Prevalence and impact of Thiopurine S-methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15) polymorphisms on the occurrence of myelosuppression in Thai patients with inflammatory bowel disease receiving thiopurine therapy.

NUDT15, TPMT

NUDT15 and TPMT variants associated with thiopurine-induced myelosuppression

This retrospective Thai cohort studied the association between TPMT and NUDT15 polymorphisms and thiopurine-induced myelosuppression in 124 patients with inflammatory bowel disease (73 Crohn's disease, 51 ulcerative colitis) receiving azathioprine, at an initial dose of 0.87 mg/kg/day titrated to 1.54 mg/kg/day. TPMT variants were found in 6 patients (4.8%; 5 heterozygous, 1 homozygous) and NUDT15 variants in 21 patients (16.9%; 20 heterozygous, 1 homozygous). Over 7.6 years of follow-up, 12 patients (9.7%) developed myelosuppression, with no significant difference by TPMT genotype but a significant difference by NUDT15 genotype (7.8% in wild-type versus 19% in heterozygous or homozygous carriers). The only patient homozygous for a NUDT15 variant developed myelosuppression within the first month. The authors suggest considering pre-treatment genotyping, taking into account local variant prevalence, test availability and cost-effectiveness.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Nothing new biologically: the link between NUDT15 and thiopurine toxicity is established, and the value lies in the frequency of NUDT15 carriers (16.9%), more than three times that of TPMT carriers (4.8%), in an under-documented Southeast Asian population. With only 12 events, the estimates remain fragile, but the practical message is clear for patients of Asian ancestry: genotyping restricted to TPMT misses most of the risk.

Analysis by Dr Thibaut Benquey