Abstract Rationale Chronic pulmonary aspergillosis (CPA) is a progressive, refractory fungal lung disease associated with high morbidity and mortality, typically developing in patients with pre-existing structural lung disease following chronic colonization or infection with Aspergillus species. Currently, azole antifungal agents are the cornerstone of CPA treatment, with voriconazole (VRCZ) being the most widely used. However, VRCZ is frequently associated with adverse effects, such as hepatotoxicity and visual disturbances, often necessitating treatment modification or discontinuation. Recently, isavuconazole (ISCZ) was approved in Japan for the treatment of CPA; however, global real-world data on its efficacy and safety are limited. Therefore, we retrospectively analyzed CPA cases treated at our institution over six years to compare the efficacy and safety of ISCZ and VRCZ. Methods We retrospectively reviewed patients diagnosed with CPA who received ISCZ or VRCZ at the Department of Pulmonology, Kameda Medical Center, between May 2019 and July 2025. Patient characteristics, treatment responses, and adverse events were evaluated. The primary endpoint was the incidence of adverse events, and the secondary endpoint was treatment success, defined as the absence of disease progression in clinical and radiological assessments, with improvement observed in at least one of these domains. Adverse events were graded according to the Common Terminology Criteria for Adverse Events, and events of grade ≥1 were considered drug-related. Results This study included 49 patients: 15 and 34 in the ISCZ and VRCZ groups, respectively. The median ages were 75 and 71 years, and 73% and 68% of the patients were men, respectively. Adverse events occurred in 40% and 85% of the patients in the ISCZ and VRCZ groups, respectively (p = 0.004). Specific adverse events included hepatotoxicity (13% vs. 60%, p = 0.005), visual disturbances (0% vs. 21%, p = 0.084), gastrointestinal symptoms (12% vs. 20%, p = 0.660), and skin rashes (9% vs. 13%, p = 0.635). Treatment success was achieved in 60% and 53% of the ISCZ and VRCZ cases, respectively (p = 0.760). Conclusions ISCZ demonstrated a significantly lower incidence of adverse events while maintaining clinical efficacy comparable to that of voriconazole in patients with CPA. Considering its favorable safety profile and oral availability, ISCZ may represent a promising and practical alternative to voriconazole as a mainstay therapy for CPA, particularly in older or treatment-intolerant patients. This abstract is funded by: None
Sakamoto et al. (Fri,) studied this question.