POS1522 CHANGES IN SERUM CYTOKINES BY WEEK 24 CORRELATE WITH LONG-TERM EFFICACY OF GUSELKUMAB THROUGH 2-YEARS IN BIO-NAÏVE ADULTS WITH PSA

Background The IL-23p19 inhibitor guselkumab (GUS) has shown robust efficacy vs placebo (PBO) in phase 3 DISCOVER-1 and -2 studies of adults with active psoriatic arthritis (PsA) [1,2] , continuous overall clinical improvement observed through 2 years DISCOVER-2 [3] . GUS previously been to significantly reduce levels inflammatory biomarkers associated PsA over 24 weeks [4] Objectives To assess whether earlier changes (by Week [W] 24) serum biomarker associate long-term (W100) response GUS. Methods enrolled biologic-naïve ≥6 months defined by the CASPAR criteria, swollen tender joint counts ≥5, C-reactive protein (CRP) ≥0.6 mg/dL. Patients (pts) were randomized 1:1:1 100mg at W0, W4, then every 4 (Q4W); Q8W; or PBO [2] Using Spearman linear regression General model, cytokine determined GUS-treated pts (pooled Q4W/Q8W) assessed for: 1) correlations between reductions levels, including selected Th17 cytokines (IL-17A, IL-17F, IL-22), acute (CRP, amyloid A [SAA], IL-6), β-defensin (BD-2), from baseline (BL) W24 disease severity BL W100, measured Disease Activity PSoriatic Arthritis (DAPSA) scores, Psoriatic Score (PASDAS), Psoriasis Area Severity Index (PASI) scores (significant correlation=r>0.25 p<0.05); 2) associations achievement ACR50 W100. Results demographics, severity, medication use available data (N=100) consistent population (N=493). With treatment, PASI score change W100 correlated BD-2, IL-17A, IL-22 (all r>0.25, p<0.05; Table 1 ), though PASDAS DAPSA did not correlate these W24. IL-6. responders (N=53) also demonstrated lower CRP, SAA, IL-6 than nonresponders (N=39) (p<0.05; Figure ). Conclusion This analysis reported substantial may portend durable improvements skin symptoms PsA. References [1]Deodhar A, et al. Lancet 2020;395:1115-25 [2]Mease P, 2020;395:1126-36 [3]McInnes IB, Rheumatol 2022;74(3):475-85 [4]Sweet K, RMD Open 2021;7:e001679 1. Rho values indicating among D2 data. Cytokine BD-2 0.096 0.128 0.599 IL-17A 0.035 0.056 0.412 IL-17F 0.016 0.068 -0.027 0.044 0.382 CRP 0.222 0.217 -0.051 SAA 0.175 0.215 0.061 0.316 0.193 -0.033 Shaded cells represent significant correlation activity (r>0.25 p<0.05). BD-2=β-defensin 2, BL=baseline, DAPSA=Disease for Arthritis, PASDAS=Psoriatic Score, PASI=Psoriasis Index, W=week Acknowledgements: NIL. Disclosure Interests Stefan Siebert Speakers bureau: AbbVie, GSK, Janssen, UCB, Consultant of: Amgen, Eli Lilly, Grant/research support from: Amgen (previously Celgene), Boehringer Ingelheim, Bristol Myers Squibb, Georg Schett Gilead, Novartis Siba P Raychaudhuri Celgene, Novartis, Pfizer, SUN Pharma, Monica Guma Genentech, Sonoma Biotherapeutics, Warner Chen Shareholder Johnson & Johnson, which Janssen Research Development is a wholly owned subsidiary, Employee Development, LLC, Sheng Gao Soumya D Chakravarty Scientific Affairs LLC Affairs, May Shawi Pharmaceutical Companies Proton Rahman Merck, Novartis.