Cost-effectiveness analysis of pretreatment screening for NUDT15 defective alleles. Issue 8 (October 2020)

• Record Type: Journal Article
• Authors: Zarca, Kevin; Chansavang, Albain; Loriot, Marie-Anne; Durand-Zaleski, Isabelle; Pallet, Nicolas
• Is Part Of: Pharmaocogenetics and genomics. Volume 30:Issue 8(2020)
• Publication Date: 2020-10
• Subjects: cost-effectiveness -- nucleotide triphosphate diphosphatase -- thiopurine methyl transferase -- thiopurines; Pharmacogenetics -- Periodicals; Pharmacogenomics -- Periodicals; Genetic toxicology -- Periodicals; Biomedical genetics -- Periodicals; 615.7
• DOI: 10.1097/FPC.0000000000000410
• Languages: English
• ISSNs: 1744-6872

Abstract

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. 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. 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. 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. 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.