Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease

  • Nicholas Carman
  • David R. Mack
  • Eric I. Benchimol
Pediatric Gastroenterology (S Orenstein, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Pediatric Gastroenterology

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.

Summary

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

Inflammatory bowel disease Pediatrics Treatment Azathioprine Biologics Therapeutic drug monitoring 

Notes

Compliance with Ethical Standards

Conflict of Interest

Nicholas Carman and Eric Benchimol report no conflicts of interest. David Mack reports patents in the area of intestinal microbiome in relation to IBD.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance ••Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Nicholas Carman
    • 1
    • 2
  • David R. Mack
    • 1
    • 2
  • Eric I. Benchimol
    • 1
    • 2
    • 3
  1. 1.CHEO Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and NutritionChildren’s Hospital of Eastern OntarioOttawaCanada
  2. 2.Department of PediatricsUniversity of OttawaOttawaCanada
  3. 3.School of Epidemiology and Public HealthUniversity of OttawaOttawaCanada

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