C3M release from the synovium.
Conclusion:
TLR2 is expressed in synovium of OA patients and their activation by synthetic ligands resulted in increased tissue turnover confirmed
by release of activated MMP3, acMMP3, and MMP-mediated degradation of type III collagen, C3M. Additionally, activation of TLR2
lead to an increased secretion of the pro-inflammatory cytokine IL-6. A synthetic peptide of the potential biological ligand of TLR2, the
aggrecan 32-mer failed to generate a significant C3M response compared to WO. We hypothesize that it may be different with the
glycosylated native aggrecan 32-mer.
Disclosure: N. Sharma, None; A. Kayed, None; C. F. Kjelgaard-Petersen, None; T. G. Christiansen, None; M. Karsdal, Nordic
Bioscience Diagnostic, 1,Symic Bio, 1,Nordic Bioscience A/S, 3; C. S. Thudium, Nordic Bioscience Diagnostic, 3; A. C. Bay-Jensen,
Nordic Bioscience A/S, 1,Nordic Bioscience A/S, 3.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/activation-of-toll-like-receptor-2-in-human-

synovium-explants-increase-tissue-turnover-and-secretion-of-interleukin-6
Characterization of Human Tolerogenic Dendritic Cells Generated with Protein

Kinase C Inhibitor and Induction from Patients with Autoimmune Diseases
Hitoshi Hasegawa1, Takuya Matsumoto1, Endy Adnan2, Jun Ishizaki1, Koichiro Suemori1 and Masaki Yasukawa1, 1Department of
Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Ehime, Japan,
2Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Ehime, Japan
SESSION INFORMATION
Background/Purpose:
Tolerogenic dendritic cells (tDCs) are a promising therapeutic tool for specific induction of immunological tolerance. Human tDCs can
be generated ex vivo using various compounds. However, the compound(s) most suitable for clinical application remain undefined. For
clinical application of tDCs, three functional characteristics are required: 1) CCR7-dependent migration toward secondary lymphoid
organs; 2) efficient induction of functional regulatory T cells; and 3) stability upon exposure to proinflammatory stimuli. We found that
DCs (PKCI-tDCs) treated with protein kinase C inhibitor (PKCI) had potent tolerogenic properties. Since aberrant activation of T cells,
especially CD4+ T cells, plays an important role in the initiation and/or perpetuation of rheumatoid arthritis (RA) and primary Sjögren’s
syndrome (pSS), both diseases may be suitable for tolerance-inducing therapy. In this study, we described the characterization of PKCI-
tDCs and examined whether PKCI-tDCs could be generated from patients with RA or pSS.
Methods:
1) Generation of human tDCs: Immature DCs (iDCs) were generated from the monocytes by culturing them in X-VIVO medium with
GM-CSF and IL-4 for 5 days. To induce mature DCs (mDCs), iDCs were incubated with a maturation cocktail for a further 48 h.
Compound-treated tDCs were generated by culturing iDCs with a maturation cocktail in the presence of each compound for 48 h. 2)
Other methods: In vitro T cell proliferation assay; cytokine production; phagocytic ability; induction of regulatory T cells; in vitro T
regulatory activity; stability of DCs under proinflammatory stimuli; and chemotaxis assay.
Results:
PKCI-tDCs had a semi-mature phenotype, showing high production of IL-10, and efficiently induced IL-10-producing T cells and
functional Foxp3+ regulatory T cells, thus eliciting a strong immunosuppressive function. They also showed CCR7 expression and
sufficient capacity for migration toward CCR7 ligands. In addition, PKCI-tDCs were highly stable when exposed to inflammatory
stimuli. PKCI inhibited NF-kB activation of both the canonical and non-canonical pathways of DC maturation, thus suppressing the
expression of costimulatory molecules and IL-12 production. High production of IL-10 in PKCI-tDCs was due to not only an increase
of intracellular cAMP, but also a synergistic effect of increased cAMP and NF-kB inhibition. PKCI-treated DCs from the patients with
RA or pSS had similar phenotypes and suppressive properties to those from healthy donors.
Conclusion:
PKCI-tDCs may be useful for tolerance-inducing therapy, since they satisfy the required functional characteristics for clinical-grade
tDCs. In addition, PKCI-tDCs were generated from patients with RA or pSS not only before but also after treatment with agents such as
methotrexate and prednisolone.
Disclosure: H. Hasegawa, None; T. Matsumoto, None; E. Adnan, None; J. Ishizaki, None; K. Suemori, None; M. Yasukawa, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/characterization-of-human-tolerogenic-dendritic-

cells-generated-with-protein-kinase-c-inhibitor-and-induction-from-patients-with-autoimmune-diseases
Mucosal-Associated Invariant T Cell Deficiency in Systemic Lupus Erythematosus Is

Realted to an Intrinsic Defect in the Ca2+/Calcineurin/NFAT1 Signaling Pathway
Yong-Wook Park1, Young-Nan Cho2, Hye-Mi Jin1, Tae-Jong Kim3 and Seung-Jung Kee4, 1Rheumatology, Chonnam National
University Medical School and Hospital, Gwangju, Korea, Republic of (South), 2Rheumatology, Chonnam National University Hospital
and Medical School, Gwangju, MN, Korea, Republic of (South), 3Chonnam Nat`l University Medical School&Hospital, Chonnam,
Korea, Republic of (South), 4Laboratory Medicine, Chonnam National University Medical School and Hospital, Gwangju, Korea,
Republic of (South)
SESSION INFORMATION
Background/Purpose: Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections
and play an important role in mucosal immunity. However, the role of MAIT cells remains enigmatic in autoimmune diseases. Here, we
examined the level and function of MAIT cells in patients with rheumatic diseases.
Methods: Patients with systemic lupus erythematosus (SLE; n = 54), rheumatoid arthritis (RA; n = 66), Behçet’s disease (n = 9),
ankylosing spondylitis (n = 21), and healthy controls (n = 136) were enrolled in the study. MAIT cell, cytokine and programmed death-1
(PD-1) levels were measured by flow cytometry.
Results: Circulating MAIT cell levels were significantly reduced in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA)
patients. In particular, this MAIT cell deficiency was more prominent in CD8+ and double-negative T cell subsets, and significantly
correlated with disease activity, such as SLE disease activity index (SLEDAI) and 28-joint disease activity score (DAS28). Interestingly,
MAIT cell frequency was significantly correlated with natural killer T (NKT) cell frequency in SLE patients. IFN-gamma in MAIT
cells was impaired in SLE patients, which was due to an intrinsic defect in the Ca2+/calcineurin/NFAT1 signaling pathway. In SLE
patients, MAIT cells were poorly activated by alphagalactosylceramide-stimulated NKT cells, thereby showing the dysfunction between
MAIT cells and NKT cells. Notably, an elevated expression of PD-1 in MAIT cells and NKT cells was associated with SLE. In RA
patients, MAIT cell levels were significantly higher in synovial fluid than in peripheral blood.
Conclusion: Our study primarily demonstrates that MAIT cells are numerically and functionally deficient in SLE. In addition, we
report a novel finding that this MAIT cell deficiency is associated with NKT cell deficiency and elevated PD-1 expression. These
abnormalities possibly contribute to dysregulated mucosal immunity in SLE.
Disclosure: Y. W. Park, None; Y. N. Cho, None; H. M. Jin, None; T. J. Kim, None; S. J. Kee, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/mucosal-associated-invariant-t-cell-deficiency-in-

systemic-lupus-erythematosus-is-realted-to-an-intrinsic-defect-in-the-ca2calcineurinnfat1-signaling-pathway
Invention and Phenotypic Evaluation of Human IgG4-Knock-in Mice

Yoshie Gon, Hajime Yoshifuji, Koji Kitagori, Toshiki Nakajima, Kosaku Murakami, Ran Nakashima, Koichiro Ohmura and Tsuneyo
Mimori, Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
SESSION INFORMATION
Background/Purpose: IgG4-related disease (IgG4-RD) is a disorder characterized by elevated serum IgG4 concentration and
infiltration of IgG4-positive plasma cells into affected organs, however, the role of IgG4 in the pathophysiology of IgG4-RD is not
sufficiently elucidated. Although animal models are required, mice only have IgG1, 2 and 3 subclasses but no IgG4. Therefore, we
invented human IgG4 (hIgG4)-knock-in (KI) mice and evaluated their phenotypes.
Methods: The hIgG4 gene is inserted in the cite of mouse IgG1 (mIgG1) gene, which is promoted by Th2 cells associated with the
pathophysiology of IgG4-RD. In order to preserve the rearrangement system of VDJ region of IgH gene, constant region of hIgG4 gene
was only transfected into ES cells of C57BL/6 mice by gene targeting method. 1) We quantitated levels of mRNA extracted from
spleens of homozygous (Homo) and heterozygous (Hetero) IgG4-KI mice by quantitative PCR method. 2) Serum IgG4 levels in Homo,
Hetero and wild-type (WT) mice were quantitated by ELISA and turbidimetric immunoassay (TIA) used in daily clinics. 3) To enhance
the production of IgG4, we established MRL-lpr/IgG4-KI mice and analyzed them by ELISA and flow cytometry (FCM).
Results: 1) Expression of hIgG4 mRNA, mIgG1 mRNA and hIgG4+mIgG1 mRNA were detected in the spleen of Homo, WT and
Hetero mice, respectively. 2) hIgG4, mIgG1 and hIgG4+mIgG1 proteins were detected in sera of Homo, WT and Hetero mice,
respectively (Fig. 1). Serum hIgG4 level in Homo mice was 7.0 mg/dL by TIA (Table 1). 3) Serum hIgG4 level in MRL-lpr/IgG4-KI
Homo mice was increased to 289 mg/dL. We detected the spleen cells that express IgG4 on surface by FCM.
Conclusion: The transfected IgG4 gene seemed to work physiologically, as we confirmed secretory IgG4 in blood and membranous
IgG4 on spleen cells in the mice. Serum IgG4 level was high in MRL-lpr/IgG4-KI mice. Their histopathology is to be examined.
Table 1. Serum hIgG4 titer by TIA

B6/WT B6/IgG4-KI MRL-lpr MRL-
Homo lpr/IgG4-KI
hIgG4 Not 7.0 Not 289
(mg/dL) detected detected
Disclosure: Y. Gon, None; H. Yoshifuji, None; K. Kitagori, None; T. Nakajima, None; K. Murakami, None; R. Nakashima, None;
K. Ohmura, None; T. Mimori, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/invention-and-phenotypic-evaluation-of-human-

igg4-knock-in-mice
Clinical Significance of Anti-Dense Fine Speckled 70 and Dense Fine Speckled

Pattern in Diagnosis of Systemic Autoimmune Rheumatic Disease
You La Jeon1, Ji Yun Ryu1, Jiyoung Baek1, Woo-In Lee2, Myeong Hee Kim1 and So Young Kang1, 1Department of Laboratory
Medicine, School of Medicine, Kyung Hee University and Kyung Hee University Hospital at Gangdong, Seoul, Korea, Republic of
(South), 2School of Medicine, Kyung Hee University and Kyung Hee University Hospital at Gangdong, Seoul, Korea, Republic of
(South)
SESSION INFORMATION
Background/Purpose: The dense fine speckled (DFS) pattern in IIF-ANA on HEp-2 cell is perhaps the most frequently observed
pattern in most clinical laboratories. The DFS70 or lens epithelium-derived growth factor p75 (LEDGFp75) is the known corresponding
antigen to the DFS pattern. Identification of this antibody can be an evidence to exclude the presence of systemic autoimmune
rheumatic diseases (SARD), however this correlation requires more definite clinical correlation. The aim of our study is to confirm the
presence of anti-DFS70 in specimens showing DFS pattern by western blot (WB) and enzyme immunoassay (EIA). Also the association
between the anti-DFS70 and SARD or certain clinical conditions is discussed.
Methods: A total of 227 serum specimens showing DFS (n=180, only DFS (158) and DFS+other (22)) and homogeneous (H) (n=47,
only H (33) and H+other (14)) patterns in IIF-ANA screening test were included. All specimens were tested twice by IIF-ANA and the
results interpreted by two separate expert specialists of Laboratory Medicine. The cases with discrepant results between the two
interpreters were excluded. The results of first and second test results of IIF-ANA were compared. In-house WB was performed using
deriving cell lysate from cultured HeLa cells. Detection of anti-DFS70 IgG was done using a commercial EIA kit. The clinical
information regarding disease status or the presence of SARD of subjects was obtained from retrospective review of individual medical
records.
Results: Forty four cases (19.4%) showed discrepant reading in their repeated IIF-ANA test results. The majority of those results
included the following: 19 cases (DFS pattern in first test result then interpreted as another in second test result, especially 14 cases as H
pattern), 9 cases (from DFS pattern to negative), and 13 cases (changed with only combined pattern). There were also 17 other cases in
which the results were complex and indeterminable. Among 155 cases with DFS pattern in the second test results of IIF-ANA, 134
cases (86.5%) were positive by WB and 114 cases (73.5%) positive by EIA. WB had covered all cases in which this autoantibody was
detected. The number of cases detected of anti-DFS70 are divided into three groups which are as follows; 114 (73.5%) in WB+/EIA+,
20 in WB+/EIA-, and 21 in WB-/EIA-. There was no case which showed only EIA positivity. More than half of the patients from each
group were referred to the department of dermatology, where many were given their diagnoses of androgenic alopecia. SARD patients
with DFS pattern were 1 (SLE) in WB+/EIA+, 3 (1 SSc, 2 RA) in WB+/EIA-, and 1 (RA) in WB-/EIA-.
Conclusion: The prevalence of SARD (2.2%) was very low in this study of randomly selected 180 DFS and 47 H pattern cases. This
result suggests the utility of anti-DFS70 to exclude SARD when detected. DFS pattern can also provide a clue to exclude SARD based
on the results that anti-DFS70 was detected in 86.5% of cases with DFS pattern given that IIF-ANA tests were conducted twice and
interpreted carefully by two separate specialists. However presence of a confusing pattern or the absence of monospecific anti-DFS70,
additional tests are necessary to rule out the diagnosis of SARD.
Disclosure: Y. L. Jeon, None; J. Y. Ryu, None; J. Baek, None; W. I. Lee, None; M. H. Kim, None; S. Y. Kang, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/clinical-significance-of-anti-dense-fine-speckled-70-

and-dense-fine-speckled-pattern-in-diagnosis-of-systemic-autoimmune-rheumatic-disease
Impact of TNF Antagonist Treatment on the Gut Microbiome In Vivo

Odile Gabay1, Jonathan Vicenty2, Grant Wunderlin3, Linda Tiffany2, Wells Wu4, Vahan Simonyan5 and Kathleen A Clouse6, 1Office
of Biotechnology Products /Center for Drug Evaluation and Research DBRRI, U.S. Food and Drug Administration, Silver Spring, MD,
2Office of Biotechnology Products, Center for Drug Evaluation and Research, DBRRI, U.S. Food and Drug Administration, Silver
Spring, MD, 3Center for Drug Evaluation and Research CDER DBRRI, U.S. Food and Drug Administration, Silver Spring, MD,
4Center for Biologic Evaluation and Research OMPT, U.S. Food and Drug Administration, Silver Spring, MD, 5Center for Biologic
Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 6Office of Biotechnology Products /Center for Drug
Evaluation and Research,DBRRI, U.S. Food and Drug Administration, Silver Spring, MD
SESSION INFORMATION
Background/Purpose: Auto-immune diseases are in constant progression in the US. Biologic therapeutics have been used successfully
to treat these diseases, but have presented some unique regulatory challenges. Although they can be very efficacious, the response to
these therapeutics can initially be quite variable among patients and patients who are initially responsive can develop resistance to them
over time. We propose that the gut microbiome could play a role in the initial variability and impact the response to treatments.
Methods: Germ Free (GF) mice colonies have been successfully developed in a sterile environment in the CBER/CDER Animal
Facility. We used these GF mice to test human monoclonal antibodies and fusion proteins, following a treatment regimen consistent
with patient regimens, to evaluate the role of the microbiome when GF mice are compared to conventional mice controls treated in
parallel. Our pilot study is analyzed from two different approaches: assessment of taxonomy changes and an immunologic variation in
the mouse gut.
Results: Our results show a break in the symbiosis of the commensal bacteria communities after TNF antagonist treatment. These mice
present a shift in the ratio Firmicutes/Bacteroidetes with a statistically significant increase in this latter family over uncultured bacteria.
Differences are reported between males and females and between young (3 month-old) and old (9 month-old) mice. When the mucosal
immune system is explored, comparing conventional and GF mice, it appears that the Innate Lymphoid Cells (ILCs) colonizing the
lamina propria of the gut have two very different profiles and therefore, are likely to respond differently to cross-talk with commensal
bacteria in the gut. A preliminary mechanistic link to the plasticity between ILC1 and LC3 is suggested in older mice.
Conclusion: Our results show that the Microbiota indeed plays a regulating role in TNF antagonist treatment, involving a dysbiosis and
a regulation through ILCs. This observational study should be followed by in vivo functionality studies.
Disclosure: O. Gabay, None; J. Vicenty, None; G. Wunderlin, None; L. Tiffany, None; W. Wu, None; V. Simonyan, None; K. A.
Clouse, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/impact-of-tnf-antagonist-treatment-on-the-gut-
microbiome-in-vivo
Significantly Elevated Serum Protein-Adduction with 4-Hydroxy-2-Nonenal but Not

Malondialdehyde in Sjogren’s Syndrome
Biji T Kurien1,2,3, Sona Nuguri4, Bre'ana Byrd5, Joey Maher6, Rohit Thomas4, Huyen Tran7 and R. Hal Scofield8, 1Arthritis and
Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, 2U.S. Department of Veterans Affairs Medical
Center, Oklahoma City, OK, 3College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 4Oklahoma
School of Science and Mathematics, Oklahoma City, OK, 5University of Central Oklahoma, Edmond, OK, 6University of Oklahoma,
Norman, OK, 7University of Oklahoma Health Sciences Center, Edmond, OK, 8Arthritis & Clinical Immunology Program, Oklahoma
Medical Research Foundation; Department of Medicine, University of Oklahoma Health Sciences Center; US Department of Veterans
Affairs Medical Center, Oklahoma City, OK
SESSION INFORMATION
Background/Purpose:
Sjögren’s syndrome (SS) is a chronic inflammatory, autoimmune disorder characterized by diminished lacrimal and salivary gland
secretion resulting in keratoconjunctivitis sicca and xerostomia. Autoantibodies, directed against 60 kD Ro protein is found in up to
90% of patients with SS. Free radical mediated oxidative damage has not been well characterized previously in SS. Therefore, we
studied oxidative damage (conjugate diene formation) and modification of serum proteins by the lipid peroxidation by-product 4-
hydroxy-2-nonenal (HNE) or malondialdehyde (MDA) in SS and age-and sex matched controls.
Methods:
Sixty nine primary SS subjects, 25 age and sex matched subjects that do not meet criteria (incomplete SS), and 18 normal controls were
studied. We studied indices of oxidative damage, namely conjugate diene formation, and HNE or MDA-protein adducts in the sera of
SS, incomplete SS and normal controls. Sera from SS subjects or normal controls were coated on ELISA plates as antigen. HNE or
MDA adducts in serum proteins was determined with rabbit anti-HNE or anti-MDA antibodies purchased commercially. Sera from SS
or normal controls were electrophoresed, transferred to nitrocellulose by electroblotting and subjected to immunoblotting with rabbit
anti-HNE antibody. For determination of conjugate diene, 25 µl of SS or incomplete SS sera were extracted with chloroform:methanol
(2:1) and the samples were centrifuged. Two ml of the clear supernatant was evaporated to dryness at 45˚C and reconstituted in one ml
methanol. The spectra ranging from 200 to 360 nm was read using a spectrophotometer.
Results:
We found significantly increased oxidative damage in the sera of primary SS subjects compared to normal controls by ELISA and
immunoblotting. Serum proteins from SS subjects were found to contain HNE adducts. There was significantly more HNE-modified
proteins in SS sera (n=10) compared to controls (n=10; age and sex matched) by ELISA (0.074 ± 0.017 versus 0.046 ± 0.007;
p=0.00015; average OD±SD). However, there was no significant difference in MDA-modified proteins between SS and controls by
ELISA. When SS sera (n=34) were analyzed by immunoblotting, we found HNE adducts in several serum proteins, and significantly in
a 18 kD protein. Control sera did not show significant HNE-modification (n=8). Our preliminary results for conjugate diene formation
show that there is no significant difference between conjugate diene levels in the Sjogrens’s syndrome patients (n=25) and incomplete
SS subjects (n=25). We are pursuing HNE-modification in the sera of incomplete SS subjects and also identifying the protein bands in
SS subjects with HNE adducts by matrix assisted time of flight mass spectrometry.
Conclusion:
Significantly elevated HNE- but not MDA-protein adducts occur in the sera of SS subjects compared to normal controls, showing that
oxidative damage occurs in SS.
Disclosure: B. T. Kurien, None; S. Nuguri, None; B. Byrd, None; J. Maher, None; R. Thomas, None; H. Tran, None; R. H.
Scofield, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/significantly-elevated-serum-protein-adduction-

with-4-hydroxy-2-nonenal-but-not-malondialdehyde-in-sjogrens-syndrome
Phenotypic Characterization of Peripheral Basophil Perturbations in the

