Retina Consultants of Texas, Retina Consultants of America, Blanton Eye Institute, Houston Methodist Hospital, Houston.
Regeneron Pharmaceuticals, Inc, Tarrytown, New York.
JAMA Ophthalmol. 2023 Sep 1;141(9):834-842. doi: 10.1001/jamaophthalmol.2023.2421.
Aflibercept, 8 mg, may have greater therapeutic benefits compared with aflibercept, 2 mg, in patients with neovascular age-related macular degeneration (nAMD), including potentially improved outcomes and decreased treatment burden.
To assess safety and efficacy of aflibercept, 8 mg, in patients with nAMD.
DESIGN, SETTING, AND PARTICIPANTS: The CANDELA trial was a phase 2, randomized, single-masked, open-label, 44-week clinical trial conducted in the US. Treatment-naive patients with active subfoveal choroidal neovascularization secondary to nAMD and a best-corrected visual acuity score of 78 to 24 letters (approximately 20/32 to 20/320) in the study eye were enrolled between November 2019 and November 2021.
Eligible participants were randomized 1:1 to receive 3 monthly doses of 8 mg (70 μL) or 2 mg (50 μL) of aflibercept followed by doses at weeks 20 and 32.
Coprimary end points were the proportion of eyes without fluid (absence of intraretinal and subretinal fluid) in the central subfield at week 16 and safety.
All 106 eligible eyes were randomized to receive aflibercept, 8 mg (n = 53), or aflibercept, 2 mg (n = 53). Overall, 66 participants (62.3%) were female. The proportion of eyes without fluid in the central subfield with 8-mg vs 2-mg aflibercept was 50.9% (n = 27) vs 34.0% (n = 18) (difference, 17.0 [95% CI, -1.6 to 35.5] percentage points; P = .08) at week 16 and 39.6% (n = 21) vs 28.3% (n = 15) (difference, 11.3 [95% CI, -6.6 to 29.2] percentage points; nominal P = .22) at week 44. At week 44, mean (SE) change in central retinal thickness was -159.4 (16.4) vs -137.2 (22.8) μm with 8 mg vs 2 mg of aflibercept, respectively (least squares mean difference, -9.5 [95% CI, -51.4 to 32.4]; nominal P = .65) and mean (SE) change in best-corrected visual acuity score was +7.9 (1.5) vs +5.1 (1.5) letters (least squares mean difference, +2.8 [95% CI, -1.4 to +7.0]; nominal P = .20). No differences in safety profiles between the groups were observed.
Although aflibercept, 8 mg, did not achieve the primary efficacy end point at week 16 at the 2-sided significance level of 5%, the observed trends in anatomic and visual improvements over 44 weeks with aflibercept, 8 mg, indicate potential additional therapeutic benefit over aflibercept, 2 mg. No new safety signals were observed over 44 weeks. These findings support further evaluation of aflibercept, 8 mg, in pivotal trials of exudative retinal diseases including nAMD and diabetic macular edema.
ClinicalTrials.gov Identifier: NCT04126317.
重要性：与阿柏西普 2mg 相比，阿柏西普 8mg 可能在治疗年龄相关性黄斑变性（AMD）患者方面具有更大的治疗益处，包括潜在改善结局和降低治疗负担。
目的：评估阿柏西普 8mg 在 nAMD 患者中的安全性和疗效。
设计、地点和参与者：CANDELA 试验是一项在美国进行的、为期 44 周的、2 期、随机、单盲、开放标签临床试验。在研究眼，治疗初治的、有活跃的脉络膜新生血管化的、与 nAMD 相关的、最佳矫正视力评分在 78 至 24 字母（约 20/32 至 20/320）的患者被纳入研究。
干预措施：符合条件的患者以 1:1 的比例随机分为 3 组，分别接受 3 个月剂量的 8mg（70μL）、2mg（50μL）阿柏西普，然后在第 20 周和第 32 周进行剂量给药。
主要终点和测量：主要终点是第 16 周时中央子场无液（无视网膜内和视网膜下液）的眼睛比例和安全性。
结果：所有 106 只符合条件的眼睛均随机接受阿柏西普 8mg（n=53）或阿柏西普 2mg（n=53）治疗。总体而言，66 名参与者（62.3%）为女性。与 2mg 阿柏西普相比，8mg 阿柏西普组中央子场无液的比例分别为 50.9%（n=27）和 34.0%（n=18）（差异为 17.0[95%CI，-1.6 至 35.5]个百分点；P=0.08），在第 16 周和 39.6%（n=21）和 28.3%（n=15）（差异为 11.3[95%CI，-6.6 至 29.2]个百分点；名义 P=0.22），在第 44 周。第 44 周时，与 2mg 阿柏西普相比，8mg 阿柏西普组中央视网膜厚度的平均（SE）变化分别为-159.4（16.4）μm 和-137.2（22.8）μm（最小二乘均数差异，-9.5[95%CI，-51.4 至 32.4]；名义 P=0.65），最佳矫正视力评分的平均（SE）变化分别为+7.9（1.5）和+5.1（1.5）个字母（最小二乘均数差异，+2.8[95%CI，-1.4 至 7.0]；名义 P=0.20）。两组间的安全性无差异。
结论和相关性：尽管在第 16 周时，阿柏西普 8mg 没有达到双侧显著性水平为 5%的主要疗效终点，但在 44 周内观察到的解剖学和视觉改善趋势表明，与阿柏西普 2mg 相比，阿柏西普 8mg 可能具有潜在的额外治疗益处。在 44 周内未观察到新的安全性信号。这些发现支持在包括 nAMD 和糖尿病性黄斑水肿在内的渗出性视网膜疾病的关键性试验中进一步评估阿柏西普 8mg。
试验注册：ClinicalTrials.gov 标识符：NCT04126317。
