D. Gladman

Background: Tumour necrosis factor a (TNFa) is a cytokine of critical importance in psoriatic arthritis. Objectives: (1) To examine the association between TNFa promoter gene polymorphisms and psoriatic arthritis in two well characterised Canadian populations with the disease; (2) to carry out a meta-analysis of all TNFa association studies in white psoriatic arthritis populations. Methods: DNA samples were genotyped for five TNF variants by time of flight mass spectrometry using the Sequenom platform. All five single nucleotide polymorphisms were in the 59 flanking region of TNFa gene at the following positions:21031 (TRC),2863 (CRA),2857 (CRT),2308 (GRA), and2238 (GRA). Primary analyses were based on logistic regression. Summary estimates of disease/genotype relations from several studies were derived from random effects meta-analyses. Results: 237 psoriatic arthritis subjects and 103 controls from Newfoundland and 203 psoriatic arthritis subjects and 101 controls from Toronto wer...

Golimumab Inhibits Progression of Radiographic Damage in Patients with Psoriatic Arthritis: 52 Week Results From the GO-REVEAL Study.: LB5 A. Kavanaugh;D. van der Heijde;D. Gladman;P. Mease;I. McInnes;G. Krueger;W. Xu;M. Rahman;J. Zrubek;A. Baratelle;A. Beutler; Arthritis & Rheumatism

ABSTRACT Background The introduction of TNF blockers in psoriatic arthritis (PsA) has altered the disease course and was shown to reduce disease activity and radiographic progression. Clinical remission requires achieving disease quiescence in all disease domains. A state of Minimal Disease Activity (MDA) was defined and validated as a target for treatment in PsA. However, data regarding the characteristics and prognostic outcomes of patients in MDA state in observational cohorts while being on TNF blockers is scarce. Objectives To identify disease characteristics of patients with PsA who achieve MDA while on TNF blockers and to identify predictors for MDA. Methods Patients were recruited from a single centre cohort. All patients fulfilled the CASPAR criteria and were followed regularly at 3-6 months intervals. TNFα blockers were prescribed when patients failed to standard of care. Patients were considered in MDA when met a least 5/7 of the following criteria: Tender joint count≤1; swollen joint count ≤1; psoriasis activity and severity index ≤1 or body surface area ≤3; patient pain visual analog scale (VAS) score of ≤15; patient global disease activity VAS score of ≤20; Health Assessment Questionnaire (HAQ) score ≤0.5; and tender entheseal points ≤1. Patients achieving MDA were compared to patients who did not achieve MDA using descriptive statistical tests. A proportional odds discrete time survival analysis model was used to identify predictors of the first onset of MDA. Results 306 patients in the database were treated with anti-TNF agents, Of whom 22 were in MDA at baseline and 57 were prescribed anti-TNF agents prior to enrolment. The remaining 227 were in non-MDA state and constituted the study population. 146/227 patients achieved MDA after an average of 1.30 (1.51) years and for a mean duration of 3.46 (2.25) years. Among patients who achieved MDA, at baseline they were more males (68.5% vs. 59.3%, P=0.01), younger at the age diagnosis (34.5 vs. 38.8, P=0.03), had a lower active joint count (8.7 vs. 15.3, P=0.0002), more likely to have clinical damage (74.4% vs. 48.6%, P=0.0003) and axial involvement (53.9% vs. 8.3%, P=0.001) compared to patients that didn’t achieve MDA. Patients with non-MDA state had higher BMI (31.6 vs. 28.5, P=0.02) at baseline, were more classified with functional class III/IV (32.9% vs. 10.1, P<0.0001%) and had a lower SF-36 physical (29.1 vs. 43.9) and mental (42.6 vs. 49.8, P=0.006) component scores compared to the MDA group. The majority of patients in both groups were also treated with DMARDs and NSAIDs. No significant difference was found in disease duration, alcohol, smoking, ESR, CRP, PASI score or radiographic damage between the two groups. The survival analysis showed that after adjusting for characteristics at each visit such as sex, age, duration of disease, abnormal ESR, PASI, obesity and active joint count that only active joint count (OR=0.70 CI 0.57-0.88, P=0.002) and PASI score (OR=0.84 CI 0.72-0.99, P=0.03) lowered the odds of achieving MDA. Conclusions 63% of the study group achieved MDA after an average duration of 1.3 years. Only lower active joint count and PASI score were predictors of response to treatment with TNF blockers. Disclosure of Interest None Declared

