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The three monoclonal antibodies ustekinumab, guselkumab and risankizumab targeting the p 40 or the 19 subunit of interleukin -23 have now been approved for the indication psoriasis and the former two also for psoriatic arthritis (PsA). Ustekinumab and risankizumab have appeared ineffective in randomised controlled trials with patients with axial spondyloarthritis (axSpA), but post-hoc analyses of PsA trials have now suggested that they may improve back pain symptoms potentially induced by axial inflammation based on PsA. Here we argue that, based on the absence of efficacy in axSpA, this is unlikely and more probably due to generic, non-specific effects, which are not adequately covered by the tools developed for the assessment of inflammation in axSpA.

ObjectiveTo evaluate the effect of guselkumab on enthesitis and dactylitis in a phase II trial of patients with active psoriatic arthritis (PsA).MethodsThis was a phase II, randomised, placebo-controlled, double-blind trial of adults with active PsA (≥3 swollen and ≥3 tender joints and C reactive protein ≥0.3 mg/dL) despite conventional synthetic disease-modifying anti-rheumatic drug, non-steroidal anti-inflammatory drug, and/or oral corticosteroid therapy. Patients were randomised to subcutaneous injections of guselkumab 100 mg or placebo at weeks 0, 4 and every 8 weeks, with placebo crossover to guselkumab at week 24. Dactylitis was scored on a scale of 0–3 on each digit; enthesitis was assessed using the Leeds Enthesitis Index (0–6). Other assessments included American College of Rheumatology (ACR) and Psoriasis Area and Severity Index responses.ResultsOf 149 randomised patients, 107 patients had enthesitis (mean score=2.7) and 81 patients had dactylitis (mean dactylitis score=5.7) at baseline. Mean improvements in enthesitis and dactylitis at week 24 were greater in the guselkumab group versus placebo and sustained through week 56. Similar results were observed for the proportions of patients with resolution of enthesitis and dactylitis. At week 56, mean improvements in enthesitis and dactylitis among patients who switched from placebo to guselkumab treatment were similar to those in the guselkumab group. In the guselkumab group, ACR20 responders had greater improvements in enthesitis and dactylitis versus non-responders (week 24).ConclusionsAt week 24, the guselkumab group had greater mean improvements in enthesitis and dactylitis and greater proportions of patients with resolution of enthesitis and dactylitis versus placebo. ACR20 response was associated with improvements in enthesitis and dactylitis.Trial registration numberClinicalTrials.gov: NCT02319759.URL: https://clinicaltrials.gov/ct2/show/NCT02319759; Registered 18 December 2014.

A possible case of ulcerative colitis (UC) developed during treatment with ixekizumab is reported. Ixekizumab is a human monoclonal antibody approved for chronic plaque psoriasis that works by blocking interleukin-17 (IL-17). Cytoquines, such as IL-17, may be involved in the pathophysiology of psoriasis and inflammatory bowel diseases. We describe the case of a 76-year-old woman who presented with an episode of acute self-limited colitis after receiving ten doses of ixekizumab. It was resolved after treatment withdrawal. A re-challenge was done after 3 months and symptoms returned. Colonoscopy results confirmed the diagnosis of UC. Symptoms remitted after drug discontinuation and treatment with corticosteroids. Four months after stopping ixekizumab, she remains asymptomatic and she is being treated with guselkumab with adequate response. The Naranjo algorithm revealed a probable causal relationship. This adverse event should be taken into account by physicians and pharmacists before prescribing or reviewing therapies in order to improve patients’ safety.

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:VOYAGE 1, a phase-3, double-blinded, placebo- and active comparator-controlled study evaluated the efficacy and safety of guselkumab (GUS; a fully human anti-interleukin-23 monoclonal antibody) in patients with moderate-to-severe plaque psoriasis.1,2,3Objectives:To assess the efficacy and safety through 5 years of continuous GUS treatment.Methods:In VOYAGE 1, patients were randomized to GUS 100 mg at Weeks 0, 4, 12, then every 8 weeks (q8w); placebo at Weeks 0, 4, 12 followed by GUS 100 mg at Weeks 16, 20 then q8w; or adalimumab 80 mg at Week 0, 40 mg at Week 1, then 40 mg every 2 weeks (q2w) through Week 47. At Week 52, all patients continued open-label GUS through Week 252. Efficacy assessments included proportions of patients achieving ≥90% or 100% improvement in Psoriasis Area and Severity Index (PASI 90, PASI 100), and Investigator’s Global Assessment scores of cleared/minimal or cleared (IGA 0/1, IGA 0). Three statistical methods were used to analyze efficacy: prespecified Treatment Failure Rules (TFR), Nonresponder Imputation (NRI), and As Observed (OBS). For TFR analyses, patients who discontinued study agent due to lack of efficacy, worsening of psoriasis, or use of a protocol-prohibited psoriasis treatment were considered nonresponders. For NRI analyses, patients with missing efficacy data (regardless of the reason) after application of TFR were counted as nonresponders. For OBS analyses, missing data were not imputed. Safety was assessed through Week 264.Results:Among a total of 494 patients randomized to GUS at Week 0 (N=329) and placebo patients who crossed over to GUS at Week 16 (N=165), 76.9% (380/494) continued study agent through Week 252. PASI 90 responses were well-maintained with up to 5 years of continuous GUS use. At Week 52, PASI 90 response rates were 79.7%, 75.5%, and 80.6% based on TFR, NRI, and OBS analyses, respectively; corresponding rates at Week 252 were 84.1%, 66.6%, and 86.6%. Likewise, PASI 100, IGA 0/1, and IGA 0 responses were maintained from Week 52 through Week 252 (Table 1). Efficacy was also maintained through Week 252 in patients randomized to GUS at Week 0 (N=329). Through the end of the study for all patients (GUS group and adalimumab→GUS crossover group; N=774), the proportion of patients reporting at least one adverse event (AE), serious AE, or discontinuation due to AEs were 87.7%, 16.4%, and 6.1%, respectively. Rates of AEs of interest through Week 264 were as follows: serious infections (2.8%), malignancies (nonmelanoma skin cancer [1.7%]; cancer other than nonmelanoma skin cancer [2.3%]), major adverse cardiovascular events (1.0%), and suicidal ideation and behavior (0.6%).Conclusion:High efficacy response rates were maintained (regardless of the method used to analyze data) and no new safety concerns were identified through 5 years of continuous GUS treatment in VOYAGE 1.References:[1]Blauvelt A et al. J Am Acad Derm 2017;76:405-417[2]Griffiths CEM et al. J Drugs Dermatol 2018;17:826-832[3]Griffiths CEM et al. J Dermatol Treat 2020;13:1-9Table 1.Proportion of Patients in the GUS Groupa Achieving Clinical Responses by Analysis Type at Week 52 and Week 252Week 52Week 252TFR (N=468)(%)NRI (N=494)(%)OBS (N=463)(%)TFR (N=391)(%)NRI (N=494)(%)OBS (N=380)(%) PASI 90 77.9 75.5 80.6 84.1 66.686.6 PASI 100 49.7 46.6 49.7 52.741.7 54.2 IGA 0 84.6 80.2 85.582.4 65.2 84.7IGA 0 53.3 50.854.254.743.356.3GUS, guselkumab; IGA, Investigator’s Global Assessment; NRI, nonresponder imputation method; OBS, As Observed method; PASI, Psoriasis Area and Severity Index; TFR, treatment failure rules methodaIncludes patients randomized to GUS and placebo patients who crossed over to GUS at Week 16Disclosure of Interests:Christopher E.M. Griffiths Speakers bureau: AbbVie, Eli Lilly, Janssen, Leo, Novartis, Pfizer, Sandoz, and Sun Pharma, Consultant of: AbbVie, Eli Lilly, Janssen, Leo, Novartis, Pfizer, Sandoz, and Sun Pharma, Grant/research support from: AbbVie, Eli Lilly, Janssen, Leo, Novartis, Pfizer, Sandoz, and Sun Pharma, Kim Papp Speakers bureau: AbbVie, Amgen, Astellas, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Sun Pharma, Takeda, UCB, and Valeant, Consultant of: AbbVie, Amgen, Astellas, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Sun Pharma, Takeda, UCB, and Valeant, Grant/research support from: AbbVie, Amgen, Astellas, Baxalta, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Takeda, UCB, and Valeant, Michael Song Shareholder of: Johnson and Johnson, Employee of: Janssen Research & Development, LLC, Megan Miller Shareholder of: Johnson and Johnson, Employee of: Janssen Research & Development, LLC, Yin You Shareholder of: Johnson and Johnson, Employee of: Janssen Research & Development, LLC, Yaung-Kaung Shen Shareholder of: Johnson and Johnson, Employee of: Janssen Research & Development, LLC, Andrew Blauvelt Speakers bureau: AbbVie, Consultant of: AbbVie, Aclaris, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dermira, Eli Lilly, FLX Bio, Forte, Galderma, Janssen, Leo, Novartis, Ortho, Pfizer, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB Pharma.

