Effectiveness of Risankizumab After Ustekinumab Failure in Crohn’s Disease: A Multicenter Retrospective Cohort Study
SHIVA MEHTA-DHAND et al.
Dysregulation of the interleukin (IL) 23–T helper 17 cell axis has emerged as a central driver of disease pathogenesis in patients with Crohn’s disease (CD). Ustekinumab was the first approved therapy targeting this pathway in CD through IL12/23p40.1 However, mechanistic studies have demonstrated that intestinal inflammation is driven predominantly by IL23 rather than IL12.2 This distinction has translated into clinically meaningful differences in efficacy in other immune-mediated diseases such as psoriasis, where IL23p19 antagonists are superior to ustekinumab in head-to-head trials and retain efficacy even after ustekinumab failure.3 Risankizumab, guselkumab, and mirikizumab are now approved for the treatment of CD, with randomized controlled trials suggesting higher rates of endoscopic remission compared with ustekinumab.4,5 For clinical practice, understanding whether patients with CD failing ustekinumab can still respond to subsequent treatment with an IL-23p19 antagonist is a priority. In addition, it remains unknown what factors may predict treatment response in this setting. We conducted a multicenter retrospective cohort study to evaluate the realworld effectiveness of risankizumab in patients with CD previously treated with ustekinumab and to identify clinically applicable predictors of response after therapeutic sequencing within the IL23 pathway.
