Endoscopic Outcomes of Risankizumab in Crohn's Disease: A Real-World Analysis of Terminal Ileal Lesions.

Abstract

Introduction: Improvement of small intestinal lesions is essential for achieving favorable long-term outcomes in patients with Crohn's disease (CD); however, evidence regarding the efficacy of biologics for small bowel involvement remains limited. Risankizumab (RZB), a selective interleukin-23 (IL-23) p19 inhibitor, has shown efficacy in large randomized trials; however, data on its effect on small intestinal inflammation are limited. This study aimed to evaluate the real-world effectiveness of RZB on small intestinal lesions using balloon-assisted enteroscopy.

Methods: We conducted a retrospective study of patients with CD who received RZB between July 2023 and January 2025. Clinical activity was assessed using the Harvey-Bradshaw Index (HBI), and serum biomarkers (albumin, C-reactive protein, and hemoglobin) were measured longitudinally. Endoscopic activity was evaluated using the Simple Endoscopic Score for CD (SES-CD) before treatment and at 28 weeks after treatment; paired endoscopic assessment was available in 16 patients.

Results: A total of 23 patients met the inclusion criteria. At baseline, 10 patients had clinically active disease (HBI ≥4), and 13 were in clinical remission (HBI ≤3). In the active group, HBI and C-reactive protein levels decreased after treatment, whereas hemoglobin and albumin concentrations increased during follow-up (HBI: p < 0.01; CRP: p < 0.05; hemoglobin: p < 0.05; albumin: p < 0.05). Among the 16 patients who underwent paired endoscopic evaluation, both total and ileal SES-CD scores decreased after 28 weeks of RZB therapy, demonstrating mucosal improvement in the terminal ileum (total SES-CD: p < 0.0001; ileal SES-CD: p = 0.0001). Notably, several patients who showed inadequate response to ustekinumab (UST) also exhibited endoscopic improvement after RZB treatment.

Conclusions: RZB was effective in improving clinical and endoscopic disease activities, including terminal ileal lesions, even in patients who were previously refractory to UST. Given the prognostic importance of small bowel inflammation, these findings highlight the potential of selective IL-23p19 inhibition as a valuable therapeutic option for patients with small bowel-dominant CD.