ArticleAlimentary pharmacology & therapeutics2025
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.
Article in Alimentary pharmacology & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Pharmacogenomics of Antineoplastic Therapy in Children: Genetic Determinants of Toxicity and Efficacy.Pharmaceutics · 2026Review
- Real-World Patterns of Immunomodulator Use in Patients with Inflammatory Bowel Disease Receiving Biologic Therapy Under a 54-Week Reimbursement Cap: A 12-Year Retrospective Single-Center Cohort from Taiwan.Journal of inflammation research · 2026Article
- Addressing genetic diversity and health inequities: RELIVAF's proposal for Latin American pharmacogenomic guidelines.Frontiers in pharmacology · 2026Review
- Examination of the TPMT and NUDT15*3 Variants to Predict the Response to Thiopurines in an Italian Cohort of Patients with Inflammatory Bowel Disease.International journal of molecular sciences · 2025Article
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35 authors.
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Abstract
backgroundThe clinical utility and cost-effectiveness of pre-thiopurine NUDT15 pharmacogenetic testing in European and admixed populations are unknown.
aimsTo 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.
methodsRetrospective 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.
resultsOverall, 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 < 0.001). Carriage of a single *3, *6 or *9 variant allele was associated with a shorter time to severe myelosuppression. Numbers needed to genotype to prevent myelosuppression in Europeans and South Asians were 786 and 23. Variant calling using the LAMP assay was fully concordant with Sanger sequencing (n = 154). It improved the safety of thiopurine dosing and was cost-effective when used to reduce the frequency and cost of thiopurine blood monitoring for patients without risk variants.
conclusionWe recommend TPMT and NUDT15 genetic testing in patients of Asian and admixed ancestry. In Europeans, reflex NUDT15 testing should be considered in patients with reduced TPMT activity or loss-of-function genotype. Thiopurines should be avoided in patients with > 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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