The cost-effectiveness of a pharmacogenetic test: a trial-based evaluation of TPMT genotyping for azathioprine.
BACKGROUND
Thiopurine-methyl transferase (TPMT) testing prior to the prescription of azathioprine in autoimmune diseases is one of the few examples of a pharmacogenetic test that has made the transition from research into clinical practice. TPMT testing could lead to improved prescribing of azathioprine resulting in a reduction in adverse drug reactions as well as an improvement in effectiveness. When allocating scarce resources robust evidence on cost-effectiveness is required.


OBJECTIVE
This study aimed to evaluate the cost-effectiveness of a TPMT genotyping test to inform azathioprine prescribing in autoimmune diseases. The secondary aim of this study was to demonstrate the complexity of undertaking a trial-based evaluation of a pharmacogenetic test.


METHODS
A prospective economic evaluation was conducted alongside the TARGET (TPMT: Azathioprine Response to Genotype and Enzyme Testing) study, a pragmatic controlled trial that randomized (1:1) patients to undergo TPMT genotyping before azathioprine (n = 167) or current practice (n = 166). Assuming the UK health service perspective and a time horizon of 4 months, resource-use and health status data were collected prospectively for all recruited patients.


RESULTS
The mean incremental cost for TPMT genotyping and subsequent care pathways compared with current practice for the 4-month follow-up was -£421.06 (95% confidence interval -£925.15 to £89.75). Mean incremental quality-adjusted life-years were close to zero but negative: -0.008 (95% confidence interval -0.017 to 0.0002). Assuming a threshold of £20,000 per quality-adjusted life-year, the expected incremental net benefit of introducing the test is £256.89 (95% CI -£425.94 to £932.86).


CONCLUSIONS
TPMT genotyping potentially offers a less expensive alternative than current practice, but it may also have a small but negative effect on health status. These findings are associated with significant uncertainty, and the causal effect of TPMT genotyping on changes in health status and health care resource use remains uncertain. The results from this study therefore pose a difficult challenge to decision makers.
The University of Manchester, Manchester, UK.
Alexander J
AJ
Thompson
Manchester Centre for Genomic Medicine, University of Manchester and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
William G
WG
Newman
The University of Nottingham, Nottingham, UK.
Rachel A
RA
Elliott
The University of Manchester, Manchester, UK.
Stephen A
SA
Roberts
Manchester Centre for Genomic Medicine, University of Manchester and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
Karen
K
Tricker
The University of Manchester, Manchester, UK. Electronic address: katherine.payne@manchester.ac.uk.
Katherine
K
Payne
D001327:Autoimmune Diseases / Q000188:drug therapy*; D001379:Azathioprine / Q000191:economics* / Q000494:pharmacology*; D003362:Cost-Benefit Analysis; D016527:Drug Costs; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000191:economics* / Q000494:pharmacology*; D008297:Male; D018803:Models, Economic; D010597:Pharmacogenetics / Q000191:economics* / Q000379:methods*; D011446:Prospective Studies; D019057:Quality-Adjusted Life Years; D016032:Randomized Controlled Trials as Topic; D011795:Surveys and Questionnaires; D006113:United Kingdom
D007166:Immunosuppressive Agents; D001379:Azathioprine
RCT; TPMT; cost-effectiveness; pharmacogenetics; prospective