Combination of NUDT15 genotyping and 6-thioguinine levelscan better predict leucopenia in NUDT15 intermediate metobolizers
Pal P, MD,MRCP, reviewing Kang B et al in Alimentary pharmacology and Therapeutics, August 2020
Recent studies have reported that a novel Nudix Hydrolase 15 (NUDT 15) gene variant (C415T) can predict thiopurine induced leucopenia in Asian patients. In a retrospective study in 167 Korean paediatric IBD patients, homozygous, heterozygous NUDT15 polymorphism and wild genotype had 100%, 44% and 16% leucopenia rates. In patients with heterozygous NUDT polymorphism, 6-thioguinine (6-TGN) cut off level of <167.1 pmol/8 × 108 RBC can reduce leucopenia rates to <15%. NUDT15 polymorphism was significantly associated with time-to-leucopenia with azathioprine.
The incidence of AZA induced leucopenia has been noted in more than 30% of Asians, much higher than the West (5%). Most Asian patients have wild type TPMT (>90%) and less than a quarter of those who develop leucopenia have TMPT polymorphisms. Hence NUDT15 polymorphism is increasingly being tested to predict thiopurine induced leucopenia in asian population. The homozygous variant of NUDT15 polymorphism predict leucopenia with high accuracy, but 6-TGN measurement can help reduce rates of leucopenia in heterozygous variants.
Kang B, Kim TJ, Choi J, et al. Adjustment of azathioprine dose should be based on a lower 6-TGN target level to avoid leucopenia in NUDT15 intermediate metabolisers. Aliment Pharmacol Ther. 2020;52(3):459-470. doi:10.1111/apt.15810