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Vedolizumab and Extraintestinal Manifestations in Inflammatory Bowel Disease

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A Correction to this article was published on 28 August 2021

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Abstract

In Crohn’s disease and ulcerative colitis, inflammation is not limited to the digestive tract. Extraintestinal manifestations (EIMs), which affect up to 50% of patients, can substantially impair quality of life. EIMs may parallel luminal disease activity or have an independent course. They most commonly involve the musculoskeletal system (e.g., peripheral or axial arthritis) and skin (e.g., erythema nodosum and pyoderma gangrenosum). Less commonly, the hepatobiliary tract (e.g., primary sclerosing cholangitis [PSC]) and the eye (e.g., episcleritis, scleritis, and uveitis) are involved. Although the pathophysiology of EIMs is poorly understood, they are likely either manifestations of a primary systemic immune disease with variable expression amongst organs, or secondary phenomena to bowel inflammation. Additional pathophysiologic mechanisms may include aberrant lymphocyte homing mediated by ectopic expression of gut-specific chemokines and adhesion molecules, cross-reactivity between microbial and self-antigens, autoantibodies against epitopes shared by the intestine and extraintestinal tissues, elevated serum concentrations of cytokines, and alterations in innate immunity. Many EIMs independent of intestinal disease activity can be successfully treated with tumor necrosis factor (TNF) antagonists. The efficacy of vedolizumab—a monoclonal antibody targeting the α4β7 integrin—for the treatment of EIMs is uncertain, but data are emerging from post hoc analyses of randomized controlled trials, prospective and retrospective cohort studies, and case series. Vedolizumab may be effective in treating EIMs related to luminal disease activity (e.g., type 1 peripheral arthritis and erythema nodosum) but has not shown biochemical improvement in PSC. Its postulated role in the development of de novo EIMs is heavily confounded by the high proportion of patients previously exposed to TNF antagonists; new EIMs could result from TNF antagonist treatment cessation rather than being caused by vedolizumab. A common limitation of clinical studies is the lack of multidisciplinary involvement in the diagnosis and monitoring of EIMs, which may lead to misdiagnosis and overreporting. Future studies should rigorously measure EIMs in parallel with objective measures of luminal disease activity to provide more robust data on the relative efficacy of new drugs, especially as increasing numbers of gut-selective compounds enter clinical development.

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Authors and Affiliations

  1. Department of Gastroenterology, University Medical Center Ljubljana, Ljubljana, Slovenia

    Jurij Hanzel

  2. Alimentiv, #200, 100 Dundas Street, London, N6A 5B6, ON, Canada

    Jurij Hanzel, Christopher Ma, Niels Vande Casteele, Vipul Jairath & Brian G. Feagan

  3. Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, 6D61 Teaching Research Wellness Building, 3280 Hospital Drive NW, Calgary, Alberta, T2N 4Z6, Canada

    Christopher Ma

  4. Department of Medicine, University of California San Diego, 9500 Gilman Drive #0956, La Jolla, CA, 92093, USA

    Niels Vande Casteele

  5. Division of Gastroenterology, University of Western Ontario, 1151 Richmond Street, London, N6A 2K7, ON, Canada

    Reena Khanna, Vipul Jairath & Brian G. Feagan

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

    Vipul Jairath & Brian G. Feagan

  7. Hullenbergweg 278–308, 1101 BV, Amsterdam, The Netherlands

    Jurij Hanzel

  8. Department of Medicine, University of Western Ontario, London, ON, Canada

    Brian G. Feagan

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  1. Jurij Hanzel
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Correspondence to Brian G. Feagan.

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Conflicts of interest

JH has received speaker’s fees from Biogen, Janssen, and Takeda. CM has received consulting fees from AbbVie, AVIR Pharma Inc, Janssen, Takeda, Pfizer, Roche, and Alimentiv (formerly Robarts Clinical Trials Inc.); speaker's fees from AbbVie, Janssen, Takeda, and Pfizer; and research support from the Canadian IBD Research Consortium and Pfizer. NVC has received research grants from R-Biopharm; grants and personal fees from Takeda and UCB; and personal fees from Alimentiv, Inc. (formerly Robarts Clinical Trials, Inc.), Celltrion, and Prometheus. These activities were all outside of the submitted work. RK has received consulting fees from AbbVie, Janssen, Takeda, Roche, Pendopharm, Lilly, Encycle, Shire, Alimentiv (formerly Robarts Clinical Trials Inc.), Pfizer, Inomar, and Merck. VJ has received consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena Pharmaceuticals, Genetech, Pendopharm, Sandoz, Merck, Takeda, Janssen, Alimentiv (formerly Robarts Clinical Trials Inc.), Topivert, and Celltrion and speaker’s fees from Takeda, Janssen, Shire, Ferring, AbbVie, and Pfizer. 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, AstraZeneca, 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, Novo Nordisk, 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, AstraZeneca, 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 Alimentiv Inc. (formerly Robarts Clinical Trials Inc.).

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Hanzel, J., Ma, C., Casteele, N.V. et al. Vedolizumab and Extraintestinal Manifestations in Inflammatory Bowel Disease. Drugs 81, 333–347 (2021). https://doi.org/10.1007/s40265-020-01460-3

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