Two-Year Safety and Efficacy of Ranibizumab 0.5 mg in Diabetic Macular Edema Interim Analysis of the RESTORE Extension Study
Two-Year Safety and Efficacy of Ranibizumab 0.5 mg in Diabetic Macular Edema Interim Analysis of the RESTORE Extension Study
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DOI：
10.1016/j.ophtha.2013.02.019
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发表时间：
2013-10-01
期刊：
影响因子：
13.7
通讯作者：
Mitchell, Paul
中科院分区：
文献类型：
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作者：
Lang, Gabriele E.;Berta, Andras;Mitchell, Paul
目的：评价雷珠单抗0.5 mg治疗糖尿病性黄斑水肿（DME）的2年安全性和有效性。设计：24个月、开放标签、多中心、IIIb期扩展研究。参与者：完成RESTORE核心研究并进入扩展研究的303例DME所致视力损害患者中的240例。方法：根据最佳矫正视力（BCVA）稳定性和疾病进展再治疗标准，所有患者都有资格从第12个月（核心研究结束）至第36个月接受雷珠单抗0.5 mg预治疗（PRN）。根据早期治疗糖尿病视网膜病变研究指南，患者也有资格接受激光PRN。在第24个月进行预先计划的中期分析，按治疗组分层，如在RESTORE核心研究中，并被称为先前的雷珠单抗，雷珠单抗加激光，或激光组的extension.Main结果Measures：眼部和非眼部不良事件（AE）的发生率和BCVA.Results的平均变化：220例（92%）完成了第24个月的访问。2年内，最常见的眼部严重AE（SAE）和AE分别为白内障（2.1%）和眼痛（14.6%）。主要非眼部AE为鼻咽炎（18.8%）和高血压（10.4%）。无眼内炎病例，非眼部SAE的发生率较低。在进入扩展期的患者中，第二年报告了4例死亡，均与研究药物或手术无关。平均BCVA增益、中央视网膜厚度（CRT）降低和国家眼科研究所视觉功能问卷-25在第12个月观察到的（NEI VFQ-25）综合评分在第24个月保持不变（雷珠单抗治疗前：分别为+7.9个字母、-140.6 μ m和5.6;雷珠单抗+激光治疗前：分别为+6.7个字母，-133.0 μ m和5.8），平均值为3.9（先前的雷珠单抗）和3.5（先前的雷珠单抗加激光）。在核心研究中仅接受激光治疗的患者中，平均BCVA、CRT和NEI VFQ-25综合评分从第12个月至第24个月有所改善（分别为+5.4个字母、-126.6 μ m和4.3），平均注射4.1次雷珠单抗。根据预先规定的目视稳定性和疾病进展标准给予雷珠单抗0.5 mg，耐受性良好，2年内未发现新的安全性问题。总的来说，平均3.8次雷珠单抗注射足以维持（雷珠单抗治疗前）或改善（激光治疗前）BCVA、CRT和NEI VFQ-25结局至第二年。
Objective: To evaluate the 2-year safety and efficacy of ranibizumab 0.5 mg in diabetic macular edema (DME).Design: Twenty-four-month, open-label, multicenter, Phase IIIb extension study.Participants: Two hundred forty of 303 patients with visual impairment due to DME who completed the RESTORE core study and entered the extension.Methods: All patients were eligible to receive ranibizumab 0.5 mg pro re nata (PRN) from month 12 (end of core study) to month 36 based on best-corrected visual acuity (BCVA) stability and disease progression retreatment criteria. Patients were also eligible to receive laser PRN according to Early Treatment Diabetic Retinopathy Study guidelines. A preplanned interim analysis was performed at month 24, stratifying by treatment groups as in the RESTORE core study and referred to as prior ranibizumab, ranibizumab plus laser, or laser groups in the extension.Main Outcome Measures: Incidence of ocular and nonocular adverse events (AEs) and mean change in BCVA.Results: Two hundred twenty patients (92%) completed the month 24 visit. Over 2 years, the most frequent ocular serious AE (SAE) and AE were cataract (2.1%) and eye pain (14.6%), respectively. The main nonocular AEs were nasopharyngitis (18.8%) and hypertension (10.4%). There were no cases of endophthalmitis, and the incidences of nonocular SAEs were low. Of the patients entering the extension, 4 deaths were reported in the second year, none of which were related to study drug or procedure. Mean BCVA gain, central retinal thickness (CRT) decrease, and National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) composite score observed at month 12 were maintained at month 24 (prior ranibizumab: +7.9 letters, -140.6 mu m, and 5.6 , respectively; prior ranibizumab plus laser: +6.7 letters, -133.0 mu m, and 5.8, respectively), with an average of 3.9 (prior ranibizumab) and 3.5 ranibizumab injections (prior ranibizumab plus laser). In patients treated with laser alone in the core study, the mean BCVA, CRT, and NEI VFQ-25 composite score improved from month 12 to month 24 (+5.4 letters, -126.6 mu m, and 4.3, respectively), with an average of 4.1 ranibizumab injections.Conclusions: Ranibizumab 0.5 mg administered according to prespecified visual stability and disease progression criteria was well tolerated, with no new safety concerns identified over 2 years. Overall, an average of 3.8 ranibizumab injections was sufficient to maintain (prior ranibizumab) or improve (prior laser) BCVA, CRT, and NEI VFQ-25 outcomes through the second year.