Personalized Medicine with IL-23 Blockers: Myth or Reality?

BACKGROUND AND AIMS The medical management of inflammatory bowel disease (IBD) has become increasingly targeted with the identification of specific immune mediators involved its pathogenesis. IL-23 is an inflammatory cytokine involved in both innate and adaptive immunity that has been identified as a therapeutic target in Crohn's disease (CD) and ulcerative colitis (UC) through its upstream inhibition of the T helper 17 (Th17) pathway. We sought to review available data on the efficacy of IL-23 inhibitors in the treatment of IBD and the potential for clinical and molecular predictors of response to facilitate a personalized medicine approach with these agents. METHODS We reviewed and summarized available clinical trial data on the use of the IL-23 inhibitors risankizumab, brazikumab, mirikizumab and guselkumab in the treatment of IBD, as well as the evidence from studies of these agents in IBD and other immune-mediated conditions that might inform prediction of response to IL-23 inhibition. RESULTS Early clinical trials have demonstrated promising results following both induction and maintenance therapy with IL-23 inhibitors in CD and UC. Pre-and post-treatment levels of IL-22 and post-treatment levels of IL-17 have been identified as potential molecular predictors of response to therapy in several studies. No significant clinical predictors of response have been identified thus far. CONCLUSIONS IL-23 antagonism is a promising therapeutic approach in IBD. Further exploration of molecular and clinical predictors of response may identify patients most likely to benefit from these medications.