Intraocular Inflammation, Safety Events, and Outcomes After Intravitreal Injection of Ranibizumab, Aflibercept, Brolucizumab, Abicipar Pegol, and Faricimab for nAMD

Purpose: To compare the rates of intraocular inflammation (IOI) in patients with neovascular age-related macular degeneration (nAMD) after injection of intravitreal (IVT) antivascular endothelial growth factor drugs. Methods: This study included all phase 3 randomized clinical trials of patients with nAMD treated with ranibizumab, aflibercept, brolucizumab, abicipar pegol, or faricimab. The outcomes assessed were the incidence of IOI, retinal artery occlusion (RAO), retinal vasculitis and choroiditis, endophthalmitis, and serious systemic adverse events (AEs) as well as the change in visual acuity (VA) (Early Treatment Diabetic Retinopathy Study letters) and in central retinal thickness (CRT). Results: Abicipar pegol was associated with a higher incidence of IOI than aflibercept, ranibizumab, faricimab, and sham injections, while brolucizumab was associated with a higher rate of IOI than aflibercept, faricimab, and sham injections. Abicipar pegol was also associated with a higher rate of endophthalmitis than aflibercept. Significantly more retinal vasculitis and choroiditis was seen with abicipar pegol and brolucizumab than with ranibizumab and aflibercept, respectively, and RAOs occurred more frequently with abicipar pegol and brolucizumab than with ranibizumab and aflibercept, respectively. There were no differences in the change in VA among the drugs. Treatment with brolucizumab resulted in a greater change in CRT than with abicipar pegol, aflibercept, ranibizumab, and faricimab, while treatment with faricimab resulted in a greater change in CRT than aflibercept and ranibizumab. Faricimab was associated with fewer serious systemic AEs than aflibercept. Conclusions: Abicipar pegol and brolucizumab were associated with a higher incidence of ocular AEs in phase 3 randomized controlled trials. The potential benefits of these drugs should be weighed against the AEs.