P1110Efficacy of intravenous and subcutaneous guselkumab induction by weight and body mass index in patients with Crohn’s disease: Results from the phase 3 GALAXI and GRAVITI 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 Similar efficacy and safety of intravenous (IV) and subcutaneous (SC) induction with GUS in participants with moderately to severely active Crohn’s disease (CD) has been established in the phase 3 GALAXI and GRAVITI 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 CD differentially affect the efficacy of GUS SC induction compared to IV induction. Methods Participants had moderately to severely active CD (CDAI 220-450 and SES-CD≥6; or ≥ 4 for ileal-only disease) and a history of inadequate response/intolerance to oral corticosteroids, AZA/6-MP/MTX, or biologics. GUS phase 3 induction regimens were 200 mg IV in GALAXI 2 150), clinical remission (CDAI150), and endoscopic response (≥50% improvement from baseline SES-CD) 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 were calculated for pooled GALAXI 2 3Q subgroup for endoscopic response, which had similar placebo and GUS responses (Figure 1). Across all baseline BMI subgroups, participants treated with GUS IV or SC induction achieved clinical response, clinical remission, and endoscopic response at Week 12 in greater proportions than those who received placebo (Figure 2). Conclusion Both IV and SC induction with GUS were similarly effective in participants with moderately to severely active CD across baseline weight quartile and BMI subgroups versus placebo, with generally similar treatment effects observed between corresponding GUS IV and SC subgroups. References: 1) Sachen K, Hammaker D, Sarabia I, et al.Front Immunol. 2025: doi:10.3389/fimmu.2025.1532852. 2) Panaccione R, Feagan BG, Afzali A, et al.Lancet. 2025; 406(10501): 358-75. 3) Hart A, Panaccione R, Steinwurz F, et al.Gastroenterology. 2025; 169(2):308-25. Conflict of interest: 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. Yarur, Andres: Personal Fees: Consultant for Takeda, Pfizer, Roche, Merck, Abbvie, Eli Lilly. Bristol Myers Squibb, Celltrion, Johnson and Johnson. 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. Van Rampelbergh, Rian: Employee of Johnson & Johnson and owns company stock/stock options Van Duijnhoven, Wilbert: Employee of Johnson & Johnson and owns company stock/stock options Adsul, Shashi: Current employee of Johnson & Johnson and owns company stock/stock options. Past Employee of Takeda Pharmaceutical. Piscitelli, Darren: Employee of Johnson & Johnson and owns company stock/stock options Rubin, David T.: 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. Board of Directors: Cornerstones Health (non-profit), iUSCAN (non-profit) Danese, Silvio: Consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity, Takeda, TiGenix, UCB and Vifor and reports lecture fees from AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer and Takeda