Journal
BRITISH MEDICAL BULLETIN
Volume 138, Issue 1, Pages 29-40Publisher
OXFORD UNIV PRESS
DOI: 10.1093/bmb/ldab001
Keywords
inflammatory bowel disease; monoclonal antibodies; interleukin-12; interleukin-23
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The aim of IBD treatment is to control symptoms and suppress gut inflammation, with IL12/23 inhibitors and IL-23 inhibitors showing promise. Currently, Ustekinumab is approved for managing IBD patients, but there is still controversy regarding treatment selection and positioning.
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.
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