Isavuconazole matches voriconazole in invasive aspergillosis with fewer liver effects

Isavuconazole and voriconazole appear statistically comparable in the treatment of invasive aspergillosis, but isavuconazole carries a significantly lower risk of drug-related adverse reactions and hepatotoxicity, according to a systematic review and meta-analysis published open access in BMC Infectious Diseases on 24 October 2026. The analysis pooled seven studies involving 587 patients, comprising four randomized controlled trials and three cohort studies, and found no statistically significant differences between the two antifungals in overall response rate or all-cause mortality. Isavuconazole has been recommended for the treatment of invasive aspergillosis, but its comparative efficacy and safety versus voriconazole remained inconclusive because of limitations in previous meta-analyses.

The researchers searched eight databases, including PubMed, Embase, Web of Science, The Cochrane Library, the China National Knowledge Infrastructure, the Wanfang Medical Database, the VIP Database and Sinomed, for studies comparing isavuconazole with voriconazole for invasive aspergillosis from inception to January 15, 2026. They extracted data on overall response rate, defined as complete or partial response per study criteria, all-cause mortality, drug-related adverse reactions, galactomannan test results, tumor necrosis factor-alpha and interleukin-6, and performed the meta-analysis using RevMan 5.4 software. The pooled results showed no statistically significant differences between the two treatment groups in overall response rate, with a relative risk of 1.11 and a 95 percent confidence interval of 0.99 to 1.24 and a p value of 0.07, or in all-cause mortality, with a relative risk of 0.94 and a 95 percent confidence interval of 0.69 to 1.28 and a p value of 0.67.

The response-rate estimate narrowly missed conventional statistical significance, a result the authors report without claiming a confirmed advantage for either drug. Isavuconazole treatment was associated with significantly lower measured levels of three biomarkers. The galactomannan test showed a mean difference of -0.32 with a 95 percent confidence interval of -0.4 to -0.21 and a p value below 0.00001, tumor necrosis factor-alpha showed a mean difference of -9.18 with a 95 percent confidence interval of -12.68 to -5.67 and a p value below 0.00001, and interleukin-6 showed a mean difference of -3.87 with a 95 percent confidence interval of -5.72 to -2.01 and a p value below 0.0001.

On safety, isavuconazole significantly decreased the incidence of drug-related adverse reactions, with a relative risk of 0.44 and a 95 percent confidence interval of 0.30 to 0.67 and a p value of 0.0001. The difference was particularly pronounced for hepatotoxicity, which showed a relative risk of 0.42 with a 95 percent confidence interval of 0.1 to 0.96 and a p value of 0.04, indicating a significantly lower liver-related risk under isavuconazole. The authors conclude that the meta-analysis shows no difference between isavuconazole and voriconazole in overall response rate or all-cause mortality for invasive aspergillosis, but that isavuconazole is associated with a lower hepatotoxicity risk.

Isavuconazole, they report, offers comparable efficacy with a potentially more favorable safety profile and may be considered an alternative in patients at risk of hepatotoxicity. The findings carry the caveats inherent to the evidence base. The pooled analysis combined four randomized controlled trials with three cohort studies, and the confidence interval around the mortality estimate was wide, spanning from 0.69 to 1.28.

The article was shared early to provide faster access to peer-reviewed, accepted research; it is citable and carries a permanent DOI, but this version is subject to further edits and will be replaced automatically by the final Version of Record, with all legal disclaimers applying. No clinical trial number was applicable to the study.

Subject of Research: Comparative efficacy and safety of isavuconazole versus voriconazole for the treatment of invasive aspergillosis

Article Title: Efficacy and safety of isavuconazole versus voriconazole for the treatment of invasive aspergillosis: a systematic review and meta-analysis

Article References: Yang, Q., Yuan, L., Zhang, X., & Tang, P. (2026). Efficacy and safety of isavuconazole versus voriconazole for the treatment of invasive aspergillosis: a systematic review and meta-analysis. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14686-5

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14686-5

Keywords: invasive aspergillosis, isavuconazole, voriconazole, meta-analysis, antifungal therapy, hepatotoxicity, infectious diseases, Efficacy, safety, versus, treatment, invasive