{"title":"莱卡单抗用于治疗早期阿尔茨海默病的人源化单克隆抗体。","authors":"Juliane Park, Carson Simpson, Katie Patel","doi":"10.1177/10600280231218253","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To review current pharmacology, pharmacokinetics/pharmacodynamics, safety, and efficacy of lecanemab in patients with Alzheimer disease.</p><p><strong>Data sources: </strong>A literature search of PubMed (April 1, 2016-November 15, 2023) and ClinicalTrials.gov search were conducted using the following search terms: lecanemab and BAN2401. Additional articles were identified by hand from references.</p><p><strong>Study selection and data extraction: </strong>We included English-language clinical trials, randomized controlled trials, reviews, and systematic reviews evaluating lecanemab pharmacology, efficacy, or safety in humans for the management of Alzheimer disease.</p><p><strong>Data synthesis: </strong>In the Clarity AD phase III trial, lecanemab led to a decrease in brain amyloid levels and showed moderate improvement in clinical measures of cognition and function. At 18 months, lecanemab 10 mg/kg biweekly exhibited a lower least squares mean change from baseline (1.21) compared to placebo (1.66) of Clinical Dementia Rating-Sum of Boxes score, signifying a significant difference of -0.45 (95% CI, -0.67 to -0.23; <i>P</i> < 0.001). In a subset of 698 participants, lecanemab reduced brain amyloid burden by -59.1 Centiloids (95% CI, -62.6 to -55.6). Lecanemab demonstrated favorable differences in Alzheimer Disease Assessment Scale-cognitive subscale 14, Alzheimer Disease Composite Score, and Alzheimer Disease Cooperative Study-Mild Cognitive Impairment-Activities of Daily Living scores. Adverse events included infusion-related reactions (26.4%) and amyloid-related imaging abnormalities (12.6%).</p><p><strong>Relevance to patient care and clinical practice: </strong>Lecanemab reduces cognitive decline but raises concerns about intravenous administration, cost, and magnetic resonance imaging needs. Ongoing trials exploring subcutaneous dosing and positron emission tomography scans may offer solutions.</p><p><strong>Conclusion: </strong>Lecanemab is a humanized monoclonal antibody that is selective for soluble amyloid-beta (Aβ) aggregates. Lecanemab has exhibited a decrease in brain Aβ plaques and moderately less decline on clinical measures of cognitive function.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"1045-1053"},"PeriodicalIF":2.3000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Lecanemab: A Humanized Monoclonal Antibody for the Treatment of Early Alzheimer Disease.\",\"authors\":\"Juliane Park, Carson Simpson, Katie Patel\",\"doi\":\"10.1177/10600280231218253\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To review current pharmacology, pharmacokinetics/pharmacodynamics, safety, and efficacy of lecanemab in patients with Alzheimer disease.</p><p><strong>Data sources: </strong>A literature search of PubMed (April 1, 2016-November 15, 2023) and ClinicalTrials.gov search were conducted using the following search terms: lecanemab and BAN2401. Additional articles were identified by hand from references.</p><p><strong>Study selection and data extraction: </strong>We included English-language clinical trials, randomized controlled trials, reviews, and systematic reviews evaluating lecanemab pharmacology, efficacy, or safety in humans for the management of Alzheimer disease.</p><p><strong>Data synthesis: </strong>In the Clarity AD phase III trial, lecanemab led to a decrease in brain amyloid levels and showed moderate improvement in clinical measures of cognition and function. At 18 months, lecanemab 10 mg/kg biweekly exhibited a lower least squares mean change from baseline (1.21) compared to placebo (1.66) of Clinical Dementia Rating-Sum of Boxes score, signifying a significant difference of -0.45 (95% CI, -0.67 to -0.23; <i>P</i> < 0.001). In a subset of 698 participants, lecanemab reduced brain amyloid burden by -59.1 Centiloids (95% CI, -62.6 to -55.6). Lecanemab demonstrated favorable differences in Alzheimer Disease Assessment Scale-cognitive subscale 14, Alzheimer Disease Composite Score, and Alzheimer Disease Cooperative Study-Mild Cognitive Impairment-Activities of Daily Living scores. Adverse events included infusion-related reactions (26.4%) and amyloid-related imaging abnormalities (12.6%).