Sera of 66 patients with progressive systemic sclerosis (PSS) were tested for cold and warm reacting lymphocytotoxins (LCT). Cold LCT were found in 30 (45%) patients, 18 of whom also had warm LCT. Warm LCT alone were found in 14 patients. Twenty-nine sera with cold LCT were tested and reacted with both peripheral B and T lymphocytes. There was predominant killing of B cells in 52% and of T cells in 14%. Ten cold LCT were absorbed to and eluted from peripheral blood lymphocytes. All eluates were cytotoxic to B and T cells; 1 killed predominantly T cells and 2 killed predominantly B cells. Clinical-laboratory and HLA correlations with cold LCT showed no significant differences between the LCT-positive group and the LCT-negative group. Granulocytotoxins were rare in PSS, but warm reacting monocytotoxins were found in 33 cases (57%). Crossreactivity of cytotoxins was tested using eluates from various cells. The majority of eluates from lymphocytes were cytotoxic against polymorphonuclea...

Skin thickening simulating scleroderma, or progressive systemic sclerosis, has previously been reported in children and adults with insulin-dependent diabetes mellitus. We have studied eighty-nine patients with insulin-dependent diabetes mellitus and twenty-five normal control subjects. Clinical evidence of skin thickening (diabetic thick skin) was found in 22% of patients with insulin-dependent diabetes mellitus and in 4% of control subjects (p less than 0.05). Full-thickness skin biopsy specimens were taken from the forearm of nine patients with insulin-dependent diabetes mellitus and diabetic thick skin, four patients with insulin-dependent diabetes mellitus and clinically normal skin, four patients with progressive systemic sclerosis, and four normal control subjects. The sections stained with hematoxylin and eosin showed increased thickness of the dermis of the forearm skin in all diabetic patients. In diabetic thick skin the collagen bundles were large, disorganized, and separated by clear spaces. Small amounts of acid mucopolysaccharides were present in the upper reticular dermis of five patients with diabetic thick skin. Electron microscopy of the dermis showed capillary basement membrane thickening in Groups 1, 2, and 3. All patients with diabetic thick skin showed active fibroblasts and extensive collagen polymerization in the rough endoplasmic reticulum. Occasional collagen flowers were noted in all patients with diabetic thick skin. Measurements of 100 collagen fibers in the upper and lower reticular dermis of each biopsy specimen showed predominance of large fibers (greater than 60 nm) in Groups 1 and 2. Unlike scleroderma, diabetic thick skin resulted in small fiber sizes (less than 60 nm) only rarely, and bimodality of fiber sizes was not seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Psoriatic arthritis and the enteropathic arthropathies are included among the seronegative spondyloarthropathies. The concept of psoriatic arthritis as a specific entity continues to be challenged by some investigators, while others report on additional findings in this condition, such as temporomandibular joint disease. The etiopathogenesis of the condition continues to be investigated by the exploration of genetic and immunologic factors. Treatment options include dietary manipulations. The prevalence of arthritis among patients with bowel disease seems to be increasing, while the presence of gut lesions among patients with spondyloarthropathy is noted to be associated with disease activity.

Objective.At OMERACT 8 a framework for levels of evidence was proposed for the validation of biomarkers as surrogate outcome measures. We aimed to adapt this scheme in order to apply it in the setting of soluble biomarkers proposed to replace the measurement of damage endpoints in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). We also aimed to generate consensus on minimum standards for the design of longitudinal studies aimed at validating biomarkers.Methods.Before the meeting, the Soluble Biomarker Working Group prepared a preliminary framework and discussed various models for association and prediction related to the statistical strength domain. In addition, 3 Delphi exercises addressing longitudinal study design for RA, PsA, and AS were conducted within the working group and members of the Assessments in SpondyloArthritis International Society (ASAS) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). T...

