目的:报告6mg布鲁单抗(Beovu®)与6mg的安全性和有效性在第52周主要终点分析后(第52周至第104周,研究终止后),新生血管性年龄相关性黄斑变性(nAMD)和持续性视网膜液的参与者每4周给予阿柏西普(Eylea®)2mg。
方法:多中心,随机化,双掩蔽阶段3a研究。
方法:患有顽固性nAMD(尽管以前经常使用抗血管内皮生长因子治疗,但持续残留的视网膜液)的参与者。
方法:研究对象随机分为2:1,每4周接受玻璃体内注射6mg布卢珠单抗或2mg阿柏西普,共100周,或直到研究终止。
方法:所有可用功效(平均最佳矫正视力的非劣效性分析[BCVA],中心子场厚度[CST],无液状态[无视网膜内液和无视网膜下液]),以及终止研究的安全性数据,包括在研究终止前完成研究的参与者直至第104周的数据。第52周后的所有P值都是标称的,并且反映了功效分析的观察数据。
结果:Brolucizumab每4周6mg从基线到第104周的平均BCVA变化不劣于阿柏西普2mg(最小二乘平均差,-0.4早期治疗糖尿病视网膜病变研究字母;95%置信区间[CI],-3.7至3.0;P=0.0169)。≥15个字母丢失的眼睛比例为:brolucizumab为6.2%,阿柏西普为4.7%。(P=0.0014),在第104周时,更大比例的眼睛没有液体(52.5%的brolucizumabvs.28.2%阿柏西普;95%CI,11.9-37.3;P<0.001)aflibercept.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,布鲁单抗为11.5%(0.8%和2.2%),阿柏西普为6.1%(0%和0.6%),分别。
结论:与52周的结果一致,从基线到第104周或研究终止,每4周6mg的brolucizumab平均BCVA变化不低于每4周2mg的解剖学结局.IOI的发病率,包括视网膜血管炎和视网膜血管阻塞,布罗珠单抗与aflibercept;因此,负荷方案后,布鲁单抗的使用频率不应超过每8周一次.
OBJECTIVE: To report the safety and efficacy of brolucizumab (Beovu®) 6 mg vs. aflibercept (Eylea®) 2 mg administered every 4 weeks in participants with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid after the Week 52 primary endpoint analysis (from Week 52 up to Week 104, post-study termination).
METHODS: Multicenter, randomized, double-masked Phase 3a study.
METHODS: Participants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti-vascular endothelial growth factor treatment).
METHODS: Study eyes were randomized 2:1 to intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks for 100 weeks, or until study termination.
METHODS: All available efficacy (analysis of noninferiority in mean best-corrected visual acuity [BCVA], central subfield thickness [CST], fluid-free status [no intraretinal fluid and no subretinal fluid]), and safety data up to study termination, including data up to Week 104 for those participants who completed the study prior to its termination. All P values after Week 52 were nominal and reflect observed data for the efficacy analyses.
RESULTS: Brolucizumab 6 mg every 4 weeks was noninferior to aflibercept 2 mg in mean BCVA change from baseline to Week 104 (least squares mean difference, -0.4 Early Treatment Diabetic Retinopathy Study letters; 95% confidence interval [CI], -3.7 to 3.0; P = 0.0169). The proportion of eyes with ≥15-letter loss was 6.2% for brolucizumab and 4.7% for aflibercept. (P = 0.0014), and a greater proportion of eyes were fluid free at Week 104 (52.5% brolucizumab vs. 28.2% aflibercept; 95% CI, 11.9-37.3; P < 0.001) in eyes treated with brolucizumab vs. aflibercept. Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, was 11.5% (0.8% and 2.2%) for brolucizumab vs 6.1% (0% and 0.6%) for aflibercept, respectively.
CONCLUSIONS: Consistent with 52-week results, brolucizumab 6 mg every 4 weeks was noninferior in mean BCVA change with anatomic outcomes superior to aflibercept 2 mg every 4 weeks from baseline to Week 104 or study termination. The incidence of IOI, including retinal vasculitis and retinal vascular occlusion, was higher with brolucizumab vs. aflibercept; therefore, brolucizumab should not be used more frequently than every 8 weeks following the loading regimen.