Lee Cho-Hao, Lin Jung-Chung, Ho Ching-Liang, Sun Min, Yen Wel-Ting, Lin Chin
Department of Hematology and Oncology Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
PLoS One. 2017 Jul 12;12(7):e0180050. doi: 10.1371/journal.pone.0180050. eCollection 2017.
Current studies that compare the efficacy and safety of micafungin (MCFG) with that of triazoles for the prophylaxis and treatment of invasive fungal infections (IFIs) demonstrate a lack of sufficient evidence and yield conflicting results. To compare the efficacy and safety of MCFG and triazoles in the prevention and treatment of IFIs, we conducted a meta-analysis and trial sequential analysis (TSA).
For the meta-analysis, we systematically searched the databases of PubMed, Embase and Cochrane Central Register of Controlled Trials and relevant database articles for randomized controlled studies published through November 2016. Comparative studies of the efficacy and safety of MCFG versus triazoles in the prevention and treatment of IFIs were selected. Meta-analysis was performed by R software with the "metafor" package. Pooled results were expressed as risk ratios (RRs) with corresponding 95% confidence intervals (CI). TSA was adopted to assess the studies' power with TSA version 0.9 beta.
Nine current studies were included in the meta-analysis (1049 cases and 959 controls). Pooled trial comparisons indicated that MCFG does have significantly higher treatment success rates (RR = 1.13; 95% CI, 1.02-1.25; p = 0.0205) and reduces the number of overall IFIs (RR = 0.75; 95% CI, 0.61-0.92; p = 0.0056). However, MCFG demonstrates no difference in all-cause mortality (RR = 0.76; 95% CI, 0.52-1.12, p = 0.1624). For the safety evaluation, MCFG had a significantly lower incidence of severe adverse events (AEs) (RR = 0.45; 95% CI, 0.25-0.83; p = 0.0105), hepatic impairment (RR = 0.70; 95% CI, 0.50-0.97; p = 0.0363) and premature discontinuation (RR = 0.51; 95% CI, 0.34-0.76, p = 0.0010). Meta-regression analysis disclosed the correction of mean age and treatment success rates (P < 0.0001). Meanwhile, TSA demonstrated sufficient power to show efficacy.
The treatment success rate of MCFG is superior to that of triazoles for the prophylaxis and treatment of IFIs, and correction of the mean patient age demonstrates that efficacy increases as patient age decreases. MCFG appears to be well-tolerated with manageable side effects and lower withdrawal rates. However, additional clinical trials should be conducted on specific drug-related mortality and AEs to gather sufficient evidence on these matters.
目前比较米卡芬净（MCFG）与三唑类药物预防和治疗侵袭性真菌感染（IFI）的疗效和安全性的研究缺乏充分证据，结果相互矛盾。为比较MCFG和三唑类药物在预防和治疗IFI方面的疗效和安全性，我们进行了一项荟萃分析和试验序贯分析（TSA）。
对于荟萃分析，我们系统检索了截至2016年11月发表的随机对照研究的PubMed、Embase和Cochrane对照试验中央注册库数据库以及相关数据库文章。选择了比较MCFG与三唑类药物在预防和治疗IFI方面疗效和安全性的对照研究。使用R软件和“metafor”包进行荟萃分析。汇总结果以风险比（RR）及相应的95%置信区间（CI）表示。采用TSA 0.9 beta版评估研究的检验效能。
荟萃分析纳入了9项当前研究（1049例病例和959例对照）。汇总的试验比较表明，MCFG确实具有显著更高的治疗成功率（RR = 1.13；95%CI，1.02 - 1.25；p = 0.0205），并减少了IFI的总数（RR = 0.75；95%CI，0.61 - 0.92；p = 0.0056）。然而，MCFG在全因死亡率方面无差异（RR = 0.76；95%CI，0.52 - 1.12，p = 0.1624）。对于安全性评估，MCFG的严重不良事件（AE）发生率显著较低（RR = 0.45；95%CI，0.25 - 0.83；p = 0.0105）、肝损伤（RR = 0.70；95%CI，0.50 - 0.97；p = 0.0363）和提前停药率（RR = 0.51；95%CI，0.34 - 0.76，p = 0.0010）。Meta回归分析揭示了平均年龄与治疗成功率之间的校正关系（P < 0.0001）。同时，TSA显示有足够的检验效能来证明疗效。
在预防和治疗IFI方面，MCFG的治疗成功率优于三唑类药物，校正平均患者年龄表明疗效随患者年龄降低而增加。MCFG似乎耐受性良好，副作用可控且停药率较低。然而，应针对特定的药物相关死亡率和AE进行更多临床试验，以收集关于这些问题的充分证据。
