Kevin Zarca1,2, Isabelle Durand-Zaleski1,2, Marie-Anne Loriot3,4, Gilles Chatellier4,5,6, Nicolas Pallet7,8. 1. Assistance Publique-Hôpitaux de Paris, DRCI-URC Eco Ile-de-France (AP-HP), Paris, France. 2. Assistance Publique-Hôpitaux de Paris, service de santé publique, Henri Mondor-Albert-Chenevier, Créteil, France. 3. Service de Biochimie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Descates, 20, rue Leblanc, 75015, Paris, France. 4. Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 5. Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Unité de Recherche Clinique, Paris, France. 6. Centre d'Investigation Clinique 1418 (CIC1418), Paris, France. 7. Service de Biochimie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Descates, 20, rue Leblanc, 75015, Paris, France. Nicolas.pallet@aphp.fr. 8. Université Paris Descartes, Sorbonne Paris Cité, Paris, France. Nicolas.pallet@aphp.fr.
Abstract
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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%.
BACKGROUND: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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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%.
Authors: M Elske van den Akker-van Marle; David Gurwitz; Symone B Detmar; Christine M Enzing; Michael M Hopkins; Emma Gutierrez de Mesa; Dolores Ibarreta Journal: Pharmacogenomics Date: 2006-07 Impact factor: 2.533
Authors: J Kirchgesner; M Lemaitre; A Rudnichi; A Racine; M Zureik; F Carbonnel; R Dray-Spira Journal: Aliment Pharmacol Ther Date: 2016-10-26 Impact factor: 8.171
Authors: Christine Hartford; Erick Vasquez; Matthias Schwab; Mathew J Edick; Jerold E Rehg; Gerard Grosveld; Ching-Hon Pui; William E Evans; Mary V Relling Journal: Cancer Res Date: 2007-05-15 Impact factor: 12.701