1.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 ; Shukuko YOSHIDA ; Yoichi KAKUTA ; Hidezumi KIKUCHI ; Shogo KAWAGUCHI ; Keisuke HASUI ; Tetsuya TATSUTA ; Daisuke CHINDA ; Tatsuya MIKAMI ; Shinsaku FUKUDA
Intestinal Research 2022;20(1):90-100
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.
2.Subtype of Achalasia and Integrated Relaxation Pressure Measured Using the Starlet High-resolution Manometry System: A Multicenter Study in Japan
Tetsuya TATSUTA ; Hiroki SATO ; Yusuke FUJIYOSHI ; Hirofumi ABE ; Akio SHIWAKU ; Junya SHIOTA ; Chiaki SATO ; Masaki OMINAMI ; Yoshitaka HATA ; Hisashi FUKUDA ; Ryo OGAWA ; Jun NAKAMURA ; Yuichiro IKEBUCHI ; Hiroshi YOKOMICHI ; Shinsaku FUKUDA ; Haruhiro INOUE
Journal of Neurogastroenterology and Motility 2022;28(4):562-571
Background/Aims:
ManoScan and Sandhill high-resolution manometry (HRM) systems are used worldwide; however, the diagnosis of achalasia on the Starlet HRM system is not fully characterized. Furthermore, the impact of calcium channel blockers and nitrites in treating achalasia has not been investigated using HRM. Management of recurrent cases is a priority issue, although few studies have examined patient characteristics.
Methods:
We conducted a multicenter, large-scale database analysis. First, the diagnosis of treatment-naive achalasia in each HRM system was investigated. Next, patient characteristics were compared between type I-III achalasia, and the impact of patient characteristics, including calcium channel blocker and nitrite use for integrated relaxation pressure (IRP) values, were analyzed. Finally, patient characteristics with recurrent achalasia were elucidated.
Results:
The frequency of type I achalasia with Starlet was significantly higher than that with ManoScan and Sandhill HRM systems. In achalasia, multivariate analysis identified male sex, advanced age, long disease duration, obesity, type I achalasia, and sigmoid type as risk factors related to normal IRP values (< 26 mmHg). Calcium channel blockers and nitrites use had no significant impact on the IRP values, although achalasia symptoms were indicated to be alleviated. In recurrent cases, the IRP value was significantly lower, and advanced age, long disease duration, and sigmoid type were more common than in treatment-naive patients.
Conclusions
We should cautiously interpret the type of achalasia and IRP values in the Starlet HRM system. Symptoms of recurrent cases are related to disease progression rather than IRP values, which should be considered in decision making.