Editorial: Real-World Effectiveness of Mirikizumab in Ulcerative Colitis—A Valuable but Preliminary Glimpse

The therapeutic landscape of ulcerative colitis (UC) is rapidly evolving, driven by biologic and small-molecule agents specifically targeting the inflammatory pathways. Among these, mirikizumab, an anti-IL-23p19 monoclonal antibody, recently gained approval based on pivotal randomised controlled trials (RCTs) demonstrating efficacy in both induction and maintenance phases of therapy [1]. While RCTs are the benchmark for establishing treatment safety and efficacy, real-world evidence (RWE) provides critical complementary insights into treatment effectiveness, safety, and patient heterogeneity beyond the rigid confines of clinical trials.

In a retrospective multicentre study, Takagi et al. have presented the largest dataset to date, evaluating the real-world effectiveness of mirikizumab in patients with UC across three referral centres [2]. Although this is not the first study to provide RWE on mirikizumab [3, 4], its contributions are particularly noteworthy due to its larger sample size. However, the number of patients included in this investigation remains very modest. The investigators evaluated early treatment response at 12 weeks using partial Mayo scores and biochemical markers, alongside safety outcomes. The inclusion of patients previously treated with ustekinumab—who were excluded from the pivotal LUCENT trials [1]—has enhanced the relevance of the results. Notably, this study represents a pioneering comparison of clinical responses between ustekinumab-naïve and experienced patients, revealing no significant difference in outcomes, thus contributing to a nuanced understanding of biologic sequencing in UC management [5].

The authors should be recognised for addressing a significant unmet need in post-marketing surveillance, particularly by assessing outcomes in a biologic-experienced population. Their findings complement those of smaller studies on mirikizumab's efficacy in real-world settings [3, 4]. However, the study has limitations; the small sample size, despite being the largest published to date, may constrain the ability to detect differences in subgroup analyses and increase the risk of type II error. Furthermore, the reliance on C-reactive protein as an inflammatory marker, without considering faecal calprotectin—a more specific UC biomarker—reduces the overall robustness of the efficacy assessment [6].

Despite these limitations, this early real-world experience is valuable but highlights the need for larger, prospective observational studies that consider biomarker-guided responses, extended follow-ups, and patient-reported outcomes. Such research is essential to refine treatment strategies and address cost-effectiveness, guiding clinicians in the evidence-based sequencing of biologic therapies [7-10].

In conclusion, this study represents a meaningful step forward in contextualising mirikizumab's role in UC management. While the findings necessitate cautious interpretation due to their preliminary nature, the inclusion of ustekinumab-experienced patients provides valuable insight and raises questions for future research. As treatment for UC becomes increasingly individualised, robust real-world data will play a crucial role in optimising therapeutic strategies across diverse clinical circumstances.

M.A.A. reviewed the paper by Takagi, M.A.A. and C.F. both drafted the editorial.

This article is linked to Takagi et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70140 and https://doi.org/10.1111/apt.70180.