Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas (UNLV), Las Vegas, NV, USA.
Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas (UNLV), Las Vegas, NV, USA.
BioDrugs. 2024 Jan;38(1):5-22. doi: 10.1007/s40259-023-00633-2. Epub 2023 Nov 13.
Two monoclonal antibodies (mAbs), aducanumab and lecanemab, have received accelerated approval from the US FDA for initiation of treatment in early Alzheimer's disease patients who have proven β-amyloid pathology (Aβ). One of these, lecanemab, has subsequently received full approval and other monoclonal antibodies are poised for positive review and approval. Anti-amyloid mAbs share the feature of producing a marked reduction in total brain Aβ revealed by amyloid positron emission tomography. Trials associated with slowing of cognitive decline have achieved a reduction in measurable plaque Aβ in the range of 15-25 centiloids; trials of agents that did not reach this threshold were not associated with cognitive benefit. mAbs have differences in terms of titration schedules, MRI monitoring schedules for amyloid-related imaging abnormalities (ARIA), and continuing versus interrupted therapy. The approximate 30% slowing of decline observed with mAbs is clinically meaningful in terms of extended cognitive integrity and delay of onset of the more severe dementia phases of Alzheimer's disease. Approval of these agents initiates a new era in Alzheimer's disease therapeutics with disease-modifying properties. Further advances are needed, i.e. greater efficacy, improved safety, enhanced convenience, and better understanding of ill-understood observations such as brain volume loss.
两种单克隆抗体（mAbs），即 aducanumab 和 lecanemab，已获得美国 FDA 的加速批准，可用于治疗已证实存在β-淀粉样蛋白病理学（Aβ）的早期阿尔茨海默病患者。其中一种，即 lecanemab，随后获得了全面批准，其他单克隆抗体也有望获得积极的审查和批准。抗淀粉样蛋白 mAbs 的共同特点是通过淀粉样蛋白正电子发射断层扫描（PET）显示总脑 Aβ 显著减少。与认知能力下降减缓相关的试验已达到可测量斑块 Aβ 减少 15-25 个百分位数；未达到这一阈值的药物试验与认知益处无关。mAbs 在滴定方案、与淀粉样蛋白相关的成像异常（ARIA）的 MRI 监测方案以及继续治疗与中断治疗方面存在差异。mAbs 观察到的约 30%的下降速度在认知完整性的延长和阿尔茨海默病更严重痴呆阶段的发病延迟方面具有临床意义。这些药物的批准开启了具有疾病修饰特性的阿尔茨海默病治疗的新时代。需要进一步的进展，即更大的疗效、更高的安全性、更高的便利性以及更好地理解理解不清的观察结果，如脑容量损失。
