Interleukin 23: Pathogenetic Involvement and Therapeutic Target for Ulcerative Colitis

Abstract

Interleukin-23 (IL-23) is a key cytokine involved in the pathogenesis of various immuno-mediated inflammatory diseases. In recent years, several drugs selectively targeting IL-23 have been developed and three of them (mirikizumab, risankizumab and guselkumab) were successfully investigated in clinical trials for ulcerative colitis (UC). All of them showed a good profile for efficacy, alleviating symptoms, and inducing endoscopic and histologic improvement, with very low incidence of adverse events. Bowel urgency also emerged as a crucial outcome from patients' perspective in the mirikizumab trials. The correct positioning of IL-23 inhibitors in the therapeutic algorithm for UC represents a new challenge for physicians, especially because it is not guided by biomarkers or predictors of effectiveness. Moreover, no comparative clinical data exist among the available IL-23 inhibitors, although molecular differences might potentially impact their effectiveness. A role for IL-23-inhibitors may also lie in combination with drugs with different mechanisms of action for complex, multi-refractory patients. This review, focusing on UC, summarizes all the clinical data available on IL-23 inhibitors and provides a perspective on the best clinical scenarios to maximize their effectiveness.

Keywords: Th17 lymphocytes; interleukin-23; monoclonal antibodies; ulcerative colitis.

Figure 1

Main molecular mechanisms in IBD. Abbreviations: APC, antigen-presenting cell; IL, interleukin; Th, T helper cell.