This retrospective real-world study used the TriNetX database (2010–2025) to compare 6-week all-cause mortality in adults with invasive pulmonary aspergillosis (IPA) treated with voriconazole (VRCZ) vs. posaconazole or isavuconazole (PSCZ/ISCZ), with propensity score matching (PSM) applied to balance 738 pairs.
6-week all-cause mortality was 18.6% with VRCZ vs. 16.4% with PSCZ/ISCZ (OR 1.16; 95% CI 0.89–1.52; p=0.273) — a non-significant difference that held across subgroup and sensitivity analyses, even though PSCZ/ISCZ patients had higher baseline severity and more renal impairment before matching.
- Retrospective database design limits causal inference and may have residual confounding despite PSM. - PSCZ and ISCZ were pooled together, masking potential outcome differences between those two agents. - TriNetX data rely on administrative coding, which may misclassify IPA diagnosis or treatment intent.
For patients with IPA who cannot tolerate voriconazole — especially those with renal impairment or higher baseline severity — posaconazole or isavuconazole appear to be viable alternatives with comparable mortality outcomes. Clinicians can use these agents in a personalized approach without expecting a mortality penalty in real-world settings.
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