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Therap Adv Gastroenterol. 2018 Jan 21;11:1756283X17750355. doi: 10.1177/1756283X17750355. eCollection 2018.

Immunogenicity of biologics in inflammatory bowel disease.

Author information

1
Department of Gastroenterology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.
2
Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
3
Pfizer Innovative Health, Pfizer S.r.l, Rome, Italy.
4
Market Access Solutions, Envision Pharma Group Ltd, London, UK.
5
Pfizer Innovative Health, Pfizer Inc, Collegeville, PA, USA.

Abstract

Crohn's disease and ulcerative colitis are chronic inflammatory disorders of the gastrointestinal tract. Treatment options include biologic therapies; however, a proportion of patients lose response to biologics, partly due to the formation of anti-drug antibodies (ADAbs). Concomitant immunosuppressive agents reduce the development of ADAbs. This review article aims to assess the immunogenicity of biologic therapies and their clinical implications. A comprehensive literature search was conducted for articles published January 2009 to August 2015 reporting immunogenicity to adalimumab (ADM), certolizumab pegol (CZP), golimumab, infliximab (IFX), ustekinumab, and vedolizumab in inflammatory bowel disease (IBD). Eligible articles were reviewed and quality assessed by independent reviewers. Overall, 122 publications reporting 114 studies were assessed. ADAbs were reported for all agents, but the percentage of patients developing ADAbs was extremely variable, with the highest (65.3%) being for IFX administration to patients with IBD. ADAb presence was frequently associated with a reduction in primary efficacy and a loss of response, and, for IFX, an increase in adverse events (AEs). Lower serum levels of ADM, CZP and IFX were seen in ADAbs-positive rather than ADAbs-negative patients; pharmacokinetic data were unavailable for other therapies. Little information was available regarding the timing of ADAb development; studies reported their detection from as early as 10-14 days up to months after treatment initiation. Biologic therapies carry an intrinsic risk of immunogenicity, although reported rates of ADAbs vary considerably. The clinical implications of immunogenicity are a concern for effective treatment; further research, particularly into the more recently approved biologics, is required.

KEYWORDS:

Crohn’s disease; anti-drug antibodies; biologic therapy; immunogenicity; ulcerative colitis

Conflict of interest statement

Conflict of interest statement: SV has received consulting fees from AbbVie, MSD, Takeda, Ferring, Genentech/Roche, Shire, Pfizer Inc, Galapagos, Mundipharma, Hospira, Celgene, Second Genome and Janssen; research grants from AbbVie, MSD and Takeda; and speaker fees from AbbVie, MSD, Takeda, Ferring, Dr Falk Pharma, Hospira and Tillot. AG has received speaker fees from AbbVie, MSD, Takeda, Pfizer, Hospira and Janssen Biologicals; consulting fees from UCB; and research grants from Pfizer Inc. SL is an employee of Engage Scientific, a Division of Envision Pharma Group Ltd, which acted as a paid consultant to Pfizer in connection with the conduct of the systematic literature review and interpretation of data. PA and AM are employees and stockholders of Pfizer Inc.

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