RESCUE-CD - Real-world effectiveness of risankizumab in moderate-to-severe Crohn's disease: a case series involving the most refractory and challenging patients.

Introduction: Selective interleukin-23 (IL-23) blockade with risankizumab (RZB) is effective in moderate-to-severe Crohn's disease (CD), but evidence in highly refractory populations remains limited. Aim: We assessed real-world effectiveness and safety of RZB in a retrospective multicenter case series of adult patients with CD previously exposed to multiple biologics and small molecules, including selected cases of dual-targeted therapy. Material and methods: Patients from four Polish tertiary IBD centers who initiated standard-dose RZB before 1 December 2025 were included. Disease activity was evaluated using the Crohn's Disease Activity Index (CDAI). Primary endpoints were clinical response and remission at week 12 and last follow-up. Secondary endpoints included corticosteroid (CS)-free remission, CS dose reduction, improvement in extraintestinal manifestations and perianal disease, and safety. Results: Fourteen highly refractory patients were analyzed (mean age: 35.2 years; mean disease duration: 13.9 years). Baseline disease activity was severe (mean: CDAI 376); 71.4% had perianal disease and 78.6% had prior CD-related surgery. CDAI declined rapidly, with a mean reduction of 279 points at last observation. At week 12, clinical response and remission were achieved in 85.7% and 57.1% of patients, respectively, increasing to 78.6% remission at follow-up. CS-free remission increased from 50.0% to 71.4%; all CS-treated patients reduced steroid dose, and 87.5% reported improvement in perianal fistulas. One mild adverse event was observed, with no serious adverse events. Conclusions: RZB showed high and durable effectiveness with a favorable safety profile in an exceptionally refractory real-world CD population, supporting IL-23 p19 inhibition as a valuable late-line therapeutic option.