University of Castilla-La Mancha, NeuroPhysiology & Behavior Lab, Biomedical Research Center (CRIB), School of Medicine of Ciudad Real, Spain.
University of Castilla-La Mancha, NeuroPhysiology & Behavior Lab, Biomedical Research Center (CRIB), School of Medicine of Ciudad Real, Spain.
Ageing Res Rev. 2023 Sep;90:102012. doi: 10.1016/j.arr.2023.102012. Epub 2023 Jul 7.
The risk-benefit profile of anti-Aβ monoclonal antibodies (mAbs) in Alzheimer's disease (AD) remains unclear, especially concerning their safety and overall effects on AD progression and cognitive function. Here, we investigated cognitive, biomarker and side effects of anti-Aβ mAbs in large phase III randomized placebo-controlled clinical trials (RCTs) in sporadic AD. The search was performed on Google Scholar, PubMed and ClinicalTrials.gov by applying Jadad score to evaluate the methodological quality of the reports. Studies were excluded if they scored < 3 on Jadad scale or if they analyzed less than 200 sporadic AD patients. We followed PRISMA guidelines and DerSimonian-Laird random-effects model in R. Primary outcomes were cognitive: AD Assessment Scale-Cognitive Subscale (ADAS-Cog), Mini Mental State Examination (MMSE) and Clinical Dementia Rating Scale-sum of Boxes (CDR-SB). Secondary and tertiary outcomes included biomarkers of Aβ and tau pathology, adverse events, and performance on Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale. The meta-analysis included 14,980 patients in 14 studies and four mAbs: Bapineuzumab, Aducanumab, Solanezumab and Lecanemab. The results of this study suggest that anti-Aβ mAbs statistically improved cognitive and biomarker outcomes, particularly Aducanumab and Lecanemab. However, while cognitive effects were of small effect sizes, these drugs considerably increased risk of side effects such as Amyloid Related Imaging Abnormalities (ARIA), especially in APOE-ε4 carriers. Meta-regression revealed that higher (better) baseline MMSE score was associated with improved ADAS Cog and CDR-SB. In order to improve reproducibility and update the analysis in the future, we developed AlzMeta.app, web-based application freely available at https://alzmetaapp.shinyapps.io/alzmeta/.
抗 Aβ 单克隆抗体（mAbs）在阿尔茨海默病（AD）中的风险-效益状况尚不清楚，特别是它们的安全性以及对 AD 进展和认知功能的总体影响。在这里，我们研究了大型 III 期随机安慰剂对照临床试验（RCT）中抗 Aβ mAbs 在散发性 AD 中的认知、生物标志物和副作用。通过应用 Jadad 评分在 Google Scholar、PubMed 和 ClinicalTrials.gov 上进行搜索，以评估报告的方法学质量。如果报告的 Jadad 评分<3 分，或分析的散发性 AD 患者少于 200 例，则将其排除在外。我们遵循 PRISMA 指南和 R 中的 DerSimonian-Laird 随机效应模型。主要结局为认知：AD 评估量表认知子量表（ADAS-Cog）、简易精神状态检查（MMSE）和临床痴呆评定量表-总评分（CDR-SB）。次要和次要结局包括 Aβ 和 tau 病理的生物标志物、不良事件以及阿尔茨海默病合作研究-日常生活活动量表的表现。荟萃分析包括 14980 名患者的 14 项研究和四种 mAbs：Bapineuzumab、Aducanumab、Solanezumab 和 Lecanemab。这项研究的结果表明，抗 Aβ mAbs 在统计学上改善了认知和生物标志物的结果，特别是 Aducanumab 和 Lecanemab。然而，虽然认知效果的效应量较小，但这些药物会大大增加不良反应的风险，例如淀粉样相关成像异常（ARIA），尤其是在 APOE-ε4 携带者中。元回归显示，较高（较好）的基线 MMSE 评分与 ADAS Cog 和 CDR-SB 的改善相关。为了提高可重复性并在未来更新分析，我们开发了 AlzMeta.app，这是一个基于网络的应用程序，可在 https://alzmetaapp.shinyapps.io/alzmeta/ 免费获得。
