Real-world safety of aflibercept 8 mg in neovascular age-related macular degeneration.

Aflibercept 8 mg is a higher-dose intravitreal anti-vascular endothelial growth factor formulation developed to extend treatment intervals in neovascular age-related macular degeneration (nAMD). Although pivotal trial data have supported its ocular safety profile, real-world evidence regarding intraocular inflammation (IOI) after aflibercept 8 mg remains limited. This study evaluated the real-world patient-level risk of newly coded IOI following aflibercept 8 mg initiation among patients with nAMD in a large multi-institutional electronic health record network. We conducted a retrospective cohort study using the TriNetX U.S. Collaborative Network. Patients with nAMD who received aflibercept 8 mg were identified using RxNorm code 1,232,150 with a strength restriction of 114.3 mg/mL and were required to have a prior or concurrent diagnosis of unspecified macular degeneration, exudative age-related macular degeneration, or retinal neovascularization. The index date was defined as the first recorded administration of aflibercept 8 mg. Newly coded IOI was assessed from 1 to 365 days after the index date and defined as acute or subacute iridocyclitis, retinal vasculitis, unspecified iridocyclitis, or posterior cyclitis. Patients with any component IOI diagnosis before the outcome window were excluded from the risk analysis. The mean age was 77.7 ± 10.1 years; 59.6% of patients were female, and 83.4% were White. After excluding patients with pre-existing IOI, 1,670 patients were eligible for outcome analysis. During the 365-day follow-up, 29 patients had newly coded IOI, corresponding to an observed patient-level risk of 1.74% (95% CI, 1.17%-2.48%). The mean follow-up was 281.5 ± 124.6 days, with a median of 365 days and an interquartile range of 162 days. Kaplan-Meier analysis showed an IOI-free survival probability of 97.89% at 365 days, corresponding to a Kaplan-Meier-estimated cumulative incidence of 2.11% (95% CI, 1.47%-3.04%). The low frequency of newly coded IOI provides preliminary descriptive reassurance. However, the absence of an active comparator, potential outcome misclassification, and the limited event count preclude definitive conclusions regarding comparative ocular safety.