MIRIKIZUMAB FOR MODERATE-TO-SEVERE INFLAMMATORY BOWEL DISEASE: AN UPDATED META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Abstract Background and Aims Previous meta-analysis of mirikizumab for inflammatory bowel disease had methodological limitations. We aim to update evidence by including a recent randomized controlled trial (RCT) and analyzing outcomes not yet explored in reviews, including subgroup analysis of biologic previous failure. METHODS A systematic search across PubMed, Embase, and Cochrane Library was conducted to identify RCTs comparing mirikizumab versus placebo in adult patients with Crohn’s disease (CD) or ulcerative colitis (UC). Binary endpoints were analyzed using risk ratios (RRs), each with corresponding 95% confidence intervals (CIs). We performed subgroup analysis comparing CD vs UC and biologic-naive vs biologic-failed patients. All analyses were performed using R software (version 4.4.3). RESULTS The meta-analysis comprised five RCTs and five corresponding post-hoc analyses with non-overlapping populations for each outcome. Our study included 2,380 patients, with 1,760 assigned to mirikizumab and 620 to placebo. Patients were followed for 12 weeks during induction and for 40 weeks during maintenance period. Compared to placebo, patients on mirikizumab showed higher rates of achieving (1) clinical remission during induction (RR 1.83; 95% CI 1.14 to 2.95) and maintenance (RR 2.37; 95% CI 1.27 to 4.43); (2) clinical response during induction (RR 1.58; 95% CI 1.14 to 2.19); (3) endoscopic remission during induction (RR 2.13; 95% CI 0.99 to 4.58) and maintenance (RR 2.03; 95% CI 1.59 to 2.69); (4) endoscopic response during induction (RR 2.83; 95% CI 1.86 to 4.3) and maintenance (RR 5.1; 95% CI 3.34 to 7.78); (5) histologic remission during induction (RR 1.92; 95% CI, 1.1 to 3.35) and maintenance (RR 1.72; 95% CI 1.12 to 2.63); (6) histologic response during induction (RR 1.93; 95% CI 1.42 to 2.63) and maintenance (RR 1.5; 95% CI 1.01 to 2.22). Across all endpoints, no significant difference was found between CD and UC. For clinical response, a significant subgroup difference was observed in biologic subgroup analysis (p < 0.009), with higher effect estimates in biologic-failed (RR 1.75; 95% CI 1.35 to 2.28) compared with biologic-naive patients (RR 1.33; 95% CI 1.08 to 1.64). Analyses of remaining outcomes showed no significant difference in biologic subgroup. Mirikizumab showed a safe profile during both periods. CONCLUSION Our findings suggest that mirikizumab improves clinical, endoscopic, and histologic outcomes during induction and maintenance phase in both CD and UC with a safe profile. Registered in PROSPERO ID: (CRD 420251141742)