Therapeutic drug monitoring (TDM) is the clinical practice of measuring drug concentrations or metabolites to attain a targeted concentration in a patient's bloodstream, thereby optimizing individual dosage regimens. With the well-established knowledge of the relationship of the genetic variability of thio-purine metabolism driven by the thiopurine S-methyltransferase pathway, and the recent data supporting pharmacokinetic variability and immunogenicity with anti-tumor necrosis factor (anti-TNF) therapies, TDM has emerged as a necessary mechanism to enhance drug efficacy. This article reviews data describing the relationship between drug concentrations and outcomes, including the achievement of a sustained and durable remission. The effect of antidrug antibodies on drug efficacy and toxicity is also examined. Furthermore, we describe different assays that are used for measuring these drug and antibody concentrations, including the advantages and pitfalls of these tools. An algorithm is proposed for clinical practitioners to utilize TDM in patients who are losing clinical response to anti-TNF therapy. A proactive, rather than reactive, approach to TDM of anti-TNF agents is supported by emerging data and will provide practitioners with the tools needed to optimally treat young inflammatory bowel disease patients.
Keywords: Inflammatory bowel disease; immunogenicity; infliximab levels; infliximab trough concentrations; pharmacokinetics; therapeutic drug monitoring; thiopurine metabolites.