Kim Papp

With the advent of biological therapies for the treatment of plaque psoriasis, guidance on the usage of these new agents has become necessary. One such agent, efalizumab, a humanized recombinant monoclonal IgG(1) antibody developed to target T-cell-mediated inflammation, provides rapid and sustained efficacy for many psoriasis patients. This article explores the pretreatment, initiation, and treatment phases with efalizumab therapy. In the pretreatment phase, physicians need to assess patients' disease state and educate them about the course of efalizumab treatment. Prior to initiation, physicians need to establish stable disease, ensure an adequate transition or washout of any prior psoriasis therapeutics, and obtain baseline platelet counts. After initiating treatment, both physician and patient must participate in disease monitoring. Patients responding favourably may receive continuous treatment. Those who do not respond to the drug or who experience adverse events should be managed appropriately in order to continue therapy or be transitioned onto another agent. A growing body of clinical evidence, as well as experience from clinical investigators, has provided much insight into the management strategies for patients undergoing treatment with efalizumab.

Psoriasis is a T-cell mediated skin disease that affects approximately 2% of the population worldwide. Despite the prevalence of the disease and long-standing efforts to develop strategies to treat it, there is a need for safe and effective therapies to treat psoriasis, particularly the more severe forms. Biological agents such as alefacept, efalizumab, etanercept, and infliximab have been recognized as a class of treatment distinct from other forms of therapy in the treatment algorithm of psoriasis. Recent national and international consensus meetings have developed statements that position biological agents as an important addition to the treatment armamentarium for moderate to severe psoriasis, along with phototherapy and traditional systemic agents. There has been consensus that treatment should be individualized to each patient's needs and circumstances. Biological agents offer the hope of safe, effective, long-term management of moderate to severe psoriasis. As new agents receive approval from Health Canada, the available range of therapeutic options for treating this chronic disease will broaden. A Canadian Psoriasis Expert Panel recently convened in February 2005 to analyze, based on a series of clinical case scenarios, the indications, contraindications, and considerations for and against each of the four biological agents, derived from product labelling, where available, and from the efficacy and safety data from phase 3 and earlier clinical trials, as well as post-marketing reports. The Panel has formulated a set of recommendations for incorporating these biological agents into the current treatment paradigm of moderate to severe plaque psoriasis and has identified the preferred biological agents for each patient based on individual needs and circumstances.

Psoriasis (PsO) requires safe and effective long-term management to reduce the risk of recurrence and decrease the frequency of relapse. Topical PsO therapies are a cornerstone in the management of PsO though safety concerns limit the chronic, continuous use of topical corticosteroids and/or vitamin D3 analogues. Evidence-based guidelines on optimal treatment targets and maintenance therapy regimens are currently lacking. This review explores the evidence supporting approaches to maintenance topical therapy for PsO including continuous long-term therapy, chronic intermittent use, step-down therapy, sequential or pulse therapy regimens, and proactive maintenance therapy. Several unaddressed questions are discussed including how and when to transition from acute to maintenance therapy, strategies for monitoring long-term treatment, the role of topical maintenance therapy in the context of systemic and biologic therapies, risks of maintenance therapy, prescribing a topical preparation suitable for patients' preferences and skin type, and key concepts for patient education to maximize long-term outcomes. Overall, emerging evidence supports a paradigm shift towards proactive treatment once skin is completely clear as a strategy to enhance disease control without compromising safety.

Celiac disease is a multifactorial, inflammatory disorder initiated and sustained by the ingestion of gluten. Occurring across a broad population, the intestinal and extraintestinal manifestations of celiac disease are variable in severity and may be nonspecific in presentation. Given that environmental, genetic, and immune factors involved in the pathogenesis of celiac disease that the digestive tract and skin share many characteristics, and with a prevalence of 0.5-1% in most populations, it is reasonable to consider varying presentations of skin conditions that are linked with celiac disease. The association between celiac disease and skin conditions has been discussed earlier, but new studies have emerged suggesting cutaneous involvement in addition to dermatitis herpetiformis. We review the current literature identifying the relationship and potential mechanisms between celiac disease and various skin conditions.

