低剂量硫唑嘌呤对维持激素依赖型溃疡性结肠炎的缓解有效：一项基于中国全地区人群的炎症性肠病登记研究结果
Low-dose azathioprine is effective in maintaining remission in steroid-dependent ulcerative colitis: results from a territory-wide Chinese population-based IBD registry.
作者信息
Shi Hai Yun, Chan Francis K L, Leung Wai Keung, Li Michael K K, Leung Chi Man, Sze Shun Fung, Ching Jessica Y L, Lo Fu Hang, Tsang Steven W C, Shan Edwin H S, Mak Lai Yee, Lam Belsy C Y, Hui Aric J, Chow Wai Hung, Wong Marc T L, Hung Ivan F N, Hui Yee Tak, Chan Yiu Kay, Chan Kam Hon, Loo Ching Kong, Ng Carmen K M, Lao Wai Cheung, Harbord Marcus, Wu Justin C Y, Sung Joseph J Y, Ng Siew C
机构信息
Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China Department of Gastroenterology & Hepatology, Beijing Friendship Hospital, Capital Medical University, Beijing Digestive Disease Center, National Clinical Research Center for Digestive Diseases, China.
Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
出版信息
Therap Adv Gastroenterol. 2016 Jul;9(4):449-56. doi: 10.1177/1756283X16643509. Epub 2016 Apr 19.
BACKGROUND
Whether low-dose azathioprine (AZA) is effective in maintaining remission in patients with steroid-dependent ulcerative colitis (UC) remains unclear. We assessed the efficacy and safety of low-dose AZA in a Chinese population with UC.
METHODS
We identified steroid-dependent UC patients in clinical remission on AZA maintenance therapy from a territory-wide IBD Registry. Standard- and low-dose AZA were defined as at least 2 mg/kg/day and less than 2 mg/kg/day, respectively. Relapse rates were analyzed by Kaplan-Meier analysis and compared using log-rank test.
RESULTS
Among 1226 UC patients, 128 (53% male, median duration on AZA 44 months) were included. Median maintenance AZA dose was 1.3 mg/kg/day. 97.7% of the patients were on concomitant oral 5-aminosalicylic acid. Cumulative relapse-free rates in patients on standard-dose and low-dose AZA were 71.2%, 52.8% and 45.2%, and 71.8%, 55.3% and 46.2% at 12, 24 and 36 months, respectively (p = 0.871). Relapse rate within 12 months was higher in patients who withdrew compared with those who maintained on AZA (52.6% versus 29.4%; p = 0.045). Mean corpuscular volume increased after AZA therapy in both of the low-dose [median (interquartile range, IQR): 88.2 (81.4-92.2) versus 95.1 (90.1-100.9) fl, p < 0.001] and standard-dose subgroups [median (IQR) 86.8 (76.9-89.9) versus 94.7 (85.9-99.7) fl, p < 0.001]. Leukopenia occurred in 21.1% of the patients. Patients on standard dose had a higher risk for leukopenia than those on low-dose AZA [odds ratio (OR) 3.9, 95% CI 1.9-8.2, p < 0.001].
CONCLUSIONS
In the Chinese population, low-dose AZA is effective for maintaining remission in steroid-dependent UC patients. Standard-dose AZA was associated with more than threefold increased risk of leukopenia.
背景
低剂量硫唑嘌呤（AZA）在维持激素依赖型溃疡性结肠炎（UC）患者缓解方面是否有效尚不清楚。我们评估了低剂量AZA在中国UC患者中的疗效和安全性。
方法
我们从一个全地区性的炎症性肠病登记处中确定了接受AZA维持治疗且处于临床缓解期的激素依赖型UC患者。标准剂量和低剂量AZA分别定义为至少2mg/kg/天和低于2mg/kg/天。通过Kaplan-Meier分析来分析复发率，并使用对数秩检验进行比较。
结果
在1226例UC患者中，有128例（男性占53%，AZA治疗的中位持续时间为44个月）被纳入研究。AZA维持治疗的中位剂量为1.3mg/kg/天。97.7%的患者同时服用口服5-氨基水杨酸。标准剂量和低剂量AZA组患者在12个月、24个月和36个月时的累积无复发率分别为71.2%、52.8%和45.2%，以及71.8%、55.3%和46.2%（p = 0.871）。与继续使用AZA治疗的患者相比，停药患者在12个月内的复发率更高（52.6%对29.4%；p = 0.045）。低剂量[中位数（四分位间距，IQR）：88.2（81.4 - 92.2）对95.1（90.1 - 100.9）fl，p < 0.001]和标准剂量亚组[中位数（IQR）86.8（76.9 - 89.9）对94.7（85.9 - 99.7）fl，p < 0.001]中，AZA治疗后平均红细胞体积均增加。21.1%的患者出现白细胞减少。标准剂量组患者白细胞减少的风险高于低剂量AZA组患者[比值比（OR）3.9，95%置信区间1.9 - 8.2，p < 0.001]。
结论
在中国人群中，低剂量AZA对维持激素依赖型UC患者的缓解有效。标准剂量AZA与白细胞减少风险增加三倍以上相关。
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