AB0526 SUSTAINED GUSELKUMAB RESPONSE IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS REGARDLESS OF BASELINE DEMOGRAPHIC AND DISEASE CHARACTERISTICS: POOLED RESULTS THROUGH WEEK 52 OF TWO PHASE 3, RANDOMIZED, PLACEBO-CONTROLLED STUDIES

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.3 Objectives: 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 naive. 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 1 Disclosure 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.