Risankizumab redefines Crohn’s treatment after ustekinumab failure

Abstract

Conventional Crohn’s disease biologic sequencing typically follows drug class transitions: Anti-tumor necrosis factor, anti-integrin, and anti-cytokine therapies. However, a landmark real-world study by Colwill et al disrupts this paradigm, revealing exceptional efficacy within the cytokine pathway, specifically with risankizumab following ustekinumab. This study asserts these provocative findings demand a critical reappraisal of treatment algorithms, while contextualizing them within the current evidence landscape. It will critically appraise the study’s impressive remission rates and favorable safety profile, contrasting them with alternative switch strategies and exploring the compelling mechanistic rationale for sequential interleukin-23 blockade. The discussion will center on integrating this preliminary evidence into clinical decision-making, advocating for further research to define its place in a new treatment hierarchy.

Keywords: Crohn disease; Ustekinumab; Risankizumab; Interleukin-23; Drug substitution; Treatment failure; Secondary loss of response; Biological therapy

Core Tip: Emerging real-world data indicate that risankizumab may induce high rates of clinical and biomarker remission after ustekinumab failure in Crohn’s disease. These findings challenge the traditional cross-class switching paradigm and suggest potential for sequential, increasingly specific interleukin-23 pathway blockade. While mechanistically plausible, the evidence remains preliminary from single-center studies. Balanced interpretation, validation in larger diverse cohorts, and rigorous cost-effectiveness analyses are needed before revising global treatment algorithms.