Suarez-Almazor M E, Belseck E, Shea B, Wells G, Tugwell P
Health Services Research, Veterans Affairs Medical Center, Mailbox Station 152, 2002 Holcombe Blvd, Houston, Texas, USA, 77024.
Cochrane Database Syst Rev. 2000(4):CD001157. doi: 10.1002/14651858.CD001157.
To assess the short-term effects of cyclophosphamide for the treatment of rheumatoid arthritis.
We searched the Cochrane Musculoskeletal Group's Register, the Cochrane Controlled Trials Register (issue 3, 2000), Medline and Embase up to and including August 2000. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search.
All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing oral cyclophosphamide against placebo (or an active drug at a dosage considered to be ineffective) in patients with rheumatoid arthritis.
Data abstraction was carried out independently by two reviewers. The same two reviewers using a validated checklist (Jadad 1996) assessed the methodological quality of the RCTs and CCTs. Rheumatoid arthritis outcome measures were extracted from the publications for baseline and end-of-study. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts. Weighted mean differences (WMDs) were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout.
A total of 70 patients were included in the pooled analysis of two trials, 31 receiving cyclophosphamide. A statistically significant benefit was observed for cyclophosphamide when compared to placebo for tender and swollen joint scores: SMDs were -0.57 and -0.59 respectively. The difference in ESR also favoured the active drug but did not reach statistical significance (-12 mm, 95%CI: -26 to 2.5). One trial reported the number of patients developing new or worse erosions: the OR for cyclophosphamide compared to placebo was 0.17 (95% CI: 0.05 to 0.57). Patients receiving placebo were six times more likely to discontinue treatment because of lack of efficacy than patients receiving cyclophosphamide. Withdrawals from adverse reactions were higher in the cyclophosphamide group (Odds ratio=2.9), although this difference was not statistically significant. Side effects from cyclophosphamide included hemorrhagic cystitis, nausea, vomiting, leucopenia, thrombocytopenia, alopecia, amenorrhea and herpes zoster infections.
REVIEWER'S CONCLUSIONS: Cyclophosphamide appears to have a clinically and statistically significant benefit on the disease activity of patients with RA, similar to some disease modifying antirheumatic drugs (DMARDs) such as antimalarials or sulfasalazine, but lower than methotrexate. Toxicity however is severe, limiting its use given the low benefit-risk ratio compared to other antirheumatic agents.
评估环磷酰胺治疗类风湿关节炎的短期疗效。
我们检索了Cochrane肌肉骨骼组注册库、Cochrane对照试验注册库（2000年第3期）、截至2000年8月的Medline和Embase。我们还对从电子检索中获得的试验的参考文献列表进行了手工检索。
所有比较口服环磷酰胺与安慰剂（或认为无效剂量的活性药物）治疗类风湿关节炎患者的随机对照试验（RCT）和对照临床试验（CCT）。
由两名评价员独立进行数据提取。同样的两名评价员使用经过验证的清单（Jadad，1996年）评估RCT和CCT的方法学质量。从出版物中提取类风湿关节炎结局指标的基线值和研究结束时的值。使用关节计数的标准化均数差值（SMD）进行汇总分析。红细胞沉降率（ESR）采用加权均数差值（WMD）。用汇总比值比评估撤药的毒性。采用卡方检验评估试验间的异质性。全程使用固定效应模型。
两项试验的汇总分析共纳入70例患者，31例接受环磷酰胺治疗。与安慰剂相比，环磷酰胺在压痛关节评分和肿胀关节评分方面具有统计学显著益处：SMD分别为-0.57和-0.59。ESR的差异也有利于活性药物，但未达到统计学显著性（-12mm，95%CI：-26至2.5）。一项试验报告了出现新的或更严重侵蚀的患者数量：环磷酰胺与安慰剂相比的OR为0.17（95%CI：0.05至0.57）。因疗效不佳而停药的患者中，接受安慰剂的患者是接受环磷酰胺患者的6倍。环磷酰胺组因不良反应撤药的比例更高（比值比=2.9），尽管这一差异无统计学显著性。环磷酰胺的副作用包括出血性膀胱炎、恶心、呕吐、白细胞减少、血小板减少、脱发、闭经和带状疱疹感染。
环磷酰胺似乎对类风湿关节炎患者的疾病活动有临床和统计学显著益处，类似于一些改善病情抗风湿药（DMARDs），如抗疟药或柳氮磺胺吡啶，但低于甲氨蝶呤。然而，由于毒性严重，与其他抗风湿药物相比，其效益风险比低，限制了其应用。
