Efficacy and safety of micafungin versus extensive azoles in the prevention and treatment of invasive fungal infections for neutropenia patients with hematological malignancies: A meta-analysis of randomized controlled trials

BACKGROUND 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). METHODS 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. RESULTS 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. CONCLUSIONS 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.