National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore.
Fundus Image Reading Centre, National Healthcare Group Eye Institute, Singapore.
JAMA Ophthalmol. 2020 Sep 1;138(9):935-942. doi: 10.1001/jamaophthalmol.2020.2443.
The 2-year efficacy and safety of combination therapy of ranibizumab administered together with verteporfin photodynamic therapy (vPDT) compared with ranibizumab monotherapy in participants with polypoidal choroidal vasculopathy (PCV) are unclear.
To compare treatment outcomes of ranibizumab, 0.5 mg, plus prompt vPDT combination therapy with ranibizumab, 0.5 mg, monotherapy in participants with PCV for 24 months.
DESIGN, SETTING, AND PARTICIPANTS: This 24-month, phase IV, double-masked, multicenter, randomized clinical trial (EVEREST II) was conducted among Asian participants from August 7, 2013, to March 2, 2017, with symptomatic macular PCV confirmed using indocyanine green angiography.
Participants (N = 322) were randomized 1:1 to ranibizumab, 0.5 mg, plus vPDT (combination therapy group; n = 168) or ranibizumab, 0.5 mg, plus sham PDT (monotherapy group; n = 154). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT (combination group) or sham PDT (monotherapy group) on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions.
Evaluation of combination therapy vs monotherapy at 24 months in key clinical outcomes, treatment exposure, and safety. Polypoidal lesion regression was defined as the absence of indocyanine green hyperfluorescence of polypoidal lesions.
Among 322 participants (mean [SD] age, 68.1 [8.8] years; 225 [69.9%] male), the adjusted mean best-corrected visual acuity (BCVA) gains at month 24 were 9.6 letters in the combination therapy group and 5.5 letters in the monotherapy group (mean difference, 4.1 letters; 95% CI, 1.0-7.2 letters; P = .005), demonstrating that combination therapy was superior to monotherapy by the BCVA change from baseline to month 24. Combination therapy was superior to monotherapy in terms of complete polypoidal lesion regression at month 24 (81 of 143 [56.6%] vs 23 of 86 [26.7%] participants; P < .001). Participants in the combination group received fewer ranibizumab injections (median, 6.0 [interquartile range (IQR), 4.0-11.0]) than the monotherapy group (median, 12.0 [IQR, 7.0-17.0]) up to month 24. The combination group required a median of 2.0 (IQR, 1.0-3.0) vPDT treatments for 24 months, with 75 of 168 participants (44.6%) requiring only 1 vPDT treatment.
The 24-month data findings confirm that ranibizumab therapy, given as monotherapy or in combination with vPDT, is efficacious and safe for treatment of PCV. Combination therapy with vPDT added to ranibizumab achieved superior BCVA gain, increased odds of complete polypoidal lesion regression, and fewer treatment episodes compared with ranibizumab monotherapy.
ClinicalTrials.gov Identifier: NCT01846273.
重要性：与单独使用雷珠单抗相比，在患有息肉状脉络膜血管病变（PCV）的患者中，联合应用雷珠单抗和维替泊芬光动力疗法（vPDT）的两年疗效和安全性尚不清楚。
目的：比较 PCV 患者使用雷珠单抗 0.5mg 联合即刻 vPDT 治疗与单独使用雷珠单抗 0.5mg 治疗 24 个月的治疗结果。
设计、地点和参与者：这是一项为期 24 个月的、四期、双盲、多中心、随机临床试验（EVEREST II），参与者为来自亚洲的 322 名患者，于 2013 年 8 月 7 日至 2017 年 3 月 2 日之间入组，所有患者均经吲哚青绿血管造影证实为有症状的黄斑 PCV。
干预措施：参与者（N=322）以 1:1 的比例随机分配至雷珠单抗 0.5mg 联合 vPDT（联合治疗组；n=168）或雷珠单抗 0.5mg 联合假 PDT（单药治疗组；n=154）。所有参与者均接受连续 3 个月的雷珠单抗注射，然后根据需要进行治疗。参与者在第 1 天还接受 vPDT（联合治疗组）或假 PDT（单药治疗组），然后根据是否存在活跃的息肉样病变，进行基于需要的治疗。
主要结局和测量指标：评估联合治疗与单药治疗在 24 个月时的主要临床结局、治疗暴露情况和安全性。息肉样病变消退定义为息肉样病变的吲哚青绿荧光消失。
结果：在 322 名参与者（平均[标准差]年龄，68.1[8.8]岁；225[69.9%]为男性）中，联合治疗组在第 24 个月时最佳矫正视力（BCVA）的平均增益为 9.6 个字母，单药治疗组为 5.5 个字母（平均差异，4.1 个字母；95%CI，1.0-7.2 个字母；P=.005），表明联合治疗在从基线到第 24 个月的 BCVA 变化方面优于单药治疗。在第 24 个月时，联合治疗在完全消退息肉样病变方面优于单药治疗（完全消退的参与者分别为 143 名中的 81 名[56.6%]和 86 名中的 23 名[26.7%]；P<0.001）。联合治疗组至第 24 个月时接受的雷珠单抗注射中位数（四分位距[IQR]）为 6.0（4.0-11.0），低于单药治疗组（中位数[IQR]，12.0[7.0-17.0]）。联合治疗组在 24 个月内需要接受中位数为 2.0（IQR，1.0-3.0）的 vPDT 治疗，其中 168 名参与者中有 75 名（44.6%）仅需要 1 次 vPDT 治疗。
结论和相关性：24 个月的数据结果证实，雷珠单抗治疗联合或不联合 vPDT 治疗对 PCV 是有效且安全的。与单独使用雷珠单抗相比，联合应用 vPDT 可获得更好的 BCVA 增益，增加完全消退息肉样病变的几率，并减少治疗次数。
试验注册：ClinicalTrials.gov 标识符：NCT01846273。