Several factors have been associated with the development of osteonecrosis (ON) in SLE but corticosteroid (CS) therapy has been the most consistent association. We sought to determine factors that predisposed to, or protected from, the development of ON in lupus patients when cumulative oral corticosteroid doses were matched between cases and controls, thereby removing presence of corticosteroid therapy and cumulative dose as risk factors. A nested case-control study of an inception cohort of SLE patients was used to determine the clinical, laboratory and therapeutic differences between patients who developed their first ON event and patients who did not develop ON, having matched these groups for their cumulative oral corticosteroid doses. Of the 570 patients seen within the first year after diagnosis 65 (11.4%) developed ON. None of the variables examined were found to confer additional ON risk in multivariate analysis. It appears that the major factor associated with the developm...

To determine the level of agreement of disease flare severity (distinguishing severe, moderate and mild flare and persistent disease activity) in a large paper patient exercise involving 988 individual cases of systemic lupus erythematosus. 988 individual lupus case histories were assessed by three individual physicians. Complete agreement about the degree of flare (or persistent disease activity) was obtained in 451 cases (46%) and these provided the reference standard for the second part of the study. This component utilised three flare activity instruments (BILAG 2004, SELENA flare index (SFI) and the revised SELENA flare index (rSFI)). The 451 patient case histories were distributed to 18 pairs of physicians being carefully randomised in a manner designed to ensure a fair case mix and equal distribution of flare according to severity. The three physician assessment of flare matched the level of flare using the three indices thus 67% for BILAG 2004, 72% for SFI and 70% for rSFI. ...

The OMERACT module on systemic lupus erythematosus (SLE) dealt with the definition of preliminary core sets of outcome domains for randomized clinical trials (RCT) and longitudinal observational studies (LOS). After lectures introducing the problems and addressing the key issues, 6 discussion groups, 3 each for LOS and RCT, discussed and weighted more than a dozen possible items for use as outcome domains. The means of the respective 3 groups were calculated. For both RCT and LOS the same outcome domains received more than 10 of a total maximum of 100 points: disease activity, health related quality of life (HRQOL), damage, and toxicity/adverse events. However, the weights for HRQOL and damage were different for LOS and RCT. A final vote led to the acceptance of these 4 variables as a preliminary core set for outcome in SLE by more than 80% of the participants. This core set will allow for improved design, performance, and evaluation of future studies in SLE. However, a number of do...

Objective.To compare health-related quality of life (HRQOL) of patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) with and without previous thrombovascular events (TE).Methods.The Medical Outcomes Study Short-Form 36 (SF-36) was used to assess HRQOL in 5 patient groups: (1) primary APS (PAPS; n = 35); (2) APS associated to SLE (SAPS; n = 37); (3) SLE+TE without persistent positive antiphospholipid antibody (SLE+TE–aPL; n = 75); (4) SLE–TE+aPL (n = 71); and (5) SLE–TE–aPL (n = 608).Results.The data on both mental component summary and physical component summary (PCS) scores showed an impaired quality of life in all patient groups. Patients in the SLE+TE–aPL group had a lower PCS score compared to patients in the SLE–TE+aPL group.Conclusion.The combination of SLE and TE has a more negative influence on reported HRQOL, compared to having SLE or APS alone.

OBJECTIVE To examine the prevalence, subspecificities, and clinical associations of antineutrophil cytoplasmic antibodies (ANCA) in patients with systemic lupus erythematosus (SLE). METHODS One hundred fifty-seven sera from 120 patients with SLE were examined for classic (c) and perinuclear (p) pattern ANCA by indirect immunofluorescence. Antibody subspecificities were determined by enzyme-linked immunosorbent assay (ELISA). Serologic results were correlated with clinical manifestations as categorized by the BILAG (British Isles Lupus Assessment Group) index. RESULTS ANCA were found in 40 of the 157 sera (25%). Only a pANCA, not a cANCA, pattern of fluorescence was seen. By ELISA testing, 16 sera reacted to lactoferrin, 8 to elastase, and 4 to lysozyme. There was no reactivity to proteinase 3 (PR3) or myeloperoxidase (MPO). No correlation of pANCA, or any of the ANCA subspecificities, with organ system involvement, as categorized by the BILAG index, was found. Notably, there was no correlation of ANCA results with lupus vasculitis. CONCLUSION The absence of cANCA, anti-PR3, and anti-MPO shows that with appropriate assay conditions, ANCA testing assists in the differentiation between SLE and the ANCA-associated vasculitides. The lack of a correlation between pANCA or any ANCA subspecificity and clinical manifestations suggests that ANCA do not identify particular clinical subsets among SLE patients, including those with lupus vasculitis.

