Twelve-Month Efficacy and Safety of 0.5 mg or 2.0 mg Ranibizumab in Patients with Subfoveal Neovascular Age-related Macular Degeneration
Twelve-Month Efficacy and Safety of 0.5 mg or 2.0 mg Ranibizumab in Patients with Subfoveal Neovascular Age-related Macular Degeneration
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DOI：
10.1016/j.ophtha.2012.10.014
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发表时间：
2013-05-01
期刊：
影响因子：
13.7
通讯作者：
Lai, Phillip
中科院分区：
文献类型：
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作者：
Busbee, Brandon G.;Ho, Allen C.;Lai, Phillip
目的：评价玻璃体内雷珠单抗0.5 mg和2.0 mg每月给药和按需（PRN）给药在未接受过治疗的中心凹下新生血管性年龄相关性黄斑变性（湿性AMD）患者中的12个月疗效和安全性。设计：一项为期24个月、III期、随机、多中心、双盲、剂量反应研究。参与者：年龄≥ 50岁的中心凹下湿性AMD患者。患者（n = 1098）被随机接受雷珠单抗0.5毫克或2.0毫克玻璃体内注射给药每月或PRN的基础上3个月后负荷doses.Main结果测量：主要疗效终点是最佳矫正视力（BCVA）从基线的平均变化在第12个月。关键的次要终点包括雷珠单抗注射的平均次数、中心凹厚度（CFT）随时间较基线的平均变化以及获得≥ 15个BCVA字母的患者比例。除非另有说明，否则终点分析采用末次观察值结转法来填补缺失数据。结果：在第12个月，4组BCVA较基线的平均变化分别为+10.1个字母（0.5 mg每月一次）、+8.2个字母（0.5 mg PRN）、+9.2个字母（2.0 mg每月一次）和+8.6个字母（2.0 mg PRN）。4组中第12个月较基线增加≥ 15个字母的患者比例分别为34.5%、30.2%、36.1%和33.0%。4组第12个月CFT较基线的平均变化分别为-172.0 μ m、-161.2 μ m、-163.3 μ m和-172.4 μ m。0.5 mg PRN和2.0 mg PRN组的平均注射次数分别为7.7和6.9。眼部和全身的安全性特征与以前的雷珠单抗试验在AMD和comparable between groups.Conclusions：在第12个月，雷珠单抗2.0毫克每月组不符合预先规定的优势比较和雷珠单抗0.5毫克和2.0毫克PRN组不符合预先规定的非劣效性（NI）比较。然而，所有治疗组均表现出具有临床意义的视力改善（+8.2至+10.1字母）和解剖结局改善，PRN组需要的注射次数（6.9-7.7）比每月一次组（11.2-11.3）少约4次。尽管研究中剂量递增4倍，但未观察到新的安全性事件。在中心凹下新生血管年龄相关性黄斑变性患者中评价0.5 mg和2.0 mg雷珠单抗每月或按需（PRN）给药的疗效和安全性的pHase III、双盲、多中心、随机、活性治疗对照研究（HARBOR）研究证实，雷珠单抗0.5 mg每月给药可为湿性AMD患者提供最佳结果。
Objective: To evaluate the 12-month efficacy and safety of intravitreal ranibizumab 0.5 mg and 2.0 mg administered monthly and on an as-needed (PRN) basis in treatment-naive patients with subfoveal neovascular age-related macular degeneration (wet AMD).Design: A 24-month, phase III, randomized, multicenter, double-masked, dose-response study.Participants: Patients aged >= 50 years with subfoveal wet AMD.Methods: Patients (n = 1098) were randomized to receive ranibizumab 0.5 mg or 2.0 mg intravitreal injections administered monthly or on a PRN basis after 3 monthly loading doses.Main Outcome Measures: The primary efficacy end point was the mean change from baseline in best-corrected visual acuity (BCVA) at month 12. Key secondary end points included the mean number of ranibizumab injections, the mean change from baseline in central foveal thickness (CFT) over time, and the proportion of patients who gained >= 15 letters of BCVA. Unless otherwise specified, end point analyses were performed using the last-observation-carried-forward method to impute missing data.Results: At month 12, the mean change from baseline in BCVA for the 4 groups was +10.1 letters (0.5 mg monthly), +8.2 letters (0.5 mg PRN), +9.2 letters (2.0 mg monthly), and +8.6 letters (2.0 mg PRN). The proportion of patients who gained >= 15 letters from baseline at month 12 in the 4 groups was 34.5%, 30.2%, 36.1%, and 33.0%, respectively. The mean change from baseline in CFT at month 12 in the 4 groups was -172.0 mu m, -161.2 mu m, -163.3 mu m, and -172.4 mu m, respectively. The mean number of injections was 7.7 and 6.9 for the 0.5-mg PRN and 2.0-mg PRN groups, respectively. Ocular and systemic safety profiles were consistent with previous ranibizumab trials in AMD and comparable between groups.Conclusions: At month 12, the ranibizumab 2.0 mg monthly group did not meet the prespecified superiority comparison and the ranibizumab 0.5 mg and 2.0 mg PRN groups did not meet the prespecified noninferiority (NI) comparison. However, all treatment groups demonstrated clinically meaningful visual improvement (+8.2 to +10.1 letters) and improved anatomic outcomes, with the PRN groups requiring approximately 4 fewer injections (6.9-7.7) than the monthly groups (11.2-11.3). No new safety events were observed despite a 4-fold dose escalation in the study. The pHase III, double-masked, multicenter, randomized, Active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg Ranibizumab administered monthly or on an as-needed Basis (PRN) in patients with subfoveal neOvasculaR age-related macular degeneration (HARBOR) study confirmed that ranibizumab 0.5 mg dosed monthly provides optimum results in patients with wet AMD.