Institute of Experimental Neurology, Department of Neurology, University Vita-Salute, Scientific Institute San Raffaele, Milan, Italy.
Ann Neurol. 2011 Jan;69(1):75-82. doi: 10.1002/ana.22316.
To evaluate the safety, tolerability, and efficacy of glatiramer acetate (GA) 40 mg compared to a 20mg dose.
Patients with multiple sclerosis (MS) with ≥ 1 documented relapse in 12 months prior to screening, or ≥ 2 documented relapses in 24 months prior to screening, and Expanded Disability Status Scale (EDSS) score 0 to 5.5 were enrolled. Patients were evaluated at screening, baseline, and at months 1, 2, 3, 6, 9, and 12. Primary endpoint was rate of confirmed relapses observed during 12-month study. Analysis was by intent-to-treat.
A total of 1,155 patients randomized to GA 20 mg (n = 586) or 40 mg (n = 569). The groups were well-matched at baseline on demographic, clinical, and magnetic resonance imaging (MRI) characteristics. The primary endpoint was similar in both groups (relative risk [RR] = 1.07; 95% confidence interval [CI], 0.88-1.31; p = 0.486) with mean annualized relapse rates (ARRs) of 0.33 for the 20 mg group, 0.35 for the 40 mg group, and 0.27 for patients from both groups who completed the entire 1-year treatment. A total of 77% of patients remained relapse-free in both groups. Both groups showed a reduction in mean number of gadolinium-enhancing and new T2 lesions over time with trend for faster reduction in the first trimester with the 40 mg dose compared with 20 mg dose. Both doses were well-tolerated with a safety profile similar to that observed in previous studies of 20 mg GA.
In relapsing-remitting MS patients, both the currently-approved GA 20 mg and 40 mg doses were safe and well-tolerated, with no gain in efficacy for the higher dose.
评估醋酸格拉替雷（GA）40mg 与 20mg 剂量相比的安全性、耐受性和疗效。
纳入了多发性硬化症（MS）患者，这些患者在筛选前 12 个月内有≥1 次记录的复发，或在筛选前 24 个月内有≥2 次记录的复发，且扩展残疾状况量表（EDSS）评分为 0 至 5.5。患者在筛选、基线以及第 1、2、3、6、9 和 12 个月时接受评估。主要终点是在 12 个月研究期间观察到的确诊复发率。分析采用意向治疗。
共有 1155 名患者随机分配至 GA 20mg 组（n=586）或 40mg 组（n=569）。两组在人口统计学、临床和磁共振成像（MRI）特征方面在基线时匹配良好。主要终点在两组中相似（相对风险[RR]为 1.07；95%置信区间[CI]，0.88-1.31；p=0.486），20mg 组的年平均复发率（ARR）为 0.33，40mg 组为 0.35，完成整个 1 年治疗的两组患者的 ARR 为 0.27。两组均有 77%的患者无复发。两组的平均钆增强和新 T2 病变数量随时间减少，40mg 剂量组在第一个三个月内的减少趋势快于 20mg 剂量组。两种剂量均具有良好的耐受性，安全性与之前的 20mg GA 研究观察到的相似。
在复发缓解型多发性硬化症患者中，目前批准的 GA 20mg 和 40mg 剂量均安全且耐受良好，高剂量无疗效增益。
