Paczynski Madeline, Hofmann Anna, Posey Zachary, Gregersen Maren, Rudman Michelle, Ellington Dawn, Aldinger Melissa, Musiek Erik S, Holtzman David M, Bateman Randall J, Long Justin M, Ghoshal Nupur, Carr David B, Dow Alan, Namazie-Kummer Sheyda, Jana Nayid, Xiong Chengjie, Morris John C, Benzinger Tammie L S, Schindler Suzanne E, Snider B Joy
Department of Neurology, Washington University School of Medicine in St Louis, St Louis, Missouri.
Knight Alzheimer Disease Research Center, Washington University School of Medicine in St Louis, St Louis, Missouri.
JAMA Neurol. 2025 May 12. doi: 10.1001/jamaneurol.2025.1232.
Two monoclonal antibodies targeting amyloid plaques, lecanemab and donanemab, have received traditional US Food and Drug Administration (FDA) approval for the treatment of early symptomatic Alzheimer disease (AD). The most significant adverse events associated with these therapies are infusion-related reactions and amyloid-related imaging abnormalities (ARIA) with edema/effusion (ARIA-E) and/or hemorrhage/hemosiderin deposition (ARIA-H). The feasibility and safety of providing these treatments in clinical practice is unclear.
To examine the feasibility and safety of treating patients in specialty memory clinics with lecanemab.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective analysis of consecutive patients in whom lecanemab was initiated between August 1, 2023, and October 1, 2024, at Washington University Memory Diagnostic Center, an outpatient specialty memory clinic. Lecanemab was initiated in 234 patients with early symptomatic AD. Eligibility was based on the FDA label and appropriate use recommendations with occasional exceptions.
Patients were treated with lecanemab, 10 mg/kg, intravenously every 2 weeks.
Infusion-related reactions, ARIA, and withdrawal from treatment were assessed.
The 234 patients treated with lecanemab had a mean age of 74.4 (SD, 6.7) years, 117 were female (50%), and 117 were male. (50%) Infusion-related reactions occurred in 87 patients (37%) and were typically mild. Of the 194 patients at risk for ARIA during the study period, 44 had at least 1 microhemorrhage and/or superficial siderosis before initiation of lecanemab (23%). Over an average treatment period of 6.5 months, 42 total patients (22%) developed ARIA; 29 developed ARIA-E with or without ARIA-H (15%) and 13 developed isolated ARIA-H (6.7%). Eleven patients (5.7%) developed symptomatic ARIA, 2 of those patients (1.0%) with clinically severe symptoms. No patients developed a macrohemorrhage or died. Patients with mild dementia had a 27% rate of symptomatic ARIA; those with mild cognitive impairment or very mild dementia had a 1.8% rate. Overall, 23 of 234 patients (9.8%) withdrew from treatment for various reasons, 10 for ARIA (4.3%).
A single-specialty memory clinic initiated lecanemab treatment in 234 patients over 14 months. The frequency of significant adverse events, including ARIA, was manageable. These results may inform discussions about the risks of anti-amyloid treatments.
两种靶向淀粉样蛋白斑块的单克隆抗体,即乐卡奈单抗和多奈单抗,已获得美国食品药品监督管理局(FDA)的传统批准,用于治疗早期有症状的阿尔茨海默病(AD)。与这些疗法相关的最显著不良事件是输液相关反应以及伴有水肿/积液(ARIA-E)和/或出血/含铁血黄素沉积(ARIA-H)的淀粉样蛋白相关成像异常(ARIA)。在临床实践中提供这些治疗的可行性和安全性尚不清楚。
研究在专科记忆诊所使用乐卡奈单抗治疗患者的可行性和安全性。
设计、地点和参与者:这项回顾性分析纳入了2023年8月1日至2024年10月1日期间在华盛顿大学记忆诊断中心(一家门诊专科记忆诊所)开始使用乐卡奈单抗的连续患者。234例早期有症状AD患者开始使用乐卡奈单抗。入选标准基于FDA标签和适当使用建议,偶尔有例外情况。
患者接受乐卡奈单抗治疗,剂量为10mg/kg,每2周静脉注射一次。
评估输液相关反应、ARIA以及停止治疗情况。
接受乐卡奈单抗治疗的234例患者平均年龄为74.4(标准差,6.7)岁,117例为女性(50%),117例为男性(50%)。87例患者(37%)发生输液相关反应,通常为轻度。在研究期间有ARIA风险的194例患者中,44例在开始使用乐卡奈单抗前至少有1处微出血和/或浅表性铁沉积(23%)。在平均6.5个月的治疗期内,共有42例患者(22%)发生ARIA;29例发生伴有或不伴有ARIA-H的ARIA-E(15%),13例发生孤立性ARIA-H(6.7%)。11例患者(5.7%)发生有症状的ARIA,其中2例患者(1.0%)有临床严重症状。没有患者发生大出血或死亡。轻度痴呆患者有症状ARIA的发生率为27%;轻度认知障碍或极轻度痴呆患者的发生率为1.8%。总体而言,234例患者中有23例(9.8%)因各种原因停止治疗,10例因ARIA(4.3%)。
一家专科记忆诊所在14个月内对234例患者开始使用乐卡奈单抗治疗。包括ARIA在内的重大不良事件发生率是可控的。这些结果可能为关于抗淀粉样蛋白治疗风险的讨论提供参考。