DOP104Efficacy and safety of guselkumab for ulcerative colitis through week 140 of the QUASAR long-term extension study

Abstract Background QUASAR (NCT04033445) is a phase 2b/3 program evaluating guselkumab (GUS) in participants (pts) with moderately to severely active ulcerative colitis (UC).1,2 GUS is a selective dual-acting IL-23p19 subunit inhibitor that potently neutralises IL-23 and binds to CD64, a receptor on cells that produce IL-23.3 Here, we report ongoing QUASAR long-term extension (LTE) efficacy and safety results through week (W) 140. Methods GUS IV induction responders were randomised to receive SC maintenance treatment: GUS 100 mg q8w (GUS100); GUS 200 mg q4w (GUS200); or placebo (PBO). Pts could receive dose adjustment to GUS200 from W8-32. Pts completing the W44 visit could enter the LTE to continue their then-current treatment regimen. PBO pts discontinued after study unblinding. We evaluated efficacy among pts randomised to GUS who entered the LTE without receiving a dose adjustment. Data analysis methods were 1) “as observed” (AO) and 2) nonresponder imputation (NRI), accounting for pts with treatment failure or missing data. Safety was evaluated among all pts receiving LTE treatment. Results Overall, 87.0% of GUS-randomised pts entered the LTE, and 88.8% of those pts completed treatment through W140. At W140, among GUS100 and GUS200 pts, respectively, 80.1% and 81.5% achieved clinical remission and 86.5% and 87.5% of W0 clinical remitters maintained clinical remission at W140 (Fig; AO). Of 210 pts in clinical remission at W140, 205 (97.6%) were corticosteroid free for ≥8W before W140. Symptomatic remission was achieved in 92.1% and 92.3% of pts, endoscopic improvement in 84.6% and 84.0%, endoscopic remission in 55.9% and 51.2%, and histo-endoscopic mucosal improvement in 77.1% and 80.3% at W140 among GUS100 and GUS200 pts, respectively (Fig; AO). NRI results were numerically lower than AO results. Efficacy was consistent regardless of biologic and/or Janus kinase (JAK) inhibitor treatment history (Fig). The number of pts with ≥1 adverse event (AE) per 100 pt-years was similar in GUS groups (GUS100, 45.0; GUS200, 48.1) and numerically higher with PBO (67.1) (Table). One death (aortic dissection) and no active tuberculosis, opportunistic infection, anaphylaxis, serum sickness, or Hy’s Law were reported in GUS-treated pts. Serious infections were infrequent and generally similar across groups. Conclusion Both GUS maintenance dose regimens demonstrated sustained clinical, endoscopic, and histologic efficacy in pts with UC through W140. Efficacy was sustained regardless of biologic and/or JAK inhibitor treatment history. Although NRI results were numerically lower than AO results, the overall trends were consistent due to the high retention rate throughout the maintenance study and LTE. No new safety concerns were observed. 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: 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. Bressler, Brian: Personal Fees: Johnson and Johnson, AbbVie, Takeda, Pfizer, Alimentiv, Pendopharm, Genentech, Merck, CSL. Stock Options: Qu Biologics, Dova Health Intelligence. Dignass, Axel: Personal Fees: AbbVie, Alfasigma, CED Service GmbH, Celltrion, Dr. Falk Pharma, Falk Foundation, Ferring, Fresenius Kabi, Gilead, High5MD, Johnson and Johnson, Lilly, Materia Prima, MSD, Pfizer, Pharmacosmos, Sandoz, Stada, Streamed-Up, Takeda, Tillotts, Vifor Pharma. Grants AbbVie, Johnson and Johnson, Takeda. Non-financial support AbbVie, Johnson and Johnson, Takeda. Other: Abivax, AbbVie, Alfasigma, Dr Falk Pharma, Ferring, Johnson and Johnson, Pfizer. Hisamatsu, Tadakazu: Grant support: Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Mochida Pharmaceutical Co. Ltd., Boston Scientific Corporation, Kissei Pharmaceutical Co. Ltd. Consulting: Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, Johnson and Johnson Pharmaceutical K.K., Pfizer Inc., Eli Lilly, Gilead Sciences, Bristol Myers Squibb, Abivax, MSD, Chugai. Lecture fee: Mitsubishi Tanabe Pharma Corporation, AbbVie GK, EA pharma Co. Ltd., Kyorin Pharmaceutical Co. Ltd., JIMRO Co., Johnson and Johnson Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Kissei Pharmaceutical Co. Ltd. Sands, Bruce E: Grant: Johnson and Johnson. Personal Fees: Abivax SA, AbbVie, Adiso Therapeutics, Agomab Therapeutics, Alimentiv, Amgen, AnaptysBio, AstraZeneca, Biora Therapeutics, Boehringer-Ingeleim, Bristol Myers Squibb, Celltrion, Inc., ClostraBio, Cytoki Pharma, EcoR1 Capital, Eli Lilly and Company, Enthera, Equilium, Inc., Ensho Therapeutics, Evommune, Ferring, Galapagos, Genentech, Inc., Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Immunyx Pharma Ltd., Index Pharmaceuticals, Innovation Pharmaceuticals, Johnson and Johnson, Kaleido, Kallyope, Kyowa Kirin, Inc., Merck and Co., Microba, Microbiotica Limited, Mirador Therapeutics, Morphic Therapeutic, MRM Health NV, Palisade Therapeutics, Pfizer, Inc., Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Inc., Q32 Bio, Sanofi, Sorriso Therapeutics, Surrozen, Takeda, Target RWE, Teva, TLL Pharmaceutical, Tr1x, Union Therapeutics, Ventyx Biosciences. Non-financial Support: Johnson and Johnson, Pfizer, Lilly, Takeda, Bristol Myers Squibb. Stock/Stock Options from Ventyx Biosciences. Alvarez, Yelina: Employee of Johnson and Johnson. Baker, Thomas: Employee of Johnson and Johnson. Shipitofsky, Nicole: Employee of Johnson and Johnson. Stock options: Johnson and Johnson. Miao, Ye: Employee of Johnson and Johnson. Zhang, Hongyan: Employee of Johnson and Johnson. 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- Wesstfield Strategic Consultants- consulting 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) Woltwr 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 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. Allegretti, Jessica R: Consultant for Johnson and Johnson, Pfizer, AbbVie, Vedanta, Genentech, Seres Therapeutics, Ferring, GSK, Merck, Bristol Myers Squibb, Roivant, Celltrion, TRXBio, Xencor, and Shattuck Labs. Speaker for AbbVie, Janssen.