S1887 Efficacy and Safety of Mirikizumab in the Treatment of Moderate to Severe Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis

Introduction: Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD) remain challenging to treat despite advances. Mirikizumab, a monoclonal antibody that selectively inhibits the p19 subunit of Interleukin-23, shows promise. This study consolidated available evidence to assess its efficacy and safety across both IBD populations. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing mirikizumab to placebo in moderate-to-severe IBD. We assessed clinical response, clinical remission, endoscopic remission, adverse events (AEs), and treatment discontinuation. We applied a random-effects model to calculate risk ratios (RR) with 95% confidence intervals (CI) and reported numbers needed to treat (NNT) and harm (NNH). Results: We included 4 RCTs (2,380 patients). Mirikizumab increased the likelihood of clinical response by 69% (61.0% vs 36.6%; RR 1.69; 95% CI [1.35, 2.10]; P < 0.00001; NNT = 4), clinical remission by 74% (37.1% vs 20.0%; RR 1.74; 95% CI [1.50, 2.02]; P < 0.00001; NNT = 7), and endoscopic remission by 92% (28.7% vs 15.4%; RR 1.92; 95% CI [1.63, 2.27]; P < 0.00001; NNT = 8). Mirikizumab-induced clinical and endoscopic remission extended to both the induction and maintenance phases of treatment and across UC and CD populations, with biologic-failed patients also experiencing significantly higher clinical response rates compared to placebo (62.0% vs 35.8%; RR 1.75; 95% CI [1.56, 1.96]; P < 0.00001). Mirikizumab was safe, with reduced rates of serious AEs (5.2% vs 9.1%; RR 0.53; 95% CI [0.41, 0.70]; P < 0.00001; NNH = 24), treatment discontinuation (2.5% vs 7.5%; RR 0.33; 95% CI [0.20, 0.56]; P < 0.0001; NNH = 20), and IBD worsening (3.3% vs 13%; RR 0.26; 95% CI [0.19, 0.36]; P < 0.00001; NNT = 11). Conclusion: Mirikizumab is effective in achieving clinical and endoscopic remission in IBD, including in biologic-experienced patients. Its favorable safety profile, with reduced serious AEs and discontinuations, aligns with its selective mechanism. While higher induction doses appear necessary, maintenance efficacy is robust, with flexible administration routes. Our findings support Mirikizumab as a valuable first or second-line treatment for moderate-to-severe IBD. Future research should focus on long-term outcomes, real-world data, diverse populations, and dose optimization, while prioritizing consistent outcome reporting, to further highlight Mirikizumab's clinical utility.