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

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.

Anion‐Dependent Layered Double Hydroxide Nanoparticles Regulate Differentiation of CD206+ CX3CR1+ Macrophages by Inhibiting the IL‐17 Signaling Pathway Contributing to Inflammatory Bowel Disease

“…[ 32 ] Th17 cells are a T cell subset that produces IL‐17 family cytokines, mainly IL‐17A and IL‐17F, whose proliferation is promoted by IL‐23. [ 33 ] Given that Th17 cells are closely related to the pathogenesis of IBD, it is an attractive alternative for IBD therapy. [ 34 ] IL‐17A cytokine accumulates in large amounts in the colon and induces the activation of the p38 mitogen‐activated protein kinase MAPK, which in turn regulates the downstream transcription factor activator protein‐1 (AP‐1) in the MAPK pathway.…”

Advancing the precision management of inflammatory bowel disease in the era of omics approaches and new technology

“…The IL23/Th17 pathway is also a central cytokine pathway involved in IBD in addition to TNF-α. The levels of IL-22 and IL-17, the downstream factors involved in this pathway, are potential molecular predictors of the response to IL-23 blockers[ 58 ]. Another category of biologics for IBD is integrin inhibitors, which act by inhibiting gut-selective lymphocyte homing.…”

A Review on Inflammatory Bowel Diseases: Recent Molecular Pathophysiology Advances

“…Clinical and molecular predictors of response should be explored to target the patients who are most likely to benefit from these therapies. 96 A promising new idea for the treatment of IBD is oligonucleotide-based treatments. The biochemical actions of oligonucleotides can activate cellular targets for immunomodulation by mimicking bacterial DNA or by inhibiting the translation of mRNA transcripts of pro-inflammatory molecules.…”