Heier Jeffrey S, Bressler Neil M, Avery Robert L, Bakri Sophie J, Boyer David S, Brown David M, Dugel Pravin U, Freund K Bailey, Glassman Adam R, Kim Judy E, Martin Daniel F, Pollack John S, Regillo Carl D, Rosenfeld Philip J, Schachat Andrew P, Wells John A
Ophthalmic Consultants of Boston, Boston, Massachusetts.
Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland3Editor, JAMA Ophthalmology.
JAMA Ophthalmol. 2016 Jan;134(1):95-9. doi: 10.1001/jamaophthalmol.2015.4110.
The Diabetic Retinopathy Clinical Research Network (DRCR Network), sponsored by the National Eye Institute, reported the results of a comparative effectiveness randomized clinical trial (RCT) evaluating the 3 anti-vascular endothelial growth factor (anti-VEGF) agents aflibercept (2.0 mg), bevacizumab (1.25 mg), and ranibizumab (0.3 mg) for treatment of diabetic macular edema (DME) involving the center of the retina and associated with visual acuity loss. The many important findings of the RCT prompted the American Society of Retina Specialists to convene a group of experts to provide their perspective regarding clinically relevant findings of the study.
To describe specific outcomes of the RCT judged worthy of highlighting, to discuss how these and other clinically relevant results should be considered by specialists treating DME, and to identify unanswered questions that merit consideration before treatment.
The DRCR Network-authored publication on primary outcomes of the comparative effectiveness RCT at 89 sites in the United States. The study period of the RCT was August 22, 2012, to August 28, 2013.
On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and with visual acuity impairment, including mean (SD) improvements by +13.3 (11.1) letters with aflibercept vs +9.7 (10.1) letters with bevacizumab (P < .001) and +11.2 (9.4) letters with ranibizumab (P = .03). Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept (+18.9 [11.5]) over bevacizumab (+11.8 [12.0]) or ranibizumab (14.2 [10.6]) 1 year later (P < .001 for interaction with visual acuity as a continuous variable, and P = .002 for interaction with visual acuity as a categorical variable). It is unknown whether different visual acuity outcomes associated with the use of the 3 anti-VEGF agents would be noted with other treatment regimens or with adequately repackaged bevacizumab, as well as in patients with criteria that excluded them from the RCT, such as persistent DME despite recent anti-VEGF treatment.
On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and visual acuity impairment. Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept over bevacizumab or ranibizumab 1 year later. Care needs to be taken when attempting to extrapolate outcomes of this RCT to differing treatment regimens. With access to adequately repackaged bevacizumab, many specialists might initiate therapy with bevacizumab when visual acuity is good (ie, 20/32 to 20/40 as measured in the DRCR Network), recognizing that the cost-effectiveness of bevacizumab outweighs that of aflibercept or ranibizumab.
由美国国立眼科研究所资助的糖尿病视网膜病变临床研究网络（DRCR网络）报告了一项比较疗效随机临床试验（RCT）的结果，该试验评估了3种抗血管内皮生长因子（抗VEGF）药物阿柏西普（2.0毫克）、贝伐单抗（1.25毫克）和雷珠单抗（0.3毫克）用于治疗累及视网膜中心且伴有视力丧失的糖尿病性黄斑水肿（DME）。该RCT的许多重要发现促使美国视网膜专家协会召集了一组专家，就该研究的临床相关发现发表他们的观点。
描述该RCT中被认为值得强调的具体结果，讨论治疗DME的专家应如何考虑这些以及其他临床相关结果，并确定治疗前值得考虑的未解决问题。
DRCR网络撰写的关于美国89个地点的比较疗效RCT主要结果的出版物。该RCT的研究期为2012年8月22日至2013年8月28日。
平均而言，所有3种抗VEGF药物都使累及视网膜中心且有视力损害的DME患者的视力得到改善，包括阿柏西普组平均（标准差）提高了+13.3（11.1）个字母，贝伐单抗组提高了+9.7（10.1）个字母（P <.001），雷珠单抗组提高了+11.2（9.4）个字母（P = .03）。开始治疗时视力较差与1年后阿柏西普（+18.9 [11.5]）比贝伐单抗（+11.8 [12.0]）或雷珠单抗（14.2 [10.6]）有更大的视力改善相关（作为连续变量与视力的交互作用P <.001，作为分类变量与视力的交互作用P = .002）。尚不清楚使用这3种抗VEGF药物相关的不同视力结果在其他治疗方案中是否会出现，或在充分重新包装的贝伐单抗中是否会出现，以及在不符合该RCT纳入标准的患者中是否会出现，例如尽管近期接受了抗VEGF治疗仍存在持续性DME的患者。
平均而言，所有3种抗VEGF药物都使累及视网膜中心且有视力损害的DME患者的视力得到改善。开始治疗时视力较差与1年后阿柏西普比贝伐单抗或雷珠单抗有更大的视力改善相关。在尝试将该RCT的结果外推到不同治疗方案时需谨慎。由于可获得充分重新包装的贝伐单抗，许多专家可能在视力良好时（即DRCR网络中测量为20/32至20/40）开始使用贝伐单抗治疗，因为认识到贝伐单抗的成本效益高于阿柏西普或雷珠单抗。
