Therapeutic drug monitoring in pediatric inflammatory bowel disease

Therapeutic drug monitoring (TDM) is the clinical practice of measuring drug concentrations to attain a targeted serum concentration and thus optimizing individual dosage regimens. TDM has emerged as a necessary mechanism to enhance drug efficacy to achieve optimal outcomes. Examples include the well-established relationship of the genetic variability of thiopurine metabolism driven by the thiopurine S-methyltransferase (TPMT) pathway, and data supporting the pharmacokinetic variability and immunogenicity with anti-tumor necrosis factor (TNF) therapies. In this chapter, we review the data describing the relationship between drug concentrations and outcomes. The effect of anti-drug antibodies on drug efficacy and toxicity has been established. Furthermore, we describe different assays which are used in measuring these drug and antibody concentrations. An algorithm is proposed for clinical practitioners to utilize TDM in the patients losing clinical response to anti-TNF therapy. The limited data around drug and antibody concentrations for vedolizumab and ustekinumab and relation to outcomes are introduced. 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 IBD patients.