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World J Gastroenterol. Apr 7, 2014; 20(13): 3475-3484
Published online Apr 7, 2014. doi: 10.3748/wjg.v20.i13.3475
Therapeutic drug monitoring in patients with inflammatory bowel disease
Andres J Yarur, Maria T Abreu, Amar R Deshpande, David H Kerman, Daniel A Sussman
Andres J Yarur, Maria T Abreu, Amar R Deshpande, David H Kerman, Daniel A Sussman, Division of Gastroenterology, University of Miami Leonard Miller School of Medicine, Miami, FL 33136, United States
Author contributions: All authors substantially contributed to the writing of this article and approved the final manuscript.
Correspondence to: Daniel A Sussman, MD, Division of Gastroenterology, University of Miami Leonard Miller School of Medicine, 1120 NW 14th Street, Suite 310F3 (D-49), Miami, FL 33136, United States. dsussman@med.miami.edu
Telephone: +1-305-2438644 Fax: +1-305-2433762
Received: October 30, 2013
Revised: January 15, 2014
Accepted: February 17, 2014
Published online: April 7, 2014
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.

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

Core tip: The use of thiopurine analogs and anti-tumor necrosis factor (TNF) agents in patients with inflammatory bowel diseases (IBD) has improved outcomes. The pharmacokinetics of thiopurines is variable among patients, and some do not benefit from these drugs. The manipulation and monitoring of thiopurines can potentially increase response to treatment and/or reduce the development of toxicity. The efficacy of anti-TNF drugs is also variable and several factors can modify drug clearance, including the concomitant use of immunomodulators, systemic inflammation, the presence of anti-drug antibodies, and body mass. The treatment of IBD has advanced with the understanding of the pharmacologic profiles of immunomodulating and TNF-inhibiting medications.