Efficacy and safety of risankizumab in moderate-to-severe Crohn’s disease: a systematic review and meta-analysis

Background: Crohn’s disease (CD) is a chronic inflammatory disorder with limited therapeutic options for treatment-refractory patients. This meta-analysis evaluates the efficacy and safety of risankizumab (IL-23 p19 inhibitor) in moderate-to-severe CD. Objectives: To evaluate the clinical, endoscopic, and safety outcomes of risankizumab in patients with moderate-to-severe CD. Design: Systematic review and meta-analysis of randomized controlled trials (RCTs). Data sources and methods: A systematic search identified seven RCTs evaluating risankizumab at different doses, including a total of 4411 patients. We searched multiple databases, including PubMed, Cochrane CENTRAL, ClinicalTrials.gov, and Web of Science. Outcomes included clinical and endoscopic remission, endoscopic response, mucosal healing, stool frequency and abdominal pain scores. Data were pooled using a random-effects model, with risk ratios (RRs) and 95% confidence intervals (CIs) reported. Separate meta-analyses were conducted for the induction and maintenance phases. Results: Risankizumab was significantly more effective than placebo or active comparator in achieving clinical remission (CDAI) during induction (RR, 1.85; 95% CI, 1.69–2.01; p < 0.00001; I 2 = 0%) and maintenance (RR, 1.40; 95% CI, 1.21–1.62; p < 0.00001; I 2 = 58%). Endoscopic outcomes were robust, with significant rates of endoscopic remission (RR, 2.81; 95% CI, 2.04–3.87; p < 0.00001; I 2 = 50%) and endoscopic response (RR, 4.17; 95% CI, 3.31–5.77; p < 0.00001; I 2 = 0%) post-induction. Risankizumab significantly increased mucosal healing (RR, 3.40; p < 0.00001; I 2 = 61%) and reduced the risk of CD-related hospitalizations by 78% (RR, 0.22; 95% CI, 0.14–0.34; p < 0.00001; I 2 = 0%). While fecal calprotectin levels significantly improved (RR, 1.79; p < 0.00001; I 2 = 0%), no significant benefit was observed for high-sensitivity C-reactive protein maintenance ( p = 0.39; I 2 = 59%). Subgroup analyses indicated consistent treatment effects across doses, with the Peyrin-Biroulet (2024) and FORTIFY trials identified as primary sources of observed heterogeneity in maintenance outcomes. Conclusion: These findings suggest that risankizumab is an effective and safe option for inducing and maintaining remission in moderate-to-severe CD. Further long-term studies should refine dosing, assess long-term outcomes, and support its integration into clinical guidelines. Trial registration: PROSPERO ID: CRD42024611707.