Benjamin Chaigne1, Veronique Le Guern2, Tali-Anne Szwebel1, Romain Paule2, Claire Le Jeunne3, Nathalie Costedoat-Chalumeau4
and Luc Mouthon5, 1Service de Médecine Interne, Centre de Référence Maladies Systémiques Autoimmunes Rares d’Ile de France,
hôpital Cochin, DHU Authors, Assistance Publique-Hôpitaux de Paris, Paris, France, 2Department of Internal Medicine, Department of
Internal Medicine, Cochin University Hospital, Paris, France, 3Service de Médecine Interne, Hôpital Cochin, Centre de référence
national pour les maladies systémiques autoimmunes rares d’Ile de France, DHU Authors, Assistance Publique-Hôpitaux de Paris (AP-
HP), Paris, France, Paris, France, 4Service de médecine interne Pôle médecine, Hôpital Cochin, Centre de référence maladies auto-
immunes et systémiques rares de l’île de France, Paris, France, 5Service de Médecine Interne, Hôpital Cochin, Centre de référence
national pour les maladies systémiques autoimmunes rares d’Ile de France, DHU Authors, Assistance Publique-Hôpitaux de Paris (AP-
HP), Paris, France ;Université Paris Descartes Sorbonne Paris, Paris, France
SESSION INFORMATION
Background/Purpose:
The antiphospholipid syndrome (APS) is an autoimmune condition characterized by thrombosis, pregnancy complications and the
presence of antiphospholipid antibodies. Basophils, which have long been associated with allergy and parasitic infections, are known to
be activated and able to enhance the production of autoantibodies in autoimmune diseases, particularly in systemic lupus erythematosus
(SLE). Herein we investigated the role of basophils in APS.
Methods:
Peripheral basophils of patients with primary APS, SLE-associated APS (SLE-APS), and healthy controls (HC) were analyzed using
flow cytometry.
Results: Forty-three consecutive patients with APS, including 10 patients with SLE-APS, and 20 HC were recruited. None of the
patients was treated with corticosteroids or immunosuppressants. Thirty-five (81.4%) patients had lupus anticoagulant, 33 (76.7%) had
anti-cardiolipin antibodies, and 24 (55.8%) had anti-ß2 glycoprotein I. Twenty (46.5%) patients had obstetric APS, 20 (46.5%) patients
experienced arterial thrombosis and 19 (44.2%) patients experienced venous thrombosis. Six patients (14%) had a catastrophic APS
(CAPS). Basophil activation markers revealed a decreased proportion of CD193+ basophils in patients with APS vs HC (63.0% [27.3 –
85.0] vs 90.4% [74.1 – 97.1]; p < 0.05) and an increased mean fluorescence intensity (MFI) of CD69 within basophils in patients with
APS vs HC (839 [436 – 1434] vs 318 [103 – 755]; p < 0.05). Basophils functional markers revealed a decreased proportion of CD62L+
basophils in APS vs HC (99.0% [95.6 – 100] vs 100% [99.6 – 100]; p < 0.05), and an increased proportion of HLA-DR+ basophils in
APS vs HC (32.3% [16.8 – 77.2] vs 10.0% [3.4 – 21.7]; p < 0.05). There was no difference between patients with APS and patients with
SLE-APS, or patients with CAPS. When compared to patients without obstetric APS, patients with obstetric APS (46.5%) had a
decreased proportion of CD196+ basophils (25.5% [11.3 – 32.5] vs 31.9% [25.8 – 66.3]; p < 0.05), an increased proportion of
CD63+basophils (34.8% [0.25 – 53.3] vs 7.4% [0 – 37.9]; p < 0.05), and an increased proportion of HLA-DR+ basophils (49.0% [23.4 –
79.6] vs 20.8% [8.7 – 70.8]; p < 0.05). Lastly, the proportion of CD154+ basophils was higher in patients who experienced miscarriages
than those who did not (47.6% [38.2 – 56.1] vs 19.7%[5.1 - 35.8]; p < 0.01) and MFI of basophil CD62L was higher in patients who
experienced fetal death in utero than those who did not (11823 [9862 – 15546] vs 7978 [4628 - 10160]; p < 0.05).
Conclusion:
Main phenotypic characteristics of basophils in APS are an increased expression of CD69 marker, a decreased expression of CD193
marker, and an increased expression of HLA-DR marker suggesting a role for basophils. Patients with obstetric APS differed from other
APS patients by a skewed distribution of CD196+, CD63+ and HLA-DR+ basophils.
Disclosure: B. Chaigne, None; V. Le Guern, None; T. A. Szwebel, None; R. Paule, None; C. Le Jeunne, None; N. Costedoat-
Chalumeau, None; L. Mouthon, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/phenotypic-characterization-of-peripheral-basophil-

perturbations-in-the-antiphospholipid-syndrome
Increased Susceptibility of SLE-Prone Mice to Pulmonary Haemophilus Influenzae

Infection Was Attributed to Dysfunctions of Innate Immune Responses
Wenchao Li and Lingyun Sun, Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing
University Medical School, Nanjing, China
SESSION INFORMATION
Background/Purpose: Aside from the disease itself, infections represent the major cause of morbidity and mortality in systemic lupus
erythematosus (SLE) patients. Although the daily usage of immunosuppressive drugs is considered to be responsible for the increased
rates of infection, inherent defects in immune system should not be overlooked.
Methods: To better understand the proclivity of SLE patients to suffer infections, we infected lupus-prone mice B6/lpr with 1X10^8
CFU of Haemophilus influenzae (Hi) intranasally and monitored bacterial clearance, body weight change and lung pathology after
infection. Apoptosis of lung cells was analyzed by TUNEL assay. Immune cells recruited by infection were determined by flow
cytometry. Cytokines in the bronchoalveolar lavage fluid (BALF) were measured by ELISA.
Results: Although both wild-type (WT) and B6/lpr mice survived after pulmonary Hi infection, a delay of bacterial clearance and
inflammatory resolution was observed in B6/lpr mice(Fig1A-C). Besides, tissue damage was more severe in B6/lpr mice, as more
apoptotic cells appeared in the lung on D2 after infection (Fig1D). When looked at the cytokine production, we found that cells from
lupus-prone lungs produced much more proinflammatory cytokines IL-6, IL-17 and chemokines MCP-1 and KC. However, TNF-¦Á is
comparable between the two groups (Fig2). NK, ¦æÄ T and CD4 T cells are very important in control of bacterial infection. Here, we
showed that compared with WT controls, in response to infection fewer NK cells were detected in B6/lpr lungs. The numbers of ¦æÄ T
and CD4 T cells in the lung were not different, but their ability to secrete IFN-¦Ã was significant lower in B6/lpr mice(Fig3).
Conclusion: The increased susceptibility of SLE-prone mice to pulmonary Haemophilus influenzae infection may due to the elevated
inflammatory responses and the deficiency of immune cells.
Disclosure: W. Li, None; L. Sun, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/increased-susceptibility-of-sle-prone-mice-to-

pulmonary-haemophilus-influenzae-infection-was-attributed-to-dysfunctions-of-innate-immune-responses
Mutated Peptidylarginine Deiminase from Porphyromonas Gingivalis Is a Target in

Rheumatoid Arthritis and Citrullinates Major RA-Autoantigens
Madeleine Jenning1, Bianka Marklein1, Jimmy Ytterberg2, Gerd R. Burmester1 and Karl Skriner1, 1Department of Rheumatology and
Clinical Immunology, Charité - University Medicine Berlin, Free University and Humboldt University Berlin, Berlin, Germany, 2Dept.
of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
SESSION INFORMATION
Background/Purpose: Previous reports showed that peptidylarginine deiminase (PPAD) form Porphyromonas gingivalis (P.g.) is not
able to citrullinate proteins internally. Mutated PPAD (mPPAD) from P.g. involved in periodontal disease (PD) cloned out of P.g.strain
was characterized and analyzed for its reactivity in sera from patients with systemic autoimmune diseases.
Methods: We cloned an enzymatically active recombinant mPPAD from P.g. Mutations and citrullination sites were analyzed by DNA
sequencing and protein mass spectrometry (MS). Autocitrullination activity, its enzymatic-activity and human autoantigen protein
citrullination was investigated by 2D-Elektrophoresis, MS, immunoblot analysis and ELISA. Furthermore we tested anti-mPPAD/cit-
mPPAD with human sera (n=123) from early rheumatoid arthritis (RA) before and after onset of RA (n=30), established RA (n=32),
systemic lupus erythematosus (n=15), osteoarthritis (n=16) and healthy blood donors (n=30) in ELISA assays. In RA mouse model
collagen antibody-induced arthritis (CAIA), mPPAD-containing vesicles from P.g. were injected by intraperitoneal injection (IP).
Results: Recombinant mPPAD lacks 43 amino acids at the N-terminus and exhibits so far two new amino acid mutations (aminoacid
position 73 (F>L) and 447 (E>V). We were able to demonstrate, mPPAD is enzymatically active over a huge pH-range (3-10) and
autocitrullinates at amino acid position 63 the arginine to citrulline. Moreover mPPAD citrullinates major autoantigens in RA
(Fibrinogen, Vimentin and hnRNP-A2/B1) which are detectable by RA patient sera and specific anti-citrulline monoclonal antibodies.
MPPAD citrullinates HeLa-protein extracts and these specific citrullinated proteins are recognized by RA patient sera. Anti-citrullinated
mPPAD antibodies were detected in 41% (n=32) of patients with RA but not in SLE (n=15), OA (n=16) and control sera (n=16). In an
RA follow-up study (n=30), we detected nearly similar antibody-sensitivities for citrullinated mPPAD before and after onset of RA
(13/20%). Only a minority (7%) of RA patients show higher mPPAD antibody levels after RA diagnosis. In the CAIA RA mouse model
mPPAD containing P.g. vesicles when injected IP showed a TLR2-dependent protective anti-inflammatory effect like P.g. LPS and
Lipomannan.
Conclusion: P.g. infection and RA disease diagnosis occurs at different time points and P.g. infection induces a TLR2-dependent
protective anti-inflammatory effect.We show the first time that mPPAD can citrullinate major human autoantigens internally and their
immunologically and diagnostic relevance in RA.
Disclosure: M. Jenning, None; B. Marklein, None; J. Ytterberg, None; G. R. Burmester, None; K. Skriner, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/mutated-peptidylarginine-deiminase-from-

porphyromonas-gingivalis-is-a-target-in-rheumatoid-arthritis-and-citrullinates-major-ra-autoantigens
Aberrant Cell Signaling in Peripheral Blood Mononuclear Cells upon Interferon

Alpha Stimulation in Patients with Primary Sjögren’s Syndrome Associates with
Type I Interferon Signature
Richard Davies1, Daniel Hammenfors1,2, Brith Bergum1, Petra Vogelsang1, Sonia Gavasso3, Johan G. Brun2,4, Roland Jonsson5,6 and
Silke Appel1, 1Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway,
2Department of Rheumatology, Haukeland University Hospital, Bergen, Norway, 3Department of Neurology, Haukeland University
Hospital, Bergen, Norway, 4Department of Clinical Science, University of Bergen, Bergen, Norway, 5Broegelmann Research laboratory,
Department of Clinical Science, University of Bergen, Bergen, Norway, 6Department of Rheumatology, Haukeland University Hospital,
Bergen, Bergen, Norway
SESSION INFORMATION
Background/Purpose: Primary Sjögren’s syndrome (pSS) is a complex heterogeneous systemic autoimmune disease. Biomarkers for
patient stratification are scarce. Several single nucleotide polymorphisms within type I interferon (IFN) signaling pathways are
associated with pSS. To define novel biomarkers for pSS patient stratification, we analyzed the temporal profile of MAPK/ERK and
JAK/STAT signalling networks in PBMCs upon stimulation with IFNα by flow cytometry.
Methods: PBMCs from pSS patients and healthy matched donors were stimulated for 15, 30, 60, 120, 180, and 240 min with IFNα at
100 ng / ml. Nine different phospho epitopes were measured, STAT4(pY693), ERK1/2(pT202/pY204), NF-κB p65(pS529),
STAT1(pS727), STAT1(pY701), p38 MAPK(pT180/pY182), STAT3(pS727), STAT3(pY705) and STAT5(pY694). Cell surface markers
were CD3, CD20 and CD56.
Results: Cells from pSS patients display significant differences in basal and IFNα induced phosphorylation levels of numerous
signaling proteins compared to cells from healthy donors. PCA using IFNα induced phosphorylation levels after 15 minutes showed
clustering of pSS patients and pSS patient subgroups. PCA visualization showed a positive shift for pSS samples away from healthy
donor samples with positive movement influenced by changes in phosphorylation of STAT1 Y701 in T, NK and B cells in PC1, and PC2
positive movement influenced by STAT1 Y701 in NK and B cells, and negative movement by STAT3 S727 in T cells. Medicated and
SSA- patients grouped closer to healthy donors than non-medicated or SSA+ patients.
Conclusion: pSS patients show increased responses to IFNα through STAT1. Increased responses to IFNα may in part drive an up-
regulation of interferon induced genes.
Disclosure: R. Davies, None; D. Hammenfors, None; B. Bergum, None; P. Vogelsang, None; S. Gavasso, None; J. G. Brun, None;
R. Jonsson, None; S. Appel, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/aberrant-cell-signaling-in-peripheral-blood-

mononuclear-cells-upon-interferon-alpha-stimulation-in-patients-with-primary-sjogrens-syndrome-associates-with-type-i-interferon-
signature
High Cholesterol Levels By ApoE Defenciency Reduce Bone Destruction in Murine

Antigen-Induced Arthritis Via Inhibition of Osteoclastogenesis
Giuliana Ascone1, Irene Di Ceglie1, Arjen B. Blom1, Birgitte Walgreen2, Annet W. Sloetjes1, Peter M. van der Kraan1, Ernst
Lindhout3, Mike Martens3 and Peter L. van Lent4, 1Experimental Rheumatology, Radboud university medical center, Nijmegen,
Netherlands, 2Experimental, Radboud university medical center, Nijmegen, Netherlands, 3Future Diagnostics Solutions (FDs), Wijchen,
Netherlands, 4Experimental Rheumatology (272), Radboud university medical center, Nijmegen, Netherlands
SESSION INFORMATION
Background/Purpose: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by immune complex- deposition in
the synovium, leading to increased bone destruction. In RA, joint destruction has been associated with high cholesterol levels, largely
transported in low density lipoprotein (LDL) particles and enhanced LDL oxidation (oxLDL). Apolipoprotein E (Apo E) is an important
regulator of LDL transportation and its absence strongly elevates LDL levels in the serum, which may lead to increased oxLDL levels
during inflammation. In this study, we investigated the effects of high LDL levels on bone destruction during antigen-induced arthritis
(AIA), which is largely immune complex driven and how increased LDL/oxLDL levels affect osteoclast formation.
Methods: AIA was induced by injection of methylated BSA (mBSA) into the right knee joint of Apo E-/- and wild type (WT) control
mice previously immunized with mBSA and complete Freund’s adjuvant (CFA). WT and ApoE -/- Hoxb8 myeloid precursor cells were
differentiated into osteoclasts using 20 ng/mL RANKL and 30 ng/mL M-CSF, then stimulated for 24h with 10 µg/mL LDL/oxLDL. Oil
Red O staining was performed to assess lipid uptake by osteoclasts. mRNA levels of NFATc1, DC-STAMP, TRAP, CTR and Cat K were
measured by qPCR, whereas TRAP activity in culture supernatants was detected using a spectrophotometric assay. Bone erosion was
quantified by histological analysis using an arbitrary scale from 0 to 3 and TRAP+ cells were determined using immunohistochemistry.
Results: Apo E-/- mice showed significantly higher LDL serum levels than WT controls. Histology showed that at day 21 after AIA
induction, bone destruction was significantly decreased in the Apo E-/- mice, as indicated by the reduction of erosion pits (25%
reduction from 1.5±0.2 to 1.1 ±0.1). ). In line with that, ApoE-/- mice showed a lower number of osteoclasts within the knee joints (36%
lower from 20±4 osteoclasts/section in WT mice to 12±5 in ApoE-/- mice), as determined by image analysis of TRAP staining. To study
the role of ApoE and high LDL levels on osteoclastogenesis in more detail, we differentiated WT and ApoE-/- myeloid precursor cells
(Hoxb8) into osteoclasts and found similar mRNA levels of osteoclast markers. Whereas the number of osteoclasts was comparable
between WT and ApoE-/- osteoclasts, we observed significantly decreased mRNA expression of TRAP (2.6 fold decrease) in ApoE-/-
cells as compared to WT cells. In line with this, TRAP activity was reduced by 49%, suggesting a decreased osteoclast activity in
ApoE-/- cells. Stimulation of osteoclasts by oxLDL strongly impaired cell fusion keeping them in a mononuclear state. mRNA levels of
DC-STAMP were significantly down-regulated in both WT and ApoE-/- osteoclasts (1.4 and 2.3 fold decrease, respectively) as well as
TRAP activity (49% and 58% reduction in WT and ApoE-/- osteoclasts, respectively), indicating a major role of oxLDL in the inhibition
of osteoclastogenesis.
Conclusion: High LDL/oxLDL levels by apoE deficiency affect bone destruction by reducing the number of osteoclasts within the
synovium during AIA probably by interfering osteoclastogenesis.
Disclosure: G. Ascone, None; I. Di Ceglie, None; A. B. Blom, None; B. Walgreen, None; A. W. Sloetjes, None; P. M. van der
Kraan, None; E. Lindhout, None; M. Martens, None; P. L. van Lent, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/high-cholesterol-levels-by-apoe-defenciency-

reduce-bone-destruction-in-murine-antigen-induced-arthritis-via-inhibition-of-osteoclastogenesis
Higher Frequencies of Lymphocytes Expressing the Natural Killer Group 2D

Receptor and Cytotoxic Potential of NK Cells in Patients with Behcet Disease
Martina Bonacini1, Stefania Croci1, Alessandra Soriano2,3, Eleonora Calò1, Alessandro Zerbini1, Luca Cimino4, Francesco
Muratore2,5, Luigi Fontana6, Maria Parmeggiani1 and Carlo Salvarani2,5, 1Unit of Clinical Immunology, Allergy and Advanced
Biotechnologies, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy, Reggio Emilia, Italy, 2Unit of Rheumatology,
Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy, Reggio Emilia, Italy, 3Campus Bio-Medico, University of Rome, Italy,
Roma, Italy, 4Unit of Ocular Immunology, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy, Reggio Emilia, Italy,
5University of Modena and Reggio Emilia, Italy, Modena, Italy, 6Unit of Ophthalmology, Arcispedale Santa Maria Nuova-IRCCS,
Reggio Emilia, Italy, Reggio Emilia, Italy
SESSION INFORMATION
Background/Purpose: Behçhet disease (BD) is a rare, systemic, inflammatory disorder with multiorgan damage and various clinical
manifestations such as oral ulcers, genital ulcers and uveitis. Pathogenesis is still unknown but it is considered a MHC-I-opathy1.
Despite HLA-B51 and some gene polymorphisms have been associated with BD2, the diagnosis is based on clinical parameters and
currently laboratory tests are only of a little help in the diagnosis of BD. The aims of this study were: 1) to increase the knowledge about
BD pathogenesis; 2) to identify laboratory tests which can support BD diagnosis.
Methods: Peripheral blood mononuclear cells (PBMCs) were collected from 40 BD patients (according to 1990 ISGB criteria) and 15
healthy subjects, aged and sex matched, used as controls. The frequency of Natural Killer (NK), Natural Killer T cells (NKT) and T
cells expressing the Natural Killer Group 2D activating receptor (NKG2D) was assessed by flow cytometry using anti-CD56, anti-CD3
and anti-NKG2D antibodies. NK, NKT and T cells were defined as CD56+CD3neg, CD56+CD3+and CD56negCD3+ cells respectively.
Cytotoxic potential of NK cells was evaluated by flow cytometry as the percentage of cells expressing on their surface the degranulation
marker CD107a, after incubation with K562 cells, optimal target for NK cell activation3. Statistical analyses were performed by Mann-
Whitney and Spearman test. P-values less than 0.05 were considered statistically significant.
Results: A significant increase in the percentages of NKG2D+ lymphocytes in the NK, NKT and T lymphocyte gates was detected in
BD patients respect to healthy subjects (P < 0.01). ROC curve analysis showed that the evaluation of NKG2D+ NKT cell percentage
better allowed to discriminate between BD patients and healthy subjects (AUC = 0.7385; P = 0.0071). In particular, a frequency higher
than 75% could identify BD patients with a 93.3% specificity and 38.5% sensitivity. After incubation of PBMCs with K562 cells, a
significant higher frequency of NK cells expressing CD107a was detected in BD patients respect to healthy subjects (13.4% versus
9.5%, P = 0.0124). In BD patients we also observed a correlation between frequencies of NK cells positive for NKG2D and CD107a (r
= 0.3573; P = 0.0255). Instead the median percentages of NKT and T cells expressing CD107a was low: 0.88% and 0.51% and similar
between groups.
Conclusion: We found that expression of NKG2D by NK, NKT and T lymphocytes might be involved in the pathogenesis of BD in a
subset of patients. BD patients were also characterized by a higher cytotoxic potential of NK cells than healthy subjects. We can
speculate that NK and NKT cells of BD patients are more prone to respond to stress signals when exposed on target cells leading to
cyclic auto-inflammation. Monitoring both the frequencies of NKT cells positive for NKG2D and of NK cells positive for CD107a after
activation with K562 cells could help to identify BD patients.
References:
1. McGonagle D. et al. Nat. Rev. Rheumatol. 2015, 11:731–740
2. Ombrello MJ. Et al. Proc Natl Acad Sci U S A. 2014, 111:8867-72
3. Alter G. et al. J Immunol Methods. 2004, 294:15-22
Disclosure: M. Bonacini, None; S. Croci, None; A. Soriano, None; E. Calò, None; A. Zerbini, None; L. Cimino, None; F.
Muratore, None; L. Fontana, None; M. Parmeggiani, None; C. Salvarani, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/higher-frequencies-of-lymphocytes-expressing-the-

natural-killer-group-2d-receptor-and-cytotoxic-potential-of-nk-cells-in-patients-with-behcet-disease
TGF-β1 Induces AXL in Murine and Human Synovium and Protects Ankle Joints,
but Not Knee Joints, during Murine Inflammatory Arthritis
Claire E.J. Waterborg, Mathijs G.A. Broeren, Esmeralda N. Blaney Davidson, Marije I. Koenders, Peter L. van Lent, Peter M. van der
Kraan and Fons A.J. van de Loo, Experimental Rheumatology, Radboud university medical center, Nijmegen, Netherlands
SESSION INFORMATION
Background/Purpose: Rheumatoid arthritis (RA) manifests in a symmetrical fashion in anatomically distinct synovial joints. The
innate immune system, which plays a crucial role in the pathogenesis of RA, is regulated by anti-inflammatory feedback mechanisms
such as the tyrosine kinase receptor family TYRO3, AXL and MER. Of importance, AXL is mainly expressed on sentinel cells. We
investigated the synovial expression of AXL and its putative anti-inflammatory role in a macrophage-dependent model of arthritis.
Methods: Tissue sections of ankle and knee joints of naïve mice were studied for protein expression of AXL. KRN serum transfer
arthritis was induced in Axl-/- and wild-type (WT) mice. Ankle and knee joints were assessed macroscopically and histologically. Naïve
WT mice were injected intra-articularly in the knee joint with adenoviruses overexpressing active TGF-β1 or Luciferase. Protein
expression of AXL on tissue sections and/or gene expression in synovial biopsies from naïve, arthritic and adenovirus-treated ankle
and/or knee joints was examined. Human RA synovium was examined for gene expression. Human monocyte-derived macrophages
were treated with recombinant TGF-β1.
Results: When examining naïve murine joints, synovial cells of the ankle joints were AXL positive, but knee joints of the same mice
were not, indicating a profound difference between these two weight-bearing joints. To examine whether AXL played a protective role
during arthritis, we induced arthritis in Axl-/- and WT mice. The ankle joints of Axl-/- mice showed an increased macroscopic disease
score during arthritis development (p<0.001 at day 7). In agreement with this, histology of ankle joints showed significantly increased
arthritis pathology in Axl-/- mice. No effect of Axl gene deletion was observed on gonarthritis pathology and the synovial expression of
inflammatory genes. To unravel the cause for the noteworthy difference in AXL expression between knee and ankle, we investigated the
role of TGF-β, a factor known to induce AXL. As hypothesized, Tgfb1 expression was significantly higher in synovium of ankle
compared to synovium of knee joints in naïve mice (p<0.01), which correlated with Axl expression (Pearson r=0.8860, p=0.0012). In
addition, adenoviral overexpression of TGFB1 induced AXL expression in synovium of knee joints (p<0.05), a tissue devoid of AXL
during homeostasis. The TGF-β1-induced AXL expression appeared to be conserved in humans. We observed a correlation between
TGFB1 and AXL expression in human RA synovium (Pearson r=0.7233, p=0.0035) and TGF-β1 stimulation enhanced the expression of
AXL in human macrophages (p<0.01).
Conclusion: Our study shows remarkable differences in synovial AXL expression between ankle and knee joints and this is in
accordance with the observation that AXL dampens arthritis in ankle but not in knee joints. We provide evidence that these local
differences in AXL are due to TGF-β1. It is tempting to speculate that the differences in AXL expression and its innate immune
protective effector role could explain the lower arthritis incidence in ankle joints compared to other weight-baring joints in humans
(reviewed in DiStefano and Pinney. Semin Arthro. 2010).
Disclosure: C. E. J. Waterborg, None; M. G. A. Broeren, None; E. N. Blaney Davidson, None; M. I. Koenders, None; P. L. van
Lent, None; P. M. van der Kraan, Contract research UCB, 2; F. A. J. van de Loo, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/tgf-%ce%b21-induces-axl-in-murine-and-human-

synovium-and-protects-ankle-joints-but-not-knee-joints-during-murine-inflammatory-arthritis
The Lectin Pathway of the Complement System Is Activated in Patients with

