INTRODUCTIONAducanumab selectively targets aggregated forms of amyloid beta (Aβ), a neuropathological hallmark of Alzheimer's disease (AD).METHODSPRIME was a Phase 1b, double‐blind, randomized clinical trial of aducanumab. During the 12‐month placebo‐controlled period, participants with prodromal AD or mild AD dementia were randomized to receive aducanumab or placebo. At week 56, participants could enroll in a long‐term extension (LTE), in which all participants received aducanumab. The primary endpoint was safety and tolerability.RESULTSAmyloid‐related imaging abnormalities–edema (ARIA‐E) were the most common adverse event. Dose titration was associated with a decrease in the incidence of ARIA‐E. Over 48 months, aducanumab decreased brain amyloid levels in a dose‐ and time‐dependent manner. Exploratory endpoints suggested a continued benefit in the reduction of clinical decline over 48 months.DISCUSSIONThe safety profile of aducanumab remained unchanged in the LTE of PRIME. Amyloid plaque levels continued to decrease in participants treated with aducanumab.Highlights PRIME was a Phase 1b, double‐blind, randomized clinical trial of aducanumab. We report cumulative safety and 48‐month efficacy results from PRIME. Amyloid‐related imaging abnormalities–edema (ARIA‐E) were the most common adverse event (AE); 61% of participants with ARIA‐E were asymptomatic. Dose titration was associated with a decrease in the incidence of ARIA‐E. Aducanumab decreased levels of amyloid beta (Aβ) in a dose‐ and time‐dependent manner.

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PRIME 长期扩展的结果：aducanumab 的随机 1b 期试验

简介aducanumab 选择性地靶向聚集形式的 β 淀粉样蛋白 (Aβ)，这是阿尔茨海默病 (AD) 的神经病理学标志。METHODSPRIME 是 aducanumab 的 1b 期、双盲、随机临床试验。在 12 个月的安慰剂对照期内，患有前驱 AD 或轻度 AD 痴呆的参与者被随机分配接受 aducanumab 或安慰剂治疗。第 56 周时，参与者可以参加长期延期 (LTE)，其中所有参与者都接受阿杜卡单抗治疗。主要终点是安全性和耐受性。 结果淀粉样蛋白相关影像学异常-水肿（ARIA-E）是最常见的不良事件。剂量滴定与 ARIA-E 发生率的降低相关。在 48 个月的时间里，aducanumab 以剂量和时间依赖性方式降低了大脑淀粉样蛋白水平。探索性终点表明在 48 个月内持续受益于减少临床衰退。讨论 aducanumab 在 PRIME 的 LTE 中的安全性保持不变。使用 aducanumab 治疗的参与者中淀粉样蛋白斑水平持续下降。亮点 PRIME 是 aducanumab 的 1b 期双盲随机临床试验。 我们报告 PRIME 的累积安全性和 48 个月疗效结果。 淀粉样蛋白相关的影像学异常-水肿（ARIA-E）是最常见的不良事件（AE）； 61% 的 ARIA-E 参与者没有症状。 剂量滴定与 ARIA-E 发生率的降低相关。 Aducanumab 以剂量和时间依赖性方式降低β淀粉样蛋白 (Aβ) 水平。