Bapineuzumab for mild to moderate Alzheimer's disease: a meta-analysis of randomized controlled trials.
Bapineuzumab for mild to moderate Alzheimer's disease: a meta-analysis of randomized controlled trials.
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DOI：
10.1186/s12883-017-0850-1
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发表时间：
2017-04-04
期刊：
影响因子：
2.6
通讯作者：
AlSafadi AM
中科院分区：
文献类型：
--
作者：
Abushouk AI;Elmaraezy A;Aglan A;Salama R;Fouda S;Fouda R;AlSafadi AM
阿尔茨海默病（Alzheimer's disease，AD）是一种全球性的神经退行性疾病，其临床特征是进行性记忆丧失和认知功能的逐渐损害。Bapineuzumab是一种完全人源化的单克隆抗体，可与大脑中的神经毒性淀粉样蛋白结合，增强其清除率。我们进行了这项系统性综述和荟萃分析，以评估bapineuzumab在轻度至中度阿尔茨海默病患者中的安全性和有效性。我们使用相关关键词对PubMed、奥维德、EBSCO、Scopus、Embase、科克伦中心和web of science进行了基于网络的文献检索。使用Review Manager软件（Windows版本5.3）从合格记录中提取数据，并合并为平均差（MD）或风险比（RR）值及其95%置信区间（CI）。通过卡方和I方检验测量异质性。来自6项随机临床试验（n = 2380）的汇总效应估计显示，bapineuzumab显著降低了磷酸化tau蛋白的脑脊液浓度（标准化MD = −5.53，95% CI [−8.29，−2.76]）。然而，在阿尔茨海默病评估量表（ADAS）-Cog 11自基线的变化方面，bapineuzumab组并不上级于安慰剂组。（MD = 0.14，95% CI [-0.72，0.99]），痴呆残疾评估（DAD）量表（MD = 1.35，95% CI [-1.74，4.43]）和简易精神状态检查（MMSE）评分（MD = 0.08，95% CI [-0.31，0.47]）。关于安全性，bapineuzumab增加了严重治疗后出现的不良事件（RR = 1.18，95% CI [1.02，1.37]）和脑血管源性水肿（RR = 40.88，95% CI [11.94，135.95]）的风险。在ADAS-cog 11、DAD和MMSE评分较基线的变化方面，所有bapineuzumab剂量（0.15、0.5、1和2 mg/kg）与安慰剂相似，但0.15 mg/kg剂量除外，其导致ADAS-cog 11量表显著恶化（MD = 5.6，95% CI [0.22，10.98]）。考虑到缺乏临床疗效，加上与严重不良事件的显著相关性，bapineuzumab不应用于治疗轻度至中度AD患者。未来的研究应探讨bapineuzumab与其他治疗策略的联合作用，并重新评估靶向淀粉样β蛋白在AD治疗中的疗效。本文的在线版本（doi：10.1186/s12883-017-0850-1）包含补充材料，可供授权用户使用。
Alzheimer’s disease (AD) is a globally prevalent neurodegenerative condition, clinically characterized by progressive memory loss and gradual impairment of cognitive functions. Bapineuzumab is a fully humanized monoclonal antibody that binds to neurotoxic amyloid proteins in the brain, enhancing their clearance. We performed this systematic review and meta-analysis to evaluate the safety and efficacy of bapineuzumab in patients with mild to moderate Alzheimer’s disease. We performed a web-based literature search of PubMed, Ovid, EBSCO, Scopus, Embase, Cochrane CENTRAL, and web of science using the relevant keywords. Data were extracted from eligible records and pooled as mean difference (MD) or risk ratio (RR) values with their 95% confidence interval (CI), using Review Manager software (version 5.3 for windows). Heterogeneity was measured by Chi-square and I-square tests. The pooled effect estimate from six randomized clinical trials (n = 2380) showed that bapineuzumab significantly reduced the cerebrospinal fluid concentration of phosphorylated tau proteins (Standardized MD = −5.53, 95% CI [−8.29, −2.76]). However, the bapineuzumab group was not superior to the placebo group in terms of change from baseline in Alzheimer’s disease assessment scale (ADAS)-Cog11 (MD = 0.14, 95% CI [−0.72, 0.99]), disability assessment for dementia (DAD) scale (MD = 1.35, 95% CI [−1.74, 4.43]), and mini-mental state examination (MMSE) scores (MD = 0.08, 95% CI [−0.31, 0.47]). Regarding safety, bapineuzumab increased the risk of serious treatment-emergent adverse events (RR = 1.18, 95% CI [1.02, 1.37]) and cerebral vasogenic edema (RR = 40.88, 95% CI [11.94, 135.95]). All bapineuzumab doses (0.15, 0.5, 1, and 2 mg/kg) were similar to placebo in terms of change from baseline in ADAS-cog11, DAD, and MMSE scores, except for the 0.15 mg/kg dose, which caused a significant worsening on the ADAS-cog11 scale (MD = 5.6, 95% CI [0.22, 10.98]). Considering the lack of clinical efficacy, combined with the significant association with serious adverse events, bapineuzumab should not be used to treat patients with mild to moderate AD. Future studies should investigate the effect of combining bapineuzumab with other therapeutic strategies and reevaluate the efficacy of targeting amyloid β proteins in AD therapy. The online version of this article (doi:10.1186/s12883-017-0850-1) contains supplementary material, which is available to authorized users.