Abstract Background Preventing Crohn’s disease (CD)-related hospitalizations and surgeries is a recommended goal in disease-modification trials preventing disease progression (SPIRIT Consensus)1. The VIVID-1 study (NCT03926130) demonstrated the efficacy and safety of mirikizumab (MIRI), a humanized antibody selectively targeting the Interleukin-23 p-19 subunit, for the treatment of CD2. Here we assessed the impact of MIRI on CD-related hospitalization and surgery rates in VIVID-1 participants. Methods This post-hoc analysis included patients randomized to MIRI or placebo (PBO) (6:2). MIRI-treat through patients received MIRI 900mg every 4W during induction phase (W0-12) and MIRI 300mg every 4W during maintenance phase (W12-52). PBO/PBO responders received PBO through W12 and were continued on PBO through W52 (Fig 1A). Baseline demographics groups were analyzed by occurrence (with) or absence (without) hospitalizations or surgeries during induction. The proportion of patients with CD-related hospitalization and/or surgery was calculated with a 95% confidence interval. Incidence rates (IRs) were also reported as exposure-adjusted hospitalization and/or surgery events per 100 patient-years. Results At baseline, CD duration, ileal disease location, Crohn’s Disease Activity Index (CDAI) total score, C-Reactive Protein (CRP)-levels, and prior biologic failure proportions were numerically higher in PBO and MIRI groups with CD-related hospitalizations/surgeries than without. (Table 1). Proportions of patients with CD-related hospitalizations and surgeries were reduced in MIRI vs PBO patients (hospitalizations or surgeries: 4.1% vs 7.5% W12 and 3.3% vs 9.8% W52) (Fig 1B and C). Furthermore, from W0 to W12, IR of patients with CD-related hospitalizations and surgeries were lower in the MIRI-treated group (hospitalizations: 16.9%, surgeries: 2.2%, hospitalizations or surgeries: 17.7%) compared to the PBO-treated group (IRs: hospitalizations: 28.7%, surgeries: 8.6%, hospitalizations or surgeries: 33.2%). From W12 to W52, the IR of patients with CD-related hospitalizations or surgeries decreased in the MIRI treat-through group (hospitalizations: 4.2%, surgeries: 1.0%, hospitalizations or surgeries: 4.5%) while increasing in PBO/PBO responders who were clinical responders in the induction period and continued on PBO during the maintenance period (hospitalizations: 14.0%, surgeries: 6.1%, hospitalizations or surgeries: 15.7%). Conclusion CD-related hospitalizations/surgeries were associated with longer CD duration, ileal disease location, and higher disease severity at baseline. MIRI treatment reduced proportions and IR of CD-related hospitalizations and/or surgeries through 1 year of treatment vs PBO, supporting the already known benefit/risk of MIRI. References: 1.Le Berre C, Peyrin-Biroulet L, Sandborn WJ, et al. Selecting End Points for Disease-Modification Trials in Inflammatory Bowel Disease: the SPIRIT Consensus From the IOIBD. Gastroenterology 2021;160(5):1452-1460.e21. DOI: 10.1053/j.gastro.2020.10.065. 