Long-term Outcomes of Ranibizumab Therapy for Diabetic Macular Edema: The 36-Month Results from Two Phase III Trials RISE and RIDE
Long-term Outcomes of Ranibizumab Therapy for Diabetic Macular Edema: The 36-Month Results from Two Phase III Trials RISE and RIDE
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DOI：
10.1016/j.ophtha.2013.02.034
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发表时间：
2013-10-01
期刊：
影响因子：
13.7
通讯作者：
Hopkins, J. Jill
中科院分区：
文献类型：
--
作者：
Brown, David M.;Quan Dong Nguyen;Hopkins, J. Jill
目的：报道RIDE(NCT00473382)和RISE(NCT00473330)治疗糖尿病黄斑水肿(DME)的36个月结果。设计：III期，随机、多中心、双掩蔽、3年，假注射对照2年。参与者：成人DME患者(n=759)，基线最佳矫正视力(BCVA)20/40~20/320 Snellen当量，中心凹厚度(CFT)和中心凹厚度(GT)；方法：将患者随机分为每月注射雷尼比单抗0.5 mg、0.3 mg或假手术组(每例1只眼)。在第三年，假患者虽然仍然戴着面具，但有资格每月服用0.5毫克的雷尼比珠单抗。从第3个月开始，所有患者都可以使用黄斑激光；必要时可以使用全视网膜激光。主要观察指标：24个月时从基线的BCVA中获得15份早期治疗糖尿病视网膜病变研究报告的患者的比例。结果：在24个月时，雷尼比单抗组的视力(VA)结果与36个月一致；获得>；=在36个月时，Sham/0.5 mg、0.3 mg和0.5 mg雷尼比单抗组的RID分别为19.2%、36.8%和40.2%，RID分别为22.0%、51.2%和41.6%。在ranibizumab组，24个月的CFT下降平均持续到36个月。在雷尼比珠单抗治疗1年后，假/0.5毫克组的平均视力增加低于治疗1年后雷尼比珠单抗患者的增加(2.8比10.6和11.1个字母)。随着时间的推移，眼内炎的每次注射比率仍然很低(类似于每次注射0.06%)。服用0.5 mg雷尼比单抗的患者严重不良事件发生率为19.7%，与0.3 mg组的16.8%相比，可能与全身血管内皮细胞生长因子抑制有关的严重不良事件的发生率为19.7%。结论：服用雷尼比单抗24个月时的视力显著增加和视网膜解剖的改善持续到36个月。在接受假治疗的患者中，延迟治疗似乎没有导致最初随机接受雷尼比单抗治疗的患者的视力改善程度相同。眼部和全身的安全性与24个月时的结果基本一致。
Purpose: To report 36-month outcomes of RIDE (NCT00473382) and RISE (NCT00473330), trials of ranibizumab in diabetic macular edema (DME).Design: Phase III, randomized, multicenter, double-masked, 3-year trials, sham injection-controlled for 2 years.Participants: Adults with DME (n = 759), baseline best-corrected visual acuity (BCVA) 20/40 to 20/320 Snellen equivalent, and central foveal thickness (CFT) >= 275 mu m on optical coherence tomography.Methods: Patients were randomized equally (1 eye per patient) to monthly 0.5 mg or 0.3 mg ranibizumab or sham injection. In the third year, sham patients, while still masked, were eligible to cross over to monthly 0.5 mg ranibizumab. Macular laser was available to all patients starting at month 3; panretinal laser was available as necessary.Main Outcome Measures: The proportion of patients gaining >= 15 Early Treatment Diabetic Retinopathy Study letters in BCVA from baseline at month 24.Results: Visual acuity (VA) outcomes seen at month 24 in ranibizumab groups were consistent through month 36; the proportions of patients who gained >= 15 letters from baseline at month 36 in the sham/0.5 mg, 0.3 mg, and 0.5 mg ranibizumab groups were 19.2%, 36.8%, and 40.2%, respectively, in RIDE and 22.0%, 51.2%, and 41.6%, respectively, in RISE. In the ranibizumab arms, reductions in CFT seen at 24 months were, on average, sustained through month 36. After crossover to 1 year of treatment with ranibizumab, average VA gains in the sham/0.5 mg group were lower compared with gains seen in the ranibizumab patients after 1 year of treatment (2.8 vs. 10.6 and 11.1 letters). Per-injection rates of endophthalmitis remained low over time (similar to 0.06% per injection). The incidence of serious adverse events potentially related to systemic vascular endothelial growth factor inhibition was 19.7% in patients who received 0.5 mg ranibizumab compared with 16.8% in the 0.3 mg group.Conclusions: The strong VA gains and improvement in retinal anatomy achieved with ranibizumab at month 24 were sustained through month 36. Delayed treatment in patients receiving sham treatment did not seem to result in the same extent of VA improvement observed in patients originally randomized to ranibizumab. Ocular and systemic safety was generally consistent with the results seen at month 24.