Long-term efficacy and tolerability of dose-adjusted thiopurine treatment in maintaining remission in inflammatory bowel disease patients with NUDT15 heterozygosity
- Author:
Takato MAEDA
1
;
Hirotake SAKURABA
;
Hiroto HIRAGA
;
Shukuko YOSHIDA
;
Yoichi KAKUTA
;
Hidezumi KIKUCHI
;
Shogo KAWAGUCHI
;
Keisuke HASUI
;
Tetsuya TATSUTA
;
Daisuke CHINDA
;
Tatsuya MIKAMI
;
Shinsaku FUKUDA
Author Information
- Publication Type:Original Article
- From:Intestinal Research 2022;20(1):90-100
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
