Department of Nephrology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, People's Republic of China.
Drugs. 2017 Feb;77(2):187-199. doi: 10.1007/s40265-016-0683-z.
The objective of this systematic review was to compare the efficacy and safety of tacrolimus with cyclophosphamide in primary membranous nephropathy (PMN) patients.
We conducted a literature search in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CCRCT). Any study that compared the efficacy or safety between tacrolimus and cyclophosphamide in the adult PMN patients was included.
We included four randomized controlled trials and two prospective cohort studies with 389 PMN patients. The pooled results using the Dersimonian and Laird method showed that renal remission rates at the longest follow-up periods were not significantly different between the tacrolimus and cyclophosphamide groups (overall remission, six trials, n = 389, relative risk [RR] 0.994 [95% confidence interval [CI] 0.768-1.286); complete remission, six trials, n = 389, RR 1.256 [95% CI 0.733-2.150]). Further analyses found that tacrolimus was comparable with cyclophosphamide for inducing renal remission within 1 year but inferior to cyclophosphamide after 1-year follow-up. It should be noted that only two studies reported the outcomes after 1-year follow-up, which might be considered as weak evidence. The rates of relapse and the drop-outs due to adverse effects were not significantly different (relapse, six trials, n = 389, RR 2.244 [95% CI 0.892-5.644]; drop-outs, six trials, n = 389, RR 1.330 [95% CI 0.412-4.291]). However, the cyclophosphamide group had a significantly higher risk of leukopenia than the tacrolimus group (four trials, n = 216, RR 0.203 [95% CI 0.045-0.916]), whereas the rates of tremor were significantly higher in the tacrolimus group than in the cyclophosphamide group (three trials, n = 202, RR 8.939 [95% CI 1.694-47.173]).
The quality and short follow-up durations of the studies limited the reliability of our conclusions.
Tacrolimus was comparable with cyclophosphamide for inducing renal remission of PMN patients within 1 year, but the long-term effects need to be investigated. The cyclophosphamide group had a significantly higher risk of leukopenia, whereas the tacrolimus group had significantly higher rates of tremor. These conclusions need to be further verified.
本系统评价旨在比较他克莫司与环磷酰胺治疗原发性膜性肾病（PMN）患者的疗效和安全性。
我们在 MEDLINE、EMBASE 和 Cochrane 对照试验中心注册库（CCRCT）进行了文献检索。纳入了比较他克莫司和环磷酰胺在成年 PMN 患者中的疗效或安全性的任何研究。
我们纳入了四项随机对照试验和两项前瞻性队列研究，共 389 名 PMN 患者。采用 DerSimonian 和 Laird 法进行的汇总分析结果显示，最长随访期间的肾脏缓解率在他克莫司组和环磷酰胺组之间无显著差异（总体缓解，六项试验，n=389，相对风险[RR]0.994[95%置信区间[CI]0.768-1.286]；完全缓解，六项试验，n=389，RR 1.256[95%CI 0.733-2.150]）。进一步分析发现，他克莫司在 1 年内诱导肾脏缓解与环磷酰胺相当，但在 1 年后的随访中劣于环磷酰胺。需要注意的是，只有两项研究报告了 1 年后的结局，这可能被认为是证据较弱。复发率和因不良反应而停药率无显著差异（复发，六项试验，n=389，RR 2.244[95%CI 0.892-5.644]；停药，六项试验，n=389，RR 1.330[95%CI 0.412-4.291]）。然而，环磷酰胺组的白细胞减少症发生率明显高于他克莫司组（四项试验，n=216，RR 0.203[95%CI 0.045-0.916]），而他克莫司组的震颤发生率明显高于环磷酰胺组（三项试验，n=202，RR 8.939[95%CI 1.694-47.173]）。
研究的质量和较短的随访时间限制了我们结论的可靠性。
他克莫司与环磷酰胺在诱导 PMN 患者 1 年内肾脏缓解方面相当，但需要进一步研究长期效果。环磷酰胺组白细胞减少症的风险明显升高，而他克莫司组震颤的发生率明显升高。这些结论需要进一步验证。