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:In the Phase 3 DISCOVER-11 & DISCOVER-22 trials, guselkumab (GUS), a human monoclonal antibody targeting the IL-23p19-subunit, was effective in psoriatic arthritis (PsA) across joint & skin endpoints. At Week 24 (W24), GUS benefit was consistent regardless of baseline (BL) demographic & disease characteristics.3Objectives:We assessed whether GUS efficacy was sustained through W52 in pooled DISCOVER-1 & -2 patients (pts) across select BL subgroups.Methods:Adults with active PsA despite standard therapies were enrolled in DISCOVER-1 (swollen [SJC] ≥3 & tender joint count [TJC] ≥3, C-reactive protein [CRP] ≥0.3 mg/dL) & DISCOVER-2 (SJC ≥5 & TJC ≥5, CRP ≥0.6 mg/dL). 31% of DISCOVER-1 pts had 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 W0, W4, then Q8W; or placebo (PBO). Pts randomized to PBO received GUS 100 mg Q4W starting at W24 & were excluded from these analyses assessing maintenance of effect from W24 to W52. GUS effects on joint (American College of Rheumatology [ACR]20/50/70) & skin (Investigator’s Global Assessment [IGA=0/1 + ≥2-grade reduction from W0] in pts with ≥3% body surface area [BSA] with psoriasis & IGA ≥2 at W0) endpoints were evaluated by pt BL SJC, TJC, conventional synthetic disease-modifying antirheumatic drug (csDMARD) use, body mass index (BMI), PsA duration, & % BSA with psoriasis. Missing data were imputed as nonresponse through W52.Results:BL pt characteristics in DISCOVER-1 (N=381) & DISCOVER-2 (N=739) were well balanced across randomized groups.1,2 Among 1120 pooled pts, mean SJC was 11, mean TJC was 21, & 68% used csDMARDs (primarily methotrexate [MTX]). At W24, 62% (232/373) & 60% (225/375), respectively, of GUS Q4W- & Q8W-treated pts achieved ACR20 vs 29% (109/372) of PBO, with GUS effect consistently observed across pt BL subgroups (Figure 1). ACR20 response rates were sustained or increased at W52 in the GUS Q4W (72%) & Q8W (70%) groups & across SJC (61-79%), TJC (68-76%), & csDMARD use (68-80%) subgroups (Table 1) & pt subgroups defined by BL BMI, PsA duration, & % BSA with psoriasis (data not shown). ACR50 & 70 response patterns were similar to ACR20 (Table 1). In pts with ≥3% BSA psoriasis & IGA ≥2 at BL, 71% (193/273) & 66% (171/258) of GUS Q4W- & Q8W-treated pts, respectively, vs 18% (47/261) of PBO, achieved IGA 0/1 at W24, with GUS effect consistently observed across pt BL subgroups (Figure 1). IGA 0/1 response rates were also sustained or increased at W52 in the GUS Q4W (80%) & Q8W (71%) groups & across % BSA with psoriasis (67-87%) & csDMARD use (68-87%) subgroups (Table 1) & pt subgroups defined by BL BMI and PsA duration (data not shown).Conclusion:Treatment with GUS 100 mg Q4W & Q8W resulted in sustained improvement in signs & symptoms of active PsA through W52 regardless of pt BL characteristics.References:[1]Deodhar A, et al. Lancet 2020;395:1115-25;[2]Mease P, et al. Lancet 2020;395:1126-36;[3]Deodhar A, et al. American College of Rheumatology 2020; Poster P0908.Figure 1Figure 1Table 1.ACR & IGA Responses at Weeks 24 & 52 & by Select BL CharacteristicsGuselkumab Q4WGuselkumab Q8WN=373N=375Week 24Week 52Week 24Week 52ACR20, %62726070 SJC (15)68/59/5379/61/6757/66/6068/68/76 TJC (15)74/67/5673/76/6962/60/6075/68/68 csDMARD use (none/any/MTX)66/60/6380/68/6862/59/5773/68/68ACR50, %34493145 SJC (15)41/32/2058/39/3834/28/2646/40/49 TJC (15)51/41/2458/53/4340/33/2652/46/43 csDMARD use (none/any/MTX)36/33/3553/46/4836/29/2751/42/40ACR70, %16271627 SJC (15)22/10/732/20/2418/10/1930/23/26 TJC (15)29/19/934/32/2227/15/1435/28/24 csDMARD use (none/any/MTX)21/13/1430/26/2721/14/1434/24/23N=273N=258IGA 0/1, %71806671 BSA % with psoriasis(≥3-61/71/8076/87/7962/64/7267/72/74 csDMARD use (none/any/MTX)84/64/6787/77/7872/63/6477/68/68Disclosure of Interests:Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, and UCB Pharma, Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN, and UCB Pharma, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB Pharma, Wolf-Henning Boehncke Speakers bureau: AbbVie, Almirall, Celgene, Janssen, Leo, Eli Lilly, Novartis, UCB Pharma, Consultant of: AbbVie, Almirall, Celgene, Janssen, Leo, Eli Lilly, Novartis, UCB Pharma, Grant/research support from: Pfizer, John Tesser Speakers bureau: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Crescendo Biosciences/Myriad, GlaxoSmithKline, Genentech, Janssen, Eli Lilly, and Pfizer, Consultant of: AbbVie, AstraZeneca, Bristol Myers Squibb, Gilead, Janssen, Eli Lilly, Novartis, and Pfizer, Grant/research support from: AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Horizon, Janssen, Eli Lilly, Merck KG, Novartis, Pfizer, Sandoz, Sun Pharma, Setpoint, and UCB Pharma, Elena Schiopu Consultant of: Janssen, Grant/research support from: Janssen, Soumya D Chakravarty Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Scientific Affairs, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, of which Janssen Research & Development 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, May Shawi Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Global Services, LLC, Yusang Jiang Employee of: Cytel, Inc., providing statistical support (funded by Janssen), Shihong Sheng Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Joseph F. Merola Consultant of: AbbVie, Arena, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma, Iain McInnes Consultant of: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma, Grant/research support from: Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, and UCB Pharma, Atul Deodhar Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, UCB Pharma.

Background:Guselkumab (GUS), a selective monoclonal antibody targeting the interleukin-23p19 subunit, has demonstrated efficacy in 2 pivotal Ph3 psoriatic arthritis (PsA) studies (DISCOVER-1,1 DISCOVER-22).Objectives:Evaluate GUS efficacy and safety in PsA patients (pts) with inadequate response (IR) to tumor-necrosis-factor inhibition (TNFi) through Week24 (W24) of the Ph3b COSMOS study.Methods:In this randomized, double-blind, placebo (PBO)-controlled trial, 285 pts with active PsA (≥3 swollen & ≥3 tender joints) who demonstrated lack of benefit or intolerance to 1-2 TNFi were randomized 2:1 to subcutaneous GUS 100mg (n=189) or PBO (n=96) at W0, W4, then every 8 weeks (Q8W) through W44 (with PBO crossover to GUS at W24). At W16, pts who met early escape (EE) criteria (Results:Baseline characteristics were similar across GUS and PBO pts, though a higher proportion of females and more severe joint symptoms were seen in the GUS group. At W24, 44.4% of GUS vs 19.8% of PBO pts achieved ACR20 (pTable 1.Baseline characteristics of, and adverse events reported by, randomized and treated COSMOS ptsGUS 100 mg Q8W (N=189)PBO (N=96) Age, y4949 Sex, Female54%46% Duration of PsA, y8.38.7 Body mass index, kg/m22931a Swollen (0-66) / tender (0-68) joint count10 / 219 / 18 Pt pain / Pt global arthritis / Physician global disease, 0-10 cm VAS6.5 / 6.5 / 6.96.0 / 6.2 / 6.4 Health Assessment Questionnaire-Disability Index, 0-31.3b1.2 C-reactive protein, mg/dL1.2b1.2 Methotrexate use at baseline56%53% Psoriatic body surface area, %17.913.4 Number of prior TNFi: 1 / 288% / 12%89% / 11% Reason for prior TNFi discontinuation: Efficacy / Safety84% / 16%* 81% / 19%*Pts with ≥1 AE / SAE37% / 3%48% / 3%Pts with ≥1 infection / serious infection18% / 0%20% / 0%Pts with ≥1 AE leading to study agent discontinuation2%2%Pts with ≥1 malignancy0.4%0Pts with ≥1 injection-site reaction2%1%Data shown are mean or %. aN=95; bN=188. *Missing for 1 pt. SAE – serious adverse events; VAS – visual analog scaleConclusion:In this Ph3b, placebo-controlled study of PsA pts with IR to 1-2 TNFi, GUS 100 mg Q8W elicited a significantly higher ACR20 response rate vs. PBO at W24; results of prespecified sensitivity and subgroup analyses were consistent. GUS safety in TNF-IR PsA pts through W24 is consistent with the favorable GUS safety profile in psoriasis and biologic-naïve PsA pts.3References:[1]Deodhar A. Lancet 2018;391: 2213–24.[2]Mease PJ. Lancet 2020;395: 1126–36.[3]Guselkumab Prescribing Information. Janssen Biotech, Inc.Disclosure of Interests:Laura C Coates Consultant of: AbbVie, Amgen, Biogen, BMS, 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, Laure Gossec Consultant of: AbbVie, Amgen, BMS, Biogen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, Grant/research support from: Amgen, Eli Lilly, Galapagos, Janssen, Pfizer, Sandoz, Sanofi, Elke Theander Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Marlies Neuhold Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, 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, Georg Schett: None declared, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, and 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), an anti-interleukin-23p19-subunit monoclonal antibody, demonstrated efficacy vs placebo (PBO) in achieving American College of Rheumatology 20% improvement (ACR20) response in patients (pts) with active psoriatic arthritis (PsA) in two phase 3 trials, DISCOVER-1 & 2.1,2Objectives:To assess the differential treatment effects of GUS across individual components of ACR response in PsA pts participating in the DISCOVER-1 & 2 trials.Methods:In DISCOVER-1 & 2, 1120 pts were randomized & treated with GUS 100 mg every 4 weeks (Q4W; N=373); GUS 100 mg at Week (W)0 and W4, then Q8W (N=375); or matching PBO (N=372). Pts were evaluated by independent joint assessors at study visits. ACR20 response is defined as ≥20% improvement from baseline in both tender joint count (0-68 [TJC68]) and swollen joint count (0-66 [SJC66]) and ≥20% improvement from baseline in ≥3 of 5 assessments: Patient Assessment of Pain [Pt Pain], Patient Assessment of Global Disease Activity (arthritis) [PtGA], Physician Assessment of Global Disease Activity [PGA], Patient assessment of physical function as measured by Disability Index of the Health Assessment Questionnaire (HAQ-DI), and C-reactive protein (CRP). For each ACR component, achievement of ≥20% improvement from baseline was assessed over time through W24 for the combined (Q4W+Q8W) GUS groups, and median time to onset of treatment effect was determined with Kaplan-Meier curves by randomized group.Results:Median time to response for all components except SJC66 occurred earlier with GUS than PBO. Time to onset of ACR20 treatment effect is shown in Figure 1. CRP data show 56% of GUS-treated pts had diminution of systemic inflammation by W4 (Table 1). Reduction in systemic inflammation was accompanied or rapidly followed by GUS-related improvement in both PtGA and PGA (median W4-8). Although SJC66/TJC68 data showed similar patterns, there was also a high PBO response (data not shown). Consistent with early reductions in systemic inflammation, 48-61% of GUS-treated pts had ≥20% improvement in TJC68/SJC66/PGA at W4 (Table 1), and 45-48% had ≥20% improvement in HAQ-DI, PtGA, and Pt Pain by W8. By W24, >80% of GUS-treated pts had ≥20% improvement in SJC66/TJC68/PGA, followed by 63-64% with this degree of improvement in PtGA, CRP, and Pt Pain, and 57% for HAQ-DI.Conclusion:GUS demonstrated ACR20 improvements with separation from PBO in ACR components as early as W4, which is consistent with reduced inflammation by GUS and prior serological studies.3 At early study time points, both pts and physicians were able to discern improvements in signs and symptoms of arthritis that rapidly followed reductions in systemic inflammation (CRP). The predominant drivers of ACR20 response rates at W24 in GUS pts were SJC66/TJC68/PGA.References:[1]Deodhar A et al. Lancet. 2020;395:1115-25[2]Mease P et al. Lancet. 2020;395:1126-36[3]Siebert S et al. EULAR 2020. Presentation OP0229Table 1.W4W8W12W16W20W24ACR20203950566061HAQ-DI score364552545657SJC66617484868788TJC68486575798081PGA506774788181PtGA354858596264Pt Pain324855586163CRP566062636464Figure 1Disclosure of Interests:Peter Nash Consultant of: AbbVie, Bristol Myers Squibb, Boehringer, Celgene, Gilead, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Sandoz, Sun, Grant/research support from: AbbVie, Bristol Myers Squibb, Boehringer, Celgene, Gilead, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Sandoz, Sun, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Janssen, Eli Lilly, Gilead, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, and UCB, Wen-Chan Tsai Consultant of: AbbVie, Eli Lilly, Janssen, Pfizer, and Novartis, Ying Ying Leung Consultant of: Abbvie, Eli Lilly, Janssen, and Novartis, Lai-Shan Tam Consultant of: AbbVie, Boehringer Ingelheim, Janssen, Lilly, Pfizer, and Sanofi, Grant/research support from: Amgen, Boehringer Ingelheim, Janssen, GSK, Novartis, and Pfizer, Daniel Furtner Employee of: Janssen, a division of Johnson & Johnson Pte. Ltd., May Shawi Employee of: Janssen Research and Development, LLC, Stephen Xu Employee of: Janssen Research and Development LLC, Shihong Sheng Employee of: Janssen Research and Development, LLC, Alexa Kollmeier Employee of: Janssen Research and Development, LLC, 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, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, 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:Psoriatic arthritis (PsA), a chronic inflammatory disease characterized by peripheral arthritis, axial inflammation, dactylitis, enthesitis & skin/nail psoriasis, causes impaired physical function, disability & loss of work productivity.Objectives:Evaluate associations between PsA clinical characteristics & outcomes including fatigue & work productivity using Work Productivity & Activity Impairment Questionnaire: PsA (WPAI-PsA).Methods:The Phase 3 DISCOVER-2 trial assessed guselkumab (GUS), an anti-IL-23p19 subunit monoclonal antibody, in bio-naïve adults with active PsA (swollen joint count [SJC] ≥5 & tender joint count [TJC] ≥5, C-reactive protein [CRP] ≥0.6 mg/dL) despite standard therapies.1 Patients (Pts) were randomized 1:1:1 to GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or placebo (PBO). WPAI-PsA assesses PsA-related work time missed (absenteeism), impairment while working (presenteeism), productivity loss (absenteeism+presenteeism), & daily activity during the previous week. Spearman correlation testing evaluated relationships between pt demographics & disease characteristics of PsA & WPAI domain scores based on observed values at baseline. Univariate linear regression assessed associations between WPAI & these variables based on observed data at W0 & at W24. Variables with pResults:As reported elsewhere,2 least-squares mean % changes from baseline at W24 were -3.8/-19.5/-20.0/-20.5 for GUS Q4W, -3.1/-19.4/-19.7/-21.5 for GUS Q8W, & -3.5/-10.2/-10.9/-10.3 for PBO for absenteeism, presenteeism, absenteeism+presenteeism, & daily activity impairment, respectively. Among 738 pts, WPAI domain scores were moderately to strongly correlated (ie, ≥0.4) with pt-reported pain (0-10 visual analog scale), physical function (Health Assessment Questionnaire Disability Index [HAQ-DI]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] scale) & 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) score, but weakly correlated with other variables (Figure 1). Based on univariate analyses & evaluation of collinearity between variables, attributes included in multivariate models were age, body mass index (BMI), gender, CRP, FACIT-F, pain, Psoriasis Area Severity Index (PASI), TJC, SJC, enthesitis & dactylitis. In final model, CRP, FACIT-F, & pain were statistically significantly associated with all WPAI domains (Table 1). Presence of enthesitis & higher PASI score were significantly associated with higher loss of work productivity & activity outside work.Conclusion:In PsA pts, extra-articular symptoms, fatigue, pain & elevated CRP were significantly associated with WPAI-assessed work & activity impairment. Treating all major clinical manifestations of PsA is needed to help pts improve work & activity impairment. GUS effectively treats all major clinical manifestations1 & improves work & activity impairment in PsA.2References:[1]Mease P. Lancet 2020;395:1126-36.[2]Curtis J. ACR 2020; Poster 0332.Table 1.Multivariate analysis of clinical characteristics/outcomes & WPAI domains at W0 & W24ParameterAbsenteeismaPresenteeismaProductivity LossaActivity ImpairmentbEstimatep-valueEstimatep-valueEstimatep-valueEstimatep-valueAge-0.050.42-0.27-0.28-0.060.17Female0.910.46-1.540.22-1.740.202.380.02CRP0.730.040.970.011.010.010.89FACIT-F-0.31-0.67-0.73-0.75Pain1.034.154.254.02PASI0.060.360.160.020.140.050.150.003SJC0.080.48-0.050.61-0.050.660.030.75TJC-0.100.130.110.090.090.190.100.04Dactylitis (Y/N)-1.100.392.470.052.580.050.540.57Enthesitis (Y/N)1.520.202.380.042.990.012.400.01aPts working at baselinebAll pts in studyDisclosure of Interests:Jeffrey Curtis Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Eli Lilly, Myriad, Pfizer, Regeneron, Roche, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Eli Lilly, Myriad, Pfizer, Regeneron, Roche, and UCB, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, and UCB, Dafna D Gladman 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, Feifei Yang Shareholder of: Janssen, Employee of: Janssen, Steve Peterson Shareholder of: Janssen, Employee of: Janssen, Prasheen Agarwal Shareholder of: Janssen, Employee of: Janssen, Alexa Kollmeier Shareholder of: Janssen, Employee of: Janssen, Elizabeth C Hsia Shareholder of: Janssen, Employee of: Janssen, Chenglong Han Shareholder of: Janssen, Employee of: Janssen, May Shawi Shareholder of: Janssen, Employee of: Janssen, William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, MSD, Pfizer, and UCB, Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, and Novartis, 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, Proton Rahman Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, 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 (PsA) and VOYAGE 1&2 (PsO) are Phase 3 trials of guselkumab (GUS).Objectives:Compare safety results through up to 1yr of GUS in PsA and PsO pts.Methods:In DISCOVER, 1120 pts with active PsA despite standard therapy were treated. Most pts were biologic-naïve; ~30% in DISCOVER 1 had previous exposure to 1-2 TNFi. Concomitant MTX (57%), oral corticosteroids (17%), and NSAIDs (64%) were permitted. Pts were randomized to SC GUS 100mg at W0, W4, then Q8W; GUS 100mg Q4W; or PBO. At W24, PBO patients were switched to GUS 100mg Q4W. In VOYAGE, in which concomitant MTX use was prohibited, 1245 pts with moderate to severe PsO were treated and randomized to SC GUS 100 mg at W0, W4, W12, then Q8W; or PBO at W0, W4, W12, with crossover to GUS at W16, W20, then Q8W. AEs and laboratory parameters, analyzed by National