title: Improving pharmacovigilance in Europe: TPMT genotyping and phenotyping in the UK and Spain.
abstract: Thiopurine S-methyltransferase (TPMT) is the rate-limiting step in the conversion of thiopurine drugs including azathioprine (AZA) to inactive metabolites. Heritable deficiency of TPMT activity increases risk for adverse events, most notably, myelosuppression leading to leukopenia and neutropenic sepsis. The reported European Commission study was undertaken to identify current evidence for the clinical utility of testing for TPMT status and extent of uptake, by either genotyping or phenotyping, in the clinical setting. Data presented here for the UK and Spain indicate that there has been a considerable increase in the uptake of TPMT testing in recent years. There are some data that support routine TPMT testing before AZA prescribing for reducing AZA-related adverse events. Key data include evidence in favor of TPMT testing in addition to the current practice of routine monitoring for reducing the number of AZA-related episodes of myelosuppression, averting deaths from neutropenic sepsis and improving health-related quality of life. Further data are needed for determining the cost-effectiveness of routine TPMT testing.
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Tel-Aviv University, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Gurwitz
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodríguez-Antona
authors.forename: Katherine
authors.initials: K
authors.lastname: Payne
authors.forename: William
authors.initials: W
authors.lastname: Newman
authors.forename: Javier P
authors.initials: JP
authors.lastname: Gisbert
authors.forename: Emma Gutiérrez
authors.initials: EG
authors.lastname: de Mesa
authors.forename: Dolores
authors.initials: D
authors.lastname: Ibarreta
mesh_terms: D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D003362:Cost-Benefit Analysis; D016903:Drug Monitoring / Q000191:economics / Q000379:methods* / Q000639:trends; D005060:Europe; D005500:Follow-Up Studies; D005820:Genetic Testing / Q000191:economics / Q000379:methods; D005838:Genotype; D006801:Humans; D008780:Methyltransferases / Q000235:genetics* / Q000502:physiology; D008954:Models, Biological; D010597:Pharmacogenetics / Q000379:methods; D010641:Phenotype; D013030:Spain; D006113:United Kingdom
chemical_list: D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine