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Incidence, Prevention and Management of Anti-Drug Antibodies Against Therapeutic Antibodies in Inflammatory Bowel Disease: A Practical Overview

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An Erratum to this article was published on 01 March 2017

Abstract

The introduction of biologic therapy has revolutionized the treatment of inflammatory bowel disease (IBD). However, like all therapeutic proteins, monoclonal antibodies have immunogenic potential which is influenced by multiple drug- and patient-related factors. The reported incidence of anti-drug antibodies (ADAs) towards biologic drugs in IBD varies greatly in the literature and depends not only on differences in sensitization but also on the assay methodology and the timepoint of measurement. Sensitization with formation of ADAs is associated with an increased risk of infusion reactions, accelerated drug clearance, and a loss of response (LOR) to drug. Recently, a greater understanding of the pharmacokinetics of therapeutic antibodies has led to the development of new strategies to reduce immunogenicity and more efficient use of these drugs. These preventive strategies include regular scheduled dosing with maintenance of stable therapeutic trough drug concentrations, and co-administration of an immunosuppressive. Sub-therapeutic drug concentrations with low levels of ADAs can generally be overcome with dose escalation, whereas the presence of high concentrations of ADAs requires a switch to another therapeutic agent.

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Authors and Affiliations

  1. Robarts Clinical Trials, University of Western Ontario, London, ON, Canada

    Pieter Hindryckx, Gregor Novak, Niels Vande Casteele, Reena Khanna, Jairath Vipul & Brian G. Feagan

  2. Department of Gastroenterology, University of Ghent, Ghent, Belgium

    Pieter Hindryckx & Debby Laukens

  3. Department of Gastroenterology, Ljubljana University Medical Centre, Ljubljana, Slovenia

    Gregor Novak

  4. Department of Medicine, University of California San Diego, La Jolla, California, USA

    Niels Vande Casteele

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

    Reena Khanna, Jairath Vipul & Brian G. Feagan

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

    Jairath Vipul & Brian G. Feagan

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  1. Pieter Hindryckx
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Correspondence to Brian G. Feagan.

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Conflict of interest

PH has received consulting fees from Abbvie and Takeda, and speaker’s fees from Ferring, Falk Pharma, Vifor Pharma, Tillotts Pharma, Chiesi, Takeda, and Abbvie. GN has received speaker’s fees from Abbvie and Merck. NVC is a Postdoctoral Fellow of the Research Foundation-Flanders (FWO). RK has received consulting fees from AbbVie, Janssen, and Takeda Pharma. DL has no relevant disclosures. VJ has received consulting fees from AbbVie and Sandoz, and speaker’s fees from Takeda and Janssen. 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, and Wyeth. VJ has received consulting fees from AbbVie and Sandoz, and speaker’s fees from Takeda and Janssen.

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An erratum to this article is available at http://dx.doi.org/10.1007/s40265-017-0719-z.

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Hindryckx, P., Novak, G., Vande Casteele, N. et al. Incidence, Prevention and Management of Anti-Drug Antibodies Against Therapeutic Antibodies in Inflammatory Bowel Disease: A Practical Overview. Drugs 77, 363–377 (2017). https://doi.org/10.1007/s40265-017-0693-5

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