Cancer Institute-Common Terminology Criteria for AEs [NCI-CTCAE] toxicity grades, were summarized through the PBO-controlled periods and 1yr.Results:Safety profiles were generally consistent across the GUS PsO and PsA clinical programs (Table 1). Time-adjusted incidence rates for numbers of AEs, serious AEs, serious infections, malignancy, MACE and AEs leading to d/c were generally similar between PsO and PsA. No cases of anaphylaxis or opportunistic infections were reported. Proportions of pts with decreased neutrophil counts and elevations in hepatic transaminases were slightly higher in PsA vs PsO. These abnormalities were mostly of NCI-CTCAE Grade 1 or 2 (3 for neutrophils; Conclusion:The GUS safety profile was generally consistent in PsA and PsO GUS-treated pts through 1yr of the DISCOVER and VOYAGE trials.Table 1.Treatment-Emergent AEs During PBO-controlled Period and Through 1Yr: VOYAGE & DISCOVER TrialsPooled VOYAGE 1&2Pooled DISCOVER 1&2Time PeriodW0-16Through 1YrW0-24bThrough 1Yr(N=)PBO(422)GUS Q8W(823)Combined GUSa(1221)PBOc(372)GUS Q8W(375)GUS Q4W (373)GUS Q8W(375)GUS Q4W (373)Combined GUS† (1100)Total pt-yrs of follow-up128255974173173172384385973Incidence/100 pt-yrs (95% CI)dAEs317 (287,349)330 (308,353)259 (249, 270)219 (198,243)256 (232,281)221 (200, 245)218 (203,233)177 (164,191)191 (182, 199)SAEs5 (2, 10)6 (4, 10)6 (5, 8)9 (5, 15)4 (2, 8)5 (2, 10)6 (4, 9)4 (2, 7)6 (4, 7)AEs leading to study agent d/c3 (0.9, 8)4 (2, 8)2 (2, 4)4 (2, 8)3 (1, 7)7 (4, 12)2 (1, 4)4 (2, 6)3 (2, 5)Infections86 (71, 104)98 (86, 111)98 (92, 104)58 (48, 71)58 (47, 71)63 (51, 76)58 (50, 66)53 (46, 61)55 (50, 60)Serious Infections0. 8 (0, 4)0.4 (0, 2)1 (0.5, 2)4 (2, 8)0.6 (0, 3)2 (0.4, 5)2 (0.6, 3)1 (0, 2)2 (0.9, 3)All Malignancy0 (0, 2)0.4 (0, 2)1 (0.4, 2)0.6 (0, 3)1 (0, 4)0 (0, 2)0.5 (0, 2)0 (0, 0. 8)0 (0, 1)MACE0 (0, 2)0.4 (0, 2)0.4 (0, 1)0.6 (0, 3)0 (0, 2)0.6 (0, 3)0 (0, 0.8)0.3 (0, 1.4)0.1 (0, 0.6)% pts with ≥1 injection site rxn3.14.55.00.31.31.11.62.41.7aPlacebo crossover pts were included in the combined GUS column after crossover to GUSbFor all pts who d/c study treatment early with the last dose of PBO/GUS prior to W24 and who did not receive any PBO/GUS at or after Wk24, all data including the final safety follow-up visit collected through 1yr were includedcFor pts in PBO group who switched to GUS due to cross-over or inadvertently, only data prior to first administration of GUS were included.dCI based on an exact method assuming observed number of events follows a Poisson distributionDisclosure of Interests:Alice B Gottlieb Consultant of: Anaptyps Bio, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers-Squibb, Eli Lilly, Janssen, LEO Pharma, Novartis, Sun Pharmaceuticals, UCB, and Xbiotech, Grant/research support from: Boehringer Ingelheim, Janssen, Novartis, Sun Pharmaceuticals, UCB, and Xbiotech, Joseph F. Merola Consultant of: AbbVie, Arena, Biogen, BMS, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, UCB, April Armstrong Consultant of: AbbVie, Janssen, Lilly, Leo, Novartis, UCB, Ortho Dermatologics, Dermira, KHK, Sanofi, Regeneron, Sun Pharma, BMS, Dermavant, and Modernizing Medicine, Richard Langley Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pizer, Sun Pharmaceutical, and UCB Pharma, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pizer, Sun Pharmaceutical, and UCB Pharma, Mark Lebwohl Consultant of: Aditum Bio, Allergan, Almirall, Arcutis, Inc., Avotres Therapeutics, BirchBioMed Inc., BMD skincare, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Evelo, Evommune, Facilitate International Dermatologic Education, Foundation for Research and Education in Dermatology, Inozyme Pharma, Kyowa Kirin, LEO Pharma, Meiji Seika Pharma, Menlo, Mitsubishi, Neuroderm, Pfizer, Promius/Dr. Reddy’s Laboratories, Serono, Theravance, and Verrica., Grant/research support from: Abbvie, Amgen, Arcutis, Boehringer Ingelheim, Dermavant, Eli Lilly, Evommune, Incyte, Janssen, Leo Pharmaceutucals, Ortho Dermatologics, Pfizer, and UCB, Christopher E.M. Griffiths Speakers bureau: AbbVie, Amgen, Almirall, BMS, Boehringer Ingelheim Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma., Consultant of: AbbVie, Amgen, Almirall, BMS, Boehringer Ingelheim Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma., Grant/research support from: AbbVie, Amgen, Almirall, BMS, Boehringer Ingelheim Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma., May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Ya-Wen Yang Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, 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, Miwa Izutsu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Paraneedharan Ramachandran Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Yin You Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Megan Miller Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, and UCB Pharma, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, and Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, 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 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:The efficacy of the interleukin (IL)-23 subunit p19 inhibitor guselkumab (GUS) for psoriatic arthritis (PsA) has recently been demonstrated in two Phase 3 trials (DISCOVER-1 & -2) but has not been evaluated versus existing targeted therapies for PsA.Objectives:To compare GUS to targeted therapies for PsA through network meta-analysis (NMA).Methods:A systematic literature review was performed to identify PsA randomized controlled trials from 2000 to 2018. Bayesian NMAs were performed to compare treatments on American College of Rheumatology (ACR) 20/50/70 response, Psoriasis Area Severity Index (PASI) 75/90/100 response, Health Assessment Questionnaire Disability Index (HAQ-DI) score, resolution of enthesitis (RoE), resolution of dactylitis (RoD), adverse events (AEs) and serious adverse events (SAEs). Analyses used random effects models that adjusted for placebo response via meta-regression on baseline risk when feasible. Results are summarized by ranking treatments according to median absolute probabilities of response derived from NMAs.Results:Twenty-six Phase 3 studies were included in the quantitative synthesis. Studies were placebo-controlled up to 24 weeks and evaluated 13 targeted therapies for PsA. Absolute probabilities are reported for PASI 90 & ACR 20 responses according toFigure 1,and a forest plot of relative risks versus placebo for AEs is reported according toFigure 2. For ACR 20 response, GUS 100 mg every 4 weeks (Q4W) and every 8 weeks (Q8W) ranked 5th and 8th out of 20 interventions and were comparable to IL-17A inhibitor (IL-17Ai) and most tumor necrosis factor inhibitor (TNFi) agents. Similar findings were observed for ACR 50 and 70 responses. For PASI 90 response, GUS Q4W and Q8W ranked 1st and 2nd out of 15 interventions and were highly likely to provide a greater benefit than most other agents. Similar findings were observed for PASI 75 and 100 responses. For HAQ-DI score, GUS Q4W and Q8W ranked 6th and 10th out of 20 interventions and were comparable to IL-17Ai and most TNFi agents. For RoE, GUS Q4W and Q8W ranked 8th and 6th out of 13 interventions and were comparable to IL-17Ai and TNFi agents. For RoD, GUS Q4W and Q8W ranked 8th and 9th out of 13 interventions and were comparable to most IL-17Ai and TNFi agents. For AEs, GUS Q4W and Q8W ranked 3rd and 2nd out of 19 interventions and were comparable to IL-17Ai and TNFi agents. Likewise, for SAEs, GUS Q4W and Q8W ranked 4th and 5th out of 20 interventions and were comparable to IL-17Ai and TNFi agents. Analyses that controlled for previous exposure to biologics or assessed outcomes at alternative timepoints were broadly consistent with primary analysis results.Conclusion:NMA results indicate that GUS is comparable to most targeted PsA treatments for improvement in arthritis, soft tissue damage, physical function, and safety outcomes. For PASI outcomes, GUS is highly likely to provide a greater benefit than other targeted PsA treatments.Disclosure of Interests: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, 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, Kiefer Eaton Shareholder of: Test Pharma, Consultant of: Janssen, Agata Schubert Employee of: Janssen-Cilag, Steve Peterson Employee of: Janssen Research & Development, LLC, Tim Disher Consultant of: Janssen, Wim Noel Employee of: Janssen Pharmaceuticals NV, Hassan Fareen Employee of: Janssen, Chetan Karyekar Shareholder of: Johnson & Johnson, Consultant of: Janssen, Employee of: Janssen Global Services, LLC. Previously, Novartis, Bristol-Myers Squibb, and Abbott Labs., Suzy Van Sanden Employee of: Janssen, Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Wolf-Henning Boehncke Grant/research support from: Janssen Research & Development, LLC, Consultant of: Janssen

