Risk of inflammation, retinal vasculitis and retinal occlusion-related events with brolucizumab: post-hoc review of HAWK and HARRIER.

Abstract Objective An independent Safety Review Committee (SRC; supported by Novartis Pharma AG [Basel, Switzerland]) analyzed investigator-reported cases of intraocular inflammation (IOI), endophthalmitis and retinal arterial occlusion in the phase 3 HAWK and HARRIER trials of brolucizumab versus aflibercept in neovascular age-related macular degeneration (nAMD). Design A post-hoc analysis of a subset of data from two 2-year, double-masked, multicenter, active-controlled randomized phase 3 trials (NCT02307682, NCT02434328). Participants Patients (N=1817) with untreated, active choroidal neovascularization due to AMD in the study eye were randomized and treated in HAWK/HARRIER. The SRC reviewed data from cases of investigator-reported IOI (60/1088 brolucizumab-treated eyes; 8/729 aflibercept-treated eyes). Methods The SRC received details and images (color fundus photography, fluorescein angiography and optical coherence tomography) for all investigator-determined cases of IOI, retinal arterial occlusion and endophthalmitis. Cases were reviewed in detail by ≥2 readers, then adjudicated by the SRC as a group. Main outcome measures Within this subset of patients: incidence of IOI, signs and incidence of retinal vasculitis and/or retinal vascular occlusion, and visual acuity loss; time since first brolucizumab injection to IOI event onset; frequency of visual acuity loss following brolucizumab injection by time of first IOI event onset. Results Fifty brolucizumab-treated eyes were considered to have definite/probable drug-related events within the spectrum of IOI, retinal vasculitis and/or vascular occlusion. Based on these cases, incidence of definite/probable IOI was 4.6% (IOI + vasculitis, 3.3%; IOI + vasculitis + occlusion, 2.1%). There were 8 cases (incidence 0.74%) of at least moderate visual acuity loss (≥15 ETDRS letters) in eyes with IOI; 7 were in eyes with IOI + vasculitis + occlusion. Of the 8 cases, 5 experienced their first IOI-related event within 3 months of the first brolucizumab injection (increasing to 7/8 within 6 months). Incidence of IOI in aflibercept-treated eyes was 1.1%, with at least moderate visual acuity loss in 0.14%. Conclusions This analysis of IOI cases following brolucizumab injection identified signs of retinal vasculitis with or without retinal vascular occlusion, and an associated risk of visual acuity loss. The findings will help physicians to evaluate the risks and benefits of brolucizumab treatment for nAMD.