Introduction Les strategies de traitement a l’objectif dans le RP recommandent de viser la remission (Rem) ou la LDA. Plusieurs criteres de mesure de l’activite de la maladie sont disponibles, notamment la VLDA/MDA, des valeurs-seuils du DAPSA et du PASDAS. Nous avons evalue les taux de pts atteignant ces criteres aux S12 et 24 en utilisant les donnees des etudes de phase 3 SELECT-PsA1 et SELECT-PsA2 [1] , [2] . De plus, nous avons evalue la distribution des composantes individuelles du score MDA parmi les pts ayant atteint ou non la MDA a la S24. Patients et methodes Il s’agit d’une analyse post hoc de 2 essais cliniques randomises. Dans SELECT-PsA1, des pts atteints de RP ayant eu une reponse inadequate (IR) ou une intolerance a ≥ 1 non-bDMARD (n = 1705) ont recu UPA15 mg 1 ×/j, UPA30 mg 1 ×/j, ADA40 mg une S/2 ou un PBO. Dans SELECT-PsA2, des pts ayant eu une IR ou une intolerance a ≥ 1 bDMARD (n = 642) ont recu UPA15, UPA30 ou un PBO. La remission et la LDA ont ete evaluees par la VLDA/MDA, le DAPSA ≤ 4/≤ 14 et le PASDAS ≤ 1,9/≤ 3,2, aux S12 et 24 ( Tableau 1 ). Pour les variables binaires et pour la MDA et les analyses associees, la NRI a ete utilisee. Les pts ayant recu un ttt de secours a S16 ont ete consideres comme non-repondeurs. Des comparaisons appariees entre UPA, le PBO ou ADA ont ete conduites au moyen du test de Cochran–Mantel–Haenszel. Resultats Au total, 2345 pts ont ete analyses ; âge moyen 51 ans, 53 % de femmes. Dans les deux etudes, des taux plus eleves de Rem et de LDA ont ete observes avec les deux doses d’UPA vs PBO aux S12 et 24 (p  Tableau 1 ). En general, des taux plus eleves de Rem et de LDA etaient aussi observes avec UPA30 vs ADA chez les pts ayant eu une IR aux non-bDMARDs (p  Fig. 1 ). A l’inverse, la proportion de pts ayant un NAD68 ≤ 1 et un score d’evaluation globale de la douleur par le pt ≤ 1,5 avait tendance a etre plus faible. Conclusion Aux S12 et 24, chez les pts en echec ou non a des ttt anterieurs par des bDMARDs, des taux plus eleves de Rem ou de LDA, mesurees par differents criteres, ont ete obtenus pour UPA15 ou UPA30 vs PBO. Chez les pts ayant eu une IR a un non-bDMARD, des taux de reponse plus eleves ont ete observes pour la plupart des mesures de la Rem et de la LDA avec UPA30 vs ADA. Parmi les pts ayant atteint ou non une MDA a S24, les mesures effectuees par le medecin telles que NAG ≤ 1, PASI ≤ 1 ou BSA-Ps ≤ 3 % et LEI ≤ 1 ont ete atteintes par une plus grande proportion de patients traites par UPA.

