Comparative Analysis of Ocular Adverse Events between Aflibercept 8 mg and Faricimab: A Global Population-Based Study across 65 Countries.

Objective

To compare the ocular safety of intravitreal aflibercept injections and faricimab using population-based, global postmarketing data in a large pharmacovigilance study.

Design

Population-based, retrospective pharmacovigilance study.

Subjects, participants, and/or controls: Patients for whom ocular adverse event (AE) reports were submitted to the US Food and Drug Administration Adverse Event Reporting System (FAERS) between January 2004 and June 2025 and for whom intravitreal aflibercept injections (2 or 8 mg, where dose was recorded) or faricimab were listed as the primary suspect drug were included.

Methods

After deduplication, disproportionality was assessed using reporting odds ratios (RORs, 95% confidence interval). Safety signals were considered statistically significant if they met Evans criteria (ROR > 2, χ 2 > 4, n ≥ 3), Bonferroni-adjusted P < 0.0003, and Bayesian threshold lower bound of the Bayesian information component (IC 025 ) >0.

Main outcome measures

Disproportionality signals for ocular AEs associated with intravitreal aflibercept 2 mg, aflibercept 8 mg, and faricimab, using aflibercept 2 mg as the reference comparator, given its longer market availability and well-established safety profile.

Results

Among 13 809 873 FAERS reports, 30 761 involved intravitreal aflibercept 2 mg (n = 21 058), aflibercept 8 mg (n = 727), or faricimab (n = 8976). After deduplication, 8352 reports remained for aflibercept 2 mg, 327 for aflibercept 8 mg, 4168 for faricimab, and 13 797 026 for other drugs. Most patients were aged 65 to 85 years; women comprised 48.6% of the 8 mg group, 39.9% of faricimab, and 20.8% of the 2 mg group. Aflibercept 8 mg showed the highest disproportionality for intraocular inflammation and infection-related events, including anterior chamber flare (ROR = 1410.5), vitritis (853.3), retinal vasculitis (352.2), infectious (1208.3), and sterile endophthalmitis (352.0), as well as blindness (71.1) and reduced visual acuity (74.6). Faricimab had the highest RORs for injection-related inflammatory and hemorrhagic events-hypopyon (112.8), retinal pigment epithelial tear (193.9), choroidal hemorrhage (142.3), and pseudoendophthalmitis (309.9)-whereas aflibercept 2 mg was more often associated with structural complications, including increased intraocular pressure (187.8), posterior capsule rupture (80.1), vitreous hemorrhage (76.9), and retinal detachment (20.8). All signals met Bonferroni-adjusted significance (P < 0.0001) and Bayesian criteria (IC 025 > 0).

Conclusions

Aflibercept 8 mg showed strong signals for intraocular inflammation, vasculitis, and endophthalmitis, aflibercept 2 mg was linked to structural complications, and faricimab had the highest disproportionality for select immunovascular events. These findings delineate agent- and dose-specific safety profiles within a unified comparative framework and reinforce the critical need for ongoing postmarketing surveillance.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.