Current relevance of pharmacogenetics in immunomodulation treatment for Crohn's disease.

Abstract

No drug therapy is completely risk free, and the costs associated with non-response and adverse effects can exceed the cost of the therapy. The ultimate goal of pharmacogenetic research is to find robust genetic predictors of drug response that enable the development of prospective genetic tests to reliably identify patients at risk of non-response or of developing an adverse effect prior to the drug being prescribed. Currently, thiopurine S-methyltransferase (TPMT) deficiency is the only pharmacogenetic factor that is prospectively assessed before azathioprine or 6-mercaptopurine immunomodulation is commenced in patients with Crohn's disease (CD). As yet no other inherited determinant of drug response has made the transition from bench to bedside for the management of this disease. In this review we summarize what is known about TPMT deficiency and explore whether there is evidence to support a role of other genetic polymorphisms in predicting the response of CD patients to thiopurine drugs, methotrexate, and anti-tumor necrosis factor α (TNFα) therapy.

• Authors: Rebecca L Roberts, Murray L Barclay
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 27 Issue 10 Pg. 1546-54 (Oct 2012) ISSN: 1440-1746 [Electronic] Australia
• PMID: 22741564 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Chemical References

• Antibodies, Monoclonal
• Genetic Markers
• Immunologic Factors
• Tumor Necrosis Factor-alpha
• Infliximab
• Mercaptopurine
• Azathioprine
• Methotrexate

Topics

• Antibodies, Monoclonal (therapeutic use)
• Azathioprine (therapeutic use)
• Biotransformation (genetics)
• Crohn Disease (drug therapy, genetics, immunology)
• Drug Hypersensitivity (diagnosis, genetics)
• Drug Interactions
• Genetic Markers
• Genetic Predisposition to Disease
• Genetic Testing
• Humans
• Immunologic Factors (adverse effects, pharmacokinetics, therapeutic use)
• Infliximab
• Mercaptopurine (therapeutic use)
• Methotrexate (therapeutic use)
• Patient Selection
• Pharmacogenetics
• Phenotype
• Polymorphism, Genetic
• Precision Medicine
• Purine-Pyrimidine Metabolism, Inborn Errors (diagnosis, genetics)
• Risk Assessment
• Risk Factors
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)