Kenneth G. Pugh, MD, MSc, Norton Neuroscience Institute Memory Center, Norton Healthcare, Norton Medical Plaza III- Brownsboro, Suite 300, 4915 Norton Healthcare Blvd. Louisville, KY 40241 U.S.A., (502) 394-6460 (Office); (502) 394-6465 (FAX), E-mail:
J Prev Alzheimers Dis. 2024;11(6):1549-1562. doi: 10.14283/jpad.2024.159.
On July 6, 2023 the U.S. Food and Drug Administration approved the anti-amyloid monoclonal antibody lecanemab (Leqembi®) for treatment of patients with mild cognitive impairment or mild dementia due to Alzheimer's disease (AD). Our early experience and lessons learned with lecanemab in a regional community medical center are described.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational study highlights the first 71 patients treated with lecanemab at our multidisciplinary Norton Neuroscience Institute Memory Center. All patients had positive cerebrospinal fluid biomarkers for AD and underwent at least 1 lecanemab infusion. Two patients had additional amyloid PET scans which were positive.
The mean age was 72 years (49-90 years), and 44 (62%) patients were female. Most were Caucasian (68 [96%]), and 54 [76%] were referred to our Memory Center by their primary care provider. Comorbidities were common, including hypertension (34 [48%]), hypercholesterolemia (51 [72%]), diabetes mellitus (17 [24%]), and cardiovascular disease excluding hypertension (22 [31%]). The mean body mass index was 27.0 (range: 17.8-45.0). A total of 36 (51%) patients were heterozygous for the ApoE4 genotype, and 9 (13%) were homozygous. A total of 61 [86%] patients had been treated with donepezil; 40 (56%) patients had received memantine. Of the 50 patients who completed 1 or more safety monitoring brain MRIs following infusion, 12 (24%) had amyloid-related imaging abnormalities (ARIA) detected: solitary ARIA-H (hemorrhage) in 5, solitary ARIA-E (edema) in 3, and both ARIA-H and ARIA-E in 4. Of the 12 patients with ARIA, 9 were asymptomatic, 4 were homozygous for the ApoE4 genotype, and 6 were heterozygous for the ApoE4 genotype. Of the 9 who were homozygous for the ApoE4 genotype in this study, 4 (44%) had evidence of ARIA. Of the 36 who were heterozygous for the ApoE4 genotype, 6 (17%) were diagnosed with ARIA. Twenty-six (37%) patients experienced infusion reactions after their first lecanemab infusion: headaches (12 patients) and shaking/chills/rigors (11 patients) were most common. Twenty-three (88%) of these 26 patients reported the side effects either at the infusion center or within the first 24 hours post-infusion. One patient died shortly after the first lecanemab infusion of a myocardial infarction. It is uncertain whether or not this death was related to lecanemab treatment.
Through our early experience with lecanemab, we have recognized several areas of improvement which have clarified and enhanced the lecanemab infusion experience.
2023 年 7 月 6 日，美国食品和药物管理局批准了抗淀粉样蛋白单克隆抗体 lecanemab（Leqembi®）用于治疗轻度认知障碍或轻度痴呆症患者，这些患者的病因是阿尔茨海默病（AD）。本文介绍了我们在一家地区性社区医疗中心使用 lecanemab 的早期经验和教训。
设计、地点和参与者：本回顾性观察性研究重点介绍了在我们的诺顿神经科学研究所记忆中心接受 lecanemab 治疗的前 71 名患者。所有患者均有 AD 阳性脑脊液生物标志物，并至少接受了 1 次 lecanemab 输注。另外 2 名患者还进行了额外的淀粉样蛋白 PET 扫描，结果均为阳性。
患者平均年龄为 72 岁（49-90 岁），44 名（62%）患者为女性。大多数为高加索人（68 [96%]），54 名（76%）患者由其初级保健提供者转诊至我们的记忆中心。合并症常见，包括高血压（34 [48%]）、高胆固醇血症（51 [72%]）、糖尿病（17 [24%]）和除高血压以外的心血管疾病（22 [31%]）。平均体重指数为 27.0（范围：17.8-45.0）。共有 36 名（51%）患者为 ApoE4 基因型杂合子，9 名（13%）为纯合子。共有 61 名（86%）患者接受过多奈哌齐治疗；40 名（56%）患者接受过美金刚治疗。在接受输注后完成 1 次或多次安全性监测脑 MRI 的 50 名患者中，发现 12 名（24%）有淀粉样蛋白相关成像异常（ARIA）：5 名出现单纯性 ARIA-H（出血），3 名出现单纯性 ARIA-E（水肿），4 名同时出现 ARIA-H 和 ARIA-E。在 12 名有 ARIA 的患者中，9 名无症状，4 名是 ApoE4 基因型纯合子，6 名是 ApoE4 基因型杂合子。在这项研究中，9 名 ApoE4 基因型纯合子中有 4 名（44%）有 ARIA 证据。在 36 名 ApoE4 基因型杂合子中，有 6 名（17%）被诊断为 ARIA。26 名（37%）患者在首次接受 lecanemab 输注后出现输注反应：最常见的是头痛（12 名患者）和震颤/发冷/寒战（11 名患者）。这 26 名患者中的 23 名（88%）在输注中心或输注后 24 小时内报告了这些副作用。1 名患者在首次接受 lecanemab 输注后不久死于心肌梗死。目前尚不清楚该死亡是否与 lecanemab 治疗有关。
通过使用 lecanemab 的早期经验，我们发现了几个需要改进的地方，这些改进明确了并增强了 lecanemab 输注体验。
