Efficacy and safety of isavuconazole versus voriconazole for the treatment of invasive fungal infections: a meta-analysis with trial sequential analysis

Background Isavuconazole has been used to treat invasive fungal infections, however, it is unclear whether the efficacy of isavuconazole is superior to that of voriconazole. The purpose of this meta-analysis was to assess the efficacy and safety of isavuconazole compared to voriconazole in treating invasive fungal infections. Methods Electronic databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, were searched to identify relevant studies. Studies evaluating the effect of isavuconazole in the treatment of patients with invasive fungal infections were included. Pooled rates of overall response, all-cause mortality, drug-related adverse events (AEs), and discontinuation due to drug-related AEs were calculated. Results Seven studies involving 890 patients were included. Meta-analysis showed that there was no significant difference between isavuconazole and voriconazole in overall response (risk ratio [RR]: 1.02, 95% confidence interval [CI]: 0.83 to 1.25, p = 0.86) and all-cause mortality (RR: 0.95, 95% CI: 0.78 to 1.16, p = 0.61). However, isavuconazole had a significantly lower incidence of drug-related AEs (RR: 0.70, 95% CI: 0.61 to 0.81, p < 0.001) and discontinuation due to drug-related AEs (RR: 0.56, 95% CI: 0.39 to 0.82, p = 0.003) compared with voriconazole. Trial sequential analysis (TSA) confirmed that the difference between isavuconazole and voriconazole in discontinuation due to drug-related AEs need further valiadation, but the results of other outcomes were conclusive. < 0.001) and discontinuation due to drug-related AEs (RR: 0.56, 95% CI: 0.39 to 0.82, p = 0.003) compared with voriconazole. Trial sequential analysis (TSA) confirmed that the difference between isavuconazole and voriconazole in discontinuation due to drug-related AEs needs further validation, but the results of other outcomes were conclusive. Conclusions Our findings support the use of isavuconazole as the primary therapy for invasive fungal infections. More research is needed to compare the discontinuation rates of isavuconazole and voriconazole.