SAT0397 GUSELKUMAB, AN IL-23 INHIBITOR THAT SPECIFICALLY BINDS TO THE IL23P19-SUBUNIT, FOR ACTIVE PSORIATIC ARTHRITIS: ONE YEAR RESULTS OF A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF PATIENTS WHO WERE BIOLOGIC-NAÏVE OR TNFΑ INHIBITOR-EXPERIENCED
Authors: C. T. Ritchlin, P. Helliwell, W. H. Boehncke, E. C. Hsia, A. Kollmeier, R. A. Subramanian, X. L. Xu, S. Sheng, Y. Jiang, B. Zhou, A. Deodhar
Journal: Annals of the Rheumatic Diseases (2020)

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 &amp; skin symptoms, physical function &amp; quality of life vs PBO; AEs were consistent with GUS safety in PsO. Objectives: Assess GUS efficacy &amp; 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] &amp; prior TNFi (Y/N) use, to GUS 100mg Q4W; GUS 100 mg at W0, W4 &amp; 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 &amp; 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) &amp; 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% &amp; 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 Efficacy 1 GUS Q4W GUS Q8W PBO (W0-24) X Q4W (W24-52 ) Data are % unless otherwise stated W24 W52 W24 W52 W24 W52 Dactylitis at W0, n 37 37 49 44 47 43 Resolution 64.9 78.4 67.3 79.5 61.7 81.4 Enthesitis at W0, n 71 70 71 64 71 63 Resolution 49.3 62.9 40.8 56.3 31.0 69.8 ≥3% BSA psoriasis, IGA ≥2 at W0, n 88 88 81 75 68 66 IGA 0/1 + ≥2-grade decrease 76.1 83.0 58.0 69.3 17.6 81.5 2 PASI75 87.5 94.3 76.5 80.0 20.6 84.8 PASI90 63.6 76.1 50.6 66.7 13.2 72.7 PASI100 45.5 64.8 25.9 48.0 7.4 62.1 HAQ-DI, n 125 124 123 114 114 104 Mean change -0.4 -0.5 -0.3 -0.4 -0.1 -0.4 SF-36 scores, n (mean change) 124 124 123 114 114 104 Physical Component - PCS 6.6 8.5 6.5 7.3 2.7 6.9 Mental Component - MCS 3.8 4.9 3.0 5.1 1.8 4.2 MDA , n 125 124 123 112 114 103 MDA response 31.2 40.3 23.6 33.9 12.3 31.1 VLDA, n 125 124 123 114 113 104 VLDA response 9.6 16.9 4.1 12.3 1.8 14.4 1 Randomized pts still on study agent at W24; 2 n=65 Conclusion: GUS Q4W &amp; 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 &amp; quality of life were also maintained through 1 year. GUS 100 mg Q4W &amp; Q8W were safe and well-tolerated through study completion and consistent with GUS safety in PsO. 1 References: [1]https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TREMFYA-pi.pdf. Acknowledgments: None Disclosure of Interests: Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Philip Helliwell: None declared, Wolf-Henning Boehncke Grant/research support from: Janssen Research &amp; Development, LLC, Consultant of: Janssen, Elizabeth C Hsia Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Alexa Kollmeier Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Ramanand A Subramanian Employee of: Janssen Research &amp; Development, LLC, Xie L Xu Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Shihong Sheng Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Yusang Jiang: None declared, Bei Zhou Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; 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