Systemic Lupus Erythematosus
Anne Troldborg1,2, Steffen Thiel3, Marten Trendelenburg4, Justa Friebus-Kardash5, Josephine Nehring5, Rudi Steffensen6, Søren
Werner Karlskov Hansen7, Magdalena Janina Laska1, Bent Deleuran8, Jens Christian Jensenius1, Anne Voss9 and Kristian Stengaard-
Pedersen10, 1Biomedicine, Aarhus University, Aarhus, Denmark, 2clinical medicine, Aarhus University, Aarhus, Denmark, 3Institute of
Biomedicine, Aarhus University, Aarhus, DK, Aarhus, Denmark, 4Department of Biomedicine, Division of Internal Medicine, Basel,
Switzerland, 5University Hospital Basel, Division of Internal Medicine, Basel, Switzerland, 6Department of Clinical Immunology,
Aalborg University Hospital, Aalborg, Denmark, 7Department of Cancer and Inflammation Research, University of Souther Denmark,
Odense, Denmark, 8Department of Biomedicine, Aarhus University, Aarhus, Denmark, 9Rheumatology, Odense University Hospital,
Odense, Denmark, 10Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark
SESSION INFORMATION
Background/Purpose:
The pathogenesis of Systemic Lupus Erythematosus (SLE) involves complement activation. It is well established that activation of
complement through the classical pathway (CP) and deficiencies of this pathway are associated with SLE. Our knowledge about the
Lectin Pathway (LP) of complement activation in relation to SLE is very limited. Since the LP is also activated through pattern
recognition of, i.e., intracellular components and apoptotic cells, we hypothesize that this pathway is also activated in SLE and could
have similar implications as the CP in the development of SLE.
Methods:
We examined the 11 known LP proteins in a large well-defined SLE cohort of 372 SLE patients and 170 controls. We estimated LP
protein concentrations using in house developed time resolved immuno-flourometric assays (TRIFMA). We assessed if changes in
concentrations were associated with complement activation and disease activity based on C3 measurements. To follow the protein
concentrations over time in relation to disease activity, a cohort of 52 SLE patients followed for five years with repeated blood samples
were additionally included.
Results:
Concentrations of the LP proteins were altered in a specific pattern in this cross sectional SLE cohort compared with the controls. The
differences in LP proteins observed between patients and controls were associated with complement activation and disease activity
based on C3 measurements and SLEDAI. M-ficolin, CL-L1, CL-K1, MASP-3 and MAp19 showed a significant negative correlation
with disease activity. When followed over time the concentrations of several LP proteins correlated with SLEDAI and particularly the
serine protease, MASP-2, increased with SLE disease activity.
Conclusion:
In this large SLE cohort, specific changes in LP proteins were associated with complement activation and disease activity, indicating
that the LP is activated in patients with SLE. These novel findings substantiate the involvement of the LP of complement activation in
the complex pathogenesis of SLE.
Disclosure: A. Troldborg, None; S. Thiel, None; M. Trendelenburg, None; J. Friebus-Kardash, None; J. Nehring, None; R.
Steffensen, None; S. W. Karlskov Hansen, None; M. J. Laska, None; B. Deleuran, Otezla, 2; J. C. Jensenius, None; A. Voss, None;
K. Stengaard-Pedersen, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-lectin-pathway-of-the-complement-system-is-

activated-in-patients-with-systemic-lupus-erythematosus
Initial Combination Therapy Versus Step-up Therapy Is More Effective and Less
Costly As a Treat to Target Strategy for RA: A Markov Model Based upon the Dutch
Rheumatoid Arthritis Monitoring Registry Cohorts
Celine J. van de Laar1, Laura M.M. Steunebrink2, Martijn A.H. Oude Voshaar3 and Harald E. Vonkeman4, 1Transparency in
Healthcare B.V., Hengelo, Netherlands, 2Medisch Spectrum Twente - Arthritis Center Twente, Enschede, Netherlands, 3University of
Twente, Department of Psychology, Health and Technology, Enschede, Netherlands, 4koningsplein, Medisch Spectrum Twente -
Arthritis Center Twente, Enschede, Netherlands
SESSION INFORMATION
Session Title: Measures and Measurement of Healthcare Quality Poster I
Background/Purpose:
Adjusting medication of patients with rheumatoid arthritis (RA) until predefined disease activity targets are met, i.e. Treat to Target
(T2T), is the currently recommended treatment approach. However, not much is known about long-term cost-effectiveness of different
T2T strategies.
We model the 5-years costs and effects of a step-up approach (MTX mono -> MTX + csDMARD combination -> Adalimumab ->
second anti-TNF-α) and an initial combination therapy approach (MTX + csDMARD + prednisone if needed -> MTX + csDMARD
high dose -> anti-TNF-α’s) from the healthcare and societal perspectives, by adapting a previously validated Markov model.
Methods:
We constructed a Markov model in which 3-monthly transitions between DAS28-defined health states of remission (≤2.6), low
(2.6<DAS28≤3.2), moderate (3.2<DAS28≤5.1), and high disease activity (DAS28>5.1) were simulated. Hypothetical patients
proceeded to subsequent treatments in case of non-remission at each (3-month) cycle start. In case of remission for two consecutive
cycles medication was tapered, until medication-free remission was achieved. Transition probabilities for individual treatment steps
were estimated using data of Dutch Rheumatology Monitoring registry Remission Induction Cohort I (step-up) and II (initial
combination). Expected costs, utility, and the ICER after 5 years were compared between the two strategies. To account for parameter
uncertainty, probabilistic sensitivity analysis was employed through Beta, Normal, and Dirichlet distributions. All utilities, costs, and
transition probabilities were replaced by fitted distributions.
Results:
Over a 5-year timespan, initial combination therapy was less costly and more effective than step-up therapy. Initial combination therapy
accrued €16226.3 and 3.552 QALY vs €20183.3 and 3.517 QALYs for step-up therapy. This resulted in a negative ICER, indicating that
initial combination therapy was both less costly and more effective in terms of utility gained. This can be explained by higher (±5%)
remission percentages in initial combination strategy at all time points. More patients in remission means less healthcare and
productivity loss costs and more accumulated utility. Additionally, higher remission percentages caused less bDMARD use in the initial
combination strategy, again lowering overall costs.
Conclusion:
Initial combination therapy was found to be favourable over step-up therapy in the treatment of Rheumatoid Arthritis, when considering
cost-effectiveness. Initial combination therapy resulted in more utility at a lower cost over 5 years.
Figure 1: Cost-effectiveness plane comparing initial combination and step-up therapy
X-axis: incremental effect (Quality-Adjusted Life Years). Y-axis: Incremental cost (€’s). Probabilistic sensitivity analysis shows initial
combination strategy is cost-effective.
Disclosure: C. J. van de Laar, None; L. M. M. Steunebrink, None; M. A. H. Oude Voshaar, None; H. E. Vonkeman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/initial-combination-therapy-versus-step-up-therapy-

is-more-effective-and-less-costly-as-a-treat-to-target-strategy-for-ra-a-markov-model-based-upon-the-dutch-rheumatoid-arthritis-
monitoring-registry
Treat to Target Adherence Measurement Tool Performance in Rheumatoid Arthritis

Rodrigo Garcia Salinas1, Sebastian Magri2 and Facundo Salvatori3, 1Section of Rheumatology, Hospital Italiano de La Plata, Buenos
Aires, Argentina, La Plata, Argentina, 2Section of Rheumatology, Hospital Italiano de La Plata, La Plata, Argentina, 3Rheumatology,
Hospital Italiano de La Plata, La Plata, Argentina
SESSION INFORMATION
Background/Purpose: The purpose of the T2T approach in RA is to achieve remission or LDA according to results from objective
activity measurements. This strategy has proven clinical benefits, however objective adherence T2T measurement tools are lacked in
daily practice. Objectives: To evaluate the setting, usage of a T2T adherence measure: T2T70 and T2T100, and its association with
sustained low disease activity (LDAS) as a measure of outcome.
Methods: Prospective study, consecutive patients with RA diagnosis (ACR / EULAR 2010) and follow-up between 1 and 24 months
were included. Data from electronic medical record (EHR) were collected. Demographic variables, characteristics of the disease and
treatment were recorded. The following T2T characteristics were defined and collected from each patient: number of visits, visits where
treatment was adjusted, CDAI measurements, use of ultrasound to measure disease activity and achievement of LDA. Sustained LDA
(LDAS) was defined when the patient had 2 or more records of that consecutive state of activity. Measures of adherence to T2T were
defined as follows: T2T-70, when therapeutic decisions were accompanied by the measurement of activity by 70% and the interval
between visits did not exceed 6 months; And T2T-100, when 100% of the decisions were accompanied with the activity measurement
and the interval between each visit did not exceed 6 months. Statistical analysis: a descriptive analysis of the variables was performed
and Chi2 test (categorical) and Student or MannWhitney test (continuous) were applied. For multivariate logistic regression analysis we
considered as dependent variable LDAs.
Results: 96 patients were included, with a mean follow-up of 15 months (DS 7.8), equivalent to 120.6 patients / year. Eighty percent of
the patients were women, mean age 53.7 years (SD 13), disease duration 36 months (RIC, 12-52), 64% had early diagnosis, 85% and
75% positive For FR and ACPA, respectively. According to T2T characteristics, 526 visits were recorded, 270 were treatment
adjustment and 208 (78%) of them were performed according to the CDAI value. The frequency of LDAS was 20% (IC95: 12-30). The
frequency of T2T-70 compliance was 62.5% (IC95: 52-72) and T2T-100 was 42% (IC95: 32-52). Compliance with T2T-70 and T2T-100
presented a statistically significant association to the achievement of LDAS in the uni and multivariate analysis (p: 0.000). Compliance
with T2T-70 and T2T-100 was associated with a shorter time course of disease; And T2T-70 also showed association with early
diagnosis.
Conclusion: T2T-70 and T2T-100 adherence were 62% and 42%, respectively, patients who met these criteria reached more LDAS. The
early diagnosis and shorter time to disease evolution at baseline were variables that were variables that were associated with more
compliance of these tools.
Disclosure: R. Garcia Salinas, None; S. Magri, None; F. Salvatori, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/treat-to-target-adherence-measurement-tool-

performance-in-rheumatoid-arthritis
Electronic Patient Reported Outcomes Increase Pediatric Rheumatology Clinic

Operations Efficiency While Increasing Patient and Caregiver Satisfaction
Y. Ingrid Goh1, Talia Goldberg2, Nicholas Lao3 and Brian M. Feldman4, 1Child Health Evaluative Sciences, The Hospital for Sick
Children, Toronto, ON, Canada, 2University of Toronto, Toronto, ON, Canada, 3University of Western Ontario, London, ON, Canada,
4Rheumatology, The Hospital for Sick Children, Toronto, ON, Canada
SESSION INFORMATION
Electronic Patient Reported Outcomes Increase Pediatric Rheumatology Clinic Operations Efficiency While Increasing Patient
and Caregiver Satisfaction
Background/Purpose: Patient reported outcomes (PROs) are powerful tools that facilitate communication between patients and their
healthcare team. In paper format, PROs may be incomplete, misplaced and incorrectly scored. Electronic version (e-form) of PROs
may reduce the occurrence of these issues. As more healthcare institutions move toward electronic medical systems, it is important to
assess its impact on healthcare. Not only is the system impact important, it is imperative to assess patients’ and caregivers’ perspective
on these changes. The objectives of this study were to a) determine whether the e-form could improve efficiency; b) assess user
satisfaction with the e-form; and c) identify additional improvements to the e-form.
Methods: An e-form of the Childhood Health Assessment Questionnaire (CHAQ) and the Quality of My Life (QoML) questionnaire
was created in REDCap. Patients/caregivers attending the rheumatology clinic at The Hospital for Sick Children were asked to
participate in this quality improvement study by completing both paper and e-form of the PROs (the order of which was determined by
a table of random numbers). They were then asked to complete a satisfaction survey which asked them about their experience and for
suggestions on how to improve the e-form. Changes in efficiency were compared by noting the time differences between both forms as
well as calculating the annual differences in cost. Prior to comparing the times, 2.5 minutes were added to the paper form times to
account for scoring and data entry times. Survey results were analysed using descriptive statistics and thematic identification.
Results: 197/209 participants completed both forms. The median times to complete the paper forms were longer than completing the e-
forms (Table 1). This was more significant when paper forms were completed prior to e-forms.
The Division’s costs for photocopying paper forms amounts to ~ $1000/year, whereas the REDCap database cost ~$300 to build and
does not require any additional maintenance funding. Therefore, an e-form results in significant cost savings.
191/209 participants completed the satisfaction survey. 64% (122/191) respondents indicated that they preferred the e-form over the
paper form.
Suggestions for improvements included improving the sliding scale mechanism and increasing the text size.
Conclusion: Implementation of an e-form resulted in greater efficiency—it was faster and saved money. Patients also liked it better.
The e-form should be modified to reflect participants’ suggestions and these modifications should be subsequently assessed.
Table 1. Time to complete paper vs. electronic form

Randomized to Paper then Electronic Form Randomized to Electronic then Paper Form
New Patient Follow-Up Patient New Patient Follow-up Patient
N 17 86 20 74
Median time to complete paper form (mm:ss) 6:17 3:45 3:58 2:56
Median total time for paper form completion, 8:47 6:15 6:28 5:26
scoring and data entry (mm:ss)
Median time to complete electronic form 3:50 4:10 6:26 4:58
(mm:ss)
P=0.0005 P=0.0002 P=0.99 P=0.06
Disclosure: Y. I. Goh, None; T. Goldberg, None; N. Lao, None; B. M. Feldman, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/electronic-patient-reported-outcomes-increase-

pediatric-rheumatology-clinic-operations-efficiency-while-increasing-patient-and-caregiver-satisfaction
Improving Patient-Reported Outcomes Collection and Documentation for Patients

with Rheumatoid Arthritis at Multilingual, Safety Net Hospital Rheumatology Clinic
Todd Liou1, Omotoke Odimayomi1, Laura Trupin2, Jinoos Yazdany2 and Mary Margaretten3, 1University of California San Francisco,
San Francisco, CA, 2Medicine/Rheumatology, University of California San Francisco, San Francisco, CA, 3Medicine, University of
California San Francisco, San Francisco, CA
SESSION INFORMATION
Background/Purpose: The Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function-10a (PF10a)
survey is a reliable and valid measure of function in patients with rheumatoid arthritis (RA). National quality measures recommend that
patient-reported outcomes such as PROMIS PF10a be collected regularly in routine care. However, safety net health systems may face
barriers in implementing PRO collection, including patients with low health literacy and limited English-language proficiency. Our
objective was to increase collection and documentation of the PROMIS PF10a from 0% to 50% for all adult RA patient visits in our
diverse, safety net clinic during a 9 month period.
Methods: We used the Institute for Healthcare ImprovementÕs Model for Improvement and Plan-Do-Study-Act (PDSA) methodology
over 4 cycles. In cycle 1, PF10a surveys were administered to English-speaking patients, after vitals were taken. Staff offered to read the
survey to all patients, an approach commonly used to ensure patients with low health literacy feel comfortable participating. Cycle 2
separated the process of collecting PROMIS PF10a scores into two steps: (1) administering the survey throughout clinic workflow
rather than only after vitals were taken and (2) uploading the score into the electronic health record (EHR), which were delegated to a
high school research volunteer and medical assistants. Cycle 3 created a folder for the volunteer and medical student team to
communicate and track weekly progress. In the final PDSA cycle, the forms were administered to Spanish-speaking patients by
language concordant staff.
Results: Our rheumatology clinic has approximately 96 RA encounters per month and 70% of the patient population speaks languages
other than English (the majority speaking Cantonese or Spanish). The quality improvement project began in the fall of 2016 and
PROMIS PF10a score collection percentage was 12.5% after the first PDSA cycle. During the second cycle, the proportion of visits
with a completed PROMIS PF10a rose to 22.2%. After the 4th PDSA cycle, there was a sustained improvement over 6 months, with
35.5% of RA patient visits having the PROMIS PF10a collected and recorded in the EHR (Figure).
Conclusion: Using an interprofessional team approach and the Model for Improvement, we significantly improved collection and
documentation of the PROMIS PF10a measure in a multilingual safety net rheumatology clinic. Although we fell short of our goal of
50% of our RA patient visits, we were able to record the PROMIS PF10a measure for 48.6% of the 212 individual patients seen
throughout the course of our project. Efforts are ongoing to expand collection to further engage our clinic staff and volunteers to create a
sustainable PRO collection workflow.
Figure. PROMIS PF10a Administration RA Quality Improvement Project Run Chart (Nov 2016 - Mar 2017). 1-4 correspond to PDSA
cycles. A is when research intern was absent due to a 3-week vacation.
Disclosure: T. Liou, None; O. Odimayomi, None; L. Trupin, None; J. Yazdany, None; M. Margaretten, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/improving-patient-reported-outcomes-collection-

and-documentation-for-patients-with-rheumatoid-arthritis-at-multilingual-safety-net-hospital-rheumatology-clinic
Responsiveness and Minimally Clinically Important Differences of Promis Measures

in Rheumatoid Arthritis
Susan J. Bartlett1, Michelle Jones2 and Clifton O. Bingham III3, 1Department of Medicine, Division of ClinEpi, Rheumatology,
Respirology, McGill University, Montreal, QC, Canada, 2Johns Hopkins University School of Medicine, Baltimore, MD,
3Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD
SESSION INFORMATION
Responsiveness and Minimally Clinically Important Differences of PROMIS Measures in Rheumatoid Arthritis
Background/Purpose: The ability to detect meaningful change in clinical status (responsiveness) is an important aspect of validity.
Minimally clinically important difference (MCID) is a patient-centered construct reflecting the smallest difference of value to patients.
PROMIS is a generic family of measures developed for use across chronic diseases. We examined the responsiveness and estimated
MCIDs of selected PROMIS measures reflecting domains that people with RA have identified.
Methods: Data are from the first two visits of an observational trial in Baltimore, MD. Patients completed PROMIS Physical Function
(PF), Pain Interference (PI), Participation Ability (PA), and Fatigue computer adapted tests and other patient-reported outcomes (PROs)
using a tablet. At the second visit, patients also completed a 5-point item assessing change in RA status from the previous visit (much
worse to much better) and the self-reported health rating. Descriptive statistics were calculated, and ANOVA was used to identify
significant differences in scores on 9 PROMIS measures.
Results: The 196 RA patients who completed outcomes at clinical visits approximately 4 months apart were mostly female (81%),
white (82%) with a mean age of 55 (13). All met ACR 1987 or 2010 criteria for RA. One-third reported the same health status at both
visits (68 [35%]); 13% were a little better; a similar number were much better; 27% were a little worse, and 7% were much worse.
Correlations between PROMIS and other measures assessing similar domains ranged from 0.32 to 0.83. Among patients reporting being
“much worse”, PROMIS scores worsened from 1.0 to 8.1 points (mean CDAI change 9.2)(Table). Among patients feeling much better,
PROMIS scores improved from 1.6 to 6.9 points (mean CDAI change -6.6). Change in PROMIS scores were largest in relation to
changing disease activity for symptoms highly relevant to RA (e.g., PI, fatigue, PF); notably patients with worsening in RA did not
report higher anxiety or depression scores.
Conclusion: These initial data suggest PROMIS measures are responsive to clinical changes in RA status and contribute to the growing
literature supporting the use of PROMIS measures to assess physical, social, emotional and health in people with RA.
Disclosure: S. J. Bartlett, None; M. Jones, None; C. O. Bingham III, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/responsiveness-and-minimally-clinically-important-