Background:Guselkumab (GUS), an IL-23 inhibitor monoclonal antibody (Mab) that specifically binds to the IL-23p19 subunit, demonstrated efficacy compared to placebo (PBO) in reducing skin and musculoskeletal signs and symptoms in patients (pts) with active psoriatic arthritis (PsA) in two phase-3 studies, DISCOVER 1 & 2.1,2Previous results from a GUS PsA Phase-2 trial3and Ustekinumab (UST, anti-IL12/23p40 MAb) PsA Phase-3 trials (PSUMMIT 1 & 2)4showed associations of baseline IL-17A, IL-17F, and CRP with baseline disease characteristics, and associations of GUS-induced cytokine reductions with clinical responses.Objectives:To investigate plausible cytokine expression in PsA and alterations after exposure to GUS therapy.Methods:In DISCOVER 1 & 2, pts were treated with GUS 100 mg at Wk 0, 4, then every 8Wks (q8w); GUS 100mg q4w; or matching PBO. 21 serum biomarkers were measured in a random subset of 300 PsA pts from the DISCOVER program at Weeks (Wks) 0, 4, & 24 and in 34 healthy controls matched for age, sex, and ethnicity. Serum proteins measured were acute phase reactants CRP & SAA (Meso Scale Discovery (MSD) Platform) and inflammatory cytokines/chemokines: Th17 effector cytokines IL-17A, IL-17F, & IL-22 (Single Molecule Counting Erenna® Immunoassay Platform) and soluble ICAM-1, soluble VCAM-1, IL-6, CXCL-8, IL-10, IL-13, IL-12p70, CCL22, IFN-γ, CCL2, CCL4, TNFα, IL-1β, IL-2, IL-4 (MSD), & YKL-40 (Quantikine Immunoassay). Serum IL-17A, IL-17B, & CRP measured in the Phase-3 PSUMMIT trials of UST for PsA4were included for comparison with GUS.Results:At baseline, serum levels of acute phase proteins CRP, SAA, & IL-6, and Th17-effector cytokines IL-17A & IL-17F were elevated in pts with PsA compared with healthy controls (p0.25). Baseline CRP, SAA, IL-6, & YKL40 were significantly associated with baseline joint disease (Disease Activity Score 28-CRP, Spearman p0.25). Baseline SAA, IL-6, IL-17A, & IL-17F were higher in pts with prior TNF inhibitor exposure than without (pGUS treatment resulted in decreases in serum CRP, SAA, IL-6, IL-17A, IL-17F, & IL-22 that were significantly greater than PBO as early as Week 4 (FIG 1). These protein levels continued to decrease through Wk 24 in GUS-treated pts with both dosing regimens (pConclusion:Comprising a strong pharmacodynamic effect, GUS treatment reduced serum protein levels of acute phase and Th17-effector cytokines (whose elevations at baseline were associated with PsA disease characteristics) and achieved comparable levels to those in healthy controls. In pts with PsA, reductions of IL-17A and IL-17F by GUS were of greater magnitude than those by UST.References:[1]Deodhar et al. ACR 2019, abs #807. Arth Rheumatol. 2019;71 S10: 1386[2]Mease et al. ACR 2019, abs #L13. Arth Rheumatol. 2019;71 S10:5247[3]Siebert et al. EULAR 2019, abs #479. Ann Rheum Dis. 2019;78 S2:293[4]Siebert et al. Arth Rheumatol. 2019;71:1660Acknowledgments:NoneDisclosure of Interests:Stefan Siebert Grant/research support from: BMS, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Boehringer Ingelheim, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Celgene, Janssen, Novartis, 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, Matthew J Loza Employee of: Janssen Research & Development, LLC, Keying Ma Employee of: Janssen Research & Development, LLC, Karen Leander, Employee of: Janssen Research & Development, LLC, Vani Lakshminarayanan Employee of: Janssen Research & Development, LLC, Carol Franks Employee of: Janssen Research & Development, LLC, Philip Cooper Employee of: Janssen Research & Development, LLC, Kristen Sweet Employee of: Janssen Research & Development, LLC

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:Assessment of disease activity in psoriatic arthritis (PsA) requires evaluation of multiple aspects. Perception of disease activity by patient and physician is frequently discordant.Objectives:The aim of our study was to evaluate factors associated with persistence of disease activity evaluated by patients yet considered in remission by their rheumatologist.Methods:We performed a transversal monocentric study. PsA patients were included if they met the CASPAR criteria and if they were considered in remission. Disease activity was evaluated by scores: Disease Activity Score (DAS28-CRP), Simple Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), Disease Activity in Psoriatic Arthritis (DAPSA), Minimal Disease Activity (MDA), modified Boolean remission criteria for PsA. We collected multiple Patient’s Reported Outcomes (PROs): Psoriatic Arthritis Impact of Disease (PsAID), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Health Assessment Questionnaire (HAQ), Dermatology Life Quality Index (DLQI), Beck Depression Inventory (BDI), Fibromyalgia Rapid Screening Tool (FiRST), Pain Catastrophizing Scale (PCS). Discordance was defined by a difference between patient’s and rheumatologist’s global assessment ≥30/100 on a Visual Analogue Scale (VAS). Univariate and multivariate analyses were performed to evaluate factors associated with the presence of discordance.Results:62 PsA patients were included. 40.3 % were women and the mean (SD) age was 55 (14) years. 61% patients were in remission (rheumatologist definition) for more than 12 months and 19% for less than 3 months. 50% met MDA, 63% DAS28-CRP < 2,6, 39% SDAI and CDAI remission, 27% DAPSA remission. 39% had a discordant disease activity assessment from their rheumatologist. In univariate analysis, factors associated with discordance were a history of depression, an associated fibromyalgia, a history of clinical enthesitis and a history of corticosteroid use (Table 1). All disease activity scores and PROs were higher in discordant group and were associated with discordance in univariate analysis. In multivariate analysis, discordance was associated with no previous corticosteroid use (OR 24.5 (95%CI 2.9-203.7), p=0.003), a higher BDI scale (OR 1.4 (95%CI 1.1-1.8) by supplementary point, p=0.017) and a higher DAPSA score (OR 1.5 (95%CI 1.2-2), pConclusion:In this PsA cohort, discordance between patient and rheumatologist is very common. Discordance in assessment of disease activity was associated with no previous corticosteroid use, probably reflecting a less severe disease, presence of depressive symptoms and an increase of DAPSA, reflecting a more active disease.Disclosure of Interests:Marie Moly: None declared, Cédric Lukas: None declared, Jacques Morel: None declared, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB, Gael Mouterde: None declaredTable 1.Factors associated with discordance: Univariate analysisDiscordant group n=24Concordant group n=38OR (95%CI)PHistory of depression, n (%)9 (37.5)1 (2,6)22 (2.58-190.84)Fibromyalgia (ACR criteria), n (%)5 (20.8)1 (2.6)9.74 (1.06-89.4)0.028At least one enthesitis on the Leeds Enthesitis Index, n (%)14 (58.3)34 (89.5)0.17 (0.04-0.61)0.006TreatmentsPrevious corticosteroid use, n (%)8 (33.3%)26 (68.4%)0.23 (0.08-0.69)0.007Disease activity scores et Patients Reported Outcomes PROsDAS28-CRP > median (2.3), n (%)19 (79.2)12 (31.6)8.23 (2.48-27.32)SDAI > median (5.09), n (%)21 (87.5)10 (26.3)19.6 (4.79-80.18)DAPSA > median (7.97), n (%)22 (91.7)9 (23.7)35.4 (6.9-180.8)BDI > median (3), n (%)14 (58.3)10 (26.3)3.92 (1.32-11.62)0.012FiRST > median (2), n (%)17 (70.8)11 (28.9)5.95 (1.94-18.37)0.001BASDAI > median (2.45), n (%)19 (79.2)12 (31.6)8.23 (2.48-27.32)HAQ> median (0.1), n (%)16 (66.7)11 (28.9)4.91 (1.63-14.76)0.004PCS > median (9), n (%)18 (75)11 (28.9)7.36 (2.3-23.5)PsAID > median (2.1), n (%)18 (75)13 (34.2)5.77 (1.84-18.06)0.002

Background:Guselkumab (GUS), an interleukin-23 p19-subunit monoclonal antibody, demonstrated efficacy compared with placebo (PBO) in reducing signs and symptoms of psoriatic arthritis (PsA) in the phase 3 DISCOVER-1 & 2 studies.1,2Objectives:To evaluate gene expression in the blood of PsA patients (pts) in the DISCOVER-1 & -2 studies and the impact of GUS on the expression of these genes.Methods:Pts were treated with GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or matching PBO. Whole transcriptome profiling by RNA-sequencing was performed using the Novaseq platform on blood samples obtained from a subset of 673 pts with PsA at baseline across the 2 DISCOVER studies, as well as from 21 demographically (age, sex, and ethnicity) matched healthy controls procured independently of the clinical program. A subgroup (N=227) also had serial blood samples (W0/W4/W24) evaluated; the subgroup pts were selected based on having baseline characteristics (demographics, disease activity, medication use) representative of the overall cross-study PsA population. Significance of differentially expressed genes (DEGs) between PsA and healthy controls was defined by a false discovery rate (FDR) 1. For cell type analysis, genes that changed with GUS treatment were tested for enrichment using Cibersort. Gene enrichment scores were calculated using Gene Set Variation Analysis (GSVA).Results:To define disease genes, we compared genes at baseline in pts with active PsA vs. healthy control whole blood transcriptomes and detected 355 upregulated and 314 downregulated (top genes shown in Table 1), defined here as core disease genes. Upregulated genes were largely related to neutrophils, monocytes, macrophages, and extracellular matrix, whereas downregulated genes were related to T cells. The upregulated disease genes were significantly decreased and the downregulated disease genes were significantly increased by GUS treatment vs. PBO at W4 and W24 (Fig 1). Upon stratification by Psoriasis Area and Severity Index 75% response and American College of Rheumatology 20% response, changes in core disease gene expression from W0 were statistically significant among responders, but not in non-responders, at W4 and W24 (data not shown). We then performed the second differential expression analysis comparing baseline to W4 and W24 for both PBO and GUS treatment arms to define genes that change with treatment arm over time. At W4 and W24 we found many DEGs from baseline with GUS treatment and none with PBO. These included genes related to B-, T-, NK-, and plasma cells (increased by GUS) and neutrophils, monocytes, eosinophils, and macrophages (decreased by GUS), suggestive of a partial normalization of immune cell composition in whole blood.Conclusion:Using whole transcriptome profiling, we detected DEGs in blood samples obtained from PsA pts vs. healthy controls, suggesting a dysregulation of immune cell profiles in PsA. The majority of these disease-associated genes were modulated by GUS, with directionality toward a normalization of whole blood transcriptomic signatures.References:[1]Deodhar A et al. Lancet. 