Adverse Events Reported with Standard-Dose and High-Dose Aflibercept: A FAERS Pharmacovigilance Study.

Area of Science:

• Pharmacovigilance and drug safety research.
• Ophthalmology and retinal disease treatment.
• Regulatory science and post-market surveillance.

Background:

• Aflibercept is used for various ocular indications.
• Two formulations exist: standard-dose (2 mg) and high-dose (8 mg).
• Understanding comparative safety profiles is crucial for clinical practice.

Purpose of the Study:

• To compare ocular and systemic adverse event (AE) reporting patterns between aflibercept 2 mg (SD) and 8 mg (HD) formulations.
• To identify potential safety signals associated with the high-dose formulation using disproportionality analysis.

Main Methods:

• Utilized the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) database.
• Employed disproportionality analysis, including reporting odds ratios (ROR), with Bonferroni correction and Evans criteria for signal detection.
• Conducted head-to-head comparisons of RORs between SD and HD using the Breslow-Day test.

Main Results:

• Compared to SD, HD showed significantly higher RORs for endophthalmitis, eye inflammation, retinal vasculitis, and systemic vasculitis.
• Specific RORs for HD vs. SD were noted for endophthalmitis (767.56 vs. 331.64), eye inflammation (118.45 vs. 43.98), retinal vasculitis (769.87 vs. 124.80), and systemic vasculitis (28.40 vs. 4.05).

Conclusions:

• The FAERS data suggest an association between the high-dose aflibercept formulation and increased reporting of specific ocular and systemic adverse events.
• These findings highlight potential safety differences that warrant further investigation to establish causality and quantify absolute risks.