Clinical Utility and Cost-Effectiveness of Pretreatment NUDT15 Pharmacogenetic Testing to Prevent Thiopurine-Induced Myelosuppression: A Genotype-First Reverse Phenotyping Cohort Study Within the UK NIHR Inflammatory Bowel Disease Bioresource

Abstract

Background: The clinical utility and cost-effectiveness of pre-thiopurine NUDT15 pharmacogenetic testing in European and admixed populations are unknown. Aim(s): To report the prevalence, penetrance, expressivity, and pathogenicity of NUDT15 variant allele carriage and the diagnostic accuracy and cost-effectiveness of an inexpensive loop-mediated isothermal amplification (LAMP) test. Method(s): Retrospective case-matched cohort study of rates of severe myelosuppression in patients with and without loss-of-function NUDT15 variant allele(s) treated with a thiopurine. Result(s): Overall, 1.3% of Europeans and 11.7% of South Asians carried a variant allele. Severe myelosuppression was associated with NUDT15 variant allele carriage (11.3% vs 0.95%; p 1 NUDT15 variant allele and in patients with both NUDT15 and TPMT variant alleles. In patients with a single NUDT15 variant allele, we recommend thiopurine dose reduction (< 1 mg/kg/day) and intensified blood test monitoring.Copyright © 2025 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.