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donanemab治疗早期阿尔茨海默病
Donanemab in Early Alzheimer’s Disease


Mark A. Mintun ... 其他 • 2021.05.06
相关阅读
• donanemab治疗早期阿尔茨海默病 • verubecestat治疗前驱期阿尔茨海默病的随机试验

摘要


背景

阿尔茨海默病的标志是β淀粉样蛋白(Aβ)积累。donanemab是针对修饰形式沉积Aβ的抗体,目前正被研究用于治疗早期阿尔茨海默病。


方法

我们在正电子发射断层扫描(PET)显示tau蛋白和淀粉样蛋白沉积的早期有症状阿尔茨海默病患者中对donanemab开展了一项2期试验。患者被随机分配(以1∶1的比例)接受每4周一次donanemab(前3剂为700 mg,之后为1,400 mg)或安慰剂静脉给药治疗,治疗最长持续72周。主要结局是76周时,综合阿尔茨海默病评定量表(Integrated Alzheimer’s Disease Rating Scale,iADRS;评分范围为0~144,评分较低表示认知和功能障碍较严重)评分相对于基线的变化。次要结局包括以下量表评分的变化:临床痴呆评定量表-总分(Clinical Dementia Rating Scale-Sum of Boxes,CDR-SB)、阿尔茨海默病评估量表的13项认知分量表(the 13-item cognitive subscale of the Alzheimer’s Disease Assessment Scale,ADAS-Cog13)、阿尔茨海默病合作研究-工具性日常生活活动量表(Alzheimer’s Disease Cooperative Study-Instrumental Activities of Daily Living Inventory,ADCS-iADL)和简明精神状态检查量表(Mini-Mental State Examination,MMSE),以及PET上淀粉样蛋白和tau蛋白负荷的变化。


结果

共计257例患者被纳入研究;131人被分配到donanemab组,126人被分配到安慰剂组。两组的基线iADRS评分均为106分。76周时,donanemab组和安慰剂组的iADRS评分相对于基线的变化分别为-6.86和-10.06(差异,3.20;95%置信区间[CI],0.12~6.27;P=0.04)。大多数次要结局的结果无显著差异。76周时,donanemab组的淀粉样斑水平和总tau蛋白负荷降幅分别比安慰剂组大85.06 centiloids和0.01。donanemab组发生了与淀粉样蛋白相关的脑水肿或积液(大多无症状)。


结论

在早期阿尔茨海默病患者中,76周时,与安慰剂相比,donanemab使患者达到了较好的认知总分和日常生活活动能力,但次要结局的结果不一致。我们需要开展更长时间、更大规模试验来研究donanemab治疗阿尔茨海默病的疗效和安全性(由礼来公司资助,TRAILBLAZER-ALZ在ClinicalTrials.gov注册号为NCT03367403)。





作者信息

Mark A. Mintun, M.D., Albert C. Lo, M.D., Ph.D., Cynthia Duggan Evans, Ph.D., Alette M. Wessels, Ph.D., Paul A. Ardayfio, Ph.D., Scott W. Andersen, M.S., Sergey Shcherbinin, Ph.D., JonDavid Sparks, Ph.D., John R. Sims, M.D., Miroslaw Brys, M.D., Ph.D., Liana G. Apostolova, M.D., Stephen P. Salloway, M.D., and Daniel M. Skovronsky, M.D., Ph.D.
From Eli Lilly (M.A.M., A.C.L., C.D.E., A.M.W., P.A.A., S.W.A., S.S., J.S., J.R.S., M.B., D.M.S.) and the Departments of Neurology, of Radiology and Imaging Sciences, and of Medical and Molecular Genetics and the Indiana Alzheimer Disease Center, Indiana University School of Medicine (L.G.A.) — both in Indianapolis; and the Departments of Psychiatry and Human Behavior and of Neurology, Butler Hospital, Warren Alpert Medical School of Brown University, Providence, RI (S.P.S.). Address reprint requests to Dr. Mintun at Eli Lilly, Lilly Corporate Center, Indianapolis, IN 46285, or at mintun@lilly.com.

 

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