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

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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.

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Author information

Authors and Affiliations

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

    Ahmed Almradi, Rocio Sedano, Brian G. Feagan & Vipul Jairath

  2. Alimentiv, Inc., London, ON, Canada

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

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

    Christopher Ma

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

    Brian G. Feagan & Vipul Jairath

Authors
  1. Ahmed Almradi
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  2. Jurij Hanzel
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Correspondence to Vipul Jairath.

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Conflict of Interest

AA has no conflicts of interest to declare. JH has received speaker’s fees from Biogen, Janssen, and Takeda. RS has no conflicts of interest to declare. CEP is an employee of Robarts Clinical Trials Inc. BGF has received grant/research support from AbbVie Inc., Amgen Inc., AstraZeneca/MedImmune Ltd., Atlantic Pharmaceuticals Ltd., Boehringer-Ingelheim, Celgene Corporation, Celltech, Genentech Inc/Hoffmann-La Roche Ltd., Gilead Sciences Inc., GlaxoSmithKline (GSK), Janssen Research & Development LLC., Pfizer Inc., Receptos Inc./Celgene International, Sanofi, Santarus Inc., Takeda Development Center Americas Inc., Tillotts Pharma AG, and UCB; consulting fees from Abbott/AbbVie, Akebia Therapeutics, Allergan, Amgen, Applied Molecular Transport Inc., Aptevo Therapeutics, Astra Zeneca, Atlantic Pharma, Avir Pharma, Biogen Idec, BioMx Israel, Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, Galapagos, GiCare Pharma, Gilead, Gossamer Pharma, GSK, Inception IBD Inc, JnJ/Janssen, Kyowa Kakko Kirin Co Ltd., Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nestle, Nextbiotix, Novonordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, Receptos, Salix Pharma, Shire, Sienna Biologics, Sigmoid Pharma, Sterna Biologicals, Synergy Pharma Inc., Takeda, Teva Pharma, TiGenix, Tillotts, UCB Pharma, Vertex Pharma, Vivelix Pharma, VHsquared Ltd., and Zyngenia; speakers bureau fees from Abbott/AbbVie, JnJ/Janssen, Lilly, Takeda, Tillotts, and UCB Pharma; is a scientific advisory board member for Abbott/AbbVie, Allergan, Amgen, Astra Zeneca, Atlantic Pharma, Avaxia Biologics Inc., Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Centocor Inc., Elan/Biogen, Galapagos, Genentech/Roche, JnJ/Janssen, Merck, Nestle, Novartis, Novonordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Sterna Biologicals, Takeda, Teva, TiGenix, Tillotts Pharma AG, and UCB Pharma; and is the Senior Scientific Officer of Robarts Clinical Trials Inc. CM has received consulting fees from AbbVie, Janssen, Pfizer, Robarts Clinical Trials, and Takeda; and speaker’s fees from AbbVie, Janssen, Pfizer, and Takeda. VJ has received consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena Pharmaceuticals, Genetech, Pendopharm, Sandoz, Merck, Takeda, Janssen, Robarts Clinical Trials Inc., Topivert, and Celltrion; and speaker’s fees from Takeda, Janssen, Shire, Ferring, Abbvie, and Pfizer.

Authors’ Contributions

All authors made substantial contributions to drafting the manuscript and critically revising it for intellectual content.

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Almradi, A., Hanzel, J., Sedano, R. et al. Clinical Trials of IL-12/IL-23 Inhibitors in Inflammatory Bowel Disease. BioDrugs 34, 713–721 (2020). https://doi.org/10.1007/s40259-020-00451-w

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