Personalized thiopurine dosing based on TPMT genotyping reduces leucopenia occurrence and results in cost-savings in IBD patients. Results from a randomized trial in the Netherlands

M. Coenen, C. Van Marrewijk, L. Derijks, S. Vermeulen, D. Wong, O. Klungel, A. Verbeek, P. Hooymans, H. Scheffer, H.-J. Guchelaar, B. Franke, D. De Jong

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: More than 20% of inflammatory bowel diseases (IBD) patients discontinue thiopurine therapy due to severe adverse drug reactions among which leucopenia is one of the most serious. Thiopurine S-methyltransferase (TPMT) pharmacogenetics has been proven effective for optimizing azathioprine/mercaptopurine safety. Nevertheless, TPMT screening is used in clinical practice on a very limited scale. The aim of our study was to assess whether pre-treatment TPMT genotype-based dosing reduces the occurrence of leucopenia and whether this strategy is cost-effective. Methods: We performed a randomized trial in thiopurine naïve IBD patients starting on thiopurine treatment [the Dutch “Thiopurine response Optimization by Pharmacogenetic testing in Inflammatory bowel disease Clinics” (TOPIC) study (ClinicalTrials.gov: NCT00521950)]. Patients were randomly assigned to pre-treatment screening for three common variants in TPMT (TPMT∗2, ∗3A and ∗3C) or standard thiopurine treatment. Patients heterozygous for a TPMT variant received 50% of the standard thiopurine dose, patients homozygous for the tested variants 0-10%. We compared pre-treatment genotyped patients with patients receiving standard dose for the occurrence of leucopenia (leucocyte count
Original languageEnglish
Article numberOP006
Pages (from-to)4
Number of pages1
JournalJournal of Crohn's & Colitis
Volume8
DOIs
Publication statusPublished - 1 Feb 2014

Keywords

  • mercaptopurine
  • thiopurine methyltransferase
  • genotype
  • leukopenia
  • cost control
  • patient
  • human
  • Netherlands
  • colitis
  • screening
  • risk
  • inflammatory bowel disease
  • control group
  • therapy
  • cost effectiveness analysis
  • leukocyte count
  • hospital
  • clinical practice
  • safety
  • pharmacogenetics
  • arm
  • genetic variability
  • adverse drug reaction

Fingerprint

Dive into the research topics of 'Personalized thiopurine dosing based on TPMT genotyping reduces leucopenia occurrence and results in cost-savings in IBD patients. Results from a randomized trial in the Netherlands'. Together they form a unique fingerprint.

Cite this