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

• Published in: British medical bulletin Vol. 138; no. 1; pp. 29 - 40
• Main Authors: Nigam, Gaurav B, Limdi, Jimmy K
• Format: Journal Article
• Language: English
• Published: England 10.06.2021
• Subjects: inflammatory bowel disease; interleukin-12; interleukin-23; monoclonal antibodies
• ISSN: 0007-1420; 1471-8391
• DOI: 10.1093/bmb/ldab001

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. This review is based on data published in peer-reviewed journals and clinical trials registry. Ustekinumab is currently approved for managing corticosteroid and biologic refractory IBD patients with a favourable safety profile. 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. 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. 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.