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

Abstract

Abstract 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.