Post-hoc analysis of the safety and efficacy of isavuconazole in older patients with invasive fungal disease from the VITAL and SECURE studies

• Published in: Scientific reports Vol. 13; no. 1; p. 6730
• Main Authors: Hamed, Kamal, Engelhardt, Marc, Kovanda, Laura L, Huang, Jin Ju, Yan, Jean, Aram, Jalal A
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 25.04.2023; Nature Publishing Group UK; Nature Portfolio
• Subjects: Aged; Antifungal activity; Antifungal Agents - adverse effects; Aspergillosis - drug therapy; Clinical trials; Fungal diseases; Humans; Invasive Fungal Infections - drug therapy; Invasive Fungal Infections - microbiology; Mortality; Nitriles - adverse effects; Patients; Prospective Studies; Safety; Triazoles - adverse effects; Voriconazole; Voriconazole - adverse effects
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-31788-1

Isavuconazole is a triazole with broad-spectrum antifungal activity. In this post-hoc analysis of two prospective clinical trials (VITAL and SECURE), the safety and efficacy of isavuconazole in patients aged ≥ 65 years with invasive fungal diseases were evaluated. Patients were divided into two subgroups (≥ 65 and < 65 years). Adverse events (AEs); all-cause mortality; and overall, clinical, mycological, and radiological response were assessed. A total of 155 patients ≥ 65 years were enrolled in both trials. Most patients reported AEs. In the isavuconazole arm of both studies, serious AEs (SAEs) were greater in patients ≥ 65 versus < 65 years: 76.7% versus 56.9% (VITAL); 61.9% versus 49.0% (SECURE). In SECURE, SAE rates were similar in the ≥ 65 years subgroup of both treatment arms (61.9% vs 58.1%), while in the < 65 years subgroup the SAE rate was lower in the isavuconazole arm (49.0% vs 57.4%). In VITAL, all-cause mortality through day 42 (30.0% vs 13.8%) was higher, and overall response at end of treatment (27.6% vs 46.8%) was lower in patients ≥ 65 years versus < 65 years. In SECURE, all-cause mortality was similar between both subgroups, and isavuconazole (20.6% vs 17.9%) and voriconazole (22.6% vs 19.4%) treatment arms. The overall response was lower in the ≥ 65 years than the < 65 years subgroup in the isavuconazole (23.7% vs 39.0%) and voriconazole (32.0% vs 37.5%) arms. The safety and efficacy of isavuconazole were better in patients < 65 versus ≥ 65 years, and the safety profile was more favorable than that of voriconazole in both subgroups.Clinicaltrials.gov identifier NCT00634049 and NCT00412893.