2020;395:1115.[2]Mease P et al. Lancet. 2020;395:1126.Table 1.Top DEGs derived from PsA vs. healthy whole blood transcriptomes.Upregulated in PsADownregulated in PsAGenelogFClogCPMFDRGenelogFClogCPMFDRADGRG75.92-0.900.02101AK8-1.36-1.061.61E-07ADAMTS24.060.820.006466FTCD-1.48-1.741.67E-05PGF3.21-0.680.006466GPR15-1.541.811.67E-05PCSK93.21-2.960.023872CHRM3-1.54-2.629.6E-08OLAH2.760.750.004539RFPL4AL1-1.69-3.340.009738MAOA2.55-0.260.005463SPACA3-1.85-3.230.000216SLC2A142.300.590.022594VANGL2-1.95-1.799.6E-08MMP12.25-1.160.004745RFPL4A-2.04-1.280.004539DAAM22.124.310.024628GLYATL2-2.77-2.781.93E-15BCAR1-3.13-2.586.24E-26Bold indicates positive change. CPM = counts per million.Disclosure of Interests:Stefan Siebert Consultant of: AbbVie, Janssen, Novartis, UCB, Grant/research support from: AbbVie, Amgen (previously Celgene), Bristol Myers Squibb, Boehringer Ingelheim, GSK, Janssen, Novartis, UCB, Kristen Sweet Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development LLC, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, and UCB, 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, Qingxuan Song Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development LLC, Michelle Miron Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development LLC

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:Guselkumab (GUS), an interleukin-23p19-subunit monoclonal antibody, demonstrated efficacy compared to placebo (PBO) in reducing skin and musculoskeletal signs and symptoms in patients with active psoriatic arthritis (PsA) in two phase-3 studies, DISCOVER-1 & -2, and in retarding structural damage in DISCOVER-2.1,2Objectives:To evaluate tissue-derived extracellular matrix (ECM) products3,4 in serum of PsA patients in the DISCOVER-2 study and their relationship with radiographic damage, clinical response, and impact of treatment.Methods:In DISCOVER-2, patients were treated with GUS 100 mg at Week (w) 0, 4, then every 8w (q8w); GUS 100 mg every 4w (q4w); or matching PBO. At w24, PBO patients were crossed over to GUS q4w. A total of 11 serum biomarkers of ECM collagen formation (PRO-C1, PRO-C2, PRO-C3, PRO-C4, and PRO-C6) and degradation (C1M, C2M, C3M, C4M, C6M, and COL10) were measured (by Nordic Bioscience) in a subset of 260 patients from the DISCOVER-2 program at Weeks 0, 4, 24, & 52 and in 76 healthy controls matched for age, sex, and ethnicity. PsA patients were selected randomly, though enriching for subjects with greatest radiographic changes, at Weeks 24 and 52. Significance defined by pResults:At baseline, collagen degradation markers C1M, C3M, C4M, C6M and collagen formation markers PRO-C3 and PRO-C6 were significantly higher in the serum of PsA patients compared to matched healthy controls. Baseline C3M, C4M, and C6M were positively correlated to baseline skin and joint disease; baseline C1M, C3M, C4M, C6M, and PRO-C1 were positively correlated to baseline radiographic damage (data not shown). Levels of C1M (a maker indicating breakdown of collagen type I, the major collagen subtype in the bone) were significantly decreased after 24w treatment with GUS (Figure 1), reaching significant differences from placebo with the GUS 100 mg q4w group. For the PBO patients who crossed over to GUS at w24, there was also a reduction in this marker observed at w52 (Figure 1). In patients treated with GUS or PBO, there were no significant differences in baseline expression levels of the analytes in responders (patients achieving ACR20 at w24) compared with non-responders. However, ACR20 responders in the combined GUS group had a significantly greater reduction in C1M levels compared to non-responders (p=0.0065) at w24.Conclusion:This work provides evidence that collagen biomarkers in serum are dysregulated in patients with PsA compared to healthy controls, and that GUS impacts levels of these proteins. Importantly, C1M serves as a biomarker that tracks with joint response. We observed a greater reduction in C1M in ACR responders compared to non-responders, providing insight into how GUS may be working to protect from degradation of bone in PsA.References:[1]Deodhar A et al. Lancet 2020;395:1115-1125[2]Mease PJ et al. Lancet 2020;395:1126-1136[3]Gudmann NS et al. Clin Exp Rheumatol 2017;35:653-659[4]Sardar S et al. Annals of the Rheum Dis 2019;78(Suppl 2): https://ard.bmj.com/content/78/Suppl_2/867.1Disclosure of Interests:Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, Novartis, Roche, UCB, Consultant of: AbbVie, BMS, Celgene, Janssen, Lilly, Novartis, Roche, UCB, Matthew J Loza Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Arumugam Palanichamy Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Oliver FitzGerald Speakers bureau: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Consultant of: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Christopher T. Ritchlin Speakers bureau: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB, Frederic Baribaud Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Kristen Sweet Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC.

Background:Guselkumab is an anti-interleukin (IL)-23 monoclonal antibody recently approved for a treatment of Psoriasis arthritis (PsA). In two large Phase III trials of patients with PsA (DISCOVER -1 & -2) guselkumab has shown to be superior versus placebo. In this indication no direct comparison is available between guselkumab and ustekinumab, a monoclonal antibody targeting IL-12 and IL-23. Indirect comparisons based on relative treatment effects versus a common comparator (placebo) only allow for analyses up to week 24 due to cross-over to active arms in available PsA trials.Objectives:To compare indirectly joint and skin efficacy of guselkumab versus ustekinumab up to week 52, using pooled patient-level trial data from DISCOVER 1&2 and PSUMMIT 1&2, adjusting for cross-trial population differences.Methods:Patient level data, including baseline characteristics and outcome data on American College of Rheumatology (ACR) response, Psoriasis Area Severity Index (PASI) response from the guselkumab arms of DISCOVER -1 & -2 were pooled with the data from the ustekinumab trials PSUMMIT -1&-2. Analyses were performed for bio-naïve and bio-experienced populations separately. Differences in patient characteristics across trial populations were adjusted for using multivariate logistic regression, including: gender, age, body mass index, previous TNF use, disease duration, PASI level, number of swollen and tender joints. This method of indirect comparisons allows for analysis of comparative efficacy beyond controlled induction period and odds ratios’ resulting from this model were translated into predicted response rates for ustekinumab, assuming same patient population, as enrolled in the guselkumab trial arms.Results:Majority of baseline characteristics for patients on guselkumab (100mg q8w; 100mg q4w) were comparable to patients on ustekinumab 45/90mg, in both in bio-naïve and bio-experienced group of patients. The probability of reaching a ACR 20 in both the bio-naïve & bio-experienced population was significantly higher for guselkumab vs ustekinumab at weeks 52 for both dosing regimens of guselkumab (bio-naïve ACR 20: q8w OR= 1.88 [1.28;2.76]), q4w (OR= 1.92 [1.29;2.86]; bio experienced ACR20 q8w OR= 2.72[1.17;6.31], q4w OR=4.77 [1.95;11.63]). Similarly guselkumab was superior over ustekinumab on PASI 90 outcome at week 52 in both bio-naïve & bio-experienced patients with BSA ≥3 % at baseline (bio-naïve: q8w OR= 2.59 [1.68;3.99]), q4w OR= 3.19 [2.03;5.00], and bio-experienced q8w OR= 3.96[1.39,11.27], q4w OR=13.10[4.18,41.04]). Figure 1 represents unadjusted pooled DISCOVER 1&2 trial results and estimated proportions of ustekinumab treated patient group achieving ACR 20 in bio-naïve patient group up to week 52 using the method described above.Conclusion:An adjusted comparison using patient level data from pivotal Phase III studies demonstrates both dosages of guselkumab to be significantly more effective versus ustekinumab in both skin and joint outcomes in both bio-naïve & bio experienced patients up to week 52.Disclosure of Interests:Joris Diels Shareholder of: Janssen, Employee of: Janssen, Pushpike Thilakarathne Employee of: Janssen, Agata Schubert Shareholder of: Janssen, Employee of: Janssen, Fareen Hassan Shareholder of: Janssen, Employee of: Janssen, Steve Peterson Shareholder of: Janssen, Employee of: Janssen, Wim Noel Shareholder of: Janssen, Employee of: Janssen.

