Sierra Eye Associates, and the University of Nevada, Reno, School of Medicine, Reno, Nevada.
Retina Consultants Texas, Retina Consultants of America, Houston, Texas.
Ophthalmology. 2022 Sep;129(9):974-985. doi: 10.1016/j.ophtha.2022.04.028. Epub 2022 May 7.
To assess the 52-week efficacy and safety of brolucizumab 6 mg administered every 4 weeks compared with aflibercept 2 mg dosed every 4 weeks in eyes with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid.
Multicenter, randomized, double-masked phase 3a study.
Participants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti-vascular endothelial growth factor treatment).
Eyes were randomized (2:1) to intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks up to and including week 100.
The primary end point was analysis of noninferiority in mean best-corrected visual acuity (BCVA) change from baseline to week 52 (margin, 4 letters). Other key end points included change in central subfield thickness (CST) from baseline to week 52, fluid-free status (no intraretinal fluid and no subretinal fluid), and safety.
At week 52, brolucizumab was noninferior to aflibercept in BCVA change from baseline (least squares mean difference, -0.6 Early Treatment Diabetic Retinopathy Study letters; 95% confidence interval [CI], -2.1 to 0.9; P < 0.001). A total of 4.8% and 1.7% of participants reported a 15-letter or more BCVA loss from baseline at week 52 in the brolucizumab and aflibercept groups, respectively. In eyes treated with brolucizumab compared with those treated with aflibercept, the CST was reduced significantly (P < 0.001), and a significantly greater proportion of eyes were fluid free at week 52 (40.4% brolucizumab vs. 19.0% aflibercept; 95% CI, 13.9-29.0; P < 0.001). Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, were 9.3% (0.8% and 2.0%) for brolucizumab versus 4.5% (0% and 0%) for aflibercept, respectively.
Visual acuity outcomes in previously treated participants with nAMD and persistent retinal fluid receiving brolucizumab 6 mg dosed every 4 weeks were noninferior to aflibercept 2 mg dosed every 4 weeks, with superior anatomic outcomes. However, incidences of IOI, including retinal vasculitis and retinal vascular occlusion, also were higher, leading to study termination.
评估 52 周内每 4 周给药 6mg 的 brolucizumab 相对于每 4 周给药 2mg 的 aflibercept 在患有新生血管性年龄相关性黄斑变性（nAMD）和持续性视网膜液的眼中的疗效和安全性。
多中心、随机、双盲 3a 期研究。
接受难治性 nAMD（尽管先前频繁接受抗血管内皮生长因子治疗，但仍存在残余视网膜液）治疗的参与者。
眼随机（2:1）接受玻璃体内 brolucizumab 6mg 或 aflibercept 2mg 每 4 周治疗，直至第 100 周。
主要终点为从基线到第 52 周时平均最佳矫正视力（BCVA）变化的非劣效性分析（边缘，4 个字母）。其他关键终点包括从基线到第 52 周时中央视网膜下厚度（CST）的变化、无液状态（无视网膜内液和无视网膜下液）和安全性。
在第 52 周时，brolucizumab 在从基线开始的 BCVA 变化方面不劣于 aflibercept（最小二乘均数差异，-0.6 早期治疗糖尿病视网膜病变研究字母；95%置信区间[CI]，-2.1 至 0.9；P<0.001）。在第 52 周时，分别有 4.8%和 1.7%的 brolucizumab 和 aflibercept 组参与者报告从基线开始 BCVA 损失 15 个字母或更多。与 aflibercept 相比，接受 brolucizumab 治疗的眼睛 CST 显著降低（P<0.001），并且在第 52 周时无液状态的比例显著更高（40.4%brolucizumab 与 19.0% aflibercept；95%CI，13.9-29.0；P<0.001）。眼内炎症（IOI）的发生率，包括视网膜血管炎和视网膜血管阻塞，分别为 brolucizumab 9.3%（0.8%和 2.0%）和 aflibercept 4.5%（0%和 0%）。
在接受过治疗的患有 nAMD 和持续性视网膜液的患者中，每 4 周接受 6mg brolucizumab 治疗的患者的视力结果不劣于每 4 周接受 2mg aflibercept 治疗的患者，且具有更好的解剖学结果。然而，IOI 的发生率，包括视网膜血管炎和视网膜血管阻塞，也较高，导致研究终止。
