Clinical Trials of IL-12/IL-23 Inhibitors in Inflammatory Bowel Disease

Ahmed Almradi; Jurij Hanzel; Rocio Sedano; Claire E Parker; Brian G Feagan; Christopher Ma; Vipul Jairath

doi:10.1007/s40259-020-00451-w

Clinical Trials of IL-12/IL-23 Inhibitors in Inflammatory Bowel Disease

BioDrugs. 2020 Dec;34(6):713-721. doi: 10.1007/s40259-020-00451-w.

Authors

Ahmed Almradi^{1

2}, Jurij Hanzel², Rocio Sedano^{1

2}, Claire E Parker², Brian G Feagan^{1

2

3}, Christopher Ma^{2

4}, Vipul Jairath^{5

6

7}

Affiliations

¹ Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada.
² Alimentiv, Inc., London, ON, Canada.
³ Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.
⁴ Division of Gastroenterology and Hepatology, Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada.
⁵ Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada. vjairath@uwo.ca.
⁶ Alimentiv, Inc., London, ON, Canada. vjairath@uwo.ca.
⁷ Department of Epidemiology and Biostatistics, Western University, London, ON, Canada. vjairath@uwo.ca.

PMID: 33105016
DOI: 10.1007/s40259-020-00451-w

Abstract

The inflammatory bowel diseases (IBDs) are chronic immune-mediated inflammatory disorders, including ulcerative colitis (UC) and Crohn's disease (CD). IBD results from a complex interplay between environmental, microbial, and genetic factors to create an abnormal immunological response leading to intestinal inflammation. Many pathways driving inflammation have been described, and different pathways may predominate in an individual patient. The interleukin (IL)-23 pathway plays a key role in IBD pathogenesis through promoting a pathological Th17 response. Targeting IL-23 is effective in the treatment of IBD. Ustekinumab, a monoclonal antibody targeting the shared p40 subunit of IL-12/23, is approved for treatment of moderate-to-severe CD and UC. Specific IL-23p19 antagonists are in development and promising results from phase II trials of mirikizumab and risankizumab underscore the potential for this class of treatment. In this review, we summarize the mechanisms of action and the evidence from clinical trials supporting the efficacy and safety of different IL-23 antagonists for IBD.

Publication types

Clinical Trial, Phase II
Randomized Controlled Trial

MeSH terms

Antibodies, Monoclonal, Humanized / chemistry
Antibodies, Monoclonal, Humanized / therapeutic use*
Humans
Inflammatory Bowel Diseases* / drug therapy
Interleukin-12 / metabolism
Interleukin-23 / metabolism

Substances

Antibodies, Monoclonal, Humanized
Interleukin-23
Interleukin-12
mirikizumab