differences-of-promis-measures-in-rheumatoid-arthritis
Rheumatoid Arthritis Patients Achieved Better Quality of Life Than Systemic Lupus
Erythematosus Patients at Sustained Remission: The Impact of Disease Diagnosis on
Health-Related Quality of Life Outcomes
Virginia Pascual-Ramos1, Irazú Contreras-Yáñez2, Katya Valencia-Quiñones3 and Juanita Romero-Diaz4, 1Department of
Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico,
2Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico,
3Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico,
4Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico city, Mexico
SESSION INFORMATION
Background/Purpose: Patients with Systemic Lupus Erythematous (SLE) and Rheumatoid Arthritis (RA) had profound negative
effects on their health-related quality of life (HRQoL) that can be assessed using the 36 item Medical Outcome Study Short-Form
survey (SF-36). Remission might have a different impact on patient´s HRQoL depending on the specific disease diagnosis.
In 2004 and 1999, respectively, recent-onset rheumatoid arthritis (RA) and systemic lupus erythematous (SLE) cohorts were initiated;
the 36 item Medical Outcome Study Short-Form survey (SF-36) was incorporated to routine assessments from 2005 onwards in the SLE
cohort and the SF-36v2 beginning from enrollment in the RA cohort. Objectives of the study were to compare the SF-36v2 scores
between patients from both cohorts who achieved sustained remission (SR) and to define the role of disease diagnosis as associated to
SF-36v2 normative data.
Methods: SLE and RA were diagnosed based on corresponding ACR classification criteria. Routine assessments were performed every
2-6 months and included at least the SLE disease activity index 2000 update (SLEDAI-2K) for SLE patients, and the Disease Activity
Score (28 joints) (DAS28) for RA patients.
SR was considered when RA and SLE patients achieved at least 12 months of continuous follow-up with either SLEDAI-2K=0 or
DAS28 ≤2.4, respectively. Up to December 2015, data from 172 RA patients and 211 SLE patients respectively, were reviewed.
SF-36v2 scores were available for the totality of SR assessments. The SF-36v2 licensee performed the re-scoring of the SF-36 that was
used in the SLE cohort. In all the cases, Spanish (for México) versions were used and scoring was adjusted by gender and age. Logistic
regression models were used to investigate factors associated with normative SF-36v2. Written informed consent was obtained from all
patients.
Results: A higher proportion of RA patients achieved SR: 106 (58%) RA patients vs. 75 (30.6%) SLE patients, p≤0.001. SR was
achieved earlier in patients from the former group: (mean±SD) follow-up was 30.8±23.9 months vs. 59.4±37.5 months in SLE patients,
p≤0.001. The length of time in SR and the number of patients who had a disease flare were similar in both cohorts.
At baseline, RA patients scored significantly lower all the domains of the SF-36v2 and both the mental and physical summary measures,
than SLE patients. At SR, RA patients scored better than SLE patients in 6 out of 8 domains of the SF-36v2 and the physical health
component summary (Figure).
Age (ß: 1.06, 95% CI: 1.02-1.1, p=0.03) and SLE diagnosis (ß: 9.64, 95% CI: 3.61-25.75, p≤0.001) were predictors of not achieving
normative physical component summary measure.
Conclusion: Patient´s perspective of (absence of) disease activity represents an important aspect of the assessment of rheumatic
diseases. RA patients in SR achieved better quality of life than SLE patients.
Figure.
Disclosure: V. Pascual-Ramos, None; I. Contreras-Yáñez, None; K. Valencia-Quiñones, None; J. Romero-Diaz, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rheumatoid-arthritis-patients-achieved-better-

quality-of-life-than-systemic-lupus-erythematosus-patients-at-sustained-remission-the-impact-of-disease-diagnosis-on-health-related-
quality-of-life-outco
Emdhaq: (electronic multidimensional health assessment questionnaire) to Record

and Document eRAPID3 (electronic routine assessment of patient index data3) and
eFAST3 (electronic fibromyalgia assessment screening tool3) in Routine
Rheumatology Care
Theodore Pincus1, Jacquelin R. Chua2, Shakeel M. Jamal2, Nathaniel Cook3, Niels Steen Krogh4, Anne-Marie Malfait1 and Joel A.
Block2, 1Rheumatology, Rush University Medical Center, Chicago, IL, 2Division of Rheumatology, Rush University Medical Center,
Chicago, IL, 3Infectious Disease, Rush University Medical Center, Chicago, IL, 4ZiteLab ApS, Copenhagen, Denmark
SESSION INFORMATION
Background/Purpose: RAPID3 (routine assessment of patient index data) on a multi-dimensional health assessment questionnaire
(MDHAQ) distinguishes active from control treatments in RA clinical trials as effectively as disease activity score 28 (DAS28) or
clinical disease activity index (CDAI), and is informative to monitor patients with osteoarthritis, spondyloarthropathies, vasculitis, gout,
etc. (1). Therefore, many versions of an electronic RAPID3 (eRAPID3) have been developed, although generally mutually
incompatible, mimicking electronic medical records (EMRs), and not easily merged into an EMR or into multicenter databases to study
patient outcomes (2). More recently, another index of MDHAQ scores, FAST3 (fibromyalgia assessment screening tool3), has been
described, which agrees >80% with ACR fibromyalgia (FM) criteria to identify FM (3). Here, we assess eFAST3 and eRAPID3 on an
eMDHAQ to recognize possible secondary FM in patients with osteoarthritis (OA) or rheumatoid arthritis (RA).
Methods: A patient- and doctor-friendly eMDHAQ meets HIPAA, privacy and security requirements, and is designed to interface with
any EMR, using FHIR (Fast Healthcare Interoperability Resources) for integration and interoperability, although requiring collaboration
with the EMR vendor, and to be merged easily into common collaborative research databases. eRAPID3 on an eMDHAQ is a 0-30 sum
of a 0-10 physical function (FN) scale and two 0-10 visual analog scales (VAS) for pain (PN) and global assessment (PATGL). eFAST3
on eMDHAQ is a 0-3 scale; 1 point is assigned if PN ≥6/10, RADAI painful joint count ≥16/48, and MDHAQ symptom checklist
≥16/60; FAST3≥2 is clue to FM (3). eRAPID3 and eFAST3 were compared in 89 osteoarthritis (OA) vs 91 rheumatoid arthritis (RA)
patients, using STATA to compute means and cross-tabulations.
Results: Mean eRAPID3 scores were 14.9 in OA vs 11.1 in RA patients. eRAPID3 was >12 (high severity) in 59 OA (66%) and 39 RA
(43%) patients. eFAST3 ≥2, suggesting secondary FM, was seen in 21 of the 59 OA patients (24% of all OA patients) and 17 of the 39
RA patients (19% of all RA patients) with RAPID3>12 (Table). No patient with RAPID3 <12 had eFAST3 ≥2, suggesting a good screen
for the absence of FM. Most patients with RAPID3>12 also had FAST3 <2 (Table), suggesting limited specificity of RAPID3 for FM.
Number of patients with OA or RA according to eRAPID3 vs eFAST3 on eMDHAQ.
(%) are of all OA or RA patients

RAPID3 Total
RAPID3 RAPID3
RAPID3 Low Moderate
OA n=89 Remission=0- High
severity=3.1-6 severity=6.1-
3 severity>12
12
FAST3=0 2 (2%) 6 (7%) 14 (16%) 8 (9%) 30
(34%)
FAST3=1 0 0 8 (9%) 30 (34%) 38
(43%)
FAST3=2 0 0 0 13 (15%) 13 (5%)
FAST3=3 0 0 0 8 (9%) 8 (9%)
Total 2 (2%) 6 (7%) 22 (25%) 59 (66%) 89
Moderate High Total
RA n= 91 Remission Low severity
severity severity
FAST3=0 15 (16%) 20 (22%) 11 (12%) 2 (2%) 48
(53%)
FAST3=1 0 0 6 (7%) 20 (22%) 26
(29%)
FAST3=2 0 0 0 10 (11%) 10
(11%)
FAST3=3 0 0 0 7 (8%) 7 (8%)
Total 15 (16%) 20 (22%) 17 (19%) 39 (43%) 91
Conclusion: An eMDHAQ offers reports of eRAPID3 and eFAST3 for improved clinical decisions, doctor-patient communication, and
documentation. Further development of the eMDHAQ, eRAPID3, and eFAST3, and interface to the EMR, are needed for optimal value.
Rheumatologists and organizations are encouraged to implement an electronic MDHAQ, rather than simply an electronic RAPID3.
References: 1. Current pharmaceutical design. 2015; 21:241-56. 2. Clin Exp Rheumatol. 2016; 34:S49-53. 3. EULAR. 2017. Poster
THU0472
Disclosure: T. Pincus, Theodore Pincus, 7; J. R. Chua, None; S. M. Jamal, None; N. Cook, None; N. S. Krogh, None; A. M.
Malfait, Galapagos, Regeneron, Ferring, 5; J. A. Block, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/emdhaq-electronic-multidimensional-health-

assessment-questionnaire-to-record-and-document-erapid3-electronic-routine-assessment-of-patient-index-data3-and-efast3-electronic-
fibromyalgia-assessme
Application of Lupus Nephritis Quality Measures to Understand Gaps in Care for

SLE
Lisa Gaynon1, Maria Dall'Era2, Patricia P. Katz2, Lindsey A. Criswell2, Cristina Lanata2, Laura Trupin3, Charles G. Helmick4 and
Jinoos Yazdany3, 1Internal Medicine, California Pacific Medical Center, San Francisco, CA, 2Medicine/Rheumatology, University of
California, San Francisco, San Francisco, CA, 3Medicine/Rheumatology, University of California San Francisco, San Francisco, CA,
4Centers for Disease Control and Prevention, Atlanta, GA
SESSION INFORMATION
Background/Purpose: In 2012, the ACR released guidelines for monitoring and treatment of lupus nephritis (LN), but studies have yet
to evaluate adherence to these recommendations. Using measures from the SLE Quality Indicators Project (Yazdany, et al., 2009) and
new measures derived from ACR guidelines, we evaluated quality of care for LN among patients enrolled in the California Lupus
Epidemiology Study (CLUES), a multi-ethnic, population-based cohort study.
Methods: We reviewed charts of CLUES patients to evaluate performance on quality measures (N=116 of 281 enrolled in the study to
date). Patients were followed either in tertiary academic centers or by community rheumatologists in the study catchment area. Seven
quality measures were assessed. For those without LN, we evaluated whether recommended screening processes were completed in the
year preceding study enrollment (2014-2016) (urinalysis, urine protein: creatinine ratio and serum creatinine checked every 6 months;
C3/C4 and anti-dsDNA levels every 6 months; and blood pressure checked every 3 months). For those with prevalent LN, we looked to
see if patients had a renal biopsy at the time of diagnosis, received an immunosuppressant within 30 days of LN diagnosis, and were
started on an ACEi/ARB and anti-malarial therapy within 1 year. "Pass rates" (% eligible patients receiving recommended care) for
these measures were analyzed for the entire group and compared for tertiary vs community treatment settings using chi-squared tests.
Results: Among the 116 patients, 55 had a diagnosis of LN. 75 were followed in tertiary care settings and 41 by community
rheumatologists. For patients with no history of LN, 40% had recommended screening of urine and renal function every 6 months, and
45% had screening for immunological activity every 6 months (Table). Adherence to blood pressure checks every 3 months was better
(74%). For patients with LN, most patients (87%) had renal biopsies for diagnostic confirmation and 82% were started on an
immunosuppressant within 1 month of diagnosis. 80% were placed on an anti-malarial and 68% on a renal protective antihypertensive
(ACEi or ARB) within 1 year of diagnosis. We found no differences between community and tertiary care settings in measures assessing
the diagnosis and treatment of LN. However, performance on measures examining screening of urine, renal function, immunological
activity, and BP for patients with no history of LN was lower among community rheumatologists (see Table).
Conclusion: We found relatively high performance on quality measures regarding LN diagnosis and treatment, with no differences
between community and tertiary care settings. For patients with no history of LN, we found that screening for renal disease was
performed less in community settings. Next steps include reviewing additional records from CLUES and validating our chart review
procedures across health care settings.
Table 1: Quality Measure Pass Rates for the Screening and

Treatment of Lupus Nephritis
With No History of LN (n=61)
Q1: UA, Urine Q2: C3/C4, anti- Q3: Blood
Protein:Creatinine dsDNA q6m pressure
ratio, Serum check q3m
Creatinine q6m
Academic 66.7% 55.6% 86.1%
Clinic
(n=36)
Community 0.0% 29.2% 56.0%
Clinic
(n=25)
P-value <0.01 <0.05 <0.01
Total 40.0% 45.0% 73.8%
With LN (n=55)
Q4: Renal biopsy Q5: Q6: Q7:
done Immuno- Anti- ACEi/ARB
suppression malarial within 1y
within 1m within
1y
Academic 89.7% 80.0% 84.8% 70.3%
Clinic
(n=39)
Community 77.8% 85.7% 66.7% 55.6%
Clinic
(n=16)
P-value 0.357 0.641 0.177 0.398
Total 86.8% 81.6% 80.0% 67.4%
Disclosure: L. Gaynon, None; M. Dall'Era, None; P. P. Katz, Bristol-Myers Squibb, 2; L. A. Criswell, None; C. Lanata, None; L.
Trupin, None; C. G. Helmick, None; J. Yazdany, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/application-of-lupus-nephritis-quality-measures-to-
understand-gaps-in-care-for-sle
Screening and Intervention of Depression in Rheumatoid Arthritis and Systemic

Lupus Erythematosus
Rui Zhang1, Priya Prakash2, Amy Wasserman3, Kirk Sperber4 and Julia Ash5, 1Medicine -Rheumatology, New York Medical College /
Westchester Medical Center, valhalla, NY, 2Rheumatology, NYMC /WMC, VALHALLA, NY, 3Medicine - Rheumatology, New York
Medical College / Westchester Medical Center, VALHALLA, NY, 4New York Medical College / Westchester Medical Center, Valhalla,
NY, 5Medicine -Rheumatology, New York Medical College / Westchester Medical Center, Valhalla, NY
SESSION INFORMATION
Background/Purpose: Depression is common and associated with worse outcomes among patients with RA and SLE. Our study
assessed depression using Patient Help Questionnaire (PHQ-9) and its correlation with disease activity. We also examined the outcome
of intervention on depression score.
Methods: This is a single center cross-sectional study of mainly uninsured patients with RA and SLE in Rheumatology clinic. PHQ-9
scores were collected at each clinic visit. Physicians assessed corresponding disease activity using Clinical Disease Activity Index
(CDAI) or SLEDAI. Patients with at least moderate depression (PHQ-9 _10) were offered depression intervention, counseling or
medications. PHQ-9 was re-administered after intervention.
Results: 45 RA patients with a mean age of 50 years (±12) and 16 SLE patients with a mean age of 42 years (±11) were screened. In
RA group 82% were females with average disease duration of 7 (±6) years. In SLE group 94% were females with average disease
duration of 8 (±7) years. Depression was diagnosed in 51% of RA patients: 29% mild, 13% moderate and 9% moderately severe
(Table.1). Severity of depression positively correlated with disease activity in RA patients (Figure. 1, Pearson R=0.636, p <0.001). In
contrast, depression was diagnosed in 25% of SLE patients: 12.5% mild and 12.5% moderate and did not correlate with disease activity
(Pearson R=0.209). RA patients with moderate/high CDAI had significantly higher PHQ-9 than those with low CDAI (7.7 vs 1.5,
p<0.001; 9.6 vs 1.5 p<0.001, t-test). Of 12 patients who met criteria for depression intervention (Table. 2), 33% were treated, 33% are
pending treatment and 33% declined. With intervention, 2 patients had improved PHQ-9 scores, 1 patientÕs score worsened confounded
by cancer surgery, and 1 patient had no change in score.
Conclusion: Our study shows higher prevalence of depression in RA (51%) and SLE (25%) than in general population (7-12%). 1
Correlation between disease activity and depression score is only found in RA. Depression intervention resulted in PHQ-9 improvement
in some patients, supporting the benefit of depression screening and treatment in rheumatology practice.
1. Pratt. LA et al. Depression in the U.S. Household Population, 2009-2012. NCHS Data Brief, 2014; No.172.
Disclosure: R. Zhang, None; P. Prakash, None; A. Wasserman, None; K. Sperber, None; J. Ash, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/screening-and-intervention-of-depression-in-

rheumatoid-arthritis-and-systemic-lupus-erythematosus
Rheumatology Clinic Smoking Cessation Protocol Markedly Increases Quit Line

Referrals
Christie M. Bartels1, Edmond Ramly2, Daniel Panyard3, Diane Lauver4, Heather Johnson5, Zhanhai Li6, Emmanuel Sampene7,
Megan Piper8 and Patrick McBride5, 1Rheumatology/Medicine, University of Wisconsin - Madison, Madison, WI, 2Industrial and
Systems Engineering, University of Wisconsin College of Engineering, Madison, WI, 3Population Health, University of Wisconsin
School of Medicine and Public Health, Madison, WI, 4University of Wisconsin-Madison School of Nursing, Madison, WI,
5Cardiology/Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 6Biostatistics and Medical
Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI, 7Biostatistics, University of Wisconsin
School of Medicine and Public Health, Madison, WI, 8University of Wisconsin Center for Tobacco Research and Intervention, Madison,
WI
SESSION INFORMATION
Background/Purpose: Smoking predicts higher incidence, greater severity, and reduced treatment responses in rheumatoid arthritis,
lupus, and spondyloarthritis. However, cessation advice and quit line referral occur in just 10% and 0.6% of rheumatology visits,
respectively. Primary care staff protocols improve guideline-based care, and electronic referrals increase use of free, state tobacco quit
lines by 13-fold. We sought to examine a similar staff protocol in rheumatology using electronic health record (EHR) tools to connect
eligible patients to a free, state quit line.
Methods: We conducted a pre- post-analysis of EHR data (2012-16) including our 6-month Quit Connect project. During
implementation, cessation experts and project staff provided an hour of Quit Connect protocol training to nurses and medical assistants
at three rheumatology clinics. The protocol included EHR prompts to assess smoking status, 30-day readiness to quit or cut back, and
willingness to try a quit line. EHR data measured process steps. Referral to the quit line (vs. our published baseline) was the primary
outcome. The quit line reported patient outcomes. The IRB exempted this as standard of care with permission to publish.
Logistic regression models examined process measures and referrals pre- and post-protocol. Multivariable process models included age,
sex, race, body mass index (BMI), socioeconomic status (SES; defined as ever receiving Medicaid), and comorbidity (Johns Hopkins
Adjusted Clinical Groups (ACG) score).
Results: For 54,090 rheumatology visits, 4,601 (9%) reported current smoking. 4,078 pre-protocol visits with patients who smoke
(2012-15) were compared to 523 visits after protocol implementation (2016). Documenting smoking status remained high (96 v. 97%).
30-day readiness to quit assessment rose from 3% to 80% post-protocol (Table 1, OR 120, 91-159). Among those asked, 29% reported
being ready to quit. Of those ready, 76% had a referral to the state tobacco quit line compared to our pre- rate of 0.6% (OR 26, 6-106).
When offered, 71% accepted referrals (54% of ready to quit; 13% of smokers).
Patients with higher comorbidity were less often ready to quit (ACG OR 0.6, 0.4-0.9 unadj.); older patients accepted fewer referrals (OR
0.8, 0.7-0.97 unadj. per 10 yrs.). Adjusted models did not change results.
Among 66 referred patients, 11 (17%) accepted counselling, nicotine replacement, and set a quit date, and 5 more reported a quit in
process. Overall, 24% of referred patients set a quit date or reported a quit attempt.
Conclusion: Our Quit Connect protocol for rheumatology staff increased quit line referrals over 20-fold. When asked, a third of
patients were ready to quit and half agreed to referral. Given the importance of cessation to reduce immune and cardiopulmonary
disease, future rheumatology studies should investigate cessation protocols to leverage quit lines, which are free in all states.
Disclosure: C. M. Bartels, Pfizer Inc, 2; E. Ramly, None; D. Panyard, None; D. Lauver, None; H. Johnson, None; Z. Li, None; E.
Sampene, None; M. Piper, None; P. McBride, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rheumatology-clinic-smoking-cessation-protocol-

markedly-increases-quit-line-referrals
Staff Protocol in Rheumatology Clinics Reduces Population-Level Rate of High

Blood Pressure
Christie M. Bartels1, Edmond Ramly2, Emmanuel Sampene3, Diane Lauver4, Patrick McBride5 and Heather Johnson5,
1Rheumatology/Medicine, University of Wisconsin - Madison, Madison, WI, 2Industrial and Systems Engineering, University of
Wisconsin College of Engineering, Madison, WI, 3Biostatistics, University of Wisconsin School of Medicine and Public Health,
Madison, WI, 4University of Wisconsin-Madison School of Nursing, Madison, WI, 5Cardiology/Medicine, University of Wisconsin
School of Medicine and Public Health, Madison, WI
SESSION INFORMATION
Background/Purpose: The Centers for Disease Control and Prevention director has said “nothing will save more lives” than protocols
to control blood pressure (BP). BP is relevant in rheumatology clinics because it is causally linked to cardiovascular disease.
Hypertension control is also one of ten RA quality measures endorsed by ACR and Medicare for 2017 quality payment reporting. Yet,
minimal evidence exists on how to improve BP control in busy rheumatology clinics. We previously implemented a staff protocol that
doubled timely follow-up after high BPs in rheumatology clinics, and now aimed to examine its impact on population BP control.
Methods: We assessed population trends in the rate of monthly high BPs (% of all visits) before and after the implementation of a staff
BP Connect Health protocol in three rheumatology clinics (10/2012-10/2014 vs. 11/2014-12/2016). During implementation, clinical
educators trained nurses and medical assistants in an hour-long session on BP in rheumatic diseases, proper BP measurement, and the
BP Connect Health protocol steps. Protocols included EHR prompts to re-measure high BPs, and if confirmed high, offer timely
primary care follow-up. Follow-up orders automatically routed to scheduling staff for patients with in-network primary care, and printed
on after visit materials for all patients. EHR data reported the monthly percentage of adult rheumatology clinic visits with an initial BP
>140/90 mmHg.
We performed time series regression with Newey-West standard errors to examine changes in rates of high BPs in the 24 months before
and after protocol implementation.
Results: A total of 28,109 pre-protocol rheumatology clinic visits were compared to 28,285 visits after protocol implementation.
Monthly rates of high BP, when averaged over the periods before and after implementation, fell from 17% pre- to 8% post-protocol.
Time series analysis demonstrated a significant reduction after protocol implementation and continued improvement over time (Figure
1. p<0.003 & p<0.03). Strengths included 2-year protocol feasibility; limitations include our single center pre-post design.
Conclusion: After implementing the rheumatology staff protocol, we observed a 9% reduction in mean rates of high BP across
rheumatology clinic populations. Early improvements likely reflected staff BP training, while later improvements may reflect improved
follow-up, adherence, and management of BP. Future multi-site studies will test the BP Connect Health protocol in other rheumatology
and specialty populations at risk for cardiovascular disease.
Disclosure: C. M. Bartels, Pfizer Inc, 2; E. Ramly, None; E. Sampene, None; D. Lauver, None; P. McBride, None; H. Johnson,
None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/staff-protocol-in-rheumatology-clinics-reduces-

population-level-rate-of-high-blood-pressure
Large Variations in Tuberculosis Testing for New Biologic Users with Rheumatoid
Arthritis Among Providers in the RISE Registry
Gabriela Schmajuk1, Michael Evans2, Julia Kay3 and Jinoos Yazdany4, 1San Francisco VA Medical Center, University of California
San Francisco, San Francisco, CA, 2University of California San Francisco, San Francisco, CA, 3Medicine/Rheumatology, University
of California - San Francisco, San Francisco, CA, 4Medicine/Rheumatology, University of California San Francisco, San Francisco, CA
SESSION INFORMATION
Background/Purpose: Tuberculosis (TB) testing prior to biologic DMARD use helps prevent potentially fatal, medication-related
adverse events and is a National Quality Forum-endorsed quality measure. We used data from a national registry to describe practice
variations on this measure among US rheumatologists.
Methods: The ACR’s RISE is a national registry that passively collects electronic health record (EHR) data on all patients seen by
participating practices. As of December 2016, RISE was connected to 632 providers representing an estimated 20% of the US clinical
rheumatology workforce. We calculated the proportion patients ≥ 18 with rheumatoid arthritis who were newly prescribed a biologic
DMARD or tofacitinib during 2016 and who had TB testing in the 12 months preceding the biologic prescription, by practice and
geographic region. We examined associated EHR data for the type of TB test performed (PPD or quantiferon-based assays). Consistent
with other national performance analyses, providers with fewer than 30 qualifying patients in the denominator were excluded.
Proportions were compared using chi-square tests.
Results: We analyzed data from 18,079 patients across 533 providers and 95 practices. 77% of patients were female, 20% were non-
white, and mean age was 58 (SD 13.5). Overall, patient-level performance on the measure was 56%, with a range of 0 to 96% across
practices (Figure), and significant variation across regions (Table; p<0.0001). Among the patients in the numerator with a TB test found
in the EHR data (N=7828), 93% received a Quantiferon test while 7% had a PPD.
Conclusion: We found large variations in TB testing prior to new biologic DMARD starts across RISE practices. Given that
quantiferon-based assays represented the majority of TB screening tests identified, we suspect that PPD testing remains undercaptured
in the EHR. As value-based incentive programs become more widespread, accurate capture of performance on patient safety measures
will be increasingly important and may require practices to standardize documentation of important safety processes such as TB testing.
Disclaimer: The data presented here was supported by the ACR’s RISE Registry. However, the views expressed represent those of the
authors and do not necessarily represent the views of the ACR.
Disclosure: G. Schmajuk, None; M. Evans, None; J. Kay, None; J. Yazdany, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/large-variations-in-tuberculosis-testing-for-new-

biologic-users-with-rheumatoid-arthritis-among-providers-in-the-rise-registry
A Multidisciplinary Performance Improvement Approach to Achieving Goal Serum

