IL23p19 therapies for moderately-to-severely active ulcerative colitis

Ulcerative colitis (UC) is a chronic, relapsing and remitting, inflammatory bowel disease. Monoclonal antibodies targeting interleukin (IL)-23p19 have been developed to treat chronic inflammatory diseases mediated by aberrant IL23/Th17 responses, including psoriasis, psoriatic arthritis, and Crohn’s disease. More recently, these agents have been evaluated for the treatment of moderately-to-severely active UC. In this review, we summarize and discuss phase 2 and pivotal phase 3 clinical trials informing the efficacy and safety of mirikizumab (AMAC, LUCENT, and SHINE), risankizumab (INSPIRE, COMMAND), and guselkumab (QUASAR, VEGA). The literature search included original research publications, secondary publications, and preliminary data from conference abstracts presented at international gastroenterology meetings from the past 5 years. The approval of IL23p19 antagonists expands the armamentarium of effective and safe therapies for patients living with moderately-to-severely active UC. These agents demonstrate potent efficacy for both inducing and maintaining symptomatic and objective disease endpoints, including endoscopic, histologic, and biomarker remission. These well-tolerated agents are effective in both advanced treatment-naïve and experienced patients. Accordingly, IL23p19 antagonists have the potential to be used in a diverse population of patients with UC, and as potential platform therapies for future combinations with other targeted immunomodulatory agents.