Clinical positioning of Voriconazole, Posaconazole, and Isavuconazole in the treatment of Invasive Pulmonary Aspergillosis: A Global Real-World Database Study.

INTRODUCTION: This study evaluated the clinical outcomes of invasive pulmonary aspergillosis (IPA) treated with voriconazole (VRCZ), posaconazole (PSCZ), or isavuconazole (ISCZ) using a large-scale real-world database. MATERIALS AND METHODS: A retrospective study using the TriNetX database (2010-2025) identified patients with IPA initiated on VRCZ, PSCZ, or ISCZ. Background factors were adjusted using Propensity Score Matching (PSM). The primary endpoint was 6-week all-cause mortality. RESULTS: Of 8,746 patients identified, 3,603 met selection criteria (VRCZ: 2,836; PSCZ/ISCZ: 767). PSM identified 738 matched pairs of balanced covariates. The 6-week mortality was 18.6% for VRCZ and 16.4% for PSCZ/ISCZ (OR 1.16; 95% CI 0.89-1.52; p=0.273). No significant differences were observed in the primary, subgroup, or sensitivity analyses. Notably, the PSCZ/ISCZ group initially included more severe cases and patients with renal impairment. CONCLUSION: No significant differences in all-cause mortality were observed among the three drugs. Despite the higher baseline risk in the PSCZ and ISCZ groups, the outcomes were comparable to those in the VRCZ group, suggesting that these agents are effective alternatives in high-risk real-world settings. PSCZ and ISCZ are valuable options in personalized medicine. Therefore, further prospective studies are warranted.