Assessment of TNF alpha antagonists and Anti Drug Antibodies

The use of TNF-alpha antagonists has revolutionized therapy in patients with immune diseases, including rheumatoid arthritis, and inflammatory bowel disease. Among initial responders to TNF-alpha antagonists, response vanishes over time in approximately half of them. The most common cause of nonresponse is the production of antibodies against the TNF-alpha antagonist, which neutralize the effect of the drug. Most patients developing treatment failure are managed empirically by increasing the dose, or shortening dose intervals, without identifying the mechanism for loss of response, or investigating if the symptoms are due to causes other than inflammation. An alternative to this empiric strategy is to use laboratory testing to measure TNF-alpha antagonist drug and antibody levels, to select a new treatment based on the most likely mechanism responsible for loss of response. Testing for drug levels and antibodies to TNF-alpha antagonists is one of the fastest growing areas in clinical laboratory. Several methodologies are available for measuring levels of TNF-alpha antagonist drug and anti-drug antibodies. The objectives of this lecture are: 1) to describe the methods available for measurement of TNF-alpha antagonists and anti-drug antibodies levels; 2) to identify the clinical indications for which measurement of TNF-alpha antagonists and anti-drug antibodies levels are applicable; and 3) to provide guidance on interpretation of test results.