</p><p><strong>Relevance to patient care and clinical practice: </strong>Lecanemab reduces cognitive decline but raises concerns about intravenous administration, cost, and magnetic resonance imaging needs. Ongoing trials exploring subcutaneous dosing and positron emission tomography scans may offer solutions.</p><p><strong>Conclusion: </strong>Lecanemab is a humanized monoclonal antibody that is selective for soluble amyloid-beta (Aβ) aggregates. 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引用次数: 0
摘要
目的回顾莱卡奈单抗在阿尔茨海默病患者中的当前药理学、药代动力学/药效学、安全性和有效性:使用以下检索词对PubMed(2016年4月1日-2023年11月15日)和ClinicalTrials.gov进行文献检索:lecanemab和BAN2401。研究选择和数据提取:我们纳入了评估lecanemab药理、疗效或安全性的英语临床试验、随机对照试验、综述和系统综述,用于治疗阿尔茨海默病:在Clarity AD III期试验中,lecanemab导致脑淀粉样蛋白水平下降,并显示认知和功能的临床指标有适度改善。在18个月时,与安慰剂(1.66)相比,每两周一次、每次10毫克/千克的lecanemab临床痴呆评级-方框总分与基线的最小二乘法平均值变化(1.21)较低,显著差异为-0.45(95% CI,-0.67至-0.23;P<0.001)。在698名参与者的子集中,来卡尼单抗使脑淀粉样蛋白负荷减少了-59.1 Centiloids(95% CI,-62.6至-55.6)。来卡尼单抗在阿尔茨海默病评估量表--认知分量表14、阿尔茨海默病综合评分和阿尔茨海默病合作研究--轻度认知障碍--日常生活活动评分方面显示出良好的差异。不良反应包括输液相关反应(26.4%)和淀粉样蛋白相关成像异常(12.6%):与患者护理和临床实践的相关性:来卡尼单抗可减轻认知功能衰退,但在静脉给药、成本和磁共振成像需求等方面存在问题。正在进行的皮下给药和正电子发射断层扫描试验可能会提供解决方案:乐卡单抗是一种人源化单克隆抗体,对可溶性淀粉样蛋白-β(Aβ)聚集体具有选择性。来卡尼单抗能减少脑部 Aβ 斑块,并能适度减轻认知功能临床指标的下降。
Lecanemab: A Humanized Monoclonal Antibody for the Treatment of Early Alzheimer Disease.
Objective: To review current pharmacology, pharmacokinetics/pharmacodynamics, safety, and efficacy of lecanemab in patients with Alzheimer disease.
Data sources: A literature search of PubMed (April 1, 2016-November 15, 2023) and ClinicalTrials.gov search were conducted using the following search terms: lecanemab and BAN2401. Additional articles were identified by hand from references.
Study selection and data extraction: We included English-language clinical trials, randomized controlled trials, reviews, and systematic reviews evaluating lecanemab pharmacology, efficacy, or safety in humans for the management of Alzheimer disease.
Data synthesis: In the Clarity AD phase III trial, lecanemab led to a decrease in brain amyloid levels and showed moderate improvement in clinical measures of cognition and function. At 18 months, lecanemab 10 mg/kg biweekly exhibited a lower least squares mean change from baseline (1.21) compared to placebo (1.66) of Clinical Dementia Rating-Sum of Boxes score, signifying a significant difference of -0.45 (95% CI, -0.67 to -0.23; P < 0.001). In a subset of 698 participants, lecanemab reduced brain amyloid burden by -59.1 Centiloids (95% CI, -62.6 to -55.6). Lecanemab demonstrated favorable differences in Alzheimer Disease Assessment Scale-cognitive subscale 14, Alzheimer Disease Composite Score, and Alzheimer Disease Cooperative Study-Mild Cognitive Impairment-Activities of Daily Living scores. Adverse events included infusion-related reactions (26.4%) and amyloid-related imaging abnormalities (12.6%).
Relevance to patient care and clinical practice: Lecanemab reduces cognitive decline but raises concerns about intravenous administration, cost, and magnetic resonance imaging needs. Ongoing trials exploring subcutaneous dosing and positron emission tomography scans may offer solutions.
Conclusion: Lecanemab is a humanized monoclonal antibody that is selective for soluble amyloid-beta (Aβ) aggregates. Lecanemab has exhibited a decrease in brain Aβ plaques and moderately less decline on clinical measures of cognitive function.
期刊介绍:
Annals of Pharmacotherapy (AOP) is a peer-reviewed journal that advances pharmacotherapy throughout the world by publishing high-quality research and review articles to achieve the most desired health outcomes.The articles provide cutting-edge information about the most efficient, safe and cost-effective pharmacotherapy for the treatment and prevention of various illnesses. This journal is a member of the Committee on Publication Ethics (COPE). Average time from submission to first decision: 14 days