Abstract Background Mirikizumab (MIRI), a p19-directed interleukin-23 monoclonal antibody, has demonstrated efficacy and safety through Week (W)212 in moderately-to-severely active ulcerative colitis (UC; LUCENT-1: W0-W12, NCT03518086; LUCENT-2: W12-W52, NCT03524092; LUCENT-3: W52-W212, NCT03519945).1 Preventing UC-related hospitalisations and surgeries is a SPIRIT consensus goal to achieve in disease-modification trials.2 Lower rates of UC-related hospitalisations and surgeries were observed in patients treated with MIRI compared to those treated with placebo (PBO) during LUCENT-1, and that impact continued through LUCENT-2 with no UC-related hospitalisations or surgeries reported in MIRI-treated patients.3 We assessed rates of UC-related hospitalizations and surgeries through W212. Methods In LUCENT-1 (induction), patients were randomized to intravenous MIRI 300mg (N = 868) or PBO (N = 294) every 4 weeks (Q4W) for 12W. Patients randomized to MIRI induction and achieving clinical response at W12 were re-randomized 2:1 in LUCENT-2 (maintenance) to subcutaneous (SC) MIRI 200mg Q4W (N = 365) or PBO (N = 179) for maintenance; 316 of the MIRI-treated patients entered the open-label extension LUCENT-3 and continued receiving SC MIRI 200 mg Q4W for 160W (W212 of continuous treatment). Hospitalisations linked to an adverse event with a stay of ≥ 24 hours were recorded. Only UC-related hospitalisations were used for analysis. UC-related surgery was defined as total colectomy, partial colectomy, and proctocolectomy. Proportions and exposure-adjusted incidence rates (IRs) of UC-related hospitalisation and UC-related surgery were analysed from the 3-year LUCENT-3 study among MIRI-treated patients. Results During LUCENT-3, total exposure among the 316 patients was 835 patient-years. Proportions and IRs for each year of the 3-year LUCENT-3 study are shown in Table 1. There was one UC-related hospitalisation due to exacerbation of UC and no UC-related surgeries observed in MIRI-treated patients (IRs 0.1 and 0 per 100 patient-years, respectively). The reduction in UC-related hospitalisations and surgeries among MIRI-treated patients was maintained through LUCENT-2 and continued in LUCENT-3 (Figure 1). Conclusion MIRI reduced UC-related hospitalisations and surgeries which were maintained through 4 years of treatment, demonstrating MIRI’s disease modifying potential and sustained long-term maintenance of efficacy, a key element of comprehensive disease control. References: 1. Sands B, et al. United European Gastroenterology Journal 2025;13(S8):S669-S670. 2. Le Berre C, Peyrin-Biroulet L. Gastroenterology 2021;160(5):1452-1460.e21. 3. Regueiro MD, et al. Gastroenterology 2025;169(1, Supplement):S-869-S-870. Conflict of interest: 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. Ananthakrishnan, Ashwin: AA reports research support from Takeda. Kobayashi, Taku: Grant: AbbVie, Alfresa Pharma, Bristol Myers Squibb, Celtrion, EA Pharma, Gilead Sciences, Kyorin Pharmaceutical, Miyarisan, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Pfizer, Sekisui Medical, Takeda, Zeria Pharmaceutical Personal Fees: AbbVie, Alfresa Pharma, Alimentiv, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Gilead Sciences, Janssen, JIMRO, Kissei Pharmaceutical, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, MSD, Nippon Kayaku, Pfizer, Sekisui Medical, Takeda Pharmaceutical, Zeria Pharmaceutical Kucharzik, Torsten: Personal Fees: MSD, Abbvie, Amgen, Falk Foundation, Biogen, Boehringer, Arena, Celgene, Celltrion, Ferring, Janssen, J&J, Lilly, CED Service GmbH, Olympus, MSD, Mundipharma, Takeda, Amgen, Pfizer, Roche, Galapagos, Gilead, Bristol Myers Squibb, Vifor Ferrante, Marc: Research grants from AbbVie, EG Pharma, Celltrion, Janssen, Pfizer, Takeda and Viatris Consultancy fees from AbbVie, AgomAb Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, MRM Health, Merck Sharp and Dohme, Pfizer, Takeda and ThermoFisher Speakers’ fees from AbbVie, Biogen, Boehringer Ingelheim, Dr Falk Pharma, Ferring, Janssen-Cilag, Merck Sharp and Dohme, Pfizer, Takeda, Truvion Healthcare and Viatris Navabi, Seyedehsan: SN has served on advisory board and speaker for Eli Lilly and Company, Pfizer, and advisory board for Madrigal and speaker for Janssen Malter, Lisa: LM reports educational grants from Abbvie, Janssen, and Pfizer advisory boards: Bristol Myers Squibb and Eli Lilly consultant for Abbvie and Pfizer. Caldera, Freddy: Freddy Caldera has received research support from Takeda Pharmaceuticals, Janssen, and Novavax and has been a consultant for Takeda, Arena Pharmaceuticals, GSK, Eli Lilly and Company, and Celgene Pellanda, Paola: Employee and minor shareholder for Eli Lilly and Company Redondo, Isabel Maria: employee and share holder Eli Lilly Arora, Ravneet: Employee and minor shareholder for Eli Lilly and Company Duan, Yajie: Employee and shareholder of Eli Lilly and Company Zhu, Baojin: Employee and minor shareholder for Eli Lilly and Company Regueiro, Miguel: Advisory Boards and Consultant (both) for AbbVie, Janssen, UCB, Takeda, Pfizer, BMS, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, Boehringer Ingelheim Pharmaceuticals Inc.
Magro et al. (Thu,) studied this question.