Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.
Department of Ophthalmology, Cole Eye Institute, Cleveland, Ohio.
Ophthalmology. 2014 Jan;121(1):193-201. doi: 10.1016/j.ophtha.2013.08.011. Epub 2013 Sep 29.
To determine efficacy and safety of intravitreal aflibercept in patients with neovascular age-related macular degeneration (AMD) during a second year of variable dosing after a first-year fixed-dosing period.
Two randomized, double-masked, active-controlled, phase 3 trials.
Two thousand four hundred fifty-seven patients with neovascular AMD.
From baseline to week 52, patients received 0.5 mg intravitreal ranibizumab every 4 weeks (Rq4), 2 mg aflibercept every 4 weeks (2q4), 0.5 mg aflibercept every 4 weeks (0.5q4), or 2 mg aflibercept every 8 weeks (2q8) after 3 monthly injections. During weeks 52 through 96, patients received their original dosing assignment using an as-needed regimen with defined retreatment criteria and mandatory dosing at least every 12 weeks.
Proportion of eyes at week 96 that maintained best-corrected visual acuity (BCVA; lost <15 letters from baseline); change from baseline in BCVA.
Proportions of eyes maintaining BCVA across treatments were 94.4% to 96.1% at week 52 and 91.5% to 92.4% at week 96. Mean BCVA gains were 8.3 to 9.3 letters at week 52 and 6.6 to 7.9 letters at week 96. Proportions of eyes without retinal fluid decreased from week 52 (60.3% to 72.4%) to week 96 (44.6% to 54.4%), and more 2q4 eyes were without fluid at weeks 52 and 96 than Rq4 eyes (difference of 10.4% [95% confidence interval {CI}, 4.9-15.9] and 9.0% [95% CI, 3.0-15.1]). Patients received on average 16.5, 16.0, 16.2, and 11.2 injections over 96 weeks and 4.7, 4.1, 4.6, and 4.2 injections during weeks 52 through 96 in the Rq4, 2q4, 0.5q4, and 2q8 groups, respectively. The number of injections during weeks 52 through 96 was lower in the 2q4 and 2q8 groups versus the Rq4 group (differences of -0.64 [95% CI, -0.89 to -0.40] and -0.55 [95% CI, -0.79 to -0.30]; P < 0.0001, post hoc analysis). Incidences of Antiplatelet Trialists' Collaboration-defined arterial thromboembolic events were similar across groups (2.4% to 3.8%) from baseline to week 96.
All aflibercept and ranibizumab groups were equally effective in improving BCVA and preventing BCVA loss at 96 weeks. The 2q8 aflibercept group was similar to ranibizumab in visual acuity outcomes during 96 weeks, but with an average of 5 fewer injections. Small losses at 96 weeks in the visual and anatomic gains seen at 52 weeks in all arms were in the range of losses commonly observed with variable dosing.
在第一年固定剂量期后，进行第二年的剂量调整，评估玻璃体内注射阿柏西普在湿性年龄相关性黄斑变性（AMD）患者中的疗效和安全性。
两项随机、双盲、阳性对照、三期临床试验。
2457 名患有新生血管性 AMD 的患者。
从基线到第 52 周，患者接受每月 3 次注射后，分别接受玻璃体内 0.5mg 雷珠单抗每 4 周（Rq4）、2mg 阿柏西普每 4 周（2q4）、0.5mg 阿柏西普每 4 周（0.5q4）或 2mg 阿柏西普每 8 周（2q8）治疗。第 52 周至第 96 周期间，患者根据需要采用定义明确的再治疗标准和至少每 12 周进行一次强制性治疗的方案，继续使用他们原有的剂量方案。
第 96 周时保持最佳矫正视力（BCVA；与基线相比损失<15 个字母）的眼睛比例；与基线相比 BCVA 的变化。
第 52 周时，各治疗组保持 BCVA 的比例为 94.4%至 96.1%，第 96 周时为 91.5%至 92.4%。第 52 周和第 96 周时平均 BCVA 增益分别为 8.3 至 9.3 个字母和 6.6 至 7.9 个字母。第 52 周至第 96 周时，无视网膜液的眼比例从 60.3%降至 44.6%，与 Rq4 眼相比，更多的 2q4 眼在第 52 周和第 96 周时无液（差异分别为 10.4%[95%置信区间{CI}，4.9-15.9]和 9.0%[95% CI，3.0-15.1]）。在第 96 周时，Rq4、2q4、0.5q4 和 2q8 组患者平均接受了 16.5、16.0、16.2 和 11.2 次注射，在第 52 周至第 96 周期间分别接受了 4.7、4.1、4.6 和 4.2 次注射。与 Rq4 组相比，2q4 和 2q8 组在第 52 周至第 96 周期间的注射次数减少（差异分别为-0.64[95% CI，-0.89 至-0.40]和-0.55[95% CI，-0.79 至-0.30]；P<0.0001，事后分析）。从基线到第 96 周，各组抗血小板治疗试验者协作组定义的动脉血栓栓塞事件的发生率相似（2.4%至 3.8%）。
在 96 周时，所有阿柏西普和雷珠单抗组在改善视力和预防视力丧失方面同样有效。在 96 周的时间内，2q8 阿柏西普组与雷珠单抗的视力结果相似，但平均注射次数少 5 次。所有治疗组在第 52 周时观察到的视力和解剖学改善，在第 96 周时出现了小的损失，这些损失在通常观察到的剂量变化范围内。
