POS1027 EFFICACY AND SAFETY OF GUSELKUMAB, A MONOCLONAL ANTIBODY SPECIFIC TO THE p19-SUBUNIT OF INTERLEUKIN-23, THROUGH 2 YEARS: RESULTS FROM A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY CONDUCTED IN BIOLOGIC-NAÏVE PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS
Authors: I. Mcinnes, P. Rahman, A. B. Gottlieb, E. C. Hsia, A. Kollmeier, X. L. Xu, S. Sheng, Y. Jiang, M. Shawi, S. D. Chakravarty, D. Van der Heijde, P. J. Mease
Journal: Annals of the Rheumatic Diseases (2021)

Background: Guselkumab (GUS), a selective IL-23 inhibitor dosed every 4 or 8 weeks (Q4W or Q8W), demonstrated efficacy for joint and skin symptoms, inhibition of structural damage progression (Q4W), and safety vs. placebo (PBO) through Week 24 (W24) of the Ph3, double-blind, PBO-controlled trial in biologic-naïve pts with PsA (DISCOVER-2). 1 Favorable benefit-risk was also seen through 1 year. 2 Objectives: To assess GUS efficacy and safety through 2 years. Methods: Biologic-naïve adults with active PsA (≥5 swollen joint count [SJC] + ≥5 tender joint count [TJC]; CRP ≥0.6 mg/dL) were randomized (1:1:1) to GUS 100 mg Q4W; GUS 100 mg at W0, W4, Q8W; or PBO with crossover to GUS 100 mg Q4W (PBO→Q4W) at W24. Clinical efficacy (ACR/PASI/IGA/HAQ-DI) was assessed in the modified intention to treat (mITT) population through W100 with missing data imputation (nonresponse for categorical endpoints; no change/multiple imputation for continuous endpoints). Observed PsA-modified van der Heijde Sharp (vdH-S) scores derived from blinded radiographic images collected at W0, W24, W52, W100 (or at discontinuation [d/c]) and adverse events (AEs) through W112 were collected. Results: 712/739 (96%) randomized pts continued study agent at W24; 687/739 (93%) continued at W52; 652/739 (88%) completed W100. ACR20 response rates in the mITT population continued to increase after W24, and at W100 were 76% for Q4W and 74% for Q8W (Figure 1). Similar response patterns were seen for ACR50/70, HAQ-DI and PASI90/100 (Table 1), and IGA0/1 and PASI75 response rates were consistent through W100 in pts randomized to Q4W and Q8W; W100 data for PBO→Q4W pts were consistent with pts treated with Q4W and Q8W (Table 1). GUS improvements in SF-36 PCS/MCS at W52 also persisted through W100 (data not shown). Low rates of radiographic progression (as measured by PsA-modified vdH-S scores) were observed during W52-100 for Q4W (n=227; 0.75) and Q8W (n=232; 0.46). In the PBO→Q4W group (n=228), radiographic progression was 1.12 during W0-24 (while on PBO), 0.51 during W24-100 (while on Q4W), and 0.13 during W52-100. Through W112, the incidences of AEs, serious AEs (SAEs), AEs leading to d/c, infections, serious infections, and injection site reactions were generally consistent with the PBO-controlled period and through 1 year. Of the pts in the Q4W (n=245), Q8W (n=248), and PBO→Q4W (n=238) groups, 9%, 9% and 7% had ≥1 SAE; 2%, 3% and 3% had ≥1 serious infection; 2 Q8W pts (fungal esophagitis, disseminated herpes zoster) and 1 PBO→Q4W pt (listeria meningitis) had opportunistic infections; 1 PBO→Q4W pt died (road traffic accident); 1 PBO-randomized pt had IBD; no pt had anaphylactic or serum sickness reaction, or active TB. Conclusion: In biologic-naïve PsA pts, GUS improvements in joint and skin symptoms, physical function, and low rates of radiographic progression persisted through 2 years. GUS safety in PsA through 2 years was comparable with safety at 6 months and 1 year, similar between Q4W and Q8W, and consistent with GUS safety in psoriasis. References: [1]Mease PJ. Lancet . 2020 Apr 4;395(10230):1126-1136. [2] McInnes IB. Arthritis Rheumatol . 2020 Oct 11. doi: 10.1002/art.41553. Table 1. Efficacy Through W100 (NRI) Data are % GUS Q4W GUS Q8W PBO→GUS Q4W W24 W52 W100 W24 W52 W100 W24 W52 W100 Analysis set, n 245 248 246 ACR 50 33 46 56 32 48 55 14 41 48 ACR 70 13 26 35 19 28 36 4 18 30 BL HAQ-DI ≥0.35, n 228 228 236 Improvement ≥0.35 a 56 59 63 50 58 64 31 48 56 BL ≥3% BSA psoriasis + IGA ≥2, n 184 176 183 IGA0/1 69 63 62 71 58 55 19 63 67 PASI75 78 87 83 79 86 82 23 83 80 PASI90 61 77 74 69 74 70 10 72 77 PASI100 45 58 59 45 53 53 3 52 61 BL, Baseline; BSA, Body surface area; HAQ-DI, Health assessment questionnaire disability index; IGA, Investigator global assessment; NRI, nonresponder imputation; PASI, Psoriasis area and severity index. a ≥0.35 improvement among pts with HAQ-DI ≥0.35 at BL. Disclosure of Interests: 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, 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, Alice B Gottlieb Consultant of: Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers Squibb Co, Incyte, Janssen, LEO Pharma, Eli Lilly, Novartis, Sun Pharmaceutical Industries Inc, UCB, and Xbiotech, Grant/research support from: Boehringer Ingelheim, Incyte, Janssen, Novartis, Sun Pharmaceuticals Industries Inc, UCB, and Xbiotech, Elizabeth C Hsia Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research and Development, LLC, Alexa Kollmeier Shareholder of: Johnson &amp; Johnson, 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 Employee of: Cytel, Inc. providing statistical support (funded by Janssen), May Shawi Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Scientific Affairs, LLC, Soumya D Chakravarty Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Scientific Affairs, LLC, Désirée van der Heijde Paid instructor for: Director of Imaging and Rheumatology BV, Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, 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.