Monitoring antigen-specific biologics: current knowledge and future prospects.

An increasing number of antigen-specific biologics have been introduced into clinical practice, and the ones that arrived first have already reached the end of their patented life span. Despite the use of these agents for over a decade, individualized dosing is not standard practice. Most patients are treated according to treatment protocols, with a fixed dose administered at fixed time intervals. Although the between-subject variability in the volume of distribution is small, there is a moderate to high between-subject variability in the clearance of these biologics. The formation of neutralizing antidrug antibodies (ADAs) further contributes to the variability in the pharmacokinetics and pharmacodynamics. After the development of assays to detect biologic drug serum concentrations and ADA titers, the first clinical studies in immune-mediated diseases such as rheumatology, gastroenterology, and dermatology have now shown clear concentration-effect relationships. By monitoring the serum trough concentrations of biologics, patients with high drug exposure could be identified and dose reductions in those patients may lead to improved safety and substantial cost savings. Low biologic drug serum concentrations may be due to the development of ADAs, and if these are detected, a switch to an alternative treatment is indicated. We envision a vast expansion of therapeutic drug monitoring to support the use of biologics, and we urge the International Association of Therapeutic Drug Monitoring and Clinical Toxicology to embark on initiatives to investigate the contribution of therapeutic drug monitoring to this field.