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Tumor necrosis factor-alpha inhibitors: Induction of antibodies, autoantibodies, and autoimmune diseases

Klaus Bendtzen, MD, DMSc
Section Editor
Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
Deputy Editor
Paul L Romain, MD


Targeted inhibitors of tumor necrosis factor-alpha (TNF) are widely used in the treatment of a number of inflammatory conditions, including rheumatoid arthritis (RA), spondyloarthritis, inflammatory bowel disease, and psoriasis (with or without arthritis). However, use of these agents has been associated in some patients with the development of anti-drug antibodies, which may promote adverse effects and diminish drug efficacy. Induction of autoimmunity, including both autoantibodies and, much less often, clinically evident autoimmune disease, may also occur during treatment.

Adverse effects associated with the use of biologic agents that inhibit TNF include injection site and infusion reactions, cytopenias, infections, autoimmune and demyelinating diseases, heart failure, malignancy, and pulmonary, liver, and skin disease. These potentially serious risks are among the factors included in the risk/benefit assessment made when deciding whether to use one of these agents in an individual patient.

TNF inhibitor-related anti-drug antibody formation, autoantibody formation, and the development of autoimmune diseases are reviewed here. Other major complications of anti-TNF therapy, such as injection site and infusion reactions, tuberculosis and other infections, malignancy, and other adverse effects, are described separately. (See "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects" and "Tumor necrosis factor-alpha inhibitors and mycobacterial infections" and "Tumor necrosis factor-alpha inhibitors: Bacterial, viral, and fungal infections" and "Tumor necrosis factor-alpha inhibitors: Risk of malignancy".)


The formation of anti-drug antibodies, especially drug-neutralizing antibodies, is a concern with biological TNF inhibitors, particularly infliximab and adalimumab, as anti-drug antibodies may cause allergic reactions, loss of responsiveness, and increased cost of therapy. The risk of developing antibodies varies with the type of TNF inhibitor; they appear least common with use of etanercept, a receptor fusion protein, and most common with infliximab, a chimeric (mouse/human) antibody construct.

The five biologic TNF inhibitors that are widely available for the treatment of a variety of inflammatory illnesses (eg, rheumatoid arthritis [RA], Crohn’s disease), their composition, and their association with anti-drug antibody induction include:


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Literature review current through: Sep 2016. | This topic last updated: Aug 4, 2015.
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