Lecanemab——用于治疗早期阿尔茨海默病的单克隆抗体。
完整摘要 · 中文译文
目的：综述lecanemab（一种人源化免疫球蛋白γ1（IgG1）单克隆抗体）治疗早期阿尔茨海默病（AD）的药理学、有效性和安全性。 数据来源：对Embase、PubMed、International Pharmaceutical Abstracts、Cochrane CENTRAL、Scopus、Web of Science和Google Scholar进行了从建库至2025年12月的全面检索。 研究选择与数据提取：纳入评估lecanemab药理学、药代动力学、有效性和安全性的I-III期临床试验、系统评价和荟萃分析。同时审阅产品说明书以补充临床数据。 数据综合：在III期Clarity AD试验中，患者按1:1随机分配至lecanemab 10 mg/kg每2周一次组或安慰剂组。主要终点为18个月时临床痴呆评定量表总分（CDR-SB）较基线的变化。lecanemab组平均变化为1.21，安慰剂组为1.66（差异，-0.45；95% CI，-0.67至-0.23；P < .001）。次要终点，即通过正电子发射断层扫描（PET）评估的淀粉样蛋白负荷（n = 698），lecanemab组显示为-55.48 centiloids，安慰剂组为3.64（差异-59.12 centiloids；95% CI，-62.64至-55.6；P < .001）。其他终点包括ADAS-cog 14、ADCOMS和ADCS-MCI-ADL评分的变化，均显示lecanemab优于安慰剂。lecanemab耐受性良好；输液部位反应发生率为26.4%。淀粉样蛋白相关影像异常（ARIA-E）发生率为12.6%。 结论：与安慰剂相比，lecanemab在统计学上显著减缓了 对CDR-SB所测量的认知功能下降及包括淀粉样蛋白负荷降低在内的次要终点具有显著疗效。然而，其临床获益必须与ARIA风险和沉重的经济负担进行权衡。现有证据支持在严格筛选的早期AD患者中，在密切监测下使用该药。
完整摘要 · 英文原文
OBJECTIVE: Review the pharmacology, efficacy, and safety of lecanemab, a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody, for the treatment of early Alzheimer's disease (AD). DATA SOURCES: Comprehensive search of Embase, PubMed, International Pharmaceutical Abstracts, Cochrane CENTRAL, Scopus, Web of Science, and Google Scholar were conducted from inception through December 2025. STUDY SELECTION AND DATA EXTRACTION: Phase I-III clinical trials, systematic reviews, and meta-analyses evaluating lecanemab pharmacology, pharmacokinetics, efficacy, and safety were included. Product labeling was reviewed to supplement clinical data. DATA SYNTHESIS: In the phase III Clarity AD trial, patients were randomized 1:1 to lecanemab 10 mg/kg every 2 weeks or placebo. The primary endpoint was change from baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) score at 18 months. Lecanemab demonstrated a mean change of 1.21 versus 1.66 with placebo (difference, -0.45; 95% CI, -0.67 to -0.23; P < .001). Secondary endpoint, amyloid burden via positron emission tomography (PET) scans (n = 698) showed -55.48 centiloids with lecanemab versus 3.64 with placebo (difference -59.12 centiloids; 95% CI, -62.64 to -55.6; P < .001). Additional endpoints included changes in ADAS-cog 14, ADCOMS, and ADCS-MCI-ADL scores favoring lecanemab over placebo. Lecanemab was well tolerated; infusion site reactions occurred in 26.4%. Amyloid-related imaging abnormalities (ARIA-E) occurred in 12.6% of participants. CONCLUSION: Compared to placebo, lecanemab demonstrated statistically significant slowing of cognitive decline on CDR-SB and secondary endpoints, including amyloid burden reduction. However, its clinical benefit must be weighed against ARIA risk and substantial financial burden. Current evidence supports its use in carefully selected patients with early AD under close supervision.