Therapeutic drug monitoring in patients with inflammatory bowel disease

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Thiopurine analogs and anti-tumor necrosis factor (TNF) agents have dramatically changed the therapeutics of inflammatory bowel diseases (IBD), improving short and long-term outcomes. Unfortunately some patients do not respond to therapy and others lose response over time. The pharmacokinetic properties of these drugs are complex, with high inter-patient variability. Thiopurine analogs are metabolized through a series of pathways, which vary according to the patients' pharmacogenetic profile. This profile largely determines the ratios of metabolites, which are in turn associated with likelihoods of clinical efficacy and/or toxicity. Understanding these mechanisms allows for manipulation of drug dose, aiming to reduce the development of toxicity while improving the efficacy of treatment. The efficacy of anti-TNF drugs is influenced by many pharmacodynamic variables. Several factors may alter drug clearance, including the concomitant use of immunomodulators (thiopurine analogs and methotrexate), systemic inflammation, the presence of anti-drug antibodies, and body mass. The treatment of IBD has evolved with the understanding of the pharmacologic profiles of immunomodulating and TNF-inhibiting medications, with good evidence for improvement in patient outcomes observed when measuring metabolic pathway indices. The role of routine measurement of metabolite/drug levels and antibodies warrants further prospective studies as we enter the era of personalized IBD care.

Original languageEnglish (US)
Pages (from-to)3475-3484
Number of pages10
JournalWorld Journal of Gastroenterology
Volume20
Issue number13
DOIs
StatePublished - Apr 7 2014

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Keywords

  • Adalimumab
  • Anti-tumor necrosis factor
  • Antibodies
  • Azathioprine
  • Drug level
  • Drug monitoring
  • Inflammatory bowel disease
  • Infliximab
  • Thioguanine
  • Thiopurines

ASJC Scopus subject areas

  • Gastroenterology

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