Ranibizumab for Diabetic Macular Edema Results from 2 Phase III Randomized Trials: RISE and RIDE
Ranibizumab for Diabetic Macular Edema Results from 2 Phase III Randomized Trials: RISE and RIDE
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DOI：
10.1016/j.ophtha.2011.12.039
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发表时间：
2012-04-01
期刊：
影响因子：
13.7
通讯作者：
Ehrlich, Jason S.
中科院分区：
文献类型：
--
作者：
Quan Dong Nguyen;Brown, David M.;Ehrlich, Jason S.
目的：评价玻璃体内注射雷珠单抗治疗糖尿病性黄斑水肿（DME）患者的疗效和安全性。设计：两项平行、方法学相同、III期、多中心、双盲、假注射对照、随机研究。参与者：因DME而导致视力丧失的成人（最佳矫正视力[BCVA]，20/40-20/320 Snellen等效值）和时域光学相干断层扫描（OCT）中心子场厚度>= 275 μ m。每月玻璃体内注射雷珠单抗（0.5或0.3 mg）或假注射。主要结果测量：24个月时BCVA从基线增加≥ 15个字母的患者比例。结果：在RISE（NCT 00473330）中，377名患者被随机分组（127名为假手术组，125名为0.3mg组，125名为0.5mg组）。在24个月时，18.1%的假手术组患者增加了≥ 15个字母，而0.3 mg组患者增加了44.8%（P < 0.0001;经随机化分层因素调整后与假手术组的差异为24.3%; 95%置信区间[CI]为13.8-34.8），39.2%的0.5 mg雷珠单抗组患者（P < 0.001;校正差异，20.9%; 95%CI，10.7-31.1）。在RIDE（NCT 00473382）中，382例患者被随机分配（130例接受假手术，125例接受0.3 mg，127例接受0.5 mg）。拉尼珠单抗治疗的患者中有更多的患者获得了≥ 15个字母：12.3%的假手术患者对33.6%的0.3 mg患者（P < 0.0001;校正差异，20.8%; 95% CI，11.4-30.2）和45.7%的0.5 mg雷珠单抗患者（P < 0.0001;校正差异，33.3%; 95%CI，23.8-42.8）。OCT显示黄斑水肿显著改善，雷珠单抗治疗患者视网膜病变不太可能恶化，更可能改善。接受雷珠单抗治疗的患者接受的黄斑激光手术显著较少（假手术组在24个月内平均接受1.8和1.6次激光手术，雷珠单抗组为0.3-0.8次）。眼部安全性与先前的雷珠单抗研究一致; 4例雷珠单抗患者发生眼内炎。血管性或不明原因死亡、非致命性心肌梗死和非致命性脑血管意外的总发生率为4.9%至5.5%，而雷珠单抗组为2.4%至8.8%，这些死亡可能是全身性血管内皮生长因子抑制的影响。雷珠单抗可快速持续地改善DME患者的视力，降低进一步视力丧失的风险，并改善黄斑水肿，眼部和非眼部损害的发生率较低。财务披露：在参考文献之后可以找到专有或商业披露。Ophthalmology 2012;119：789-801（C）2012，美国眼科学会。
Purpose: To evaluate the efficacy and safety of intravitreal ranibizumab in diabetic macular edema (DME) patients.Design: Two parallel, methodologically identical, phase III, multicenter, double-masked, sham injection-controlled, randomized studies.Participants: Adults with vision loss from DME (best-corrected visual acuity [BCVA], 20/40-20/320 Snellen equivalent) and central subfield thickness >= 275 mu m on time-domain optical coherence tomography (OCT).Intervention: Monthly intravitreal ranibizumab (0.5 or 0.3 mg) or sham injections. Macular laser was available per-protocol-specified criteria.Main Outcome Measures: Proportion of patients gaining >= 15 letters in BCVA from baseline at 24 months.Results: In RISE (NCT00473330), 377 patients were randomized (127 to sham, 125 to 0.3 mg, 125 to 0.5 mg). At 24 months, 18.1% of sham patients gained >= 15 letters versus 44.8% of 0.3-mg (P < 0.0001; difference vs sham adjusted for randomization stratification factors, 24.3%; 95% confidence interval [CI], 13.8-34.8) and 39.2% of 0.5-mg ranibizumab patients (P < 0.001; adjusted difference, 20.9%; 95% CI, 10.7-31.1). In RIDE (NCT00473382), 382 patients were randomized (130 to sham, 125 to 0.3 mg, 127 to 0.5 mg). Significantly more ranibizumab-treated patients gained >= 15 letters: 12.3% of sham patients versus 33.6% of 0.3-mg patients (P < 0.0001; adjusted difference, 20.8%; 95% CI, 11.4-30.2) and 45.7% of 0.5-mg ranibizumab patients (P < 0.0001; adjusted difference, 33.3%; 95% CI, 23.8-42.8). Significant improvements in macular edema were noted on OCT, and retinopathy was less likely to worsen and more likely to improve in ranibizumab-treated patients. Ranibizumab-treated patients underwent significantly fewer macular laser procedures (mean of 1.8 and 1.6 laser procedures over 24 months in the sham groups vs 0.3-0.8 in ranibizumab groups). Ocular safety was consistent with prior ranibizumab studies; endophthalmitis occurred in 4 ranibizumab patients. The total incidence of deaths from vascular or unknown causes, nonfatal myocardial infarctions, and nonfatal cerebrovascular accidents, which are possible effects from systemic vascular endothelial growth factor inhibition, was 4.9% to 5.5% of sham patients and 2.4% to 8.8% of ranibizumab patients.Conclusions: Ranibizumab rapidly and sustainably improved vision, reduced the risk of further vision loss, and improved macular edema in patients with DME, with low rates of ocular and nonocular harm.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012;119:789-801 (C) 2012 by the American Academy of Ophthalmology.