P0598 MIRACLE-UC: Mirikizumab Investigation of Real-world Assessment of Clinical and Long-term Effectiveness and Adverse Events in Patients with Ulcerative Colitis - A Multicenter Prospective Study from the Italian Group for the Study of Inflammatory Bowel Diseases (IG-IBD).

Abstract Background Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease. Mirikizumab has demonstrated efficacy in clinical trials, but real-world, long-term multicenter data remain limited. MIRACLE-UC, a prospective study promoted by the Italian Group for the Study of Inflammatory Bowel Diseases (IG-IBD), evaluated real-world effectiveness and safety of mirikizumab in clinical practice. Methods This is a preliminary analysis from a prospective, multicenter observational study, enrolling adult patients with active UC treated with mirikizumab across several Italian referral centers. Consecutive patients were included with systematic collection of clinical and endoscopic data. Effectiveness endpoints were assessed at baseline, 3, and 6 months; 12-month follow-up data collection is still ongoing. The outcomes analyzed include clinical response (a reduction of at least 2 points in the partial Mayo score and improvement in rectal bleeding), clinical remission (partial Mayo ≤2, no subscore >1, no rectal bleeding), endoscopic improvement (MES ≤1) and remission (MES=0), steroid-free status, and changes in biomarkers (CRP and fecal calprotectin). Dropouts were counted as non-responders from discontinuation onward, and missing data excluded. Analyses were performed using R software. Results A total of 407 patients were included. Previous biologic use was recorded in 83.8% (Table 1). Clinical response rates were 55.6% at 3 months and 69.4% at 6 months (p < 0.001). Clinical remission was achieved in 41.2% and 55.5% respectively (p < 0.001). Steroid-free clinical response occurred in 52.1% and 63.9%, and steroid-free clinical remission in 32.4% and 53.1% of patients at 3 and 6 months, respectively (all p < 0.001). Endoscopic improvement was achieved in 49.3% of patients at 6 months (p < 0.001); endoscopic remission was reached by 42.1% at 6 months (p < 0.001). Mean levels of fecal calprotectin decreased over time from 1731 (±3051) ug/g at baseline to 718 (±1649) ug/g at 6 months (p < 0.001), while CRP levels decreased from 69.5 (±162.0) at baseline to 42.7 (±91.1) mg/L at 6 months p < 0.001). Mirikizumab was discontinued in 4.9% by month 6 due to inefficacy or adverse events (n = 3/407). Conclusion In this large multicenter real-world cohort, mirikizumab was associated with substantial rates of clinical, steroid-free, and endoscopic remission in patients with refractory UC. Improvements in fecal calprotectin levels supported clinical and endoscopic outcomes. These results confirm the effectiveness and safety of mirikizumab in clinical practice and support its use as part of a treat-to-target strategy for UC. Conflict of interest: Dr. Barberio, Brigida: Brigida Barberio: has served as speaker for Abbvie, Agave, Alfasigma, AGpharma, Johnson & Johnson, Eli Lilly, MSD, Pfizer, Procise, Sofar, Takeda, Unifarco. BB has served as consultant for Abbvie, Eli Lilly, ohnson & Johnson. Todeschini, Alessia: The author has served as a consultant and/or received lecture fees from Abbvie, Alfasigma, Celltrion, Johnson & Johnson, Ely Lilly, Ferring, Lion Health,Takeda. Laterza, Lucrezia: Employment full time / part time None Research Grant (P.I., collaborator or consultant pending and received grants) None Other research support None Speakers Bureau / Honoraria Company name/Lecturer Abivax, Biocure Ownership interest (stock, stock-options, patent or intellectual property None Consultant / advisory board Actial Farmaceutica, Abbvie, Lilly, J & J