Biological anti-TNF drugs: immunogenicity underlying treatment failure and adverse events
Abstract
INTRODUCTION: Genetically engineered monoclonal antibodies and fusion proteins directed against cytokines or their receptors represent a breakthrough in the treatment of various chronic immune-inflammatory diseases. Areas covered: Studies show high remission rates in several diseases, but clinical practice shows a significant percentage of individuals who do not exhibit the desired response. Loss of therapeutic benefit after initial successful response is designated secondary failure. Immune-biological agents are not self-antigens and are therefore potentially immunogenic. Secondary failure is frequently caused by antibodies against immune-biologicals, known as anti-drug antibodies (ADA). ADA that neutralize circulating immune-biologicals and/or promote their clearance can reduce treatment efficacy. Furthermore, ADA can induce adverse events by diverse immunological mechanisms. This review provides a comprehensive overview of ADA in rheumatoid arthritis patients treated with anti-TNF immune-biologicals, and explores the concept of therapeutic drug monitoring (TDM) as an effective strategy to improve therapeutic management. Expert opinion: Monitoring circulating ADA and therapeutic immune-biological drugs is helpful when evaluating patients with secondary failure. However, immunological tests for ADA vary considerably regarding their ability to detect different types of ADA. Several assays are not designed to determine ADA-induced drug neutralizing capacity, and they may report clinically non-relevant data, especially if drug is present in test samples.
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Studies have shown that ADA response in rheumatoid arthritis patients treated with anti-TNF immunobiologicals leads to loss of therapeutic benefit after an initial positive response.
“For example, studies have shown that ADA response in rheumatoid arthritis patients treated with anti‐TNF immunobiologicals leads to loss of therapeutic benefit after an initial positive response.46”
From Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development (2018) · cites this paper as [46]
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- Authors
- Prado, M. S., Bendtzen, K., & Andrade, L. E. C.
- Affiliations
- Universidade Federal de São Paulo (BR)
- Rigshospitalet (DK)
- Rheumatology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo, Brazil
- ORCID
- Prado, Mônica Simon
- Venue
- Expert Opinion on Drug Metabolism & Toxicology
- Publisher
- Informa UK Limited
- Published
- 2017-08-14
- Volume
- 13
- Issue
- 9
- Pages
- 985-995
- ISSN
- 1742-5255 (ISSN-L)
- 1744-7607
- OpenAlex
- W2744702511
- Cited by
- 58
- References
- 61
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 4 · 2023: 10 · 2022: 5 · 2021: 4 · 2020: 10 · 2019: 7 · 2018: 8
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Opinion on Drug Metabolism & Toxicology (publishedVersion)
- PubMed (publishedVersion)
- UNIFESP Institutional Repository (Universidade Federal de São Paulo) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- anti-TNF drugs, anti-drug antibodies, immunogenicity, secondary treatment failure, rheumatoid arthritis, therapeutic drug monitoring, adverse drug reactions
- MeSH terms
- Animals, Antibodies, Antibodies, Monoclonal, Arthritis, Rheumatoid, Biological Factors, Humans, Inflammation, Tumor Necrosis Factor-alpha, Drug Monitoring, Treatment Failure, Antirheumatic Agents
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