Biological anti-TNF drugs: immunogenicity underlying treatment failure and adverse events

Introduction: Genetically engineered monoclonal antibodies and fusion proteins directed against cytokines or their receptors represent a breakthrough in the treatment of various chronic immuneinflammatory 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.