多剂量泊奈单抗治疗轻至中度阿尔茨海默病：安全性与疗效
Multiple-dose ponezumab for mild-to-moderate Alzheimer's disease: Safety and efficacy.
作者信息
Landen Jaren W, Cohen Sharon, Billing Clare B, Cronenberger Carol, Styren Scot, Burstein Aaron H, Sattler Catherine, Lee Jae-Hong, Jack Clifford R, Kantarci Kejal, Schwartz Pamela F, Duggan William T, Zhao Qinying, Sprenger Ken, Bednar Martin M, Binneman Brendon
机构信息
Pfizer Inc., Groton, CT, USA.
Toronto Memory Program, Toronto, Ontario, Canada.
出版信息
Alzheimers Dement (N Y). 2017 May 10;3(3):339-347. doi: 10.1016/j.trci.2017.04.003. eCollection 2017 Sep.
INTRODUCTION
Multiple intravenous doses of ponezumab, an anti-amyloid antibody, were evaluated in subjects with mild-to-moderate Alzheimer's disease (AD).
METHODS
In part A, 77 subjects were randomized to ponezumab 0.1, 0.5, or 1 mg/kg (75 treated) and 26 to placebo (24 treated). In part B, 63 subjects were randomized and treated with ponezumab 3 or 8.5 mg/kg and 32 with placebo. Subjects received 10 infusions over 18 months and were followed for 6 months thereafter.
RESULTS
Ponezumab was generally safe and well tolerated. Most common adverse events were fall (16.7% ponezumab, 21.4% placebo), headache (13.8%, 21.4%), and cerebral microhemorrhage (13.8%, 19.6%). Plasma ponezumab increased dose-dependently with limited accumulation. Cerebrospinal fluid penetration was low. Plasma Aβ and Aβ showed robust increases, but cerebrospinal fluid biomarkers showed no dose response. Ponezumab had no effects on cognitive/functional outcomes or brain volume.
CONCLUSIONS
Multiple-dose ponezumab was generally safe, but not efficacious, in mild-to-moderate AD.
引言
对轻度至中度阿尔茨海默病（AD）患者评估了多次静脉注射抗淀粉样蛋白抗体泊奈单抗的效果。
方法
在A部分，77名受试者被随机分为接受0.1、0.5或1mg/kg泊奈单抗治疗组（75人接受治疗）和26名接受安慰剂组（24人接受治疗）。在B部分，63名受试者被随机分为接受3或8.5mg/kg泊奈单抗治疗组和32名接受安慰剂组。受试者在18个月内接受10次输注，之后随访6个月。
结果
泊奈单抗总体安全且耐受性良好。最常见的不良事件为跌倒（泊奈单抗组16.7%，安慰剂组21.4%）、头痛（13.8%，21.4%）和脑微出血（13.8%，19.6%）。血浆泊奈单抗随剂量依赖性增加且蓄积有限。脑脊液穿透率较低。血浆Aβ和Aβ显著升高，但脑脊液生物标志物无剂量反应。泊奈单抗对认知/功能结局或脑容量无影响。
结论
多次给药的泊奈单抗在轻度至中度AD中总体安全，但无效。
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