Introduction Les recentes recommandations de l’EULAR proposent que l’objectif de la prise en charge du rhumatisme psoriasique (RP) soit la remission (REM) ou a defaut un faible niveau d’activite (LDA) de la maladie evaluee regulierement a l’aide de scores composites integrant une ou plusieurs des principales manifestations de la maladie [1] , [2] . L’etude EXCEED a compare le secukinumab (SEC) et l’adalimumab (ADA) en monotherapie chez des patients (pts) atteints de RP actif avec une reponse insuffisante ou une intolerance aux csDMARD. Cette analyse post hoc presente les niveaux d’activite residuelle de la maladie (RDA) des scores composites chez les pts RP ayant obtenu une LDA et/ou une REM respectivement a S24 et S52. Patients et methodes Etude face-face, de phase 3b, en double aveugle : pts atteints de RP actif, naifs de biotherapie, randomises dans le groupe SEC 300 mg SC administre a l’inclusion, toutes les semaines pendant 4 semaines puis toutes les 4 semaines jusqu’a S48 ou dans le groupe ADA 40 mg SC administre a l’inclusion, puis toutes les deux semaines jusqu’a S50. Les resultats du critere primaire et des principaux criteres secondaires a S52 ont ete precedemment rapportes [3] . LDA et REM ont ete evalues en utilisant les scores MDA, VLDA, DAPSA REM/LDA et PASDAS REM/LDA. Les proportions de RDA ont ete etablies pour les manifestations cliniques du RP (articulaire, enthesite et psoriasis), HAQ, douleur EVA, evaluation globale par le patient (PtGA) et evaluation globale par le medecin (PGA) de l’activite de la maladie. Les scores composites ont ete analyses par regression logistique et les donnees manquantes ont ete traitees par imputation multiple. Les niveaux de RDA sont presentes chez les pts ayant atteint une LDA et/ou la REM. Resultats Une proportion similaire de pts traites par SEC et ADA a atteint une LDA et une REM a S24. Une augmentation du taux de LDA/REM a ete observee de S24 jusqu’a S52. La VLDA a ete obtenue par une proportion plus faible de pts que la LDA + REM/REM PASDAS et la LDA + REM/REM DAPSA a S24 et S52. La proportion de pts ayant atteint la VLDA, le PASDAS REM et le DAPSA REM dans les groupes de traitement a S24 avait une faible RDA (10–19 %) pour les composantes de base, a l’exception de PGA et du PASI ≤ 1. Au moins 66 %, 59 % et 49 % des patients qui ont respectivement obtenu une reponse MDA, PASDAS LDA + REM et DAPSA LDA + REM, dans les deux groupes de traitement, n’avaient pas de RDA a S24, ce qui suggere que la MDA est l’indice composite le plus stringent. Une diminution supplementaire de la RDA a ete observee chez les patients qui ont obtenu une REM ou une LDA a S52 pour tous les scores composites dans les deux groupes de traitement. Conclusion Une proportion similaire de pts a atteint une LDA et/ou une REM a S24 dans les deux groupes de traitement, avec une amelioration supplementaire a S52. Les patients qui ont atteint une VLDA ou une MDA ont eu tendance a avoir une activite residuelle de la maladie plus faible que ceux qui ont atteint un PASDAS REM/LDA + REM ou un DAPSA REM/LDA + REM. L’activite residuelle de la maladie etait plus faible chez les patients en REM que chez ceux ayant atteint le stade LDA et legerement plus faible chez les patients ayant atteint le stade VLDA que chez ceux ayant atteint le stade PASDAS REM ou DAPSA REM.

Objectives:Clinical research data are often collected on paper and later inputted onto an electronic database. This method is time consuming and potentially introduces errors. Therefore, to make primary data collection more efficient and less error prone we aimed to develop a touch-screen application for data collection in a psoriatic arthritis research clinic and compared it with the pre-existing paper-based system.Methods:We developed a Web application using Java and optimized it for the iPad®. It highlights missing fields for physicians in real time, and only permits submission of data collection form after corrections are made. For its evaluation, seven physicians participated, and before each patient visit they were randomly assigned paper or iPad®data entry. Number of errors, length of visit, and time between clinic visit and completion of data entry were measured.Results:A total of 106 patients seen in the clinic who agreed to participate were randomly assigned to be evaluate...