Background:DISCOVER-2 was a Phase 3 trial of the first-in-class anti-IL-23-specific mAb guselkumab (GUS) in patients (pts) with psoriatic arthritis (PsA). PsA impacts patients’ productivity at work and in daily activity.1Objectives:To evaluate the effect of GUS on work productivity and daily activity in DISCOVER-2 through 1 year using the Work Productivity and Activity Impairment Questionnaire: PsA (WPAI- PsA).Methods:Bio-naïve adults with active PsA despite nonbiologic DMARDs &/or NSAIDs received subcutaneous GUS 100 mg every 4 weeks (Q4W); GUS 100 mg W0, W4, then Q8W; or placebo (PBO). At W24, PBO pts crossed over to GUS 100 mg Q4W. WPAI-PsA assesses PsA-related work time missed (absenteeism), impairment while working (presenteeism), impaired overall work productivity (absenteeism + presenteeism), and daily activity during the previous week. A shift analysis evaluated proportions of pts employed vs unemployed (regardless of desire to work) over time. Among pts working at baseline, least-squares (LS) mean changes from baseline in WPAI-PsA domains were determined using a mixed-effects model for repeated measures analysis, whereby mean changes in WPAI-PsA domains were calculated for each multiple imputation (MI) dataset using an analysis of covariance (ANCOVA); the reported LSmean is the average of all MI datasets. Also, among pts employed at baseline, indirect savings from improved overall work productivity were estimated using 2020 EU mean yearly wage estimate (all occupations).2Results:In pts working at baseline, significant improvement in work productivity and non-work activity vs PBO was observed at W24. Productivity gains seen with GUS at W24 continued to improve through 1 year (Table 1). Shift analysis showed relatively stable employment in pts employed at baseline (62% of shift analysis cohort) through 1 year of GUS (>91% continued to work when assessed at W16, W24, and W52 [data not shown]). For those unemployed at baseline (38% of cohort), the proportion of pts working increased by ~10% following 1 year of GUS (Figure 1). Potential yearly indirect savings from improved overall work productivity were: €7409 GUS Q4W and €7039 GUS Q8W vs €4075 PBO at W24 and were €8520 GUS Q4W, €9632 GUS Q8W, and €6668 PBO→GUS Q4W at W52.Conclusion:Improvement in work productivity and non-work activity was greater with GUS vs PBO among pts with active PsA through W52. Improvements demonstrated may result in reduction in PsA costs associated with work productivity.References:[1]Tillett W et al. Rheumatol (Oxford). 2012;51:275–83.[2]OECD (2020). Average wages (indicator). https://data.oecd.org/earnwage/average-wages.htmTable 1.Model-based estimates of LSmean changea (95% CI) from baseline in WPAI-PsA domains among pts working at baseline and with an observed change through W24 (N=474) and W52 (N=475)Change from baselineGUS 100mg Q4WGUS 100mg Q8WPBO(W0-24)PBO → GUS 100 mg Q4W (W24-52)VisitW24W52W24W52W24W52Absenteeism, N145145147147162163LSmean-3.4 (-6.5,-0.3)-4.1 (-6.8,-1.5)-3.0 (-6.0,0.1)-4.0 (-6.6,-1.3)-3.0 (-6.0, 0.04)-3.0 (-5.5,-0.4)Diff vs. PBO-0.4 (-4.6,3.8)-0.01 (-4.2, 4.2)Presenteeism, N145145147147162163LSmean-20.1 (-23.7,-16.6)-22.4 (-26.3,-18.6)-19.6 (-23.2,-16.1)-25.7 (-29.5,-21.8)-10.5 (-13.9,-7.0)-18.5 (-22.2,-14.7)Diff vs PBO-9.7* (-14.4,-5.0)-9.2* (-13.9,-4.5)Work productivity, N145145147147162163LSmean-20.1 (-24.1,-16.1)-22.6 (-26.8,-18.3)-19.2 (-23.1,-15.2)-25.9 (-30.0,-21.7)-10.6 (-14.4,-6.8)-17.6 (-21.7,-13.6)Diff vs PBO-9.5* (-14.8,-4.2)-8.6* (-13.9,-3.3)Non-work Activity, N242242246246245245LSmean-20.5 (-23.3,-17.7)-25.7 (-28.6,-22.7)-21.2 (-23.9,-18.4)-25.4 (-28.4,-22.5)-9.9 (-12.6,-7.1)-22.3 (-25.3,-19.4)Diff vs PBO-10.6* (-14.4,-6.8)-11.3* (-15.1,-7.5)CI=Confidence intervala. LSmean for each MI dataset is calculated based on an ANCOVA model for the change from baseline at W24/W52. The combined LSmean, which is the average of the LSmean, taken over all the MI datasets, is presented.*pDisclosure of Interests:Jeffrey Curtis Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, and UCB, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Steve Peterson Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Prasheen Agarwal Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Feifei Yang Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, 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, Chenglong Han Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer Inc, and UCB, Consultant of: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer Inc, and UCB, Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, and UCB, Philip J Mease Speakers bureau: Boehringer Ingelheim and GlaxoSmithKline, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB, 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:Guselkumab (GUS), a fully human monoclonal antibody, selectively binds and blocks interleukin-23. VOYAGE 1 and VOYAGE 2 are two ongoing Phase 3, randomized, double-blind, placebo (PBO)/active comparator-controlled clinical trials of GUS in patients (pts) with moderate-to-severe psoriasis (PsO).Objectives:This post-hoc analysis reports pooled results through 4 years among a subgroup of moderate-to-severe PsO pts with self-reported psoriatic arthritis (PsA) at baseline.Methods:1829 pts were randomized to GUS 100 mg at Weeks (Wks) 0, 4, and 12, then every 8 wks (q8wk); PBO at Wks 0, 4, and 12, GUS at Wks 16 and 20 then q8wk; or adalimumab (ADA) 80 mg at Wk 0, 40 mg at Wk 1, then 40 mg q2wk until Wk 47 (VOYAGE 1) or Wk 23 (VOYAGE 2). In VOYAGE 1, all pts received open-label GUS 100 mg q8wk during Wks 52-204. VOYAGE 2 incorporated a randomized withdrawal study design, followed by open-label GUS during Wks 76-204. Pooled subgroup analyses using the combined GUS group were conducted based on self-reported PsA status at baseline. Efficacy based on Investigator Global Assessment (IGA) score and Psoriasis Area and Severity Index (PASI) response was assessed using prespecified treatment failure rules (nonresponder status for all time points after discontinuing due to lack of efficacy, worsening of PsO, or use of a prohibited treatment).Results:For pooled VOYAGE 1 and VOYAGE 2 pts (N=1721), combined GUS and ADA to GUS response rates at Wks 100, 156, and 204 were: PASI 90 80.6%, 80.0%, and 80.4%; PASI 100 50.1%, 49.9%, and 52.2%; IGA 0/1 83.6%, 83.3%, and 81.7%; and IGA 0 54.3%, 52.9%, and 53.9, respectively. In the pooled subgroup analysis of pts with and without PsA, response rates were similar across the Wk 100, Wk 156, and Wk 204 evaluations (Table). Rates of adverse events through Wk 204 were comparable for pts with PsA vs those without PsA at baseline.Conclusion:Among GUS-treated pts with moderate-to-severe PsO with and without self-reported PsA at baseline, stable, durable, and high levels of skin responses, as well as comparable safety outcomes, through 4 years were observed.Table.Pooled GUS Response RatesWithout PsA at BaselineWith PsA at BaselineWk 100Wk 156Wk 204Wk 100Wk 156Wk 204N=1301N=1239N=1191N=289N=276N=264PASI 901049(80.6%)1001(80.8%)964(80.9%)233(80.6%)211 (76.4%)206(78.0%)PASI 100648(49.8%)631(50.9%)635(53.3%)149(51.6%)125 (45.3%)125 (47.3%)N=1300N=1235N=1189N=288N=276N=264IGA 0/11086(83.5%)1042(84.4%)979(82.3%)241(83.7%)217 (78.6%)208(78.8%)IGA 0702(54.0%)664(53.8%)649(54.6%)160(55.6%)135 (48.9%)134(50.8%)Acknowledgments:NoneDisclosure of Interests:Kristian Reich Grant/research support from: Janssen Research & Development, LLC, Jan Dutz Grant/research support from: Janssen Research & Development, LLC, Peter Foley Grant/research support from: Janssen Research & Development, LLC, Diamant Thaçi Grant/research support from: Janssen Research & Development, LLC, Ronald Vender Grant/research support from: Janssen Research & Development, LLC, Michael Song Employee of: Janssen Research & Development, LLC, Megan Miller Employee of: Janssen Research & Development, LLC, Yin You Employee of: Janssen Research & Development, LLC, Shu Li Employee of: Janssen Research & Development, LLC, Yaung-Kaung Shen Employee of: Janssen Research & Development, LLC, April Armstrong Grant/research support from: Janssen Research & Development, LLC

Background:Guselkumab (GUS), a monoclonal antibody that specifically binds to the p19-subunit of IL-23, is approved to treat psoriasis. Through Week24 (W24) of the Ph3, double-blind, placebo (PBO)-controlled trial in biologic-naïve pts with active PsA (DISCOVER-2), GUS every 4 or 8 weeks (Q4W or Q8W) demonstrated efficacy for joint & skin symptoms and inhibition of structural damage progression (Q4W), and was well tolerated.Objectives:Assess GUS efficacy and safety through W52.Methods:Biologic-naïve adults with active PsA (≥5 swollen+≥5 tender joints; CRP ≥0.6mg/dL) were randomized (1:1:1) to GUS 100 mg Q4W; GUS 100 mg at W0, W4, Q8W; or PBO. At W24, PBO pts crossed over to GUS 100 mg Q4W (PBO X Q4W). ACR response rates at W52, based on nonresponder imputation (NRI) for missing data and as observed in pts who continued study agent at W24, are shown. Observed data for additional endpoints, including PsA-modified van der Heijde Sharp (vdH-S) scores derived from blinded radiographic images collected at W0, W24, W52 (or at d/c) and scored in a new Read Campaign, are shown.Results:712/739 (96.3%) randomized & treated pts continued study agent at W24; 689/739 (93.2%) completed Wk52. NRI ACR20 response rates continued to increase after W24, and at W52 were 70.6% for GUS Q4W and 74.6% for GUS Q8W (Fig 1A). Similar response patterns were observed for the more stringent ACR50/70 criteria (Fig 1C,E). Observed ACR (Fig, 1B,D,F), IGA, PASI & MDA/VLDA responses; dactylitis & enthesitis resolution; and mean improvements in HAQ-DI