Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, Netherlands.
Inflamm Bowel Dis. 2010 Sep;16(9):1541-9. doi: 10.1002/ibd.21221.
Thiopurines have proven efficacy in long-term maintenance therapy of inflammatory bowel disease (IBD). Limited data are available with regard to factors predicting effectiveness and failure of long-term thiopurine use in IBD patients.
The data in this retrospective study are based on an 8-year intercept cohort of previous or present thiopurine-using IBD patients. Both cohorts are assessed by descriptive and statistical analysis aimed at determining thiopurine effectiveness and the variables that are predictive for failure of thiopurine therapy.
In all, 363 IBD patients were included (60% female), 63% with Crohn's disease and 33% with ulcerative colitis. Overall, thiopurines were continued in 145/363 (40%) and discontinued in 208/363 (57%) patients. The proportion of patients still using thiopurines at 3, 6, 12, 24, and 60 months was 73%, 69%, 63%, 51%, and 42%, respectively. Patients discontinued thiopurines due to adverse events (39%), refractoriness (16%), and ongoing remission / patient's request (4%). 6-methylmercaptopurine (6-MMP) concentration and 6-MMP/6-thioguanine nucleotides (6-TGN) ratio were significant higher in the failure group. Prolonged continuation of thiopurines was associated with a decreased risk of discontinuation.
Azathioprine and 6-mercaptopurine were considered effective in approximately 40% of IBD patients after 5 years of treatment. A quarter of the patients discontinued thiopurines within 3 months, mostly due to adverse events. A high 6-MMP concentration or 6-MMP/6-TGN ratio was associated with therapeutic failure. If thiopurine use was successfully initiated in the first months, its use was usually extended over many years, as long-term use was associated with continuation of therapy.
硫嘌呤类药物已被证明在炎症性肠病（IBD）的长期维持治疗中有效。关于预测 IBD 患者长期使用硫嘌呤类药物的有效性和失败的因素，仅有有限的数据可用。
本回顾性研究的数据基于以前或现在使用硫嘌呤类药物的 IBD 患者的 8 年截距队列。两个队列都通过描述性和统计分析进行评估，旨在确定硫嘌呤类药物的有效性以及预测硫嘌呤类药物治疗失败的变量。
共有 363 名 IBD 患者入组（60%为女性），63%为克罗恩病，33%为溃疡性结肠炎。总体而言，硫嘌呤类药物在 145/363（40%）名患者中继续使用，在 208/363（57%）名患者中停用。在 3、6、12、24 和 60 个月时仍使用硫嘌呤类药物的患者比例分别为 73%、69%、63%、51%和 42%。由于不良反应（39%）、难治性（16%）和持续缓解/患者要求（4%），患者停用硫嘌呤类药物。失败组的 6-甲基巯基嘌呤（6-MMP）浓度和 6-MMP/6-硫鸟嘌呤核苷酸（6-TGN）比值显著较高。硫嘌呤类药物的长期持续使用与停药风险降低相关。
阿扎胞苷和 6-巯基嘌呤在治疗 5 年后被认为对大约 40%的 IBD 患者有效。四分之一的患者在 3 个月内停用硫嘌呤类药物，主要是由于不良反应。高 6-MMP 浓度或 6-MMP/6-TGN 比值与治疗失败相关。如果硫嘌呤类药物在最初几个月成功使用，其使用通常会延长多年，因为长期使用与治疗的延续相关。
