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Background:In patients (pts) with psoriatic arthritis (PsA), fatigue is a major driver of perceived impact of disease and has been identified as an important domain to be assessed in clinical trials.1,2 The association between fatigue and other PsA domains (eg, physical function) or clinical response is not well understood.Objectives:Fatigue was measured with the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue questionnaire in the pivotal DISCOVER-1 and DISCOVER-2 Phase 3 studies of guselkumab (GUS) vs placebo (PBO). This post hoc analysis explores the correlation between FACIT-Fatigue and physical function and clinical response in the DISCOVER program.Methods:This analysis used pooled data from pts (N=1120) treated with GUS or PBO. In DISCOVER-1 and DISCOVER-2, 381 pts with active PsA (swollen joint count [SJC] ≥3, tender joint count [TJC] ≥3, C-reactive protein [CRP] ≥0.3 mg/dL) and 739 pts with active PsA (SJC ≥5, TJC ≥5, CRP ≥0.6 mg/dL) and inadequate response to standard therapies, respectively, were randomized 1:1:1 to GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or PBO. PBO pts switched to GUS 100 mg Q4W at W24. The FACIT-Fatigue questionnaire has 13 items that assess self-reported fatigue/tiredness over the last 7 days. Items are scored from 0 (very much fatigued) to 4 (not at all fatigued). FACIT-Fatigue response was defined as an increase of ≥4 points from baseline. Physical function was evaluated with the Health Assessment Questionnaire-Disability Index (HAQ-DI). HAQ-DI response was defined as a decrease of ≥0.35 points from baseline. Clinical response was defined as achievement of ≥20% improvement in the American College of Rheumatology (ACR 20) criteria. Relationships between FACIT-Fatigue and HAQ-DI at W8/16/24 were assessed by Pearson correlation coefficients. Mean changes in HAQ-DI scores at W8/16/24 were summarized in FACIT-Fatigue responders and nonresponders. A logistic regression model was applied to estimate odds ratios (ORs) for achievement of HAQ-DI and ACR 20 response by FACIT-Fatigue response status at each visit. A multiple linear regression model was used to evaluate the association between FACIT-Fatigue and HAQ-DI at W24 after adjusting for SJC, TJC, CRP, and pt assessment of pain.Results:FACIT-Fatigue and HAQ-DI scores and changes from baseline were negatively correlated at W8, W16, and W24 (Table 1). Mean changes in HAQ-DI were −0.31, −0.43, and −0.48 at W8, W16, and W24, respectively, in FACIT-Fatigue responders and −0.06, −0.07, and −0.09, respectively, in FACIT-Fatigue nonresponders. FACIT-Fatigue responders were significantly more likely than nonresponders to achieve HAQ-DI and ACR 20 response (OR [95% CI] at W8, 2.8 [2.2-3.7] and 2.4 [1.9-3.1]; at W16, 3.6 [2.8-4.7] and 2.9 [2.3-3.7]; and at W24, 4.4 [3.4-5.7] and 3.2 [2.5-4.2], respectively; Figure 1). Correlations between FACIT-Fatigue and HAQ-DI remained significant after adjusting for SJC, TJC, CRP, and pt assessment of pain.Conclusion:In pts with PsA, fatigue response is a clinically meaningful predictor of improvements in physical function and achievement of ACR 20 response, reinforcing the importance of assessing fatigue in PsA disease management.References:[1]Leung YY et al. J Rheumatol. 2020;96:46-9.[2]Gudu T et al. Joint Bone Spine. 2016;83:439-43.Table 1.Correlation* of FACIT-Fatigue and HAQ-DIVisitHAQ-DI and FACIT Fatigue ScoresChanges From Baseline in HAQ-DI and FACIT-Fatigue ScoresW8−0.61 (p−0.42 (pW16−0.60 (p−0.47 (pW24−0.62 (p−0.50 (p*Determined by Pearson correlation coefficient; p-values derived from hypothesis tests of correlation ρ=0 (ie, no correlation).Figure 1Disclosure of Interests:Arthur Kavanaugh Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Genentech, Janssen, Eli Lilly, Merck, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Genentech, Janssen, Eli Lilly, Merck, Novartis, Pfizer and UCB, Yan Liu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GSK, Janssen, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Philip J Mease Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB; and personal fees from Boehringer Ingelheim and GlaxoSmithKline, Philip Helliwell Consultant of: Galapagos, Janssen, Novartis, Grant/research support from: Abbvie, Janssen, Pfizer, Laure Gossec Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Biogen, Celgene, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, Grant/research support from: Amgen, Galapagos, Janssen, Eli Lilly, Pfizer, Sandoz, Sanofi, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Chenglong Han Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Proton Rahman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Janssen and Novartis.

Background:DISCOVER 1 & 2, two double-blind, phase-3, psoriatic arthritis (PsA) trials of guselkumab (GUS, an IL-23 inhibitor), demonstrated significant improvement with GUS vs placebo (PBO) in signs and symptoms of PsA, with good tolerability, at week (w) 24 during the PBO-controlled period.1,2 Beyond w24, all patients (pts) switched to GUS. Continued treatment maintained efficacy through w52.3,4Objectives:To describe pooled safety results from the DISCOVER 1 & 2 trials through 1-year of GUS treatment.Methods:Adults with active PsA (DISCOVER 1: ≥3 tender/swollen joints and C-Reactive protein [CRP] ≥0.3 mg/dL; DISCOVER 2: ≥5 tender/swollen joints and CRP ≥0.6 mg/dL) were randomized to subcutaneous GUS 100 mg at w0, w4, then every 8 w (q8w); GUS 100 mg q4w; or PBO. At w24, PBO pts switched to GUS 100 mg q4w. Pts were biologic naive except ~30% pts in DISCOVER 1. Safety was reported through w60 in DISCOVER 1 and through w52 in DISCOVER 2.Results:Baseline characteristics were similar between treatment groups in the pooled studies. Through w24 and 1 year, numbers of pts per 100 patient years with ≥1 event were similar among treatment groups for adverse events (AEs), serious AEs, infections, serious infections, and discontinuations due to AE (Table 1). At 1 year, there were no cases of active tuberculosis, opportunistic infections (including candida), or inflammatory bowel disease in GUS-treated pts; 2 deaths in PBO pts; and low incidences that were similar across treatment groups for malignancy, major adverse cardiac events, and injection-site reactions. Incidence of anti-GUS antibodies was 4.5%, and most were not neutralizing. Mild elevations in serum hepatic transaminases and decreases in neutrophil counts were consistent at 1 year with the results at w24 (Table 1).Conclusion:GUS regimens of q8w and q4w were well tolerated in PsA pts through 1 year of treatment in the phase-3 DISCOVER trials, consistent with the w24 results. No meaningful differences between incidences of AEs were reported in the q8w and q4w groups. The safety profile of GUS in PsA pts is generally comparable with the previously established safety profile of GUS.References:[1]Deodhar A et al. Lancet. 2020;395:1115[2]Mease P et al. Lancet. 2020;395:1126[3]Ritchlin C et al. EULAR 2020 # SAT0397[4]McInnes I et al. EULAR 2020 # SAT0402Table 1.Number of Patients with AEs per 100 PY and Incidence of AEs of InterestTime Period24 Weeks1 Year*Treatment GroupPBOGUS SC 100 mgPBO to GUS‡GUS SC 100 mgDosing ScheduleMatchingq8wq4wGUSCombined†q4wq8wq4wGUSCombined‡ N3723753737483523753731100Total PY Follow-Up173173172346204384385589Patients with AEs per 100 PY, n (95% CI)≥1 AE143 (123, 166)148 (127, 171)154 (132, 178)151 (136, 167)92 (77, 108)114 (100, 130)115 (101, 131)109 (100, 117)≥1 Serious AE7.1 (3.7, 12)4.1 (1.6, 8.4)4.7 (2.0, 9.3)4.4 (2.5, 7.3)7.0 (3.8, 11.8)4.8 (2.9, 7.6)4.0 (2.2, 6.6)4.9 (3.6, 6.6)≥1 Infection50 (39, 62)47 (37, 59)52 (42, 65)49 (42, 58)39 (31, 49)41 (34, 48)38 (31, 45)39 (35, 44)≥1 Serious Infection1.7 (0.4, 5.1)0.6 (0.0, 3.2)1.8 (0.4, 5.1)1.2 (0.3, 3.0)2.5 (0.8, 5.8)1.3 (0.4, 3.1)0.8 (0.2, 2.3)1.3 (0.7, 2.3)Discontinued due to AE4.1 (1.6, 8.4)2.9 (1.0, 6.8)4.7 (2.0, 9.3)3.8 (2.0, 6.5)3.5 (1.4, 7.1)2.1 (0.9, 4.1)2.6 (1.3, 4.8)2.6 (1.7, 3.8)AEs of Interest§, n (%)Death2 (0.5)0000000Malignancy1 (0.3)2 (0.5)02 (0.3)1 (0.3)2 (0.5)03 (0.3)Major Adverse Cardiac Events1 (0.3)01 (0.3)1 (0.1)001 (0.3)1 (0.1)Opportunistic Infections00000000Tuberculosis00000000Inflammatory Bowel Disease1 (0.3)0000000Injection-Site Reaction1 (0.3)5 (1.3)4 (1.1)9 (1.2)4 (1.1)6 (1.6)9 (2.4)19 (1.7)Anti-GUS Antibody+-6/373 (1.6)9/371 (2.4)15/744 (2.0)14/350 (4.0)18/373 (4.8)17/371 (4.6)49/1094 (4.5)*Through w60 for DISCOVER 1 and w52 for DISCOVER 2; †Combined GUS q8w and q4w; ‡For patients who switched from PBO to GUS, only data on and after first GUS administration were included in this group; §PBO N=370.AE, adverse event; CI, confidence interval; GUS, guselkumab; PBO, placebo; PY, patient year; q4w, every 4 weeks; q8w, every 8 weeks; SC, subcutaneous; w, weekDisclosure of Interests:Christopher T. Ritchlin Grant/research support from: Received grant/research support from UCB Pharma, AbbVie, Amgen, consultation fees from UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Proton Rahman Speakers bureau: Received speakers fees from Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Grant/research support from: Received grant/research support from Janssen and Novartis, consultation fees from Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Philip Helliwell Consultant of: Consultation fees paid to charity (AbbVie, Amgen, Pfizer, UCB) or himself (Celgene, Galapagos), Grant/research support from: Received grants/research support paid to charity (AbbVie, Janssen, Novartis), Wolf-Henning Boehncke Consultant of: Received consultation fees from Janssen, Grant/research support from: Received grant/research support from Janssen Research & Development, LLC, Iain McInnes Consultant of: Received consultation fees from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Received grant/research support from Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Alice B Gottlieb Speakers bureau: Received speakers fees from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, Consultant of: Received consultation fees from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, Grant/research support from: Received grant/research support from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, Shelly Kafka Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Alexa Kollmeier Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Xie L Xu Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, May Shawi Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Prasheen Agarwal Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Bei Zhou Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Paraneedharan Ramachandran Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Philip J Mease Speakers bureau: Received speakers fees from Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Consultant of: Received consultation fees from Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB, Grant/research support from: Received grant/research support from Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB.

Background:In the DISCOVER-1 study, the interleukin-23 p19 subunit inhibitor guselkumab (GUS) demonstrated robust efficacy across joint and skin clinical manifestations of psoriatic arthritis (PsA).1 Patients (pts) with PsA also experience a broad range of symptoms that negatively impact health-related quality of life (eg, pain, fatigue, anxiety, depression, sleep disturbance, poor physical function).2Objectives:Assess the treatment effect of GUS on general health outcomes in pts with PsA in the DISCOVER-1 trial through Week (W) 52 using the Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) instrument.Methods:Pts with active PsA (≥3 swollen + ≥3 tender joints; C-reactive protein ≥0.3 mg/dL) and inadequate response to standard conventional therapies were randomized 1:1:1 to GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or placebo (PBO). PBO pts switched to GUS 100 mg Q4W at W24. PROMIS-29 contains 4 items for each of 7 domains (anxiety, depression, fatigue, pain interference, physical function, sleep disturbance, social participation) and 1 pain intensity item; 28 items are scored on a 5-point Likert-type scale, and pain intensity is rated from 0-10. The raw score of each domain is converted to a standardized T-score, with norms based on a general population mean score=50 and a standard deviation (SD)=10. Higher scores in anxiety, depression, fatigue, pain interference, and sleep disturbance indicate more severe symptoms; higher physical function and social participation scores indicate better health outcomes. Changes ≥5 points (1/2 SD of T-score) are considered clinically meaningful. Analyses were performed using both observed (mean scores/changes, effect sizes) and imputed (clinically meaningful response, whereby change from baseline was set to 0 at W24/52 for pts who had missing data or at W24 for pts who met treatment failure criteria prior to W24).Results:At baseline, mean PROMIS-29 T-scores for physical function, social participation, sleep disturbance, pain, and fatigue were worse in the 381 PsA pts enrolled in DISCOVER-1 than in the general US population. Across all 7 domains, observed mean PROMIS-29 T-scores showed improvements in GUS-treated pts from baseline to W24 and W52 (Figure 1). Observed mean changes from baseline to W24 and W52, with calculated effect size, are shown (Table 1). In all pts, including those with imputed data, significantly higher percentages of pts in both GUS treatment groups vs PBO had ≥5-point improvements in fatigue, pain interference, physical function, sleep disturbance, social participation, and pain intensity domains at W24 (all nominal pConclusion:In pts with active PsA, PROMIS-29 results indicate that GUS treatment was associated with clinically meaningful reductions in fatigue and pain and improvement in physical function and social participation, which were maintained through 1 year.References:[1] Deodhar A et al. Lancet. 2020;395:1115-25.[2] Orbai A et al. Ann Rheum Dis. 2017;76:673-80.Table 1.Mean Change and Effect Size of Change From Baseline in PROMIS-29 Domain Scores at W24 and W52 (Observed)Mean Change From Baseline [Effect Size]GUS Q4WGUS Q8WPBOW0-24GUS Q4WW24-52W24W52W24W52W24W52Anxiety−3.1 [−0.3]−3.1 [−0.3]−3.7 [−0.4]−4.3 [−0.5]−1.5 [−0.2]−3.6 [−0.4]Depression−2.7 [−0.3]−3.0 [−0.4]−4.0 [−0.4]−4.0 [−0.4]−0.6 [−0.1]−2.5 [−0.3]Fatigue−4.8 [−0.5]−5.6 [−0.6]−4.8 [−0.5]−6.8 [−0.7]−2.1 [−0.2]−5.7 [−0.6]Pain interference−5.4 [−0.8]−6.2 [−1.0]−5.8 [−1.0]−7.0 [−1.1]−2.8 [−0.4]−6.3 [−1.0]Physical function5.0 [0.8]5.9 [0.9]4.1 [0.6]5.0 [0.7]1.7 [0.2]4.2 [0.6]Sleep disturbance−2.5 [−0.4]−3.9 [−0.6]−3.8 [−0.6]−4.4 [−0.6]−1.5 [−0.2]−3.3 [−0.5]Social participation4.2 [0.5]5.3 [0.7]5.3 [0.6]6.6 [0.8]1.7 [0.2]4.9 [0.6]Pain intensity*−2.3 [−1.2]−2.8 [−1.5]−2.1 [−1.1]−2.7 [−1.4]−0.7 [−0.4]−2.5 [−1.3]*Raw score; all other domains reported as T-score.Disclosure of Interests:Ana-Maria Orbai Consultant of: Eli Lilly, Janssen, Novartis, Pfizer, UCB, Grant/research support from: Abbvie, Eli Lilly and Company, Celgene, Novartis, Janssen, Horizon, Laura C Coates Consultant of: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Boehringer Ingelehim, Celgene, Domain, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Novartis, Pfizer, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GSK, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, and UCB, Philip Helliwell Consultant of: Galapagos, Janssen, and Novartis, Grant/research support from: Abbvie, Janssen, and Pfizer, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie, Amgen, UCB Pharma, Alexa Kollmeier Shareholder of: Johnson & Johnson, of which Janssen Research & Development, LLC is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, of which Janssen Research & Development, LLC is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, of which Janssen Research & Development, LLC is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Yusang Jiang Employee of: Cytel, Inc., providing statistical support (funded by Janssen), Yan Liu Shareholder of: Johnson & Johnson, of which Janssen Research & Development, LLC is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Chenglong Han Shareholder of: Johnson & Johnson, of which Janssen Research & Development, LLC is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC.

Background:Since the 2015 GRAPPA treatment recommendations were published, therapeutic options and management strategies for psoriatic arthritis (PsA) have advanced considerably.Objectives:The goal of the GRAPPA recommendations update is to develop high quality, evidence-based recommendations for the treatment of PsA, including related conditions and comorbidities.Methods:GRAPPA rheumatologists, dermatologists and patient research partners (PRPs) updated overarching principles for the management of adults with PsA by consensus. Principles considering use of biosimilars and tapering/discontinuing of therapy were added to this update. Systematic literature searches based on data publicly available from three databases (MEDLINE, EMBASE, and Cochrane CENTRAL) were conducted from the end of the previous recommendations’ searches through August 2020. Additional abstract searches were performed for conference presentations in 2017-2020. Searches covered PsA treatments (peripheral arthritis, axial arthritis, enthesitis, dactylitis, skin, and nail disease). Additional searches were performed for related conditions (uveitis and IBD) and comorbidities evaluating their impact on safety and treatment outcomes. Individual groups assessed the risk of bias and applied the GRADE system to generate strong or conditional recommendations for therapies within the domain groups and for the management of comorbidities and related conditions. These recommendations were then incorporated into an overall treatment schema.Results:Updated, evidence-based treatment recommendations are shown (Table 1). Since 2015, many new medications have been incorporated. Additional results for older medications, such as methotrexate, have been published across PsA domains. Based on the evidence, the treatment recommendations developed by individual groups were incorporated into the overall schema including principles for management of arthritis, spondylitis, enthesitis, dactylitis, skin, and nail disease in PsA, and associated conditions (Figure 1). Choice of therapy for an individual should ideally address all of the domains that impact on that patient, supporting shared decision making with the patient involved. Additional consideration in the recommendations was given to key associated conditions and comorbidities as these often impact on therapy choice.Conclusion:These GRAPPA treatment recommendations provide up to date, evidence-based guidance to providers who manage and treat adult patients with PsA. These recommendations are based on domain-based strategy for PsA and supplemented by overarching principles developed by consensus of GRAPPA members.IndicationStrongForConditional ForConditionalAgainstStrongAgainstInsufficient evidencePeripheral Arthritis DMARD NaïvecsDMARDs, TNFi, PDE4i, IL-12/23i, IL-17i, IL-23i, JAKiNSAIDs, oral CS, IA CS,IL-6i,Peripheral Arthritis DMARD IRTNFi, IL-12/23i, IL-17i, IL-23i, JAKiPDE4i, other csDMARD, NSAIDs, oral CS, IA CS,IL-6i,Peripheral ArthritisbDMARD IRTNFi, IL-17i, IL-23i, JAKi,NSAIDs, oral CS, IA CS, IL-12/23i, PDE4i, CTLA-4-IgIL-6i,Axial arthritis, Biologic NaïveNSAIDs, Physiotherapy, simple analgesia, TNFi, IL-17i, JAKiCS SIJ injections, bisphosphonatescsDMARDs, IL-6i,IL-12/23i, IL-23iAxial PsA, Biologic IRNSAIDs, Physiotherapy, simple analgesia, TNFi, IL-17i, JAKi csDMARDs, IL-6i,IL-12/23i, IL-23iEnthesitisTNFi, IL-12/23i, IL-17i, PDE4i, IL-23i, JAKiNSAIDs, physiotherapy, CS injections, MTXIL-6i,Other csDMARDsDactylitisTNFi IL-12/23i, IL-17i, IL-23i, JAKi, PDE4iNSAIDs, CS injections, MTXOther csDMARDsPsoriasisTopicals, phototherapy, csDMARDs, TNFi, IL-12/23i, IL-17i, IL-23i, PDE4i, JAKi AcitretinNail psoriasisTNFi, IL12/23i, IL17i, IL23i, PDE4iTopical CS, tacrolimus and calcipotriol combination or individual therapies, Pulsed dye laser, csDMARDs, acitretin, JAKiTopical Cyclosporine / Tazarotene, Fumarate, Fumaric Acid Esters, UVA and UVB Phototherapy, AlitretinoinIBDTNFi (not ETN), IL-12/23i, JAKiIL-17iUveitisTNFi (not ETN)Disclosure of Interests:Laura C Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Gilead, Eli Lilly, Janssen, Medac, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Pfizer, and Novartis, Enrique Soriano Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb,GSK, Genzyme, Janssen, Lilly, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb,GSK, Genzyme, Janssen, Lilly, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Grant/research support from: AbbVie, Janssen, Novartis Pharma, Pfizer, Roche, and UCB, Nadia Corp: None declared, Heidi Bertheussen Consultant of: Pfizer, Kristina Callis-Duffin Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Lilly, Janssen, Novartis, Pfizer, Sienna Biopharmaceuticals, Stiefel Laboratories, UCB, Ortho Dermatologics, Inc, Regeneron Pharmaceuticals, Inc., Anaptys Bio, Boehringer Ingelheim., Cristiano Barbosa Campanholo Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Jeffrey Chau: None declared, Lihi Eder Consultant of: Abbvie, UCB, Janssen, Eli Lily, Pfizer, Novartis, Grant/research support from: Abbvie, UCB, Janssen, Eli Lily, Pfizer, Novartis, Daniel Fernandez Consultant of: Abbvie, UCB, Roche, Janssen, Pfizer, Amgen and Brystol, Grant/research support from: Abbvie, UCB, Roche, Janssen, Pfizer, Amgen and Brystol, Oliver FitzGerald Speakers bureau: AbbVie, Janssen and Pfizer Inc, Consultant of: BMS, Celgene, Eli Lilly, Janssen and Pfizer Inc, Grant/research support from: AbbVie, BMS, Eli Lilly, Novartis and Pfizer Inc, Amit Garg Consultant of: Abbvie, Amgen, Asana Biosciences, Bristol Myers Squibb, Boehringer Ingelheim, Incyte, InflaRx, Janssen, Pfizer, UCB, Viela Biosciences, Grant/research support from: Abbvie, Dafna D Gladman Consultant of: Abbvie, Amgen, BMS, Eli Lilly, Galapagos, Gilead, Jansen, Novartis, Pfizer and UCB, Grant/research support from: Abbvie, Amgen, Eli Lilly, Jansen, Novartis, Pfizer and UCB, Niti Goel: None declared, Suzanne Grieb: None declared, Philip Helliwell Speakers bureau: Janssen, Novartis, Pfizer, Consultant of: Eli Lilly, M Elaine Husni Consultant of: Abbvie, Amgen, Janssen, Novartis, Lilly, UCB, Regeneron, and Pfizer, Deepak Jadon Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Healthcare Celltrion, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, UCB, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Healthcare Celltrion, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Healthcare Celltrion, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, UCB, Arnon Katz: None declared, Dhruvkumar Laheru: None declared, John Latella: None declared, Ying Ying Leung Speakers bureau: Novartis, AbbVie, Eli Lilly, Janssen, Consultant of: Pfizer and Boehringer Ingelheim, Grant/research support from: Pfizer and conference support from AbbVie, Christine Lindsay Shareholder of: Amgen, Employee of: Aurinia pharmaceuticals, Ennio Lubrano Speakers bureau: Alfa-Sigma, Abbvie, Galapagos, Janssen Cilag, Lilly., Consultant of: Alfa-Sigma, Abbvie, Galapagos, Janssen Cilag, Lilly., Luis Mazzuoccolo Speakers bureau: Abbvie, Amgen, Novartis, Elli Lilly, Jansen, Consultant of: Abbvie, Amgen, Novartis, Elli Lilly, Jansen, Roland McDonald: None declared, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer, SUN and UCB, Denis O’Sullivan: None declared, Alexis Ogdie Consultant of: AbbVie, Amgen, BMS, Celgene, Corrona, Gilead, Janssen, Lilly, Novartis, and Pfizer, Grant/research support from: Novartis and Pfizer and Amgen, Wendy Olsder: None declared, Lori Schick: None declared, Ingrid Steinkoenig: None declared, Maarten de Wit Consultant of: AbbVie, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, Roche, Danielle van der Windt: None declared, Arthur Kavanaugh Speakers bureau: AbbVie, Amgen, BMS, Eli Lilly, Gilead Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, BMS, Eli Lilly, Gilead Janssen, Novartis, Pfizer, UCB

Background:The monoclonal antibody guselkumab (GUS; anti- IL-23p19-subunit) is approved to treat psoriatic arthritis (PsA). Post hoc analyses of DISCOVER-1&2 suggested that GUS may be effective in improving symptoms of axial manifestation of PsA.Objectives:Evaluate the efficacy of GUS across components of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in improving symptoms of axial manifestations of active PsA patients (pts) using data from Phase 3, randomized, placebo (PBO)-controlled studies.Methods:DISCOVER-1&2 enrolled pts with active PsA; pts were randomized to subcutaneous injections of guselkumab 100 mg every 4 weeks (Q4W) or at Wk0, 4, and Q8W, or PBO. These post hoc analyses included pts who were identified by the investigator as having axial symptoms and sacroiliitis (prior X-ray or MRI or screening X-ray). BASDAI scores were assessed at Wks 0, 8, 16, 24, and 52. Mean BASDAI component scores through Wk52 are reported by treatment group. Pooled data from the two studies are reported. Mean BASDAI component scores are reported using observed data; total BASDAI scores with missing components were set to missing. The proportion of pts achieving ≥50% improvement in BASDAI (BASDAI 50) was also determined; pts with missing data or who met the treatment failure criteria (discontinued study agent or used prohibited medications) were considered nonresponders at all subsequent timepoints.Results:These analyses included 312 pts from DISCOVER-1&2 (103 GUS Q4W, 91 GUS Q8W, 118 PBO); mean total BASDAI scores at Wk0 were 6.4, 6.5, and 6.6, respectively. Demographics and mean baseline BASDAI component scores (ie, fatigue, spinal pain, joint pain, enthesitis, qualitative morning stiffness, and quantitative morning stiffness) were similar across treatment groups (Table 1). In comparison with the total study population, this subgroup of pts had a higher mean C-reactive protein level at baseline and a higher proportion of pts with enthesitis and included a slightly higher proportion of males. Mean scores for all six BASDAI components, including spinal pain, decreased through Wk24 in GUS-treated pts, with separation from PBO observed as early as Wk8; improvements were maintained at Wk52. At Wk24, BASDAI 50 response rates were higher in the Q4W and Q8W groups vs PBO (38% and 40% vs 19%).1 At WK52, mean BASDAI component scores for PBO pts who crossed over to GUS Q4W at Wk24 were similar to those for pts who were randomized to GUS.2 A similar trend was observed for BASDAI50 response.Conclusion:Among PsA pts with axial symptoms and sacroiliitis (via investigator-confirmed imaging) in the DISCOVER-1&2 trials, GUS treatment resulted in lower mean scores for all six BASDAI components compared with PBO as early as Wk 8 and through Wk24, with mean scores maintained at Wk52.References:[1]Helliwell P, et al. Ann Rheum Dis. 2020; 79; Suppl 1.[2]Mease PJ, et al. Arthritis Rheumatol. 2020; 72 (suppl 10).Table 1.Baseline demographic and disease characteristics for patients who were identified by physicians as having symptoms consistent with spondylitis and had sacroiliitis confirmed via prior radiograph/MRI or screening radiographGUS Q4WGUS Q8WPlaceboPatients, n10391118Male, n (%)68 (66)54 (59)69 (59)Age, years44.9 ± 11.845.0 ± 10.745.3 ± 11.0BASDAIPatients, n9584110Score6.4 ± 1.76.5 ± 1.86.6 ± 1.5BASDAI ComponentsFatigue6.4 ± 2.06.7 ± 1.96.5 ± 1.9Spinal pain6.6 ± 2.16.5 ± 2.36.7 ± 2.0Joint pain6.3 ± 1.96.5 ± 2.26.8 ± 1.7Enthesitis6.3 ± 2.16.4 ± 2.26.3 ± 2.2Qualitative morning stiffness6.8 ± 2.16.7 ± 2.57.0 ± 2.0Quantitative morning stiffness6.2 ± 2.95.7 ± 2.96.1 ± 2.8Data are mean ± standard deviation unless otherwise noted.BASDAI, Bath ankylosing spondylitis disease activity indexDisclosure of Interests:Frank Behrens Speakers bureau: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Genzyme, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Genzyme, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: Celgene, Chugai, Janssen, Pfizer, and Roche, Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB, Philip Helliwell Consultant of: Galapagos, Janssen, Novartis, Grant/research support from: AbbVie, Janssen, Pfizer, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, Wim Noel Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, Stephen Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, Yanli Wang Employee of: IQVIA providing statistical support (funded by Janssen), Xenofon Baraliakos Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB.

Background:Guselkumab (GUS) is a human monoclonal antibody specific to the p19-subunit of interleukin-23. GUS significantly improved signs and symptoms of PsA through Week24 (Wk24), and improvements were maintained through Wk52 in the Phase 3 DISCOVER-11 and DISCOVER-22 studies.Objectives:Assess GUS efficacy through Wk52 in both studies utilizing composite indices.Methods:Adult patients (pts) enrolled had active PsA despite standard therapies. Pts in DISCOVER-1 had ≥3 swollen and ≥3 tender joints and C-reactive protein (CRP) ≥0.3 mg/dL; in DISCOVER-2, pts had ≥5 swollen and ≥5 tender joints and CRP ≥0.6 mg/dL. 31% of DISCOVER-1 pts received 1-2 prior tumor necrosis factor inhibitors; DISCOVER-2 pts were biologic-naïve. Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at Wk0, Wk4, then every 8 weeks (Q8W); or placebo (PBO); PBO pts crossed over to GUS 100 mg Q4W at Wk24. Composite endpoints pooled across the two studies were: Disease Activity Index for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Disease Activity Score (PASDAS), Minimal Disease Activity (MDA), and Very Low Disease Activity (VLDA). GUS vs PBO comparisons through Wk24 employed a Cochran-Mantel-Haenszel test with baseline stratification factors or Fisher’s exact test; no treatment group comparisons were performed beyond Wk24. P-values were not adjusted for multiplicity. From Wk24 -Wk52, pts with missing data were considered nonresponders (>90% of pts completed study treatment through Wk52).Results:In randomized and treated pts from DISCOVER-1 (N=381) and DISCOVER-2 (N=739), pooled baseline characteristics were generally well-balanced across treatment groups and reflected active disease. Differences in response rates between GUS Q4W or Q8W and PBO were seen as early as Wk8 and increased over time through Wk24. In pts continuing GUS Q4W or Q8W, respectively, post-Wk24 response rates associated with these composite indices continued to increase through Wk52, at which time they were 54.2% and 52.5% for DAPSA LDA, 45.3% and 41.9% for PASDAS LDA, 35.9% and 30.7% for MDA, 18.2% and 17.6% for DAPSA remission, and 13.1% and 14.4% for VLDA, with no discernable difference between the GUS Q4W and Q8W dosing regimens (Table 1 and Figure 1). After PBO pts crossed over to GUS Q4W at Wk24, response rates increased through Wk52.Conclusion:GUS 100 mg Q4W and Q8W provided robust and sustained benefits to pts with active PsA across multiple domains, indicating that GUS may provide an alternative treatment option for the diverse manifestations of PsA.References:[1]Ritchlin CR et al. RMD Open 2021; 1–11. doi: rmdopen-2020-001457[2]McInnes IB, et al. Arthritis Rheumatol 2020 Oct 11. doi: 10.1002/art.41553.Table 1.Pooled response rates for DISCOVER-1 and DISCOVER-2 randomized and treated patients.DISCOVER-1&2GUS Q4WGUS Q8WPBO -->GUS Q4W1Randomized and treated patients, n373375372PASDAS2LDAWk 2427.9%**30.1%**8.9%Wk 5245.3%41.9%36.8%MDA3Wk 2422.8%**24.3%**7.8%Wk 5235.9%30.7%28.2%DAPSA4RemissionWk 2410.2%**8.3%**2.2%Wk 5218.2%17.6%11.0%VLDA3Wk 246.4%**4.3%*1.3%Wk 5213.1%14.4%8.3%Data reported as proportions of patients, %. Unadjusted p values at Wk24 vs PBO: *p1 Pts randomized to PBO crossed over to GUS Q4W at Wk24.2 PASDAS is derived from Pt global assessment of arthritis and psoriasis (0-100), Physician global assessment (0-100), swollen joint count (0-66), tender joint count (0-68), CRP (mg/L), Leeds enthesitis index score, tender dactylitis count, and the 36-item Short-Form Health Survey Physical Component Summary score. PASDAS LDA ≤3.2.3 MDA is 5/7 criteria met; VLDA is 7/7 criteria met: tender joint count ≤1, swollen joint count ≤1, Psoriasis Activity and Severity Index ≤1, Pt assessment of pain ≤15 (0-100), Pt global assessment of disease activity ≤20 (0-100), Health Assessment Questionnaire-Disability Index score ≤0.5, Tender entheseal points ≤1.4 DAPSA Remission: score ≤4 (definition in Figure 1 legend).Disclosure of Interests:Laura C Coates Consultant of: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Novartis, Pfizer, Christopher T. Ritchlin Consultant of: Amgen, AbbVie, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, and UCB, Laure Gossec Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Biogen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, and UCB., Grant/research support from: Amgen, Eli Lilly, Galapagos, Janssen, Pfizer, Sandoz, and Sanofi, Philip Helliwell Consultant of: Galapagos, Janssen, and Novartis, Grant/research support from: AbbVie, Janssen, Pfizer, Proton Rahman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Janssen and Novartis, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Chetan Karyekar Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Wim Noel Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Yusang Jiang Employee of: Cytel, Inc. providing statistical support (funded by Janssen), Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Yanli Wang Employee of: IQVIA providing statistical support (funded by Janssen), Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB.

Background:DISCOVER 1 & 2 are phase 3 psoriatic arthritis (PsA) trials investigating guselkumab (GUS), an IL-23 inhibitor that specifically binds the IL-23p19 subunit. In both studies, GUS showed significant improvement vs placebo (PBO) through week (W) 24 in the PBO-controlled period.1,2Objectives:To present integrated safety results of DISC 1 & 2 through the PBO-controlled periods.Methods:Adult patients (pts) with active PsA despite standard therapy were enrolled. All pts were biologic-naïve, except ~30% in DISC 1 with previous exposure to 1-2 TNF inhibitors. Pts were randomized to SC GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or PBO. Adverse events (AEs) and lab results were analyzed from pooled data.Results:The rates of pts experiencing ≥1 AE, serious AE, infection, serious infection, and discontinuation due to an AE were similar between GUS and PBO (Table 1). There were 2 deaths, 3 malignancies, 2 Major Adverse Cardiac Events (MACE), and no opportunistic infections (treatment group not shown to prevent unblinding). Among the AEs reported by ≥5% pts in any group (Table 1), nasopharyngitis and elevated serum hepatic aminotransferases were more common with GUS vs PBO. Laboratory ALT and AST elevations were mostly mild, transient, and not associated with significant bilirubin elevation. There was a trend to decreased neutrophil count (mostly Grade 1, transient, and not associated with infection) with GUS vs PBO (Table 2). Low rates of injection-site reactions were seen with GUS vs PBO. Anti-drug antibody development was also low (Table 1).Table 1.Patient Reported AEs, n (%)GUS100 mgQ8WGUS100 mgQ4WPBON375373372≥1 AE182 (48.5)182 (48.8)176 (47.3)≥1 Serious AE7 (1.9)8 (2.1)12 (3.2)Discontinuation due to AE5 (1.3)8 (2.1)7 (1.9)≥1 Infection73 (19.5)80 (21.4)77 (20.7)≥1 Serious infection1 (0.3)3 (0.8)3 (0.8)≥1 Opportunistic Infection (including Candida)000Active Tuberculosis000≥1 Injection-site reaction5 (1.3)4 (1.1)1 (0.3)Anti-GUS antibody +, n/N (%)6/373 (1.6)9/371 (2.4)--AEs* reported by ≥5% of patients in any treatment groupNasopharyngitis26 (6.9)19 (5.1)17 (4.6)Upper respiratory tract infection13 (3.5)23 (6.2)17 (4.6)Increased ALT23 (6.1)28 (7.5)14 (3.8)Increased AST23 (6.1)14 (3.8)9 (2.4)*Medical Dictionary for Regulatory Activities (MedDRA) preferred termTable 2.Lab Results*GUS100 mgQ8WGUS100 mgQ4WPBON373371370ALT Increased (%)Grade 128.235.030.121.12.71.43-40.81.10.8Neutrophil Count Decreased (%)Grade 15.65.93.221.61.60.83-400.30.3*NCI toxicity gradeALT=Alanine aminotransferaseConclusion:GUS was safe and well tolerated through the PBO-controlled period in 2 randomized, phase 3 trials of patients with active PsA. There were no meaningful safety differences between the Q8W and Q4W groups, no significant safety issues identified when comparing GUS to PBO, and no safety signals with regards to infections, malignancy, and MACE. The safety profile of GUS Q4W and Q8W in PsA pts was generally consistent with that in the Phase 3 trials of GUS Q8W for psoriasis.3,4References:[1]Deodhar et al. ACR 2019 (#807). Arth Rheum 2019;71 S10:1386[2]Mease et al. ACR 2019 (#L13). Arth Rheum 2019;71 S10:5247[3]Blauvelt et al. J Am Acad Derm 2017;76:405[4]Reich et al. J Am Acad Derm 2017;76:418Acknowledgments:NoneDisclosure of Interests:Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Philip Helliwell: None declared, Wolf-Henning Boehncke Grant/research support from: Janssen Research & Development, LLC, Consultant of: Janssen, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Alice B Gottlieb Grant/research support from:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Consultant of:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Speakers bureau:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Shelly Kafka Employee of: Janssen Scientific Affairs, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Prasheen Agarwal Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Bei Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Paraneedharan Ramachandran Employee of: Janssen Research & Development, LLC, Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB

Background:Guselkumab (GUS), a monoclonal antibody that specifically binds to the p19-subunit of IL-23, is approved to treat PsO. At Week24 (W24) of the Phase 3, double-blind, PBO-controlled trial in pts with active PsA who were biologic-naïve or prior TNFα inhibitor (TNFi)-treated (DISCOVER-1), GUS 100 mg, given every 4/8 weeks (Q4W/Q8W), demonstrated efficacy for joint & skin symptoms, physical function & quality of life vs PBO; AEs were consistent with GUS safety in PsO.Objectives:Assess GUS efficacy & safety in PsA through 1 year.Methods:Adults with active PsA (≥3 swollen+≥3 tender joints; CRP ≥0.3mg/dL) despite standard therapies were eligible. Approx. 30% of pts could have previously received ≤2 TNFi. Pts were randomized 1:1:1, stratified by W0 DMARD [Y/N] & prior TNFi (Y/N) use, to GUS 100mg Q4W; GUS 100 mg at W0, W4 & Q8W; or PBO. At W24, PBO pts crossed over to GUS 100 mg Q4W (PBO X Q4W). W48 marked the last dose of study agent. ACR response rates at W52, based on nonresponder imputation (NRI) for missing data and as observed in pts still on study agent at W24, are shown. Observed data for additional endpoints are shown. AEs through W60 are reported.Results:362/381 (95%) randomized pts continued study agent at W24 (125 Q4W, 123 Q8W, 114 PBO X Q4W), 347/381 (91%) pts completed treatment & 343/381 (90%) completed study. NRI ACR20 response rates were maintained at W52 (Q4W 73%, Q8W 60%; Fig 1A). Similar responses patterns were seen for the more stringent ACR50/70 criteria (Fig 1C,E). Observed ACR responses, overall (Fig, 1B,D,F) and in pts with (Fig 2A,C,E) & without (Fig 2B,D,F) prior TNFi use, were also maintained at W52. Improvements in other clinical outcomes were also maintained at W52, and responses for pts crossing over from PBO X Q4W at W24 were generally consistent with other GUS-treated pts by W52 (Table 1). Through W24, 4 (2%) GUS- and 5 (4%) PBO-treated pts had serious AEs; no GUS-treated and 2 (2%) PBO-treated pts had a serious infection. Through W60, serious AEs and serious infections occurred in 4% & 1%, respectively, of all 369 GUS-treated pts; no GUS-treated pt died or had IBD, opportunistic infections or active TB, or anaphylactic or serum sickness-like reactions.Table 1.Observed Efficacy1GUSQ4WGUSQ8WPBO(W0-24) XQ4W(W24-52)Data are % unless otherwise statedW24W52W24W52W24W52Dactylitis at W0,n373749444743Resolution64.978.467.379.561.781.4Enthesitis at W0,n717071647163Resolution49.362.940.856.331.069.8≥3% BSA psoriasis, IGA ≥2 at W0,n888881756866IGA 0/1 + ≥2-grade decrease76.183.058.069.317.681.52PASI7587.594.376.580.020.684.8PASI9063.676.150.666.713.272.7PASI10045.564.825.948.07.462.1HAQ-DI,n125124123114114104Mean change-0.4-0.5-0.3-0.4-0.1-0.4SF-36 scores,n (mean change)124124123114114104Physical Component - PCS6.68.56.57.32.76.9Mental Component - MCS3.84.93.05.11.84.2MDA, n125124123112114103MDA response31.240.323.633.912.331.1VLDA,n125124123114113104VLDA response9.616.94.112.31.814.41Randomized pts still on study agent at W24;2n=65Conclusion:GUS Q4W & Q8W maintained improvements in joint symptoms through 1 year in pts with active PsA who were biologic-naïve or previously TNFi-treated. In pts continuing in the study, improvements in skin symptoms, dactylitis, enthesitis, physical function & quality of life were also maintained through 1 year. GUS 100 mg Q4W & Q8W were safe and well-tolerated through study completion and consistent with GUS safety in PsO.1References:[1]https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TREMFYA-pi.pdf.Acknowledgments:NoneDisclosure of Interests:Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Philip Helliwell: None declared, Wolf-Henning Boehncke Grant/research support from: Janssen Research & Development, LLC, Consultant of: Janssen, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Ramanand A Subramanian Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Yusang Jiang: None declared, Bei Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB

Background:Guselkumab (GUS), an interleukin-23 inhibitor, was efficacious in reducing signs and symptoms of active psoriatic arthritis (PsA) in patients (pts) in two phase 3 trials (DISCOVER-1 and DISCOVER-2).Objectives:To evaluate the efficacy of GUS in PsA pts with imaging-confirmed axial involvement consistent with sacroiliitis in DISCOVER-1&2.Methods:In DISCOVER-1, 381 pts with active PsA (≥ 3 swollen joints, ≥ 3 tender joints; C-reactive protein ≥ 0.3mg/dL despite standard therapies) and in DISCOVER-2, 739 pts with active PsA (≥ 5 swollen joints, ≥ 5 tender joints, CRP ≥ 0.6mg/dL despite standard therapies) were randomized 1:1:1 to GUS 100mg Q4W, GUS 100mg Q8W (Wk0, Wk4, then Q8W), or PBO. This analysis included pts with sacroiliitis at baseline who had either documented imaging confirmation of sacroiliitis in the past or pelvic X-ray confirmation of sacroiliitis at screening (pooled data from DISCOVER-1&2) based on investigators’ judgment of presence/absence of sacroiliitis. Efficacy was assessed by BASDAI score, BASDAI50, modified BASDAI (mBASDAI; excludes Q#3), spinal pain (BASDAI Q#2), ASDAS-CRP score, and ASDAS responses of inactive disease (Results:312 pts presented with axial involvement (PBO, n= 118; GUS q8w, n = 91; GUS q4w, n = 103). The LS mean changes from baseline to wk24 in BASDAI, spinal pain, mBASDAI, and ASDAS-CRP were greater in the two GUS groups vs PBO (Table). Greater proportions of GUS-treated pts achieved BASDAI50 (Table) and ASDAS responses of inactive disease, major improvement, and clinically important improvement (Figure) at wk24 vs PBO.Conclusion:GUS improved axial symptoms over 24 weeks in active PsA patients with imaging-confirmed sacroiliitis.Table.Efficacy of GUS in PsA patients with axial involvement at week 24.aPBO(n=118)GUS 100 mg every 8 weeks(n=91)GUS100 mg every 4 weeks(n=103)LS Mean change in BASDAI-1.35-2.67*-2.68*LS Mean change in spinal painb-1.30-2.73*-2.48*BASDAI50c, %21/110 (19.1%)34/84 (40.5%)**36/95 (37.9%)**LS Mean change in modified BASDAId-1.13-2.16*-2.18*LS Mean change in ASDAS-CRP-0.71-1.43*-1.46*aPts with axial involvement consistent with sacroiliitis at baseline and either a history of imaging confirmation or pelvic X-ray at screening (pooled data from DISCOVER-1 & 2)bQuestion 2 of the BASDAI.cPts with BASDAI > 0 at baseline.dExcludes question 3 of the BASDAI.Unadjusted p-values as noted: *p < 0.001, ** p < 0.01Acknowledgments:NoneDisclosure of Interests:Philip Helliwell: None declared, Dafna D Gladman Grant/research support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/research support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Philip J Mease Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Eli Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer, Sun Pharma, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer, UCB Pharma, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Prasheen Agarwal Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Bei Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Chetan Karyekar Shareholder of: Johnson & Johnson, Consultant of: Janssen, Employee of: Janssen Global Services, LLC. Previously, Novartis, Bristol-Myers Squibb, and Abbott Labs., Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV

Background:DISCOVER 1 & 2 are phase-3 trials of guselkumab (GUS, an IL-23 inhibitor) in patients with psoriatic arthritis (PsA). In both trials, treatment with GUS led to significantly more improvement than placebo (PBO) in the primary endpoint (American College of Rheumatology 20% improvement criteria [ACR20]) and in other measures of arthritis and psoriasis at week (w) 24,1,2 and these improvements were maintained through 1 year of active treatment.3,4Objectives:To evaluate the effect of GUS on fatigue in DISCOVER 1 & 2 using the patient reported outcome (PRO) FACIT-Fatigue, which has demonstrated content validity and strong psychometric properties in clinical trials.5Methods:DISCOVER 1 & 2 enrolled patients with active PsA, despite non-biologic DMARDS or NSAIDS, who were biologic naïve except ~30% of patients in DISCOVER 1 who had received 1-2 TNFi. Patients were randomized (1:1:1) in a blinded fashion to subcutaneous GUS 100 mg at w0, w4, then every (q) 8w; GUS 100 mg q4w; or matching PBO. At w24, PBO patients were switched to GUS q4w. Concomitant treatment with select non-biologic DMARDS, oral corticosteroids, and NSAIDs was allowed. The FACIT-Fatigue is a 13-item PRO assessing fatigue and its impact on daily activities and function over the past 7 days, total score ranging from 0 to 52, higher score denoting less fatigue. A change of ≥4 points is considered clinically meaningful.5 The change from baseline in FACIT-Fatigue presented below is based on observed data. Mediation analysis6 was applied to the treatment effect of GUS on FACIT-Fatigue to estimate the natural direct and indirect effects, after adjusting for ACR20 response (Table 1).Results:At baseline in DISCOVER 1 & 2, the mean FACIT-fatigue scores (SD) were 30.4 (10.4) and 29.7 (9.7), respectively, indicating that patients with PsA experienced fatigue worse than the general population. At w24 in the DISCOVER trials, treatment with GUS led to significant improvements in FACIT-Fatigue scores compared with PBO, as early as w16 in DISCOVER 1 and w8 in DISCOVER 2. Improvements in fatigue were similar between GUS q4w and q8w doses, and the improvements at w24 were maintained through w52 (Figure 1). After a switch to GUS q4w at w24, PBO patients achieved FACIT-Fatigue scores that were comparable to those of GUS patients (Figure 1). 54%-63% of GUS patients compared with 35%-46% of PBO patients achieved clinically meaningful improvement (≥4 points) in FACIT-Fatigue at w24 (P≤0.003). At w52, 61%-70% of both GUS and PBO to GUS groups reached this improvement. As evaluated by mediation analysis at w24, GUS had independent positive treatment effects on fatigue (12%-36% in the q8w GUS dosing group and 69%-70% in the q4w GUS group) after adjustment for ACR20 response (Table 1).Conclusion:In 2 phase-3 trials, GUS treatment improved fatigue when compared to PBO during PBO-controlled periods and maintained improvements through 1 year of active treatment. Substantial proportions of those effects were independent of the effects on ACR20, especially for the q4W dosing group.References:[1]Deodhar et al. Lancet 2020;395:1115[2]Mease et al. Lancet 2020;395:1126[3]Ritchlin et al. EULAR20. SAT0397[4]McInnes et al. EULAR20. SAT0402[5]Cella et al. J Patient-Reported Outcomes 2019;3:30[6]Valeri et al. Psychologic Meth 2013;18:137Table 1.Mediation Analysis: Guselkumab Has Direct Effects and Indirect Effects (Mediated through ACR20) on Fatigue in PsAEffectGUS 100 mg q8w vs. PBO (95% CI)GUS 100 mg q4w vs. PBO (95% CI)DISCOVER-1Total Effect3.1 (1.0, 5.2)(p3.8 (1.9, 5.4)(p% Direct Effect11.7%68.5%% Indirect effect mediated by ACR2088.3%31.5%DISCOVER-2Total Effect4.0 (2.4, 5.5)(p3.6 (2.1, 5.0)(p% Direct Effect36.3%69.7%% Indirect effect mediated by ACR2063.7%30.3%ACR, American College of Rheumatology; CI, confidence interval; GUS, guselkumab; PBO, placebo; PsA, psoriatic arthritis; q4W, every 4 weeks; q8W, every 8 weeksDisclosure of Interests:Proton Rahman Speakers bureau: Received speakers fees from Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Grant/research support from: Received grant/research support from Janssen and Novartis, consultation fees from Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer, Philip Helliwell Consultant of: Consultation fees paid to charity (AbbVie, Amgen, Pfizer, UCB) or himself (Celgene, Galapagos), Grant/research support from: Received grants/research support paid to charity (AbbVie, Janssen, Novartis), Atul Deodhar Speakers bureau: Received speakers fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Consultant of: Received consultation fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Grant/research support from: Received grant/research support from AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Alexa Kollmeier Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Bei Zhou Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Xiwu Lin Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Chenglong Han Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Philip J Mease Speakers bureau: Received speakers fees from Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB, Consultant of: Received consultation fees from Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB, Grant/research support from: Received grant/research support from Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB.

Background:Filgotinib (FIL), a novel preferential Janus kinase 1 inhibitor, was assessed in patients with active psoriatic arthritis (PsA) in the 16-week, Phase 2, EQUATOR trial (NCT03101670).1 EQUATOR2 (NCT03320876) is the open-label extension (OLE). As previously reported, an interim analysis of the OLE showed that the majority of patients had clinical resolution of enthesitis by Week 52.2Objectives:This post-hoc analysis evaluated the effect of FIL on clinical enthesitis after 100 weeks of treatment in the OLE, as assessed using the Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada (SPARCC) index, and evaluated the discriminatory capacity of the two indices. In addition, we assessed which of the sites included in LEI and SPARCC were most frequently involved and whether treatment effect was consistent across sites.Methods:In EQUATOR, patients with active moderate-to-severe PsA (≥5 swollen joints and ≥5 tender joints, fulfilling Classification for PsA criteria) were randomised 1:1 to receive oral FIL 200 mg or placebo (PBO) once daily (QD) for 16 weeks. At Week 16, all patients could continue into the OLE, receiving FIL 200 mg QD for up to an additional 304 weeks. We compared changes from core baseline in LEI and SPARCC measures, the effect on enthesitis at sites included in LEI and SPARCC assessments and the discriminatory capacity of both enthesitis indices.Results:Of 131 patients randomised to EQUATOR, 122 entered the OLE. There was strong agreement between LEI and SPARCC at baseline. While most patients had enthesitis at baseline according to either index (76/131 [58.0%] by LEI; 85/131 [64.9%] by SPARCC), a minority had enthesitis at a large number of sites (6.9% with 5–6 LEI sites; 12.2% with ≥9 SPARCC sites). The sites most frequently involved at baseline were the lateral epicondyle humerus and Achilles tendon, sites common to both LEI and SPARCC. There was greater variability in the change from baseline to Week 16 in SPARCC compared with LEI (Table 1). LEI showed a greater discriminatory capacity than SPARCC when change from baseline was compared for FIL vs PBO at Week 16, as shown by higher absolute standardised mean difference: −0.70 (LEI) and −0.30 (SPARCC) (observed cases; Table 1). Subgroup analyses indicated that the treatment effect of FIL vs PBO at Week 16 for all sites was consistent with the overall treatment effect seen for LEI or SPARCC, and indicative of an improvement with FIL vs PBO for nearly all sites. The proportion of patients with enthesitis decreased from baseline up to OLE Week 100 (Figure 1). There were no major differences in long-term effect on enthesitis between sites.Conclusion:FIL improved enthesitis consistently across sites compared with PBO. Rapid improvement in enthesitis was seen up to Week 16 of the core study and improvements continued up to Week 52, after which responses were generally stable up to Week 100. LEI assesses fewer locations than SPARCC, but reassuringly captured the sites most commonly affected by enthesitis; LEI also had greater discriminatory capacity.References:[1]Mease P, et al. Lancet 2018;392:2367–77[2]Mease P, et al. Arthritis Rheumatol 2020;72(suppl 10): abstract 0910Figure 1.Acknowledgements:EQUATOR and EQUATOR2 were sponsored by Galapagos NV (Mechelen, Belgium) and co-funded by Galapagos NV and Gilead Sciences, Inc (Foster City, CA, USA). Eline Vetters, Leen Gilles, Benjamin Pett and his team, all employees of Galapagos, provided assistance with statistical analyses. Medical writing/editorial support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), and funded by Galapagos NV.Disclosure of Interests:Philip Helliwell Speakers bureau: Janssen, Novartis, Paid instructor for: Pfizer, Consultant of: Eli Lilly, Laura C Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, and Pfizer, Filip van den Bosch Consultant of: AbbVie, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Merck and UCB, Dafna D Gladman Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Lien Gheyle Shareholder of: Galapagos, Employee of: Galapagos, Mona Trivedi Shareholder of: Gilead Sciences, Amgen, Employee of: Gilead Sciences, Muhsen Alani Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Franck Olivier Le Brun Shareholder of: Galapagos, Employee of: Galapagos, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer, SUN and UCB.

Background:Dactylitis, a hallmark of psoriatic arthritis (PsA), is a uniformly diffuse and sometimes painful swelling of the fingers and/or toes.1 Up to 50% of patients (pts) with PsA may experience dactylitis;1,2 as such, dactylitis is an accepted domain of PsA that should be considered in treatment decisions.3 In PsA, dactylitis typically involves feet more than hands; dactylitic joints more frequently have erosive damage, compared with non-dactylitic joints.2 There remains a need for effective therapies to treat dactylitis in pts with PsA. Improvements in dactylitis have been associated with tofacitinib, an oral Janus kinase inhibitor for the treatment of PsA.4,5Objectives:To assess the effect of tofacitinib on dactylitis by location (hands/feet) and individual digit involvement in pts with PsA.Methods:These post hoc analyses used data pooled from two Phase 3 studies (12-month OPAL Broaden [NCT01877668];5 6-month OPAL Beyond [NCT01882439]4) in pts with active PsA treated with tofacitinib 5 mg twice daily (BID; approved dose; to Month [M] 6), tofacitinib 10 mg BID (to M6) or placebo (PBO; to M3); pts were treated continuously with a single conventional synthetic disease-modifying antirheumatic drug. Pts were categorised by the presence of dactylitis at baseline (BL) in the hands and/or feet. Endpoints included change from BL in Dactylitis Severity Score (DSS),6 the number of dactylitic digits and the proportion of pts with dactylitis in individual digits at M1, M3 and M6. Descriptive statistics were generated by visit and treatment arm.Results:Data were pooled from 373 pts with DSS >0 at BL. BL characteristics, including gender, age, race, body mass index, PsA duration, BL DSS and dactylitic digits count were similar across dactylitis groups and treatment groups, except for pts with dactylitis in both the hands and feet, who had higher DSS compared to those with dactylitis in the hands or feet only, likely due to having more dactylitic digits (data not shown). Regardless of location, pts treated with tofacitinib had cumulative improvements from BL to M6 in DSS (Figure 1a) and in the number of dactylitic digits (Figure 1b); improvements in DSS were greater at M1 and M3, compared with PBO. Pts treated with tofacitinib 10 mg BID typically had numerically greater improvements in DSS, compared with pts treated with tofacitinib 5 mg BID (Figure 1a). Most pts treated with tofacitinib experienced improvement of dactylitis across all fingers and toes (Figure 1c–f); mean dactylitis presence was ≤15% at M6 in pts treated with tofacitinib for all digits. Generally, at M1 and M3, fewer pts treated with tofacitinib had dactylitis in any digit, compared with PBO (Figure 1c–f).Conclusion:Among pts with pre-existing dactylitis, treatment with tofacitinib resulted in improvements in dactylitis in hands, feet, or both, and in all digits as early as M1, and up to M6.References:[1]Kaeley et al. Semin Arthritis Rheum 2018; 48: 263-273.[2]Brockbank et al. Ann Rheum Dis 2005; 64: 188-190.[3]Coates et al. Arthritis Rheumatol 2016; 68: 1060-1071.[4]Gladman et al. N Engl J Med 2017; 377: 1525-1536.[5]Mease et al. N Engl J Med 2017; 377: 1537-1550.[6]Helliwell et al. J Rheumatol 2005; 32: 1745-1750.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Ana-Maria Orbai Consultant of: Eli Lilly, Novartis, Pfizer Inc, Grant/research support from: AbbVie, Eli Lilly, Horizon, Janssen, Novartis, Philip J Mease Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer Inc, Sun, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer Inc, Sun, UCB, Philip Helliwell Paid instructor for: Janssen, Novartis, Pfizer Inc, Consultant of: Eli Lilly, Oliver FitzGerald Speakers bureau: AbbVie, Janssen, Pfizer Inc, Consultant of: Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Pfizer Inc, Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Novartis and Pfizer Inc, Mohammed Bdewi Speakers bureau: AbbVie, Pfizer Inc, Dona Fleishaker Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Rajiv Mundayat Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Pamela Young Shareholder of: Pfizer Inc, Employee of: Pfizer Inc.

Background:Psoriatic arthritis (PsA) is a heterogeneous, inflammatory disease involving multiple clinical domains including arthritis/synovitis, enthesitis, dactylitis, spondylitis and psoriasis. Effects on each domain should be assessed to determine the overall quality of treatment. Filgotinib (FIL) is a novel preferential Janus kinase 1 inhibitor that is in development for inflammatory conditions including PsA. EQUATOR (NCT03101670) was a 16-week, Phase 2, double-blind, randomised, placebo (PBO)-controlled trial of FIL for patients with active PsA.1 EQUATOR2 (NCT03320876) is an open-label extension (OLE) of the study.Objectives:This post-hoc analysis of EQUATOR and EQUATOR2 assessed the patient-level correlation between changes over time in the three PsA clinical disease domains of skin, joint and enthesitis in patients treated with FIL.Methods:In EQUATOR, patients with active moderate-to-severe PsA (≥5 swollen joints and ≥5 tender joints, fulfilling Classification for PsA criteria) were randomised 1:1 to receive oral FIL 200 mg or PBO once daily (QD) for 16 weeks. At Week 16, patients could continue into the 304-week OLE, with all patients receiving FIL 200 mg QD regardless of previous treatment in EQUATOR. This post-hoc analysis was limited to patients with skin involvement (≥3% body surface area), joint involvement and enthesitis at baseline, with changes from baseline in the three domains assessed using the Psoriasis Area and Severity Index (PASI), swollen/tender joint count (S/TJC), and the Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada (SPARCC) index, respectively. Analyses that used LEI as the enthesitis index to assess change from baseline included patients with LEI score ≥1 at baseline; those using SPARCC included patients with SPARCC score ≥1 at baseline.Results:The EQUATOR study enrolled 131 patients and 122 patients continued into the EQUATOR2 OLE. Of the 131 patients enrolled in EQUATOR, 49 and 56 patients had PsA involving all three domains at core study baseline when enthesitis was assessed using LEI and SPARCC index, respectively. Pooled data for all patients receiving FIL during the OLE indicate that improvements from baseline in the clinical domains continued with long-term treatment, with 22/42 (52%) and 23/38 (61%) patients having both SJC66 and LEI resolution at Weeks 52 and 100, respectively. For the 22 patients with both SJC and LEI resolution at Week 52, the mean percent change from baseline for PASI was –64%; for the 23 patients with both SJC and LEI resolution at Week 100, the mean percent change from baseline for PASI was –60%. The Figure 1 shows correlation between SJC, LEI and PASI at Week 100. A relationship between the three clinical domains was observed at the individual level; within a single patient, an improvement in one domain was generally followed by improvements in the other two domains. With regard to the sequence in which changes were observed, joints improved first, followed by improvements in the skin and enthesitis. There were no notable differences between changes in LEI and SPARCC enthesitis index in terms of their correlation with improvements in joint and skin involvement. Similarly, there were no notable differences in correlation between the three domains when joints were assessed using TJC rather than SJC.Conclusion:Patients with improvements in skin, joints or enthesitis following treatment with FIL generally also had improvements in the other clinical domains of PsA. The joints were found to be the first of the three domains to improve.References:[1]Mease P et al. Lancet 2018;392:2367–77Acknowledgements:EQUATOR and EQUATOR2 were sponsored by Galapagos NV (Mechelen, Belgium) and co-funded by Galapagos NV and Gilead Sciences, Inc (Foster City, CA, USA). Medical writing/editorial support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), funded by Galapagos NV.Disclosure of Interests:Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer, SUN and UCB, Laura C Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, and Pfizer, Filip van den Bosch Consultant of: AbbVie, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Merck and UCB, Dafna D Gladman Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Lien Gheyle Shareholder of: Galapagos, Employee of: Galapagos, Mona Trivedi Shareholder of: Gilead Sciences, Amgen, Employee of: Gilead Sciences, Muhsen Alani Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Eline Vetters Employee of: Galapagos, Franck Olivier Le Brun Shareholder of: Galapagos, Employee of: Galapagos, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Philip Helliwell Speakers bureau: Janssen and Novartis, Paid instructor for: Pfizer, Consultant of: Eli Lilly.

Background:EQUATOR (NCT03101670) was a Phase 2, double-blind, randomised placebo (PBO)- controlled trial of the preferential Janus kinase 1 inhibitor filgotinib (FIL) for the treatment of psoriatic arthritis (PsA); EQUATOR2 (NCT03320876) is the open-label extension (OLE).Objectives:This post-hoc analysis assessed the effect of FIL on individual Psoriatic Arthritis Disease Activity Score (PASDAS) components; and the association between PASDAS disease activity (DA) levels and DA levels achieved for each PASDAS component and patient-reported outcomes (PROs) up to OLE Week (Wk) 100.Methods:In EQUATOR, patients with active moderate-to-severe PsA were randomised 1:1 to oral FIL 200 mg or PBO once daily (QD) for 16 wks.1 At Wk 16, patients could continue into the 304-wk OLE, in which all patients received FIL 200 mg QD. The proportions of patients with PASDAS of very low DA (VLDA; ≤1.9), LDA (>1.9–Results:At OLE Wk 52, LDA and VLDA were achieved by 27.5% and 16.8% of randomised patients, respectively (44.3% combined). At OLE Wk 100, LDA and VLDA were achieved by 26.0% and 17.6% of patients (43.6% combined; Figure 1). Of patients with HDA at BL, 69% improved to MoDA/LDA/VLDA, Conclusion:The proportion of patients achieving PASDAS VLDA or LDA increased over time and remained stable between OLE Wk 52 and 100. Important factors in determining whether VLDA/LDA was met were PtGDA, PhGDA, and SF-36 PCS, although the low patient numbers is a limitation.References:[1]Mease P, et al. Lancet. 2018;392:2367–77Table 1.Mean % change from baseline in PASDAS components and PROs (observed cases)Core Wk 16 (FIL + PBO groups combined)n=122OLE Wk 52n=110OLE Wk 100n=97VLDAn=8(7%)LDAn=22(18%)Othersn=92(75%)VLDAn=22(20%)LDAn=36(33%)Othersn=52(47%)VLDA n=23(24%)LDAn=34(35%)Othersn=40(41%)PhGDA−93−75−44−94−82−56−96−84−54PtGDA−87−69−13−86−58−24−90−57−13Tender joint count 68−94−80−42−99−84−64−98−87−61Swollen joint count 66−99−80−64−99−96−78−99−94−80LEI−100−86−32−96−100−78−100−99−78Dactylitis−100−100−73−100−100−97−100−100−98C-reactive protein−66−2217138*−32−25−12−1324SF-36 PCS53261133239472316FACIT1195032975134994636HAQ-DI−84−68−18−85−51−18−88−45−19PASI−84−66−29−54−59−56−49−76−42Components or PRO measures in bold are those for which numerical differences between VLDA and LDA are greatest across timepoints*Due to outlier (3784)FACIT, Functional Assessment of Chronic Illness Therapy; HAQ-DI, Health Assessment Questionnaire Disability Index; LEI, Leeds Enthesitis Index; PASI, Psoriasis Area Severity Index; PhGDA, Physician Global Assessment of Disease Activity; PtGDA, Patient Global Assessment of Disease Activity; SF-36 PCS, Short Form-36 physical component summary; (V)LDA, (very) low disease activityAcknowledgements:EQUATOR and EQUATOR2 were sponsored by Galapagos NV Mechelen, Belgium) and co-funded by Galapagos NV and Gilead Sciences, Inc (Foster City, CA, USA). Benjamin Pett and his team, employees of Galapagos, provided assistance with statistical analyses. Medical writing/editorial support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), and was funded by Galapagos NV.Disclosure of Interests:Laura C Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, and Pfizer, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer, SUN, and UCB, Philip Helliwell Paid instructor for: Janssen, Novartis, and Pfizer, Consultant of: Eli Lilly, Filip van den Bosch Consultant of: AbbVie, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Merck, and UCB, Mona Trivedi Shareholder of: Gilead Sciences, Amgen, Employee of: Gilead Sciences, Muhsen Alani Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Franck Olivier Le Brun Shareholder of: Galapagos, Employee of: Galapagos, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Lien Gheyle Shareholder of: Galapagos, Employee of: Galapagos, Emilia Gvozdenovic Employee of: Galapagos, Dafna D Gladman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB., Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB.

Background:There is a recognised need for a continuous composite measure of disease activity for the assessment of Psoriatic Arthritis (PsA) in routine clinical settings to allow objective assessment of response and implementation of treat to target.1 Longer multidimensional measures are considered less feasible in routine care and a number of shorter measures have been proposed including, the Disease Activity Score for Psoriatic Arthritis (DAPSA), Disease Activity Score 28 (DAS28), the 3 Visual Analogue Scale (VAS) (comprising physician global VAS, patient global VAS and patient skin VAS) or 4 VAS (comprising physician global VAS, patient pain VAS, joint VAS and patient skin VAS). Testing of these measures in clinical trial datasets has been suggested but thresholds of meaning have not been established.2Objectives:To estimate clinically relevant thresholds of disease activity and improvement for composite measures for routine clinical practice in PsA.Methods:Clinical and patient reported outcome measures were assessed in patients fulfilling CASPAR criteria for PsA at three consecutive follow up visits in a UK multicentre observational study. Participants underwent clinical assessment and completed patient reported measures including health anchor questions. Estimates for Minimal Detectible Change (MDC) were derived using 1.96*2*Standard Error of the Mean (SEM). Minimal Clinically Important Difference (MCID) for improvement were derived using the health anchor method and two distribution methods (Table 1). Thresholds for low, moderate and high disease activity were triangulated from established cut-off values for the patient global VAS, PASDAS and DAPSA.Table 1.Minimal Clinically Important Difference (MCID) and Minimal detectable change (MDC)ANCHOR (MEDIAN)DISTRIBUTION#1DISTRIBUTION #2MDCCPDAI0.51.491.54.16GRACE0.260.60.772.18PASDAS1.220.640.761.58DAS280.20.850.621.463VAS1.131.160.913.124VAS1.110.960.942.45DAPSA7.259.0910.4035.63Disease Activity Score for Psoriatic Arthritis (DAPSA); Psoriatic Arthritis Disease Activity Score (PASDAS); Composite Psoriatic Arthritis Disease Activity Index (CPDAI); Disease Activity Score 28 (DAS28).Distribution #1: Baseline standard deviation (sd) * √ 1 – Cronbach’s alphaDistribution #2: 0.5 * baseline sdMinimal detectable change (MDC): 1.96*2*SEM where SEM = baseline sd √1 - ICCResults:139 subjects were recruited (59 male, 80 female, mean (range) age (years) 52.7 (19 – 83), mean (range) duration of psoriasis (years) 21.9 (2 – 71), mean (range) duration of psoriatic arthritis (years) 6.1 (0 – 41). Cut-off values for low, moderate and high disease activity were 1.3, 2.4, and 4.8 for the 3 Vas and 1.6, 2.8 and 5.0 for the 4 VAS (Figure 1). Estimates for the MCID and MDC for the continuous composite measures and are reported in Table 1.Conclusion:We report estimates of clinically relevant improvements for continuous composite measures in PsA and estimates of low, moderate and high disease activity for the 3 and 4 VAS scales. The thresholds of meaning can now be tested in independent observational and clinical trial datasets.References:[1]Coates et al 2018 A&R Mar;70(3):345-355.[2]Tillett W et al 2021 J Rheum In PressAcknowledgements Funding:This report is independent research funded by the National Institute for Health Research, Programme Grants for Applied Research [Early detection to improve outcome in patients with undiagnosed PsA (‘PROMPT’), RP-PG-1212-20007]. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.Disclosure of Interests:William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer, and UCB, Consultant of: AbbVie, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, BMS, Janssen, Novartis, Pfizer, and UCB., Julia Day: None declared, Neil McHugh: None declared, Oliver FitzGerald Speakers bureau: AbbVie, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, BMS, Janssen, Novartis, Pfizer, and UCB., Laura C Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Gilead, Eli Lilly, Janssen, Medac, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Pfizer, and Novartis, Philip Helliwell: None declared

Background:EQUATOR (NCT03101670) was a 16-week, Phase 2, multicenter, double-blind, placebo-controlled, randomized controlled trial (RCT) of filgotinib in patients with active psoriatic arthritis.1Filgotinib demonstrated rapid efficacy compared with placebo across multiple domains, including the primary endpoint of Week 16 American College of Rheumatology (ACR) 20 response.1Patients completing the RCT could join an ongoing 148-week OLE (EQUATOR2;NCT03320876).Objectives:In this prespecified interim analysis at Week 52 of the OLE, individual patient responses with respect to disease activity were evaluated.Methods:Placebo-treated RCT patients switched to filgotinib (200 mg once daily) at Week 16 and entered the OLE; patients previously assigned to filgotinib continued. Individual response patterns at Week 52 of the OLE were evaluated for ACR20/50/70, Psoriatic Arthritis Disease Activity Score (PASDAS) low disease activity (LDA), minimal disease activity (MDA), and MDA/very low disease activity (VLDA).Results:124 patients (95%) completed EQUATOR; 122 (93%) enrolled in the OLE. At Week 52, 11 patients (9%) had discontinued treatment in the OLE. Median (range) exposure to filgotinib was 66.0 (0.4–104.1) weeks. In patients originally assigned to filgotinib, sustained efficacy was seen through to OLE Week 52 for ACR20, 50, and 70; PASDAS LDA; MDA (Table;Figure 1a); and MDA/VLDA. In total, 77% and 93% of those achieving MDA and ACR50 response in the RCT period maintained this at Week 52 (Table). A substantial proportion of RCT non-responders also achieved a treatment response in the OLE, meeting MDA and ACR50 criteria (22% and 37%, respectively;Table). Response patterns in the OLE were similar regardless of prior RCT treatment. In total, at Week 52 of the OLE, 33.6% of patients achieved MDA response (Figure 1a); 55.0% achieved ACR50 response. Figure 1bshows individual patient response over time for MDA.Conclusion:Data from this 52-week OLE interim analysis suggest that further improvement in disease activity can be expected with filgotinib beyond 16 weeks in patients with active psoriatic arthritis. Sustained efficacy was demonstrated across several measures of disease activity, including MDA and ACR50.References:[1]Mease P, et al. Lancet 2018;392:2367–77.Table.Responders at Week 52 of the OLE, by treatment and previous RCT responder status (observed cases).TreatmentFilgotinib (N=59) → Filgotinib (N=54)aPlacebo (N=63) → Filgotinib (N=57)an/N, %OLE responders/RCT respondersOLE responders/RCT non-respondersOLE responders/RCT respondersOLE responders/RCT non-respondersACR2040/47 (85.1)5/7 (71.4)17/18 (94.4)27/38 (71.1)ACR5025/27 (92.6)10/27 (37.0)5/8 (62.5)21/49 (42.9)ACR7010/13 (76.9)12/41 (29.3)3/4 (75.0)12/53 (22.6)PASDAS LDAb19/21 (90.5)12/32 (37.5)5/6 (83.3)21/48 (43.8)MDA10/13 (76.9)9/41 (22.0)4/5 (80.0)14/51 (27.5)aIndicates number remaining at OLE Week 52 interim analysis, after dropoutsbPASDAS information was not available for one patient at Week 16 of the RCTAcknowledgments:EQUATOR and EQUATOR2 were sponsored by Galapagos NV and co-funded by Galapagos NV and Gilead Sciences. Medical writing support was provided by Hannah Mace MPharmacol, CMPP (Aspire Scientific Ltd, Bollington, UK) and funded by Galapagos NV.Disclosure of Interests:Dafna D Gladman Grant/research support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/research support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Laura C Coates: None declared, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Philip Helliwell: None declared, Chantal Tasset Shareholder of: Galapagos (share/warrant holder), Employee of: Galapagos, Luc Meuleners Employee of: Galapagos, Leen Gilles Consultant of: Galapagos, Lien Gheyle Employee of: Galapagos, Mona Trivedi Shareholder of: Amgen and Gilead Sciences, Employee of: Gilead Sciences, Muhsen Alani Employee of: Gilead Sciences, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

Background:Obesity is highly prevalent in PsA (~45%)1and is associated with a reduced response to TNF inhibitors.2Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA.Objectives:This post hoc analysis assessed tofacitinib efficacy and safety in patients (pts) with PsA by baseline (BL) body mass index (BMI) category.Methods:Data were pooled from two placebo (PBO)-controlled, double-blind, Phase 3 studies in pts with active PsA and an inadequate response to ≥1 conventional synthetic DMARD (OPAL Broaden [12 months;NCT01877668]) or to ≥1 TNF inhibitor (OPAL Beyond [6 months;NCT01882439]).3,4This analysis included pts randomised to tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID or PBO, stratified by BL BMI: 2, ≥25–2, ≥30–2, or ≥35 kg/m2. Efficacy and safety were reported to Month (M)3. M3 efficacy outcomes included ACR20/50/70 and HAQ-DI responses, dactylitis and enthesitis resolution rates and changes from BL in HAQ-DI, Short Form-36 Version 2 (SF-36v2) Physical (PCS) and Mental Component Summary (MCS) scores, and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scores. Safety outcomes included adverse events (AEs), such as cardiovascular (CV) events and changes in lipid levels and liver function tests (LFTs).Results:This analysis included 710 pts; 43.8% were obese (BMI ≥30). At BL, 161 (22.7%) pts had a BMI 2.87 mg/L (49.1% in BMI Conclusion:Regardless of BL BMI, tofacitinib demonstrated greater efficacy than PBO at M3 in pts with PsA. Similar to other advanced therapies,2reduced efficacy was generally observed in tofacitinib and PBO pts with a BL BMI ≥35. Tofacitinib safety appeared consistent across all BL BMI categories.References:[1]Labitigan et al. Arthritis Care Res (Hoboken) 2014;66:600-07.[2]Singh et al. PLoS One 2018;13:e0195123.[3]Mease et al. NEJM 2017;377:1537-50.[4]Gladman et al. NEJM 2017;377:1525-36.Acknowledgments:Medical writing support was provided by Mark Bennett of CMC Connect, McCann Health Medical Communications, and funded by Pfizer Inc.Disclosure of Interests:Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Alexis Ogdie Shareholder of: Amgen, Novartis, Pfizer Inc, Grant/research support from: Novartis, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly, Novartis, Pfizer Inc, Jon T Giles Grant/research support from: Pfizer Inc, Juan Jesus Gomez-Reino Grant/research support from: AbbVie, Novartis, Pfizer Inc, Roche, UCB, Consultant of: Pfizer Inc, Speakers bureau: AbbVie, Bristol-Myers Squibb, Janssen, MSD, Pfizer Inc, Roche, UCB, Philip Helliwell: None declared, Lori Stockert Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Pamela Young Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Wael Joseph Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Rajiv Mundayat Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Daniela Graham Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, John Woolcott Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ana Belen Romero Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

Background:Patients (pts) with psoriatic arthritis (PsA) experience broad systemic symptoms including pain, fatigue, depression, sleep disturbance, poor physical function, and diminished social participation.Objectives:DISCOVER 1 is a Phase 3 trial (NCT03162796) evaluating the efficacy and safety of guselkumab (GUS), an anti-interleukin 23 inhibitor that binds to the p19-subunit of IL-23, in pts with active PsA. PROMIS-29 (Patient-Reported Outcomes Measurement Information System-29), a validated generic health instrument,1assessed the treatment effect of GUS on symptoms in pts with PsA.Methods:Pts with active PsA despite nonbiologic DMARDs were enrolled, and ~30% of pts could have previously received ≤2 TNFi. Pts were randomized (1:1:1) to subcutaneous GUS 100 mg at Week 0 (W0), W4 then q8W (n=127), GUS 100 mg q4W (n=128), or PBO (n=126). Concomitant stable use of select csDMARDs, oral steroids, and NSAIDs was allowed. PROMIS-29 consists of 7 domains (Depression, Anxiety, Physical Function, Pain Interference, Fatigue, Sleep Disturbance, and Social Participation) and a pain intensity 0-10 numeric rating scale (NRS). The raw score of each domain is converted into a standardized T-score with a mean of 50 (general population mean) and a standard deviation (SD) of 10. Higher PROMIS scores represent more of the concept being measured. A >= 5-point improvement (1/2 SD of T-score) is defined as clinically meaningful.1Results:At baseline, mean PROMIS-29 T-scores for physical function, social participation, sleep disturbance, pain, and fatigue were worse than the general US population. At W24, GUS q8W-treated pts achieved greater improvements from baseline in all PROMIS-29 domains vs PBO (pConclusion:Active PsA pts treated with GUS achieved clinically meaningful reduction in symptoms and improvement in physical function and social participation vs PBO at W24.References:[1]http://www.healthmeasures.net/score-and-interpret/interpret-scores/meaningful-change/165-meaningful-changeTable.PROMIS-29 Domain T-Scores Least Square (LS) Mean Change from BaselineLS Mean Change from BaselinePBOGUS q8WGUS q4WAnxiety-1.37-3.23*-2.92Depression-0.85-3.4**-2.67*Fatigue-1.86-4.79**-5.08**Pain interference-2.30-5.49**-5.69**Physical function1.343.89**5.05**Sleep disturbance-1.17-3.48**-2.46Social participation1.454.90**4.52**Pain intensity-0.56-1.98**-2.32**Nominal p-values vs placebo: *Acknowledgments:NoneDisclosure of Interests:Ana-Maria Orbai Grant/research support from: Abbvie, Eli Lilly and Company, Celgene, Novartis, Janssen, Horizon, Consultant of: Eli Lilly; Janssen; Novartis; Pfizer; UCB. Ana-Maria Orbai was a private consultant or advisor for Sun Pharmaceutical Industries, Inc, not in her capacity as a Johns Hopkins faculty member and was not compensated for this service., Laura C Coates: None declared, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Philip Helliwell: None declared, Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Bei Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Chenglong Han Employee of: Janssen Research & Development, LLC

Background:Cardiovascular (CV) comorbidities are common in psoriatic arthritis (PsA); patients are at high risk for major adverse cardiovascular events (MACE).1In the Phase 2, double-blind, randomized EQUATOR trial, significant improvements across multiple PsA domains were observed with the oral selective Janus kinase (JAK) 1 inhibitor filgotinib compared with placebo.2Inhibition of JAK signal transducer and activator of transcription signaling is associated with raised serum lipids.3Objectives:To evaluate the effects of filgotinib on the lipid profile of PsA patients and determine if those with higher MACE risk show similar changes in lipid profile compared with the overall population.Methods:In EQUATOR, 131 patients with active PsA received filgotinib 200 mg (n=65) or placebo (n=66) once daily for 16 weeks. Patients completing EQUATOR could enter the ongoing EQUATOR2 open-label extension (OLE;NCT03320876), in which patients receive filgotinib 200 mg for up to 148 weeks. Effects of filgotinib on total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and TC/HDL-C ratio at OLE Week 52 (68 weeks after EQUATOR initiation) were analyzed. In a post hoc analysis, patients were classified into subgroups according to presence/absence of obesity (baseline body mass index [BMI]; ≥30 vs 2, respectively), diabetes mellitus, arterial hypertension (≥130/80 mmHg), hyperlipidemia, and metabolic syndrome. Changes in lipid levels were explored graphically.Results:124 patients (95%) completed EQUATOR; 122 (93%) enrolled in the OLE. Of these, 11 patients (9%) discontinued treatment by OLE Week 52. Median (range) exposure to filgotinib was 66.0 (0.4–104.1) weeks. In the OLE, TC, LDL-C, and HDL-C levels increased versus baseline with filgotinib, resulting in a decreased TC/HDL-C ratio. Changes in lipid levels were consistent irrespective of presence of obesity (n=56;Fig), diabetes (n=53), arterial hypertension (n=80), hyperlipidemia (n=108), or metabolic syndrome (n=36); baseline lipid values were greater in the higher risk groups. In patients who were assigned placebo in the randomized controlled trial (RCT), HDL-C increased on switching to filgotinib in the OLE (in a manner similar to that seen in filgotinib-treated patients during the RCT), and remained elevated compared with baseline (Fig). Triglyceride levels remained stable throughout, across all subgroups. Seventeen patients (13%) were taking lipid-lowering drugs (LLDs) prior to the start of the trial (and continued to do so); the effect of filgotinib on the lipid profile in these patients was similar to that in the overall population. During the RCT phase, another six patients in the filgotinib group and one in the placebo group began taking LLDs.Conclusion:In patients exposed to filgotinib for ≥52 weeks, the effects on lipid profile were consistent regardless of baseline CV risk. Lipid changes included an elevation in TC and HDL-C, with a decrease in TC/HDL-C ratio.References:[1]Haddad A & Zisman D. Rambam Maimonides Med J 2017;8:e0004[2]Mease P, et al. Lancet 2018;392:2367–77[3]Sands B, et al. Clin Gastroenterol Hepatol 2020;18:123–32Acknowledgments:Studies were sponsored by Galapagos NV; co-funded by Galapagos NV and Gilead Sciences. Writing support from Hannah Mace MPharmacol, CMPP (Aspire Scientific Ltd, Bollington, UK) was funded by Galapagos NV (Mechelen, Belgium).Disclosure of Interests:M Elaine Husni Grant/research support from: Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Regeneron, and UCB, Dafna D Gladman Grant/research support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/research support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Philip Helliwell: None declared, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Chantal Tasset Shareholder of: Galapagos (share/warrant holder), Employee of: Galapagos, Luc Meuleners Employee of: Galapagos, Leen Gilles Consultant of: Galapagos, Lien Gheyle Employee of: Galapagos, Mona Trivedi Shareholder of: Amgen and Gilead Sciences, Employee of: Gilead Sciences, Muhsen Alani Employee of: Gilead Sciences, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

Background:Randomized controlled trials (RCTs) in psoriatic arthritis (PsA) have traditionally enrolled a homogenous subgroup of patients with more polyarticular disease, and the outcome measure used in PsA RCTs (ACR20) may not be ideal to measure differences between two active therapies nor capture change in patients with lower joint counts.Objectives:We conducted a simulation study to determine how changing the inclusion criteria and the primary outcome measure would impact the outcome of a future RCT.Methods:We used the Tight Control of PsA (TICOPA)1trial to inform simulation of two hypothetical head-to head trials comparing MTX to TNFi with 100 patients per arm. Within TICOPA, we identified MTX and TNFi new users; the visit at drug initiation became the hypothetical trial baseline visit, and the follow up visit was 12 weeks later. These data informed prediction models to simulate enrolled patients. We utilized propensity score-adjusted outcome models to account for potential confounding by indication. Trial 1, modeled after the SEAM-PsA trial,2used typical enrollment criteria (≥3 tender joint count (TJC) and ≥3 swollen joint count (SJC))2; Trial 2 required ≥1 TJC/SJC.1For each trial, five binary outcomes were simulated: ACR20, Disease Activity in PsA (DAPSA), clinical DAPSA (cDAPSA), Routine Assessment of Patient Index Data (RAPID3), and PsA Disease Activity Score (PASDAS), where low disease activity was the cutoff for continuous measures. Each hypothetical trial was simulated 1000 times, and the distribution of estimated effects was summarized using standard summary statistics and graphs.Results:Among 188 patients in TICOPA, 179 patients initiated MTX, and 43 patients initiated TNFi within the first 36 weeks. Among these, 107 MTX initiators and 15 TNFi initiators had ≥3 TJC and ≥3 SJC at drug initiation. Baseline characteristics of those in the “severe” (≥3 TJC and ≥3 SJC) and not severe (not meeting ≥3 TJC and ≥3 SJC) are shown in Table 1. Among “severe” patients, the mean probability of achieving ACR20 across simulations was approximately 0.27 in both arms and the observed relative risk (RR) TNFi vs MTX severe cohort across simulations was 1.0, IQR 0.84-1.17 (the RR in the SEAM trial at 24 wks was 1.20, 95%CI:1.05-1.35). In the “full cohort”, the median RR was 1.0, IQR 0.81-1.04. Trials using PASDAS, cDAPSA, and RAPID3 were more likely to differentiate between TNFi and MTX in the severe cohort (figure) but in the full cohort the results favored MTX.Table 1.Observed characteristics at drug initiationSevere (n=148)Not Severe (n=75)MTX (n=127)TNFi (n=21)SMDMTX (n=52)TNFi (n=23)SMDTICOPA Arm (no. (%))Standard Care57 (45%)4 (19%)0.5828 (54%)3 (13%)0.96Intensive Management70 (55%)17 (81%)24 (46%)20 (87%)Female (no. (%))65 (51%)11 (52%)0.0222 (42%)12 (52%)0.20TJC (mean (SD))17.8 (15.3)19.1 (17.3)0.083.5 (4.6)16.4 (19.1)0.93SJC (mean (SD))9.2 (7.4)10.2 (12.1)0.102.4 (3.4)2.2 (2.4)0.05Severe = ≥3 tender and ≥3 swollen jointsNot-severe = *Pseudo-baseline characteristics were at the time of drug initiation. In cases where the patient started a TNFi between visits, these were the values at the previous visit.Abbreviations: SMD = standardized mean difference, TJC=tender joint count, SJC=swollen joint countConclusion:Including patients with lower joint counts in an RCT reduced the ability to detect change with therapy. Additionally, among the outcome measures used to detect a difference between two active therapies, PASDAS, cDAPSA, and RAPID3 outperformed ACR20.References:[1]Coates et al. Lancet 2015; 2. Mease et al. Arthritis Rheumatol 2019Figure 1.Risk Ratios (TNFi vs MTX) by Outcome Across 1000 SimulationsFigure 2.Risk Differences (TNFi – MTX) by Outcome Across 1000 SimulationsDisclosure of Interests:Alexis Ogdie Grant/research support from: Pfizer, Novartis, Consultant of: Abbvie, Amgen, BMS, Celgene, Corrona, Janssen, Lilly, Pfizer, Novartis, Sarah Weinstein: None declared, Laura C Coates: None declared, Philip Helliwell: None declared, Alisa Stephens-Shields: None declared

Background:DISCOVER 1 and 2 are phase-3 trials of guselkumab (GUS, a monoclonal antibody that specifically binds the p19-subunit of IL-23) in patients with psoriatic arthritis (PsA). In both trials, treatment with GUS led to significantly more improvement than placebo (PBO) in the primary endpoint (ACR20) as well as in other measures of arthritis and psoriasis at week (W) 24.1,2Objectives:To evaluate the effect of GUS on fatigue in DISC 1 & 2 using the patient reported outcome (PRO) FACIT-Fatigue, which has demonstrated content validity and strong psychometric properties in clinical trials.3Methods:DISC 1 & 2 enrolled patients with active PsA, despite nonbiologic DMARDS and/or NSAIDS, who were mostly biologic naïve except for ~30% of patients in DISC 1 who had received 1-2 TNFi. Patients were randomized (1:1:1) in a blinded fashion to subcutaneous GUS 100 mg at W0 and W4 then every (q) 8W, to GUS 100 mg q4W, or to matching PBO. Concomitant treatment with select non-biologic DMARDS, oral corticosteroids, and NSAIDs was allowed. The FACIT-Fatigue is a 13-item PRO instrument assessing fatigue and its impact on daily activities and function over the past seven days, with a total score ranging from 0 to 52, higher score denoting less fatigue. A change of ≥4 points is identified as clinically meaningful.3Change from baseline in FACIT-Fatigue was analyzed using MMRM (Figure). Independence of treatment effect on FACIT-Fatigue from effect on ACR20 was assessed using Mediation Analysis4(Table) to estimate the natural direct effect (NDE) and natural indirect effect (NIE) mediated by ACR20 response.Results:At baseline in DISC 1 & 2, the mean FACIT-fatigue scores (SD) were 30.4 (10.4) and 29.7 (9.7), respectively, indicating moderate to severe fatigue. In both DISCOVER 1 & 2 trials, treatment with GUS led to improvements in FACIT-Fatigue scores compared with PBO as early as W8 (Figure). 54%-63% of GUS patients compared with 35%-46% of PBO patients achieved clinically meaningful improvement (≥4 points) in FACIT-Fatigue (P≤0.003). Mediation analysis revealed that the independent treatment effects on fatigue after adjustment for ACR20 response (Natural Direct Effect [NDE], Table) were 12-36% in the q8W GUS dosing group and 69% -70% in the q4W GUS group.Conclusion:In 2 phase-3 trials, treatment with GUS of patients with active PsA led to significant improvements compared to PBO in fatigue, including substantial effects on FACIT-Fatigue that were independent of the effects on ACR 20, especially for the q4W dosing group.References:[1]Deodhar et al. ACR 2019. Abstract #807. Arthr Rheumatol. 2019;71 S10: 1386[2]Mease et al. ACR 2019. Abstract # L13. Arthr Rheumatol. 2019;71 S10:5247[3]Cella et al. Journal of Patient-Reported Outcomes. 2019;3:30[4]Valeri et al. Psychologic Meth. 2013;18:137Table.Mediation Analysis of the Effect of ACR 20 Response on Change from Baseline in FACIT-Fatigue Score at Week 24EffectGUS 100 mg q8W vs. PBOEstimate (95% CI)GUS 100 mg q4W vs. PBOEstimate (95% CI)DISCOVER 1NDE0.36 (-1.7, 2.4)2.60 (0.6, 4.5)*NIE2.75 (1.4, 4.3)*1.20 (0.3, 2.3)*Total Effect3.12 (1.0, 5.2)*3.79 (1.9, 5.4)*Proportion Independent11.7%68.5%Proportion Mediated88.3%31.5%DISCOVER 2NDE1.44 (-0.1, 3.0)2.49 (1.0, 4.1)*NIE2.53 (1.6, 3.6)*1.09 (0.4, 1.9)*Total Effect3.97 (2.4, 5.5)*3.58 (2.1, 5.0)*Proportion Independent36.3%69.7%Proportion Mediated63.7%30.3%*P vs placeboNDE=Natural Direct Effect (effect on FACIT-F beyond effect on ACR20), NIE=Natural Indirect Effect (effect on FACIT-F mediated by ACR20)Mediation analysis4used linear and logistics regression models with Bootstrapping methodAcknowledgments:NoneDisclosure of Interests:Philip Helliwell: None declared, Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Bei Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xiwu Lin Employee of: Janssen Research & Development, LLC, Chenglong Han Employee of: Janssen Research & Development, LLC, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

Background:With multiple disease domains affected in PsA, clinical and patient-reported outcome (PRO) measures are important to assess disease improvement following treatment. Rapid, meaningful improvements in disease activity are a priority for physicians and patients (pts). Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Higher proportions of pts achieved responses in PROs and clinical measures when treated with tofacitinib for 3 months vs placebo (PBO).1-5Proportions of responders were also similar between tofacitinib and adalimumab (ADA) after 3, 6 and 12 months.2,3,5Objectives:To determine the time to initial response using responder definitions for selected PROs and clinical endpoints in pts with active PsA treated with tofacitinib, ADA or PBO switching to tofacitinib.Methods:In this post hoc analysis, data were collected from two Phase 3 studies (OPAL Broaden [12 months;NCT01877668]; OPAL Beyond [6 months;NCT01882439]).3,4Pts receiving tofacitinib 5 or 10 mg twice daily (BID), subcutaneous ADA 40 mg once every two weeks (Q2W; OPAL Broaden only), or PBO switching to tofacitinib 5 or 10 mg BID at Month (M)3, were included. Responder definitions included: HAQ-DI ≥0.35-point improvement from baseline (BL), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) total score ≥4-point improvement from BL, minimal disease activity (MDA) yes/no composite response (meeting at least 5 of 7 criteria) and PsA Disease Activity Score (PASDAS) post-BL score of ≤3.2 and >1.6-point improvement from BL. First post-BL data were collected at Week 2 (eg for HAQ-DI) or M1. Time-to-event analyses were performed using the Kaplan-Meier (KM) method, with pts censored at the last observed visit. Log-rank tests compared time to initial response across treatment groups.Results:KM analyses show days to initial response (Figure 1, Figure 2). Time to initial HAQ-DI response was significantly different between treatment groups in OPAL Broaden (pConclusion:Times to initial response in functional ability and disease activity were similar in pts treated with either tofacitinib or ADA. Time to initial response prior to first post-BL observation (Week 2 or M1) was not estimable in this analysis. These results may help physicians better understand the time frame for a meaningful response in pts receiving tofacitinib.References:[1]Strand et al. RMD Open 2019;5:e000808.[2]Strand et al. RMD Open 2019;5:e000806.[3]Mease et al. NEJM 2017;377:1537-50.[4]Gladman et al. NEJM 2017;377:1525-36.[5]Helliwell et al. Arthritis Res Ther 2018;20:242.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Dafna D Gladman Grant/research support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/research support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Laura C Coates: None declared, Joseph Wu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ming-Ann Hsu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Elizabeth Bacci Employee of: Evidera, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Philip Helliwell: None declared

Background:Inflammatory involvement of the axial skeleton (sacroiliac joints and / or spine) is one of the relatively frequent musculoskeletal manifestations associated with psoriasis / psoriatic arthritis (PsA). There is an urgent need for an evidence-based definition for axial involvement in PsA that would identify a subgroup of patients within the heterogeneous PsA population to conduct observational, interventional and translational studies. ASAS and GRAPPA embarked on a collaborative initiative to develop a definition of axial involvement in PsA.Objectives:To perform a survey to identify variables relevant in the identification of the presence of axial involvement in PsA among members of ASAS and GRAPPA.Methods:The online survey utilized thePAPRIKAmethodology (PotentiallyAllPairwiseRanKings of all possibleAlternatives) that determines decision-makers’ part-worth utilities representing the relative importance of the attributes. Participants were exposed to number of clinical scenarios and were prompted to decide which of the scenarios is more compatible with axial involvement in PsA unless they are equal (Figure). The constant stem of each scenario was “a patient diagnosed with psoriatic arthritis fulfilling the CASPAR criteria”; the variable part included 13 common spondyloarthritis variables (Table). Variables were ranked according to their relative importance.Results:The survey was completed by 186 ASAS/GRAPPA members (63 ASAS only, 80 GRAPPA only, and 43 both societies). The ranking of the variables is presented inTable. The highest ranked parameters indicative of axial involvement in a patient with PsA were presence of typical radiographic or MRI changes in the sacroiliac joints and/or spine followed by the presence of chronic back pain and then inflammatory back pain. A separate analysis of ASAS and GRAPPA members provided the similar results concerning the relevance of the variables.Conclusion:Objective signs of inflammatory involvement of the axial skeleton are the most important indicators of axial disease in PsA in the opinion of the experts. A prospective cohort study is currently being planned to address the value of these and other variables in defining axial involvement in PsA.Table.Ranking of the parameters relevant to deciding on the presence of axial involvement in a PsA patient in the opinion of ASAS and GRAPPA members (n=186).NParametersMedian rankMean rank1Presence of structural damage on an X-ray of SIJ22.82Presence of structural damage on an X-ray of spine3.54.13Presence of subchondral BME / osteitis on MRI of SIJ compatible with SpA44.54Presence of BME / osteitis on MRI of spine compatible with SpA455History or current presence of back pain5.55.86History of or current presence of inflammatory back pain5.567Good response of back pain to non-steroidal anti-inflammatory drugs87.88HLA-B2788.19Family history for SpA9.5910Elevated C-reactive protein109.311Presence of peripheral arthritis and/or enthesitis and/or dactylitis109.412Presence of anterior uveitis109.513Presence of inflammatory bowel disease109.6BME=bone marrow edema, MRI=magnetic resonance imaging, SIJ=sacroiliac joints, SpA=spondyloarthritisDisclosure of Interests:Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Juergen Braun Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Eli Lilly and Company, Medac, MSD (Schering Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi- Aventis, and UCB Pharma, Consultant of: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma, Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma, Alice Gottlieb Grant/research support from: Boehringer Ingelheim, Incyte, Janssen, Novartis, UCB, Xbiotech, Consultant of: AbbVie, Allergan, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, BMS, Celgene, Dermira, Incyte, Eli Lilly, Janssen, LEO Pharma, Novartis, Reddy Labs, Sun Pharmaceutical Industries, UCB, Valeant, Xbiotech, Laura C Coates: None declared, Vinod Chandran Grant/research support from: Abbvie, Celgene, Consultant of: Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lily, Janssen, Novartis, Pfizer, UCB, Employee of: Spouse employed by Eli Lily, Philip Helliwell: None declared, Deepak Jadon: None declared, Joachim Sieper Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Speakers bureau: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Dafna D Gladman Grant/research support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/research support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant

Background:Treatment with the oral selective Janus kinase 1 inhibitor filgotinib was associated with rapid and significant improvements in multiple domains of active psoriatic arthritis versus placebo in the 16-week Phase 2, multicenter, double-blind, randomized EQUATOR trial (NCT03101670).1A significantly greater proportion of patients receiving filgotinib, versus placebo, achieved the primary endpoint of 20% improvement in American College of Rheumatology (ACR) 20 response at Week 16 (80% vs 33%, respectively).1Objectives:The aim of this predefined analysis was to evaluate the consistency of the response to filgotinib across predefined relevant subpopulations participating in the EQUATOR trial.Methods:In EQUATOR, patients with active psoriatic arthritis were treated with filgotinib 200 mg (n=65) or placebo (n=66) once daily for 16 weeks. Key clinical endpoints, including ACR20 and ACR50 (50% improvement) response rates, Psoriatic Arthritis Disease Activity Score (PASDAS), and Disease Activity Index for Psoriatic Arthritis (DAPSA) were evaluated according to the following baseline characteristics: sex, body mass index, disease duration, baseline disease severity, concurrent use of disease-modifying antirheumatic drug(s), and prior exposure to tumor necrosis factor inhibitor(s). For PASDAS and DAPSA scores, statistical analysis of changes from baseline was performed using analysis of covariance with factors for treatment, randomization stratification, subgroup, and an interaction between treatment and subgroup. Least-squares (LS) mean difference between treatment arms and the corresponding 95% confidence intervals (CI) were calculated. For ACR20 and ACR50 response rates, statistical analysis used the point estimate and corresponding 95% CI, based on the Newcombe method.Results:Sixty patients (92%) in the filgotinib group and 64 (97%) in the placebo group completed the study. The total number of patients in each subpopulation ranged from 18 to 104 (Figure 1). Differences in the proportions of patients achieving ACR20 consistently favored filgotinib, compared with placebo, across all subgroups (Figure 1); all differences reached statistical significance. Similarly, differences in the proportions of ACR50 responders and LS mean treatment differences for PASDAS and DAPSA consistently favored filgotinib, reaching statistical significance in most subgroups. No clinically relevant differences in the effect of filgotinib were observed across subgroups. Filgotinib was generally well tolerated and no new safety signals were identified.Conclusion:In the 16-week EQUATOR trial, the effects of filgotinib on key efficacy endpoints were generally consistent across a range of subgroups based on patient, disease, and treatment characteristics.References:[1]Mease P, et al. Lancet 2018;392:2367–77.Acknowledgments:The EQUATOR trial was sponsored by Galapagos NV and co-funded by Galapagos NV and Gilead Sciences. Medical writing support was provided by Hannah Mace MPharmacol, CMPP (Aspire Scientific Ltd, Bollington, UK) and funded by Galapagos NV (Mechelen, Belgium).Disclosure of Interests:Philip Helliwell: None declared, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Laura C Coates: None declared, Dafna D Gladman Grant/research support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/research support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Chantal Tasset Shareholder of: Galapagos (share/warrant holder), Employee of: Galapagos, Luc Meuleners Employee of: Galapagos, Leen Gilles Consultant of: Galapagos, Lien Gheyle Employee of: Galapagos, Mona Trivedi Shareholder of: Amgen and Gilead Sciences, Employee of: Gilead Sciences, Muhsen Alani Employee of: Gilead Sciences, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

Background and objective: Since the original description of psoriatic arthritis (PsA) subgroups by Moll and Wright, there has been some discrepancy in the precise prevalence of the different subgroups and in particular the proportion of patients with polyarthritis. The higher prevalence of the polyarthritis subgroup may be due to the inclusion of patients with seronegative rheumatoid arthritis with coincidental psoriasis. The classification of psoriatic arthritis (CASPAR) study database provided an opportunity to examine this question. Methods: The CASPAR study collected clinical, radiological and laboratory data on 588 patients with physician-diagnosed PsA and 525 controls with other inflammatory arthritis, 70% of whom had rheumatoid arthritis. Patients with PsA were divided into two groups: polyarthritis and non-polyarthritis (which included the Moll and Wright subgroups of spinal disease, distal interphalangeal predominant and arthritis mutilans) and were compared with patients with rheumatoid arthritis. Comparisons were made between all three groups and, if a significant difference occurred, between the two groups with PsA. Results: The three groups differed significantly with regard to all clinical and laboratory variables except duration of disease. Significant differences were also found between the two groups of PsA in terms of age, sex, total number of involved joints, disability score and symmetry. However, no differences were found between the groups of patients with PsA in terms of seropositivity for rheumatoid factor and antibodies to cyclic citrullinated peptide, enthesitis, and spinal pain and stiffness. Further, dactylitis was commonly seen in patients with PsA (57% in the polyarticular group and 45% in non-polyarticular group), and uncommonly found in patients with rheumatoid arthritis (5%). With the exception of entheseal changes, syndesmophytes and osteolysis, typical radiological features of PsA could not be used to distinguish between the PsA subgroups. Conclusions: The evidence suggests that the changing prevalence of the polyarticular subgroup of PsA is not because doctors include patients with seronegative rheumatoid arthritis with coincidental psoriasis.

To understand better a complex disease such as psoriatic arthritis (PsA), collection of a large amount of information on clinical, laboratory, and radiological features is required over an extended period of time. Longitudinal data can be effectively collected and stored in clinical registries and databases. This article reviews current databases in PsA and proposes a structure for an international PsA registry. Careful collection and analysis of patient data through collaborative efforts will likely advance our knowledge of pathogenesis and provide new and much needed insights about the course and prognosis of the disease.

Background Psoriatic arthritis (PsA) is an inflammatory arthritis that is associated with psoriasis. Although the majority of PsA genetic risk loci identified also confer risk for psoriasis, we have recently reported evidence of loci that are associated with PsA and not psoriasis, including an association at the IL23R locus which is also independent of a psoriasis variant at the same locus. Methods The PsA-specific SNP rs12044149, and the psoriasis SNP rs9988642 at the IL23R locus were genotyped in a cohort of 914 PsA cases and 6,945 controls from Spain, Crete, Germany and the UK, with the Life Technologies QuantStudio genotyping platform. Association testing was carried out using PLINK, and a meta-analysis was performed with PsA Immunochip data (1,962 cases, 8,923 controls). Genotype data was also available from the psoriasis WTCCC2 study (excluding known PsA, n=1,784) to compare effect sizes between PsA and psoriasis using multinomial logistic regression in Stata, and to directly compare PsA and psoriasis genotypes. Credible SNP sets were calculated for the PsA and psoriasis IL23R associations using the Bayesian refinement method, and functionally annotated. Results We replicated the association rs12044149 with PsA ( P =4.03x10 –6 ), which remained significant when conditioning upon the psoriasis variant, rs9988642 ( P cond =4.86x10 –6 ), and reached genome-wide significance during meta-analysis of the combined PsA dataset ( P meta =4.76x10 –20 ). Only a modest association was found for rs9988642 ( P =0.04), with no genome-wide significance found during meta-analysis ( P =4.61x10 –4 ). Within the psoriasis dataset, this association remained significant when conditioning upon rs12044149 ( P =1.0x10 –07 vs. P cond =1.63x10 –5 ). Effect estimates for rs12044149 were significantly different between PsA and psoriasis ( P =2.0x10 –3 ), and direct comparison of genotypes for PsA and psoriasis found the risk allele to be significantly increased in PsA ( P =4.52x10 –4 , OR=1.3). Credible SNPs for rs12044149 mapped to promoter and enhancer regions within memory CD8 + T cells, which we have previously reported to be critical for PsA. Conclusions We have successfully replicated a PsA-specific (associated with PsA but not psoriasis) risk variant at the IL23R locus in an independent cohort, confirming rs12044149 to be distinct from rs9988642 (r 2 =0.02). This gives five PsA-specific associations that have now been identified. Disclosure of Interest None declared

Background RAPID3 is a patient completed outcome measure assessing disease activity in inflammatory arthritis consisting of the health assessment questionnaire (HAQ) and two VAS scales. It is feasible for use in clinical practice and has been well validated in rheumatoid arthritis (RA) and other conditions, but there is little data on its use in psoriatic arthritis (PsA). Objectives To investigate the responsiveness and discrimination of RAPID3 and a modified version with skin VAS in the Tight Control of Psoriatic Arthritis (TICOPA) trial. Methods Data from the TICOPA trial were used to assess the performance of the RAPID3 index. RAPID3 was calculated using the HAQ-DI, patient completed pain VAS and global disease activity VAS. Due to concerns about skin involvement in PsA, we also calculated a novel RAPID3Ps score which also included a skin activity VAS to see if performance was superior. Results from the RAPID3 measures were correlated with the PsA disease activity score (PASDAS) a composite disease activity score already validated by GRAPPA. Change in the RAPID3 measures and other outcome measures were compared between the tight control arm and the standard care arm of the TICOPA study using t-test for continuous variables and chi-squared for categorical measures of disease state. Results RAPID3 scores strongly correlated with PASDAS (Pearson correlation 0.794, p When looking at differentiation between treatment groups, change in RAPID3 score at 48 weeks was highly discriminant (t value -3.43, p Looking at specific cutpoints, RAPID3 “near remission” was also highly discriminant between treatment groups (chi squared 7.48, p=0.006) although with a lower value than the minimal disease activity criteria for PsA (chi squared 10.11, p=0.001). Conclusions RAPID3 shows good correlation with other validated measures of disease activity in PsA and addition of a psoriasis measure does not seem necessary in this population. The RAPID3 score and “near remission” definition are able to effectively discriminate between two active treatment groups in an interventional trial. Acknowledgement We acknowledge all collaborators and participants in the TICOPA trial. Disclosure of Interest None declared

Repetitive strain injury, or work related upper limb disorder, provides an interesting paradigm for the study of the relative contribution of physical and psychological factors to the resulting pain and disability. Sixty three subjects were studied, comprising the work-force of a subsection of a large local industrial company, in whom pain in the arm related to work was known to be common. Ergonomic data were obtained by estimating the cumulative daily load on the wrist joint for each of four identified tasks. Data on the occurrence of pain, treatment sought, and disability were obtained by a structured self administered questionnaire. Psychological data were obtained by administering the Hospital Anxiety and Depression (HAD) scale, a self reported measure of anxiety and depression, and the Bradford Somatic Inventory (BSI), an inventory of somatic symptoms associated with anxiety and depression. The employment specific period prevalence of work related upper limb disorder was 81%, with 30% of the subjects having pain at the time of the study. Domestic disability was minimal in all but two subjects, though the use of devices such as jar openers at home was common (12 of 51 subjects). Medical advice was seldom sought. Twenty per cent of subjects had received anti-inflammatory drugs, 10% had received physiotherapy, and 47% had wrist splints. Pain was related to the tasks with the highest estimated daily loads, but a history of pain and current pain were associated with higher scores on the HAD and BSI scales, suggesting an interaction between physical and psychological factors.

Background Previous studies have shown that around 25% of patients with psoriatic arthritis (PsA) have radiographic erosions at presentation but the level of erosive disease is usually very low. Previous data in established PsA has suggested a higher sensitivity for bone erosions with US compared to plain radiography. Objectives The aim of this analysis was to investigate how many early PsA patients had erosions only visible using US at presentation. Methods Within the Tight Control of Psoriatic Arthritis (TICOPA study), all patients had radiographs of the hands and feet at baseline and week 48. Patients seen in Leeds also underwent an US assessment of their most symptomatic or dominant hand assessing MCPs and PIPs at the same timepoints. The presence of erosions seen on radiographs and US were compared at an individual joint level and at a patient level. Joints with erosive changes seen only on US at baseline were checked at 48 weeks for presence of radiographic and/or ultrasound erosions. Results There were 89 patients who had US scans of the MCP and PIP joints with corresponding radiographs at baseline, the majority of whom had repeat scans at 48 weeks (n=74) contributing a total of 163 scans for analysis. In the majority of cases (81/89 91.0% of patients) there was no evidence of erosive disease on radiographs at baseline, however an additional 19 patients had erosions visible on US alone. 25 (3.5%) joints at baseline and 32 (5.6%) at 48 weeks showed erosive disease spread across the MCPs and PIPs (see table). At follow up, none of these erosions were visible on radiographs, with 13 of 23 joints re-scanned still showing erosions on US. Conclusions There was a low frequency of erosive disease seen in the TICOPA study with little progression over the 48 week study period. Of those with normal radiographs, 23% of patients had additional erosions in the fingers visualised on US, with less erosions identified in the middle MCP joints where US access can be limited. Disclosure of Interest L. Coates Grant/research support from: Pfizer, Consultant for: Pfizer, J. Freeston Grant/research support from: Pfizer, J. Nam Grant/research support from: Pfizer, P. Conaghan Grant/research support from: Pfizer, Consultant for: Pfizer, P. Helliwell Grant/research support from: Pfizer, Consultant for: Pfizer

Background Methotrexate (MTX) is a common first line DMARD in psoriatic arthritis (PsA) but until recently no RCTs evaluating its efficacy in PsA were available. The MIPA trial found no significant difference in arthritis outcomes at 6 months but was criticised as the target dose was only 15mg. Objectives The aim of this analysis was to investigate clinical outcomes in patients with early PsA treated with MTX in the TICOPA study. Methods Within the Tight Control of Psoriatic Arthritis, patients (in either arm) could be treated with methotrexate. All patients in the tight control arm received MTX as first line monotherapy for the first 12 weeks while patients in the standard care arm the majority of the patients in the standard care arm also received MTX. Clinical outcomes were recorded at the 12 week visit including joint counts, PASI, NAPSI, enthesitis and dactylitis measures. Results Of the 206 patients enrolled in TICOPA, 188 received oral methotrexate in the first 12 weeks of the trial. Of these, 175 patients reached a dose of at least 15mg by 12 weeks, with 122 reaching a dose of at least 20mg and 86 reaching the top dose of 25mg. The proportions of patients achieving the ACR outcomes at 12 weeks were ACR20 40.8%, ACR50 18.8% and ACR70 8.6% with 22.4% achieving minimal disease activity (MDA). Improvements were also seen in PASI scores with 27.2% reaching a PASI75. For those with enthesitis at baseline (n=148) the median change in enthesitis score was 0 (IQ range -1, 0 for LEI and IMPACT, -2, 1 for MASES). For those with baseline dactylitis (n=59), there was a median change in LDI scores of -59.7 (-157.4, -26.4). 117 patients had nail involvement and these patients showed a median change in mNAPSI score of -2 (IQ range -8, 0) with changes more commonly in the nail bed due to the short follow up time. Slightly higher proportions of patients receiving 180mg MTX or more over the 12 week period (equivalent to an average of 15mg per week) achieved ACR20, 50 and PASI 75 but the numbers were small so this did not reach significance. Conclusions Despite this data being open-label, it does show improvements in multiple clinical outcomes associated with MTX use in PsA. The proportion reaching ACR20 is slightly higher than that in MIPA (41 vs 34%) but no comparative data are available for the other outcomes. There is a suggestion of better responses with doses above 15mg per week but the dose-response is harder to assess in such a study where confounding exists as patients doing well may be left on lower doses. Disclosure of Interest L. Coates: None declared, P. Helliwell Grant/research support from: Pfizer, Consultant for: Pfizer

OBJECTIVE--To relate weakness of grip to loss of forearm muscle bulk, hand joint deformity, and hand joint tenderness in patients with rheumatoid arthritis (RA). METHODS--Using anthropometric data we have estimated the anatomical cross-sectional area (CSA) of forearm muscles in 100 subjects with RA compared with 100 aged and sex-matched normal subjects. We also recorded hand joint tenderness using a modification of the Ritchie articular index, and a simple index of hand joint deformity. RESULTS--We found a significant reduction in anatomical CSA in RA (forearm CSA in normal subjects 29.7 cm2 and in RA 25.9 cm2; p = 0.002). In simple linear regression we found that 46.3% of the variation in grip strength in normal subjects was explained by variation in muscle CSA; in RA this figure decreased to 33.4%. Adding terms for joint deformity and pain in a multiple regression model improved the amount of variation explained to 37.9%. CONCLUSIONS--Although there is significant muscle wasting in RA, it is likely that reduction in strength is also attributable to joint deformity and pain leading to inhibition of grip directly and, indirectly, by arthrogenous muscle inhibition. Doubts remain about the quality of muscle in RA.

Objectives The purpose of this study was to compare radiographic outcomes according to the magnitude of the response utilizing 2 new psoriatic composite disease activity measures (the Psoriatic Arthritis Disease Activity Score (PASDAS),and the GRAPPA Composite Exercise (GRACE)) [1] with DAS28 as a comparator. The data were taken from the GO-REVEAL dataset, a large (N=324) randomised, double-blind, study which evaluated the safety and efficacy of 2 doses of golimumab in subjects with active PsA. Methods Data collected in the GO-REVEAL study was not sufficient to calculate all the components of the GRACE index, soimputation was used to obtain values for the PsA quality of life measure (PsAQoL). Response criteria at 24 weeks were applied across the whole dataset, irrespective of treatment group. Radiographic scores at baseline and 24 weeks were assessed. Results Radiographic progression was greater in subjects with a poor outcome with treatment, and less in those with a good outcome. Radiographic scores were intermediate for those with a moderate outcome (Table). Analysis of variance statistics were significant for all three measures but were more significant for the psoriatic arthritis specific indices. Data were also generated for the proportion of subjects in whom no radiographic progression was seen, and these data were compared across the outcome measures using chi-squared statistics: PASDAS, 82% in good outcome group did not have radiographic progression χ2 =8.5, GRACE 80%, χ2 =6.6, DAS28, 76% χ2 =4.6. View this table: Conclusions Response criteria for disease specific composite measures enable better separation between groups in terms of radiographic progression and may therefore be used as suitable targets for interventional studies and in the clinic. References 1. Helliwell PS, Fitzgerald O, Fransen J: Composite Disease Activity and Responder Indices for Psoriatic Arthritis: Development of Cut-offs for Both Disease Activity States and Response. J Rheum, in press (2014). Disclosure of Interest P. Helliwell Consultant for: Janssen, A. Kavanaugh Grant/research support: Janssen DOI 10.1136/annrheumdis-2014-eular.4692

Background Psoriatic arthritis (PsA) is a heterogeneous condition with variable clinical phenotype and highly variable radiographic progression. Previous radiographic data in early PsA from the Dublin cohort recruited between 1994 and 2000 showed that 27% of patients had erosions at baseline assessment and this increased to 47% at 2 year follow up despite active treatment1. Since that time there has been an improving awareness of PsA and better access to effective therapies which may have impacted on radiographic changes seen in early PsA. Objectives To assess extent of radiographic change seen in an early PsA cohort at presentation and after one year of active treatment. Methods 206 patients recruited to the TICOPA trial between 2008 and 2012 had radiographs of the hands and feet performed at baseline and 48 weeks. All patients were required to be DMARD naive with symptom duration of less than 2 years. During the course of the trial all patients received active therapy either with a treat-to-target approach or standard care. The majority of patients received only standard DMARDs but 23.4% of patients were on anti-TNF therapy at the end of the trial. Radiographs were scored using the modified Sharp van der Heijde (SvdH) scoring system for PsA including DIPJs of the hands. Results Radiographs of the hands and feet were available for 195 patients at baseline and 176 at follow up. Overall SvdH scores were low at both baseline and follow up (see table). Although median erosion scores were zero, 25.4% of patients had some erosive disease at baseline rising to 30.1% at 48 weeks. Presence of erosive disease was not associated with the presence of rheumatoid factor or anti-citrillinated peptide antibodies (ACPA). Of 9 patients with positive ACPA titres, only 1 had any erosive disease. There was also no significant association with raised C-reactive protein (CRP) levels or pattern of arthritis (polyarticular vs oligoarticular) although there was a trend suggesting that erosive patients were more likely to be polyarticular (78.0 vs 69.6%) or have a raised CRP (45.0 vs 39.6%). The majority of radiographic change seen represented JSN in the hands. Patients with JSN were slightly older than those without but this did not reach significance (p=0.053) Conclusions This study highlights the low level of radiographic change seen in early PsA but does confirm that a similar proportion of patients present with some, albeit very few erosions compared to a decade earlier (25 vs 27%). Progression of erosive disease once patients are on active therapy is low with only an additional 5% developing erosive change. There was a suggestion of association between radiographic erosions and known predictors such as polyarticular disease and raised CRP. References 1Kane et al, Rheumatology 2003; 42(12): 1460. Acknowledgements The TICOPA study was funded by Arthritis Research UK and Pfizer. Disclosure of Interest L. Coates Grant/research support: Pfizer, P. Helliwell Grant/research support: Pfizer DOI 10.1136/annrheumdis-2014-eular.2907

Background Several new disease-specific composite disease activity measures have been developed for psoriatic arthritis (PsA). Objectives Using data from a randomized double-blind placebo-controlled trial of certolizumab pegol (CZP) in PsA (RAPID-PsA, NCT01087788) we aimed to compare the performance of the Psoriatic Arthritis Disease Activity Score (PASDAS), the Composite Psoriatic Disease Activity Index (CPDAI), and modifications of the CPDAI with the Disease Activity Score 28 (DAS28), which was developed for use in rheumatoid arthritis. Methods The CPDAI and PASDAS composite measures have been described previously. 1,2 In RAPID-PsA not all components of CPDAI were collected, therefore psoriasis body surface area was substituted for Psoriasis Area Severity Index, and the Health Assessment Questionnaire was used as the function modifier for the axial component of this measure (CPDAIm). The CPDAI was further modified by the addition of a patient (pt)-completed outcome domain, based on the pt visual analogue scale scores for arthritis pain and global disease activity (CPDAIpro). The performance of these measures was assessed after 12 weeks of CZP treatment by calculating, for the change from baseline, the standardized response mean, the baseline-adjusted effect size compared to placebo (ESadj, based on analysis of covariance), and the required sample size based on the ESadj. Data are reported for those pts with all outcome components available. Only observed data were used, without imputation. Results The largest ESadj was found for PASDAS, followed by DAS28, CPDAIm and CPDAIpro (Table). These figures translated into differences in sample size estimation for further studies. Conclusions The PASDAS and CPDAI composite measures demonstrated good responsiveness and discriminative ability in this trial, supporting further exploration of their use in PsA clinical trials. Differences in the performance of these new PsA-specific composite measures were seen in this dataset. These results may help inform the selection of appropriate composite measures for PsA in future studies. Addition of a pt-completed outcome domain to the CPDAI did not appear to improve performance of the composite score. References Helliwell P. Ann Rheum Dis 2013; 72(6):986-991. Mumtaz A. Ann Rheum Dis 2011; 70(2):272-277 Acknowledgements The authors acknowledge Costello Medical Consulting for editorial assistance which was funded by UCB Pharma Disclosure of Interest P. Helliwell Grant/research support: Abbvie, Celgene, Janssen, MSD, Pfizer, UCB Pharma, Novartis, Bristol-Myers Squibb, Roche, Speakers bureau: Abbvie, Celgene, Janssen, MSD, Pfizer, UCB Pharma, Novartis, Bristol-Myers Squibb, Roche, P. Mease Grant/research support: (Abbott) AbbVie, Amgen, BiogenIdec, Bristol-Myers Squibb, Celgene, Crescendo, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB Pharma, Vertex, Consultant for: (Abbott) AbbVie, Amgen, BiogenIdec, Bristol-Myers Squibb, Celgene, Crescendo, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB Pharma, Vertex, Speakers bureau: (Abbott) AbbVie, Amgen, BiogenIdec, Bristol-Myers Squibb, Crescendo, Genentech, Janssen, Lilly, Pfizer, UCB Pharma, T. Nurminen Employee of: UCB Pharma, O. FitzGerald Grant/research support: Pfizer, Abbvie, Roche, MSD, Bristol-Myers Squibb, Speakers bureau: Janssen, Pfizer, Abbvie, UCB Pharma, Cellgene DOI 10.1136/annrheumdis-2014-eular.1654

Background Fatigue is an important aspect of disease for people suffering from psoriatic arthritis (PsA) (ref 1). However, little is known about the factors explaining fatigue in PsA. The causes of fatigue in inflammatory rheumatic diseases such as PsA, spondyloarthritis or rheumatoid arthritis are unclear; fatigue is diversely reported as being related either to patient characteristics, e.g., demographic, psychological and social factors, or to disease characteristics, e.g. disease activity. Objectives To evaluate the magnitude of fatigue in PsA and to assess if fatigue appears more strongly associated with patient- or with disease-related characteristics. Methods Patients: international cross-sectional study of unselected patients with a definite diagnosis of PsA according to the CASPAR criteria, in 13 countries [1]. Magnitude of fatigue was assessed by a numeric rating scale (range 0-10). Factors associated with high fatigue (>5/10) were assessed by multivariate logistic regression. The factors tested for association were patient related characteristics including demographic variables (age, gender, disease duration and country, education level); disease-related characteristics including articular activity (number of tender joints and number of swollen joints), skin activity (current psoriasis of more than 5% body surface); other activity (axial involvement, enthesitis, dactylitis, extra-articular involvement) and structural damage. Other patient reported outcomes including quality of life were not analysed since usually highly associated to fatigue. Results Data from 246 patients were analysed: mean age 51.2±13.0 yrs; N=119 (48.8%) males. Most had long-standing disease. Mean (±SD) fatigue was 5.0 (±3.0); 44.7% of patients had a fatigue level above 5 out of 10. High fatigue was well explained (AUC of the model, 0.73) by the following elements in multivariate analysis: higher skin activity (odds ratio, OR=4.7 [1.1; 20.7]), higher tender joint count (OR=1.1 [1.0; 1.1]) and lower education level (OR=0.9 [0.8; 1.0]). Conclusions Fatigue levels were high in this population of patients with PsA. High fatigue was explained mainly by disease activity rather than patient-related variables, indicating fatigue may be closely related to the disease process in PsA. Further studies are needed. References Gossec et al. PsAID study, EULAR 2013. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2309

Background Polyarthritis (PA) is defined by inflammation of ≥5 joints differentiating it from oligoarthritis (OA) which affects 2-4 joints. There are limited data on the demographic and disease characteristics of psoriasis patients with either OA or PA. Objectives Our analyses examined and characterized the baseline attributes of psoriasis subjects with PA and OA in the PREPARE trial. Methods PREPARE was a multicenter non-interventional study conducted to estimate PsA prevalence in patients with psoriasis. Diagnosis of PA and OA was based on clinical examination by rheumatologists. Demographic and disease characteristics were assessed among patients with PA or OA at baseline. Results A total of 406 subjects were included in these analyses; of these 222 (54.7%) had PsA following rheumatologist assessment (based on physical examination, medical history and laboratory analysis). At baseline, 253 patients had PA and 153 had OA. A significantly greater proportion of patients with PA (161/252; 63.9%) had PsA than those with OA (61/152; 40.1%) (P

Background In the absence of a psoriatic arthritis (PsA)-specific composite disease activity score, rheumatoid arthritis composite scores have predominantly been utilized although they do not incorporate outcomes for accurate PsA assessment. Several PsA-specific composite measures are in development. Objectives The purpose of this analysis is to assess the performance and relationship between existing and novel PsA composite measures for evidence of validation. Methods Observed data from the PRESTA trial, a randomized study evaluating 2 etanercept (ETN) dose regimens in psoriasis patients with active PsA, were analyzed. Patients with values to 4 composite indices: the modified composite psoriatic disease activity index (mCPDAI), disease activity index for PsA (DAPSA), PsA disease activity score (PASDAS), and arithmetic mean desirability function (AMDF) at all 3 time points: baseline (BL) and Week 12 and 24 were included. Correlations among endpoints were evaluated using Spearman correlations and dosing regimens were compared using ANCOVA. Parameters influencing each composite index were determined using forward stepwise regression analyses. mCPDAI uses 4 domains: joints (66/68 SJC/TJC, HAQ), skin (PASI andDLQI), dactylitis, and enthesitis for a score of 0–12. DAPSA sums patient global health and joint pain VAS assessments, 66/68 SJC/TJC, and CRP for a score of 0–160. PASDAS utilizes patient global health and physician global arthritis VAS, 66/68 SJC/TJC, CRP, predicted physical component score, dactylitis, and enthesitis. AMDF is calculated from patient psoriasis, joints, and global health VAS assessments, PASI, 66/68 SJC/TJC and HAQ for a score 0–1. Results All indices could distinguish response to treatment comparing BL and 12/24-week values. Of the 4 measures, mCPDAI and AMDF were able to differentiate between the dosing regimens at Week 12 (P 0.86) and PASDAS versus DAPSA (r>0.84). mCPDAI was correlated with all indices (absolute r>0.72) at Weeks 12/24. AMDF, CPDAI, DAPSA, and PASDAS were largely influenced by patient VAS assessments and joint scores (r 2 >0.90), dactylitis and enthesitis (r 2 >0.69), TJC and CRP (r 2 >0.94) and physician and patient VAS (r 2 >0.73), respectively. Interestingly, PASI was found to be the least influential on AMDF (r 2 =0.01) and CPDAI (r 2 =0.08). Conclusions In addition to distinguishing treatment responses, both AMDF and mCPDAI which better reflect most PsA disease domains, strongly correlate with other composite measures. Further clinical trial analysis and validation of measures is required. Acknowledgements The PRESTA trial was funded by Pfizer Inc. Medical writing support was provided by Stephanie Eide of UBC Scientific Solutions and funded by Pfizer Inc. Disclosure of Interest P. Helliwell Speakers bureau: Pfizer Inc, O. FitzGerald Speakers bureau: Pfizer Inc, L. Marshall Employee of: Pfizer Inc, R. Pedersen Employee of: Pfizer Inc, E. Bananis Employee of: Pfizer Inc

Background Many screening questionnaires have been developed to identify PsA amongst patients with psoriasis but their performance in head to head studies has been diappointing. Objectives To combine most discriminatory questions from established PsA screening questionnaires to create a more sensitive and specific screening test for PsA. Methods Data from the CONTEST study, a head-to-head study of the PEST, PASE and ToPAS screening questionnaires in secondary care dermatology clinics, were used to establish which questions from any of the three questionnaires had a Youden’s index of >0.1 using CASPAR criteria for PsA as the gold standard. Optional weighting was included based on logistic regression of individual questions. The number of painful joint areas on the PEST mannequin predictive of PsA was identified using ROC analysis. CART analysis was used to identify other questions that showed good differentiation. Data from comparative head-to-head studies based in Dublin and Utah were used to independently validate the new proposed questionnaires. Results In this individual analysis, only 2 of 25 questions showed significant differentiation of PsA cases using Fishers exact test: ToPAS 2A “Have you ever noticed any of these changes in your fingernails – pits in the nails?” and PEST 4 “Have you had pain in your heel?”. These were the only questions identified using logistic regression with an OR of 5 and 2 respectively. A further 10 questions had a Youden score of ≥0.1 and these were considered for inclusion into the first candidate questionnaire. Where overlapping questions about similar symptoms (eg nail psoriasis) were identified, the most discriminatory question was chosen. One question (ToPAS 7A) was excluded as many patients did not complete that question. This resulted in the CONTEST questionnaire of 8 yes/no questions. The weighted CONTEST questionnaire used the OR identified above and weighted all other questions as 1 giving a score of 0-13. CONTEST-joint included the presence of joint areas on the PEST mannequin with a cut off of ≥6 areas being positive. CART analysis identified a further 5 questions for inclusion giving a total of 13 questions for CONTEST-tree. In the original CONTEST data the AUC for the CONTEST, CONTEST-weighted, CONTEST-joint and CONTEST-tree were 0.69, 0.74, 0.70, 0.59 respectively with p Conclusions The CONTEST questionnaires provide a new tool which could improve sensitivity and specificity of identifying PsA compared to existing questionnaires. Further research in independent populations is required to identify the optimal cut point for referral. Disclosure of Interest None Declared

Background Prompt diagnosis and treatment of psoriatic arthritis (PsA) are essential to reduce the risk of permanent joint damage. Although composite measures established in rheumatoid arthritis are often used in PsA for monitoring disease activity, their utility as an aid to identification of PsA, compared to the utility of other features of PsA such as dactylitis and enthesitis, has not been established. Objectives To compare various clinical assessments in their ability to diagnose PsA in a post-hoc analysis of findings from the PREPARE study, a multicenter non-interventional study conducted to estimate PsA prevalence in patients with psoriasis. Methods Consecutive psoriasis patients seen in dermatology centers were evaluated by rheumatologists to establish/exclude a clinical diagnosis of PsA based on physical examination, medical history, and laboratory findings. With the latter diagnosis serving as the standard for comparison, several rheumatologic signs/symptoms/indexes were assessed. The cutoff value for each assessment that best corresponded to the clinical PsA diagnosis was obtained by maximizing sensitivity plus specificity in receiver operating characteristic (ROC) analyses. Kappa (K) coefficient analyses determined the level of agreement between the clinical PsA diagnosis and assessment cutoffs (1=perfect agreement). Results Of 949 psoriasis patients assessed by rheumatologists, 285 (30%) had PsA based on clinical diagnosis (95% CI: 27%, 33%). Results varied from dactylitis in ≥1 joint, a cutoff with low sensitivity and high specificity, to a tender joint count of ≥1, a cutoff with surprisingly high sensitivity and specificity in lower and upper extremities (Table). K values were modest for all cutoffs. Of the composite tools, DAS44 (including foot joints) performed better than DAS28. Conclusions In this large prevalence study, nearly one third of psoriasis patients seen in dermatology centers received a clinical diagnosis of PsA by a rheumatologist. Although a statistically significant level of agreement was observed between the clinical PsA diagnosis and the cutoffs for the various assessment tools analyzed, none of the K values were high, suggesting that clinicians may be using combinations of recorded features with or without unrecorded features to make the diagnosis. Acknowledgements This study was sponsored by Pfizer Inc. Medical writing support was provided by Donna McGuire of UBC Scientific Solutions and was funded by Pfizer Inc. Disclosure of Interest P. Helliwell Speakers bureau: Pfizer, O. FitzGerald Grant/research support from: Abbott, BMS, Pfizer, MSD, Consultant for: Abbott, UCB, Pfizer, Speakers bureau: Abbott, Pfizer, MSD, D. Alvarez Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, A. Szumski Consultant for: Pfizer Inc, H. Jones Employee of: Pfizer Inc

Background Psoriatic Arthritis (PsA) is a complex condition involving both axial and peripheral joints, together with enthesitis, dactylitis and skin. A complete assessment of PsA is challenging within the short time available in routine clinics. Assessment of these components is important as they all contribute significantly to disease burden, and may require specific treatments for optimal outcome. Objectives As part of an initiative programme promoting the “Treat-to-Target” concept, a group of rheumatologists, dermatologists and nurse specialists considered ways of assessing all components of psoriatic disease in routine clinics. A modular approach for assessing psoriatic disease was proposed, with skin and axial disease initially assessed by questionnaire. Patients identified with significant symptoms could then be further clinically assessed. This study reports patient acceptability and utility of this proposal in a routine clinic setting. Methods A trained receptionist handed two questionnaires to sequential patients with psoriatic arthritis attending routine clinics at Guy’s Hospital, asking two questions:Questionnaire 1: Have you been suffering from any neck or back pain recently? Questionnaire 2: Do you have psoriasis at the moment? If patients answered yes to question 1, the questionnaire invited them to complete the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), on the reverse side. If they answered yes to question 2, they completed the Dermatology Life Quality Index (DLQI). Questionnaires had a tick-box format, and were completed in the waiting area prior to their appointment, then reviewed at their consultation with the doctor. Patients who had BASDAI scores >4 were seen again in a follow-up consultation at 3 months. Results 70 pairs of questionnaires were distributed and completed. All patients found them easy to understand and to answer. 47 patients (67.1%) identified co-existing neck or back pain, with 28 (59.6%) scoring BASDAI >4. On further review, 19 had axial pain due to degenerative spinal disease, and 9 cases had active spondylitis. 45 patients (62.6%) identified themselves as having co-existing psoriasis, with 24 patients (51%) scoring DLQI >5 and 8 patients (17%) a DLQI >10. Conclusions This preliminary use of screening questionnaires to facilitate a modular approach to the assessment of PsA showed high patient acceptability, and clinicians found the scores useful to indicate the extent of skin and axial involvement. We closely monitored our cohort with active spondylitis, and initially optimized NSAID therapy if possible. At three month follow up, 2 patients had repeat BASDAI >4, making them eligible for tumour necrosis factor inhibitor therapy. This was started in these 2 patients with good effect. DLQI >5 indicates significant skin involvement. 62.6% of our patient group reported skin involvement, of whom over a third had a DLQI >5, but only 8 of 70 patients had a score >10 suggesting more severe psoriasis activity. We propose the use of these questionnaires in routine practice. This patient acceptable approach helps identify skin and axial skeleton involvement early, so that treatment can be optimized quickly. In the future this approach will assist new composite disease activity measures for the assessment and treatment of psoriatic arthritis. Acknowledgements Abbott Immunology supported the Psoriatic Arthritis Assessment Academy programme. Disclosure of Interest None Declared

Background Four new disease specific composite disease activity measures have been developed for psoriatic arthritis (PsA). Further validation of these measures in interventional trial data is now required. Objectives The objective of this study was to compare the performance of the Psoriatic Arthritis Disease Activity Score (PASDAS), the Arithmetic Mean of the Desirability Function (AMDF), the Composite Psoriatic Disease Activity Index (CPDAI), and the Disease Activity Index for Psoriatic arthritis (DAPSA) using data from a large (n=324) interventional trial (GO-REVEAL). Thisrandomised, double-blind, study evaluated the safety and efficacy of 2 doses of the TNF inhibitor golimumab in subjects with active PsA. As a comparator the Disease Activity Score for rheumatoid arthritis was used. Methods Data on various outcomes was excerpted from the GO-REVEAL data set; however, imputation was used to calculate some components (e.g. the PsA quality of life measure: PsAQoL: Domains not addressed in GO- REVEAL (e.g. axial disease) were excluded. The performance of the scores at baseline and follow-up (weeks 14 and 24) was compared and also between the 2 treatment schedules (golimumab 50mg and 100mg 4 weekly). Spearman correlations and stepwise regression analyses were also used. Results All indices could distinguish response to treatment at 14 and 24 weeks. Effect sizes at 24 weeks for the 50mg (100mg) doses were 2.17 (2.36), 2.08 (2.36), 1.09 (1.41), 1.80 (1.78), and 1.13 (1.18) for PASDAS, AMDF, CPDAI, DAS28 and DAPSA respectively. Comparison of 24 week values across treatment groups by an analysis of covariance using the baseline values as covariates gave the following F statistics for the PASDAS (F = 18.3), AMDF (F = 19.6), CPDAI (F = 9.4), DAS28 (F = 13.6) and DAPSA (F = 7.9). For PASDAS score change was largely predicted by patient and physician global VAS scores, although significant contributions were also made by the physical component summary scale of the SF36, dactylitis and enthesitis scores, the tender joint count and the PASI. Both AMDF and CPDAI reflected a similar range of predictors but DAS28 and DAPSA were largely predicted by articular measures and CRP. Conclusions All measures are effective in determining treatment response in patients treated with a highly active treatment (the TNF inhibitor golimumab) for active psoriasis and psoriatic arthritis. Joint responses were equally reflected by all composite scores but PASDAS, AMDF and CPDAI better reflect other domains such as skin, enthesitis and dactylitis. PASDAS and AMDF were better able to distinguish between the three treatment groups and had much bigger effect sizes at 24 weeks, an important consideration in trial design and statistical power calculations, particularly when considering other therapeutic approaches. Acknowledgements We are grateful to Janssen Pharmaceuticals for data from the GO-REVEAL study Disclosure of Interest P. Helliwell Consultant for: Janssen Pharmaceuticals, A. Kavanaugh Consultant for: Janssen Pharmaceuticals

Background Foot problems associated with systemic sclerosis (SSc; scleroderma) are common and disabling. To-date there have been no formal studies of interventions directed at the foot problems experienced in people with SSc. Objectives The main objective of this randomized controlled trial was to evaluate whether foot pain in SSc can be improved through the routine provision of a simple pressure-relieving and insulating insole. Methods A multicentre RCT conducted in four UK participating centres. A total of 141 consenting patients with confirmed SSc (ARA/ACR 1980 criteria) and plantar foot pain were randomised to receive either a commercially available pressure-relieving thermally insulating insole (Prothotic™ Duoform, RRP £8.55) or a sham insole identical in appearance to the active intervention but with minimal cushioning or thermal properties. Randomisation on a 1:1 basis was performed centrally using a 24-hour, automated randomisation system at a UKCRC registered clinical trials research unit. The primary end point was a reduction in pain measured using the 100mm pain subscale of the Foot Function Index, after 12 weeks of intervention. Sample size was determined a priori on a requirement to detect a 15mm difference (SD 25.7, alpha =0.05 and power =90%). In a subset of 49 patients at the lead centre (Leeds), plantar pressure measures (maximum mean pressure at heel and forefoot, with and without insoles in situ) were also obtained for entry into an exploratory analysis. Results Analysis of baseline characteristics indicated excellent comparability between the active intervention and sham group for centre, gender, age, SSc subset and Rodnan skin score. One hundred and thirty patients provided valid data for the primary endpoint. In both groups there was a systematic improvement in FFI pain subscale scores from baseline to 12 weeks (Active group -13.1mm, 95%CI -18.66 to-7.55 ; Sham group -10.7, 95%CI -16.17 to -5.28). An ANCOVA model adjusting for centre, gender and baseline FFI score confirmed no difference in effect between the intervention and sham groups (difference=-2.4, 95%CI -7.70 to 2.94, p=0.3778). Compared to a shoe-only baseline measure, pressure was lowered in the heel region by use of the active insole (median difference (range) -24kPa (-75,22)) compared to the sham -4.6kPa ((-23,10), (p Conclusions The study compared a simple therapeutic insole with a sham device and found that over 12 weeks both produced a clinically worthwhile improvement in patient reported foot pain but with no difference between intervention arms. The active device produced a significantly greater reduction in pressure than the sham at the heel although not at the forefoot. This exploratory analysis suggests therefore, that despite careful selection the sham device introduced some unintended physical effect. The difficulty with employing a true sham as a control in physical intervention trials such as this may suggest the need for a zero intervention arm for similar studies in future. Acknowledgements Funding: Arthritis Research UK Clinical Studies Group for Autoimmune Rheumatic Diseases (award number 18826). Trial regn. ISRCTN 02824122 Our thanks to all TSC and TMG contributors and to the clinical staff at each site. Disclosure of Interest : None Declared

Psoriatic arthritis is a multifaceted disease and it provides a challenge to outcome methodologists. A number of measures have been used to define remission in PsA but they have been mostly articular. Composite measures of disease activity and low disease states are now emerging but further work is required to assess the implication of achieving these goals and in developing cost-effective treatment strategies to achieve them. Disclosure of Interest None Declared

Background Early intensive treatment with infliximab (IFX), high dose IV steroids and treating to target have been shown to be effective for remission induction in pts with early RA. Objectives To compare MTX+IFX vs. MTX+high dose IV steroid as induction therapy on radiographic progression in pts with DMARD naive RA. Methods A 78 wk RCT of pts with early (3-12 months symptoms),DMARD naive RA (1987 ACR criteria, DAS>2.4). Pts were randomised to 1of 2 grps:IFX or IVsteroid. Treatment was blinded to wk 26 then guided using a treat to target approach. Both grps received MTX 10mg wkly increasing to 20mg by wk 6. The IFX grp received: IFX 3mg/kg (wks 0,2,6,14,22)+dose adjustment from wk 26 according to DAS44. The IVsteroid grp received: IV methylprednisolone (MP) 250mg at wk 0, placebo infusions at wks 2,6,14,22 & from wk 26 treatment escalation as follows if DAS >2.4: add SSZ+HCQ, then stop SSZ+HCQ & add LEF, then 1 of the following: MTXs/c+LEF or MTX+ciclosporin or MTX+LEF+prednisolone 5-7.5mg dly.IM MP 120mg was administered if DAS >2.4 at wks 6,14,22,38,50 & 62 for both grps. Other biologics were allowed from wk 26 per NICE guidelines. Radiographs of hands & feet done at 0,26,52 & 78 wks were scored using the modified Sharp-van der Heijde (vdH-S) method by 2 independent radiologists blinded to treatment grp;mean of the readers’ scores was taken. Smallest detectable change was calculated to be 2 units. Results 112 pts were randomised to MTX+IFX (n=55) or MTX+IVsteroid (n=57). Baseline mean (SD) age IFX 53.7 (13.3) vs. IVsteroid grp 53.1 (12.8); mean (SD) DAS28CRP IFX 4.2 (1.1) vs. IVsteroid 3.6 (1.1). Remission (DAS Baseline median (IQR) joint space narrowing (JSN), erosion (ERO) and total vdH-S scores (TS) in the IFX (n=42) and IVsteroid (n=51) grps were: JSN 2.0 (0.0-7.5) and 1.5 (0.0-7.0), ERO 0.0 (0.0-1.6) and 0.5 (0.0-2.5), TS 3.0 (0.0-9.5) and 2.5 (0.5-9.5) respectively. At wk 52 (primary endpt), the median change in total vdH-S score was 0.0 (0.0-1.1) units in the IFX and 0.0 (0.0-2.0) units in the IVsteroid arm (p=0.157); median changes did not differ at 26 wks [IFX=0.0 (0.0-0.6) IVsteroid=0.0 (0.0-1.0), p=0.295] or 78 wks [IFX=0.0 (0.0-2.6) IVsteroid=0.5 (0.0-2.4), p=0.325]. Similar results were seen for JSN and ERO scores. Proportions of pts with radiographic non-progression (vdH-S Conclusions In this study of DMARD naive pts with moderate to severe RA, initial therapy with IFX+MTX and high dose IV steroid+MTX, together with tight disease control prevented radiographic progression in a significant majority of patients. Disclosure of Interest None Declared

Objectives The PsA impact of disease (PsAID) project is a EULAR initiative to elaborate a questionnaire reflecting the impact of PsA based on the patients’ perception, with the involvement of patient research partners. Methods (1) Selection of domains: Patient research partners from 11 European countries, members of the Task Force, identified 16 important domains (areas of health). In a subsequent survey, 139 patients from 13 countries prioritised the 16 domains of health according to importance. The 12 top-ranking domains were kept for the next step; 9 domains had the highest individualised priority. (2) Phrasing of questions: discussions within the group allowed the formulation of 12 numeric rating scale (NRS) questions, one for each domain. These questions were translated into 11 languages. (3) Relative importance of each domain: Relative weight of the domains was determined by asking the patients in the validation study to “spend 100 points” across the domains. This process was performed twice, once for 9 domains and once for 12 domains. The ‘points’ were analysed by their ranks and linearly transformed to a 0-10 scale. (4) Validation study : An international cross-sectional and longitudinal study was performed in 13 countries to examine the psychometric properties of the PsAID. Results (a) The 12 domains of health relate both to physical and to psychological domains (e.g. pain, skin problems, fatigue but also embarrassment and/or shame with appearance, social participation and depression). The decision was taken to have 2 PsAID scores: one with 9 domains for use in clinical trials (for feasibility reasons), and one with 12 domains for use in clinical practice (to assess all the aspects important for patients). (b) Each domain is assessed by a single NRS question with a time-frame of one week. (c) A relative importance was calculated for each domain in order to combine data into a single result. The PsAID12 (clinical practice score) uses simplified weights. Pain, fatigue and skin problems are the domains with highest relative importance. (d) In all, 474 patients participated in the validation study: the population had long disease duration and moderately active disease. Correlations were, as expected, high with other patient-reported outcomes, particularly patient global (R=0.82-0.84). Test-retest reliability assessed in 71 stable patients was high (ICC, 0.94-0.95). Sensitivity to change assessed in 71 other patients 3 months after a DMARD/biologic change, was also acceptable and comparable to other outcomes (standardised response means, 0.90-0.91). Conclusions A questionnaire to assess the impact of PsA on patients’ lives has been developed and validated. Two versions of the questionnaire are available, one for clinical practice and one for clinical trials. They should allow a better assessment of the patient’s perspective in PsA, but further validation is needed in other cohorts of patients and in clinical trials. Disclosure of Interest None Declared

Background Despite recommendations to use full joint counts to assess patients with PsA, reduced joint counts designed for RA are often used for reporting outcomes in PsA registry studies and are used in clinical practice to assess patients with PsA. Analysis of RCTs suggested that 28 joint counts were responsive in PsA but this analysis was based on polyarticular patients enrolled into drug trials. Objectives The aim of this analysis was to investigate full and reduced joint counts in patients with oligoarticular PsA. Methods The study was an analysis of baseline visits for patients in the GRACE study, an international observational cohort recruited to develop new outcome measure in PsA. Oligoarthritis was defined as less than 5 tender and swollen joints. At baseline, full 76/78 tender and swollen joint counts were assessed. Reduced joint counts used for RA including the 28 and 44 joint count were analysed for comparison. In addition, new proposed shortened joint counts for PsA were tested to investigate their possible future use: PsA-44 (elbows, wrists, MCPs, PIPs, DIPs, knees and MTPs) and PsA-56 (as before plus ankles and PIP toes). ROC analysis was used to see how well different joint counts predicted treatment change for high disease activity. The proportion of patients with active disease missed by reduced joint counts was also analysed. Results In the cohort of 503 patients, 270 were classified as oligoarthritis. ROC analysis revealed that tender joint counts did not predict treatment change for high disease activity even when using a full 78 joint count (AUC 0.54, p=0.32). A 76 SJC did predict treatment change (AUC 0.61, p=0.008) as did a 66 SJC and the SJC PsA44 and PsA56 (p Of the 270 patients, 164 patients did not have any tender joints identified on a 28 joint count. However, of these 164, 38 did have 1 or more tender joints that had been missed (23%), leaving 126 patients with no tender joints. The PsA-44 and PsA-56 missed tender joints in 18 and 7 patients respectively. When considering swollen joints, 256 patients did not have any swollen joints identified on a 28 joint count but 48 of these (19%) did have swollen joints elsewhere. The PsA-44 and PsA-56 missed swollen joints in 26 and 7 patients respectively. Conclusions Patients with oligoarticular PsA cannot be assessed using joint counts borrowed from RA. Ideally full joint counts should be performed to assess PsA patients with the 66/68 joint count being the preferred measure due to difficulties distinguishing between the PIPs and DIPs of the toes. Reduced joint counts designed specifically for PsA do show correlation with treatment change but can still underestimate disease activity. Disclosure of Interest None Declared

Background Minimal disease activity (MDA) is defined by OMERACT as “that state of disease activity deemed a useful target of treatment by both the patient and physician, given current treatment possibilities and limitations” and criteria for MDA in psoriatic arthritis (PsA) have been developed using consensus opinion of international experts. Objectives The aim was to investigate if the criteria correlated well with the opinion of rheumatologists treating PsA and their patients and investigate how they compare with other composite outcome measures in development for PsA. Methods The study was an analysis of baseline visits for patients in the GRACE study, an international observational cohort recruited to develop new outcome measure in PsA. At baseline, data on all aspects of disease activity and patient reported outcomes were collected. The treating physician was asked “Do you think this patient is in an MDA state?” and the patient was asked “Do you think your disease is well controlled?” Patients were classified as MDA if they fulfilled 5 of 7 from: tender joint count≤1; swollen joint count≤1; psoriasis activity and severity index≤1 or body surface area≤3; patient pain visual analogue score (VAS)≤15; patient global disease activity VAS≤20; health assessment questionnaire≤0.5; tender entheseal points≤1. ROC analysis was used to test the MDA criteria using physician and patient opinion as the gold standard. Composite measure scores for those patient in MDA and those not were compared and tested using Mann-Whitney U statistics. Results In total, data on 503 patients were collected at baseline. Using the physician’s opinion as a gold standard, the MDA criteria performed well with an area under the curve of 0.82 (95% CI 0.79, 0.86, p Comparison was made with proposed composite outcome measures for PsA including the CPDAI, DAPSA, PASDAS and AMDF. Scores for those in MDA and those not showed good separation for all of these composite measures (p Conclusions The MDA criteria for PsA correlate well with both physician and patient opinion in a large real-life observational cohort. The criteria had a high specificity for identifying patients with adequate disease control meaning that patients would not be undertreated using these criteria. The lower sensitivity identifies some patients who did not fulfil the criteria, but were still felt to have good disease control, identifying a tolerance by both physicians and patients for mild levels of disease activity in multiple domains of PsA. Disclosure of Interest None Declared

Background Therapeutic targets have been defined for diseases like diabetes, hypertension or rheumatoid arthritis and adhering to them has improved outcomes. Such recommendations are unavailable for spondyloarthritis. Objectives To define the treatment target for spondyloarthritis including ankylosing spondylitis (AS) and psoriatic arthritis (PsA) and develop recommendations for achieving the target, including a treat-to-target management strategy. Methods Based on results of a systematic literature review (performed by MS) and expert opinion, a task force of expert physicians and patients developed recommendations, which were broadly discussed and voted upon in a Delphi-like process. Level of evidence, grade of recommendation and strength of recommendation were derived by respective means. Results The literature review did not reveal trials comparing a treat-to-target approach with another or no strategy, but provided indirect evidence that facilitated the development of recommendations. The task force agreed on 5 overarching principles and 11 recommendations. Based on the current perception and classification of spondyloarthritis (including PsA, axial SpA (AS and non-radiographic axial SpA), peripheral SpA), only the last 2 recommendations are separate for axial spondyloarthritis, peripheral spondyloarthritis and PsA, while principles and 9 of the recommendations form a common trunk for all types of spondyloarthritis. The main treatment target, which should be based on a shared decision with the patient, was defined as remission, with an alternative target being low disease activity. Means to assess disease activity are discussed. Regular follow-up examinations should safeguard the evolution of disease activity toward the targeted goal. Additional items relate to extraarticular and extramusculoskeletal aspects and other factors, such as comorbidity. While the level of evidence was low for all items, the mean strength of recommendation was 9-10 (10: maximum agreement) for all recommendations. A research agenda was formulated. Conclusions The recommendations shall inform patients, rheumatologists, dermatologists and other experts as well as other stakeholders about expert opinion that allows reaching optimal outcomes of spondyloarthritis including AS and PsA. Acknowledgements This work was supported by an unrestricted educational grant from Abbott. Disclosure of Interest J. Smolen Grant/research support from: Abbott, Consultant for: Abbott, J. Braun: None Declared, M. Dougados: None Declared, P. Emery: None Declared, O. FitzGerald: None Declared, P. Helliwell: None Declared, A. Kavanaugh: None Declared, T. Kvien: None Declared, R. Landewe: None Declared, T. Luger: None Declared, P. Mease: None Declared, I. Olivieri: None Declared, J. Reveille: None Declared, C. Ritchlin: None Declared, M. Rudwaleit: None Declared, M. Schoels: None Declared, J. Sieper: None Declared, M. de Wit: None Declared, D. van der Heijde: None Declared

A study was conducted to compare the gait pattern of 12 patients with ankylosing spondylitis with axial disease only with that of 11 healthy controls using a telemeterised electrogoniometer gait analysis system. The reproducibility of the gait variables was found to be acceptable. Angles for movement at the hip and knee were less in patients with ankylosing spondylitis, but hip/knee angle ratios did not differ between the two groups. The stride length was shorter in the patients with ankylosing spondylitis. These findings are due to the increased rigidity of the spine, which results in decreased shock absorption and consequently a more cautious gait pattern in the absence of clinically and radiologically detectable peripheral joint disease.