and SF-36 PCS/MCS scores were also sustained through W52 in pts receiving Q4W & Q8W; W52 data for PBO X Q4W pts were generally consistent with other GUS-treated pts (Fig 1, Table 1). Changes in vdH-S scores were similar for W24-52 (0.62) and W0-24 (0.46) for Q4W; less radiographic progression occurred from W24-52 v W0-24 for Q8W (0.23 v 0.73) & PBO X Q4W (0.25 v 1.00). In 731 GUS-treated pts, 4.2% had SAEs; 1.2% had serious infections; no pt died; and no pt had IBD, opportunistic infections or active TB, or anaphylactic or serum sickness-like reactions.Table 1.Observed Efficacy1GUSQ4WGUSQ8WPBO X(W0-24)GUS Q4W(W24-52)Data are % unless otherwise statedW24W52W24W52W24W52Dactylitis at W0,n1161111071059593Resolution68.181.160.781.941.178.5Enthesitis at W0,n165160151148172168Resolution45.560.057.665.532.667.3≥3% BSA psoriasis, IGA ≥2 at W0,n176173172170176172IGA 0/1 + ≥2-grade decrease71.084.472.177.119.984.3PASI7581.891.980.888.823.388.4PASI9063.681.570.377.110.276.7PASI10046.661.346.554.72.855.2HAQ-DI,n234229238234237230Mean change-0.4-0.5-0.4-0.5-0.2-0.4SF-36 scores,n (mean change)234229238234237230Physical Component - PCS7.29.07.89.53.88.1Mental Component - MCS4.14.14.54.52.24.3MDA/VLDA, n234228238234238231MDA19.736.826.532.96.331.6VLDA5.112.224.6317.11.36.91Randomized pts still on study agent at W24;2N=229;3N=237Conclusion:In biologic-naïve pts with active PsA, GUS elicited sustained improvements in joint & skin symptoms; inhibition of radiographic progression & improvements in physical function, quality of life & composite indices through W52. GUS safety in PsA was similar at W241& W52 and consistent with GUS safety in psoriasis.References:[1]Mease P (A#L13), Arthritis Rheumatol 2019;71(suppl 10)Acknowledgments:NoneDisclosure of Interests: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, 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, 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., 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, Ramanand A Subramanian Employee of: Janssen Research & Development, LLC, Prasheen Agarwal 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, 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, 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: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:DISCOVER 2 (DISC 2) is a Phase 3 trial of anti-IL-23-specific mAb guselkumab (GUS) in psoriatic arthritis (PsA) pts, who experience impaired physical function, resulting in disability, work productivity loss, and economic consequences.1Objectives:To evaluate the effect of GUS on impaired work productivity and daily activity in DISC 2 using the Work Productivity and Activity Impairment Questionnaire: Psoriatic Arthritis (WPAI-PsA).Methods:Bio-naïve adults with active PsA despite nonbiologic DMARDs &/or NSAIDs received subcutaneous GUS 100 mg every (q) 4 weeks (W); GUS 100 mg W0, W4, q8W; or placebo (PBO). WPAI-PsA assesses, due to PsA over the previous week, work time missed (absenteeism), impairment while working (presenteeism), and impaired overall work productivity (absenteeism + presenteeism) and daily activity. Percentage change from baseline was analyzed for WPAI-PsA domains using mixed-effect model repeated measure (MMRM). Indirect savings from improved overall work productivity were estimated with 2018 US mean yearly wage estimate (all occupations).2Results:At Week 24, impaired overall work productivity and daily activity were improved 20-22% in GUS-treated and 10-11% in PBO-treated pts (Table). Potential yearly indirect savings from improved overall work productivity was $10,242 with GUS q8W and $10,404 with GUS q4W vs $5,648 with PBO; $4,594 and $4,756 difference, respectively.Conclusion:Improvement in overall work productivity and daily activity was greater with GUS versus PBO among pts with moderate-to-severe PsA, resulting in potential annual incremental economic gains.References:[1]Tillett W et al. Rheumatol (Oxford). 2012;51:275–283.[2]US Bureau of Labor Statistics. May 2018 National Occupational Employment and Wage Estimates United States.https://www.bls.gov/oes/current/oes_nat.htm#00-000Table.Model-based estimates of mean change from baseline in WPAI-PsA domains% change from baselinePBOGUS 100 mg q8WGUS 100 mg q4WW16W24W16W24W16W24Work time missed (absenteeism), n155152141145145143LSMean-4.6 (-7.2,-1.9)-3.5 (-6.4,-0.6)-3.5 (-6.2,-0.7)-3.1 (-6.1,-0.1)-4.7 (-7.4,-2.0)-3.8 (-6.8,-0.8)LSMean diff1.1 (-2.6,-4.8)*0.4 (-3.7,4.5)*-0.2 (-3.9,3.5)*-0.3 (-4.4,3.8)*Impairment while working (presenteeism), n131130125129133130LSMean-10.3 (-13.9,-6.7)-10.2 (-13.7,-6.7)-16.1 (-19.7,-12.4)-19.4 (-22.9,-15.9)-15.1 (-18.7,-11.5)-19.5 (-23.0,-16.0)LSMean diff-5.8 (-10.8,-0.8)†-9.2 (-14.0,-4.4)‡-4.8 (-9.7,0.1)*-9.3 (-14.1,-4.5)‡Overall work productivity impairment (absenteeism + presenteeism), n131130125129133130LSMean-11.2 (-15.0,-7.5)-10.9 (-14.6,-7.1)-15.9 (-19.7,-12.2)-19.7 (-23.4,-16.0)-15.8 (-19.5,-12.1)-20.0 (-23.7,-16.3)LSMean diff-4.7 (-9.9,0.5)*-8.8 (-14.0,-3.7)‡-4.6 (-9.7,0.5)*-9.2 (-14.3,-4.0)‡Daily activity impairment, n244244247246243245LSMean-10.6 (-13.3,-7.9)-10.3 (-13.1,-7.6)-17.1 (-19.8,-14.4)-21.5 (-24.2,-18.7)-17.0 (-19.7,-14.3)-20.5 (-23.2,-17.7)LSMean diff-6.5 (-10.2,-2.8)‡-11.1 (-15.0,-7.4)‡-6.5 (-10.2,-2.7)‡-10.2 (-14.0,-6.4)‡Data are % (95% CI)*p>0.05, †p‡pLSmeans, p values based on MMRMLSmean diffs, p values vs PBOAcknowledgments:NoneDisclosure of Interests:Jeffrey Curtis Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, 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, 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, William Tillett Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer Inc, UCB, Speakers bureau: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer Inc, UCB, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Bei Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Prasheen Agarwal Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Steve Peterson Employee of: Janssen Research & Development, LLC, Chenglong Han Employee of: Janssen Research & Development, LLC

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

Background:Guselkumab (GUS), a novel monoclonal antibody that specifically binds to the p19-subunit of IL-23, demonstrated efficacy in the Ph 3 DISCOVER-1 (D1) & DISCOVER-2 (D2) trials of pts with active psoriatic arthritis (PsA).1,2Dactylitis & enthesitis, key PsA clinical manifestations, can be difficult to treat and may portend more significant disease burden.3,4Objectives:In pts with dactylitis or enthesitis at baseline, assess: 1) changes in symptoms over time and 2) relationships between improvements in dactylitis or enthesitis and other PsA domains.Methods:Adults with active PsA despite standard therapies were eligible for D1 & D2. Approx. 30% of D1 pts previously received 1-2 TNF inhibitors; D2 pts were biologic-naïve. Pts were randomized 1:1:1 to GUS 100mg Q4W; GUS 100mg at W0, W4, Q8W; or PBO. Independent assessors evaluated dactylitis (total score: 0-60) & enthesitis (Leeds Enthesitis Index [LEI]; total score 0-6). Dactylitis and enthesitis findings through W24 were prespecified to be pooled across D1 & D2. P-values are unadjusted. We assessed changes in dactylitis and LEI scores over time (ANCOVA); associations between dactylitis or enthesitis resolution and ACR/PASI responses at W24 (Chi-square); and correlations between dactylitis or LEI and HAQ-DI/SF-36 change scores at W24 (Spearman’s correlation). AEs through W24 were reported.1,2Results:At W0, 42% of pooled D1+D2 pts had dactylitis; 65% had enthesitis. GUS improved dactylitis and LEI scores vs PBO at W8, W16, W24. GUS vs PBO differences were significant for dactylitis changes at W16 & W24 and LEI changes at W8 (Q4W only), W16 & W24; no dose response was observed (Fig). Rates of dactylitis or enthesitis resolution by W24 were consistently significantly (pTable). In GUS-treated pts at W24, significant correlations were observed between dactylitis change scores and PASI (pConclusion:In PsA pts with dactylitis or enthesitis at W0, GUS improved dactylitis or LEI scores vs PBO by W8; treatment differences were significant at W16 & W24. Resolution of dactylitis or enthesitis was significantly associated with clinically meaningful improvements in PsA joint & skin symptoms. Improved dactylitis scores correlated with improved skin symptoms and mental health; improved LEI scores correlated with improved physical function.References:[1]Deodhar A (A#807),[2]Mease P (A#L13), Arthritis Rheumatol 2019;71(suppl 10);[3]DOI: 10.1186/s13075-017-1399-5;4DOI: 10.1016/j.semarthrit.2018.02.002Table.Pooled DISCOVER-1&2: associations between dactylitis/enthesitis resolution and joint/skin responseACR20ACR50ACR70PASI75aPASI90aDactylitis resolutionbN%pts%pts%ptsN%pts%pts Q4W37355*34*16*12178*55* Q8W37553*31*16*11680*65* PBO37226*12*5*11519*10*Enthesitis resolutionc Q4W24334*31*11*18782*63* Q8W23040*7*12*16277*62* PBO25514*13*5*18219*9** p < 0.001 (Chi-square)aIn pts with ≥3% BSA psoriasis & IGA ≥2 at W0bIn pts with D at W0cIn pts with E at W0Acknowledgments:NoneDisclosure of Interests:Dennis McGonagle Grant/research support from: 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, 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, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shelly Kafka Employee of: Janssen Scientific Affairs, LLC, Chetan Karyekar Shareholder of: Johnson & Johnson, Consultant of: Janssen, Employee of: Janssen Global Services, LLC. Previously, Novartis, Bristol-Myers Squibb, and Abbott Labs., 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, Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, 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