Retina Consultants of Nevada, Las Vegas, Nevada.
Genentech, Inc., South San Francisco, California.
Ophthalmology. 2014 May;121(5):1059-66. doi: 10.1016/j.ophtha.2013.11.022. Epub 2014 Jan 11.
To assess time to first achievement of clinically significant visual acuity (VA) gains from baseline in patients with retinal vein occlusion (RVO) receiving ranibizumab versus sham treatment.
Post hoc analyses of 2 phase 3 clinical trials assessing efficacy and safety of ranibizumab in patients with branch RVO (Ranibizumab for the Treatment of Macular Edema following Branch Retinal Vein Occlusion: Evaluation of Efficacy and Safety [BRAVO] study; NCT00061594) and central RVO (Ranibizumab for the Treatment of Macular Edema after Central Retinal Vein Occlusion Study: Evaluation of Efficacy and Safety [CRUISE]; NCT00056836) over 12 months.
Seven hundred eighty-nine patients (BRAVO, n = 397; CRUISE, n = 392).
Randomization to monthly intraocular ranibizumab injections (0.3 mg/0.5 mg) or sham. After 6 monthly injections (treatment period), patients meeting prespecified criteria received as-needed (pro re nata [PRN]) ranibizumab at their assigned dose (sham patients, ranibizumab 0.5 mg) through month 12 (observation period). BRAVO patients meeting specific eligibility criteria could receive rescue laser treatment once during the treatment and once during the observation periods.
Time to first gain of 15 letters or more from baseline, analyzed using Kaplan-Meier methods. To evaluate the effect of delaying ranibizumab treatment, sham patients' VA data also were analyzed, with month 6 considered as baseline to assess vision gains during the 6 months of receiving ranibizumab PRN.
Median time to first 15-letter or more gain from baseline was 12.0 (sham), 4.8 (ranibizumab 0.3 mg), and 4.0 months (ranibizumab 0.5 mg) in BRAVO and 12.2, 5.9, and 5.2 months, respectively, in CRUISE. The cumulative proportion of patients who had ever gained 15 letters or more from baseline by month 12 was 50% (sham), 68% (ranibizumab 0.3 mg), and 71% (ranibizumab 0.5 mg) in BRAVO and 42%, 61%, and 66%, respectively, in CRUISE. After 6 months of ranibizumab PRN treatment, a cumulative 10.8% (BRAVO) and 26.2% (CRUISE) of initially sham-treated patients ever gained 15 letters or more.
This retrospective analysis shows that more than 50% of patients treated with monthly ranibizumab achieved clinically significant vision gains during the initial 6 months of treatment, which largely were maintained using PRN treatment to 12 months. In comparison, less than 50% of patients initially randomized to sham (and later receiving ranibizumab 0.5 mg PRN treatment) ever achieved clinically significant vision gains. These results suggest that initiating treatment immediately after diagnosis may provide the greatest vision gains. The potential benefits of early treatment should be evaluated further in prospective clinical studies.
评估接受雷珠单抗与假治疗的视网膜静脉阻塞（RVO）患者从基线开始首次达到临床显著视力（VA）改善的时间。
评估雷珠单抗治疗分支 RVO（分支视网膜静脉阻塞治疗中应用雷珠单抗治疗黄斑水肿：疗效和安全性评估[BRAVO]研究；NCT00061594）和中央 RVO（治疗中央视网膜静脉阻塞后黄斑水肿的雷珠单抗治疗研究：疗效和安全性评估[CRUISE]；NCT00056836）的 2 项 3 期临床试验的事后分析，时间为 12 个月。
789 名患者（BRAVO，n=397；CRUISE，n=392）。
每月玻璃体腔内雷珠单抗注射（0.3mg/0.5mg）或假治疗随机分组。6 个月的注射治疗期（治疗期）后，符合预设标准的患者接受了指定剂量的按需（即需即给）雷珠单抗治疗（假治疗患者，雷珠单抗 0.5mg），持续到第 12 个月（观察期）。符合特定入选标准的 BRAVO 患者可在治疗期和观察期各接受一次激光抢救治疗。
从基线开始首次获得 15 个字母或更多的时间，采用 Kaplan-Meier 方法分析。为了评估延迟雷珠单抗治疗的效果，也分析了假治疗患者的 VA 数据，将第 6 个月视为基线，以评估接受雷珠单抗即需即给治疗的 6 个月内的视力改善情况。
BRAVO 中，从基线开始首次获得 15 个字母或更多的中位数时间分别为 12.0（假）、4.8（雷珠单抗 0.3mg）和 4.0 个月（雷珠单抗 0.5mg），CRUISE 中分别为 12.2、5.9 和 5.2 个月。至第 12 个月，累计有 50%（假）、68%（雷珠单抗 0.3mg）和 71%（雷珠单抗 0.5mg）的患者从基线开始获得了 15 个字母或更多的视力改善，在 CRUISE 中分别为 42%、61%和 66%。雷珠单抗即需即给治疗 6 个月后，最初接受假治疗的患者中，累计有 10.8%（BRAVO）和 26.2%（CRUISE）获得了 15 个字母或更多的视力改善。
这项回顾性分析表明，接受每月雷珠单抗治疗的患者中有 50%以上在治疗的最初 6 个月内获得了有临床意义的视力改善，这些改善在第 12 个月时主要通过即需即给治疗维持。相比之下，最初随机接受假治疗（随后接受雷珠单抗 0.5mg 即需即给治疗）的患者中，不到 50%获得了有临床意义的视力改善。这些结果表明，在确诊后立即开始治疗可能会获得最大的视力改善。早期治疗的潜在益处应在前瞻性临床研究中进一步评估。
