{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:43:57Z","timestamp":1790869437014,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MRC\/X502820\/1"],"award-info":[{"award-number":["MRC\/X502820\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000737","name":"University of Exeter","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000737","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The clinical utility and cost\u2010effectiveness of pre\u2010thiopurine <jats:italic>NUDT15<\/jats:italic> pharmacogenetic testing in European and admixed populations are unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To report the prevalence, penetrance, expressivity, and pathogenicity of <jats:italic>NUDT15<\/jats:italic> variant allele carriage and the diagnostic accuracy and cost\u2010effectiveness of an inexpensive loop\u2010mediated isothermal amplification (LAMP) test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Retrospective case\u2010matched cohort study of rates of severe myelosuppression in patients with and without loss\u2010of\u2010function <jats:italic>NUDT15<\/jats:italic> variant allele(s) treated with a thiopurine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 1.3% of Europeans and 11.7% of South Asians carried a variant allele. Severe myelosuppression was associated with <jats:italic>NUDT15<\/jats:italic> variant allele carriage (11.3% vs 0.95%; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). 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 (<jats:italic>n<\/jats:italic>\u2009=\u2009154). It improved the safety of thiopurine dosing and was cost\u2010effective when used to reduce the frequency and cost of thiopurine blood monitoring for patients without risk variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We recommend <jats:italic>TPMT<\/jats:italic> and <jats:italic>NUDT15<\/jats:italic> genetic testing in patients of Asian and admixed ancestry. In Europeans, reflex <jats:italic>NUDT15<\/jats:italic> testing should be considered in patients with reduced TPMT activity or loss\u2010of\u2010function genotype. Thiopurines should be avoided in patients with &gt;\u20091 <jats:italic>NUDT15<\/jats:italic> variant allele and in patients with both <jats:italic>NUDT15<\/jats:italic> and <jats:italic>TPMT<\/jats:italic> variant alleles. In patients with a single <jats:italic>NUDT15<\/jats:italic> variant allele, we recommend thiopurine dose reduction (&lt;\u20091\u2009mg\/kg\/day) and intensified blood test monitoring.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.70232","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T07:33:44Z","timestamp":1750664024000},"page":"630-645","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Clinical Utility and Cost\u2010Effectiveness of Pretreatment <i>NUDT15<\/i> Pharmacogenetic Testing to Prevent Thiopurine\u2010Induced Myelosuppression: A Genotype\u2010First Reverse Phenotyping Cohort Study Within the <scp>UK NIHR<\/scp> Inflammatory Bowel Disease Bioresource"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6215-8044","authenticated-orcid":false,"given":"Christopher","family":"Roberts","sequence":"first","affiliation":[{"name":"University of 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