Suarez-Almazor M E, Spooner C, Belseck E
Health Services Research, Veterans Affairs Medical Center, Mailbox Station 152, 2002 Holcombe Blvd, Houston, Texas, USA, 77024.
Cochrane Database Syst Rev. 2000(4):CD001461. doi: 10.1002/14651858.CD001461.
To assess the short-term effects of azathioprine for the treatment of rheumatoid arthritis (RA).
We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register (issue 3, 2000), Medline up to and including August 2000 and Embase from 1988 to August 2000. We also conducted a handsearch of the reference lists of the trials retrieved from the electronic search.
All randomized controlled trials and controlled clinical trials comparing azathioprine against placebo in patients with rheumatoid arthritis.
Data was extracted independently by two reviewers (CS, EB); disagreements were resolved by discussion or third party adjudication (MS). The same reviewers (CS, EB) assessed the methodological quality of the trials using a validated quality assessment tool. Rheumatoid arthritis outcome measures were extracted from the publications for the six-month endpoint. The pooled analysis was performed using standardized mean differences for joint counts, pain and functional status assessments. Weighted mean differences were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals and for adverse reactions. The 95% confidence intervals (95% CI) are presented. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout, since no statistical heterogeneity was found.
Three trials with a total of 81 patients were included in the analysis. Forty patients were randomized to azathioprine and forty-one to placebo. A pooled estimate was calculated for two outcomes. A statistically significant benefit was observed for azathioprine when compared to placebo for tender joint scores. The standardized weighted mean difference between treatment and placebo was -0.98 (95% CI -1.45, -0.50). Withdrawals from adverse reactions were significantly higher in the azathioprine group OR=4.56 (95% CI 1.16, 17.85).
REVIEWER'S CONCLUSIONS: Azathioprine appears to have a statistically significant benefit on the disease activity in joints of patients with RA. This evidence however is based on a small number of patients, included in older trials. Its effects on long-term functional status and radiological progression were not assessed due to lack of data. Toxicity is shown to be higher and more serious than that observed with other disease-modifying anti-rheumatic drugs (DMARDs). Given this high risk to benefit ratio, there is no evidence to recommend the use of azathioprine over other DMARDs.
评估硫唑嘌呤治疗类风湿关节炎（RA）的短期效果。
我们检索了Cochrane肌肉骨骼组试验注册库、Cochrane对照试验注册库（2000年第3期）、截至2000年8月的Medline以及1988年至2000年8月的Embase。我们还对电子检索获得的试验的参考文献列表进行了手工检索。
所有比较硫唑嘌呤与安慰剂治疗类风湿关节炎患者的随机对照试验和对照临床试验。
由两名审阅者（CS、EB）独立提取数据；分歧通过讨论或第三方裁决（MS）解决。相同的审阅者（CS、EB）使用经过验证的质量评估工具评估试验的方法学质量。从出版物中提取类风湿关节炎结局测量指标用于六个月的终点。使用标准化均数差对关节计数、疼痛和功能状态评估进行汇总分析。对红细胞沉降率（ESR）使用加权均数差。用汇总比值比评估撤药和不良反应的毒性。给出95%置信区间（95%CI）。使用卡方检验评估试验间的异质性。由于未发现统计学异质性，始终使用固定效应模型。
三项试验共81例患者纳入分析。40例患者随机分配至硫唑嘌呤组，41例至安慰剂组。对两个结局计算汇总估计值。与安慰剂相比，硫唑嘌呤治疗压痛关节评分有统计学显著益处。治疗组与安慰剂组的标准化加权均数差为-0.98（95%CI -1.45，-0.50）。硫唑嘌呤组因不良反应撤药显著更高，OR = 4.56（95%CI 1.16，17.85）。
硫唑嘌呤似乎对类风湿关节炎患者关节的疾病活动有统计学显著益处。然而，该证据基于早期试验纳入的少量患者。由于缺乏数据，未评估其对长期功能状态和放射学进展的影响。已表明其毒性高于且比其他改善病情抗风湿药（DMARDs）更严重。鉴于这种高风险效益比，没有证据推荐使用硫唑嘌呤而非其他DMARDs。
