Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, and Department of Surgery (Ophthalmology), University of Melbourne, Melbourne, Australia.
Markey Medical Consulting Pty. Ltd., Belrose, Australia.
Ophthalmology. 2019 May;126(5):723-734. doi: 10.1016/j.ophtha.2018.11.025. Epub 2018 Nov 29.
To test the hypothesis that tolerating some subretinal fluid (SRF) in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab using a treat-and-extend (T&E) regimen can achieve similar visual acuity (VA) outcomes as treatment aimed at resolving all SRF.
Multicenter, randomized, 24-month, phase 4, single-masked, noninferiority clinical trial.
Participants with treatment-naïve active subfoveal choroidal neovascularization (CNV).
Participants were randomized to receive ranibizumab 0.5 mg monthly until either complete resolution of SRF and intraretinal fluid (IRF; intensive arm: SRF intolerant) or resolution of all IRF only (relaxed arm: SRF tolerant except for SRF >200 μm at the foveal center) before extending treatment intervals. A 5-letter noninferiority margin was applied to the primary outcome.
Mean change in best-corrected VA (BCVA), and central subfield thickness and number of injections from baseline to month 24.
Of the 349 participants randomized (intensive arm, n = 174; relaxed arm, n = 175), 279 (79.9%) completed the month 24. The mean change in BCVA from baseline to month 24 was 3.0 letters (standard deviation, 16.3 letters) in the intensive group and 2.6 letters (standard deviation, 16.3 letters) in the relaxed group, demonstrating noninferiority of the relaxed compared with the intensive treatment (P = 0.99). Similar proportions of both groups achieved 20/40 or better VA (53.5% and 56.6%, respectively; P = 0.92) and 20/200 or worse VA (8.7% and 8.1%, respectively; P = 0.52). Participants in the relaxed group received fewer ranibizumab injections over 24 months (mean, 15.8 [standard deviation, 5.9]) than those in the intensive group (mean, 17 [standard deviation, 6.5]; P = 0.001). Significantly more participants in the intensive group never extended beyond 4-week treatment intervals (13.5%) than in the relaxed group (2.8%; P = 0.003), and significantly more participants in the relaxed group extended to and maintained 12-week treatment intervals (29.6%) than the intensive group (15.0%; P = 0.005).
Patients treated with a ranibizumab T&E protocol who tolerated some SRF achieved VA that is comparable, with fewer injections, with that achieved when treatment aimed to resolve all SRF completely.
检验这样一个假设，即在接受雷珠单抗治疗的新生血管性年龄相关性黄斑变性（nAMD）患者中，使用治疗-延长（T&E）方案容忍一定量的视网膜下液（SRF）可以达到与旨在完全消除所有 SRF 相似的视力（VA）结局。
多中心、随机、24 个月、4 期、单盲、非劣效性临床研究。
治疗-naive 活动性黄斑下脉络膜新生血管（CNV）患者。
参与者被随机分配接受雷珠单抗 0.5mg 每月一次，直到完全消除 SRF 和视网膜内液（IRF；强化组：不耐受 SRF）或仅消除所有 IRF（放松组：除了黄斑中心凹 SRF>200μm 外，容忍 SRF），然后再延长治疗间隔。主要结局采用 5 个字母的非劣效性边界。
从基线到第 24 个月时最佳矫正视力（BCVA）、中央视网膜下厚度和注射次数的平均变化。
349 名随机参与者（强化组 n=174；放松组 n=175）中，279 名（79.9%）完成了第 24 个月的随访。强化组从基线到第 24 个月时 BCVA 的平均变化为 3.0 个字母（标准差 16.3 个字母），放松组为 2.6 个字母（标准差 16.3 个字母），表明放松组与强化组相比非劣效（P=0.99）。两组均有相似比例的患者获得了 20/40 或更好的 VA（分别为 53.5%和 56.6%；P=0.92）和 20/200 或更差的 VA（分别为 8.7%和 8.1%；P=0.52）。放松组在 24 个月内接受的雷珠单抗注射次数少于强化组（平均 15.8[标准差 5.9]）（平均 17[标准差 6.5]；P=0.001）。强化组从未延长至 4 周治疗间隔的患者比例（13.5%）明显高于放松组（2.8%；P=0.003），而放松组延长至并维持 12 周治疗间隔的患者比例（29.6%）明显高于强化组（15.0%；P=0.005）。
接受雷珠单抗 T&E 方案治疗、容忍一定量 SRF 的患者获得的 VA 与完全消除所有 SRF 的治疗方案相当，但注射次数更少。
