Immunogenicity of Therapeutic Antibodies Used for Inflammatory Bowel Disease: Treatment and Clinical Considerations

Ole Haagen Nielsen*, Alexander Hammerhøj, Mark Andrew Ainsworth, John Gubatan, Geert D'Haens

*Corresponding author for this work

Research output: Contribution to journalReviewResearchpeer-review

Abstract

The introduction of tumor necrosis factor inhibitors has led to a paradigm shift in the management of inflammatory bowel disease (IBD). The subsequent introduction of both anti-integrins and cytokine blockers has since expanded the biologic armamentarium. However, immunogenicity, defined as the production of anti-drug antibodies (ADAs) to the prescribed biopharmaceutical, means a significant fraction of patients exposed to biologic agents will experience a secondary loss of response to one or more of the drugs. In clinical settings, immunogenicity may be caused by several factors, both patient related (e.g., underlying chronic disease, systemic immune burden, including previous biologic therapy failure, and [epi]genetic background) and treatment related (e.g., dose and administration regimens, drug physical structure, photostability, temperature, and agitation). Here, we outline these elements in detail to enhance biopharmaceutical delivery and therapy for patients with IBD. Moreover, concurrent immunomodulator medication may reduce the risks of ADA generation, especially when using the chimeric drug infliximab. Summarizing the latest developments and knowledge in the field, this review aims to provide strategies to prevent ADA production and information on managing non-responsiveness or loss of response to biologics. Better understanding of the molecular mechanisms underlying the formation of ADAs and the critical factors influencing the immunogenicity of biopharmaceuticals may lead to improved health outcomes in the IBD community that may benefit both the individual patient and society through lower healthcare expenses.

Original languageEnglish
JournalDrugs
Volume85
Issue number1
Pages (from-to)67-85
Number of pages19
ISSN0012-6667
DOIs
Publication statusPublished - 2025

Bibliographical note

© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

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