Curry Beverley A, Sanfilippo Paul G, Chan Sarah, Hewitt Alexander W, Verma Nitin
Hobart Eye Surgeons, Hobart, TAS, Australia.
Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, VIC, Australia.
Ophthalmol Ther. 2020 Mar;9(1):87-101. doi: 10.1007/s40123-019-00224-x. Epub 2019 Nov 21.
Treat-and-extend (T&E) and pro re nata (PRN; 'as needed') regimens of intravitreal anti-vascular endothelial growth factor (VEGF) treatment have been found to reduce the injection burden on patients and improve the cost effectiveness of the treatment of macular edema. The aim of this study was to assess the effectiveness of a T&E regimen of aflibercept, in a clinical setting, in patients with diabetic macular edema (DME) who were either intravitreal anti-VEGF therapy naive or with minimal exposure to anti-VEGF (≤ 6 treatments) in the previous 12 months.
This prospective, single arm, open label study recruited patients with DME (macular thickness of ≥ 300 µm) and best-corrected visual acuity (BCVA) between 28-78 ETDRS letters. Participants received five loading doses of intravitreal aflibercept at 4-weekly intervals. BCVA measurements and macular optical coherence tomography were performed at each visit. If no disease activity was detected, treatment intervals were increased by 2 weeks to a maximum of 12 weeks. Outcome measures included: changes in BCVA and retinal anatomical measures (central foveal thickness [CFT] and central macular volume within 6 mm of the fovea [CSVol]) between baseline and 2 years, patient treatment intervals; and adverse events.
Of the 36 patients who provided informed consent to participate in the study and were screened, 26 patients (eyes) were eligible to participate in the study. After regression analysis, adjustment for repeated measures, and significant covariates, the mean BCVA increased by 3.8 letters (95% confidence interval [CI] 1.1, 6.4) and the CFT and CSVol decreased by 127.2 µm (95% CI 91.7, 162.5) and 1.6 mm (95% CI 1.2, 2.0), respectively, over the course of the study. In the second year, 16 of the 25 patients still participating had their treatment intervals extended to 12 weeks. There was no evidence of any new adverse events that would require changes to the aflibercept safety profile.
For the majority of patients presenting with DME, a T&E regimen of aflibercept in the first 2 years of therapy is a practical alternative to PRN treatment with regular review.
Australian New Zealand Clinical Trials Registry number, ACTRN12618000428268.
This investigator-initiated study was supported by Bayer Australia Ltd. who provided the study treatment and some financial assistance.
玻璃体内注射抗血管内皮生长因子（VEGF）治疗的“治疗并延长（T&E）”方案和“按需（PRN）”方案已被证实可减轻患者的注射负担，并提高黄斑水肿治疗的成本效益。本研究旨在评估阿柏西普T&E方案在临床环境中对糖尿病性黄斑水肿（DME）患者的有效性，这些患者既往未接受过玻璃体内抗VEGF治疗，或在过去12个月内接受抗VEGF治疗的次数较少（≤6次）。
这项前瞻性、单臂、开放标签研究招募了DME患者（黄斑厚度≥300µm），其最佳矫正视力（BCVA）在28-78个ETDRS字母之间。参与者每隔4周接受5次玻璃体内注射阿柏西普的负荷剂量。每次就诊时均进行BCVA测量和黄斑光学相干断层扫描。如果未检测到疾病活动，则将治疗间隔延长2周，最长延长至12周。观察指标包括：基线至2年期间BCVA和视网膜解剖学指标（中心凹厚度[CFT]和中心凹周围6mm内的中心黄斑体积[CSVol]）的变化、患者的治疗间隔以及不良事件。
在36名提供知情同意并接受筛查以参与研究的患者中，26名患者（眼）符合参与研究的条件。经过回归分析、重复测量调整和显著协变量调整后，在研究过程中，平均BCVA提高了3.8个字母（95%置信区间[CI]1.1, 6.4），CFT和CSVol分别降低了127.2µm（95%CI 91.7, 162.5）和1.6mm（95%CI 1.2, 2.0）。在第二年，仍在参与研究的25名患者中有16名患者的治疗间隔延长至12周。没有证据表明存在任何需要改变阿柏西普安全性的新不良事件。
对于大多数DME患者而言，在治疗的前2年采用阿柏西普T&E方案是一种切实可行的替代方案，可替代定期复查的PRN治疗。
澳大利亚新西兰临床试验注册中心编号，ACTRN12618000428268。
这项由研究者发起的研究得到了拜耳澳大利亚有限公司的支持，该公司提供了研究治疗药物和部分资金援助。
