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

This pharmacovigilance study drew upon the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) database to compare the reporting patterns of ocular and systemic adverse events (AEs) for the 2 mg (standard-dose [SD]) and 8 mg (high-dose [HD]) formulations of aflibercept given for any ocular indication. Disproportionality analysis, including reporting odds ratios (ROR), was used to compare each dose individually to the background reporting rate for the AE. Statistical significance of the RORs was evaluated using Bonferroni correction, alongside signal detection based on Evans criteria, and Bayesian information components. The Breslow-Day test was used to conduct a head-to-head comparison of RORs between each dose. We identified 953 SD and 314 HD AE reports within the 750-day period after the approval of HD by the U.S. Food and Drug Administration (FDA; 8/18/2023). Compared to SD, HD had a higher ROR for endophthalmitis (HD: ROR 767.56 [95% CI, 466.11-1263.95]; SD: ROR 331.64 [95% CI, 216.71-507.51]), eye inflammation (HD: ROR 118.45 [95% CI, 55.85-251.20]; SD: 43.98 [95% CI, 21.87-88.44]), retinal vasculitis (HD: ROR 769.87 [95% CI, 337.13-1758.04]; SD: ROR 124.80 [95% CI, 39.67-392.63]), and systemic vasculitis (HD: ROR 28.40 [95% CI, 14.63-55.14]; SD: ROR 4.05 [1.52-10.82]). These results, based on FAERS, indicate associations rather than causal relationships. Further studies are needed to quantify the absolute risks and elucidate the mechanisms underlying differences in safety signals, if any.