P0980Association of endoscopic, histologic, and composite outcomes with long-term guselkumab efficacy in ulcerative colitis: 2-year results from the QUASAR long-term extension

Abstract Background The QUASAR (NCT04033445) phase 2b/3 program demonstrated that guselkumab (GUS) is efficacious in participants (pts) with moderately to severely active ulcerative colitis (UC).1,2 GUS is a dual-acting interleukin (IL)-23p19 subunit inhibitor that potently neutralises IL-23 and binds to CD64, a receptor on cells that produce IL-23.3 Reliable, clinically meaningful efficacy outcomes are needed to guide treat-to-target decisions in UC. Thus, we explored whether achievement of select efficacy outcomes at QUASAR maintenance baseline (week W 0) and at maintenance W44 was associated with achievement of corticosteroid (CS)-free clinical remission at W92 in the QUASAR long-term extension (LTE). Methods GUS intravenous induction responders were randomised to receive subcutaneous maintenance treatment: GUS 100 mg every 8 weeks, GUS 200 mg every 4 weeks (q4w), or placebo (PBO; GUS withdrawal). Dose adjustment to GUS 200 mg q4w was allowed in pts who lost response from maintenance W8–32. Pts completing the W44 visit could continue their then-current treatment regimen in the LTE. PBO pts discontinued after study unblinding. We evaluated achievement of CS-free clinical remission at W92 by achievement of endoscopic, histologic, and composite outcomes (Table) at W0 (among GUS-randomised pts regardless of whether they entered the LTE) and at W44 (among GUS-treated pts who entered the LTE). Results Among GUS-randomised pts, achievement of efficacy outcomes at W0 was associated with greater achievement of CS-free clinical remission at W92 (Fig A). Across outcomes, 66.8–77.3% of pts who achieved an outcome at W0 achieved CS-free clinical remission at W92 versus 48.6–57.6% of pts who did not (11.1–20.8% difference; all nominal p 0.05 except improvement composite). Achievement of efficacy outcomes at W44 among GUS-treated pts who entered the LTE was also associated with greater achievement of CS-free clinical remission at W92 (Fig B). Across outcomes, 72.1–81.3% of pts who achieved an outcome at W44 achieved CS-free clinical remission at W92 versus 44.0–59.4% of pts who did not (22.0–28.3% difference; all nominal p 0.001). Conclusion In QUASAR, achievement of endoscopic, histologic, and composite outcomes following induction and 1 year of maintenance therapy was associated with achievement of CS-free clinical remission at W92. Composite outcomes did not appear to be more strongly associated with CS-free clinical remission than endoscopic or histologic outcomes alone. These findings support endoscopic and histologic outcomes as sensible shorter-term targets associated with longer-term clinical outcomes in moderately to severely active UC. References: 1. Peyrin-Biroulet L, et al. Gastroenterology 2023;165:1443-57. 2. Rubin DT, et al. Lancet. 2025;405:33-49. 3. Sachen K, et al. Frontiers in Immunology. 2025;16:1532852. Conflict of interest: Magro, Fernando: Speaker honoraria from AbbVie, Arena, Biogen, Bristol Myers Squibb, Falk, Ferring, Hospira, Johnson and Johnson, Laboratórios Vitoria, Pfizer, Lilly, Merck Sharp and Dohme, Sandoz, Takeda, UCB, Vifor. Rubin, David T.: Grant support: Takeda Pharmaceuticals. Consultant: AbbVie, Abivax SA, Altrubio, Athos Therapeutics, Inc, Bristol Myers Squibb, Celltrion, Connect BioPharma, Eli Lilly and Co., Genentech (Roche) Inc., Iterative Health, Johnson and Johnson, Merck and Co., Mirador, Odyssey Therapeutics, Pfizer, Sanofi, Spyre, Takeda Pharmaceuticals, Vedanta Biosciences, and Ventyx. Lichtenstein, Gary: AbbVie: Consultant Support of University of Pennsylvania IBD Fellowship American College of Gastroenterology: Honoroarium for CME American Gastroenterological Association: CME American Regent: Consultant, Honorarium (CME Program) Bausch Health-Westfield Strategic Consultants: Consultant Bristol Meyers Squibb: Consultant Celgene: Consultant Celltrion: Consultant, CME CME Outfitters-support from Americal Regent-A Daiichi Sankyo Group Company: CME Eli Lilly: Consultant DSMB (Data Safety Monitoring Board), Focus Medical Education (GI Health Foundation): CME Gastroenterology and Hepatology-(Gastro-Hep Communications)-Executive Editor (Honorarium) Ironwood: CME Janssen Orthobiotech: Consultant, Research, Funding to University of PA (IBD Fellow Education) MedEd Consultants: Consultant Merck: Consultant, Honorarium (CME Program) Pfizer Pharmaceuticals: Consultant, Funding to University of PA (IBD Fellow Education) Pharmacosmos: Consulting Professional Communications, Inc.- Royalty for writing Textbook: “Clinical Management of Ulcerative Colitis” SLACK, Inc, Book Royalty Springer Science and Business Media Editor (Honorarium) Takeda: Consultant, Funding to University of PA (IBD Fellow Education), Research, Up-To-Date- Author (Honorarium) Wolter Kluwers Health-Editor of “Up to Date”- Honorarium for writing Vindico: CME Boston University Medical Center: CME Columbia University Medical Center: CME Bristol Meyers Squibb/Celgene: Consultant Orlando Health System: CME IBD Horizons: CME Program Texas Society of Gastroenterology: CME Saint Lukes Medical Center- CME Mayo Clinic Jacksonville, Florida. Alvarez, Yelina: Employee of Johnson and Johnson. Baker, Thomas: Employee of Johnson and Johnson. Miao, Ye: Employee of Johnson and Johnson. Peyrin-Biroulet, Laurent: CONSULTING: AbbVie, Abivax, Adacyte, Alimentiv, Alfasigma, Amgen, Apini, Banook, BMS, Celltrion, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Iterative Health, Johnson and Johnson, Lilly, LifeMine, Medac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Par’ Immune, Pfizer, Prometheus, Roche, Roivant, Samsung, Sandoz, Sanofi, Sorriso, Spyre, Takeda, Teva, ThirtyfiveBio, Tillots, Vectivbio, Vedanta, Ventyx. LECTURE: AbbVie, Alfasigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Iterative Health, Johnson and Johnson, Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots.