Real-world effectiveness and safety of risankizumab in multirefractory Crohn’s disease: A multicenter AIRIS-Crohn registry analysis

Abstract

BACKGROUND

Many patients with Crohn’s disease (CD) remain uncontrolled despite multiple biologic therapies. Risankizumab, a selective interleukin-23p19 inhibitor, has shown efficacy in clinical trials, but real-world data in multirefractory CD are still scarce.

AIM

To evaluate the 12-month effectiveness and safety of risankizumab in a real-world cohort of patients with moderate-to-severe CD treated across multiple centers in Andalusia, Spain.

METHODS

Multicenter ambispective real-world study including adults with CD treated with risankizumab across 12 Andalusian hospitals (AIRIS-Crohn registry). Effectiveness outcomes were clinical remission (Harvey-Bradshaw index < 5), steroid-free remission (SFR), biochemical remission, and endoscopic response/remission at week 12, 6 months and 12 months. Modified non-responder imputation was applied to discontinuations.

RESULTS

Among 205 patients with highly refractory CD (median 2 prior failed advanced therapies; 81% prior ustekinumab exposure; 61% extraintestinal manifestations; 39% prior intestinal surgery), risankizumab rapidly improved clinical activity and maintained stable remission rates over 12 months. Clinical remission improved from 20% at baseline to 49% at week 12, 46% at 6 months and 49% at 12 months (P < 0.05 for all). SFR was maintained in 41%-44% throughout follow-up. Perianal disease response was observed in 65% at week 12 and 80% at 6 months. Endoscopic remission was achieved in 32% at 6 months. Treatment persistence exceeded 90% at one year. In multivariable analysis, prior vedolizumab exposure was related to lower odds of SFR (odds ratio = 0.41; 95% confidence interval: 0.17-0.99). Risankizumab demonstrated a reassuring safety profile: Only 3.4% of patients discontinued due to adverse events, and no serious infections, opportunistic infections, malignancies, or deaths occurred during follow-up.

CONCLUSION

In one of the largest real-world cohorts of multirefractory CD, risankizumab delivered rapid and sustained clinical benefit, meaningful SFR, robust treatment persistence, and a reassuring safety profile. These findings strengthen the role of interleukin-23 blockade as a key therapeutic strategy for patients with limited treatment options in everyday practice.

Keywords: Crohn’s disease; Inflammatory bowel disease; Risankizumab; Real-world evidence; Interleukin-12/23

Core Tip: Risankizumab, a selective interleukin-23p19 inhibitor, emerges as a promising therapeutic option for patients with multirefractory Crohn’s disease. This multicenter real-world study of 205 patients demonstrates that risankizumab rapidly achieves clinical remission (49% at week 12) and maintains steroid-free remission in over 40% of patients throughout one-year follow-up. The excellent safety profile and high treatment persistence (> 90%) establish interleukin-23 blockade as a key strategy for patients with limited biologic alternatives in routine clinical practice.