Gizem Dağcı1 , Adem Sarıca2 , Besim Fazıl Ağargün1 , Aslı Çiftçibaşı Örmeci1 , Mehmet Akif Yağlı1 , Bilger Çavuş1 , Kadir Demir1 , Selman Fatih Beşışık1 , Sabahattin Kaymakoglu1 , Filiz Akyüz1 2Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
Abstract
Objective: Mirikizumab, a p19-directed anti-interleukin-23 monoclonal antibody, has been evaluated as induction and maintenance therapy for moderately to severely active ulcerative colitis (UC). We conducted a systematic review and meta-analysis of randomized, placebo-controlled trials to quantify its efficacy and safety.
Methods: PubMed, Web of Science, and Scopus were searched for randomized controlled trials of mirikizumab versus placebo in UC. Two independent RCT programs met the eligibility criteria: the Phase 2 trial (Sandborn et al.; comprising a 12-week double-blind induction period and a double-blind 52-week maintenance re-randomization of induction responders, with the latter reported through its ClinicalTrials.gov registry record) and the Phase 3 LUCENT program (D’Haens et al.; LUCENT-1 induction and LUCENT-2 maintenance). Outcome data (clinical remission, clinical response, endoscopic remission/response, symptomatic remission, histologic remission, and serious adverse events [SAEs]) were extracted from the primary ClinicalTrials.gov results records (NCT02589665, NCT03518086, and NCT03524092) and pooled using random-effects (DerSimonian–Laird) meta-analysis of risk ratios (RRs).
Results: During induction (12 weeks), mirikizumab increased clinical remission (RR 2.45, 95% CI 1.03–5.83; I²=56%), clinical response (RR 1.98, 95% CI 1.05–3.73), and endoscopic remission (RR 1.72, 95% CI 1.36–2.18; I²=0%) compared with placebo. During maintenance (weeks 40–52), mirikizumab increased clinical remission (RR 1.98, 95% CI 1.51–2.61) and endoscopic remission (RR 2.03, 95% CI 1.59–2.59; I²=0%). Serious adverse events were numerically less frequent with mirikizumab than with placebo during both induction (RR 0.56, 95% CI 0.32–0.99) and maintenance (RR 0.36, 95% CI 0.19–0.70).
Conclusions: Mirikizumab is significantly more effective than placebo in inducing and maintaining clinical, endoscopic, symptomatic, and histologic remission in moderately to severely active UC, with a favorable serious adverse event profile relative to placebo. The evidence base remains limited to two independent RCT programs; the wider confidence intervals and moderate-to-high heterogeneity observed for some induction outcomes reflect the small Phase 2 sample and should be interpreted cautiously.
