Sandborn W, Sutherland L, Pearson D, May G, Modigliani R, Prantera C
Division of Gastroenterology, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Cochrane Database Syst Rev. 2000(2):CD000545. doi: 10.1002/14651858.CD000545.
To determine the effectiveness of azathioprine and 6-mercaptopurine in inducing remission of active Crohn's disease.
Studies were selected using the MEDLINE data base (1966 - December 1997), abstracts from major gastrointestinal meetings and references from published articles and reviews. The Cochrane Controlled Trials Register and the Inflammatory Bowel Disease Review Group Trials Register was also searched.
Eight randomized placebo controlled trials of azathioprine and 6-mercaptopurine therapy in adult patients were identified: five dealt with active disease and three had multiple therapeutic arms.
Data were extracted by three independent observers based on the intention to treat principle. Each study was given a quality score based on predetermined criteria. Extracted data were converted to 2X2 tables (response versus no response and antimetabolite versus placebo) and then synthesized into a summary test statistic using the pooled odds ratio and 95% confidence intervals as described by Cochran and Mantel and Haenszel ('Odds Ratio' in MetaView).
The odds ratio of a response to azathioprine or 6-mercaptopurine therapy compared with placebo in active Crohn's disease was 2.36 (95% CI 1.57-3.53). This corresponded to a number needed to treat of about 5 to observe an effect of therapy in one patient. When the two trials using 6-mercaptopurine in active disease were excluded from the analysis, the odds ratio of response was 2.04 (CI 1.24 - 3.35). Treatment >/= 17 weeks increased the odds ratio of a response to 2.51 (CI 1.63-3. 88). A steroid sparing effect was seen with an odds ratio of 3.86 (CI 2.14 - 6.96), corresponding to a number needed to treat of about 3 to observe steroid sparing in one patient. Adverse events requiring withdrawal from a trial, principally allergy, leukopenia, pancreatitis, and nausea were increased on therapy with an odds ratio of 3.01 (CI 1.30 - 6.96). The number needed to treat to observe one adverse event in one patient treated with azathioprine or 6-mercaptopurine was 14.
REVIEWER'S CONCLUSIONS: Azathioprine and 6-mercaptopurine are effective therapy for inducing remission in active Crohn's disease. The odds ratio of response increases after >/= 17 weeks of therapy, suggesting that there is a minimum length of time for a trial of azathioprine or 6-mercaptopurine therapy. Adverse events were more common among patients on therapy.
确定硫唑嘌呤和6-巯基嘌呤诱导活动期克罗恩病缓解的有效性。
使用MEDLINE数据库（1966年 - 1997年12月）、主要胃肠病学会议的摘要以及已发表文章和综述中的参考文献来选择研究。还检索了Cochrane对照试验注册库和炎症性肠病综述组试验注册库。
确定了八项关于硫唑嘌呤和6-巯基嘌呤治疗成年患者的随机安慰剂对照试验：五项针对活动期疾病，三项有多个治疗组。
由三名独立观察者根据意向性治疗原则提取数据。每项研究根据预定标准给出质量评分。提取的数据转换为2×2表格（缓解与未缓解以及抗代谢物与安慰剂），然后使用Cochran、Mantel和Haenszel描述的合并比值比和95%置信区间（MetaView中的“比值比”）合成汇总检验统计量。
在活动期克罗恩病中，与安慰剂相比，硫唑嘌呤或6-巯基嘌呤治疗缓解的比值比为2.36（95%CI 1.57 - 3.53）。这相当于约5名患者接受治疗才能使1名患者观察到治疗效果。当分析中排除两项在活动期疾病中使用6-巯基嘌呤的试验时，缓解的比值比为2.04（CI 1.24 - 3.35）。治疗≥17周可使缓解的比值比增加至2.51（CI 1.63 - 3.88）。观察到有类固醇节省效应，比值比为3.86（CI 2.14 - 6.96），相当于约3名患者接受治疗才能使1名患者观察到类固醇节省。因不良事件需要退出试验的情况（主要是过敏、白细胞减少、胰腺炎和恶心）在治疗时增加，比值比为3.0(CI 1.30 - 6.96)。接受硫唑嘌呤或6-巯基嘌呤治疗的患者中，观察到1例不良事件所需治疗的患者数为14。
硫唑嘌呤和6-巯基嘌呤是诱导活动期克罗恩病缓解的有效疗法。治疗≥17周后缓解的比值比增加，提示硫唑嘌呤或6-巯基嘌呤治疗试验有最短治疗时间。不良事件在接受治疗的患者中更常见。
