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Cost-effectiveness analysis of pretreatment screening for NUDT15 defective alleles.
- Source :
-
Pharmacogenetics and genomics [Pharmacogenet Genomics] 2020 Oct; Vol. 30 (8), pp. 175-183. - Publication Year :
- 2020
-
Abstract
- Background: Nucleotide triphosphate diphosphatase (NUDT15) genetic testing in addition to thiopurine methyl transferase (TPMT) is recommended to reduce the incidence of adverse severe myelotoxicity episodes induced by thiopurines.<br />Objective: We assessed the cost-effectiveness ratio of combined screening for TMPT and NUDT15 defective alleles by genotyping or next-generation sequencing (NGS) using TPMT genotyping as the reference. Because of the genetic differences in thiopurine toxicity, we tested the screening strategies on individuals of Caucasian and Asian descent.<br />Methods: A decision tree compared conventional TPMT genotyping with combined TPMT/NUDT15 genotyping or NGS using a Monte-Carlo microsimulation model of patients with inflammatory bowel disease. The main outcome was the incremental cost-effectiveness ratios (ICER) with effectiveness being one averted severe myelotoxicity requiring hospitalization.<br />Results: The mean estimated cost of the TPMT genotyping for one year is twice in Asian compared with Caucasian patients (980 euro/patient versus 488 euro/patient), and the effectiveness of TPMT genotyping in Caucasian avoided 43 severe myelosuppressions per 10 000 patients over a year compared with 3.6 per 10 000 patients in Asian. Combined TPMT/NUDT15 genotyping compared with TPMT genotyping had an ICER of 7 491 281 euro per severe myelotoxicity averted in Caucasian, compared to 619 euro in Asian. The ICER of the NGS-based screening strategy is disproportionally high compared with genotyping, irrespective of ethnic descent.<br />Conclusion: With a low cost-effectiveness threshold, combined screening for NUDT15 and TPMT defective alleles is cost-effective compared to TMPT screening alone in patients of Asian descent, but is unrealistic from a cost-effectiveness point of view in Caucasians.
- Subjects :
- Asian People genetics
Azathioprine pharmacokinetics
Bone Marrow Diseases chemically induced
Bone Marrow Diseases genetics
Cost-Benefit Analysis
Decision Trees
Drug Hypersensitivity genetics
France ethnology
Genotyping Techniques methods
High-Throughput Nucleotide Sequencing economics
Humans
Inflammatory Bowel Diseases genetics
Monte Carlo Method
Sequence Analysis, DNA economics
White People genetics
Azathioprine adverse effects
Bone Marrow Diseases diagnosis
Drug Hypersensitivity diagnosis
Genotyping Techniques economics
Inflammatory Bowel Diseases drug therapy
Methyltransferases genetics
Pyrophosphatases deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 1744-6880
- Volume :
- 30
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Pharmacogenetics and genomics
- Publication Type :
- Academic Journal
- Accession number :
- 32433339
- Full Text :
- https://doi.org/10.1097/FPC.0000000000000410