The Efficacy and Safety of Brolucizumab for the Treatment of nAMD: A Systematic Review and Meta-Analysis

Abstract

Introduction: As demonstrated in pivotal clinical trials, brolucizumab can be used to treat neovascular age-related macular degeneration (nAMD) because it antagonizes vascular endothelial growth factor (VEGF) in the vitreous. However, brolucizumab may cause retinal vasculitis obliterans in the presence of inflammation in the eyes. In the present study, a meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the efficacy and safety of brolucizumab.Methods:ClinicTrail.gov., Embase, Cochrane Library, and PubMed were retrieved from inception until 31 December 2021 for RCTs assessing the efficacy and safety of brolucizumab. Changes in best corrected visual acuity (BCVA) and central sub-field thickness (CSFT) and incidence of adverse events, serious adverse events, and serious ocular adverse events were extracted from eligible RCTs. A meta-analysis was performed using RevMan 5.4.1.Results: A total of six RCTs with 3,574 participants were finally involved in this meta-analysis. The changes of best corrected visual acuity (BCVA) showed no statistically significant difference between the brolucizumab-treated group and aflibercept-treated group. Brolucizumab induced higher central sub-field thickness (CSFT) reduction than the control agent (aflibercept). The incidence of adverse events was similar between the brolucizumab group and control group (OR 0.63, 95% CI 0.37 to 1.08, p = 0.09), and brolucizumab caused fewer serious adverse events (OR 0.78, 95% CI 0.63 to 0.95, p = 0.01). However, brolucizumab could lead to more serious ocular adverse events than Lucentis and aflibercept (OR 2.15, 95% CI 1.11 to 4.16, p = 0.02).Conclusion: Brolucizumab was non-inferior to other anti-VEGF agents in improving BCVA and decreasing CSFT. But it caused more serious ocular adverse events which is worthy of special attention by ophthalmologists.

Review on the Safety and Efficacy of Brolucizumab for Neovascular Age-Related Macular Degeneration From Major Studies and Real-World Data

“…They found that brolucizumab-treated eyes exhibited a greater reduction in thickness at 1, 3, 6, 9, and 12 months postinjection compared with aflibercept. 58 These findings are consistent with several case series, which also reported significant decreases in CST. 42,44 Enriquez et al 44 reported 50 eyes that experienced complete fluid resolution after a single injection.…”

“…Regarding modification of dosing or administration frequency to improve safety outcomes, a recent meta-analysis evaluating 6 RCTs and 3574 patients revealed that there is no significant difference between brolucizumab 6 mg and 3 mg dosing regarding serious adverse events and serious ocular adverse events. Brolucizumab was more likely to lead to severe ocular adverse events compared with aflibercept and ranibizumab (odds ratio: 2.15, 95% CI: 1.11–4.16; P = 0.02) 58. Notably, the study did not delineate between types of serious ocular events, so specific conclusions about IOI, RV, and RVO cannot be drawn.…”

“…In a meta-analysis involving 6 randomized controlled trials (RCTs), no significant difference was found in BCVA between brolucizumab and aflibercept-treated eyes between 1 and 12 months after the first injection. 58 In addition, in 1 case series of 172 previously treated eyes from 152 patients, investigators found no significant difference between baseline and final visual acuity, even when stratifying analyses by the number of injections, IOI, and retinal fluid. 44 Conversely, a study evaluating short-term real-world outcomes in 63 eyes reported a significant increase in mean BCVA in patients with recalcitrant fluid accumulations.…”

“…Brolucizumab was more likely to lead to severe ocular adverse events compared with aflibercept and ranibizumab (odds ratio: 2.15, 95% CI: 1.11-4.16; P = 0.02). 58 Notably, the study did not delineate between types of serious ocular events, so specific conclusions about IOI, RV, and RVO cannot be drawn. In addition, the MERLIN trial, Primary endpoint Mean change in VA between baseline and 1 y: 8.0 letters in bevacizumab monthly vs 8.5 letters in ranibizumab monthly 5.9 letters in bevacizumab PRN vs 6.8 letters in ranibizumab PRN Ranibizumab vs bevacizumab: Both had equivalent effects on visual acuity at all time points throughout the first year of follow-up, when comparing the same dosing regimens.…”

“…By Komodo Health Care Map and the Intelligent Research in Sight Registry in the United States, over 90% of patients had switched from another anti-VEGF treatment;55 thus, it may approximate real-world outcomes in this population. In a meta-analysis involving 6 randomized controlled trials (RCTs), no significant difference was found in BCVA between brolucizumab and aflibercept-treated eyes between 1 and 12 months after the first injection 58. In addition, in 1 case series of 172 previously treated eyes from 152 patients, investigators found no significant difference between baseline and final visual acuity, even when stratifying analyses by the number of injections, IOI, and retinal fluid 44.…”