Uric Acid Levels in Patients with Gout
Luke Monteagudo1, Jefferson Roberts2, Donna Kido3, Collette Chin3 and Susan Fujii3, 1Internal Medicine, Tripler Army Medical
Center, Honolulu, HI, 2Rheumatology, Tripler Army Medical Center, Honolulu, HI, 3Pharmacy, Tripler Army Medical Center,
Honolulu, HI
SESSION INFORMATION
Background/Purpose: In patients with gout, hyperuricemia leads to inflammation induced by mono-sodium urate crystal deposition.
This causes irreversible physical and radiographically evident destruction of the affected joint. Current guidelines recommend a serum
uric acid (sUA) level < 6 mg/dL, while data has shown that sUA of < 5 mg/dL has benefit. The aim of this performance improvement
project was to assess how to better achieve these goals. We hypothesized that through a multidisciplinary approach, we could more
effectively achieve sUA goal levels.
Methods: We enrolled patients with a new or chronic diagnosis of gout. We excluded pregnant women and those under the age of 18.
Baseline sUA levels were obtained on all patients. If elevated and not already on urate lowering therapy, patients were started on 100mg
Allopurinol daily and 0.6mg Colchicine twice daily. A clinical pharmacist followed our algorithm for a step wise increase in therapy
intensity every two weeks, with a corresponding sUA level.
Results: A total of 40 patients participated. The average starting uric acid level of the experimental group was 8.06 mg/dL. After 12
months, 48% (n=19) of patients reached a level below 6 mg/dL. After an average of 18.5 months of enrollment, 33% of patients (n=13)
reached a serum uric acid level below 5 mg/dL and 53% (n=21) reached a serum uric acid level below 6 mg/dL.
Conclusion: The aim of our approach to gout treatment is to decrease sUA, gout attacks, and ultimately joint damage. We were able to
show that a multidisciplinary approach could improve sUA level compared with primary physicians alone. This effect is due to clinical
pharmacists’ ability to perform more frequent sUA evaluations and medication changes for patients. Future work will evaluate
secondary end points, like the number of acute care visits and gout attacks during the study period. The summation of this data supports
the multidisciplinary approach to the treatment of gout.
Disclosure: L. Monteagudo, None; J. Roberts, None; D. Kido, None; C. Chin, None; S. Fujii, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-multidisciplinary-performance-improvement-
approach-to-achieving-goal-serum-uric-acid-levels-in-patients-with-gout
The Utility of Electronic Consultation in the Management of Gout at the Veterans

Affairs Medical Center
Juliana Chang1, Michelle DiFiore1 and Maida Wong2,3, 1Internal Medicine, University of California, Irvine, School of Medicine,
Orange, CA, 2Rheumatology, University of California, Irvine, School of Medicine, Orange, CA, 3Rheumatology, Tibor Rubin VA
Medical Center in Long Beach, Long Beach, CA
SESSION INFORMATION
Background/Purpose: Gout is the most common inflammatory arthritis in adults worldwide. It can be managed by primary care
physicians (PCPs), but complex cases often require rheumatology input. However, the average wait time for a first rheumatology clinic
visit varies from 38 days to 47 weeks. By utilizing electronic consultation (e-consult) which allows two-way communications between
referring and rheumatology physicians (pre-consult exchange), rheumatologists can decide whether patients can be managed by
addressing the clinical questions electronically, or a face-to-face patient evaluation is necessary. We analyzed the effectiveness of gout
management via e-consult compared to PCP and face-to-face rheumatology visits at the VA Medical Center in Long Beach.
Methods: A retrospective study of 133 VA gout patients from 2013 to 2014 was constructed and grouped by their management under
rheumatology e-consults (n = 33), rheumatology clinic visits (n = 52), or PCP visits (n = 37). Electronic medical records were reviewed
for a 24-month period from their initial gout flare or e-consult date. The effectiveness in management was measured by the change in
frequency of gout flares and related emergency department (ED) visits, renal function and serum uric acid levels (sUA).
Results: Of the 48 gout e-consults, 33 cases were resolved electronically, and 15 were converted to rheumatology clinic visits. The wait
time for recommendations from e-consult was 3.7 days. Face-to-face clinic visit took 20.3 days after pre-consult exchange (vs 71.3 days
for direct clinic consult). Compared to PCP managed patients, both e-consult and rheumatology clinic patients have more gout attacks
and related ED visits at baseline (p =0.08). They have fewer attacks in the first 12 months of management, with decreased sUA and
improved renal function (p =0.06), (p =0.1), and are more likely to be treated with allopurinol, colchicine, febuxostat and corticosteroids
than with NSAIDs alone (p <0.05). E-consult management was comparable but second to rheumatology clinical visits (p not
significant), but beyond 12 months, disease activity was stable and similar in all groups.
Conclusion: More effective gout management can be achieved by referring patients with uncontrolled disease to direct rheumatology
visits or e-consults in the first 12 months. Patients can be transitioned to PCP management after 12 months if disease is stable. Overall,
e-consult serves as a reasonable alternative in managing gout. Clinical questions can be addressed electronically resulting in a shorter
wait time and more efficient referrals to the rheumatology clinic.
Disclosure: J. Chang, None; M. DiFiore, None; M. Wong, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-utility-of-electronic-consultation-in-the-

management-of-gout-at-the-veterans-affairs-medical-center
The Ottawa Biologics Safety and Screening Tool

Chrisanna Dobrowolski1, Ines Midzic2, Denise Boone2, Anne McCarthy3, Doug Smith2, John Thomson2, Sheryl Izzi4 and Susan
Humphrey-Murto2, 1Internal Medicine, The Ottawa Hospital - University of Ottawa, Ottawa, ON, Canada, 2Division of Rheumatology,
Department of Medicine, The Ottawa Hospital - University of Ottawa, Ottawa, ON, Canada, 3Division of Infectious Diseases,
Department of Medicine, The Ottawa Hospital - University of Ottawa, Ottawa, ON, Canada, 4Division of Endocrinology, Department of
Medicine, The Ottawa Hospital - University of Ottawa, Ottawa, ON, Canada
SESSION INFORMATION
Background/Purpose : A large proportion of patients with rheumatologic diseases are now being treated with biologic therapies.
Estimates of the use of biologics in patients with rheumatoid arthritis (RA), for example, now range from 30-40%. While biologics
improve disease outcomes, they also increase the risk of infections, autoimmunity, and possibly malignancy. Screening for these
conditions, as well as completion of routine vaccinations, has shown to decrease complication rates. Despite these benefits, compliance
with current guideline recommendations tends to be low in practice. Development of The Ottawa Biologic Safety & Screening Tool
(OBSST) is a quality initiative at The Ottawa Hospital with the objective to increase compliance with guideline recommendations and
ultimately improve patient safety. The Ottawa Hospital is an academic teaching hospital in Ontario, Canada with 1,122 beds, facilitating
1.155 million ambulatory care visits each year. Our rheumatology clinic serves more than 880 patients using biologic therapies.
Methods: A chart review of randomly selected patients (n=50) who started a biologic treatment at our centre from 2011 to 2013
revealed baseline rates of compliance with guidelines. American College of Rheumatology and Canadian Rheumatology Association
Guidelines for treatment of rheumatoid arthritis were used to determine screening goals (Singh et al, 2012; Bombardier et al, 2011-
2012). The OBSST was then developed using a Nominal Group Technique, and implemented by a multidisciplinary team. OBSST is a
checklist reviewing 1) patient characteristics which may preclude the use of certain biologics, 2) recommended laboratory and imaging
screening, and 3) vaccination counselling. After one year of OBSST use, a chart review of randomly selected patients (n=50) initiating
biologic therapy from October 2015 to September 2016 was completed. Descriptive statistics are reported for pre- and post-
implementation rates.
Results: Following implementation of the OBSST, rates of documented Hepatitis B serology increased significantly from 50% to 94%
(25/50 to 47/50 patients, P<0.0001). Hepatitis C serology documentation showed similar rates of improvement, from 46% to 98%
(23/50 to 49/50 patients, P<0.0001). Prior to the implementation of OBSST, the rate of documented vaccination counselling was low;
6% of patients (3/50) had documented counselling regarding influenza, herpes zoster, and pneumococcal vaccines. With the OBSST,
vaccination counselling increased to 98% (49/50, P<0.0001) for influenza, 96% (48/50, P=0.0003) for herpes zoster, and 94% (47/50,
P<0.0001) for pneumococcal vaccines. Screening rates for tuberculosis with a TB skin test and chest X-ray were relatively high at
baseline. Rates increased with OBSST but not reach statistical significance.
Conclusion: The Ottawa Biologics Safety & Screening Tool, administered by a multidisciplinary team, led to significantly increased
rates of recommended screening and vaccine counselling of patients starting biologic therapies. Use of a standardized tool, combined
with a team approach, may be beneficial in aligning institutional practices with current guideline recommendations when initiating
biologics.
Disclosure: C. Dobrowolski, None; I. Midzic, None; D. Boone, Novartis Pharmaceutical Corporation, 5; A. McCarthy, None; D.
Smith, None; J. Thomson, None; S. Izzi, None; S. Humphrey-Murto, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-ottawa-biologics-safety-and-screening-tool
Effectiveness of the Outreach Model for Rheumatology Specialty Clinics to On-

Reserve First Nations in Canada: System-Level and Individual Measures of
Performance and Outcomes
Sujay Nagaraj1, Claire Barber2, Margaret Kargard3, Tyler White3 and Cheryl Barnabe4, 1McCaig Institute for Bone and Joint Health,
University of Calgary, Calgary, AB, Canada, 2Medicine, University of Calgary, Calgary, AB, Canada, 3Siksika Health Services, Siksika,
AB, Canada, 4Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
SESSION INFORMATION
Background/Purpose: Inflammatory arthritis (IA) disproportionately affects Canada’s First Nations population. A Model of Care
(MoC) consisting of rheumatology specialty services embedded in the primary care context on-reserve was instituted to reduce barriers
to care and improve treatment outcomes. This study assessed the system-level performance of the MoC as well as its effectiveness on
disease activity measures and patient-reported outcomes over 7 years (2011 - 2017) at one centre.
Methods: Patients with incident and prevalent IA were enrolled in a longitudinal cohort. Clinical characteristics, disease activity
measures, and treatment recommendations were systematically recorded over follow-up. System-level performance was evaluated
according to established measures including: wait times for new referral, proportion of patients seen in yearly follow-up, proportion of
patients prescribed DMARD treatment, and time to DMARD initiation. Treatment escalation (new DMARD or biologic prescribed) was
characterized in relation to disease activity state at each visit. Mixed-model regression was performed to determine rates of change for
disease activity measures over time, with adjustment for baseline demographics and disease activity measures.
Results: 59 participants (78% female, mean age 47 (SD 13)) with IA (n=39 RA, n=7 PsA, n=7 SLE and related CTD, n=3 JIA, n=1
SpA, n=2 crystal arthritis; 29 with incident and 30 with prevalent disease, mean 16 (SD 13) years duration) were followed for a mean of
29 (SD 23) months with a mean of 6 (SD 5) visits per participant.
At the system-level, the 50th and 90th percentile wait times were 69 and 695 days, respectively. Only 33% of patients were seen in the
benchmark waiting time of 4 weeks but 83% of patients were followed up in each measurement year. Nearly all (96%) of patients
received a DMARD in each measurement year and 90% were prescribed a DMARD within 2 weeks of diagnosis.
At the baseline visit, 70% of participants were in DAS28 moderate or high disease activity. Treatment was escalated at 60% of visits
where the individual was in moderate or high disease activity. Swollen and tender joint counts significantly improved during follow-up
(SJC28 adjusted slope -0.16, 95%CI -0.27 to -0.05, p=0.004; TJC28 adjusted slope -0.16, 95%CI -0.32 to -0.0057, p=0.04.). Pain
(adjusted slope -0.014, 95%CI -0.70 to -0.04, p=0.62), MD Global (adjusted slope -0.028, 95%CI -0.095 to 0.040, p=0.42), HAQ
(adjusted slope 0.0028, 95%CI -0.0088 to 0.014, p=0.64), and DAS28 (adjusted slope -0.038, 95% CI -0.078 to 0.0016, p=0.060) did
not significantly improve over time. Patient global continued to increase over time (adjusted slope 0.081, 95%CI 0.025 to 0.137,
p=0.005). No significant differences were found in a sensitivity analysis comparing outcomes for incident and prevalent patients.
Conclusion: Evaluation of the MoC highlighted areas for further improvement. The program met several system-level performance
measure targets however patients still experience long wait times. Despite improvement in swollen and tender joint counts, disease
activity measures and patient-reported outcomes did not significantly improve during follow-up. This suggests that there are still gaps in
meeting relevant outcomes.
Disclosure: S. Nagaraj, None; C. Barber, None; M. Kargard, None; T. White, None; C. Barnabe, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effectiveness-of-the-outreach-model-for-

rheumatology-specialty-clinics-to-on-reserve-first-nations-in-canada-system-level-and-individual-measures-of-performance-and-
outcomes
A Model for Improved Management of Fragility Fractures: Navigating the Fracture

Liaison Service
Marcy B. Bolster1, Smriti Cevallos2, Lisa Beyer2, Henry M. Kronenberg2 and Ben Leder2, 1Massachusetts General Hospital, Boston,
MA, 2Endocrine, Massachusetts General Hospital, Boston, MA
SESSION INFORMATION
Background/Purpose: Fragility fractures are associated with significant morbidity, mortality and healthcare costs, yet most fracture
patients are neither evaluated nor treated for their underlying osteoporosis (OP). A Fracture Liaison Service (FLS) can improve OP
treatment in patients with fragility fractures, including hip fractures. Our model uses a physician assistant Navigator to coordinate
interdisciplinary care and provide a seamless transition between inpatient surgical care and outpatient OP management. The Navigator
enhances patient education, facilitates communication amongst all providers, performs diagnostic evaluation as warranted, and initiates
OP treatment.
Methods: A patient-centered care algorithm (Figure 1) begins in the Emergency Department (ED), continues for inpatient hospital care
with Geriatric, FLS and Orthopaedic co-management, and the FLS Navigator then transitions care to the outpatient setting (orthopaedic
clinic). Communication between the FLS Navigator and patientÕs PCP occurs at each step.
Results: A comparison of outcomes (Table 1) is made from 1/1/2013-12/31/2013 (Group 1, pre-MGH FLS) to 2/1/2016-1/31/2017
(Group 2, year 1 of MGH FLS). There were 314 hip fragility fractures in Group 1 (66% female, 83% age ≥ 65 years), and 259 fragility
fractures in Group 2 (71% female, 91% age ≥ 65 years).
Of 314 Group 1 inpatients treated for a hip fragility fracture, 127 (40%) had a PCP in our health care system. Treatment was prescribed
for 7 of 127 (5.5%) patients within 6 months of hip fracture and 11/314 (3.5%) were seen by an OP specialist within 1 year of fracture.
Of 259 Group 2 inpatients, 102 (39%) were seen as an outpatient by the FLS Navigator in the orthopaedic clinic or by a specialist in OP
clinic. Of Group 2 patients, 68 (26%) declined a follow up appointment with the FLS Navigator and 32 (12%) did not keep the FLS
outpatient appointment. Preliminary data reveal that 62 of 259 (24%) Group 2 patients were receiving OP therapy 6 months post-
hospitalization, a greater than 4-fold increase compared to Group 1 (additional data not available for many Group 2 patients due to
insufficient time since fracture).
Conclusion: The MGH FLS utilizes an innovative model to improve health outcomes, including morbidity, mortality and reduced
healthcare costs, in a high risk population. Future goals include increasing the FLS scope to ensure all patients admitted with all
fragility fractures are evaluated, improving 6-month treatment rates to >80%, expanding the FLS to fracture patients not requiring
inpatient care, and using telemedicine to develop networks with regional hospitals.
Disclosure: M. B. Bolster, Johnson and Johnson, 1,Eli Lilly and Company, 2,Rheumatology Research Foundation Amgen Fellow
Award, 9; S. Cevallos, None; L. Beyer, None; H. M. Kronenberg, Amgen, 2,Chugai, 2,Novartis Pharmaceutical Corporation, 5; B.
Leder, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-model-for-improved-management-of-fragility-

fractures-navigating-the-fracture-liaison-service
Increasing Lipid Panel Monitoring in a Rheumatology Clinic

Anju Mohan1 and Beth Scholz2, 1Internal Medicine-Rheumatology, University of Texas Health Science Center at Houston, Houston,
TX, 2Internal Medicine - Rheumatology, University of Texas Health Science Center at Houston, Houston, TX
SESSION INFORMATION
Background/Purpose:
Patients with autoimmune conditions are at increased risk for cardiovascular disease (CVD) compared to the general population. It is
not routine practice at UT Rheumatology to manage lipids. Since rheumatologists often play the role of PCP for patients with
autoimmune diseases, they are at a unique position to modulate the CVD risk. Our aim was to increase the percentage of patients with
an annual lipid panel checked to 50% and to prescribe statin therapy for LDL more than or equal to 190 or if the 10-year risk for
atherosclerotic cardiovascular disease (ASCVD) is more than or equal to 7.5%.
Methods:
Patients over 18 years of age with RA, SLE, Psoriatic arthritis, Polymyositis and Dermatomyositis were included in this study. This
quality improvement project was undertaken by a single attending provider at a single clinic location. The baseline data from chart
review was collected from July 2016 to August 2016. The post-intervention data was collected in 3 phases between December 2016 and
May 2017. For the first phase of intervention a reminder card with a flowchart was attached to the work stations, and ASCVD risk
calculator was downloaded to the providerÕs cell phone. For appropriate patients, lipid profiles were ordered and ASCVD risk
calculated. If indicated, atorvastatin was prescribed. During the second intervention phase, in addition to the above the provider
reviewed the daily schedule and printed appropriate lab orders for each patient the day prior to the visit.
Results:
During baseline period, lipid profiles were ordered on 20% of appropriate patients (5/30) with 13% (4/30) on statins. After the first
intervention, lipids were checked in 33% (12/36) with 13.8% (5/36) on statins. During the second intervention phase, lipids were
checked in 77% (10/13) with 23% (3/13) on statins. During maintenance (about 3 months later), lipids were ordered on 81% (13/16)
with 25% (4/16) placed on statins. It was also noted that 5 of the 65 patients in the intervention phases declined having lipid panel
measured.
Conclusion:
The initial intervention did not result in significant improvement. For the second intervention, pre-clinic reviews with labs checks were
performed, which increased success. Next steps will involve spread to other rheumatology providers in the clinic and interventions to
increase appropriate prescribing of statins based on lipid panel results.
Disclosure: A. Mohan, None; B. Scholz, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/increasing-lipid-panel-monitoring-in-a-

rheumatology-clinic
Clinical Significance of RNP Antibodies in Diagnosis of Systemic Autoimmune

