Current use of pharmacogenetic testing: a national survey of thiopurine methyltransferase testing prior to azathioprine prescription

Abstract

Two-thirds of the consultants surveyed in England are using TPMT enzyme-level testing, prior to AZA treatment. Uptake differs between specialities. High uptake of TPMT enzyme-level testing by dermatologists, compared with gastroenterologists and rheumatologists, may reflect national guidelines advocating its use prior to AZA. Uptake of enzyme-level testing may alter in other specialties as other guidelines are developed.

Pharmacogenomic Biomarkers for Improved Drug Therapy—Recent Progress and Future Developments

“…Importantly, TPMT genotype is a strong predictor for TPMT activity and even patients heterozygous for the TPMT loss-of-function alleles *2A or *3 showed significantly higher incidences of dose reductions due to toxicity [67,68]. Due to the substantial body of evidence that links TPMT genotype to thiopurine treatment outcomes and adverse events, TPMT genotyping is already widely applied in clinical practice [69,70]. The costeffectiveness of preemptive TPMT genotyping remains however inconclusive [71,72] and data from randomized controlled trials is currently lacking.…”

Improving pharmacovigilance in Europe: TPMT genotyping and phenotyping in the UK and Spain

“…28 According to a UK survey, conducted in 2005, TPMT phenotypic testing was used by 68% of respondents, with more dermatologists (95%) using testing compared to gastroenterologists (60%) and rheumatologists (49%). 29 The reasons for this lag in uptake were multifold and probably reflected a lack of knowledge about the utility of testing, a lack of evidence to support routine testing, a lack of clinical testing services, concerns about costs, concerns that TPMT activity did not predict all episodes of leukopenia, 30 and the fact that TPMT testing would not obviate the need for routine post-treatment monitoring. Genotypic TPMT testing is limited, at this stage, in both the UK and Spain for research only.…”

Scientific Challenges and Implementation Barriers to Translation of Pharmacogenomics in Clinical Practice

“…Given these limitations as well as the lack of cost-effectiveness data, it is not surprising that the SSRIs are not good candidates for genotype-based pharmacogenomic therapy and, hence, the recommendation of the EGAPP Working Group. Other pharmacogenomic biomarkers could be better candidates for testing association between specific genotype and clinical phenotype [55][56][57][58][59][60][61][62][63], as indicated by published guidelines. Pharmacogenetic dosing algorithms [37,39] based on the patient's CYP2C9 and VKORC1 genotypes and other nongenetic factors (e.g., age, body size, and concurrent interacting drug) have been used to determine warfarin dosage regimens.…”

“…Although the International Society for Pharmacogenomics recommended incorporating pharmacogenomics education in medical, pharmacy, and health science curricula [109], pharmacogenomics courses or materials have only been included to a variable extent at most pharmacy schools [110,111]. The gap in knowledge can currently be addressed through clinical guidelines available from professional organizations (Clinical Pharmacogenetics Implementation Consortium, the International AIDS Society-USA panel, the European Science Foundation, the British Association of Dermatology, and the Pharmacogenomics Working Group of the Royal Dutch Association for the Advancement of Pharmacy) [55][56][57][58][59][60][61][62][63]112], availability of simple dosing algorithm such as that for warfarin [79], and further effort to include specific dosing recommendation in product label [99,107].…”