Therapeutic drug monitoring in patients with inflammatory bowel disease

• Published in: World journal of gastroenterology : WJG Vol. 20; no. 13; pp. 3475 - 3484
• Main Authors: Yarur, Andres J, Abreu, Maria T, Deshpande, Amar R, Kerman, David H, Sussman, Daniel A
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Co., Limited 07.04.2014
• Subjects: Adalimumab; Anti-tumor; Antibodies - administration & dosage; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Humanized - administration & dosage; Azathioprine - administration & dosage; bowel; disease; Drug Monitoring - methods; fac; Genotype; Humans; Immunologic Factors; Inflammation; Inflammatory; Inflammatory Bowel Diseases - drug therapy; Infliximab; Methyltransferases - genetics; necrosis; Phenotype; Purines - chemistry; Thioguanine - administration & dosage; Thionucleosides - chemistry; Topic Highlight; Treatment Outcome; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Inflammatory bowel disease; Anti-tumor necrosis factor; Infliximab; Drug level; Antibodies; Drug monitoring; Thiopurines; Adalimumab; Azathioprine; Thioguanine
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v20.i13.3475

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 outcomesobserved 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.