Memantine in patients with Alzheimer's disease receiving donepezil: new analyses of efficacy and safety for combination therapy.
Memantine in patients with Alzheimer's disease receiving donepezil: new analyses of efficacy and safety for combination therapy.
复制标题
DOI：
10.1186/alzrt160
复制
发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Wilkinson D
中科院分区：
文献类型：
--
作者：
Atri A;Molinuevo JL;Lemming O;Wirth Y;Pulte I;Wilkinson D
美金刚和胆碱酯酶抑制剂一起使用时，可能会对阿尔茨海默病（AD）提供额外的益处。本研究评估了美金刚与稳定的多奈哌齐联合治疗中度至重度AD患者和中度AD亚组的疗效和安全性。对两项为期24周、随机、双盲、安慰剂对照试验（美金刚20 mg/天与安慰剂相比，添加至稳定的胆碱酯酶抑制剂）的数据进行事后荟萃分析。包括接受多奈哌齐10 mg/天且简易精神状态检查（MMSE）评分< 20的所有患者的数据（n = 510）。使用认知、功能和整体状态的测量来评估疗效。此外，还评估了明显的临床恶化（定义为三个主要疗效领域相对于基线的同时恶化）和安全性（通过治疗后出现的不良事件测量）。对中度至重度AD患者（MMSE 5-19; MOD-SEV亚组）和中度AD患者（MMSE 10-19; MOD亚组; n = 367）进行分析。在第24周，在MOD-SEV亚组中，接受美金刚加多奈哌齐的患者在认知测量方面显著优于接受安慰剂加多奈哌齐的患者。（P < 0.0001），功能（P = 0.02）和总体状态（P = 0.010），标准化平均差异（SMD）分别为0.36、0.21和0.23（所有末次观察值结转）。同样，在MOD亚组中，观察到认知（P = 0.008）、功能（P = 0.04）和整体状态（P = 0.008）的显著获益，SMD分别为0.28、0.21和0.28。在两个亚组中，与接受安慰剂加多奈哌齐的患者相比，接受美金刚加多奈哌齐的患者显示出明显的临床恶化（MOD-SEV：8.7% vs 20.4%，P = 0.0002; MOD：5.9% vs 15.0%，P = 0.006）。治疗组间不良事件的发生率相似。这些结果支持并扩展了先前的证据，即在中度AD患者和中度至重度AD患者中，将美金刚添加到稳定的多奈哌齐的联合治疗与减少认知，功能和整体状态的24周下降的显着益处相关。联合治疗显著降低了显著临床恶化的发生率，具有良好的安全性和耐受性，并产生了统计学显著性和临床意义的效应量。
Memantine and cholinesterase inhibitors potentially offer additional benefits in Alzheimer's disease (AD) when used together. This study assessed the efficacy and safety of combination treatment with memantine added to stable donepezil in patients with moderate to severe AD, and in a subset with moderate AD. Post hoc meta-analyses of data combined from two 24-week, randomised, double-blind, placebo-controlled trials of memantine 20 mg/day versus placebo, added to a stable cholinesterase inhibitor, were conducted. Data were included for all patients receiving donepezil 10 mg/day with Mini-Mental State Examination (MMSE) scores < 20 (n = 510). Efficacy was assessed using measures of cognition, function, and global status. Furthermore, marked clinical worsening, defined as concurrent deterioration from baseline in the three main efficacy domains, and safety, measured by treatment-emergent adverse events, were assessed. Analyses were performed for patients with moderate to severe AD (MMSE 5-19; MOD-SEV subgroup), and also for patients with moderate AD (MMSE 10-19; MOD subgroup; n = 367). At week 24, in the MOD-SEV subgroup, patients receiving memantine added to donepezil significantly outperformed those receiving placebo added to donepezil in measures of cognition (P < 0.0001), function (P = 0.02), and global status (P = 0.010), with standardised mean differences (SMDs) of 0.36, 0.21, and 0.23, respectively (all last observation carried forward). Similarly, in the MOD subgroup, significant benefits were observed for cognition (P = 0.008), function (P = 0.04) and global status (P = 0.008), with SMDs of 0.28, 0.21, and 0.28, respectively. Significantly fewer patients receiving memantine added to donepezil showed marked clinical worsening than those receiving placebo added to donepezil, in both subgroups (MOD-SEV: 8.7% versus 20.4%, P = 0.0002; MOD: 5.9% versus 15.0%, P = 0.006). The incidence of adverse events was similar between treatment groups. These results support and extend previous evidence that combination treatment with memantine added to stable donepezil in patients with moderate AD, and in those with moderate to severe AD, is associated with significant benefits in reducing 24-week decline in cognition, function and global status. Combination treatment produces substantially reduced rates of marked clinical worsening, has good safety and tolerability, and generates effect sizes that are both statistically significant and clinically meaningful.
登录
查看更多内容
DOI：
10.1159/000335156
发表时间：
2012
期刊：
Neuro-degenerative diseases
影响因子：
--
作者：
Atri A;Rountree SD;Lopez OL;Doody RS
通讯作者：
Doody RS
DOI：
10.1016/j.jalz.2006.07.001
发表时间：
2006-10-01
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Cummings, Jeffrey L
通讯作者：
Cummings, Jeffrey L
DOI：
10.1097/01.wad.0000213859.35355.59
发表时间：
2006-10-01
影响因子：
2.1
作者：
Feldman, Howard H.;Schmitt, Frederick A.;Olin, Jason T.
通讯作者：
Olin, Jason T.
影响因子：
9.9
作者：
Rogers, SL;Farlow, MR;Walshe, TM
通讯作者：
Walshe, TM
影响因子：
14
作者：
Gillette-Guyonnet, Sophie;Andrieu, Sandrine;Vellas, Bruno
通讯作者：
Vellas, Bruno