Etanercept, a dimeric soluble form of the p75 tumor necrosis factor (TNF) receptor, has been shown to be efficacious for the treatment of psoriatic arthritis and moderate to severe chronic plaque psoriasis, as well as rheumatoid arthritis, juvenile rheumatoid arthritis, and ankylosing spondylitis. In this article, we review the mechanism of action, pharmacokinetics, and drug interactions of etanercept. Differences between etanercept and other anti-TNF antagonists with respect to membrane binding, the effect on T lymphocytes, the effect on the blood-brain barrier, adverse event profiles, and disease efficacy are also discussed.

BACKGROUND Psoriasis is a chronic inflammatory skin disease requiring prolonged treatment. New biologic therapies require long-term evaluation to assess durability of their efficacy and safety profile over time. OBJECTIVES To evaluate long-term efficacy and safety of risankizumab (RZB) for the treatment of psoriasis. METHODS LIMMitless is an ongoing, phase 3, open-label extension study evaluating long-term efficacy and safety of RZB in adults with moderate-to-severe plaque psoriasis following multiple phase 2/3 studies. This analysis assessed efficacy through 172 weeks of continuous RZB treatment by examining the proportion of patients achieving ≥ 90% or 100% improvement in Psoriasis Area and Severity Index (PASI 90 and PASI 100), static Physician's Global Assessment of clear or almost clear (sPGA 0/1), and Dermatology Life Quality Index of no effect on quality of life (DLQI 0/1). Safety was assessed by recording adverse events (AEs) through the data cutoff date. RESULTS Of 955 patients randomized to RZB 150 mg in the base studies, 897 patients continued into LIMMitless; 799 patients were still receiving treatment in LIMMitless at the time of data cutoff for this analysis. After 172 weeks of continuous RZB treatment, 85·5% of patients achieved PASI 90, 54·4% achieved PASI 100, 85·2% achieved sPGA 0/1, and 78·4% achieved DLQI 0/1 using modified non-responder imputation. Rates of AEs leading to discontinuation and AEs of safety interest were low with long-term treatment and comparable to those identified in the base studies. CONCLUSION Overall, long-term continuous RZB was well tolerated and showed high and durable efficacy over 172 weeks.

Receptor‐interacting protein kinase 1 (RIPK1), a regulator of inflammation and cell death, is a potential therapeutic target in immune‐mediated inflammatory diseases (IMIDs). The objective of this phase IIa multicenter, randomized, double‐blind, placebo‐controlled study was to evaluate safety, tolerability pharmacokinetics, pharmacodynamics, and preliminary efficacy of GSK2982772, a RIPK1 inhibitor, in plaque‐type psoriasis. Psoriasis patients (N = 65) were randomized to 60 mg twice daily (b.i.d.) or three times daily (t.i.d.), or placebo for 84 days. Most adverse events (AEs) were mild with no severe drug‐related AEs reported. Plaque Lesion Severity Sum improved with b.i.d. treatment compared with placebo; interpretation of t.i.d. treatment results was complicated by a high placebo response. Reductions in epidermal thickness and infiltration by CD3+ T cells in the epidermis and dermis were observed compared with placebo. Results support the rationale for additional studies on RIPK1 inhibition in IMIDs.

