Therapeutic drug monitoring of biologics for inflammatory bowel disease.
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.
Department of Hepatogastroenterology, Hôpital Claude Huriez, Centre Hospitalier Universitaire de Lille, Lille, France. jean-frederic.colombel@mssm.edu
Jean-Frédéric
JF
Colombel
Brian G
BG
Feagan
William J
WJ
Sandborn
Gert
G
Van Assche
Anne M
AM
Robinson
D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001688:Biological Products / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008297:Male; D016896:Treatment Outcome; D000079424:Tumor Necrosis Factor Inhibitors
D000911:Antibodies, Monoclonal; D001688:Biological Products; D000079424:Tumor Necrosis Factor Inhibitors