Lee, C.H., Lin, J.C., Ho, C.L., Sun, M., Yen, W.T., & Lin, C. (2017). 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. PLOS One, 12, e0180050.

STUDY PURPOSE: To compare the efficacy and safety of micafungin (MCFG) with triazoles for the prophylaxis and treatment of invasive fungal infections (IFIs) among patients with hematologic malignancies with neutropenia

TYPE OF STUDY: Meta analysis and systematic review

DATABASES USED: PubMed, Embase, Cochrane Central Register of Controlled Trials, and relevant database articles for RCTs

YEARS INCLUDED: (Overall for all databases) through November 2016

INCLUSION CRITERIA: Randomized controlled studies comparing MCFG to the use of triazoles in neutropenic fever. Inclusion criteria consisted of studies that compared efficacy or incidence of AEs in two comparable populations: received IV MCFG for antifungal prevention or treatment and FN defined as absolute neutrophil count less than 1,500/mcl. Search terms included micafungin, micafungin sodium, micamine, FK 463, Echinocandin, Lipopep- tides, antifungal agents, FN, and neutropenic fever

EXCLUSION CRITERIA: Studies that had incomplete data, included duplicate data, did not contain any predetermined clinical outcomes, or could not be pooled with other included studies

TOTAL REFERENCES RETRIEVED: 181

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: PRISMA checklist and a quality assessment of two reviewers following the Cochrane Collaboration Reviewers’ Handbook for Systematic Reviews of Interventions. Articles were scored form 0 (lowest quality level) to 7 (highest quality level) with 1 point given to each area addressed for randomization, concealment of allocation, blinding, reporting of withdrawals, selective reporting, and other bias. Disagreements of assessments were resolved through reviewer discussions.

• FINAL NUMBER STUDIES INCLUDED: 9
• TOTAL PATIENTS INCLUDED IN REVIEW: 2,008 (1,049 cases and 959 controls)
• SAMPLE RANGE ACROSS STUDIES: 70-882
• KEY SAMPLE CHARACTERISTICS: Patients with hematologic malignancies undergoing treatment with intensive chemotherapy or hematopoietic cell transplantation. Mean age ranged from 6.01 to 53 years old. Studies were conducted in China, Korea, Japan, Egypt, and the United States. MCFG dosage ranged from 1 mg/kg per day to 150 mg/day and FLCZ ranged from 8 mg/kg per day to 400 mg/day. Two studies compared MCFG and azoles for empiric treatment and seven for prophylaxis. Patients were followed from 28 days to 6 months.

PHASE OF CARE: Active anti-tumor treatment     

APPLICATIONS: Pediatrics

MCFG was found to have a better treatment success rate compared to triazoles (RR = 1.13; 95% CI [1.02, 1.25]; I² = 87%) in the pooled data for the absence of IFIs during and following treatment. The prophylactic model studies showed better success rates compared to triazoles (RR = 1.15; 95% CI [1.05, 1.25], I² = 69.1%), but no differences were found with the empiric model studies (RR = 1.04; 95% CI [0.67, 21.61], I² = 91%). A 20% RR was found for use of MCFG. MCFG also showed a lower incidence of infections compared to triazoles for rotation of anti-fungal agents in eight pooled trials (n = 1,901; RR = 0.66; 95% CI [0.47, 0.94]; I² = 71.5%). No difference was found between agents for overall mortality. MCFG had a significantly lower rate of premature discontinuation (p < 0.05) and a lower incidence of AEs for hepatic impairment (RR = 0.67; 95% CI [0.22–2.09]; I² = 67%), neurological complications (RR = 0.7; 95% CI [0.5–0.98]; I ² = 3.3%), and GI upset (RR = 0.62; 95% CI [20.42, 0.92]; I² = 0%). There was no publication bias. Heterogeneity was found with age group differences with analyses showing a stronger effect from MCFG in patients younger than age 45 years. Stratified analyses also showed better outcomes with MCFG.

MCFG was better than triazoles for efficacy and fewer AEs when used prophylactically and as effective as triazoles for the treatment of IFIs. MCFGs were also found to be more effective among patients younger than age 45 years. However, mortality was not lower in one group compared to the other.

High heterogeneity

Recommending the use of MCFG prophylactically can decrease the risk of IFIs and related adverse events among patients undergoing treatment for hematologic malignancies.