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Targeting IL-23 for IBD: Rationale and Progress to Date

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Abstract

Inflammatory bowel disease, including Crohn’s disease and ulcerative colitis, comprises multiple complex immune-mediated disorders. Early diagnosis and prompt disease control may prevent long-term complications and hospitalization. The therapeutic options have expanded in the last two decades, with the development of biologics and small molecules targeting specific pathways implicated in inflammatory bowel disease pathogenesis. The interleukin (IL)-23/Th-17 axis is one such example. Targeting IL-12/23 is effective for the treatment of both moderate-to-severe Crohn’s disease and ulcerative colitis, and ustekinumab (an IL-12/23p40 antagonist) is approved for both indications. In patients with psoriasis, improved clinical outcomes were observed with agents that more selectively targeted IL-23 (IL-23p19 antagonists) compared with those that target both IL-12 and IL-23. Many specific IL-23p19 antagonists are currently being investigated in Crohn’s disease and ulcerative colitis, and risankizumab has been recently approved for moderate-to-severely active Crohn’s disease. In this review, we summarize the mechanisms of action and the evidence from clinical trials supporting the efficacy and safety of IL-23p19 antagonists for the treatment of inflammatory bowel disease.

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Acknowledgements

We would like to thank Alexa Zayadi for helping to prepare the figure presented in this manuscript.

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Gastroenterology, Western University, London, ON, Canada

    Sudheer K. Vuyyuru, Vipul Jairath & Brian G. Feagan

  2. Alimentiv Inc., London, ON, Canada

    Sudheer K. Vuyyuru, Lisa M. Shackelton, Jurij Hanzel, Christopher Ma, Vipul Jairath & Brian G. Feagan

  3. Department of Gastroenterology, UMC Ljubljana, University of Ljubljana, Ljubljana, Slovenia

    Jurij Hanzel

  4. Division of Gastroenterology and Hepatology, Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada

    Christopher Ma

  5. Department of Epidemiology and Biostatistics, Western University, London, ON, Canada

    Brian G. Feagan

Authors
  1. Sudheer K. Vuyyuru
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  2. Lisa M. Shackelton
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  3. Jurij Hanzel
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  4. Christopher Ma
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  5. Vipul Jairath
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  6. Brian G. Feagan
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Corresponding author

Correspondence to Brian G. Feagan.

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Conflict of interest

SKV is an employee of Alimentiv Inc. LMS has received consulting fees from Alimentiv Inc. JH has received speaker’s fees from Abbvie, Janssen, and Takeda, and consulting fees from Alimentiv Inc. CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda, Tillotts Pharma; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Takeda; royalties from Springer Publishing; research support from Ferring, Pfizer. VJ has received consulting/advisory board fees from AbbVie, Alimentiv Inc (formerly Robarts Clinical Trials), Arena pharmaceuticals, Asieris, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genetech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Reistone Biopharma, Roche, Sandoz, Takeda, Topivert; and speaker’s fees from Abbvie, Ferring, Janssen Pfizer Shire, and Takeda. BGF has received grant/research support from Millennium Pharmaceuticals, Merck, Tillotts Pharma AG, AbbVie, Novartis Pharmaceuticals, Centocor Inc., Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech, ActoGenix, and Wyeth Pharmaceuticals Inc.; consulting fees from Millennium Pharmaceuticals, Merck, Centocor Inc., Elan/Biogen, Janssen-Ortho, Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, UCB Pharma, AbbVie, Astra Zeneca, Serono, Genentech, Tillotts Pharma AG, Unity Pharmaceuticals, Albireo Pharma, Given Imaging Inc., Salix Pharmaceuticals, Novonordisk, GSK, Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GiCare Pharma Inc., and Sigmoid Pharma; and speakers bureaux fees from UCB, AbbVie, and J&J/Janssen. Alimentiv Inc. is an academic gastrointestinal contract research organization (CRO), operating under the Alimentiv Health Trust. Alimentiv Inc. provides comprehensive clinical trial services, precision medicine offerings, and centralized imaging solutions for endoscopy, histopathology, and other imaging modalities. The beneficiaries of the Alimentiv Health Trust are the employees of the enterprises it holds. LMS, JH, CM, VJ, and BGF are consultants to Alimentiv Inc.; they do not hold equity positions or shares in Alimentiv Inc. JH, CM, VJ, and BGF have a primary academic appointment.

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Authors contributions

VJ and BGF supervised the work. All authors drafted and critically advised the manuscript for important intellectual content, and approved the final submitted version of the work.

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Vuyyuru, S.K., Shackelton, L.M., Hanzel, J. et al. Targeting IL-23 for IBD: Rationale and Progress to Date. Drugs 83, 873–891 (2023). https://doi.org/10.1007/s40265-023-01882-9

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  • DOI: https://doi.org/10.1007/s40265-023-01882-9