From the Department of Neurology (G.S.D.), Mayo Clinic, Jacksonville, FL; National and Kapodistrian University of Athens (N.S.), Greece; Columbia University (N.S.), New York, NY; University of Kansas Medical Center (R.D.), Kansas City; Rocky Mountain Neurology (K.C.), Lone Tree, CO; Patient Representative (A.M.), San Antonio, TX; Care Partner Representative (B.W.), Telluride, CO; American Academy of Neurology (S.R.W.), Minneapolis, MN; and Department of Neurology (M.J.A.), University of Florida, Gainesville.
Neurology. 2022 Apr 12;98(15):619-631. doi: 10.1212/WNL.0000000000200176. Epub 2022 Feb 23.
To identify the class of evidence for aducanumab use for the treatment of Alzheimer disease and present clinical considerations regarding use.
The author panel systematically reviewed available clinical trial data detailing aducanumab use in individuals with early symptomatic Alzheimer disease. Level of evidence statements were assigned in accordance with the American Academy of Neurology's 2017 therapeutic classification of evidence scheme. Safety information, regulatory decisions, and clinical context were also reviewed.
Data were identified from 4 clinical trials, 1 rated Class I and 3 rated Class II. The Class I study showed that single doses of aducanumab up to 30 mg/kg were safe and well tolerated. All 3 Class II studies provided evidence that aducanumab (3-10 mg/kg) decreased amyloid deposition on brain PET at 1 year vs placebo. Efficacy data in the Class II studies varied by dose and outcome, but aducanumab either had no effect on mean change on the Clinical Dementia Rating Sum of Boxes scores or resulted in less worsening (vs placebo) that was of uncertain clinical importance. Adverse amyloid-related imaging abnormalities occurred in approximately 40% of individuals treated with aducanumab vs 10% receiving placebo.
Administration of aducanumab will require expanded clinical infrastructure. Evidence-based guidance is needed to address key questions (e.g., safety in populations not enrolled in phase 3 studies, expected benefits on daily function, treatment duration) and critical issues relating to access to aducanumab (e.g., coverage, costs, burden of monthly infusions) that will inform shared decision making between patients and providers.
确定阿杜卡努单抗用于治疗阿尔茨海默病的证据级别，并提出关于使用该药物的临床注意事项。
作者小组系统地回顾了详细描述阿杜卡努单抗在早期有症状的阿尔茨海默病患者中使用的现有临床试验数据。证据级别的陈述是根据美国神经病学学会 2017 年的治疗分类证据方案确定的。还回顾了安全性信息、监管决策和临床背景。
从 4 项临床试验中确定了数据，其中 1 项为 I 级，3 项为 II 级。I 级研究表明，高达 30mg/kg 的单次剂量阿杜卡努单抗是安全且耐受良好的。所有 3 项 II 级研究都提供了证据，表明与安慰剂相比，阿杜卡努单抗（3-10mg/kg）在 1 年内减少了脑 PET 上的淀粉样蛋白沉积。II 级研究中的疗效数据因剂量和结果而异，但阿杜卡努单抗要么对临床痴呆评定量表总分的平均变化没有影响，要么导致（与安慰剂相比）改善程度不确定，无临床重要意义。接受阿杜卡努单抗治疗的个体中约有 40%发生了与淀粉样蛋白相关的影像学异常，而接受安慰剂治疗的个体中这一比例为 10%。
阿杜卡努单抗的使用将需要扩大临床基础设施。需要循证指导来解决关键问题（例如，未参加 3 期研究的人群的安全性、对日常功能的预期益处、治疗持续时间）和与获得阿杜卡努单抗相关的关键问题（例如，覆盖范围、成本、每月输注负担），这些问题将为患者和提供者之间的共同决策提供信息。
