Abstract Background Ulcerative colitis (UC) is a chronic, relapsing-remitting inflammatory bowel disease characterized by mucosal inflammation of the colon. Interleukin-23 (IL-23) has emerged as a pivotal cytokine in UC pathogenesis and a promising therapeutic target. Mirikizumab, a selective anti-IL-23p19 monoclonal antibody, has demonstrated efficacy and safety in phase 3 clinical trials. However, real-world evidence—particularly regarding its use in biologic-experienced populations and outside of controlled trial settings—remains limited. Methods We conducted a retrospective, multicenter cohort study across five IBD centers five Italian centers from Latium Net evaluating the effectiveness and safety of mirikizumab in routine clinical practice. Ninety-five consecutive adult patients with moderate-to-severe UC who initiated mirikizumab between November 2024 and May 2025 were included. The primary endpoint was steroid-free clinical remission (SFCR) at 12 weeks. Secondary outcomes included clinical response, biochemical response at 12 weeks. Follow-up data at 24 weeks were collected, when available. Subgroup analyses examined outcomes according to prior exposure to biologics (including ustekinumab) and the use of extended induction regimens. Results At week 12, 43.2% of patients (41/95) achieved SFCR, while 61.1% (58/95) experienced a clinical response. No statistically significant differences were observed between biologic-naïve and biologic-experienced patients. Notably, 17 patients who required extended induction had lower SFCR rates at week 12 compared to standard induction. A trend toward reduced SFCR at week 24 was seen in patients previously exposed to ustekinumab (p = 0.052). No new or unexpected safety concerns were reported during the follow-up. Conclusion In this real-world Italian cohort, mirikizumab demonstrated meaningful clinical effectiveness and a favorable safety profile, including in biologic-experienced patients. The early clinical response was sustained over time, and SFCR rates improved with continued therapy. Comparable outcomes in biologic-experienced patients, together with trends related to prior ustekinumab exposure and extended induction, support the therapeutic utility of mirikizumab across diverse clinical scenarios. Conflict of interest: Mr. Murgiano, Marco: No conflict of interest Balestrieri, Paola: No conflict of interest Calabrese, Emma: No conflict of interest Fiorino, Gionata: No conflict of interest Festa, Stefano: No conflict of interest Pugliese, Daniela: No conflict of interest Di Vincenzo, Federica: No conflict of interest Puca, Pierluigi: No conflict of interest Parello, Simone: No conflict of interest Vespasiano, Valeria: No conflict of interest Colella, Alice: No conflict of interest Marafini, Irene: No conflict of interest Profeta, Francesca: No conflict of interest Foscarini, Elisa: No conflict of interest Papa, Alfredo: No conflict of interest Lopetuso, Loris Riccardo: Personal Fees: none Monteleone, Giovanni: No conflict of interest Cicala, Michele: No conflict of interest Gasbarrini, Antonio: No conflict of interest Laterza, Lucrezia: No conflict of interest Scaldaferri, Franco: No conflict of interest
Murgiano et al. (Thu,) studied this question.