Prospective real-world experience with risankizumab in difficult-to-treat Crohn's disease: results from the Dutch Initiative on Crohn and Colitis Registry

Background: Risankizumab, a monoclonal antibody targeting interleukin-23, is approved for the treatment of Crohn's disease (CD). Real-world evidence on its effectiveness remains limited. We assessed 1-year effectiveness and safety of risankizumab in a prospective cohort of patients with CD, emphasizing difficult-to-treat disease. Methods: Data were retrieved from the Dutch Initiative on Crohn and Colitis Registry. At baseline and at weeks 12, 24, and 52, clinical remission (Harvey-Bradshaw Index <= 4), biochemical remission (fecal calprotectin <= 250 & micro;g/g and C-reactive protein levels <= 5 mg/L), systemic corticosteroids use, and safety outcomes were determined. The primary outcome was corticosteroid-free clinical remission (CSFCR) at week 24. Difficult-to-treat disease was defined as the failure of advanced therapies with at least 2 different mechanisms of action. Results: In total, 151 patients initiated risankizumab before August 1, 2025; 136 (90.1%) of 151 patients had difficult-to-treat disease. At baseline, 90 (59.6%) patients had Harvey-Bradshaw Index >4. Of those, at week 24, 31 (50%) of 62 patients were in CSFCR; this rate was 53.3% when including all patients. Analysis including only patients with difficult-to-treat disease revealed that 51.8% of these patients were in CSFCR at week 24. Twenty-two (14.6%) patients discontinued treatment after a median of 183.5 days (Q1-Q3: 90.0-295.2 days), most following nonresponse. Regarding adverse events, 35.3 possibly and 16.6 probably risankizumab-related events per 100 person-years were reported. Conclusion: In this prospective multicenter study, risankizumab demonstrated favorable effectiveness and safety profile in patients with CD, including those with difficult-to-treat disease, bowel surgery, and stoma. These findings support the use of risankizumab in patients with difficult-to-treat disease.