Abstract Background In recent phase 3 trials, risankizumab (RZB), a humanised monoclonal IgG1 antibody targeting the interleukin 23 p19 subunit, proved to be superior to placebo in inducing and maintaining clinical remission and endoscopic response in patients with moderate-to-severe Crohn’s disease. In this study, we aimed to evaluate the effectiveness and safety of RZB in a real-world cohort of multi-refractory CD patients. Methods Adult CD patients from six Belgian IBD centres who initiated RZB prior to May 2021 as part of a medical need program were prospectively followed. Patients with an ostomy were excluded for the main analyses. The primary endpoint was steroid-free clinical remission at week 24 (average daily liquid stool frequency [SF] ≤2.8 and average abdominal pain [AP] score ≤1, both not worse than baseline). Secondary endpoints included clinical response, endoscopic remission, endoscopic response, biological remission, biological response, need for CD-related hospitalisation or surgery, and serious adverse events (definitions in Figure 1). Given that a follow-up endoscopy has not yet been performed in some patients, results are shown for both “all patients” (with non-responder imputation) and “as observed”. Results A total of 27 patients started RZB of whom 19 patients were eligible for this study with a minimal follow-up of 24 weeks (Table 1). Eight patients were excluded as they had an ostomy at time of RZB initiation. Eighteen patients (95%) had been exposed to more than 3 biologicals and 13 (68%) previously underwent a CD-related intestinal resection. By week 24, 7/19 (37%) and 7/19 (37%) patients achieved steroid-free clinical remission and endoscopic response, respectively (Figure 1). In the “as observed” analyses, these rates were 7/18 (39%) and 7/9 (78%), respectively (Figure 2). Five patients used concomitant steroids at baseline and were all able to stop it after a median of 10 weeks. Eventually, three patients had to be hospitalized for bowel resection (2 with placement of an ostomy) ...