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Time to incorporate preemptive NUDT15 testing before starting thiopurines

Time to incorporate preemptive NUDT15 testing before starting thiopurines in inflammatory bowel disease in Asia and beyond: a review.

Devendra Desai, Anuraag Jena, Vishal Sharma, Toshifumi Hibi

Published in Jul 2023, Expert review of clinical pharmacology.



Thiopurine toxicity is related to genetic polymorphism. Thiopurine methyltransferase (TPMT) variants do not explain thiopurine toxicity in more than half of patients. Asians, despite the low prevalence of TPMT variants, are more susceptible to thiopurine toxicity. Since 2014, studies from many Asian countries have shown a strong association between nucleoside diphosphate-linked moiety X-type motif (NUDT) 15 polymorphism and thiopurine-induced myelotoxicity.

Areas covered:

An English language literature search was performed for TPMT and NUDT15 genetic variants in inflammatory bowel disease and other diseases. This article discusses the merits of preemptive NUDT15 and TPMT testing in Asian and non-Asian IBD populations.

Expert opinion:

The NUDT polymorphism occurs in up to 27% of the Asian and Hispanic population. Hematological toxicity occurs in up to one-third of patients with this genetic variant. Given this, preemptive testing for NUDT15 variant is worthwhile and is probably more cost-effective than TPMT testing in these groups. Prevalence of NUDT15 variants is low in non-Finnish European population, but NUDT15 variants have been linked to myelotoxicity along with TPMT genetic variants. NUDT15 preemptive testing should be considered in the migrant Asian population in Europe and North America and in Caucasian populations who develop myelotoxicity.


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