Mirikizumab Is Equally Effective in Ustekinumab-Exposed and Ustekinumab-Naïve Patients With Uc: A Multicentre Real-World Cohort

Background Mirikizumab, a selective IL-23p19 monoclonal antibody, has demonstrated efficacy in moderate-to-severe ulcerative colitis (UC) although real-world data are limited. In addition, registrational trials excluded patients previously treated with ustekinumab, which targets the IL-12/23 p40 subunit. We aimed to evaluate the real-world effectiveness and safety of mirikizumab in a multicentre UK cohort of patients with UC, including those with prior ustekinumab exposure. Methods A retrospective observational study was conducted across three tertiary UK centres. Adults with confirmed UC who received mirikizumab and had ≥12 weeks of follow-up were included. Data on demographics, disease activity (SCCAI, UCEIS), biomarkers (CRP, faecal calprotectin), and treatment persistence were analysed at 3 and 6 months. Outcomes were compared between ustekinumab-exposed and -naïve patients. Results Among 100 patients (36 ustekinumab-exposed), treatment persistence at 3 months was 72% with no significant difference between groups. SCCAI scores decreased from 5.8 to 3.3 at 3 months (p < 0.00001), and faecal calprotectin decreased from 1094 µg/g to 586 µg/g (p = 0.006). UCEIS scores (n = 36) improved significantly post-induction (mean 4.4 to 2.7, p < 0.000001). Multivariable logistic regression did not reveal any factors associated with treatment persistence, including prior ustekinumab exposure. Adverse events were infrequent and mild. Conclusion Mirikizumab is effective and well tolerated in a real-world UC population, including patients with prior ustekinumab exposure. These findings support the use of IL-23p19 inhibition regardless of previous IL-12/23 blockade.