P1169Mirikicu: Real-World Effectiveness of Mirikizumab in Refractory Ulcerative Colitis

Abstract Background Mirikizumab is a novel anti-IL-23p19 monoclonal antibody recently approved for moderate-to-severe ulcerative colitis (UC). Real-world evidence on its effectiveness in highly refractory patients is limited. This study aimed to evaluate the real-world effectiveness of mirikizumab in UC patients with multiple prior treatment failures. Methods Multicenter, prospective, observational cohort study including UC patients initiating mirikizumab across 7 hospitals in Andalusia and Asturias, Spain. We assessed clinical response and remission at 12 weeks and 6 months using partial Mayo score. Clinical remission was defined as partial Mayo score ≤2 with no individual subscore 1. Clinical-biochemical remission required clinical remission plus C-reactive protein (CRP) ≤5 mg/L. Fecal calprotectin and CRP were measured at baseline, 12 weeks, and 6 months. Steroid-free remission was evaluated at both timepoints. Results Twenty-one patients (65.0% male, mean age 51.7 years, mean disease duration 11.2 years) were included. Distribution by extension: extensive colitis 42.9%, left-sided 33.3%, proctitis 23.8%. Extraintestinal manifestations were present in 57.2% (articular 38.1%, dermatologic 14.3%, ophthalmologic 4.8%). Patients were highly treatment-experienced with prior exposure to infliximab (76.2%), ustekinumab (85.7%), vedolizumab (71.4%), and JAK inhibitors (57.1%). At baseline, 55.0% were receiving concomitant corticosteroids. Median partial Mayo score decreased significantly from 6 at baseline to 3 at 12 weeks (p = 0.003) and remained at 3 at 6 months (p = 0.002). Median fecal calprotectin decreased from 1826 μg/g at baseline to 722 μg/g at 12 weeks and 404 μg/g at 6 months (p = 0.326). Clinical remission rates were 26.7% at 12 weeks and 44.4% at 6 months (p = 0.013 vs baseline). Clinical-biochemical remission was achieved in 6.7% at 12 weeks and 11.1% at 6 months. Steroid-free remission rates were 20.0% at 12 weeks and 38.9% at 6 months (p = 0.500). Treatment discontinuation occurred in 1/16 patients by 12 weeks and 2/17 by 6 months, all due to primary failure. No adverse events were reported. Conclusion Mirikizumab demonstrated sustained effectiveness in this real-world cohort of highly treatment-refractory UC patients, with progressive improvement in clinical outcomes between 12 weeks and 6 months. Clinical remission rates doubled from induction to maintenance phase, with nearly 40% achieving steroid-free remission at 6 months despite extensive prior biologic and small molecule exposure. These results support mirikizumab as a valuable therapeutic option in difficult-to-treat UC. Conflict of interest: Dr. Caballero Mateos, Antonio M: has received fees for lectures, consultancy work, or research support from: Lilly, Abbvie, Johnson & Johnson, Takeda, Pfizer, Alfasigma, Ferring, Farmasierra, Kern, Faesfarma Trapero Martinez, Ana María: None Florez Diez, Pablo: None Rodriguez Gonzalez, Francisco Jose: None Olmedo-martín, Raúl: Dr. Raúl Olmedo-Martín has served as a speaker and consultant for Janssen, Abvvie, Kern, Takeda, Lilly, Otsuka, Ferring and Alfasigma Rodríguez Delgado, Cristina: None Martin Rodríguez, María Del Mar: As a speaker or recipient of educational funding from MSD, Takeda, Janssen, Johnson & Johnson, Dr. Falk Pharma, Abbvie, Tillotts Pharma, Chiesi, Otsuka Pharmaceutical, Pfizer, Galápagos, Ferring and Lilly. Mata Perdigón, Francisco Jesús: has received fees for lectures, consultancy work, or research support from: Lilly, Abbvie, Johnson & Johnson, Takeda, Pfizer, Alfasigma, Ferring, Farmasierra, Kern. Sáez Díaz, Antonia: None