Faculty Collaboration Database

Therapeutic drug monitoring in patients with inflammatory bowel disease. World J Gastroenterol 2014 Apr 07;20(13):3475-84

Date

04/08/2014

Pubmed ID

24707130

Pubmed Central ID

PMC3974514

DOI

10.3748/wjg.v20.i13.3475

Scopus ID

2-s2.0-84897483249 (requires institutional sign-in at Scopus site)   55 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.

Author List

Yarur AJ, Abreu MT, Deshpande AR, Kerman DH, Sussman DA

MESH terms used to index this publication - Major topics in bold

Adalimumab
Antibodies
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Azathioprine
Drug Monitoring
Genotype
Humans
Immunologic Factors
Inflammation
Inflammatory Bowel Diseases
Infliximab
Methyltransferases
Phenotype
Purines
Thioguanine
Thionucleosides
Treatment Outcome
Tumor Necrosis Factor-alpha