Lundbeck SA, Paris, France.
Clin Drug Investig. 2004;24(7):373-84. doi: 10.2165/00044011-200424070-00001.
In patients with moderately severe to severe Alzheimer's disease, the N-methyl-D-aspartate (NMDA) antagonist memantine has been shown to improve outcomes and to be associated with reductions in resource utilisation and total healthcare costs relative to no pharmacological intervention after 28 weeks in phase III clinical and pharmacoeconomic studies. However, the longer term cost implications of treatment with memantine are not known.
To evaluate the effect of treatment with memantine in patients with moderately severe to severe Alzheimer's disease on resource use and on cost and patient outcomes in Finland over a 5-year time horizon.
A Markov model was constructed to simulate a patient's progression through a finite series of health states with a time horizon of 5 years. The states were defined in terms of physical dependency, place of residency (community or institution), and cognitive function. Each 6-month Markov cycle was repeated ten times. A 5% rate was used to discount costs. Inputs for the model were derived from epidemiological data collected during the Kuopio 75+ Study, a Finnish population-based health survey of dementia and functional capacity among in-dividuals aged >/=75 years. Costs were considered from a societal perspective. Probabilities used in the model, together with cost and resource use differences between treatment with memantine (Ebixa((R)), Namenda((R)), Axura((R))) and no pharmacological intervention, were derived from a randomised, double-blind, placebo-controlled clinical trial that included an economic assessment. This study enrolled 252 patients with moderately severe to severe Alzheimer's disease. We took a conservative approach that assumed that the effectiveness of treatment with memantine was limited to 12 months' duration. Monte Carlo simulations were performed to evaluate the effect of treatment with memantine on duration of independence and time to institutionalisation. Sensitivity analyses included memantine efficacy best- (5 years) and worst- (6 months) case scenarios, and an analysis in which 5% discounting was not applied.
Memantine therapy was associated with approximately 4 extra months of independence, 1 additional month of residence in the community, and a cost reduction relative to placebo of approximately euro1700 per patient over 5 years, despite the limiting of persistence of efficacy to 12 months (year of costing, 2001). Monte Carlo simulations and sensitivity analyses supported the findings.
According to the model, over 5 years the additional drug costs of treating patients with moderately severe to severe Alzheimer's disease with memantine were amply offset by cost savings related chiefly to increased independence and delayed institutionalisation.
在中度至重度阿尔茨海默病患者中，N-甲基-D-天冬氨酸（NMDA）拮抗剂美金刚已被证明可改善结局，并与 28 周的 III 期临床和药物经济学研究中无药物干预相比，降低资源利用和总医疗保健成本相关。然而，美金刚治疗的长期成本影响尚不清楚。
评估在芬兰，中度至重度阿尔茨海默病患者使用美金刚治疗对资源利用以及 5 年内成本和患者结局的影响。
构建了一个马尔可夫模型，以模拟患者在 5 年时间内通过一系列有限的健康状态的进展。这些状态是根据身体依赖、居住地点（社区或机构）和认知功能来定义的。每个 6 个月的马尔可夫周期重复 10 次。以 5%的速率对成本进行贴现。模型的输入来自于在库奥皮奥 75+研究中收集的流行病学数据，这是一项针对 75 岁及以上人群的芬兰基于人群的痴呆症和功能能力健康调查。从社会角度考虑成本。模型中使用的概率，以及美金刚（Ebixa（R））、盐酸美金刚（Namenda（R））和盐酸美金刚（Axura（R））治疗与无药物干预之间的成本和资源利用差异，均源自一项包括经济评估的随机、双盲、安慰剂对照临床试验。这项研究纳入了 252 名中度至重度阿尔茨海默病患者。我们采取了保守的方法，假设美金刚治疗的有效性仅限于 12 个月的持续时间。进行了蒙特卡罗模拟，以评估美金刚治疗对独立性持续时间和机构化时间的影响。敏感性分析包括美金刚疗效的最佳（5 年）和最差（6 个月）情况，以及不应用 5%贴现的分析。
与安慰剂相比，美金刚治疗可使患者的独立性延长约 4 个月，在社区居住时间延长 1 个月，每位患者的成本降低约 1700 欧元，尽管将疗效持续时间限制在 12 个月（成本计算年度为 2001 年）。蒙特卡罗模拟和敏感性分析支持了这些发现。
根据模型，在 5 年内，治疗中度至重度阿尔茨海默病患者使用美金刚的额外药物成本被主要与增加独立性和延迟机构化相关的成本节约所抵消。
