Genotype-Guided Thiopurine Dosing Does not Lead to Additional Costs in Patients With Inflammatory Bowel Disease

Author:

Sluiter Reinier L1,van Marrewijk Corine2,de Jong Dirk3,Scheffer Hans2,Guchelaar Henk-Jan4,Derijks Luc5,Wong Dennis R6,Hooymans Piet6,Vermeulen Sita H12,Verbeek André L M1,Franke Barbara2,van der Wilt Gert Jan1,Kievit Wietske1,Coenen Marieke J H2

Affiliation:

1. Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands

2. Department of Human Genetics, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands

3. Department of Gastroenterology, Radboud Institute Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands

4. Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands

5. Department of Clinical Pharmacy, Máxima Medical Center, Veldhoven, The Netherlands

6. Department of Clinical Pharmacy, Pharmacology and Toxicology, Zuyderland Medical Center, Sittard-Geleen, The Netherlands

Abstract

Abstract Background and Aims Decreased thiopurine S-methyltransferase [TPMT] enzyme activity increases the risk of haematological adverse drug reactions [ADRs] in patients treated with thiopurines. Clinical studies have shown that in patients with inflammatory bowel disease [IBD], pharmacogenetic TPMT-guided thiopurine treatment reduces this risk of ADRs. The aim of this study was to investigate whether this intervention impacts on healthcare costs and/or quality of life. Methods An a priori defined cost-effectiveness analysis was conducted in the Thiopurine response Optimization by Pharmacogenetic testing in Inflammatory bowel disease Clinics [TOPIC] trial, a randomized controlled trial performed in 30 Dutch hospitals. Patients diagnosed with IBD [age ≥18 years] were randomly assigned to the intervention [i.e. pre-treatment genotyping] or control group. Total costs in terms of volumes of care, and effects in quality-adjusted life years [QALYs], based on EuroQol-5D3L utility scores, were measured for 20 weeks. Mean incremental cost savings and QALYs with confidence intervals were calculated using non-parametric bootstrapping with 1000 replications. Results The intervention group consisted of 381 patients and the control group 347 patients. The mean incremental cost savings were €52 per patient [95% percentiles −682, 569]. Mean incremental QALYs were 0.001 [95% percentiles −0.009, 0.010]. Sensitivity analysis showed that the results were robust for potential change in costs of screening, costs of biologicals and costs associated with productivity loss. Conclusions Genotype-guided thiopurine treatment in IBD patients reduced the risk of ADRs among patients carrying a TPMT variant, without increasing overall healthcare costs and resulting in comparable quality of life, as compared to standard treatment.

Funder

Netherlands Organization for Health Research and Development

Publisher

Oxford University Press (OUP)

Subject

Gastroenterology,General Medicine

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