European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging-measured disease activity and burden in patients with relapsing multiple sclerosis
European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging-measured disease activity and burden in patients with relapsing multiple sclerosis
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DOI：
10.1002/ana.64
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发表时间：
2001-03-01
影响因子：
11.2
通讯作者：
Wolinsky, JS
中科院分区：
文献类型：
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作者：
Comi, G;Filippi, M;Wolinsky, JS
两项先前的双盲、安慰剂对照、随机试验证明醋酸格拉替雷（GA）可降低复发缓解型多发性硬化症（RRMS）患者的复发率。本研究旨在确定GA对RRMS患者的疾病活动性的影响、发作和持久性，这些影响通过磁共振成像（MRI）进行监测。239名符合条件的患者随机接受20 mg GA（n = 119）或安慰剂（n = 120），每日皮下注射。入选资格要求在入选前2年内有一次或多次复发，并且在筛选MRI上至少有一处增强病变。该研究是一个随机、双盲、安慰剂对照阶段，在此期间，所有研究患者在9个月内每月接受MRI扫描和临床评估。主要结果指标为TI加权图像上增强病灶的总数。次要结果指标包括增强病灶的患者比例，新增强病灶的数量及其体积变化; T2加权图像上检测到的新病灶数量及其体积变化，以及未增强T1加权图像上观察到的低信号病灶体积变化。疾病活动的临床措施也进行了评价。活性药物治疗组和安慰剂组在入组时的所有人口统计学、临床和MRT变量均相当。与安慰剂相比，GA治疗显示增强病变总数显著减少（-10.8，95%置信区间-18.0至-3.7; p = 0.003）。几乎在所有次要终点检查中均观察到支持GA治疗的一致性差异：新增强病灶数量（p < 0.003），增强病灶体积的每月变化（p = 0.01），以及体积变化（p = 0.006）和T2加权图像上新病灶数量（p < 0.003）。GA治疗患者的复发率也显着降低了33%（p = 0.012）。所有的影响都随着时间的推移而增加。醋酸格拉替雷显著降低了MRI测量的疾病活动和负担。
Two prior double-blind, placebo-controlled, randomized trials demonstrated that glatiramer acetate (GA) reduces relapse rates in patients with relapsing remitting multiple sclerosis (RRMS). This study was designed to determine the effect, onset, and durability of any effect of GA on disease activity monitored with magnetic resonance imaging (MRI) in patients with RRMS. Two hundred thirty-nine eligible patients were randomized to receive either 20 mg GA (n = 119) or placebo (n = 120) by daily subcutaneous injection. Eligibility required one or more relapses in the 2 years before entry and at least one enhancing lesion on a screening MRI. The study was a randomized, double-blind, placebo-controlled phase during which all patients studied underwent monthly MRI scans and clinical assessments over 9 months. The primary outcome measure was the total number of enhancing lesions on TI-weighted images. Secondary outcome measures included the proportion of patients with enhancing lesions, the number of new enhancing lesions and change in their volume; the number of new lesions detected on T2-weighted images and change in their volume, and the change in volume of hypointense lesions seen on unenhanced T1-weighted images. Clinical measures of disease activity were also evaluated. The active treatment and placebo groups were comparable at entry for all demographic, clinical, and MRT variables. Treatment with GA showed a significant reduction in the total number of enhancing lesions compared with placebo (-10.8, 95% confidence interval -18.0 to -3.7; p = 0.003). Consistent differences favoring treatment with GA were seen for almost all secondary end points examined: number of new enhancing lesions (p < 0.003), monthly change in the volume of enhancing lesions (p = 0.01), and change in volume (p = 0.006) and number of new lesions seen on T2-weighted images (p < 0.003). The relapse rate was also significantly reduced by 33% for GA-treated patients (p = 0.012). All effects increased over time. Glatiramer acetate significantly reduced MRI-measured disease activity and burden.