Atopic dermatitis (AD) is a chronic heterogeneous condition characterized by erythematous, pruritic, and inflamed skin. Janus kinase (JAK) inhibitors are a new class of drugs that target proteins in the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. These drugs can be administered orally or topically to inhibit signaling of the JAK-STAT pathway and minimize the production of proinflammatory cytokines. The efficacy and safety of JAK inhibitors have been investigated in phase 2 and 3 clinical trials for AD. The safety of new medications, which are immunosuppressive by nature, is of utmost concern for the prescriber and patient alike. Herein we summarize the safety results of clinical trials using oral abrocitinib, upadacitinib, and baricitinib, as well as topical ruxolitinib and delgocitinib for the treatment of AD. The most prevalent (2-5% occurrence rate) treatment-emergent adverse events from oral JAK inhibitor use in AD were nausea, upper respiratory tract infection, headache, herpes zoster, herpes simplex, acne, increased blood creatine phosphokinase levels, and decreased platelet counts. Topical JAK inhibitors were not associated with systemic effects. All studies reported that JAK inhibitors were well tolerated in patients with AD in comparison with the control group. While the use of JAK inhibitors in patients suffering from AD is very promising, trials reported to date are of short duration (maximum 16 weeks), and more information on the long-term safety of these novel agents is required.

ABSTRACT Introduction Atopic dermatitis (AD) is a common and debilitating dermatosis that often impacts the physical and psychological quality of life in children and adults. A limited number of treatment options are available for AD, and often these treatments result in an insufficient response or may be contraindicated for some patients. This treatment gap creates an increasing demand for alternative AD therapies. The Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway is known to play a critical role in the dysregulation of immune responses in AD. Inhibition of the JAK enzymes in the JAK-STAT pathway has shown potential for the treatment of this chronic skin condition. Areas covered We review the evolving efficacy and safety profile of abrocitinib, an oral JAK1 inhibitor, in the treatment of AD based on the data available from phase I, II, and III clinical trials. Expert opinion Evidence supports clinical efficacy, improved pruritus and an acceptable safety profile, making abrocitinib a viable alternative to conventional AD therapies. Pivotal phase III trials included subjects aged 12 years and above, providing a new mechanism of action for future treatment of adolescent and adult AD. Further investigations are required to have a thorough understanding of abrocitinib in the treatment of AD.

Long‐term efficacy and safety of ixekizumab [160 mg at week 0, then 80 mg every 2 weeks (Q2W) for 12 weeks, followed by every 4 weeks (Q4W) thereafter (i.e. Q2W/Q4W), which is the labelled psoriasis dosing where approved, except in Japan] have been established for the treatment of adults with moderate‐to‐severe plaque psoriasis. However, some patients may benefit from remaining on Q2W dosing beyond 12 weeks.

BACKGROUND Atopic dermatitis (AD) is a highly pruritic chronic inflammatory skin disorder. Ruxolitinib, a selective inhibitor of Janus kinase (JAK)-1 and JAK2, potently suppresses cytokine signaling involved in AD pathogenesis. OBJECTIVE To evaluate the efficacy and safety of ruxolitinib (RUX) cream in adults with AD. METHODS In this phase 2 study (NCT03011892), 307 adult patients with AD, an Investigator's Global Assessment (IGA) score of 2 or 3 (mild or moderate), and 3%‒20% affected body surface area were equally randomized for 8 weeks of double-blind treatment to RUX (1.5% twice daily [BID], 1.5% once daily [QD], 0.5% QD, 0.15% QD), vehicle, or triamcinolone cream (0.1% BID for 4 weeks then vehicle for 4 weeks). Subsequently, patients could apply 1.5% RUX BID for 4 additional weeks of open-label treatment. The primary endpoint was the comparison between 1.5% RUX cream BID and vehicle in mean percentage change from baseline in Eczema Area and Severity Index (EASI) at Week 4. RESULTS All RUX regimens demonstrated therapeutic benefit at Week 4; 1.5% BID provided the greatest improvement in EASI (71.6% vs 15.5%; P<0.0001) and IGA responses (38.0% vs 7.7%; P<0.001) versus vehicle. Rapid reductions in the itch numerical rating scale score occurred within 36 hours (1.5% BID vs vehicle, ‒1.8 vs ‒0.2; P<0.0001) and were sustained through 12 weeks. Patients who transitioned to 1.5% RUX BID improved in all measures. RUX was not associated with clinically significant application site reactions. CONCLUSION RUX cream provided rapid and sustained improvements in AD symptoms and was well tolerated. CLINICAL IMPLICATIONS Ruxolitinib cream significantly reduced signs of atopic dermatitis (AD) throughout the study and rapidly decreased itch. These data support possible addition of ruxolitinib cream to the topical armamentarium for AD.

