Medel Sánchez Andrea, Ortiz Hernández Arturo, Moreno Moreno Ramiro A, Salas López Diana, Madrigal Gómez Luz E, Dominguez Ibarra Anna K, Gutiérrez Rojas Beatriz A, Garcia Navarro Cesar O, Moreno Becerril Gerardo T, Montelongo Quevedo Mauricio, Flores Valdés Jose R
General Practice, Universidad de Guanajuato, Leon, MEX.
General Medicine, Universidad Autónoma de Tamaulipas, Ciudad Victoria, MEX.
Cureus. 2024 Dec 17;16(12):e75907. doi: 10.7759/cureus.75907. eCollection 2024 Dec.
Alzheimer's disease (AD) is the leading cause of dementia, characterized by progressive cognitive decline. Cholinesterase inhibitors are commonly used to manage symptoms but have limited efficacy as the disease progresses. Aducanumab, a monoclonal antibody targeting amyloid-β (Aβ) plaques, has emerged as a novel therapeutic approach. Despite its Food and Drug Administration (FDA) approval, its efficacy and safety remain contentious, particularly following the European Medicines Agency's (EMA's) rejection. This systematic review aims to evaluate the efficacy, safety, and clinical outcomes of aducanumab in treating mild AD. Adhering to Preferred Reporting Items for Systematic Reviews (PRISMA) 2020 guidelines, we conducted a comprehensive search of PubMed and Science Direct databases, including randomized controlled trials (RCTs), cohort studies, and case-control studies focusing on aducanumab versus placebo in mild AD. Studies were screened based on predefined inclusion and exclusion criteria, and data were extracted on clinical outcomes, biomarkers, and neuroimaging markers. The risk of bias was assessed using the Cochrane Handbook and Newcastle-Ottawa Scale. Out of 967 identified records, seven studies met the inclusion criteria. Findings indicated a dose-dependent reduction in Aβ plaques with aducanumab, but clinical outcomes varied. High-dose aducanumab (10 mg/kg) demonstrated significant improvements in some studies but not others. Adverse events, notably amyloid-related imaging abnormalities (ARIA), were frequent, especially at higher doses. The studies exhibited heterogeneous treatment effects and underscored the potential of cerebrospinal fluid biomarkers as an alternative to amyloid positron emission tomography (PET) scans. Aducanumab shows promise in reducing Aβ plaques and has potential clinical benefits at high doses; however, its safety profile, particularly concerning ARIA, remains a significant concern. The variability in clinical efficacy highlights the need for further research to optimize dosing regimens and identify patient populations most likely to benefit from treatment. Future studies should focus on refining treatment protocols and exploring alternative biomarkers to improve therapeutic outcomes for AD.
阿尔茨海默病（AD）是痴呆症的主要病因，其特征是进行性认知衰退。胆碱酯酶抑制剂通常用于控制症状，但随着疾病进展，其疗效有限。阿杜卡努单抗是一种靶向淀粉样β蛋白（Aβ）斑块的单克隆抗体，已成为一种新型治疗方法。尽管它已获得美国食品药品监督管理局（FDA）的批准，但其疗效和安全性仍存在争议，尤其是在欧洲药品管理局（EMA）拒绝批准之后。本系统评价旨在评估阿杜卡努单抗治疗轻度AD的疗效、安全性和临床结局。我们遵循系统评价的首选报告项目（PRISMA）2020指南，对PubMed和科学Direct数据库进行了全面检索，包括随机对照试验（RCT）、队列研究和病例对照研究，重点关注阿杜卡努单抗与安慰剂在轻度AD中的对比。根据预先定义的纳入和排除标准对研究进行筛选，并提取有关临床结局、生物标志物和神经影像标志物的数据。使用Cochrane手册和纽卡斯尔-渥太华量表评估偏倚风险。在967条识别出的记录中，有7项研究符合纳入标准。研究结果表明，阿杜卡努单抗可使Aβ斑块呈剂量依赖性减少，但临床结局各不相同。高剂量阿杜卡努单抗（10mg/kg）在一些研究中显示出显著改善，但在其他研究中并非如此。不良事件，尤其是淀粉样蛋白相关成像异常（ARIA）很常见，尤其是在高剂量时。这些研究显示出异质性的治疗效果，并强调了脑脊液生物标志物作为淀粉样蛋白正电子发射断层扫描（PET）扫描替代方法的潜力。阿杜卡努单抗在减少Aβ斑块方面显示出前景，高剂量时具有潜在的临床益处；然而，其安全性，尤其是与ARIA相关的安全性，仍然是一个重大问题。临床疗效的变异性凸显了进一步研究以优化给药方案并确定最可能从治疗中受益的患者群体的必要性。未来的研究应专注于完善治疗方案并探索替代生物标志物，以改善AD的治疗效果。
