Thirty-nine RCTs (number of patients reported as 8,745, range 28 to 1,111) were included. Thirteen studies were double blinded, 13 had adequate concealment of treatment allocation, 12 had adequate allocation generation and 31 were analysed on an intention-to-treat basis.
Treatment discontinuation due to adverse events was most common for itraconazole (18.8%, 95% CI 14.3% to 23.2%; three treatment arms) and Amphotericin B formulations (13.4%, 95% CI 8.9% to 17.8%; 41 treatment arms). Rates were less than 10% for all other agents and were lowest for fluconazole (2.2%, 95% CI 0 to 4.6%; 10 treatment arms).
The proportion of patients who discontinued treatment due to elevated liver enzyme tests was highest for micafungin (2.7%, 95% CI 0.7% to 4.6%; three treatment arms) and itraconazole (1.5%, 95% CI 0 to 4%; three treatment arms). Summary rates were less than 1% in all other studies.
The proportion of patients with elevated liver enzyme levels that did not required stopping treatment was highest for voriconazole (19.7%, 95% CI 16.8% to 22.6%), itraconazole (17.4%, 95% CI 3.9% to 31%; three treatment arms) and amphotericin B formulations (14.1%, 95% CI 10.3% to 18%). Values were less than 10% for all other agents.
An auxiliary analysis was conducted for an additional 37 non-randomised studies (n=3,191). The order of the safety profiles of the different antifungal agents was generally the same as for the RCTs.