The use of immunosuppressive therapies for immune-mediated disease is associated with an elevated risk of infections and related comorbidities. While many infectious diseases can generally be prevented by vaccines, immunization rates in this specific patient population remain suboptimal, due in part to uncertainty about their efficacy or safety under these clinical situations. To address this concern, a multidisciplinary group of Canadian physicians with expertise in dermatology, gastroenterology, infectious diseases, and rheumatology developed evidence-based clinical guidelines on vaccinations featuring 13 statements that are aimed at reducing the risk of preventable infections in individuals exposed to immunosuppressive and immunomodulatory agents.

Background:Patients with immune-mediated diseases on immunosuppressive therapies have more infectious episodes than healthy individuals, yet vaccination practices by physicians for this patient population remain suboptimal.Objectives:To evaluate the safety and efficacy of vaccines in individuals exposed to immunosuppressive therapies and provide evidence-based clinical practice recommendations.Methods:A literature search for vaccination safety and efficacy in patients on immunosuppressive therapies (2009-2017) was conducted. Results were assessed using the Grading of Recommendation, Assessment, Development, and Evaluation system.Results:Several immunosuppressive therapies attenuate vaccine response. Thus, vaccines should be administered before treatment whenever feasible. Inactivated vaccines can be administered without treatment discontinuation. Similarly, evidence suggests that the live zoster vaccine is safe and effective while on select immunosuppressive therapy, although use of...

BACKGROUND Guselkumab, a human monoclonal antibody that binds to the p19 subunit of interleukin 23, has been approved for the treatment of moderate-to-severe psoriasis. Psoriatic arthritis is a common comorbidity of psoriasis with an umet need for novel treatments. We assessed the efficacy and safety of guselkumab in patients with active psoriatic arthritis. METHODS We did a randomised, double-blind, placebo-controlled, phase 2a trial at 34 rheumatology and dermatology practices in Canada, Germany, Poland, Romania, Russia, Spain, and the USA. Eligible participants were aged 18 years or older with active psoriatic arthritis and plaque psoriasis affecting at least 3% of their body surface area, with three or more of 66 tender joints and three or more of 68 swollen joints, who had an inadequate response or intolerance to standard treatments. We randomly assigned patients (2:1) via a central interactive web-response system using computer-generated permuted blocks with a block size of six, stratified by previous anti-tumour necrosis factor-α use, to receive subcutaneous guselkumab 100 mg or placebo at week 0, week 4, and every 8 weeks thereafter for 24 weeks. Patients, investigators, and site staff were masked to treatment assignment until final database lock at week 56. At week 16, patients with less than 5% improvement in swollen and tender joint counts were eligible for early escape to ustekinumab. At week 24, the remaining placebo-treated patients crossed over to receive guselkumab 100 mg at weeks 24, 28, 36, and 44 and guselkumab-treated patients received a placebo injection at week 24, followed by guselkumab injections at weeks 28, 36, and 44. The primary endpoint was the proportion of patients with at least 20% improvement at week 24 in signs and symptoms of psoriatic arthritis according to American College of Rheumatology criteria (ACR20) in the modified intention-to-treat population (ie, all randomly assigned patients who received at least one dose of study treatment). Safety analyses included patients according to the study drug received. This study is registered with ClinicalTrials.gov, number NCT02319759. FINDINGS Between March 27, 2015, and Jan 17, 2017, we randomly assigned 149 patients to treatment: 100 to guselkumab and 49 to placebo. 17 (35%) of 49 patients in the placebo group and ten (10%) of 100 patients in the guselkumab group were eligible for early escape to ustekinumab at week 16. 29 (59%) of 49 patients in the placebo group crossed over and received guselkumab at week 24. Three (6%) of 49 patients in the placebo group, one (3%) of 29 patients who crossed over from placebo to guselkumab, and six (6%) of 100 patients in the guselkumab group discontinued study treatment before week 44. 58 (58%) of 100 patients in the guselkumab group and nine (18%) of 49 patients in the placebo group achieved an ACR20 response at week 24 (percentage difference 39·7% [95% CI 25·3-54·1]; p<0·0001). Between week 0 and week 24, 36 (36%) of 100 guselkumab-treated patients and 16 (33%) of 49 placebo-treated patients had at least one adverse event. The most frequent adverse event was infection in both groups (16 [16%] of 100 patients in the guselkumab group vs ten [20%] of 49 patients in the placebo group). The prevalence of adverse events between week 0 and week 56 in guselkumab-treated patients (51 [40%] of 129) indicated no disproportional increase with longer guselkumab exposure. No deaths occurred. INTERPRETATION Guselkumab, a novel anti-interleukin 23p19 antibody, significantly improved signs and symptoms of active psoriatic arthritis and was well tolerated during 44 weeks of treatment. The results of this study support further development of guselkumab as a novel and comprehensive treatment in psoriatic arthritis. FUNDING Janssen Research & Development.

