Background:: Although tumor necrosis factor (TNF) antagonists are effective for the treatment of Crohn's disease and ulcerative colitis, lack and loss of clinical response is a clinical challenge. Accordingly, the use of therapeutic drug monitoring has been proposed as a means to optimize treatment. This article reviews the mechanisms of and factors which influence clearance of biologics, the relationship between serum drug concentrations and antidrug antibody presence and treatment efficacy, and identifies areas for future research needs regarding the use of therapeutic drug monitoring in clinical practice.
Methods:: Publications regarding these topics were identified from literature searching and supplemented by review of gastroenterology meeting presentations and reference lists.
Results:: The clearance of monoclonal antibodies and pegylated antibody fragments is complex, and may be affected by demographic variables, concomitant medications, inflammatory burden, and immunogenicity, leading to high interpatient variability in plasma concentration of drug and clinical response. Several observational studies have demonstrated a relationship between anti‐TNF agent serum drug concentrations and/or antidrug antibody presence and various symptomatic and objective clinical endpoints. However, these relationships are not absolute, and although some algorithms for the use of therapeutic drug monitoring in clinical practice have been proposed, none have yet been validated in a prospective clinical trial.
Conclusions:: Further research to identify the most appropriate use of therapeutic drug monitoring is needed. (Inflamm Bowel Dis 2011;)
1Department of Hepatogastroenterology, Hôpital Claude Huriez, Centre Hospitalier Universitaire de Lille, Lille, France, and Department of Gastroenterology, Mount Sinai School of Medicine, New York, New York, USA
2Robarts Research Institute, University of Western Ontario, London, Ontario, Canada
3Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
4Department of Gastroenterology, University Hospital of Gasthuisberg, Leuven, Belgium
5Abbott Laboratories, Abbott Park, Illinois, USA
*Department of Gastroenterology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1069, New York, NY 10029
Received 6 June 2011; Accepted 20 June 2011
Published online 21 October 2011 in Wiley Online Library (wileyonlinelibrary.com).