The Vitreous Retina, Macula Consultants of New York, New York, New York; and.
Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts.
Retina. 2023 Jul 1;43(7):1064-1069. doi: 10.1097/IAE.0000000000003796.
To evaluate available rationale and outcomes of randomized trial results for complement inhibition for geographic atrophy.
Data from recently completed randomized trials of complement inhibition, particularly for pegcetacoplan and avacincaptad pegol, were evaluated for both the outcome, area of autofluorescence loss, and functional vision tests.
Pegcetacoplan 2 mg showed statistically significant reduction in expansion of the area of autofluorescence loss with monthly, but not every-other-month dosing, in a 12-month phase two trial. Nearly 40% of patients recruited for the monthly arm did not complete the treatment. In two parallel phase 3 studies there was a statistically significant reduction in the area of atrophy in one but not both studies as compared with untreated controls. Data released at 24 months follow-up showed statistically significant reduction in the area of autofluorescence-detected atrophy in both studies compared with sham. Patients did not show functional difference in best-corrected visual acuity, maximum reading speed, Functional Reading Independence Index, and mean microperimetry threshold sensitivities in the treatment versus sham arms. Avacincaptad pegol was evaluated in two randomized pivotal studies and showed a statistically significant reduction in the expansion of autofluorescence loss at 12 months. Patients in the treatment arms did not show any difference as compared with sham in the best-corrected visual acuity or low luminance visual acuity, the only functional outcomes mentioned. Both drugs increased the risk of macular neovascularization.
Both avacincaptad pegol and pegcetacoplan show significant differences compared with sham in autofluorescence imaging but no benefit in visual function at 12 and 24 months, respectively.
评估补体抑制治疗地图状萎缩的随机试验结果的现有原理和结果。
评估最近完成的补体抑制随机试验的数据，特别是对于培格司亭和阿伐西普他单抗，评估结果、自发荧光损失面积和功能视力测试。
培格司亭 2mg 在为期 12 个月的二期试验中，每月而非每两个月给药，在自发荧光损失面积的扩展方面显示出统计学上的显著减少。招募的每月治疗组近 40%的患者未完成治疗。在两项平行的三期研究中，与未治疗对照组相比，一项研究中萎缩面积有统计学显著减少，但另一项研究中没有。在 24 个月的随访中发布的数据显示，与假手术相比，两项研究中自发荧光检测到的萎缩面积均有统计学显著减少。与 sham 相比，患者在最佳矫正视力、最大阅读速度、功能性阅读独立性指数和平均微视野阈值敏感度方面在治疗与 sham 手臂之间没有显示出功能差异。阿伐西普他单抗在两项随机关键研究中进行了评估，显示在 12 个月时自发荧光损失的扩展有统计学显著减少。与 sham 相比，治疗组的患者在最佳矫正视力或低亮度视力方面均没有任何差异，这是唯一提到的功能结果。这两种药物都增加了黄斑新生血管形成的风险。
与 sham 相比，阿伐西普他单抗和培格司亭在自发荧光成像方面均显示出显著差异，但在 12 个月和 24 个月时分别在视觉功能方面没有获益。