Risankizumab is a humanised IgG1 monoclonal antibody that binds to the p19 subunit of interleukin-23, inhibiting this key cytokine and its role in psoriatic inflammation. We aimed to assess the efficacy and safety of risankizumab compared with placebo or ustekinumab in patients with moderate-to-severe chronic plaque psoriasis. UltIMMa-1 and UltIMMa-2 were replicate phase 3, randomised, double-blind, placebo-controlled and active comparator-controlled trials done at 139 sites in Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Japan, Mexico, Poland, Portugal, South Korea, Spain, and the USA. Eligible patients were 18 years or older, with moderate-to-severe chronic plaque psoriasis. In each study, patients were stratified by weight and previous exposure to tumour necrosis factor inhibitor and randomly assigned (3:1:1) by use of interactive response technology to receive 150 mg risankizumab, 45 mg or 90 mg ustekinumab (weight-based per label), or placebo. Following...

This study evaluated pharmacokinetics (PK), efficacy, safety, and tolerability of bleselumab - a fully-human anti-CD40 monoclonal recombinant IgG4. Patients with moderate-to-severe psoriasis were randomized on Day 1 to receive bleselumab or placebo on Days 1, 15, and 29 in a dose-escalation of bleselumab 0.1, 0.3, 1.0, or 3.0mg/kg. The safety-analysis set (SAF) and full-analysis set (FAS) included all patients who received bleselumab or placebo, and the PK-analysis set (PKAS) included patients in the SAF with ≥1 quantifiable serum bleselumab concentration. Serial blood samples were collected after each dose, and bleselumab serum concentration was measured. After each dose, area-under-the-concentration-time curve over 336 hours (AUC ) and maximum serum concentration (C ), and dose proportionality of AUC and C were determined. Psoriasis Area and Severity Index (PASI) score, Physician Static Global Assessment (PSGA) score, percentage body surface area (%BSA) affected with psoriasis, ad...

Neutralizing interleukin (IL)-17F in addition to IL-17A may provide a more complete and specific approach to inhibiting inflammation. Assess the efficacy and safety of bimekizumab, a monoclonal antibody that potently and selectively neutralizes IL-17A and IL-17F, in patients with moderate-to-severe plaque psoriasis. Double-blinded, placebo-controlled phase 2b study (NCT02905006). Patients (randomized 1:1:1:1:1:1) received subcutaneous bimekizumab every four weeks at doses of 64mg, 160mg, 160mg with 320mg loading dose, 320mg, 480mg, or placebo. Primary endpoint was ≥90% reduction in Psoriasis Area Severity Index (PASI90) at Week 12. There was a significant (P<0.0001) dose-response for PASI90 (Week 12); more patients achieved PASI90 than placebo (46.2-79.1% versus 0%, P<0.0001 all doses). Across all doses, there were significant improvements from baseline for all secondary endpoints (PASI90 [Week 8], PASI75 and PASI100 [Week 12], Investigators Global Assessment "clear"...

