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

  • Kevin Zarca
  • Isabelle Durand-Zaleski
  • Marie-Anne Loriot
  • Gilles Chatellier
  • Nicolas PalletEmail author
Original Research Article



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.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Kevin Zarca
    • 1
    • 2
  • Isabelle Durand-Zaleski
    • 1
    • 2
  • Marie-Anne Loriot
    • 3
    • 4
  • Gilles Chatellier
    • 4
    • 5
    • 6
  • Nicolas Pallet
    • 3
    • 4
    Email author
  1. 1.Assistance Publique-Hôpitaux de Paris, DRCI-URC Eco Ile-de-France (AP-HP)ParisFrance
  2. 2.Assistance Publique-Hôpitaux de Paris, service de santé publique, Henri Mondor-Albert-ChenevierCréteilFrance
  3. 3.Service de BiochimieHôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris DescatesParisFrance
  4. 4.Université Paris Descartes, Sorbonne Paris CitéParisFrance
  5. 5.Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Unité de Recherche CliniqueParisFrance
  6. 6.Centre d’Investigation Clinique 1418 (CIC1418)ParisFrance

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