Rheumatic Disease When Detected By Multiplex Immunoassay
Heather Bukiri1, Amish Dave2, Erin Bauer2, Vivian Stone2, Chris Chong3 and Punam Verma4, 1Graduate Medical Education, Virginia
Mason Medical Center, Seattle, WA, 2Rheumatology, Virginia Mason Medical Center, Seattle, WA, 3Virginia Mason Medical Center,
Seattle, WA, 4Microbiology/Immunology General Lab, Virginia Mason Medical Center, Seattle, WA
SESSION INFORMATION
Background/Purpose: A large multicenter healthcare system recently adopted multiplex immunoassay as an initial screen for
antinuclear antibody (ANA) with confirmatory reflex testing by immunofluorescence antibody assay (IFA). When both are positive, a 3-
tiered cascade reporting algorithm is activated (Figure 1A). This ANA testing method led to an increase in rheumatology referrals for
RNP antibody (ab) positivity in patients lacking clinical features of systemic autoimmune rheumatic diseases (SARD). We conducted a
multiphase quality improvement project to determine the clinical significance of RNP ab positivity.
Methods: A retrospective review of all ANA tests completed at our institution was conducted from July to September 2016. Specimens
positive in the multiplex assay were further reviewed for both RNP ab and ANA by IFA positivity. A titer of ≥ 1:160 was considered
positive. Positive RNP ab results (> 1 antibody index (AI)) were characterized as either low (1-3 AI) or high (>3 AI). Two independent
physicians conducted chart review on all RNP results to determine if diagnosis of SARD was made. Methods are summarized in Figure
2.
Results: Of 1058 ANA multiplex performed, 183 were positive (17.3%) and 60 were positive for RNP ab. Of the 60 RNP ab positive
samples, 28 had negative ANA IFA testing (47%). One-hundred and twenty-three ANAs were positive both multiplex and IFA (11.6%),
32 of which were also RNP ab positive (26.2%). Fifteen out of 32 were positive to only RNP ab, and negative to abs to all other
extractable nuclear antigens (ENAs). Thirteen of those 15 patients (87%) had no evidence of SARD. PPV for SARD among RNP ab
positive patients, sorted by AI is summarized by Table 1.
Conclusion: Within our testing, an isolated positive RNP ab has a poor PPV for SARD and likely represents type I error. When RNP ab
is positive with ≥ 1 additional ab to ENA, there is a higher probability for SARD. The highest probability for SARD exists when RNP
ab is >3 AI with ≥ 1 additional ab to ENA. Healthcare systems should consider a modified algorithm for reporting RNP positivity as
either low (1-3 AI) or high (>3) to help clarify the clinical significance of RNP ab positivity with multiplex testing (Figure 1B).
Disclosure: H. Bukiri, None; A. Dave, None; E. Bauer, None; V. Stone, None; C. Chong, None; P. Verma, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/clinical-significance-of-rnp-antibodies-in-diagnosis-

of-systemic-autoimmune-rheumatic-disease-when-detected-by-multiplex-immunoassay

Investigating Opportunities for Cost Conscious Care: A Review of Physician Practice
in Ordering Anti-Nuclear Antibody Testing at an Academic Community Hospital
Hrudya Abraham, Jorge Espinal and Sindhu Joseph, Internal Medicine, MacNeal Hospital, Berwyn, IL
SESSION INFORMATION
Background/Purpose:
More than 94,000 ANA tests are performed each year resulting in an estimated cost of 2.24 million dollars annually. The American
College of Rheumatology Choosing Wisely Campaign emphasizes the appropriate use of autoantibody testing focusing on high value
and cost conscious care. Besides rheumatologic diseases, positive ANA results can be seen in several non-rheumatic pathologies and in
normal healthy individuals. Improper use of immunologic testing can result in misdiagnosis, patient concerns, inappropriate therapy and
wasted health care resources. We sought to review physician practicing habits of utilizing the ANA screen prior to ordering ANA panel,
unless otherwise warranted in specific clinical settings.
Methods:
We conducted a retrospective chart review of patients aged 18 years or older admitted to our teaching hospital from Jan 1st, 2012 to
December 31st, 2014 who had an ANA screen and/or an ANA panel ordered. Fifty percent of these charts were selected using a random
number generator and a total of 625 charts were reviewed. Data was collected on the ANA test that was ordered, date of the test
performed, result of the tests, history of prior SLE, history of other autoimmune diseases, and prior positive ANA testing.
Results:
Of the 625 patient charts that were reviewed, five patients (0.8%) had a preexisting diagnosis of SLE and 20 patients (3.2%) had
previously been diagnosed with non-SLE autoimmune disorders. 208 (33%) patients had an ANA screen ordered, and 417 (67%) had
only an ANA panel. Of those patients who had an ANA screen ordered (208), 73% appropriately had the ANA screen ordered first, and
27% had an ANA screen ordered at the same time or after the ANA panel. In those patients who had an ANA screen ordered, 91% of
those screens were negative and 9% were positive. Interestingly, in those patients where only an ANA panel was ordered without any
prior ANA screening, only 0.05% (2/417) was actually positive.
Conclusion:
Sixty six percent (417) of patients had an ANA panel ordered without an ANA screen, of which 99.5% were negative, leading to an
estimated excess cost of 342,254 dollars over 3 years in this test alone. Our Electronic Medical Recording system has different ANA
testing options which currently includes the option to only order an ANA panel without the ANA screen. An expanded ANA panel
without specific clinical suspicion may result in falsely positive results leading to unnecessary workup. Our next step in implementing
change is to remove the option of ‘ANA panel only’ in our Electronic Medical Recording system, and to replace it with ‘ANA screen
with reflex to ANA pattern, titer and panel’ to avoid unnecessary testing.
Disclosure: H. Abraham, None; J. Espinal, None; S. Joseph, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/investigating-opportunities-for-cost-conscious-care-

a-review-of-physician-practice-in-ordering-anti-nuclear-antibody-testing-at-an-academic-community-hospital
Glucose-6-Phosphate Dehydrogenase Testing in a US Veterans Healthcare System:

Are We Ordering Unnecessary Tests?
Tracy Driver1, Kevin Hsu2, Meika A. Fang3 and Ari Weinreb3, 1Medicine, Rheumatology, David Geffen School of Medicine at
UCLA, Los Angeles, CA, 2Cedars-Sinai Medical Center, Los Angeles, CA, 3VA Greater Los Angeles Healthcare System, Los Angeles,
CA
SESSION INFORMATION
Background/Purpose:
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic defect that causes a non-immune hemolytic anemia
affecting more than 400 million people worldwide. When initiating medications with oxidant potential such as sulfasalazine (SSZ),
patients are frequently tested for G6PD deficiency. The objectives of this study include determining the prevalence of G6PD deficiency
among those tested and characterizing G6PD test ordering patterns.
Methods:
Retrospective chart review was performed using the electronic medical record at the VA Greater Los Angeles Healthcare System. The
database was searched for all patients who had a G6PD test ordered between 2009-2014. Data collected included demographics, reasons
G6PD testing was done, number of patients who underwent repeat testing, and the specialty of the provider who ordered the test.
Prevalence of G6PD deficiency was determined. Descriptive analysis of categorical variables was done with the Chi-Square test. The
odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the association between ethnicity and G6PD deficiency.
Results:
G6PD levels were measured in 737 patients. The study population included 661 males (89.7%) and 76 females (10.3%) with a mean age
of 56.6 (± SD 14.9). There were 60 (8.1%) patients with G6PD deficiency. The percentage of patients with G6PD deficiency by gender
and within each self-reported race/ethnicity was as follows: 8.4% (N=56) males, 5.3% (N=4) females, 18.2% (N=2) American Indian,
17.9% (N=47) African American, 7.7% (N=2) Asian, 2.5% (N=7) Caucasian, 1.1% (N=1) Hispanic, and 100% (N=1) Brazilian.
Observed differences in G6PD deficiency prevalence were statistically significant based on gender and self-reported race/ethnicity
(p<0.001 for both). Odds ratios were calculated to evaluate the association between race/ethnicity and G6PD deficiency: African
American (OR 7.77, [95% CI 4.12-14.66]), American Indian (OR 2.56, [95% CI 0.54-12.12]), Asian (OR 0.94, [95% CI 0.22-4.07]),
Caucasian (OR 0.20, [95% CI 0.09-0.45]), and Hispanic (OR 0.11, [95% CI 0.02-0.82]). Repeated testing was carried out in 105
(14.2%) patients. Reasons for G6PD testing included initiation of SSZ for inflammatory arthritis (52.3%), dapsone for PCP prophylaxis
(14.2%), and anemia workup (11.1%). Rheumatology ordered the majority of repeat tests (60.7%) for the following reasons: SSZ (65),
hydroxychloroquine initiation (1), anemia workup (4), and dapsone initiation (4).
Conclusion:
G6PD deficiency occurred in 8% of our study population, mainly in African Americans, American Indians, and Asians.
Rheumatologists ordered most of the tests measuring G6PD levels primarily before considering SSZ therapy and were more likely to
order duplicate tests when compared to other specialists. Unnecessary repeat testing is an issue that could be reduced with pop-up
computer reminder. This study supports G6PD deficiency testing for high risk populations, including African Americans, American
Indians, and Asians, but routine screening of all rheumatology patients for G6PD deficiency when considering SSZ therapy may not be
needed.
Disclosure: T. Driver, None; K. Hsu, None; M. A. Fang, None; A. Weinreb, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/glucose-6-phosphate-dehydrogenase-testing-in-a-us-

veterans-healthcare-system-are-we-ordering-unnecessary-tests
Hepatitis B Reactivation in Rheumatologic Patients

Yassir Daghistani1, Fergus To2, Patrick Doyle3,4, Hin Hin Ko5, Mel Krajden3,4, Jason Kur2, Alnoor Ramji6, Kam Shojania2, Edward
Tam5, John Wade2, Eric Yoshida5, Graham Reid2, Siegfried Erb5 and Mollie Carruthers2, 1Medicine, University of British Columbia,
Vancouver, BC, Canada, 2Rheumatology, University of British Columbia, Vancouver, BC, Canada, 3Pathology and Laboratory
Medicine, University of British Columbia, Vancouver, BC, Canada, 4BC Centre for Disease Control, Vancouver, BC, Canada,
5Gastroenterology, University of British Columbia, Vancouver, BC, Canada, 6Gatroenterology, University of British Columbia,
Vancouver, BC, Canada
SESSION INFORMATION
Background/Purpose: The widespread usage of biologic disease modifying anti-rheumatic drugs (bDMARDs) in rheumatology has
increased the risk of hepatitis B virus (HBV) re-activation. The prevalence of chronic HBV infection was estimated at 3.0% and 3.5%,
respectively in two large, cross-sectional studies in rheumatoid arthritis and spondyloarthropathies internationally. HBV reactivation
(HBVr) after using immunosuppressive medicines has been observed in 6.8% of fulminant hepatitis cases in Japan. We aimed to
quantify the knowledge gap in the practice of rheumatologists with regards to management of HBVr in rheumatologic patients using a
Canada-wide survey.
Methods: In order to assess the discrepancy in practice with regards to dealing with HBV infection in patients started on biologic and
non-biologic DMARDs, we conducted a short pilot survey of 15 rheumatologists and 2 rheumatology fellows at an inter-city
rheumatology rounds aimed at assessing any knowledge gap. Subsequently, an expert panel of five hepatologists, two infectious disease
specialists and four rheumatologists helped generate a final questionnaire. The final survey included questions regarding chronic
hepatitis B monitoring and anti-viral prophylaxis with either biologic or non-biologic DMARDs or corticosteroids. A Canada-wide
survey was sent to the Canadian Rheumatology Association (CRA) members. The results were compared to the American
Gastroenterology Association (AGA) guidelines.
Results: There were 17 respondents to the pilot survey. Of 7 questions in the pilot survey, there were 47% of questions that were either
answered incorrectly or marked “I don’t know”. The final survey was sent to 521 members of CRA. The response rate was 27.25% for a
total of 142 responses. Interestingly, 8.8% of the responders thought not to send their HBsAg positive patients to a gastroenterologist,
although anti-viral prophylaxis would be indicated and hepatology monitoring. There were 58% of the respondents who would order
unnecessary test like anti-HBs for monitoring a patient who is HBsAg positive and is on immunosuppressive medication. Another 43%
answered incorrectly to start anti-viral prophylaxis for patients who are HBsAg positive and are on DMARDs.
Conclusion: The results of our survey highlight the knowledge gap in monitoring and treating chronic hepatitis B in rheumatology
patients. All patients with hepatitis B surface antigen positivity on immunosuppression including prednisone should be referred to
gastroenterology. Similarly, patients on high risk medicines with hepatitis B core antibody positivity despite hepatitis surface antibody
status should be monitored and started early on anti-viral prophylaxis.
Disclosure: Y. Daghistani, None; F. To, None; P. Doyle, None; H. H. Ko, None; M. Krajden, None; J. Kur, None; A. Ramji, None;
K. Shojania, None; E. Tam, None; J. Wade, None; E. Yoshida, None; G. Reid, None; S. Erb, None; M. Carruthers, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/hepatitis-b-reactivation-in-rheumatologic-patients
Communication between Inpatient and Outpatient Specialty Clinicians: Developing a

Better Understanding of Patients with Rheumatoid Arthritis Who Are Admitted to
the Hospital
Abraham Tacang1, Christina Downey2, Alfred Denio1, Eric Newman3 and Lisa L. Schroeder4, 1Rheumatology, Geisinger Medical
Center, Danville, PA, 2Geisinger Medical Center, Danville, PA, 3Department of Rheumatology, Geisinger Medical Center, Danville, PA,
4Rheumatology, Geisinger Health System, Danville, PA
SESSION INFORMATION
Background/Purpose:
Effective communication is essential in caring for medically complex patients with rheumatoid arthritis (RA). Communication between
clinicians becomes even more crucial when a patient gets admitted to the hospital. Our study aims to investigate how often
communication gaps occur at our institution, focusing primarily on RA patients, and subsequent consequences.
Methods:
This is a retrospective cohort study of RA patients admitted to our institution from July 1, 2015 to June 30, 2016. All patients were seen
by a rheumatologist at least twice within a 14-month period prior to the admission date. Data gathered include: admission type based on
principal diagnosis (infection, cardiac, surgical, other), baseline glucocorticoid and immunosuppressive therapy, rheumatology service
notification of a patient’s current or upcoming admission and communication mode (inpatient consult, clinic visit, telephone encounter,
discharge instructions or summary), flare up and/or glucocorticoid dose increase up to 3 months after discharge, appropriate
preoperative C-spine xray, appropriate medication continuation or discontinuation, and appropriate re-initiation of discontinued
medications.
Results:
Two hundred twenty-nine admissions were included. Rheumatology was notified 57.6% of the time across all admission types.
Medications (immunosuppressive and/or glucocorticoid) were appropriately held 36.4% of the time. Medications were rightfully
continued for 73% of our patient cohort. Nineteen percent of our patients developed a flare within 3 months after discharge. Only 11%
of our patients admitted for surgery had a preoperative C-spine xray. Among our surgical patients, 4 developed non-life-threatening
infection and 1 patient had wound healing issues within 3 months after surgery.
Conclusion:
Our retrospective study highlights both gaps in communication between rheumatology and admitting services, and in the care of RA
patients admitted to the hospital. To our knowledge, this is the first study to investigate these gaps, and subsequent consequences,
among RA patients followed in a large integrated healthcare system. One potential intervention to address the problem in
communication is integrating an automated notification system within our electronic record to inform rheumatology clinicians when one
of our RA patients is scheduled for an elective surgery, or gets admitted to the hospital. To bridge gaps in patient care, we are exploring
ways to increase our rates of appropriate preoperative C-spine xrays, as well as appropriate medication continuation or discontinuation
among our RA patients. This will be done through collaboration with our surgeons to establish a standardized evidence-based approach
to the perioperative management of patients with RA.
Table 1. Summary data of hospital admissions, Rheumatology notification, and patient outcomes
Disclosure: A. Tacang, None; C. Downey, None; A. Denio, None; E. Newman, None; L. L. Schroeder, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/communication-between-inpatient-and-outpatient-

specialty-clinicians-developing-a-better-understanding-of-patients-with-rheumatoid-arthritis-who-are-admitted-to-the-hospital
Systematic Physician Assessment Beyond Inflammation in Routine Rheumatology

Care Using Visual Analog Scale Scores for Inflammation, Damage, and Distress to
Document Patient Status and Support Clinical Decisions: Analysis of Inter-Rater
Reliability
Shakeel M. Jamal1, Theodore Pincus2, Isabel Castrejón2, Jacquelin R. Chua1, Aman Kugasia1, Juan Schmukler1, Stacy Weinberg1 and
Joel A. Block3, 1Division of Rheumatology, Rush University Medical Center, Chicago, IL, 2Rheumatology, Rush University Medical
Center, Chicago, IL, 3Rush University Medical Center, Chicago, IL
SESSION INFORMATION
Background/Purpose: A physician global estimate of patient status (DOCGL) on a 0-10 visual analog scales (VAS) is as effective as
any rheumatoid arthritis (RA) Core Data Set measure to quantify inflammatory activity in patients selected for clinical trials1. However,
in routine care, DOCGL may be affected by joint damage and/or distress (e.g., fibromyalgia, depression, etc.), in addition to
inflammation. Different physicians may consider these findings variably in formulating DOCGL. One approach to document the
contribution of inflammation, damage, and distress to DOCGL is for the physician to complete 3 additional 0-10 VAS. We analyze inter-
rater reliability between two rheumatologists for DOCGL and 3 VAS subscales for inflammation, damage, and distress.
TABLE: Mean and SD for the four physician estimates according to the rheumatologist (rheum) and the fellow, intraclass
correlations and levels of concordance and discordance for each estimate. *p<0.003
VAS (0-10) Rheum Fellow Mean Intraclass Correlation Rheumatologist (Rheum) and Fellows
Difference (95% Confidence concordance and discordance by 2/10 units,
Mean (SD) Mean (SD) Interval) number (%)
Rheum> Rheum= Rheum<
Fellow Fellow Fellow

Overall DOCGL 3.8 (1.9) 3.8 (2.2) 0.01 0.63 (0.46, 0.75) 22 (22%) 73 (68%) 12 (11%)
DOCINF 1.8 (1.5) 1.5 (1.6) 0.25 0.74 (0.62, 0.82) 7 (7%) 91 (85%) 9 (8%)
DOCDAM 2.7 (2.2) 2.7 (2.2) -0.04 0.80 (0.70, 0.86) 20 (19%) 76 (71%) 11 (10%)
DOCSTR 3.2 (3.0) 2.2 (2.4)* 1.02 0.69 (0.55, 0.79) 11 (10%) 68 (63%) 28 (26%)
Methods: At one academic site, 4 VAS for overall DOCGL, and levels of inflammation [or reversible findings] (DOCINF), organ
damage [or irreversible findings] (DOCDAM), and distress [or symptoms not explained by inflammation or damage such as
fibromyalgia, depression] (DOCSTR), are scored in patients with all rheumatic diagnoses in routine care. At a weekly fellows’ clinic,
the four 0-10 VAS estimates scores were recorded independently by a senior rheumatologist and a rheumatology fellow at the same
visit. The estimates of the 2 observers for each subscale were analyzed for mean levels, differences, intraclass correlation coefficients
(ICCs), and possible discordance - defined as a difference of 2 units/10 between the 2 observers.
Results: Estimates of 2 rheumatologists were analyzed in 107 patients with different rheumatic diseases. Mean differences ranged from
0.01 for DOCGL to 1.02 for DOCSTR, significant only for DOCSTR (Table). The ICC ranged from 0.63 (DOCGL) to 0.80
(DOCDAM), a range higher than for joint counts2. Concordance of estimates (within 2/10 units) ranged from 63% (DOCSTR) to 85%
(DOCINF).
Conclusion: Good agreement between two observers with different levels of clinical experience was seen for 4 physician 0-10 VAS
estimates for overall global assessment, inflammation, damage, and distress. These data extend evidence for the value of physician VAS,
as DOCGL distinguishes active from control treatments in rheumatoid arthritis (RA) clinical trials more efficiently than joint counts or
laboratory tests1. Mean scores for damage and distress were higher than for inflammation, indicating the possible value for doctors,
patients, and payers of quantitating damage, in addition to inflammation, to document patient status and support clinical decisions in
routine care.
References: 1. Clin Exp Rheumatol. 2014;32 Suppl 85(5):47-54. 2.Ann Rheum Dis. 2009;68(6):972-5. 2. Bull NYU Hosp Jt Dis.
2008;66(3):216-23
Disclosure: S. M. Jamal, None; T. Pincus, Theodore Pincus, 7; I. Castrejón, None; J. R. Chua, None; A. Kugasia, None; J.
Schmukler, None; S. Weinberg, None; J. A. Block, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/systematic-physician-assessment-beyond-
inflammation-in-routine-rheumatology-care-using-visual-analog-scale-scores-for-inflammation-damage-and-distress-to-document-
patient-status-and-support-clinical
Choosing Unwisely: HLA-B27 Testing and Adherence to Choosing Wisely Practices

in a Large Integrated Academic Healthcare System
Marc W. Nolan1,2, Morgan M. Brown3 and Elie Gertner1,2, 1Section of Rheumatology, Regions Hospital, St. Paul, MN, 2Division of
Rheumatology, University of Minnesota Medical School, Minneapolis, MN, 3HealthPartners Institute, St. Paul, MN
SESSION INFORMATION
Background/Purpose:
The ACR in 2013 and the Canadian Rheumatology Association (CRA) in 2015 published their respective Choosing Wisely
recommendations to promote evidence-based care and reduce medical services that may have questionable value. HLA-B27 testing was
#7 in ACR’s and #2 in CRA’s Choosing Wisely list of recommendations. HLA-B27 testing is not to be ordered unless features
suggestive of a SpA are present. We sought to assess adherence to CRA’s Choosing Wisely recommendations (presence of 2 or more
features or 1 feature with radiographic sacroiliitis) by primary care physicians (PCP) ordering HLA-B27 within a large integrated
healthcare system and to identify additional areas for quality improvement.
Methods:
Retrospective analysis of all patients who had HLA-B27 testing at Regions Hospital/Health Partners, a large academic vertically and
horizontally integrated healthcare system, from 1/1/2014 - 7/1/2015. Chart review identified features of SpA (defined as inflammatory
back pain > 3 months with onset < 45 years old, peripheral synovitis, enthesitis, dactylitis, psoriasis, or uveitis) at the time of HLA-B27
testing. We assessed if any imaging (Xray, CT, or MRI) identifying sacroiliitis +/- 6 months from HLA-B27 order was present, the
presence of inflammatory markers (ESR or CRP) +/- 1 month from the HLA-B27 order, and if an eventual diagnosis of SpA was made.
Data were analyzed to generate descriptive information regarding frequency, demographics, as well as a cost analysis.
Results:
During the 18 months, a total of 627 tests were ordered; 336 by Rheumatologists, 68 by Ophthalmology, and 223 by PCPs. Age ranged
from 1 to 92 years. We focused on PCP ordered HLA-B27 testing habits. Applying Choosing Wisely recommendations, only 31 of 223
tests (13.9%) were ordered correctly; 20 (9%) had two or more features, and 11 (4.9%) had one feature with a positive imaging result.
Even if ONE feature alone was allowed to be an indication for testing (as opposed to the CRA recommended TWO), only 38.1% of tests
were ordered correctly. In comparison, 80% of tests ordered by rheumatologists had one feature and 35% had at least two. The average
cost of HLA-B27 test within our payer system is $70-100. Thus, a cost savings of $15,000-20,000 would have occurred if ordered
correctly. This does not include secondary costs of referrals to specialists for positive results.
Conclusion:
Improperly ordered HLA-B27 tests occurred nearly 86% of the time from PCPs within our large integrated healthcare system resulting
in a cost of $15,000-20,000. EMR educational implementation plans have been shown to be effective for quality improvement. We are
planning on utilizing EMR ordering alerts to aid HLA-B27 ordering that is more consistent with Choosing Wisely recommendations
which promote evidence-based care.
Table 1. Demographics and features in HLA-B27 testing between 1/2014 and 7/2015 in a large integrated healthcare system.
N (%), N (%), N (% of total)
PCP Correctly Ordered PCP Incorrectly Ordered

