Efficacy, Safety, and Durability of Brolucizumab: An 8-Month Post-Marketing Surveillance Analysis

Abstract

Importance Brolucizumab (Beovu ® ) is an anti-vascular endothelial growth factor (anti-VEGF) agent approved for the treatment of neovascular age-related macular degeneration (nvAMD). Brolucizumab was marketed for its noninferiority to aflibercept and its potential for greater durability. However, post-marketing utilization has been tempered by safety concerns. Objective We evaluate the visual and anatomic efficacy of brolucizumab, examine changes in treatment intervals after switching to brolucizumab, and estimate the incidence of drug-related adverse events in the real world. Design, Setting, and Participants This was a retrospective consecutive case series of 626 eyes (543 patients) with nvAMD treated with 1438 brolucizumab injections at a single retina practice between 10/1/2019 and 5/15/2020. Main Outcomes and Measures Changes in visual acuity (VA); anatomic outcomes assessed by optical coherence tomography (OCT) including central subfield thickness (CST), macular volume (MV), presence of intraretinal fluid (IRF), subretinal fluid (SRF), and serous pigment epithelial detachment (sPED) on foveal line scans; treatment intervals before and after receiving brolucizumab; and the incidence of brolucizumab-related adverse events. Results The majority of eyes (N = 531, 89.7%) had received prior anti-VEGF therapy with aflibercept, ranibizumab, and/or bevacizumab. VA improved in treatment-naïve eyes (+3.7 letters, p = 0.04), and was maintained in previously treated eyes. There were significant improvements in all anatomic outcomes in both groups (p < 0.001). We observed a 4.8% incidence of intraocular inflammation (IOI) and a 0.6% incidence of retinal vasculitis. The average treatment interval increased from 6.3 to 6.8 weeks (p = 0.001). Conclusions and Relevance Brolucizumab treatment was associated with VA improvement in naïve eyes and maintenance of VA in previously treated eyes. Switching to brolucizumab was associated with improved anatomic outcomes and extended treatment intervals in most eyes. We observed a similar incidence of IOI and a lower incidence of retinal vasculitis compared to the Safety Review Committee’s analysis of HAWK and HARRIER.

Central retinal artery occlusion after intravitreal brolucizumab injection for treatment-naïve neovascular age-related macular degeneration; a case report

“…In the HAWK and HARRIER studies, however, the brolucizumab injection group had a significantly higher incidence of IOI at 4.7%, compared to the aflibercept group which had a much lower rate of 0.6% [ 4 ]. Similarly, Saba et al reported that the incidence of IOI was comparable at 4.8% in the 8-month post-marketing surveillance analysis [ 7 ].…”

“…Visual prognosis of most patients who underwent IOI revealed relatively good during the follow-up period [ 4 ]. However, there were several cases with relatively poor visual prognosis, such as retinal vasculitis with RAO [ 4 , 7 – 9 ]. A retrospective analysis of 26 eyes from 25 patients evaluated retinal vasculitis following the administration of brolucizumab, and 92% of cases of retinal vasculitis were accompanied by anterior chamber inflammation and/or posterior segment inflammation [ 8 ].…”

Testing the Homogeneity of Differences between Two Proportions for Stratified Bilateral and Unilateral Data across Strata

“…Also, in fact, many studies in clinical ophthalmology focus only on the eye instead of a person with paired organs. For example, Saba and Walter [20] worked on a retrospective consecutive case series of 626 eyes (543 patients) with nvAMD treated with 1438 Brolucizumab injections. Some of these patients contributed one eye and some contributed two eyes, and it would be imprudent to ignore the correlation between two eyes from the same patient in a statistical analysis.…”