Biologics have transformed the management of moderate to severe psoriasis. The persistency of biologics lacks real-world data. To quantify drug survival of infliximab (IFX), adalimumab (ADA), etanercept (ETA), and ustekinumab (UST) and to identify potential factors affecting drug survival. An observational, retrospective 2-centre study consisting of 906 patients from private practices in Ontario between July 2003 and June 13, 2016, was conducted, including patients with plaque psoriasis receiving commercial treatment with ADA, ETA, IFX, and UST. Paper and electronic records of each patient were reviewed. Median survival times for UST, IFX, ADA, and ETA were respectively, in months, 68, 23, 33, and 28. Female sex was determined to be a statistically significant positive predictor of drug survival. Our study was consistent with the literature in that UST had the highest survival rate compared to the other biologics, and the shape of our drug survival curve suggested that loss of drug ...

Atopic dermatitis (AD) is a common and chronic inflammatory skin disease. Approximately 10% of adults with AD do not respond adequately to topical therapies and require phototherapy and/or systemic therapy. To provide a patient-focused approach to the identification and management of adults with AD who require systemic treatment. A working group of clinicians experienced in managing AD was convened to review and discuss current evidence on the identification and clinical management of adults with moderate to severe AD. We propose a set of simple and practical clinical criteria for selecting candidates for systemic treatment of AD based on their response to first-line topical therapy and 4 clinical measures that are easily incorporated into routine practice. We also suggest a framework for evaluating systemic treatments according to attributes that are important from both a clinician's and a patient's perspective. An algorithm was developed proposing a pathway for treatment o...

Physicians rely on safety and efficacy data from pivotal trials to guide treatment decisions and manage patients. Even with robust clinical trial data, there remain questions regarding rare safety events and generalizability. Registries complement clinical trials. By evaluating effectiveness and safety in broad patient populations and often providing longer term or larger numbers of patients or both compared to clinical trials, registries consolidate and may extend the safety observations derived from pivotal trials. Our review of phase 3 clinical trial data, long-term extension studies and biologics registries shows biologics to be a safe option for short- and long-term use. Tumor necrosis factor (TNF)-, interleukin (IL)-12/23- and IL-17-antagonists yield similar safety profiles regarding infections, malignancy and major adverse cardiovascular events. The known risk of tuberculosis activation with TNF agonists appears to be readily handled by screening. Mild to moderate candida inf...

Previous clinical trials have not evaluated improvement in nail psoriasis as a primary end point. This phase 3 trial evaluated the safety and efficacy of adalimumab in patients with moderate-to-severe fingernail psoriasis and moderate-to-severe plaque psoriasis. Patients were randomized 1:1 to 40 mg adalimumab every other week or placebo. The primary efficacy end point was at least 75% improvement in total-fingernail modified Nail Psoriasis Severity Index (NAPSI75) response rate at week 26. Ranked secondary end point scores evaluated at week 26 were total-fingernail NAPSI and modified NAPSI, nail pain, Nail Psoriasis Physical Functioning Severity, Brigham Scalp Nail Inverse Palmo-Plantar Psoriasis Index, and Physician's Global Assessment (fingernail psoriasis). Of the 217 randomized patients (108 received placebo and 109 received adalimumab), 188 (86.6%) completed 26 weeks of treatment (period A) or escaped early to the open-label period. The study met the primary end point (res...

