- IBD
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Long-term efficacy and tolerability of dose-adjusted thiopurine treatment in maintaining remission in inflammatory bowel disease patients with NUDT15 heterozygosity
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Takato Maeda, Hirotake Sakuraba, Hiroto Hiraga, Shukuko Yoshida, Yoichi Kakuta, Hidezumi Kikuchi, Shogo Kawaguchi, Keisuke Hasui, Tetsuya Tatsuta, Daisuke Chinda, Tatsuya Mikami, Shinsaku Fukuda
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Intest Res 2022;20(1):90-100. Published online January 22, 2021
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DOI: https://doi.org/10.5217/ir.2020.00133
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 Abstract
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- Background/Aims
Thiopurines are key drugs for inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD). Recently, NUDT15 polymorphism (R139C, c.415C > T) has been shown to be associated with thiopurineinduced adverse events in Asian populations. In patients with the C/T genotype, low-dose thiopurine treatment is recommended, but its long-term efficacy and tolerability remain unclear. This study aimed to uncover the long-term efficacy and appropriate dosage of thiopurine for IBD patients with the C/T genotype.
Methods
A total of 210 patients with IBD (103 UC and 107 CD) determined to have NUDT15 R139C variants were enrolled. Clinical data were retrospectively reviewed from medical records.
Results
Of 46 patients (21.9%) with the C/T genotype, 30 patients (65.2%) were treated with thiopurines. Three of whom (10.0%) discontinued thiopurine treatment due to adverse events and 27 of whom continued. The median maintenance dosage of 6-mercaptopurine was 0.25 mg/kg/day (range, 0.19–0.36 mg/kg/day), and 6-thioguanine nucleotides level was 230 (104–298) pmol/8 × 108 red blood cells. Cumulative thiopurine continuation rates for 120 months for patients with the C/C and C/T genotypes were not significantly different (P= 0.895). Cumulative non-relapse rates in the patients with UC treated with thiopurine monotherapy and surgery-free rates in CD patients treated with combination therapy (thiopurines and anti-tumor necrosis factor-α agents) for maintenance remission were not significantly different at 60 months (C/C vs. C/T, P= 0.339 and P= 0.422, respectively).
Conclusions
Low-dose thiopurine treatment is an effective and acceptable treatment for patients with C/T genotype.
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Citations
Citations to this article as recorded by  - Effectiveness and Tolerability of Methotrexate Combined with Biologics in Patients with Crohn’s Disease: A Multicenter Observational Study
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World Journal of Gastroenterology.2021; 27(19): 2353. CrossRef - Importance of NUDT15 Polymorphisms in Thiopurine Treatments
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