Male 17 (54.84%) 104 (54.17%) 121 (54.26%)
Female 14 (45.16%) 88 (45.83%) 102 (45.74%)
<= 17 years old 0 (0.00%) 26 (13.54%) 26 (11.66%)
>= 18 years old 31 (100.00%) 166 (86.46%) 197 (88.34%)
<= 45 years old 22 (70.97%) 106 (55.21%) 128 (57.40%)
>45 years old 9 (29.03%) 86 (44.79%) 95 (42.60%)
Inflammatory Back Pain 20 (64.52%) 28 (14.58%) 48 (21.52%)

Peripheral Synovitis 13 (41.94%) 7 (3.65%) 20 (8.97%)
Enthesitis 1 (3.23%) 3 (1.56%) 4 (1.79%)
Dactylitis 5 (16.13%) 0 (0.00%) 5 (2.24%)
Psoriasis 11 (35.48%) 9 (4.69%) 20 (8.97%)
Uveitis 3 (9.68%) 7 (3.65%) 10 (4.48%)
Disclosure: M. W. Nolan, None; M. M. Brown, None; E. Gertner, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/choosing-unwisely-hla-b27-testing-and-adherence-

to-choosing-wisely-practices-in-a-large-integrated-academic-healthcare-system
Towards Recommendations on Functional Assessment Status Measures for

Rheumatoid Arthritis: Preliminary Results from a Systematic Review
Claire Barber1, JoAnn Zell2, Jinoos Yazdany3, Aileen Davis4, Linda S. Ehrlich-Jones5, Carter Thorne6, Donna Everix7, Laura
Cappelli8 and Kaleb Michaud9, 1Medicine, University of Calgary, Calgary, AB, Canada, 2National Jewish Medical Center, Denver, CO,
3Medicine/Rheumatology, University of California San Francisco, San Francisco, CA, 4Health Care and Outcomes Rsrch, Toronto
Western Research Institute, University Health Network, Institute of Health Policy, Management and Evaluation, University of Toronto,
Toronto, ON, Canada, 5Rehabilitation Institute Chicago, Chicago, IL, 6Southlake Regional Health Centre, Newmarket, Newmarket, ON,
Canada, 7OnMyCare Home Health, Fremont, CA, 8Division of Rheumatology, Johns Hopkins University School of Medicine,
Baltimore, MD, 9Rheumatology & Immunology, University of Nebraska Medical Center and National Data Bank for Rheumatic
Diseases, Omaha, NE
SESSION INFORMATION
Background/Purpose: Functional status assessment measures (FSAMs) are important outcomes in rheumatology and used to monitor
response to treatment and aid in prediction of rheumatic disease outcomes. We conducted a systematic review of FSAMs used in the
evaluation of patients with rheumatoid arthritis (RA). In this first phase of the study, we report on the identification and characteristics
of the FSAMS. The ultimate objective is to develop American College of Rheumatology (ACR) recommendations for the use of
FSAMs in clinical practice and quality measurement.
Methods: A search strategy was developed in consultation with a medical librarian and based on a published strategy for finding studies
that evaluate the measurement properties of clinical instruments from the COnsensus-based Standards for the selection of health
Measurement Instruments (COSMIN) group. This strategy involves the use of MeSH terms/keywords in three themes: #1 construct
search (functional status), #2 population search (rheumatoid arthritis), #3 instrument search (including terms for instruments of interest).
MEDLINE, EMBASE, Cochrane Library and CINHAL were searched from inception until March 16th 2017. Two reviewers
independently considered papers for inclusion with disagreements resolved by consensus. FSAMs were included if the primary
objective of the study was to develop, validate or establish the psychometric properties of a patient-reported FSAMs. Performance-
based measures (e.g., grip strength, walk tests) and FSAMs addressing function of a single body part/region were excluded. Health
related quality of life or health status measures that only in part addressed function were also excluded as they captured different
constructs.
Results: 11,835 unique citations were found and 649 were selected for full-text review. Twenty-three FSAMs met inclusion criteria
including 7 published variations of the Health Assessment Questionnaire (HAQ). Eleven measures were developed in the USA (48%),
while the remainder were developed in Europe or with international participation. All of the FSAMs were questionnaires varying in
length from 2 to 47 items with the exception of a single visual analogue scale. Eight (35%) FSAMs included questions about the use of
assistive devices and one FSAM was specific to valued life activities. Range of scores was also often based on the original HAQ range
of 0-3 (52% of measures). Where reported, time to administer scores was universally <10 minutes. Preliminary results indicate that the
Patient-Reported Outcomes Measurement Information System (PROMIS) physical function questionnaires were highly robust and were
correlated with the HAQ but had fewer ceiling effects, were sensitive to change and had high convergent validity.
Conclusion: There are 23 FSAMs for RA in the published literature of varying complexity. Further evaluation of the FSAMs along the
9 domains of COSMIN rating (internal consistency, reliability, measurement error, hypothesis testing, responsiveness and validity
(content, structural, criterion and cross-cultural) is presently ongoing and will help determine final ACR recommendations for FSAM
use in clinical practice.
Disclosure: C. Barber, None; J. Zell, None; J. Yazdany, None; A. Davis, Osteoarthritis & Cartilage, 6,OARSI, 6,Ontaril Trillium
Foundation, 2,The Arthritis Society, 2,Bone and Joint Canada, 6; L. S. Ehrlich-Jones, Eation Vance, 1,Abbott Labs, 1,CMS, 2,NIH-
NIAMs, 2,Craig H. Neilsen Foundation, 2,NIDILRR, 2,Rehabilitation Institute of Chicago, 3,Rush University Medical Center,
3,University of Illinois at Chicago, 3,Northwestern University, 3; C. Thorne, AbbVie, Amgen, Celgene, Lilly, Novartis, Pfizer, Sanofi,
and UCB, 2,Medexus/Medac, 8,AbbVie, Amgen, Celgene, Centocor, Genzyme, Hospira, Janssen, Lilly, Medexus/Medac, Merck,
Novartis, Pfizer, Sanofi, and UCB, 5; D. Everix, None; L. Cappelli, Bristol-Myers Squibb, 2; K. Michaud, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/towards-recommendations-on-functional-

assessment-status-measures-for-rheumatoid-arthritis-preliminary-results-from-a-systematic-review
A Genome-Wide Association Study of Gout in People of European Ancestry

Tony R. Merriman1, Murray Cadzow1, Marilyn E. Merriman1, Amanda Phipps-Green1, Ruth Topless1, Abhishek Abhishek2, Mariano
Andrés3, Linda A. Bradbury4, Russell Buchanan5, Katie Cremin6, Erika De Guzman6, Janak de Zoysa7, Michael Doherty8, Catherine
Hill9, Tom W.J. Huizinga10, Tim Jansen11, M. Janssen12, Leo .A.B. Joosten13, Fina Kurreeman14, Susan Lester15, Frederic Liote16,
Donia Macartney-Coxson17, Hirotaka Matsuo18, Geraldine M. McCarthy19, Sally McCormick20, Rinki Murphy21, Karel Pavelka22,
Fernando Perez-Ruiz23, Juan Puig24, Timothy RDJ Radstake25, Philip Riches26, Maureen Rischmueller27, Edward Roddy28, Malcolm
Smith29, Eli A. Stahl30, Blanka Stiburkova31, Richard Stubbs32, Anne-Kathrin Tausche33, Rosa Torres34, Rob Walker1, Ken
Yamamoto35, Matthew A. Brown6, Hyon K. Choi36, Nicola Dalbeth21, Jeffrey N. Miner37, Alexander So38, Lisa K. Stamp39 and Tanya
Major40, 1University of Otago, Dunedin, New Zealand, 2Devision of Rheumatology, University of Nottingham, NG5 1PB, England,
3Reumatología, Hospital General Universitario Alicante, Alicante, Spain, 4Queensland University of Technology, Brisbane, Australia,
5University of Melbourne, Melbourne, Australia, 6Translational Genomics Group, Institute of Health and Biomedical Innovation,
Queensland University of Technology, Translational Research Institute, Brisbane, Australia, Brisbane, Australia, 7Waitemata District
Health Board, Auckland, New Zealand, 8Academic Rheumatology, University of Nottingham, Nottingham, Great Britain, 9Medicine,
The University of Adelaide, Adelaide, Australia, 10Rheumatology, Leiden University Medical Center, Leiden, Netherlands, 11VieCuri
Medical Center, Venlo, Netherlands, 12Department of Rheumatology, Rijnstate Hospital Arnhem, Arnhem, Netherlands, 13Internal
Medicine, Radboud University Medical Center, Nijmegen, Netherlands, 14Department of Rheumatology, Leiden University Medical
Center, Leiden, Netherlands, Leiden, Netherlands, 15Rheumatology, Queen Elizabeth Hospital, Woodville South, Australia,
16University Paris Diderot, Paris, France, 17Institute if Environmental and Scientific Reseacrh, Wellington, New Zealand, 18Department
of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Japan, 19Div of Rheumatology,
Mater Misericordiae University Hospital, Dublin, Ireland, 20Department of Biochemistry, University of Otago, Dunedin, New Zealand,
21University of Auckland, Auckland, New Zealand, 22Institute of Rheumatology, Prague, Czech Republic, 23BioCruces Health
Research Institute, Barakaldo, Spain, 24Hospital Universitario La Paz, Madrid, Spain, 25Rheumatic Diseases, Radboud University
Nijmegen Medical Centre, Nijmegen, Netherlands, 26University of Edinburgh, Edinburgh, United Kingdom, 27Rheumatology, The
Queen Elizabeth Hospital, South Australia, Adelaide, Australia, 28Research Institute for Primary Care and Health Sciences, Keele
University, Keele, United Kingdom, 29Flinders Medical Centre and Repatriation Hospital, Adelaide, Australia, 30Divisions of
Rheumatology and Genetics, Brigham and Women's Hospital, Boston, MA, 31Institute of Inherited Metabolic Disorders, First Faculty of
Medicine, Charles University, Prague, Czech Republic, 32P3 Research Limited, Wellington, New Zealand, 33Medizinische Klinik und
Poliklinik III, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Germany, 34La Paz University
Hospital, Madrid, Spain, 35Department of Medical Chemistry, Kurume University School of Medicine, Kurume, Japan, 36Division of
Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 37Discovery
Biology, Ardea Biosciences, Inc., San Diego, CA, 38Rheumatology, CHUV, Univ of Lausanne, Lausanne, Switzerland, 39University of
Otago, Christchurch, New Zealand, 40Biochemistry, University of Otago, Dunedin, New Zealand
SESSION INFORMATION
Session Title: Metabolic and Crystal Arthropathies Poster I
A genome-wide association study of gout in people of European ancestry
Background/Purpose: Genome wide association studies (GWAS) have provided considerable insight into the molecular control of urate
levels. However, less is known about the progression from asymptomatic hyperuricemia to gout. Our aim was to conduct a GWAS for
gout in people of European ancestry using the largest number of cases of gout to date.
Methods: This GWAS (7,431 cases and 105,631 controls) was comprised of three data sets: a mixed New Zealand (NZ), Eurogout, and
Ardea Biosciences group (3,961 cases; 1,547 controls; genotyped using the Illumina CoreExome v24 array, 547,644 markers), a
composite set from the Health Professionals Follow-Up (HPFS) and NursesÕ Health Studies (NHS) (1,038 cases; 1,095 controls;
genotyped using the Illumina OmniExpress v12 array, 730,525 markers), and UK Biobank (2,432 cases; 102,989 controls; genotyped
using an Affymetrix Axiom array, 820,967 markers). The UK Biobank genotypes were imputed to ~73.3M SNPs. Neither the
NZ/Eurogout/Ardea nor NHS/HPFS genotype sets were imputed. Markers found within all three data sets (234,062) were identified and
associated with gout (adjusted for sex and age), within each data set separately, using PLINK v1.9. An inverse-variance weighted meta-
analysis of the results was then performed using the meta v4.4 package within R v3.2.3. The overall genome inflation factor was 0.90.
Results: There were nine loci with experiment-wide significance (0.05/234,062; P < 2x10-7) for association with gout: ABCG2
(OR=1.77), SLC2A9 (OR=1.69), GCKR (OR=1.24), MLXIPL (OR=1.18), SLC17A1-A4 (OR=1.22), SLC16A9 (OR=1.18), SLC22A12
(OR=1.16), PDZK1 (OR=1.16), TRIM46 (OR=1.15). All nine of these loci have been previously associated with serum urate levels in
genome-wide studies with the urate-increasing alleles also associated with increased risk of gout in this study.
Conclusion: Our data emphasize the central importance of genetic involvement in serum urate levels, compared to the genetic
involvement in MSU crystal formation, or the innate immune response, in determining gout.
Disclosure: T. R. Merriman, Ardea Biosciences, 2; M. Cadzow, None; M. E. Merriman, Ardea Biosciences, Inc, 2; A. Phipps-
Green, None; R. Topless, None; A. Abhishek, AstraZeneca, 7; M. Andrés, None; L. A. Bradbury, None; R. Buchanan, None; K.
Cremin, None; E. D. Guzman, None; J. de Zoysa, None; M. Doherty, None; C. Hill, None; T. W. J. Huizinga, Reasearch grants
from Arthritis Foundation, ZonMW and European Union, 2,Tom WJ Huizinga/the department of rheumatology LUMC has received
lecture fees/consultancy fees from Bristol Myers Squibb, Janssen, Pfizer, Roche, Sanofi-Aventis, Crescendo Bioscience,, Boeringher,
Epirus and Eli Lilly, 5; T. Jansen, None; M. Janssen, None; L. A. B. Joosten, None; F. Kurreeman, None; S. Lester, None; F. Liote,
None; D. Macartney-Coxson, None; H. Matsuo, None; G. M. McCarthy, None; S. McCormick, None; R. Murphy, None; K.
Pavelka, None; F. Perez-Ruiz, Asociacion de reumatologos de Cruces, 2,Grünenthal, 5,Grünenthal, 8,Menarini, 5,Menarini, 8; J. Puig,
None; T. R. Radstake, None; P. Riches, None; M. Rischmueller, None; E. Roddy, None; M. Smith, None; E. A. Stahl, None; B.
Stiburkova, None; R. Stubbs, None; A. K. Tausche, None; R. Torres, None; R. Walker, None; K. Yamamoto, None; M. A. Brown,
None; H. K. Choi, None; N. Dalbeth, Takeda, AstraZeneca, Abbvie, 9; J. N. Miner, Ardea biosciences, 3; A. So, None; L. K. Stamp,
Amgen, 8; T. Major, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-genome-wide-association-study-of-gout-in-

people-of-european-ancestry
Allopurinol Dose Escalation to Achieve Serum Urate below 6mg/Dl: An Open Label
Extension Study
Lisa K. Stamp1, Peter T. Chapman2, Murray Barclay3, Anne Horne4, Christopher Frampton1, Paul Tan5, Jill Drake6 and Nicola
Dalbeth5, 1University of Otago, Christchurch, New Zealand, 2Christchurch Hospital, Christchurch, New Zealand, 3Medicine, University
of Otago, Christchurch, New Zealand, 4Department of Medicine, University of Auckland, Auckland, New Zealand, 5University of
Auckland, Auckland, New Zealand, 6Rheumatology, Immunology and Allergy, Christchurch Hospital, Christchurch, New Zealand
SESSION INFORMATION
Background/Purpose: Allopurinol at higher than CrCL based doses remains controversial due to concerns over increased risk of
adverse events (AE). A recent 12month randomized controlled trial (RCT) reported that allopurinol above CrCL-based doses is effective
and well tolerated. Here, we report the results of the 12month open label extension phase of this RCT. The aims were to determine the
long-term safety and efficacy of allopurinol dose escalation to achieve target serum urate (SU) in people with gout.
Methods: People who completed the first 12months of a randomized, controlled, parallel-group, comparative clinical trial continued
into a 12month open label extension study (from Month 12 to 24). Participants randomised to the control group who continued their
usual dose of allopurinol for the first 12months began allopurinol dose escalation at month 12 if SU was ≥6mg/dl (control (C)/dose
escalation (DE)). Those in the DE arm for the first 12months who had achieved target SU maintained the dose of allopurinol, while
those with SU≥6mg/dl continued dose escalation (DE/DE). Allopurinol was increased monthly until SU was <6mg/dl. The primary
endpoints were reduction in SU and AEs at month 24. Secondary endpoints included the proportion of individuals with gout flares.
Results: Of the 183 participants who entered the study, 143 (78.1%) completed the month 12 visit and 137 (74.9%) completed month
24. The mean (SE) change in SU from month 12 to month 24 was -1.1 (0.2) mg/dl in the C/DE group and 0.1 (0.2) mg/dl in the DE/DE
group (p<0.001) with a mean difference of 1.3mg/dl (95%CI 0.8-1.7), p<0.001). In the C/DE group mean (SE) SU was 7.13 (0.16)
mg/dl at baseline and 5.7 (0.2) mg/dl at final visit, and 7.18 (0.2) mg/dl and 5.4 (0.1) mg/dl in the DE/DE group (Fig). SU was <6mg/dl
at final visit in 69.1% of the C/DE group and 79.7% in the DE/DE group (p=0.16); odds ratio (OR) 1.8 (95%CI 0.8-3.8). There was a
significant reduction in the percentage of individuals having a gout flare in the month prior to month 12 and month 24 in both groups
(p<0.001), but no difference between randomised groups (p=0.29). There were similar numbers of AEs and serious AEs between
groups. Mild elevations of AST, ALT and ALP were noted while some higher grade abnormalities in GGT were observed.
Conclusion: The majority of people with gout can achieve and maintain target SU with dose escalation of allopurinol above CrCL-
based doses. Higher doses of allopurinol are well tolerated.
Disclosure: L. K. Stamp, Amgen, 8; P. T. Chapman, None; M. Barclay, None; A. Horne, None; C. Frampton, None; P. Tan, None;
J. Drake, None; N. Dalbeth, Takeda, AstraZeneca, Abbvie, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/allopurinol-dose-escalation-to-achieve-serum-urate-

below-6mgdl-an-open-label-extension-study
Association between ABCG2 rs2231142 and Poor Response to Allopurinol:

Replication and Meta-Analysis
Mary Wallace1, Rebecca Roberts2, Payal Nanavati3, Jeffrey N Miner3, Nicola Dalbeth4, Ruth Topless5, Tony R. Merriman6 and Lisa K.
Stamp7, 1Surgical Sciences, University of Otago, Dunedin, New Zealand, 2University of Otago, Dunedin, New Zealand, 3Ardea
Biosciences, San Diego, CA, 4University of Auckland, Auckland, New Zealand, 5Department of Biochemistry, University of Otago,
Dunedin, New Zealand, 6Biochemistry Dept, PO Box 56, University of Otago, Dunedin, New Zealand, 7University of Otago,
Christchurch, New Zealand
SESSION INFORMATION
Background/Purpose: Allopurinol is the most widely used urate-lowering drug. However, some patients treated with allopurinol do not
achieve serum urate (SU) treatment target of <6mg/dl, despite daily doses >300mg. ABCG2 rs2231142 has been reported to be
associated with poor response to allopurinol, while there are conflicting data on the association between ABCG2 rs10011796 and
allopurinol response. The aim of this study was to replicate the association of ABCG2 rs2231142 and rs10011796 with allopurinol
response and perform a meta-analysis.
Methods: Participants in the Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients (LASSO) with available
allopurinol dose, plasma allopurinol, oxypurinol, serum urate and genotyping data from a single visit were studied (n=395). In patients
with evidence of adherence to allopurinol therapy (oxypurinol >20μmol/l), good response was defined as serum urate (SU) <6mg/dl on
allopurinol ≤300mg/d and poor response as SU≥6mg/dl despite allopurinol >300mg/d. Association of rs2231142 and rs10011796 with
poor response was tested in logistic regression models that included age, sex, body mass index (BMI), ethnicity and estimated
glomerular filtration rate (eGFR). Results from the LASSO study and a subset of participants in Genetics of Gout in Aotearoa study on
allopurinol with available data as outlined above (n=296, including 264 from the previously published report) were combined by meta-
analysis.
Results: 24.3% (96/395) of the LASSO cohort and 13.5% (40/296) of the NZ cohort either did not fit the pre-defined response criteria
and/or had plasma oxypurinol suggestive of non-adherence (<20μmol/l) and were therefore excluded. 46.5% (139/299) of patients in the
LASSO cohort and 50.8% (130/256) of patients in the NZ cohort were defined as poor responders. There was evidence for association
of rs22322142 with allopurinol response (OR=2.35A allele, P=7.3x10-4) but not for rs10011796 (OR=1.21 G allele, P=0.33) in the
LASSO cohort using a fully adjusted logistic regression model. Meta-analysis with the Genetics of Gout in Aotearoa study participants
provided strong and consistent evidence of an association for rs2231142 with allopurinol response (OR=2.43, P=6.2x10-7), but not for
rs10011796 (OR=1.06, P=0.69) (Figure).
Conclusion: This study replicates the association of ABCG2 rs2231142 with poor response to allopurinol. Testing ABCG2 rs2231142
may assist in prediction of SU response in people treated with allopurinol.
Disclosure: M. Wallace, None; R. Roberts, None; P. Nanavati, Ardea Biosciences, 3; J. N. Miner, Ardea Biosciences, 3; N. Dalbeth,
Takeda, AstraZeneca, Abbvie, 9; R. Topless, None; T. R. Merriman, Ardea Biosciences, 2; L. K. Stamp, Ardea Biosciences, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/association-between-abcg2-rs2231142-and-poor-

response-to-allopurinol-replication-and-meta-analysis
An Illness By Any Other Name: The Effect of Changing the Disease Label of Gout on
the Perceptions of the Illness and Its Management
Keith Petrie1, Kate MacKrill1, Christina Derksen2 and Nicola Dalbeth1, 1University of Auckland, Auckland, New Zealand, 2University
of Marburg, Marburg, Germany
SESSION INFORMATION
Background/Purpose: Gout is a chronic disease caused by deposition of monosodium urate crystals. Although diet is a risk factor,
many other factors also contribute to development of gout, including age, male sex, kidney disease and genetic variants. Historical and
contemporary narratives frequently depict gout as an acute condition caused by dietary overindulgence. These perceptions of illness
may have a negative impact on healthcare-seeking and management strategies. The aim of this study was to examine the effect of
changing the disease label of gout on the perceptions of the illness and its management.
Methods: Supermarket shopper participants were recruited into this study (n=189). Participants were advised that the aim of the study
was to examine the perceptions of different types of arthritis. Participants were randomised to read an identical description of an illness
labelled as either gout or urate crystal arthritis (UCA), and complete a questionnaire examining their perception of the illness, likely
causal factors, and the usefulness of various management strategies. The label urate crystal arthritis was selected to represent the core
pathophysiological elements of disease, including urate as the causative biochemical substrate, crystal deposition, and joint
inflammation. Differences between the two illness labels were tested using independent sample t-tests.
Results: The gout-labelled illness was attributed more to patient behaviour (p = 0.030) through poor diet (p = 0.013) and
overconsumption of alcohol (p = 0.039), while the UCA- labelled illness was attributed more to aging (p = 0.006). There were no
differences in beliefs about other causal factors. The gout-labelled illness was viewed as under more personal control (p = 0.001) and as
more socially embarrassing (p < 0.001), whereas the UCA- labelled illness was viewed as having a more chronic timeline (p = 0.044)
and as a more serious condition (p = 0.037). Changing to a healthier diet was perceived as more helpful for the gout-labelled illness (p
= 0.014). In contrast, taking long-term medications for the condition was viewed as more helpful for the UCA-labelled illness (p =
0.041). There was no significant difference between the illness labels in perceptions that reducing stress, adopting regular exercise,
losing weight or using alternative medicine would be helpful for managing the illness (p for all >0.08).
Conclusion: The negative cultural stereotypes surrounding the disease label gout may be a barrier to effective treatment. Changing the
name of the illness from gout to a pathophysiological illness label such urate crystal arthritis may have a positive benefits for patient
understanding of the condition and the adoption of effective management strategies.
Disclosure: K. Petrie, None; K. MacKrill, None; C. Derksen, None; N. Dalbeth, Takeda, AstraZeneca, Abbvie, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/an-illness-by-any-other-name-the-effect-of-

