Long-term efficacy and tolerability of dose-adjusted thiopurine treatment in maintaining remission in inflammatory bowel disease patients with NUDT15 heterozygosity

• Published in: Intestinal research (Intest Res) Vol. 20; no. 1; pp. 90 - 101
• Main Authors: Takato Maeda, Hirotake Sakuraba, Hiroto Hiraga, Shukuko Yoshida, Yoichi Kakuta, Hidezumi Kikuchi, Shogo Kawaguchi, Keisuke Hasui, Tetsuya Tatsuta, Daisuke Chinda, Tatsuya Mikami, Shinsaku Fukuda
• Format: Journal Article
• Language: Korean
• Published: 대한장연구학회 30.01.2022
• Subjects: Inflammatory bowel disease; Maintain remission; NUDT15 heterozygosity; Thiopurine
• ISSN: 1598-9100

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/8×10 8 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. (Intest Res 2022;20:90-100)