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
Authors: C. T. Ritchlin, P. J. Mease, W. H. Boehncke, J. Tesser, E. Schiopu, S. D. Chakravarty, A. Kollmeier, E. C. Hsia, X. L. Xu, M. Shawi, Y. Jiang, S. Sheng, J. F. Merola, I. McInnes, A. Deodhar
Journal: Annals of the Rheumatic Diseases (2021)

Background: In the Phase 3 DISCOVER-1 1 &amp; DISCOVER-2 2 trials, guselkumab (GUS), a human monoclonal antibody targeting the IL-23p19-subunit, was effective in psoriatic arthritis (PsA) across joint &amp; skin endpoints. At Week 24 (W24), GUS benefit was consistent regardless of baseline (BL) demographic &amp; disease characteristics. 3 Objectives: We assessed whether GUS efficacy was sustained through W52 in pooled DISCOVER-1 &amp; -2 patients (pts) across select BL subgroups. Methods: Adults with active PsA despite standard therapies were enrolled in DISCOVER-1 (swollen [SJC] ≥3 &amp; tender joint count [TJC] ≥3, C-reactive protein [CRP] ≥0.3 mg/dL) &amp; DISCOVER-2 (SJC ≥5 &amp; 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 &amp; 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) &amp; skin (Investigator’s Global Assessment [IGA=0/1 + ≥2-grade reduction from W0] in pts with ≥3% body surface area [BSA] with psoriasis &amp; 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, &amp; % BSA with psoriasis. Missing data were imputed as nonresponse through W52. Results: BL pt characteristics in DISCOVER-1 (N=381) &amp; DISCOVER-2 (N=739) were well balanced across randomized groups. 1,2 Among 1120 pooled pts, mean SJC was 11, mean TJC was 21, &amp; 68% used csDMARDs (primarily methotrexate [MTX]). At W24, 62% (232/373) &amp; 60% (225/375), respectively, of GUS Q4W- &amp; 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%) &amp; Q8W (70%) groups &amp; across SJC (61-79%), TJC (68-76%), &amp; csDMARD use (68-80%) subgroups (Table 1) &amp; pt subgroups defined by BL BMI, PsA duration, &amp; % BSA with psoriasis (data not shown). ACR50 &amp; 70 response patterns were similar to ACR20 (Table 1). In pts with ≥3% BSA psoriasis &amp; IGA ≥2 at BL, 71% (193/273) &amp; 66% (171/258) of GUS Q4W- &amp; 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%) &amp; Q8W (71%) groups &amp; across % BSA with psoriasis (67-87%) &amp; csDMARD use (68-87%) subgroups (Table 1) &amp; pt subgroups defined by BL BMI and PsA duration (data not shown). Conclusion: Treatment with GUS 100 mg Q4W &amp; Q8W resulted in sustained improvement in signs &amp; 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 Figure 1 Table 1. ACR &amp; IGA Responses at Weeks 24 &amp; 52 &amp; by Select BL Characteristics Guselkumab Q4W Guselkumab Q8W N=373 N=375 Week 24 Week 52 Week 24 Week 52 ACR20, % 62 72 60 70 SJC (&lt;10/10-15/&gt;15) 68/59/53 79/61/67 57/66/60 68/68/76 TJC (&lt;10/10-15/&gt;15) 74/67/56 73/76/69 62/60/60 75/68/68 csDMARD use (none/any/MTX) 66/60/63 80/68/68 62/59/57 73/68/68 ACR50, % 34 49 31 45 SJC (&lt;10/10-15/&gt;15) 41/32/20 58/39/38 34/28/26 46/40/49 TJC (&lt;10/10-15/&gt;15) 51/41/24 58/53/43 40/33/26 52/46/43 csDMARD use (none/any/MTX) 36/33/35 53/46/48 36/29/27 51/42/40 ACR70, % 16 27 16 27 SJC (&lt;10/10-15/&gt;15) 22/10/7 32/20/24 18/10/19 30/23/26 TJC (&lt;10/10-15/&gt;15) 29/19/9 34/32/22 27/15/14 35/28/24 csDMARD use (none/any/MTX) 21/13/14 30/26/27 21/14/14 34/24/23 N=273 N=258 IGA 0/1, % 71 80 66 71 BSA % with psoriasis (≥3-&lt;10/≥10-&lt;20/≥20) 61/71/80 76/87/79 62/64/72 67/72/74 csDMARD use (none/any/MTX) 84/64/67 87/77/78 72/63/64 77/68/68 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 &amp; Johnson, of which Janssen Research &amp; Development is a wholly owned subsidiary, Employee of: Janssen Scientific Affairs, LLC, Alexa Kollmeier Shareholder of: Johnson &amp; Johnson, of which Janssen Research &amp; Development is a wholly owned subsidiary, Employee of: Janssen Research &amp; Development, LLC, Elizabeth C Hsia Shareholder of: Johnson &amp; Johnson, of which Janssen Research &amp; Development is a wholly owned subsidiary, Employee of: Janssen Research &amp; Development, LLC, Xie L Xu Shareholder of: Johnson &amp; Johnson, of which Janssen Research &amp; Development is a wholly owned subsidiary, Employee of: Janssen Research &amp; Development, LLC, May Shawi Shareholder of: Johnson &amp; Johnson, of which Janssen Research &amp; 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 &amp; Johnson, of which Janssen Research &amp; Development is a wholly owned subsidiary, Employee of: Janssen Research &amp; 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.