Individuals with psoriasis are at increased risk for psychiatric comorbidities, including suicidal ideation and behavior (SIB). To distinguish between the underlying risk and potential for treatment-induced psychiatric adverse events in patients with psoriasis being treated with brodalumab, a fully human anti-interleukin 17 receptor A monoclonal antibody. Data were evaluated from a placebo-controlled, phase 2 clinical trial; the open-label, long-term extension of the phase 2 clinical trial; and three phase 3, randomized, double-blind, controlled clinical trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3) and their open-label, long-term extensions of patients with moderate-to-severe psoriasis. The analysis included 4464 patients with 9161.8 patient-years of brodalumab exposure. The follow-up time-adjusted incidence rates of SIB events were comparable between the brodalumab and ustekinumab groups throughout the 52-week controlled phases (0.20 vs 0.60 per 100 patient-years). In the brodaluma...

Objectives To describe safety of UST during double-blind, PBO-controlled portion of the PsA & PsO programs. Methods Safety for PsA were pooled from a Ph2(n=146)& 2 Ph3(PSUMMIT I[n=615], PSUMMIT II[n=312]) studies in pts with active PsA. Safety for PsO were pooled from 1 Ph2(n=320) & 2 Ph3(PHOENIX1[n=766] & PHOENIX2[n=1230]) studies of UST in mod-to-sev PsO, including sub-grp of pts with PsA (hx/current) at baseline(BL) [n=628]. Pts were rand to PBO, UST45mg or 90mg. PBO-controlled period was 16wks for PsA studies, 20wks for Ph2 PsO study, & 12wks for Ph3 PsO studies. Concomitant therapy(stable doses of MTX/oral corticosteroids/NSAIDs) were permitted in PsA studies;no concurrent therapies for PsO/PsA were permitted in PsO studies. Overall safety rates were compared between PBO&UST grps within each population. UST dose grps were analyzed as combined grp. Pts who received ≥1dose were included. Results reported as # of events/100 pt-yrs of follow-up(PY). Results 1071 treated pts (379 PBO, 692 UST) were included in PsA population & 2314 treated pts (732 PBO, 1582 UST) were included in PsO population (including 207 PBO, 421 UST in PsA sub-grp). BL demographics & medical history were generally comparable between PsA & PsO populations with similar proportions reporting relevant comorbidities, including diabetes, hyperlipidemia, hypertension & family history of CHD. In PsA, median duration of PsA at BL was ≥4yrs &>75% had PsO with ≥3% BSA skin involvement. In PsO, median BSA involvement was 21%;median PASI score was 17&27% had PsA. Safety observed during the PBO-controlled period are detailed(Table). Within each population, rates of overall AEs, infections, & SAEs in pts receiving PBO or UST were generally comparable. Slightly higher rates of AEs leading to d/c were observed across all PBO grps & slightly higher rate of SAEs was observed in the PBO grp in the PsA population. Rates of AEs of interest were generally comparable, with overlapping confidence intervals, between PBO & UST grps within the PsA & PsO populations. Image/graph Conclusions During the PBO-controlled portion, UST was well-tolerated. Overall safety were consistent between populations & safety event rates were generally comparable between pts receiving PBO & UST within each population. Disclosure of Interest I. McInnes Grant/research support from: Janssen R&D, LLC, K. Papp Grant/research support from: Janssen R&D, LLC, L. Puig Grant/research support from: Janssen R&D, LLC, K. Reich Grant/research support from: Janssen R&D, LLC, C. Ritchlin Grant/research support from: Janssen R&D, LLC, B. Strober Grant/research support from: Janssen R&D, LLC, P. Rahman Grant/research support from: Janssen R&D, LLC, A. Kavanaugh Grant/research support from: Janssen R&D, LLC, A. Mendelsohn Employee of: Janssen R&D, LLC, M. Song Employee of: Janssen R&D, LLC, D. Chan Employee of: Janssen R&D, LLC, Y. K. Shen Employee of: Janssen R&D, LLC, S. Li Employee of: Janssen R&D, LLC, A. B. Gottlieb Grant/research support from: Janssen R&D, LLC