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Published online February 7, 2022.
Are thiopurines safe and effective for patients with NUDT15 heterozygosity?
Long-term efficacy and tolerability of dose-adjusted thiopurine treatment in maintaining remission in inflammatory bowel disease patients with NUDT15 heterozygosity

Takato Maeda, Hirotake Sakuraba, Hiroto Hiraga, et al. Intest Res. 2022;20(1):90-100

Thiopurines are widely used as steroid-sparing agents for maintaining the remission of inflammatory bowel diseases. Two genes (TPMT and NUTD15) are associated with development of leukopenia by thiopurines. TPMT variants are generally rare among Asian populations, and its testing before thiopurine administration has a limited value. In contrast, NUDT15 genetic variation is more common in East Asians and is one of the predominant genetic causes of thiopurine myelotoxicity. Accordingly, genotyping of NUDT15 R139C has been shown to be the best way to predict thiopurine-induced myelotoxicity in East Asian IBD patients. Patients with NUDT15 C/T or T/T genotypes have a higher risk of developing thiopurine-induced myelotoxicity than those with NUDT15 wild type. Low-dose thiopurines can be administered in patients with the C/T genotype, but its long-term efficacy and tolerability remains unclear.

The present study demonstrates the long-term efficacy and appropriate dosage of thiopurines for IBD patients with the C/T genotype.

  1. The percentages of patients who required discontinuation of thiopurine treatment and the cumulative continuation rate of thiopurine treatment for 120 months were not significantly different between patients with C/C and C/T genotypes.
  2. In patients with UC, the cumulative non-relapse rates for 60 months after initiation of thiopurine monotherapy were not significantly different between patients with C/C and C/T genotypes.
  3. In patients with CD, the cumulative surgery-free rates without change of therapy for 60 months after initiation of thiopurine combination therapy were not significantly different between patients with the C/C and C/T genotypes.
  4. Low-dose thiopurine treatment is an effective and acceptable treatment for patients with C/T genotype.
Read more about the metabolic pathways and appropriate administration of thiopurines in IBD patients.

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