Thiopurine S-methyltransferase (TPMT) assessment prior to starting thiopurine drug treatment; a pharmacogenomic test whose time has come

Abstract

Thiopurine S-methyltransferase (TPMT) is involved in the metabolism of thiopurine drugs. Patients that due to genetic variation lack this enzyme or have lower levels than normal, can be adversely affected if normal doses of thiopurines are prescribed. The evidence for measuring TPMT prior to starting patients on thiopurine drug therapy has been reviewed and the various approaches to establishing a service considered. Until recently clinical guidelines on the use of the TPMT varied by medical specialty. This has now changed, with clear guidance encouraging clinicians to use the TPMT test prior to starting any patient on thiopurine therapy. The TPMT test is the first pharmacogenomic test that has crossed from research to routine use. Several analytical approaches can be taken to assess TPMT status. The use of phenotyping supported with genotyping on selected samples has emerged as the analytical model that has enabled national referral services to be developed to a high level in the UK. The National Health Service now has access to cost-effective and timely TPMT assay services, with two laboratories undertaking the majority of the work at national level and with several local services developing. There appears to be adequate capacity and an appropriate internal market to ensure that TPMT assay services are commensurate with the clinical demand.