Further to the conclusions of the meta-analysis described above, the Cochrane database of systematic reviews, part of The Cochrane Library, also recently analysed the results of multiple memantine clinical studies.³⁷

Based upon references from all major healthcare databases, ongoing trial databases, and registries of unpublished trials, all double-blind, parallel-group, placebo-controlled, randomised trials of memantine in people with dementia were selected for collective review.³⁷ Data were pooled where possible, and ITT and OC analyses were reported.³⁷

The review concluded that in moderate to severe AD, pooled data indicate a bene?cial effect of memantine at six months on cognition, activities of daily living, and behaviour.³⁷ Furthermore, the effects of memantine were supported by a signi?cant improvement in the clinical impression of change, and patients taking memantine appeared to be less likely to develop agitation.³⁷

Prevention of worsening is a clinically relevant treatment goal in a progressive neurodegenerative disease such as AD, and rapidly deteriorating patients are most in need of treatment. In order to provide a measure for clinical relevance of memantine’s effects in moderate to severe AD (MMSE <20), analyses on the prevention of clinical worsening were de?ned based on concurrent clinical worsening in the three domains: cognition, function and global status during the 6-month treatment period, as follows:

        marked clinical worsening – a decline of ≥4 points on ADAS-Cog, or ≥5 points on SIB, plus any decline on ADCS-ADL/ADCS-ADL_19/23 and CIBIC-Plus scales

        any clinical worsening – any decline on ADAS-Cog or SIB, plus any decline on ADCS-ADL_19/23 and CIBIC-Plus scales.

Results were analysed for the whole moderate to severe patient population (MMSE <20; n=1,475) from six studies, as well as for the patients with moderate AD (MMSE 10–19; n=1,116).

        Twice as many placebo-treated patients as memantine-treated patients with moderate to severe AD (MMSE <20) showed ‘marked clinical worsening’ (21% vs 11%; p<0.0001, OC) (Figure 6.7).

        This statistically signi?cant ?nding was also observed for the moderate AD group (MMSE 10–19) in which nearly twice as many placebo-treated patients as memantine-treated patients showed ‘marked clinical worsening’ (16% vs 9%; p=0.0001, OC) (Figure 6.7).

        In addition, signi?cantly more placebo-treated patients showed ‘any clinical worsening’ than memantine-treated patients (MMSE <20: 28% vs 18%, p<0.0001; MMSE 10–19: 25% vs 16%, p=0.0001, OC analyses).

        LOCF analyses provided similar results to OC analyses in all these assessments, and the magnitude of the memantine effect in monotherapy studies was similar to the effect in studies in which patients were also receiving stable AChEIs.

            Memantine has a bene?cial effect in the prevention of clinical worsening in patients with moderate to severe AD. The effect was evident for the whole study population, as well as for the moderate subgroup.

 

We translated the file about Prevention of clinical worsening from English into Chinese.

 

对上述Meta分析的结论进行深入，系统性综述了Cochrane 数据库，部分Cochrane图书馆最近也分析了多个美金刚临床研究的结果³⁷。

基于所有主要医疗保健数据库的参考文献、正在开展临床试验的数据及未发表的临床试验的注册数据，所有双盲、平行对照、安慰剂对照的美金刚治疗痴呆的随机试验被选入进行文献综述。³⁷

该综述得出结论：对于中、重度AD患者，汇总的数据表明6个月时，美金刚对患者认知能力、日常生活活动能力及行为等方面具有良好受益³⁷。而且，临床印象的极大改善以及服用美金刚的患者不容易出现焦虑不安的症状也支持美金刚的上述效应。³⁷

对进行性神经变性疾病，例如AD，防止病情恶化是一种临床相关的治疗目标。并且快速恶化的患者最需要治疗。为了提供一种方法评价美金刚治疗中、重度AD（MMSE<20）的临床意义，根据在6个月的治疗期间三个域（认知能力、功能及整体状况）同时发生的临床恶化的情况，防止临床恶化的分析被定义如下：

         显著的临床恶化 ADAS-Cog恶化≥4分，或者SIB恶化≥5分，外加任何ADCS-ADL/ADCS-ADL_19/23恶化及CIBIC-Plus恶化。

         任何临床恶化 ― 任何ADAS-Cog 或者 SIB恶化，外加任何ADCS-ADL_19/23 及 CIBIC-Plus 恶化。

对六个研究中全部中、重度AD患者（MMSE<20；n=1475）以及中度AD患者（MMSE 10-19;n=1116）的结果进行了分析。

         中、重度AD患者（MMSE<20）经治疗后，安慰剂组出现“显著临床恶化”的患者比例是美金刚组的2倍（安慰剂组：21%，美金刚组11%；p<0.0001,OC）(图6.7)。

         在中度AD患者组（MMSE 10-19）也观察到这种有显著统计学意义的结果，安慰剂出现“显著临床恶化”的患者比例接近美金刚组的2倍（安慰剂组：16%，美金刚组9%；P=0.0001，OC）（图6.7）。

         另外，与美金刚组相比，更多的安慰剂组患者出现“任何临床恶化”（MMSE<20:安慰剂组28%，美金刚组18%；MMSE10-19:安慰剂组25%，美金刚组16%，p=0.0001，OC分析）。

         在所有的这些评价中，LOCF分析得出的结果与OC分析的结果相似，并且在单一治疗研究中美金刚治疗效应的强度与美金刚联合稳定剂量的AChEIs治疗的效应强度相似。

         美金刚可以防止中、重度AD患者临床恶化，对整个研究人群以及中度AD患者亚组而言，该效应很明显。

原件下载：