An update on the role of anti-IL-12/IL23 agents in the management of inflammatory bowel disease

Abstract

Introduction: The aim of treatment in inflammatory bowel disease (IBD) is to control symptoms and suppress gut inflammation with minimal systemic side effects. A large proportion of patients are either primary non-responders or lose response to currently licensed therapies. The development of monoclonal antibodies, blocking interleukin (IL)-12 and IL-23 pathways are a promising therapeutic advance. We review the data on IL12/23 inhibitors and emerging data on IL-23 inhibition in IBD treatment.

Sources of data: This review is based on data published in peer-reviewed journals and clinical trials registry.

Areas of agreement: Ustekinumab is currently approved for managing corticosteroid and biologic refractory IBD patients with a favourable safety profile.

Areas of controversy: Despite a growing therapeutic armamentarium and convergence on the role of biological therapies in patients with greater disease severity, there remains considerable uncertainty with selection and positioning of treatment.

Growing points: Efficacy data from clinical trials and a growing body of real-world data have established a role for IL12/23 inhibitor Ustekinumab in IBD. There is resurgent interest in IL-23 specificity and the potential for incremental benefit. The potential for IL-22 to act as a biomarker for IL-23 inhibitors has exciting implications for personalized medicine.

Areas timely for developing research: Head-to-head trials exploring efficacy and combination with other biologics with the potential for synergistic benefit are under investigation. Results of phase 3 trials with IL-23 inhibitors incorporating clinical, biochemical and endoscopic parameters and also exploring biomarkers as predictors of response are urgently needed.

Keywords: inflammatory bowel disease; interleukin-12; interleukin-23; monoclonal antibodies.