2.Ferrante M, D’Haens G, Jairath V, et al. Efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn’s disease: a phase 3, multicentre, randomised, double-blind, placebo-controlled and active-controlled, treat-through study. Lancet 2024;404(10470):2423-2436. DOI: 10.1016/S0140-6736(24)01762-8. Conflict of interest: Sands, Bruce E: Grant: Janssen 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 Janssen Janssen Biotech Janssen Pharmaceutica NV Janssen Research & Development, LLC Janssen Scientific Affairs, LLC Janssen-Cilag PTY, Ltd. Johnson & Johnson Kaleido Kallyope Kyowa Kirin, Inc. Merck & 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: Janssen, Pfizer, Lilly, Takeda, Bristol Myers Squibb Other: Stock/Stock Options from Ventyx Biosciences Magro, Fernando: Fernando Magro served as speaker and received honoraria from Abbvie, Arena, Biogen, Bristol-Myers Squibb, Falk, Ferring, Hospira, Janssen, Laboratórios Vitoria, Pfizer, Lilly, Merck Sharp & Dohme, Sandoz, Takeda, UCB, Vifor. Redondo, Isabel Maria: employee and share holder Eli Lilly Dignass, Axel: Personal Fees: AbbVie, Alfasigma, CED Service GmbH, Celltrion, Dr. Falk Pharma, Falk Foundation, Ferring, Fresenius Kabi, Gilead, High5MD, J & J, Lilly, Materia Prima, MSD, Pfizer, Pharmacosmos, Sandoz, Stada, Streamed-Up, Takeda, Tillotts, Vifor Pharma Grant Abbvie, J & J, Takeda Non-financial support Abbvie, J & J, Takeda Other: Abivax, AbbVie, Alfasigma, Dr Falk Pharma, Fewrring, J & J, Pfizer Chen, Minhu: No conflict of interest Hisamatsu, Tadakazu: T. Hisamatsu performed joint research with Alfresa Pharma Co. Ltd., and EA Pharma Co. Ltd. grant support from Mitsubishi-Tanabe Pharma Corporation, EA Pharma Co. Ltd., AbbVie GK, Jimro Co. Ltd., Zeria Pharmaceutical Co. Ltd., Daiichi-Sankyo, Kyorin Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Mochida Pharmaceutical Co., Ltd, Jimro Co. Ltd consulting fees from EA Pharma Co. Ltd., AbbVie GK, Celgene K.K., Janssen Pharmaceutical K.K., Pfizer Inc., Nichi-Iko Pharmaceutical Co., Ltd. and lecture fees 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., and Pfizer Inc. Gordon, Hannah: No conflict of interest Long, Millie: ML has served as a consultant for AbbVie, Pfizer, Takeda, Lilly, Bristol-Meyers Squibb, Target RWE, and Prometheus and has received research support from Pfizer, Takeda, and Janssen. IS, RM, SM, THG, and NM are employees of Eli Lilly and Company. Marín Jimenez, Ignacio: Dr. Ignacio Marín-Jiménez has served as a speaker, a consultant and advisory member for or has received research funding from Abbvie, Amgen, Chiesi, Dr. Falk Pharma, Faes Farma, Ferring, Fresenius, Galapagos, Gebro Pharma, Janssen, Kern Pharma, Lilly, MSD, Otsuka Pharmaceutical, Pfizer, Sandoz, Shire Pharmaceuticals, Takeda, Tillotts Pharma, and Vifor Pharma. Yu, Guanglei: Employee of Eli Lilly and Company. Liu, Chunyuan: Employee of Tigermed-BDM Inc., Consulting for Eli Lilly. Lopes, Michelle: I currently work at Eli Lilly as a Global Patient Safety Physician De La Torre Ortega, Inmaculada: Lilly employee Lichtenstein, Gary: G.R.L.: consulting, advisory board and/or speaking honoraria (CME)—AbbVie, Allergan, American Gastroenterological Association, American Regent, Annenberg Center for Health Sciences at Eisenhower, Bristol Meyers Squibb, Celgene, Celltrion, Eli Lilly, Endo Pharmaceuticals, Ferring, Focus Medical Communications, Gilead, Ironwood, Johnson and Johnson, Kabi Fresenius, Med Ed Consultants, Pharmacosmos, Pfizer, Professional Educational Resources, Prometheus, Sandoz, Vindico research—Bristol Meyers Squibb, Johnson and Johnson support of University of Pennsylvania IBD fellowship—Janssen Orthobiotech, Pfizer, AbbVie editorship—Gastroenterology and Hepatology (Gastro-Hep Communications), Professional Communications, SLACK, Walters Kluwer, Springer Science and Business Media.
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