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

Plain Language SummaryThe treatment of patients with inflammatory bowel diseases (ulcerative colitis andCrohn's disease) is based on the severity of the disease. They may need drugs called 'thiopurines' if the disease is not controlled by initial therapy. These drugs have side effects which are related to genetic variations. These side effects can be potentially prevented by testing for these genetic variants prior to starting these drugs. These tests include thiopurine methyltransferase (TPMT) genotype testing and nucleoside diphosphate-linked moiety X-typemotif (NUDT) 15 genotype testing. By doing these tests before starting the drugs, the dose can be modified to prevent side effects on the bone marrow and other tissues. IntroductionThiopurine 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 coveredAn 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 opinionThe 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.