J Crohns Colitis. 2022 May 11;16(Supplement_2):ii73-ii94.doi: 10.1093/ecco-jcc/jjab190.

Zoë S Gottlieb ¹, Bruce E Sands ¹

Author information

¹Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Abstract

Background and aims: The medical management of inflammatory bowel disease [IBD] has become increasingly targeted, through the identification of specific immune mediators involved in its pathogenesis. IL-23 is an inflammatory cytokine involved in both innate and adaptive immunity, which 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 personalised medicine approach with these agents.

Methods: We reviewed and summarised 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 which 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.