Imbimbo B P, Verdelli G, Martelli P, Marchesini D
Medical Department, Mediolanum Farmaceutici, Milan, Italy.
Dement Geriatr Cogn Disord. 1999 Mar-Apr;10(2):139-47. doi: 10.1159/000017114.
The effectiveness of long-term treatment of Alzheimer's disease with cholinesterase inhibitors is a matter of controversy. We evaluated the effects of prolonged treatment with eptastigmine in 176 patients with mild to moderate Alzheimer's disease participating in the open-label extension phase of a 25-week double-blind, placebo-controlled trial of eptastigmine. The effects of eptastigmine on cognition and daily functioning were evaluated with the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-Cog) and the Instrumental Activities of Daily Living (IADL) scale, respectively. Safety was monitored by physical examination, laboratory tests, vital functions and electrocardiogram measurements and by the assessment of adverse events. One hundred and fifty-three patients (87%) completed 1 year of treatment, 77 patients (44%) 18 months and 33 patients (19%) 2 years of treatment. Patients treated for 2 years showed an improvement of mean ADAS-Cog scores compared to baseline for 31 weeks and mean IADL scores remained close to baseline for 25 weeks. Cognitive and functional scores then worsened as expected in this progressive disease. After 2 years, patients deteriorated compared to baseline by 13.4 points on the ADAS-Cog and 6.1 points on IADL. Historical untreated controls with identical disease severity are expected to have an annual worsening of approximately 10.9 points on ADAS-Cog and 4.9 points on IADL. Thus patients treated with eptastigmine for 2 years had a benefit of 8.5 points on ADAS-Cog and 3.8 points on IADL. These benefits translate to about 9 months difference between eptastigmine-treated patients and untreated historical patients. The drug was generally well tolerated with 14 patients (7.9%) withdrawing due to adverse events. Adverse events, not necessarily drug-related, were recorded in 66 patients (37.5%) and were transient and generally mild in severity. This study indicates that prolonged treatment with eptastigmine is safe and produced a clinically long-term benefit in patients with Alzheimer's disease.
用胆碱酯酶抑制剂对阿尔茨海默病进行长期治疗的有效性存在争议。我们评估了176例轻至中度阿尔茨海默病患者在一项为期25周的依替斯明双盲、安慰剂对照试验的开放标签延长期中接受依替斯明延长治疗的效果。分别用阿尔茨海默病评估量表认知部分（ADAS-Cog）和日常生活工具性活动（IADL）量表评估依替斯明对认知和日常功能的影响。通过体格检查、实验室检查、生命体征和心电图测量以及不良事件评估来监测安全性。153例患者（87%）完成了1年治疗，77例患者（44%）完成了18个月治疗，33例患者（19%）完成了2年治疗。接受2年治疗的患者与基线相比，平均ADAS-Cog评分在31周内有所改善，平均IADL评分在25周内接近基线水平。在这种进行性疾病中，认知和功能评分随后如预期那样恶化。2年后，患者与基线相比，ADAS-Cog恶化了13.4分，IADL恶化了6.1分。预计疾病严重程度相同的未治疗历史对照患者ADAS-Cog每年恶化约10.9分，IADL每年恶化约4.9分。因此，接受依替斯明治疗2年的患者在ADAS-Cog上有8.5分的获益，在IADL上有3.8分的获益。这些获益相当于依替斯明治疗患者与未治疗历史患者之间约9个月的差异。该药物总体耐受性良好，14例患者（7.9%）因不良事件退出。66例患者（37.5%）记录到不良事件，不一定与药物相关，且这些不良事件是短暂的，严重程度一般较轻。这项研究表明，依替斯明延长治疗对阿尔茨海默病患者是安全的，并产生了临床上的长期获益。
