Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Israel.
J Gastroenterol Hepatol. 2019 Apr;34(4):679-685. doi: 10.1111/jgh.14465. Epub 2018 Sep 27.
Measuring 6-thioguanine nucleotide (6-TGN) level is useful in optimizing dose of azathioprine (AZA) and monitoring for toxicity. Lower dose of AZA was suggested for maintenance of clinical remission in Asian patients than Caucasian patients with Crohn's disease (CD). However, the optimal 6-TGN threshold required in Asian patients is undetermined. Therefore, the aim of the current study is to explore the optimal 6-TGN threshold required in Asian patients with CD for maintenance of clinical remission.
A retrospective cohort study in a tertiary referral center recruited 252 CD patients. The primary endpoint was disease relapse. The levels of 6-TGN and AZA dose were compared in remission group and relapse group. Remission rate was compared across the increased 6-TGN level and dose range.
Patients with 6-TGN range of 0-180.94 pmol/8 × 10 red blood cells (RBC) had lower remission rate compared with those with 180.94-255.50 pmol/8 × 10 RBC (P = 0.020). Quartile analysis showed that increasing 6-TGN level beyond 180 pmol/8 × 10 RBC produced negligible gain in rate of remission. Frequency of adverse events significantly increased in patients with 6-TGN level > 355 pmol/8 × 10 RBC (8.0% with 6-TGN > 355 pmol/8 × 10 RBC vs 2.7% with 6-TGN < 355 pmol/8 × 10 RBC, P = 0.035).
Our study suggested that optimal 6-TGN threshold required to maintain clinical remission in Chinese patients was 180-355 pmol/8 × 10 RBC.
测量 6-硫鸟嘌呤核苷酸(6-TGN)水平有助于优化硫唑嘌呤(AZA)的剂量并监测其毒性。与白人克罗恩病(CD)患者相比,亚洲 CD 患者维持临床缓解所需的 AZA 剂量较低。然而,亚洲患者所需的最佳 6-TGN 阈值尚未确定。因此,本研究旨在探讨亚洲 CD 患者维持临床缓解所需的最佳 6-TGN 阈值。
本研究是在一家三级转诊中心进行的回顾性队列研究,共纳入 252 例 CD 患者。主要终点是疾病复发。比较缓解组和复发组的 6-TGN 水平和 AZA 剂量。比较不同 6-TGN 水平和剂量范围内的缓解率。
6-TGN 范围为 0-180.94 pmol/8×10 个红细胞(RBC)的患者缓解率低于 6-TGN 范围为 180.94-255.50 pmol/8×10 RBC 的患者(P=0.020)。四分位分析表明,6-TGN 水平超过 180 pmol/8×10 RBC 后,缓解率的增加微不足道。6-TGN 水平>355 pmol/8×10 RBC 的患者不良事件的发生率显著增加(6-TGN>355 pmol/8×10 RBC 的患者为 8.0%,6-TGN<355 pmol/8×10 RBC 的患者为 2.7%,P=0.035)。
本研究提示,中国患者维持临床缓解所需的最佳 6-TGN 阈值为 180-355 pmol/8×10 RBC。