Viola, Anna: No conflict of interest Bezzio, Cristina: Personal Fees: I received consulting/advisory board/lecture fees from Alfa Sigma, AbbVie, Celltrion, Eli Lilly, Ferring, Gilead, Johnson & Johnson MSD, Pfizer and Takeda Mendolaro, Marco: None Caprioli, Flavio: Flavio Caprioli served as consultant to: Abbvie, Amgen, MSD, Takeda, Janssen, Roche, Celgene, Bristol-Meyers Squibb, Galapagos, Gllead, Pfizer, Mundipharma, Biogen, Ferring, Eli-Lilly, Nestlè, Lionhealth, AlfaSigma, Dr Falk, Celltrion, Abivax. He received lecture fees from Abbvie, Ferring, Takeda, Allergy Therapeutics, Janssen, Pfizer, Biogen, Sandoz, Tillotts Pharma, Vifor Pharma, AlfaSigma, Celltrion, Eli-Lilly. and unrestricted research grants from Giuliani, Sofar, MSD, Takeda, Abbvie, Celltrion, Pfizer, Actial. Saibeni, Simone: Consultancy, lecture fees, and advisory board for AbbVie, Alfasigma, Arena, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, Johnson & Johnson, MSD, Pfizer, and Takeda. Gerardi, Viviana: No conflict of interest Marafini, Irene: Irene Marafini served as advisory board member for Abbvie, Eli Lilly, Galapagos and received speaker honoraria from Abbvie and Eli Lilly Ribaldone, Davide Giuseppe: Davide Giuseppe Ribaldone declares the following paid consultancies, lecture fees for the past two years: Johnson & Johnson, Takeda, Celltrion, Alfasigma, Pfizer, Eli Lilly, Abbvie, Sandoz Monico, Maria Camilla: No conflict of interest Viganò, Chiara: Consultancy and lecture fees from: AbbVie, Galapagos, Janssen-Cilag, Johnson & Johnson, Pfizer, Takeda, Celltrion, Alfasigma, Eli Lilly and research grant from Celltrion and Pfizer. Cappello, Maria: None Dragoni, Gabriele: Grant: ECCO Grant 2020 ECCO/AOCC Travel Grant 2021 ECCO IIS Registry Grant 2023 ECCO/IBUS Research Grant 2023 Personal Fees: - Speaker’s fees from: 2020: Novartis 2022: Janssen 2023: Alfasigma, Janssen, Pfizer, and Takeda 2024: Ferring, Johnson & Johnson, Eli Lilly, Pfizer, and Takeda 2025: Abbvie, Alfasigma, Ferring, Eli Lilly, LionHealth, Pfizer, Takeda - Advisory board fees from: 2023: Celltrion Healthcare and Pfizer 2024: AbbVie 2025: AbbVie, Johnson & Johnson Gravina, Antonietta Gerarda: Gravina AG has conducted training activities [e.g. educational continuing medical activities (ECM), preceptorship] for Pfizer, Galapagos Biopharma, and AbbVie. Miranda, Agnese: No conflict of interest Mocci, Giammarco: NO CONFLICTS OF INTEREST Felice, Carla: Advisory board for AbbVie, MSD, J & J. Principi, Maria Beatrice: No conflict of interest Mazzuoli, Silvia: No conflict of interest Ferracane, Concetta: nothing to declare Cocomazzi, Francesco: No conflict of interest Bertani, Lorenzo: No conflict of interest Balestrieri, Paola: Advisory board for Alfasigma- Janssen- Abbvie- Takeda- Eli Lilly Bodini, Giorgia: No conflict of interest Onali, Sara: Consultant/lecture fees to: Abbvie, Alfasigma, MSD, Takeda, J & J, Galapagos, Pfizer, Eli Lilly Di Sario, Antonio: No conflict of interest Pastorelli, Luca: Luca Pastorelli served as consultant for Giuliani, received lecture fees and/or advisory board fees from Abbvie, Takeda, Ferring, Pfizer, Sandoz, Janssen, Johnson & Johnson, Galapagos, Arena, Eli-Lilly Grossi, Laurino: none Piagnani, Alessandra: No conflict of interest Desideri, Federico: No conflict of interest Palmisano, Chiara Maria: None Urbano, Maria Teresa: Consultant for Abbvie Scarozza, Patrizio: No Conflict of Interest to declare Festa, Stefano: Personal Fees: Consultant and/or Advisory board member for: Takeda, Johnson & Johnson, Pfizer, Galapagos, Abbvie, Ferring, Eli Lilly Fanigliulo, Libera: No conflict of interest Spagnuolo, Rocco: no Zingone, Fabiana: No conflict of interest Savarino, Edoardo Vincenzo: Personal Fees: Takeda, Abbvie, MSD, Janssen, Sofar