Wells John A, Glassman Adam R, Ayala Allison R, Jampol Lee M, Bressler Neil M, Bressler Susan B, Brucker Alexander J, Ferris Frederick L, Hampton G Robert, Jhaveri Chirag, Melia Michele, Beck Roy W
Palmetto Retina Center, Columbia, South Carolina.
Jaeb Center for Health Research, Tampa, Florida.
Ophthalmology. 2016 Jun;123(6):1351-9. doi: 10.1016/j.ophtha.2016.02.022. Epub 2016 Feb 27.
To provide 2-year results comparing anti-vascular endothelial growth factor (VEGF) agents for center-involved diabetic macular edema (DME) using a standardized follow-up and retreatment regimen.
Randomized clinical trial.
Six hundred sixty participants with visual acuity (VA) impairment from DME.
Randomization to 2.0-mg aflibercept, 1.25-mg repackaged (compounded) bevacizumab, or 0.3-mg ranibizumab intravitreous injections performed up to monthly using a protocol-specific follow-up and retreatment regimen. Focal/grid laser photocoagulation was added after 6 months if DME persisted. Visits occurred every 4 weeks during year 1 and were extended up to every 4 months thereafter when VA and macular thickness were stable.
Change in VA, adverse events, and retreatment frequency.
Median numbers of injections were 5, 6, and 6 in year 2 and 15, 16, and 15 over 2 years in the aflibercept, bevacizumab, and ranibizumab groups, respectively (global P = 0.08). Focal/grid laser photocoagulation was administered in 41%, 64%, and 52%, respectively (aflibercept vs. bevacizumab, P < 0.001; aflibercept vs. ranibizumab, P = 0.04; bevacizumab vs. ranibizumab, P = 0.01). At 2 years, mean VA improved by 12.8, 10.0, and 12.3 letters, respectively. Treatment group differences varied by baseline VA (P = 0.02 for interaction). With worse baseline VA (20/50 to 20/320), mean improvement was 18.1, 13.3, and 16.1 letters, respectively (aflibercept vs. bevacizumab, P = 0.02; aflibercept vs. ranibizumab, P = 0.18; ranibizumab vs. bevacizumab, P = 0.18). With better baseline VA (20/32 to 20/40), mean improvement was 7.8, 6.8, and 8.6 letters, respectively (P > 0.10, for pairwise comparisons). Anti-Platelet Trialists' Collaboration (APTC) events occurred in 5% with aflibercept, 8% with bevacizumab, and 12% with ranibizumab (global P = 0.047; aflibercept vs. bevacizumab, P = 0.34; aflibercept vs. ranibizumab, P = 0.047; ranibizumab vs. bevacizumab, P = 0.20; global P = 0.09 adjusted for potential confounders).
All 3 anti-VEGF groups showed VA improvement from baseline to 2 years with a decreased number of injections in year 2. Visual acuity outcomes were similar for eyes with better baseline VA. Among eyes with worse baseline VA, aflibercept had superior 2-year VA outcomes compared with bevacizumab, but superiority of aflibercept over ranibizumab, noted at 1 year, was no longer identified. Higher APTC event rates with ranibizumab over 2 years warrants continued evaluation in future trials.
采用标准化的随访和再治疗方案，提供比较抗血管内皮生长因子（VEGF）药物治疗累及黄斑中心的糖尿病性黄斑水肿（DME）的2年结果。
随机临床试验。
660例因DME导致视力（VA）受损的参与者。
随机分为接受2.0毫克阿柏西普、1.25毫克重新包装（配制）的贝伐单抗或0.3毫克雷珠单抗玻璃体注射，每月注射一次，采用特定方案的随访和再治疗方案。如果DME持续存在，则在6个月后加用局部/格栅激光光凝。第1年每4周进行一次随访，此后当VA和黄斑厚度稳定时，随访间隔延长至每4个月一次。
VA变化、不良事件和再治疗频率。
阿柏西普、贝伐单抗和雷珠单抗组第2年的注射中位数分别为5次、6次和6次，2年的注射中位数分别为15次、16次和15次（总体P = 0.08）。分别有41%、64%和52%的患者接受了局部/格栅激光光凝（阿柏西普与贝伐单抗相比，P < 0.001；阿柏西普与雷珠单抗相比，P = 0.04；贝伐单抗与雷珠单抗相比，P = 0.01）。2年时，平均VA分别提高了12.8、10.0和12.3个字母。治疗组差异因基线VA而异（交互作用P = 0.02）。基线VA较差（20/50至20/320）时，平均改善分别为18.1、13.3和16.1个字母（阿柏西普与贝伐单抗相比，P = 0.02；阿柏西普与雷珠单抗相比，P = 0.18；雷珠单抗与贝伐单抗相比，P = 0.18）。基线VA较好（20/32至20/40）时，平均改善分别为7.8、6.8和8.6个字母（两两比较，P > 0.10）。阿柏西普组发生抗血小板试验协作组（APTC）事件的比例为5%，贝伐单抗组为8%，雷珠单抗组为12%（总体P = 0.047；阿柏西普与贝伐单抗相比，P = 0.34；阿柏西普与雷珠单抗相比，P = 0.047；雷珠单抗与贝伐单抗相比，P = 0.20；校正潜在混杂因素后总体P = 0.09）。
所有3个抗VEGF组从基线到2年时VA均有改善，且第2年注射次数减少。基线VA较好的眼睛，视力结果相似。在基线VA较差的眼睛中，与贝伐单抗相比，阿柏西普在2年时的VA结果更优，但1年时观察到的阿柏西普优于雷珠单抗的情况在2年时不再明显。雷珠单抗在2年中的APTC事件发生率较高，值得在未来试验中继续评估。
