Efficacy and Safety of Risankizumab in Crohn's Disease: A Systematic Review and Meta-Analysis of Randomized Trials...

Crohn's disease (CD) management remains challenging, particularly in patients refractory to multiple biologics. Risankizumab (RZB), a selective IL-23 p19 inhibitor, has recently been approved for CD. We performed a systematic review and meta-analysis to assess the efficacy and safety of RZB in moderate-to-severe CD using both randomized controlled trials (RCTs) and real-world evidence (RWE).

We searched PubMed, Scopus, Web of Science, and Embase from inception to April 2025. We included RCTs comparing RZB with placebo and observational studies evaluating RZB in CD. Primary endpoints were clinical remission at induction and maintenance. Secondary endpoints included endoscopic remission and safety outcomes. This study was registered with PROSPERO (CRD420251030978).

Five RCTs and nine observational studies (n = 3275) were included. In RCTs, RZB significantly increased clinical remission rates at induction (RR: 1.90, 95% CI [1.63; 2.20]) and maintenance (RR: 1.34, 95% CI [1.15; 1.55]) compared with placebo. Endoscopic remission was also significantly higher with RZB compared to placebo at induction (RR: 3.25, 95% CI [2.43; 4.35]) and maintenance (RR: 2.04, 95% CI [1.22; 3.42]). Pooled RWE demonstrated clinical remission rates of 57% at 12 weeks and 44% at 1 year. Subgroup analyses confirmed efficacy in patients with prior ustekinumab failure. No increased risk of serious adverse events was observed.

Risankizumab demonstrates robust efficacy in inducing and maintaining clinical and endoscopic remission in moderate-to-severe CD. Real-world data confirm its sustained effectiveness and favorable safety profile in refractory populations (defined as patients with prior failure of one or more biologics or advanced therapies), supporting its positioning in the therapeutic landscape.