DOP103Intravenous and subcutaneous guselkumab induction are similarly efficacious in patients with ulcerative colitis across weight quartile and BMI subgroups: Week 12 results from the phase 3 QUASAR and ASTRO studies

Abstract Background Guselkumab (GUS) is a dual-acting IL-23p19 subunit inhibitor that potently neutralizes IL-23 and binds to CD64, a receptor on cells that produce IL-23.1 The similar efficacy and safety of intravenous (IV) and subcutaneous (SC) induction with GUS in participants with moderately to severely active ulcerative colitis (UC) has been established in the phase 3 QUASAR and ASTRO studies.2,3 Obesity has the potential to impact the pharmacokinetic and pharmacodynamic parameters of subcutaneously administered medications. The aim of this post-hoc analysis was to determine whether body mass and body mass index (BMI) in participants with UC differentially affects the efficacy of GUS SC induction compared to IV induction. Methods Participants had moderately to severely active UC (modified Mayo score of 5-9, baseline Mayo rectal bleeding subscore ≥1, and Mayo endoscopic subscore ≥2) and a history of inadequate response/intolerance to oral corticosteroids, AZA/6-MP/MTX, biologics, Janus kinase inhibitors, and/or sphingosine-1-phosphate (S1P) inhibitors (ASTRO only). GUS phase 3 induction regimens were 200 mg IV in QUASAR (N = 421) or 400 mg SC in ASTRO (N = 279) at Weeks 0, 4, and 8, with matching placebo IV/SC (N = 280 and N = 139, respectively) as the comparator. Clinical response (decrease from baseline in the modified Mayo score by ≥ 30% and ≥ 2 points, with either a ≥ 1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1) and clinical remission (stool frequency subscore of 0 or 1 and not increased from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0, or 1 with no friability present on the endoscopy) were evaluated at Week 12 across baseline weight quartiles and standard BMI subgroups (i.e., underweight 18 kg/m2, healthy weight ≥18 to 25 kg/m2, overweight ≥25 to 30 kg/m2, and obese ≥30 kg/m2). Weight quartiles and BMI subgroups were calculated for QUASAR and ASTRO separately. Results QUASAR and ASTRO had similar eligibility criteria, and the baseline demographics and disease characteristics of the randomized study populations were also similar (data not shown). Participants treated with GUS IV or SC induction achieved clinical response and clinical remission at Week 12 in similar proportions, with similar treatment effects compared to placebo, across all baseline weight quartile (Figure 1) and all baseline BMI (Figure 2) subgroups. Conclusion GUS IV and SC induction were similarly effective in participants with moderately to severely active UC compared with placebo regardless of participants’ baseline body weight or BMI. Obesity does not appear to diminish the efficacy of GUS SC induction. References: 1)Sachen K, Hammaker D, Sarabia I, et al. Front Immunol. 2025: doi:10.3389/fimmu.2025.1532852. 2)Rubin DT, Allegretti JR, Panés J, et al. Lancet. 2025; 405(10472): 33-49. 3)Long M, Allegretti JR, Danese S, et al. Lancet Gastroenterol Hepatol. 2025: in press Conflict of interest: Yarur, Andres: Personal Fees: Consultant for Takeda, Pfizer, Roche, Merck, Abbvie, Eli Lilly. Bristol Myers Squibb, Celltrion, Johnson and Johnson. Deepak, Parakkal: Research support under a sponsored research agreement unrelated to the data in the abstract from AbbVie, Johnson and Johnson, Sanofi, Merck, Teva, Direct Biologics, Tr1x, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Prometheus Biosciences, Takeda Pharmaceuticals, Roche Genentech, Eli Lilly, AstraZeneca, Spyre and Agomab, has received consulting fees from Johnson and Johnson, Abbvie, Merck, Sobi, Celltrion, Fresenius Kabi, Asahi Kasei Pharma, Sandoz and CorEvitas, LLC and has served on the board of the Srategic Alliance for Intercultural Advocacy in GI. Hisamatsu, Tadakazu: Grant support from Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Mochida Pharmaceutical Co. Ltd., Boston Scientific Corporation, Kissei Pharmaceutical Co. Ltd., consulting fees from Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, Janssen Pharmaceutical K.K., Pfizer Inc., Nichi-Iko Pharmaceutical Co. Ltd., Eli Lilly, Gilead Sciences, Bristol Myers Squibb, and lecture fee from Mitsubishi Tanabe Pharma Corporation, AbbVie GK, EA pharma Co. Ltd., Kyorin Pharmaceutical Co. Ltd., JIMRO Co., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc. Kissei Pharmaceutical Co. Ltd. Alvarez, Yelina: Employee of Johnson & Johnson and owns company stock/stock options Baker, Thomas: Employee of Johnson & Johnson and owns company stock/stock options Adsul, Shashi: Current employee of Johnson and Johnson Innovative Medicine and owns company stock/stock options. Past Employee of Takeda Pharmaceutical. Piscitelli, Darren: Employee of Johnson & Johnson and owns company stock/stock options Miao, Ye: Employee of Johnson & Johnson and owns company stock/stock options Rubin, David T.: Has received grant support from Takeda and has served as a consultant for 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. 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