Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema.
Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema.
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DOI：
10.1056/nejmoa1414264
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发表时间：
2015-03-26
期刊：
影响因子：
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通讯作者：
Beck RW
中科院分区：
文献类型：
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作者：
Diabetic Retinopathy Clinical Research Network;Wells JA;Glassman AR;Ayala AR;Jampol LM;Aiello LP;Antoszyk AN;Arnold-Bush B;Baker CW;Bressler NM;Browning DJ;Elman MJ;Ferris FL;Friedman SM;Melia M;Pieramici DJ;Sun JK;Beck RW
玻璃体内注射阿柏西普、贝伐单抗和雷珠单抗治疗糖尿病性黄斑水肿的相对疗效和安全性尚不清楚。在89个临床试验机构，我们随机分配了660名患有累及黄斑中心的糖尿病黄斑水肿的成人（平均年龄61±10岁），接受2.0 mg剂量的玻璃体内阿柏西普（224名参与者），1.25 mg剂量的贝伐单抗（218名参与者）或0.3 mg剂量的雷珠单抗（218名参与者）。根据方案规定的算法，研究药物每4周一次给药。主要结果是1年时视力的平均变化。从基线到1年，平均视力字母评分（范围，0 - 100，评分越高表示视力越好; 85分约为20/20）使用阿柏西普改善了13.3，贝伐单抗改善了9.7，雷珠单抗改善了11.2。虽然阿柏西普的改善大于其他两种药物（阿柏西普与贝伐单抗的P<0.001，阿柏西普与雷珠单抗的P = 0.03），但没有临床意义，因为这种差异是由基线时视力较差的眼睛驱动的（相互作用的P<0.001）。当初始视力字母评分为78至69（相当于约20/32至20/40）（51%的参与者）时，aflibercept组的平均改善为8.0，贝伐单抗组为7.5，雷珠单抗组为8.3（每对比较P>0.50）。当初始字母评分小于69（约20/50或更差）时，阿柏西普的平均改善为18.9，贝伐单抗为11.8，雷珠单抗为14.2（阿柏西普与贝伐单抗的P<0.001，阿柏西普与雷珠单抗的P = 0.003，雷珠单抗与贝伐单抗的P = 0.21）。研究组间严重不良事件（P = 0.40）、住院（P = 0.51）、死亡（P = 0.72）或主要心血管事件（P = 0.56）的发生率无显著差异。玻璃体内注射阿柏西普、贝伐单抗或雷珠单抗可改善中心受累的糖尿病黄斑水肿患者的视力，但相对效果取决于基线视力。当最初的视力损失是轻微的，没有明显的差异，平均而言，研究组之间。在初始视力水平较差的情况下，aflibercept在改善视力方面更有效。（由美国国立卫生研究院资助; ClinicalTrials.gov编号，NCT 01627249。
The relative efficacy and safety of intravitreous aflibercept, bevacizumab, and ranibizumab in the treatment of diabetic macular edema are unknown. At 89 clinical sites, we randomly assigned 660 adults (mean age, 61±10 years) with diabetic macular edema involving the macular center to receive intravitreous aflibercept at a dose of 2.0 mg (224 participants), bevacizumab at a dose of 1.25 mg (218 participants), or ranibizumab at a dose of 0.3 mg (218 participants). The study drugs were administered as often as every 4 weeks, according to a protocol-specified algorithm. The primary outcome was the mean change in visual acuity at 1 year. From baseline to 1 year, the mean visual-acuity letter score (range, 0 to 100, with higher scores indicating better visual acuity; a score of 85 is approximately 20/20) improved by 13.3 with aflibercept, by 9.7 with bevacizumab, and by 11.2 with ranibizumab. Although the improvement was greater with aflibercept than with the other two drugs (P<0.001 for aflibercept vs. bevacizumab and P = 0.03 for aflibercept vs. ranibizumab), it was not clinically meaningful, because the difference was driven by the eyes with worse visual acuity at baseline (P<0.001 for interaction). When the initial visual-acuity letter score was 78 to 69 (equivalent to approximately 20/32 to 20/40) (51% of participants), the mean improvement was 8.0 with aflibercept, 7.5 with bevacizumab, and 8.3 with ranibizumab (P>0.50 for each pairwise comparison). When the initial letter score was less than 69 (approximately 20/50 or worse), the mean improvement was 18.9 with aflibercept, 11.8 with bevacizumab, and 14.2 with ranibizumab (P<0.001 for aflibercept vs. bevacizumab, P = 0.003 for aflibercept vs. ranibizumab, and P = 0.21 for ranibizumab vs. bevacizumab). There were no significant differences among the study groups in the rates of serious adverse events (P = 0.40), hospitalization (P = 0.51), death (P = 0.72), or major cardiovascular events (P = 0.56). Intravitreous aflibercept, bevacizumab, or ranibizumab improved vision in eyes with center-involved diabetic macular edema, but the relative effect depended on baseline visual acuity. When the initial visual-acuity loss was mild, there were no apparent differences, on average, among study groups. At worse levels of initial visual acuity, aflibercept was more effective at improving vision. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01627249.)