Abstract Background Mirikizumab is a monoclonal antibody directed against the p19 subunit of interleukin (IL)-23 approved for the management of patients with moderate-to-severe ulcerative colitis (UC). This study aims to evaluate the effectiveness and safety of mirikizumab in real-life setting. Methods This was a retrospective multicenter cohort study including adult patients with diagnosis of UC treated with mirikizumab. Patients were enrolled in 5 third-level Italian centers from June 2024 to August 2025. All patients with at least 3 months of follow-up after therapy initiation were eligible. The primary outcome was the clinical remission rate (defined as partial Mayo Score (pMS) 2 with a rectal bleeding subscore of 0) at week 12 (w12) and 24 (w24). Secondary outcomes included intestinal ultrasound (IUS) remission (defined as MUC ≤ 6.2), changes in mayo endoscopic score (MES), bowel urgency (BU, measured by the Numeric Rating Scale (NRS) urgency score), fecal calprotectin (FC) levels up to w24 and safety profile of mirikizumab. Results A total of 236 patients were included (60.2% male; median age 47.8 ± 18.1 years). Most (77.5%) had prior exposure to ≥ 1 advanced therapy (including 62 patients treated with ustekinumab), and 14.8% had received ≥4 agents before mirikizumab. Mirikizumab induced a significant reduction in pMS at w12 (p = 1.42 × 10−¹9; r = 0.83; n = 210) and w24 (p = 4.11 × 10−²¹; r = 0.89; n = 179). Steroid-free clinical remission at w12 was achieved by 46.6% of patients. MES improved significantly at w12 (p = 3.89 × 10−³; r = 0.68; n = 38) and w24 (p = 2.39 × 10−¹¹; r = 0.90; n = 85). IUS remission was not significant at w12 (p = 0.17; n = 151) but increased by w24 (p = 1.69 × 10−5; V = 0.35; n = 142). BU improved significantly at w12 (p = 4.05 × 10−¹¹; r = 0.73; n = 174) and w24 (p = 1.08 × 10−10; r = 0.78; n = 132). FC reductions were significant at both w12 (p = 4.31 × 10−¹¹; r = 0.57; n = 182) and w24 (p = 5.34 × 10−8; r = 0.52; n = 147). Extended induction was required in 59.3% of patients at w12, and 3.4% underwent intravenous re-induction at w24. Mirikizumab was discontinued in 11 patients by w12 and 16 by w24, mainly due to treatment failure (one allergic reaction). Adverse events (AEs) were uncommon (6 at w12; 3 at w24), including upper respiratory tract infection, cytomegalovirus ( CMV ) infection, herpes zoster, infusion reaction, rash, pyrexia, and arthralgia. No serious AEs were recorded. No clinically relevant liver enzyme changes were observed. Conclusion In this real-world UC cohort, mirikizumab demonstrated robust and durable effectiveness across clinical, endoscopic, biochemical, and IUS outcomes, with low discontinuation rates, and no serious safety signals through 24 weeks. Conflict of interest: Dr. D’Amico, Ferdinando: Grant: ECCO fellowship grant 2020 ECCO grant 2021 Personal Fees: F D’Amico has served as a speaker for Abbvie, Alfasigma, Ferring, Lilly, Sandoz, Janssen, Fresenius Kabi, Galapagos, Giuliani, MSD, Pfizer, Takeda, Tillotts, and Omega Pharma he also served as an advisory board member for Abbvie, AnaptysBio, Ferring, Fresenius Kabi, Galapagos, Janssen, Lilly, MSD, Takeda, and Nestlè. Fanizzi, Fabrizio: No conflict of interest Dal Buono, Arianna: speaker’s fees from AbbVie, Alphasigma, Ferring, Lilly, Janssen, and Celltrion Nardone, Olga Maria: Advisory board fees from Eli Lilly, Nestlè, Janssen Speaker fees from AbbVie, Janssen, Eli Lilly, Ferring, Alfa Sigma, Recordati, Noòs, and Pfizer Lauriola, Giorgia Michela: No conflict of interest Zilli, Alessandra: Personal Fees: Speaking and consulting fees from Tillotts, Galapagos, Abbvie, Takeda, Janssen, Alfasigma, Sandoz, Lilly, Pfizer Allocca, Mariangela: Personal Fees: consulting fees from Nikkiso Europe, Mundipharma, Janssen, Abbvie, Pfizer, Ferring, Galapagos, Sandoz, Lilly and Alfasigma Peyrin-Biroulet, Laurent: CONSULTING Abbvie, Abivax, Adacyte, Alimentiv, Alfasigma, Amgen, Apini, Banook, BMS, Celltrion, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Iterative Health, Janssen, 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, Janssen, Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots Fiorino, Gionata: Personal Fees: Takeda, Johnson & Johnson, Alfasigma, AbbVie, Celltrion, Pfizer, Sandoz, Abivax, Lilly, STADA Castiglione, Fabiana: Honoraria from: Takeda, AbbVie, Celltrion, Johnsson Johnsson, Cadigroup, Sandoz, Pfizer, Lilly, Lionhealth, Nestlè Massimino, Luca: No conflict of interest Mastronardi, Mauro: none Armuzzi, Alessandro: Consulting fees from AbbVie, Abivax, Alfa Sigma, Astra Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Enthera, Ferring, Galapagos, Gilead, Giuliani, Janssen, Lionhealth, MSD, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sanofi, Sandoz, Takeda, Teva Pharmaceuticals, Tillots Pharma Speaker’s fees from AbbVie, Abivax, AG Pharma, Alfa Sigma, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Teva Pharmaceuticals Research support from Biogen, MSD, Takeda, and Pfizer Non-financial support from Abbvie, Janssen, MSD, Pfizer, Takeda Danese, Silvio: Personal Fees: AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, Vifor Lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, Takeda
D’Amico et al. (Thu,) studied this question.