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
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Roberts,Christopher;Peters,Jaime;Sazonvos,Aleksejs;Goodman,Neil;Sharip,Mohmmed;Smith,Rebecca;Bishara,Maria;Bewshea,Claire;Lin,Simeng;Chanchlani,Neil;Hodges,Phoebe;Badrulhisham,Fakhirah;Saifuddin,Aamir;Carlson,Sean;Centritto,Andrea;Marley,Alexandra;Saad,Muhammad;Sethi-Aora,Karishma;White,Laura;Abdelmeguid,Alaa;Pele,Laetitia;Sebastian,Shaji;Selinger,Christian;Irving,Peter;Fachal,Laura;Walker,Gareth;Palmer,Rachel;Kennedy,Nick;Houghton,Jayne;Doona,Mary;Lamb,Christopher;Hyde,Chris;Parkes,Miles;Goodhand,James;Ahmad,Tariq
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Issue Date
2025
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Article
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Abstract
BACKGROUND: The clinical utility and cost-effectiveness of pre-thiopurine NUDT15 pharmacogenetic testing in European and admixed populations are unknown. AIMS: 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. METHODS: 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. RESULTS: 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.
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Alimentary Pharmacology & Therapeutics
Volume
62
Issue
6