Interpretation of clinical application recommendations for anti-Aβ monoclonal antibodies （2025 Edition）

doi:10.16150/j.1671-2870.2026.02.005

Abstract

Abstract:

The Clinical Application Recommendations for Anti-Aβ Monoclonal Antibodies (2025 Edition) systema-tically integrates Phase Ⅲ clinical trial data for aducanumab, lecanemab, and donanemab, referencing relevant drug labels, domestic real-world evidence, and clinical practice experience. With a focus on lecanemab and donanemab, it provides a comprehensive update to the 2024 edition. The recommendations provide detailed guidance on patient screening before treatment, treatment regimen evaluation, medication protocol standardization, adverse event monitoring, discontinuation criteria, and management of special populations, with significant progress in individualizing discontinuation criteria, specif-ying that lecanemab is recommended as an 18-month fixed course. For donanemab, the treatment completion criterion is defined as achieving a Centiloid value measured by amyloid-β positron emission tomography (Aβ-PET) that reaches a preset threshold, specifically a single Centiloid value ≤11 or two consecutive Centiloid values both in the range of 11-25. Regarding safety management, the recommendations further refine the stratified monitoring and management protocol for amyloid-related imaging abnormalities (ARIA) and establish precise risk management strategies for special populations, including patients on anticoagulant therapy and apolipoprotein E (APOE) ε4/ε4 homozygotes. Currently, the clinical application of anti-Aβ monoclonal antibodies still faces several key challenges. The integrated application system of multidimensional biomarkers has not yet been systematically established, which constrains the development of individualized treatment pathways. Meanwhile, real-world evidence on long-term medication use in the Chinese population remains insufficient, hindering the local optimization of treatment strategies and refined risk management. Future efforts should focus on strengthe-ning research in the above directions to promote the continuous development of anti-Aβ monoclonal antibody therapy from a standardized model toward individualized precision medicine based on biomarkers and clinical phenotypes.

Key words: Alzheimer's disease, Amyloid β-protein, Monoclonal antibody, Guideline interpretation, Treatment

CLC Number:

R446
R741

ZHI Nan, GENG Jieli, CAO Wenwei, SONG Yaying, WANG Gang. Interpretation of clinical application recommendations for anti-Aβ monoclonal antibodies （2025 Edition）[J]. Journal of Diagnostics Concepts & Practice, 2026, 25(02): 148-156.

Figures/Tables 2

Table 1

Comparison of clinical trial inclusion criteria and clinical practice suitability between the 2024 and 2025 Editions of Anti-Aβ Monoclonal Antibody Guidelines

项目	临床试验入组标准		临床实践适用标准
项目	2024版	2025版	2024版	2025版
年龄	50~85岁	50~90岁	≤85岁	同2024版
诊断	AD源性MCI或轻度AD痴呆临床标准	AD源性MCI或轻度AD痴呆临床标准	AD源性MCI或轻度AD痴呆临床标准	同2024版
基线评分	MMSE评分24~30分，CDR-GS评分0.5分，RBANS延迟记忆指数≤85分	CDR-GS评分0.5~1.0分，MMSE评分22~30分	MMSE评分21~30分或同等认知水平	同2024版
淀粉样蛋白状态	Aβ-PET阳性	淀粉样蛋白PET阳性或者脑脊液检查符合AD诊断标准	Aβ-PET阳性或脑脊液检查符合阿尔茨海默病诊断标准并经Aβ-PET/CT或Aβ-PET/MRI验证	同2024版，补充建议可结合标准化Centiloid值进行评估
基因	包括ApoE基因型	非必需	应与患者和（或）照料者讨论基因检测的意愿和必要性	同2024版
神经系统检查	排除非AD的神经系统变性疾病、脑卒中和TIA	排除非AD病因所致的认知功能障碍患者，或近12个月内有卒中、TIA、癫痫发作史者	排除非AD的神经系统变性疾病	排除非AD病因所致的认知功能障碍患者，或近12个月内有卒中、TIA、癫痫发作史者
心血管病病史	排除心绞痛、心肌梗死、充血性心力衰竭	排除未得到稳定或充分控制的心脏疾病	心血管病稳定（近3个月无症状或经心脏科评定病情稳定）；根据患者安全参与治疗方案的能力制定临床决策	同2024版
其他基础疾病病史	排除其他有临床意义的系统性疾病、无法控制的糖尿病、未控制的高血压、不稳定的恶性肿瘤、肝炎或肝功能障碍、HIV感染	排除任何其他未得到稳定或充分控制的医疗状况，或研究者认为可能影响参与者安全或干扰研究评估的疾病	基础疾病稳定（主要指标如血压和血糖等无明显波动、相应药物治疗≥3个月或经专科评定病情稳定）；根据患者安全参与治疗方案的能力制定临床决策	同2024版
精神疾病病史	排除既往6个月内病情不稳定的精神疾病；物质成瘾性或药物性精神障碍	排除2年内有已知或可疑的药物或乙醇滥用或依赖史，或在筛选时有阳性尿液药物检测结果的患者	精神状态稳定（经专科评定病情稳定）；根据患者安全参与治疗方案的能力制定临床决策	同2024版
生殖	排除妊娠期或哺乳期女性；育龄期女性须采取避孕措施	排除妊娠期或哺乳期女性；育龄期女性须采取避孕措施	与临床试验入组标准相同	同2024版
凝血功能	排除出血性疾病、正在服用抗凝药	排除未得到充分控制的出血性疾病[包括血小板计数或未接受抗凝治疗者的INR>1.5。接受抗凝治疗的参与者应优化其抗凝状态，并在筛查前至少4周内保持稳定剂量	与临床试验入组标准相同	排除出血性疾病，原则上正在服用抗凝药物（如华法林、达比加群、艾多沙班、利伐沙班、阿哌沙班、贝曲沙班或肝素）的患者不推荐使用单抗治疗
合并用药	允许应用胆碱酯酶抑制药和美金刚	允许应用胆碱酯酶抑制剂和美金刚	与临床试验入组标准相同	同2024版
基线 MRI检查	排除急性或亚急性出血、大出血、4个以上微出血灶、皮质梗死（>1.5 cm）、1个以上梗死灶（>1.5 cm）、表面铁沉积症、弥漫性白质疾病	排除超过4个微出血点（定义为最大直径10 mm或更小）；单一的脑出血的最大直径>10 mm；表面铁沉积证据；血管源性水肿；多发腔隙性梗死或涉及主要血管区域的梗死；严重的脑小血管病变	与临床试验入组标准相同	与临床试验标准相同，补充对于脑内存在5~9个微出血灶（单个直径<10 mm）的患者，可在全面评估及充分沟通的基础上，谨慎考虑抗Aβ单克隆抗体治疗。如有条件，建议头颅MRI在用药前1个月内完成。
知情同意	须由受试者和照料者共同签署	须由受试者和照料者共同签署	受试者和照料者应了解治疗性质、要求和预期结局	同2024版

Table 1

Figure 1

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