Therapeutic drug monitoring in patients with inflammatory bowel disease.
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.
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.
Andres J
AJ
Yarur
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.
Maria T
MT
Abreu
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.
Amar R
AR
Deshpande
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.
David H
DH
Kerman
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.
Daniel A
DA
Sussman
D000068879:Adalimumab; D000906:Antibodies / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D001379:Azathioprine / Q000008:administration & dosage; D016903:Drug Monitoring / Q000379:methods*; D005838:Genotype; D006801:Humans; D007155:Immunologic Factors; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D000069285:Infliximab; D008780:Methyltransferases / Q000235:genetics; D010641:Phenotype; D011687:Purines / Q000737:chemistry; D013866:Thioguanine / Q000008:administration & dosage; D013872:Thionucleosides / Q000737:chemistry; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D011687:Purines; D013872:Thionucleosides; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D013866:Thioguanine; D000068879:Adalimumab; D001379:Azathioprine
Adalimumab; Anti-tumor necrosis factor; Antibodies; Azathioprine; Drug level; Drug monitoring; Inflammatory bowel disease; Infliximab; Thioguanine; Thiopurines