Modeling the Outcome of Systematic TPMT Genotyping or Phenotyping Before Azathioprine Prescription: A Cost-Effectiveness Analysis View Full Text


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Article Info

DATE

2019-04-08

AUTHORS

Kevin Zarca, Isabelle Durand-Zaleski, Marie-Anne Loriot, Gilles Chatellier, Nicolas Pallet

ABSTRACT

BackgroundThiopurine 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.ObjectiveOur 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.MethodsA 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.ResultsThe 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.ConclusionThe 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%. More... »

PAGES

429-438

References to SciGraph publications

  • 2017-06-13. Cost-effectiveness of pharmacogenetic-guided treatment: are we there yet? in THE PHARMACOGENOMICS JOURNAL
  • 2008-06-28. Thiopurine-Induced Myelotoxicity in Patients With Inflammatory Bowel Disease: A Review in THE AMERICAN JOURNAL OF GASTROENTEROLOGY
  • 2005-10-01. A Cost-Effectiveness Analysis of Alternative Disease Management Strategies in Patients with Crohn's Disease Treated with Azathioprine or 6-Mercaptopurine in THE AMERICAN JOURNAL OF GASTROENTEROLOGY
  • 2010-01-12. Thiopurine S-Methyltranferase Testing in Idiopathic Pulmonary Fibrosis: A Pharmacogenetic Cost-Effectiveness Analysis in LUNG
  • 2004-03-12. Phenotype and genotype for thiopurine methyltransferase activity in the French Caucasian population: impact of age in EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
  • 2000-04-01. Genetic polymorphism of thiopurine methyltransferase and its clinical relevance for childhood acute lymphoblastic leukemia in LEUKEMIA
  • 2016-02-15. NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity in NATURE GENETICS
  • 2016-04-13. 6-Mercaptopurine attenuates tumor necrosis factor-α production in microglia through Nur77-mediated transrepression and PI3K/Akt/mTOR signaling-mediated translational regulation in JOURNAL OF NEUROINFLAMMATION
  • 2006-08. Pharmacoeconomic Analyses of Azathioprine, Methotrexate and Prospective Pharmacogenetic Testing for the Management of Inflammatory Bowel Disease in PHARMACOECONOMICS
  • 2008-01. Thiopurines in current medical practice: molecular mechanisms and contributions to therapy-related cancer in NATURE REVIEWS CANCER
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    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1113301248

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30963516


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