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三十六个月的淀粉样蛋白正电子发射断层扫描结果显示,皮下注射甘特努单抗可持续降低淀粉样蛋白负担。

Thirty-Six-Month Amyloid Positron Emission Tomography Results Show Continued Reduction in Amyloid Burden with Subcutaneous Gantenerumab.

机构信息

Gregory Klein, Biomarkers and Translational Technology, Neuroscience and Rare Diseases, Basel, Switzerland. Email:

出版信息

J Prev Alzheimers Dis. 2021;8(1):3-6. doi: 10.14283/jpad.2020.68.

DOI:10.14283/jpad.2020.68
PMID:33336218
Abstract

Previous findings from the positron emission tomography (PET) substudy of the SCarlet RoAD and Marguerite RoAD open-label extension (OLE) showed gantenerumab doses up to 1200 mg every 4 weeks administered subcutaneously resulted in robust beta-amyloid (Aβ) plaque removal over 24 months in people with prodromal-to-moderate Alzheimer's disease (AD). In this 36-month update, we demonstrate continued reduction, with mean (standard error) centiloid values at 36 months of -4.3 (7.5), 0.8 (6.7), and 4.7 (8.0) in the SCarlet RoAD (double-blind pooled placebo and active groups), Marguerite RoAD double-blind placebo, and Marguerite RoAD double-blind active groups respectively, representing a change of -57.0 (10.3), -90.3 (9.0), and -74.9 (10.5) centiloids respectively. These results demonstrate that prolonged gantenerumab treatment, at doses up to 1200 mg, reduces amyloid plaque levels below the amyloid positivity threshold. The ongoing GRADUATE Phase III trials will evaluate potential clinical benefits associated with gantenerumab-induced amyloid-lowering in people with early (prodromal-to-mild) AD.

摘要

先前正电子发射断层扫描 (PET) 子研究的结果表明,在有前驱期至中度阿尔茨海默病 (AD) 症状的患者中,每 4 周皮下注射高达 1200mg 的 gantenerumab 可在 24 个月内有效清除β-淀粉样蛋白 (Aβ) 斑块。在这项 36 个月的更新中,我们证明了持续减少,在 Scarlet RoAD(双盲安慰剂和活性药物组)、Marguerite RoAD 双盲安慰剂组和 Marguerite RoAD 双盲活性药物组中,36 个月时的 centiloid 值平均值(标准误差)分别为 -4.3(7.5)、0.8(6.7)和 4.7(8.0),分别代表 -57.0(10.3)、-90.3(9.0)和 -74.9(10.5)centiloids 的变化。这些结果表明,延长 gantenerumab 治疗时间,剂量高达 1200mg,可将淀粉样蛋白斑块水平降低到淀粉样蛋白阳性阈值以下。正在进行的 GRADUATE 三期试验将评估 gantenerumab 诱导的淀粉样蛋白降低与早期(前驱期至轻度)AD 患者相关的潜在临床益处。

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