Abstract
Abstract
Purpose
Post-marketing reports have associated faricimab, the first intravitreal bispecific antibody, with intraocular inflammation (IOI). Its inflammatory phenotype, temporal pattern, and systemic safety relative to established anti-VEGF agents remain unclear. We compared faricimab with aflibercept and ranibizumab across three independent pharmacovigilance databases.
Design
Triangulated Pharmacovigilance study.
Methods
We analyzed FAERS reports (Q1 2022-Q2 2026) with external validation in JADER (Japan) and EudraVigilance (Europe). After de-duplication and restriction to primary-suspect reports, we computed reporting odds ratios (RORs) with false discovery rate control, derived confounder-adjusted RORs by logistic regression, modeled time-to-onset (TTO) with Weibull distributions, and graded signals with a pre-specified bidirectional cross-database evidence framework.
Results
The FAERS cohort comprised 6,833 faricimab, 6,714 aflibercept, and 2,533 ranibizumab reports. Faricimab showed higher reporting of anterior-chamber and vitreal inflammation: adjusted RORs (comparator versus faricimab; values P
= 2.6E-14) with a markedly flatter Weibull distribution (shape 0.81 vs ≈0.42). Aflibercept predominated for endophthalmitis-spectrum and intraocular pressure events; ranibizumab for vitreous hemorrhage (confirmed in JADER). Faricimab showed lower reporting across cardiac, nervous system, vascular, and renal organ classes, confirmed in EudraVigilance. An unadjusted death signal did not survive adjustment and was absent in outcome-based JADER analyses.
Conclusions
Faricimab exhibits a reproducible, delayed-onset, anterior-predominant IOI phenotype alongside a comparatively favorable systemic safety profile. Clinicians should recognize that faricimab-associated IOI may arise weeks to months after injection.
Highlights
Faricimab showed higher reporting of anterior and intermediate intraocular inflammation than aflibercept and ranibizumab across three independent databases.
Faricimab-associated inflammation arose late, with a median onset of 100 days versus 7 days for the comparators.
Aflibercept predominated for endophthalmitis-spectrum events and ranibizumab for vitreous haemorrhage.
No drug showed excess death reporting after adjustment and outcome-field verification.