changing-the-disease-label-of-gout-on-the-perceptions-of-the-illness-and-its-management
Effect of Body Mass Index on Serum Urate and Renal Uric Acid Handling Responses
to an Oral Inosine Load
Nicola Dalbeth1, Jordyn de Kwant1, Gregory Gamble2, Amanda Phipps-Green3, Anne Horne2, Lisa K. Stamp4 and Tony R.
Merriman5, 1University of Auckland, Auckland, New Zealand, 2Department of Medicine, University of Auckland, Auckland, New
Zealand, 3University of Otago, Dunedin, New Zealand, 4University of Otago, Christchurch, New Zealand, 5Biochemistry Dept, PO Box
56, University of Otago, Dunedin, New Zealand
SESSION INFORMATION
Background/Purpose: Increased body mass index (BMI) is an important risk factor for hyperuricemia and gout. It is unknown whether
overweight and obesity influences serum urate primarily through increased urate production or reduced renal clearance of uric acid.
Inosine is a purine nucleoside that functions as an intermediate in the purine salvage and degradation pathways. Oral administration of
inosine allows analysis of the effects of a standardized purine load on both serum urate concentrations and renal uric acid handling. The
aim of this study was to determine the influence of body mass index on the response to an inosine load.
Methods: Following an overnight fast, 100 healthy participants, recruited by public advertising, attended a study visit. Exclusion
criteria included chronic kidney disease stage 3 or worse, gout, diabetes mellitus and diuretic use. Blood and urine samples were
obtained for urate and creatinine, prior to and then 15, 30, 60, 120, and 180 minutes after a single oral 1.5g dose of inosine. Clinical
features including age, sex, ethnicity and BMI were recorded. Data were analysed according to increased BMI (25kg/m2 or more) and
low/normal BMI (less than 25kg/m2). The primary endpoint was change in serum urate and secondary endpoint was change in fractional
excretion of uric acid (FEUA). Data were analysed using a mixed models approach to repeated measures.
Results : In the entire study population, oral intake of inosine led to large increases in serum urate (mean increase 1.6mg/dL) and FEUA
(mean increase 3.7%) over the 180 minute study period (P<0.0001 for both). Although participants in the increased BMI group (n=52)
had higher serum urate concentrations at baseline (age, sex, ethnicity-adjusted P=0.002), this group had a smaller increase in serum
urate following the inosine load (age, sex, ethnicity-adjusted ANCOVA P=0.0035, Figure 1A). The two BMI groups had a similar
FEUA at baseline (age, sex, ethnicity-adjusted P=0.98), but those in the increased BMI group had a smaller increase in FEUA following
the inosine load (age, sex, ethnicity-adjusted ANCOVA P=0.0003, Figure 1B).
Conclusion: People with increased BMI do not have an exaggerated hyperuricemic response to a standardized purine load. However,
those with increased BMI do have reduced renal excretion of uric acid following inosine loading. These data demonstrate impaired renal
clearance of uric acid following dietary purine intake in those with overweight and obesity.
Figure 1. A Change in serum urate, and B. Change in FEUA following an oral inosine load in different BMI groups. Data are presented
as unadjusted mean (95% CI). Age, sex and ethnicity-adjusted ANCOVA P values are shown.
Disclosure: N. Dalbeth, Takeda, AstraZeneca, Abbvie, 9; J. de Kwant, None; G. Gamble, None; A. Phipps-Green, None; A. Horne,
None; L. K. Stamp, Amgen, 8; T. R. Merriman, Ardea Biosciences, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/effect-of-body-mass-index-on-serum-urate-and-

renal-uric-acid-handling-responses-to-an-oral-inosine-load
Sex Differences in Gout Patients: Epidemiology, Flares and Hospitalization Data in a

Population Based Cohort
Mohanad Elfishawi1,2,3, Clement J. Michet Jr.4, Cynthia S. Crowson5, Eric L. Matteson6 and Tim Bongartz7, 1Rheumatology, Mayo
Clinic, Rochester, MN, 2Rheumatology, Kasr Alainy Hospital, Cairo University, Cairo, Egypt, 3Internal Medicine, Icahn School of
Medicine at Mount Sinai, Queens Hospital Center, New York, NY, 4Division of Rheumatology, Mayo Clinic, Rochester, MN, 5Health
Sciences Research, Mayo Clinic College of Medicine and Science, Rochester, MN, 6Rheumatology, Mayo Clinic College of Medicine
and Science, Rochester, MN, 7Emergency Medicine, Vanderbilt University, Nashville, TN
SESSION INFORMATION
Background/Purpose:
While gout is the most common form of inflammatory arthritis, there are relatively few studies on the influence of sex with regard to
disease presentation and comorbidities as well as flare and hospitalization rates among patients with gouty arthritis. Possible
determinants of these outcomes in patients with gouty arthritis based upon sex were evaluated using a population-based cohort.
Methods:
The individual medical records of all patients with a potential diagnosis of gout in a geographically defined area were retrospectively
reviewed using a resource insuring complete capture. All individuals with a possible diagnosis of incident gout in 2009-2010 were
identified. Incident cases had to fulfill at least 1 of 3 criteria: the 1977 American College of Rheumatology proposed criteria for gout,
the Rome or New York criteria. All identified cases were followed up through their records for 5 years after incident gout attack, death
or migration, whichever came first. Clinical characteristics were compared using chi-square and rank sum tests. Person-year methods
were used to estimate and compare flare and hospitalization rates over time.
Results:
A total of 271 patients (196 males; 72%) with incident gout in 2009-2010 were identified. Females had significantly higher mean (SD)
age at diagnosis 66.3 (15.7) years compared to males 57.6 (16.9) years (p<0.001). Although the mean (SD) body mass index (BMI) for
females 32.1 (8.9) did not differ from males 32.0(5.8) (p=0.48), more females were morbidly obese (BMI ≥40 kg/m2) than males (25%
vs 8%; p<0.001). Podagra was less common in females than males (51%vs 62%), but this did not reach statistical significance (p=0.10).
Females had significantly more chronic kidney disease stage 3/4 (36% vs 20%; p=0.006) while hypertension, diabetes and heart disease
were non- significantly increased in females compared to males.
During a median of 4.7 years of follow up, 127 males and 31 females experienced at least one gout flare with no significant difference
in the number of involved joints. Males reported a total of 323 flares with a rate of 3.97 person-years (py), higher than the 74 flares
experienced by females with a rate of 2.28 per 10 py (rate ratio: 1.73; 95% confidence interval [CI]: 1.36-2.25). This difference
persisted after adjustment for multiple flares per person (hazard ratio: 1.51; 95% CI: 1.14-2.00).
In the follow up period, 69 male patients and 41 female patients were hospitalized. Males were hospitalized 169 times for a rate of 2.08
per 10 py which is less than the reported 137 hospitalizations for females with a rate of 4.22 per 10 py (rate ratio: 0.49; 95% CI: 0.39
-0.62). However, this difference was no longer significant after accounting for the older age of the females
Conclusion:
Female patients with gout are older at incidence than males and tend to have more associated common co-morbidities, particularly
chronic kidney disease. Podagra is less common in females than males. Female patients tend to have fewer flares as compared to males.
Adjusted for age, there was no difference in hospitalization rates between males and females.
Disclosure: M. Elfishawi, None; C. J. Michet Jr., None; C. S. Crowson, None; E. L. Matteson, None; T. Bongartz, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/sex-differences-in-gout-patients-epidemiology-

flares-and-hospitalization-data-in-a-population-based-cohort
Clinical Features and Risk of Recurrent Attack in Gout Patients According to Serum
Urate Levels during an Acute Gout Attack
Jung Sun Lee1, Seokchan Hong2, Oh Chan Kwon2, Byeongzu Ghang2, Wook Jang Seo3, Doo-Ho Lim4, Yong-Gil Kim2, Chang Keun
Lee2 and Bin Yoo2, 1Internal medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea, Republic of
(South), 2Division of Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center,
Seoul, Korea, Republic of (South), 3Seoul Veterans Hospital, Seoul, Korea, Republic of (South), 4Division of Rheumatology,
Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea, Republic of
(South)
SESSION INFORMATION
Background/Purpose: To investigate the clinical features and risk of gout recurrence in patients with normouricemia during an acute
attack
Methods:
This study was conducted in patients diagnosed with acute gout attack by the presence of urate crystals. Clinical features of
normouricemic and hyperuricemic patients were compared. Multivariate analysis was performed to determine whether normouricemic
patients during an acute attack were less likely to have a recurrent gout attack.
Results: Among a total of 221 gout patients, 88 (39.8%) had normouricemia during an acute attack. Postsurgical gout (22.7% vs 6.0%,
P < 0.001), hemodialysis initiation (9.1% vs 2.3%, P = 0.029) and inflammatory activity were higher in normouricemic patients than in
hyperuricemic patients. The frequency of renal insufficiency was lower in normouricemic patients (25.0% vs 53.4%, P < 0.001).
However, the recurrence rate of gout attack was not different between the two groups during the follow-up period (24.7% vs 33.0%, P =
0.220). In multivariate analysis, female sex, history of urinary stone, presence of tophi, and use of thiazide were associated with risk of
recurrent gout attack, but not with serum urate status during an acute attack (HR 1.075, 95% CI 0.972-1.190, P = 0.159).
Conclusion: Normouricemia during an acute gout attack was more frequently observed in postsurgical episodes, hemodialysis initiation
and patients with preserved renal function. The recurrent attack was not associated with serum urate levels during an acute gout attack.
Thus, careful follow-up should be considered in gout patients regardless of serum urate levels during an acute attack.
Disclosure: J. S. Lee, None; S. Hong, None; O. C. Kwon, None; B. Ghang, None; W. J. Seo, None; D. H. Lim, None; Y. G. Kim,
None; C. K. Lee, None; B. Yoo, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/clinical-features-and-risk-of-recurrent-attack-in-

gout-patients-according-to-serum-urate-levels-during-an-acute-gout-attack
Protective Effect of Allopurinol Use on Kidney Function Among Patients with Gout
and Chronic Kidney Disease
Ana Beatriz Vargas-Santos1, Christine Peloquin2, Yuqing Zhang3,4 and Tuhina Neogi4, 1Internal Medicine - Rheumatology, State
University of Rio de Janeiro, Rio de Janeiro, Brazil, 2Clinical Epidemiology Unit, Boston University School of Medicine, Boston, MA,
3School Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA,
4Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, MA
SESSION INFORMATION
Background/Purpose: There is increasing evidence that allopurinol may be protective of kidney function among hyperuricemic
subjects, though clinicians are often cautious about using allopurinol in renal insufficiency. Further, studies have been conflicting and
few have involved patients with gout. We sought to evaluate the relation of allopurinol to kidney function among gout patients with
chronic kidney disease (CKD) stage 3-4 at the start of therapy.
Methods: We conducted a time-stratified propensity score (PS)-matched cohort study in The Health Improvement Network (THIN), a
general practitioner electronic medical records database representative of the UK general population. Our study sample included
subjects 18-89 years-old with gout and CKD 3 or 4 who had not previously been on urate-lowering therapy. We used PS matching to
minimize the effects of confounding by indication. Specifically, we identified new users of allopurinol among this cohort, and matched
them 1:1 with an unexposed subject based on the PS using greedy matching within 1-year cohort accrual blocks. We computed the PS
using logistic regression, with incident allopurinol use as the dependent variable and potential confounders that reflect indication for
allopurinol use and/or risk of CKD (table) as the independent variables. Subjects were followed from the index date (date of 1st
allopurinol prescription for the exposed, and randomly assigned date for the unexposed within the 1-year accrual block) until the last
glomerular filtration rate (GFR) assessment within 1 year after the index date (before dialysis, kidney transplant, or death if they
occurred), or end of study. We analyzed the relation of incident allopurinol use to the changes in GFR using linear regression adjusted
for the potential confounders included in the PS model.
Results: Of those with a diagnosis of gout and CKD 3-4, we PS-matched 9,830 allopurinol initiators to 9,830 non-users, among whom
41% and 42% were female. Other covariates were also well-balanced, with mean age of 74 years, mean BMI of 30 kg/m2 and 9% of
CKD4 subjects in both groups. Time to post-baseline GFR, and dialysis/transplant were similar in both groups. The mean GFR prior to
study entry was 46.8 mL/min among allopurinol initiators and 49.8 mL/min among non-users, while the last GFR within one year was
47.8 and 50.0 mL/min, respectively. Allopurinol initiators had an adjusted mean increase in GFR that was 0.8 mL/min (95% CI 0.6-1.1)
greater than that of the non-users (Table).
Conclusion: In this community-based cohort, allopurinol use appeared to confer a renoprotective effect among those with pre-existing
CKD 3-4 and gout, suggesting that allopurinol does not contribute to worsening renal function among gout patients with renal
insufficiency. Physicians should seek other contributors to renal function decline in patients on allopurinol with concomitant gout and
CKD if renal function deteriorates.
Disclosure: A. B. Vargas-Santos, None; C. Peloquin, None; Y. Zhang, None; T. Neogi, None.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/protective-effect-of-allopurinol-use-on-kidney-

function-among-patients-with-gout-and-chronic-kidney-disease
Efficacy of High Dose Versus Moderate Dose Prednisone in the Treatment of Acute
Gout
Rochella A. Ostrowski1, Elizabeth Araujo2, Richard Hariman3 and Elaine Adams4, 1Division of Rheumatology, Loyola University
Medical Center, Maywood, IL, 2Rheumatology and Immunology, Department of Internal Medicine 3, Universitätsklinikum Erlangen,
Erlangen, Germany, Erlangen, Germany, 3Rheumatology, Medical College of Wisconsin, Milwaukee, WI, 4Rheumatology, Edward
Hines Jr Hospital, Veterans Administration, Hines, IL
SESSION INFORMATION
Background/Purpose:
Despite the use of corticosteroids in acute gout, there exist wide variations in treatment doses and duration. No studies have evaluated
the ideal dose of steroids for gout flares. However, occurrences of treatment failure and side effects from treatment warrant an
evaluation for the lowest effective dosing. The goal of this double blinded prospective pilot study is to compare efficacies of a moderate
dose and high dose prednisone course in treating acute gout.
Methods:
Male subjects age 18 years and older at Edward Hines Jr Hospital VA with acute gout were included. Patients with heart failure
exacerbation, uncontrolled diabetes mellitus, infection, pseudogout, or chronic prednisone use were excluded. Subjects were
randomized to a high or moderate dose of prednisone (high: 60mg on day 1, decreased by 10mg each day for a 6 day course; moderate:
30mg on day 1, decreased by 5mg each day for 6 days).
The primary endpoint was improvement in pain at 48 hours based on a 200mm visual analog scale. Secondary endpoints included the
proportion of patients with resolution of synovitis by Day 7; absence of recurrent flares at 28 days; the proportion of patients who
returned to baseline pain by day 7; and the number of days to return to baseline pain levels.
An intention-to-treat approach was used for analysis. Student t-test was used to compare mean values and Fishers exact test was used to
compare proportions (STATA 11.1).
Results:
139 patients were screened, and 33 patients were enrolled between September 2007 and December 2014. All patients enrolled were
male, with a mean age of 62.2 (± 11.8) and 63.4 (± 15.8) years in the moderate and high dose groups respectively. Results are
summarized in Table 1. The mean percent improvement in pain severity at 48 hours was higher in the high dose group (51.9 vs 43.7%),
though it did not achieve statistical significance. Of 26 patients examined at day 7, a higher proportion of patients in the moderate dose
group experienced resolution of synovitis, though this finding did not reach statistical significance (0.75 in moderate group vs 0.36 in
high group).
The proportion of patients back at baseline pain on day 7 was significantly higher in the moderate dose group (0.73 vs 0.26, p=0.013).
The time to return to baseline pain levels was also shorter in the moderate dose group but did not achieve statistical significance.
Conclusion:
In this randomized double blinded pilot study, there were no significant differences between the response of acute gout to high dose
versus moderate dose prednisone at 48 hours and exam findings on day 7. Furthermore, the proportion of patients who returned to
baseline pain levels was lower in the high dose group, contrary to what investigators hypothesized would occur. Despite size limitations
of this pilot study, our findings warrant larger trials to establish a standardized, evidence based practice for appropriate dosing of
steroids in acute gout.
Disclosure: R. A. Ostrowski, None; E. Araujo, None; R. Hariman, None; E. Adams, None.

View Abstract and Citation Information Online - http://acrabstracts.org/abstract/efficacy-of-high-dose-versus-moderate-dose-
prednisone-in-the-treatment-of-acute-gout
Risk of Cardiovascular Events in Older Patients with Gout Initiating Probenecid

Versus Allopurinol: A Population-Based Cohort Study
Seoyoung C. Kim1, Tuhina Neogi2, Eun Ha Kang3, Jun Liu4, Rishi J. Desai5, MaryAnn Zhang6 and Daniel H. Solomon7,
1Rheumatology, Immunology and Allergy; Pharmacoepidemiologyand Pharmacoeconomics, Brigham and Women's Hospital, Boston,
MA, 2Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, MA, 3Division of
Rheumatology, Department of Internal Medicine, Division of Rheumatology, Department of Internal Medicine, Seoul National
University Bundang Hospital, Seongnam, Korea, Republic of (South), 4Division of Pharmacoepidemiology and Pharmacoeconomics,
Brigham and Women's Hospital, Boston, MA, 5Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s
Hospital, Boston, MA, 6Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, 7Brigham
and Women's Hospital and Harvard Medical School, Boston, MA
SESSION INFORM

Abstract Supplement: 2017 ACR/ARHP Annual Meeting November 3-8, 2017 San Diego, CA

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Volume 69 • Number S10 • October 2017

Efficacy and Safety of Intra-Articular Sprifermin in

Background/Purpose: Sprifermin, anovel recombinant human fibroblast growth

Conclusion: To our knowledge, sprifermin is thefirst investigational agent to show

View Abstract and Citation Information Online -

Efficacy and Safety Results from a Phase 2 Trial of

Background/Purpose: Interleukin-23(IL-23), a key regulator of multiple effector

View Abstract and Citation Information Online -

Secukinumab Demonstrates Low Radiographic

Background/Purpose: Secukinumab, a fully human anti–interleukin-17A monoclonal

Conclusion: Secukinumab 150 mg demonstrates lower radiographic progression vs 75

References: 1. Braun J et al. Ann Rheum Dis 2016;0:1‒8

Table. Summary of efficacy data at Wk 208

Other efficacy outcomes

View Abstract and Citation Information Online -

Final Results of an Open Label Phase 2 Study of a

First publication: October 13, 2017

Background/Purpose: IgG4-related disease (IgG4-RD) is an immune-mediated

Conclusion: XmAb5871 is tolerated well in patients with active IgG4-RD and is a

Disclosure: J. H. Stone, Xencor, 2; Z. S. Wallace, None; C. A. Perugino, None; A. D.

View Abstract and Citation Information Online - http://acrabstracts.org/abstract/final-

RAPAMI is a prospective, randomized, controlled, double blind, monocentric, phase IIb

Disclosure: O. Benveniste, None; J. Y. Hogrel, None; M. Annoussamy, None; D.

View Abstract and Citation Information Online -

Efficacy and Safety of Ustekinumab, an Interleukin

Background/Purpose: TheIL-12/23 pathway has been implicated in the pathogenesis of

Methods: Weconducted a phase 2, placebo (PBO)-controlled study in 102 adults with

Results: Baselinept demographic and disease characteristics were well-balanced between

Conclusion: USTshowed significantly better efficacy in clinical and laboratory

bOne-sidedtest for no difference between two treatment groups based upon a

BICLA, BILAG-based Combined Lupus Assessment; BILAG, British Isles

View Abstract and Citation Information Online -

A Phase 2 Study of Safety and Efficacy of Anabasum

Methods: A double-blind, randomized placebo-controlled16-week Phase 2 trial

Disclosure: V. P. Werth, None; E. Hejazi, None; S. M. Pena, None; J. S. Haber, None;

View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-

Prevalence of Blindness in a Cohort of Rheumatologic

Background/Purpose: Hydroxychloroquine (HCQ) is widely used in the treatment of

Of our 31 patients with a diagnosis of ‘blindness’ or ‘toxic maculopathy’, 11 had

Conclusion: There were no cases of blindness attributable to toxic maculopathy from

Disclosure: D. Singh, None; L. Muhieddine, None; D. Einstadter, None; S. Ballou,

View Abstract and Citation Information Online -

Circulating Type I, II and III Interferons (IFNs)

Disclosure: V. Oke, None; I. Gunnarsson, None; J. M. Dorschner, None; A. Zickert,

View Abstract and Citation Information Online -

Abstract Number: 10L

Upadacitinib (ABT-494) in Patients with Active

Background/Purpose: Upadacitinib (ABT-494, UPA), an oral,selective JAK-1 inhibitor

Methods: Pts with active RA (TJC≥6, SJC≥6;hsCRP≥3 mg/L) on stable csDMARDs

Conclusion: In this treatment-refractory, bDMARD-IRRA population, rapid, significant

View Abstract and Citation Information Online -

Abstract Number: 11L

Risk of Second Malignant Neoplasm and Mortality in

First publication: October 13, 2017

View Abstract and Citation Information Online - http://acrabstracts.org/abstract/risk-

Abstract Number: 12L

Evaluation of Intravenous Injection of Tc 99m

Background/Purpose:Activatedmacrophages play a critical role in RA by perpetuating

Tc 99m Tilmanocept is asynthetic radiopharmaceutical imaging agent that binds to the