P0805Predictors of Endoscopic Remission at 1 Year in Patients with Ulcerative Colitis Treated with Guselkumab: Post-hoc Analyses of the QUASAR Trial

Abstract Background Ulcerative colitis (UC) management aims to achieve sustained clinical remission and long-term endoscopic and histological healing. In the Phase 2b/3 QUASAR trial in UC, guselkumab (GUS) significantly improved clinical remission by Week (W) 44 of the maintenance (M) study, with one-third of patients (pts) achieving endoscopic remission (ER; endoscopic Mayo subscore EMS=0).1 Post-hoc analyses of QUASAR evaluated predictors of ER at 1 year of GUS treatment in pts with moderately-to-severely active UC. Methods In the maintenance study of QUASAR, GUS (intravenous 200mg at W0, W4, and W8) responders at W12 of the induction study were re-randomized to receive subcutaneous (SC) GUS 100mg every 8W (Q8W), GUS 200mg SC Q4W, or placebo. Data from pts re-randomized to GUS were analyzed. Predictors of ER at M-W44 were assessed via logistic regression. Univariate models were run for each variable of interest at induction and M-baseline (BL). Variables with p 0.1 were entered into reduced multivariate models using stepwise backward selection (Wald method); separate models were run for induction BL and M-BL variables. Results Of 378 GUS responders re-randomized to GUS 100mg SC Q8W or GUS 200mg SC Q4W, 129 (34%) achieved M-W44 ER. Rates of M-W44 ER did not differ across GUS regimens. In univariate models, induction BL factors associated with achieving M-W44 ER included female sex, extensive UC, concomitant oral aminosalicylate use, elevated C-reactive protein levels (CRP; 3mg/L), and no prior advanced drug therapy (ADT) failure (Table 1; Table 2). At M-BL, lower CRP (≤3mg/L or ≥ 50% reduction from induction BL) and fecal calprotectin (FC; ≤250μg/g or ≥ 50% reduction from induction BL) levels, and endoscopic healing (EMS=0 or 1) were also individually associated with M-W44 ER. After adjusting for GUS regimen, female sex (odds ratio OR 95% confidence interval; CI: 1.8 1.2, 2.9; nominal P = 0.007), extensive UC (1.8 1.2, 2.9; nominal P = 0.007), and concomitant oral aminosalicylate use (1.9 1.1, 3.4; nominal P = 0.022) were identified as independent induction BL predictors of M-W44 ER. Achievement of endoscopic healing (3.1 1.9, 4.9; nominal P 0.0001) at M-BL was independently associated with M-W44 ER. Conclusion Among GUS responders in the QUASAR maintenance study, female sex, extensive UC, and concomitant oral aminosalicylate use at induction BL were independently associated with ER at 1 year of GUS treatment. Importantly, achieving endoscopic healing after induction (i.e., at M-BL) was strongly associated with higher likelihood of ER at 1 year, irrespective of GUS dosing regimen, suggesting that this factor may help inform long-term endoscopic outcomes. Reference: 1. Rubin DT, Allegretti JR, Panés J, et al. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies. Lancet. 2025;405(10472):33-49. doi:10.1016/S0140-6736(24)01927-5. Conflict of interest: Rubin, David T.: Grant support: Takeda Pharmaceuticals Consultant: Abbvie, Abivax SA, Altrubio, Athos Therapeutics, Inc, Bristol-Myers Squibb, Celltrion, Connect BioPharma, Eli Lilly & Co., Genentech (Roche) Inc., Iterative Health, Janssen Pharmaceuticals, Johnson & Johnson, Merck & Co., Mirador, Odyssey Therapeutics, Pfizer, Sanofi, Spyre, Takeda Pharmaceuticals, Vedanta Biosciences, and Ventyx. Fumery, Mathurin: Grant: Pfizer Personal Fees: Abbvie, Janssen, Takeda, MSD, Biogen, Amgen, Sandoz, Fresenius, Gilead, Celgene, Galapagos, Mylan, Tillots, Ferring, Pfizer, Hospira, CTMA, Boehringer, Lilly, Arena Non-financial Support: Abbvie, Janssen, Takeda, MSD, Galapagos, Ferring, Pfizer Armuzzi, Alessandro: Consulting fees from AbbVie, Abivax, Alfa Sigma, Astra Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Enthera, Ferring, Galapagos, Gilead, Giuliani, Janssen, Lionhealth, MSD, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sanofi, Sandoz, Takeda, Teva Pharmaceuticals, Tillots Pharma Speaker’s fees from AbbVie, Abivax, AG Pharma, Alfa Sigma, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Teva Pharmaceuticals Research support from Biogen, MSD, Takeda, and Pfizer Non-financial support from Abbvie, Janssen, MSD, Pfizer, Takeda Ferrante, Marc: Research grants from AbbVie, EG Pharma, Celltrion, Janssen, Pfizer, Takeda and Viatris Consultancy fees from AbbVie, AgomAb Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, MRM Health, Merck Sharp and Dohme, Pfizer, Takeda and ThermoFisher Speakers’ fees from AbbVie, Biogen, Boehringer Ingelheim, Dr Falk Pharma, Ferring, Janssen-Cilag, Merck Sharp and Dohme, Pfizer, Takeda, Truvion Healthcare and Viatris Baker, Thomas: Employee of Johnson & Johnson Alvarez, Yelina: Employee of Johnson & Johnson Bravatà, Ivana: Employee of Johnson & Johnson Nazar, Maciek: Employee of Johnson & Johnson Van Denderen, Jacqueline: Employee of Johnson & Johnson Mccaffrey, Victoria: Employee of Johnson & Johnson Atreya, Raja: RA has served as a speaker, or consultant, or received research grants from AbbVie, Abivax, AlfaSigma, Arena Pharmaceuticals, Astra-Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion Healthcare, Dr Falk Pharma, Galapagos, Gilead, GlaxoSmithKline, InDex Pharmaceuticals, Johnson & Johnson, Lilly, Materia Prima, Merck Sharpe & Dohme, Pfizer, Roche Pharma, Takeda Pharma, Viatris.