Modeling the Outcome of Systematic TPMT Genotyping or Phenotyping Before Azathioprine Prescription: A Cost-Effectiveness Analysis
- 20 Downloads
Thiopurine S-methyltransferase (TPMT) testing, either by genotyping or phenotyping, can reduce the incidence of adverse severe myelotoxicity episodes induced by azathioprine. The comparative cost-effectiveness of TPMT genotyping and phenotyping are not known.
Our aim was to assess the cost-effectiveness of phenotyping-based dosing of TPMT activity, genotyping-based screening and no screening (reference) for patients treated with azathioprine.
A decision tree was built to compare the conventional weight-based dosing strategy with phenotyping and with genotyping using a micro-simulation model of patients with inflammatory bowel disease from the perspective of the French health care system. The time horizon was set up as 1 year. Only direct medical costs were used. Data used were obtained from previous reports, except for screening test and admission costs, which were from real cases. The main outcome was the cost-effectiveness ratios, with an effectiveness criterion of one averted severe myelotoxicity episode.
The total expected cost of the no screening strategy was €409/patient, the total expected cost of the phenotyping strategy was €427/patient, and the total expected cost of the genotyping strategy was €476/patient. The incremental cost-effectiveness ratio was €2602/severe myelotoxicity averted in using the phenotyping strategy, and €11,244/severe myelotoxicity averted in the genotyping strategy compared to the no screening strategy. At prevalence rates of severe myelotoxicity > 1%, phenotyping dominated genotyping and conventional strategies.
The phenotype-based strategy to screen for TPMT deficiency dominates (cheaper and more effective) the genotype-based screening strategy in France. Phenotype-based screening dominates no screening in populations with a prevalence of severe myelosuppression due to azathioprine of > 1%.
Compliance with Ethical Standards
No funding to declare.
Conflict of interest
The authors (KV, IDZ, MAL, GC and NP) declare that they have no competing interests.
Ethical approval and informed consent
This study did not involve human subjects.
- 7.Stet EH, Abreu RAD, Janssen YP, Bökkerink JP, Trijbels FJ. A biochemical basis for synergism of 6-mercaptopurine and mycophenolic acid in Molt F4, a human malignant T-lymphoblastic cell line. Biochem Biophys Acta. 1993;1180:277–82.Google Scholar
- 8.Huang H-Y, Chang H-F, Tsai M-J, Chen J-S, Wang M-J. 6-mercaptopurine attenuates tumor necrosis factor-α production in microglia through Nur77-mediated transrepression and PI3K/Akt/mTOR signaling-mediated translational regulation. J Neuroinflamm. 2016;13(78):1–20.Google Scholar
- 9.Zochowska D, Zegarska J, Hryniewiecka E, Samborowska E, Jazwiec R, Tszyrsznic W, et al. Determination of concentrations of azathioprine metabolites 6-thioguanine and 6-methylmercaptopurine in whole blood with the use of liquid chromatography combined with mass spectrometry. Transplant Proc. 2016;48:1836–9.CrossRefGoogle Scholar
- 35.Schaeffeler E, Fischer C, Brockmeier D, Wernet D, Moerike K, Eichelbaum M, et al. Comprehensive analysis of thiopurine S-methyltransferase phenotype-genotype correlation in a large population of German-Caucasians and identification of novel TPMT variants. Pharmacogenetics. 2004;14(7):407–17.CrossRefGoogle Scholar
- 36.Kirchgesner J, Lemaitre M, Rudnichi A, Racine A, Zureik M, Carbonnel F, et al. Therapeutic management of inflammatory bowel disease in real-life practice in the current era of anti-TNF agents: analysis of the French administrative health databases 2009–2014. Aliment Pharmacol Ther. 2017;45(1):37–49.CrossRefGoogle Scholar
- 41.van den Akker-van Marle ME, Gurwitz D, Detmar SB, Enzing CM, Hopkins MM, Gutierrez de Mesa E, et al. Cost-effectiveness of pharmacogenomics in clinical practice: a case study of thiopurine methyltransferase genotyping in acute lymphoblastic leukemia in Europe. Pharmacogenomics. 2006;7(5):783–92.CrossRefGoogle Scholar
- 50.Gisbert JP, Luna M, Mate J, Gonzalez-Guijarro L, Cara C, Pajares JM. Choice of azathioprine or 6-mercaptopurine dose based on thiopurine methyltransferase (TPMT) activity to avoid myelosuppression. A prospective study. Hepatogastroenterology. 2006;53(69):399–404.Google Scholar
- 51.Briggs A, Sculpher M, Claxton K. Decision modelling for health economic evaluation. Oxford: Oxford University Press; 2006.Google Scholar