Efficacy and Safety of Risankizumab in Patients with Moderately to Severely Active Crohn’s Disease: Interim Results from the SEQUENCE Open-Label Extension Study

Abstract Background and Aims Risankizumab, a selective interleukin-23 p19 inhibitor, is approved to treat moderately to severely active Crohn’s disease in adults. We report interim results from part 2 of the ongoing SEQUENCE trial evaluating long-term efficacy and safety of risankizumab in patients with active Crohn’s disease and previous anti-TNF failure. Methods Patients randomized to risankizumab who completed the part 1 week 48 visit could continue receiving open-label subcutaneous risankizumab 360 mg every 8 weeks (part 2). Patients with inadequate response could receive rescue therapy (intravenous risankizumab 600 mg) before continuing regular treatment. This interim analysis assessed efficacy at weeks 52, 76, and 100 of treatment; safety was evaluated throughout. Results Overall, 224 patients who received risankizumab 600 mg intravenous induction therapy and 360 mg subcutaneous maintenance therapy entered part 2. Clinical remission rates remained stable through week 100 (as observed, ≥74.5%; nonresponder and modified nonresponder imputation analyses showed similar trends). Most patients (99%) achieving clinical remission were corticosteroid-free at the corresponding visit. Crohn’s disease–related hospitalization and surgery incidence were low (≤0.03 n/patient year), and Inflammatory Bowel Disease Questionnaire and 36-Item Short Form Health Survey improvements were sustained. Safety data were consistent with the known risankizumab safety profile; the exposure-adjusted serious adverse event rate was 11.8/100 patient-years. Conclusions This interim analysis of continuous open-label risankizumab therapy showed durable long-term clinical efficacy and no new safety signals in patients with moderately to severely active Crohn’s disease. Future analyses will evaluate longer-term clinical and endoscopic outcomes and safety. Clinical trial registration number NCT04524611