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
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Publication date
2014-02-01
Authors
Coenen, M.
Van Marrewijk, C.
Derijks, L.
Vermeulen, S.
Wong, D.
Klungel, Olaf H.
Verbeek, A.
Hooymans, P.
Scheffer, H.
Guchelaar, H.-J.
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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
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, SDG 3 - Good Health and Well-being
Citation
Coenen, M, Van Marrewijk, C, Derijks, L, Vermeulen, S, Wong, D, Klungel, O, Verbeek, A, Hooymans, P, Scheffer, H, Guchelaar, H-J, Franke, B & De Jong, D 2014, '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', Journal of Crohn's & Colitis, vol. 8, OP006, pp. 4. https://doi.org/10.1002/cpt.56