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Aflibercept: a review of its use in the treatment of choroidal neovascularization due to age-related macular degeneration

机译:Aflibercept:综述其在治疗年龄相关性黄斑变性引起的脉络膜新血管形成中的应用

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摘要

Choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) is an important cause of visual morbidity globally. Modern treatment strategies for neovascular AMD achieve regression of CNV by suppressing the activity of key growth factors that mediate angiogenesis. Vascular endothelial growth factor (VEGF) has been the major target of neovascular AMD therapy for almost two decades, and there have been several intravitreally-administered agents that have enabled anatomical restitution and improvement in visual function with continual dosing. Aflibercept (EYLEA®), initially named VEGF Trap-eye, is the most recent anti-VEGF agent to be granted US Food and Drug Administration approval for the treatment of neovascular AMD. Biologic advantages of aflibercept include its greater binding affinity for VEGF, a longer intravitreal half-life relative to other anti-VEGF agents, and the capacity to antagonize growth factors other than VEGF. This paper provides an up-to-date summary of the molecular mechanisms mediating CNV. The structural, pharmacodynamic, and pharmacokinetic advantages of aflibercept are also reviewed to rationalize the utility of this agent for treating CNV. Results of landmark clinical investigations, including VIEW 1 and 2 trials, and other important studies are then summarized and used to illustrate the efficacy of aflibercept for managing treatment-naïve CNV, recalcitrant CNV, and CNV due to polypoidal choroidal vasculopathy. Safety profile, patient tolerability, and quality of life measures related to aflibercept are also provided. The evidence provided in this paper suggests aflibercept to be a promising agent that can be used to reduce the treatment burden of neovascular AMD.
机译:年龄相关性黄斑变性(AMD)引起的脉络膜新生血管形成(CNV)是全球视觉发病的重要原因。新生血管AMD的现代治疗策略通过抑制介导血管生成的关键生长因子的活性来实现CNV的消退。近二十年来,血管内皮生长因子(VEGF)一直是新血管AMD治疗的主要目标,并且有几种玻璃体内给药的药物可以通过持续给药实现解剖学上的恢复和视觉功能的改善。 Aflibercept(EYLEA ®)最初名为VEGF Trap-eye,是美国食品和药物管理局批准用于治疗新生血管AMD的最新抗VEGF药物。 aflibercept的生物学优势包括其与VEGF的更大结合亲和力,相对于其他抗VEGF剂更长的玻璃体内半衰期以及拮抗除VEGF以外的生长因子的能力。本文提供了介导CNV的分子机制的最新摘要。还回顾了阿柏西普的结构,药效学和药代动力学优势,以合理化该药物治疗CNV的效用。然后总结了具有里程碑意义的临床研究结果,包括VIEW 1和2试验,以及其他重要研究结果,并用它们来说明aflibercept在治疗初治的CNV,顽固性CNV和由于息肉样脉络膜脉管炎引起的CNV中的疗效。还提供了与阿柏西普有关的安全性,患者耐受性和生活质量衡量指标。本文提供的证据表明,阿柏西普是一种有前途的药物,可用于减轻新血管AMD的治疗负担。

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