Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease

Curr Gastroenterol Rep. 2018 Apr 5;20(5):18. doi: 10.1007/s11894-018-0623-z.

Abstract

Purpose of review: Therapeutic drug monitoring (TDM) has emerged as a useful tool to optimize the use of drug therapies in adults with inflammatory bowel disease (IBD), including both Crohn's disease (CD) and ulcerative colitis (UC), especially during the use of biological therapies, for which the pharmacokinetics and pharmacodynamics are highly variable among patients. Fewer data exist in children. This review examines the current literature on TDM in pediatric IBD.

Recent findings: Drug clearance is affected by a number of patient and disease factors. For thiopurines, adjusting dosing by monitoring 6-thioguanine (6TGN) and 6-methylmercaptopurine ((6MMP) levels is demonstrated to maximize response and minimize toxicity, while monitoring metabolite levels when treating with anti-tumor necrosis factor (anti-TNF) remain controversial. While in adults the use of TDM in the setting of loss of response to anti-TNF therapy is established, in children, only a small number of studies exist, but these too have encouraging results. There are however, conflicting data regarding the optimal timing of TDM, comparing "reactive" monitoring and "proactive" monitoring. No such data exist in pediatrics. TDM is cost-effective, and dose reduction may represent a safety benefit. There are limited adult data for use of TDM for the newer biologics, vedolizumab and ustekinumab, but early results suggest similarly promising utility. The use of TDM in pediatric IBD is increasing in clinical practice, with similar efficacy to adults demonstrated in children with loss of response to anti-TNF therapy. More prospective studies are needed in children to examine proactive monitoring and utility of TDM with newer biologics.

Keywords: Azathioprine; Biologics; Inflammatory bowel disease; Pediatrics; Therapeutic drug monitoring; Treatment.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / blood
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Azathioprine / administration & dosage
  • Azathioprine / blood
  • Azathioprine / therapeutic use
  • Biological Products / administration & dosage
  • Biological Products / blood*
  • Biological Products / therapeutic use
  • Child
  • Drug Monitoring / methods*
  • Gastrointestinal Agents / administration & dosage
  • Gastrointestinal Agents / blood*
  • Gastrointestinal Agents / therapeutic use
  • Humans
  • Inflammatory Bowel Diseases / blood*
  • Inflammatory Bowel Diseases / drug therapy*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Ustekinumab / administration & dosage
  • Ustekinumab / blood
  • Ustekinumab / therapeutic use

Substances

  • Antibodies, Monoclonal, Humanized
  • Biological Products
  • Gastrointestinal Agents
  • Tumor Necrosis Factor-alpha
  • vedolizumab
  • Ustekinumab
  • Azathioprine