KMID : 0988920220200010090
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Intestinal Research 2022 Volume.20 No. 1 p.90 ~ p.100
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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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Maeda Takato
Sakuraba Hirotake Hiraga Hiroto Yoshida Shukuko Kakuta Yoichi Kikuchi Hidezumi Kawaguchi Shogo Hasui Keisuke Tatsuta Tetsuya Chinda Daisuke Mikami Tatsuya Fukuda Shinsaku
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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 thiopurine-induced 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-¥á 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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KEYWORD
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NUDT15 heterozygosity, Inflammatory bowel disease, Thiopurine, Maintain remission
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