Malakoplakia is a chronic granulomatous inflammatory disorder. It is suspected clinically by the presence of chronic infection and diagnosed by histologic examination of affected tissues. Studies of 4 patients with malakoplakia--2 renal transplant recipients, 1 patient with systemic lupus erythematosus, and 1 patient with polymyositis--are reported. All patients were receiving prednisone and azathioprine at the time of diagnosis and had an infection caused by Escherichia coli. Leukocytes from all patients failed to kill Staphylococcus aureus and E coli normally in vitro. Cholinergic agonists had no apparent effect on bacterial killing in vitro or in vivo in the 2 patients examined. Clinically, malakoplakia improved significantly when immunosuppressive therapy was tapered or discontinued, and leukocyte function returned to normal in all 4 patients. The cases reported here and those documented previously suggest that the pathogenesis of malakoplakia and its treatment may not be the sa...

Among the different types of arthritis associated with meningococcal disease, isolated primary meningococcal arthritis is unusual. A case of isolated group C meningococcal septic arthritis in an HIV negative homosexual male is described and its possible implication discussed.

Background Psoriatic arthritis (PsA) is associated with severe work disability and loss of productivity.1 The efficacy and safety of certolizumab pegol (CZP), a PEGylated Fc-free anti-TNF, in PsA has been reported in RAPID-PsA (NCT01087788).2 Objectives To report the effect of CZP on productivity of paid and household work, and daily activities, in PsA. Methods The ongoing 158-week (wk) Phase 3 RAPID-PsA trial is double-blind and placebo (PBO)-controlled to Wk24.2 Recruited pts had active PsA, had failed ≥1 DMARD, and could have experienced secondary failure to 1 prior anti-TNF. Pts were randomized 1:1:1 to PBO every 2 wks (Q2W), or CZP 400mg at Wk0, 2 and 4 (loading dose) followed by either 200mg CZP Q2W or 400mg CZP every 4 wks (Q4W). Primary efficacy endpoints were ACR20 response at Wk12 and change from baseline (BL) to Wk24 in the van der Heijde modified Total Sharp Score (mTSS). The arthritis-specific Work Productivity Survey (WPS, administered Q4W) was used to assess the impact of PsA on productivity at work, at home and daily activities during the preceding month. WPS responses (LOCF imputation) were compared between treatment arms of the randomized population (RS) using a non-parametric bootstrap-t method. Results 409 pts were randomized. 56.6%, 60.1%, and 61.5% of pts in the PBO, CZP 200mg Q2W, and CZP 400mg Q4W treatment arms were employed at study BL; 13%–16% of pts were unable to work due to PsA; 13%–14% were retired. Treatment groups were comparable at BL in terms of workplace and household productivity. At BL, PsA had an impact on absenteeism and presenteeism, and interfered with work productivity; however, the burden of PsA on household productivity and participation in social activities was greater (Table). Compared to PBO, employed pts in both CZP arms reported reduced workplace absenteeism and presenteeism from Wk4 through to Wk24 (Table). CZP arms also reported greater reductions vs PBO in days lost of household work and of family/social/leisure activities per month, in days with reduced household productivity and in PsA interference with household duties as early as Wk4 through to Wk24 (Table). Image/graph Conclusions CZP significantly improved work productivity in pts with PsA in the workplace by reducing absenteeism, presenteeism and PsA interference with work. CZP also improved household productivity and increased participation in social and daily activities. References Tillett W. Rheumatology 2012;51: 275-283, Mease P. Ann Rheum Dis 2012;71(Suppl3): 150 Acknowledgements The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma. Disclosure of Interest A. Kavanaugh Grant/research support from: Abbott, Amgen, BMS, Pfizer, Roche, Janssen, UCB Pharma, D. Gladman Grant/research support from: Abbott, BMS, Celgene, Johnson & Johnson, MSD, Novartis, Pfizer, UCB Pharma, Consultant for: Abbott, BMS, Celgene, Johnson & Johnson, MSD, Novartis, Pfizer, UCB Pharma, D. van der Heijde Grant/research support from: AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli Lilly, GSK, Janssen, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB Pharma, Vertex, Consultant for: AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli Lilly, GSK, Janssen, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB Pharma, Vertex, Employee of: Imaging Rheumatology bv, O. Purcaru Employee of: UCB Pharma, P. Mease Grant/research support from: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Consultant for: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Speakers bureau: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma