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Objective To assess performance of psoriatic arthritis (PsA) composite indices and evaluate guselkumab’s effect on achieving low disease activity or remission. Methods In this phase II trial, patients with active PsA (≥3 tender and ≥3 swollen joints, C‐reactive protein level ≥0.3 mg/dl, ≥3% body surface‐area with psoriasis involvement) were randomized 2:1 to subcutaneous guselkumab 100 mg (n = 100) or placebo (n = 49) at week 0, week 4, and every 8 weeks through week 44. At week 16, patients with

Background:Ultrasound (US) is an imaging adjunct to clinical joint examination adding sensitivity and objectivity to the assessment of inflammation. Previous studies in PsA have shown disparity between ultrasound and clinical findings with significant subclinical joint inflammation. A clinical challenge in PsA is to interpret tender joints (TJ) that are not swollen (SJ). As US is not widely used, alignment of clinical with US assessment is needed to determine its future role.Objectives:To determine how joint clinical examination relates to US findings in very early DMARD naïve PsA.Methods:Newly diagnosed DMARD naïve PsA patients, fulfilling CASPAR criteria, were recruited into the Leeds Spondyloarthropathy Register for Research and Observation (SpARRO), a prospective observational cohort study. US examination of 48 joints per patient was conducted by trained ultra-sonographers, blinded to clinical details with semi-quantitative scoring (0-3) for gray scale (GS) and power Doppler (PD). TJ and SJ counts were independently recorded. Cross-sectional baseline analysis was performed. The prevalence-adjusted and bias-adjusted kappa (PABAK) was calculated to determine agreements between clinical and US parameters. Spearman’s rank correlation coefficient was calculated to identify permutations of TJ/SJ correlating with GS ≥2, PD≥1 or both.Results:A total 5927 joints were scanned in 155 PsA patients. The mean age was 44.4 years, (SD 12.8), median disease duration 5.1 weeks (0.4-13.1); median TJC=7 (3-14) and SJC=2 (1-7). Oligoarthritis was present in 63.9% (99/155). US GS≥2 was frequently detected in the feet at MTPs1-4 (37.4- 53.6 %) and wrists (26.5- 33.6%). PD was most prevalent at wrists (17.5%) and MTP1 (12.6%) but observed less in other joints. Erosions were less frequent, the commonest site being MTP5 (17/310, 5.4%).Overall, SJ demonstrated high agreement (pTable 1.Agreement between TJ or SJ with GS≥2 & PD ≥1 and correlations for tender with/ without swollen combinations for right sided hand/feet joints.TenderSwollenT+ S-T+ S+Joint (Right)A (%)PABAKA (%)PABAKrrWrist75.50.51*89.10.78*-0.090.35*MCP184.10.68*87.50.75*0.090.44*MCP277.70.55*83.10.66*0.080.35*MCP379.10.58*84.50.69*0.0050.50*MCP478.40.57*86.40.72*0.070.22†MCP587.80.76*95.60.91*-0.030.49*MTP169.80.40*83.90.68*-0.03-MTP279.10.58*90.50.81*0.060.11MTP377.00.54*88.50.77*0.050.22‡MTP477.70.55*87.20.74*-0.0020.23‡MTP579.90.60*89.90.80*0.150.09T+= tender, S+ =swollen, S- = not swollen, A=agreement (%), r =coefficient, † pConclusion:Swollen joints demonstrate higher agreement with US synovitis (PD≥1 alone or GS ≥2 & PD ≥1 combined) than tender joints in early PsA. In addition, joints that are tender but not swollen have poor correlation with US synovitis at the individual joint level indicating that swelling is a better clinical discriminator of active synovitis, and factors other than synovial inflammation may drive tenderness in very early, DMARD naïve PsA. These results suggest re-appraisal of clinical joint counts is needed to refine treatment decision making in early PsA.Disclosure of Interests:Sayam Dubash: None declared, Oras Alabas: None declared, Xabier Michelena: None declared, Leticia Garcia-Montoya: None declared, Gabriele De Marco: None declared, Mira Merashli: None declared, Richard Wakefield Speakers bureau: Novartis, Janssen, GE, Philip Helliwell: None declared, Dennis McGonagle Grant/research support from: Janssen Research & Development, LLC, Ai Lyn Tan: None declared, Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), Helena Marzo-Ortega Grant/research support from: Janssen, Novartis, Consultant of: Abbvie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Takeda, UCB

Background:Dactylitis is a hallmark feature of Psoriatic arthritis (PsA) and Spondyloarthritis (SpA) defined as a uniform swelling of a digit (“sausage digit”). Dactylitis is associated with radiographic damage in chronic PsA. However, there are a paucity of data on the significance of dactylitis and its potential impact in disease burden in early PsA.Objectives:To characterize a very early DMARD naïve PsA cohort based on clinical presence or absence of dactylitis at disease onset.Methods:PsA subjects fulfilling the CASPAR classification criteria, were recruited into a prospective observational cohort, the Leeds Spondyloarthropathy Register for Research and Observation (SpARRO) after providing informed written consent. Clinical data including tender (TJC) and swollen joint counts (SJC) were independently assessed. Dactylitis was recorded per digit (finger or toe) as tender (hot) or non-tender (cold). Differences in baseline characteristics were evaluated using percentages to describe categorical variables and means and standard deviations for continuous variables, p value of the mean/proportion difference was calculated. Ultrasound (US) examination was conducted by trained ultra-sonographers blinded to clinical details. Bone erosions were defined on US if intra-articular discontinuity was present in two perpendicular planes at any of 46 joints: wrists, MCP1-5, PIP2-5, DIP2-5, MTP1-5, knees, ankles, subtalar, talonavicular.Results:A total of 177 PsA patients were recruited. Dactylitis was seen in nearly half the cohort [n=83 (47%)]. Patients with dactylitis had significantly more early morning stiffness, higher TJC and SJC, compared with non-dactylitis (Table 1). A total of 211 digits with dactylitis were recorded in 83 patients. Dactylitis of multiple digits was seen in 47/83 (57%) patients whilst a single dactylitic digit occurred in 36/83 (43%). Foot involvement was more prevalent (141/211, 67%) than hands (70/211, 33%). “Hot” or tender dactylitis was more frequently detected (153/211, 72.5%) than “cold” or non-tender dactylitis (58/211, 27.5%). The most prevalent sites for hot dactylitis were toes 2-4thand fingers 2-3rd.Table 1.VariableNo Dactylitis (n=94)Dactylitis (n=83)P valueAge, mean (SD) years44.4 (12.8)43.7 (13.2)>0.05Male38 (40.4%)42 (50.6%)>0.05Disease duration, median (IQR) weeks4.7 (0.0-11.4)5.2 (1-22.4)>0.05Early Morning stiffness, mean (SD) mins82.8 (145.4)170.5 (230.2)0.0025*TJC (78), mean (SD)8.3 (10.9)13.7 (14.0)0.004*SJC (76), mean (SD)2.2 (3.2)8.4 (8.0)Psoriasis94/94 (100.0%)76/83 (91.6%)0.004*PASI, mean (SD)3.6 (4.0)3.0 (4.1)>0.05Nail Dystrophy51/94 (54.3%)41/83 (49.4%)>0.05mNAPSI, mean (SD)4.9 (7.1)7.5 (14.0)>0.05MASES, mean (SD)1.6 (2.9)1.5 (2.4)>0.05BMI, mean (SD)29.1 (6.4)28.6 (5.6)>0.05Smoker19.0 (20.2%)9.0 (10.8%)>0.05Elevated CRP (>10 mg/L)24 (25.5%)36 (43.4%)>0.05PsAQoL, mean (SD)6.2 (6.6)6.2 (6.1)>0.05HAQ, mean (SD)0.79 (0.71)0.84 (0.65)>0.05US Erosions (n=154)12/83 (14.4%)21/71 (29.5%)0.023*US defined erosions were significantly more prevalent in the dactylitis group: 34 erosions in 21/71 patients (29.5%) versus 16 erosions in 12/83 (14.4%) patients in non-dactylitis. Sites prone to erosive damage in both groups were the wrists, MCP1,2 and MTP4,5. The right MCP2 (n=6) and MTP5 (n=6) were most commonly eroded in the dactylitis group, but erosions corresponding at the dactylitic digit level were overall low.Conclusion:This study identifies a more severe phenotype in very early DMARD naïve PsA presenting with dactylitis with higher prevalence of ultrasound erosions. Longitudinal follow up will determine whether dactylitis represents a poor prognostic factor in very early PsA, which may be a useful discriminator for risk stratification in future PsA management recommendations.Disclosure of Interests:Sayam Dubash: None declared, Oras Alabas: None declared, Xabier Michelena: None declared, Gabriele De Marco: None declared, Leticia Garcia-Montoya: None declared, Richard Wakefield Speakers bureau: Novartis, Janssen, GE, Ai Lyn Tan: None declared, Philip Helliwell: None declared, Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), Dennis McGonagle Grant/research support from: Janssen Research & Development, LLC, Helena Marzo-Ortega Grant/research support from: Janssen, Novartis, Consultant of: Abbvie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Takeda, UCB

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most widely prescribed drugs in general practice. They also head the list of drugs whose side-effects are reported to the Committee on Safety of Medicines. Many of their therapeutic effects and side-effects result from inhibition of the enzyme (cyclo-oxygenase) responsible for the production of prostaglandins from arachidonic acid, as originally suggested by Vane (1971). NSAIDs have little effect on cell migration, unless they also inhibit the enzyme lipo-oxygenase (as did benoxaprofen; see Leader, 1982), when an effect on cell migration may be seen. In this chapter it will be assumed that the novel NSAID inhibits cyclo-oxygenase and that it has been shown to have anti-inflammatory activity in animal models such as the rat adjuvant arthritis and/or carrageenin paw oedema model.

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

Introduction Les comorbidites et les complications cardiovasculaires sont frequentes dans le rhumatisme psoriasique [1] . L’inhibition des JAK est associee a une augmentation des lipides seriques [2] . Patients et methodes Au cours de l’essai EQUATOR ( NCT03101670 ), 131 patients atteints de rhumatisme psoriasique actif ont recu du FIL 200 mg (n = 65) ou le placebo (PBO) (n = 66) 1 fois/jour pendant 16 semaines. Les patients ayant termine l’essai EQUATOR pouvaient integrer l’extension en ouvert EQUATOR2 ( NCT03320876 ), au cours duquel les patients ont recu du FIL 200 mg pendant une duree maximale de 148 semaines. Les effets du FIL sur le cholesterol total (CT), le HDL-C, le LDL-C et le rapport CT/HDL-C ont ete analyses lors de la semaine 52 de l’etude d’extension (soit 68 semaines apres le debut d’EQUATOR). Dans une analyse post hoc, les patients ont ete classes en sous-groupes selon la presence/l’absence d’obesite (IMC ≥ 30 vs Resultats Cent vingt-quatre patients (95 %) ont termine l’essai EQUATOR. Cent vingt-deux patients (93 %) ont integre EQUATOR2, dont 11 patients (9 %) ont interrompu le traitement avant S52. L’exposition mediane (intervalle) au FIL etait de 66,0 (0,4–104,1) semaines. Au cours d’EQUATOR2, les niveaux de CT, LDL-C et HDL-C ont augmente sous FIL par rapport a l’inclusion, avec pour consequence une baisse du rapport CT/HDL-C. Les variations des parametres lipidiques ont ete coherentes, independamment de la presence d’obesite (n = 56, Fig. 1 ), de DT2 (n = 53), d’HTA (n = 80), d’hyperlipidemie (n = 108) ou d’un syndrome metabolique (n = 36). Chez les patients ayant recu le PBO au cours d’EQUATOR, le taux de HDL-C a augmente sous FIL lors de l’extension en ouvert (de maniere similaire a l’augmentation observee chez les patients traites par FIL pendant EQUATOR). Les niveaux de triglycerides sont restes stables tout au long de l’essai dans tous les sous-groupes. L’effet du FIL sur le profil lipidique des patients prenant un traitement hypolipemiant a ete similaire a celui de la population globale. Conclusion Les effets de l’exposition au FIL pendant ≥ 52 semaines sur le profil lipidique ont ete coherents, quel que soit le risque cardiovasculaire a l’inclusion, avec une hausse du CT et du HDL-C, et une baisse du rapport CT/HDL-C.

Introduction EQUATOR ( NCT03101670 ) est un essai de phase 2, randomise, multicentrique, en double aveugle, controle versus placebo, d’une duree de 16 semaines, evaluant l’efficacite du FIL, inhibiteur selectif de la janus kinase-1 per os, chez des patients atteints de rhumatisme psoriasique actif [1] . Cet essai a demontre l’efficacite rapide du FIL versus placebo sur plusieurs parametres, y compris sur le critere de reponse principal ACR20 a 16 semaines [1] . Les patients ayant termine EQUATOR pouvaient integrer l’extension en ouvert d’une duree de 148 semaines (EQUATOR2 ; NCT03320876 ). Cette analyse intermediaire post-hoc predefinie a S52 d’EQUATOR2 a evalue l’efficacite sur differents criteres d’activite de la maladie. Patients et methodes Les patients traites par placebo ont switche pour le FIL (200 mg 1 fois/jour) a S16 et ont integre l’extension en ouvert. Les patients qui recevaient deja FIL ont poursuivi ce traitement. Les profils de reponse ACR20/50/70 a S52 d’EQUATOR2 ont ete evalues selon le Psoriatic Arthritis Disease Activity Score (PASDAS) : faible activite de la maladie (LDA), activite minimale de la maladie (MDA) et MDA/tres faible activite de la maladie (VLDA). Resultats Cent vingt-quatre patients (95 %) ont termine l’essai EQUATOR. Cent vingt-deux patients (93 %) ont integre EQUATOR2, dont 11 patients (9 %) ont interrompu le traitement avant S52. L’exposition mediane (intervalle) au FIL etait de 66,0 (0,4–104,1) semaines. Chez les patients ayant recu initialement le FIL, une efficacite prolongee a ete constatee jusqu’a S52 pour la proportion de patients atteignant une reponse ACR20 (85,1 %), ACR50 (92,6 %), ACR70 (76,9 %), LDA (90,5 %), MDA (76,9 %) et MDA/VLDA (80,0 %). Les donnees PASDAS n’etaient pas disponibles a S16 pour un patient. Une proportion importante de patients n’ayant pas repondu au traitement lors d’EQUATOR a repondu plus tardivement au cours d’EQUATOR2, atteignant le score MDA et le critere ACR50 (22 % et 37 % respectivement). Les profils de reponse lors d’EQUATOR2 etaient similaires, quel que soit le traitement recu precedemment lors d’EQUATOR. Au total, a S52, 33,6 % des patients ont atteint un score MDA et 55,0 % ont atteint une reponse ACR50. Conclusion Ces donnees suggerent que le FIL est susceptible d’apporter une amelioration supplementaire au-dela de 16 semaines chez les patients atteints de rhumatisme psoriasique actif. Son efficacite prolongee a ete demontree a travers plusieurs criteres d’evaluation de l’activite de la maladie, dont le score MDA et l’ACR50.

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