Thirty-Six-Month Amyloid Positron Emission Tomography Results Show Continued Reduction in Amyloid Burden with Subcutaneous Gantenerumab
Thirty-Six-Month Amyloid Positron Emission Tomography Results Show Continued Reduction in Amyloid Burden with Subcutaneous Gantenerumab
复制标题
DOI：
10.14283/jpad.2020.68
复制
发表时间：
2020-12-03
影响因子：
6.4
通讯作者：
Doody, R.
中科院分区：
文献类型：
--
作者：
Klein, Gregory;Delmar, P.;Doody, R.
之前对猩红路和玛格丽特路开放标签延伸(OLE)进行的正电子发射断层扫描(PET)子研究发现，每4周皮下注射高达1200毫克的Gantenerumab可以在24个月内有效清除前驱至中度阿尔茨海默病(AD)患者的β-淀粉样蛋白(A-beta)斑块。在这36个月的更新中，我们展示了持续的减少，在猩红路(双盲汇集安慰剂和活动组)、玛格丽特路双盲安慰剂和玛格丽特路双盲活动组中，36个月的平均(标准误差)百分位数分别为-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)百分位数的变化。这些结果表明，长期服用甘特纳单抗，剂量高达1200毫克，可将淀粉样斑块水平降低到淀粉样阳性阈值以下。正在进行的研究生阶段III试验将评估与Gantenerumab诱导早期(前驱到轻度)AD患者的淀粉样蛋白降低相关的潜在临床益处。
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 (A beta) 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.