Placebo-Controlled Trial of Oral Laquinimod for Multiple Sclerosis
Placebo-Controlled Trial of Oral Laquinimod for Multiple Sclerosis
复制标题
DOI：
10.1056/nejmoa1104318
复制
发表时间：
2012-03-15
影响因子：
158.5
通讯作者：
Filippi, Massimo
中科院分区：
文献类型：
--
作者：
Comi, Giancarlo;Jeffery, Douglas;Filippi, Massimo
背景：两项概念验证临床试验提供了拉喹莫德降低复发缓解型多发性硬化症患者疾病活动性的证据。方法：我们在24个国家的139个地点进行了一项随机、双盲、3期研究。共有1106例复发-缓解型多发性硬化症患者按1:1的比例随机分配，接受0.6 mg口服拉喹莫德，每日一次或安慰剂，为期24个月。主要终点是24个月期间的年复发率。次要终点包括确认的残疾进展（定义为扩展残疾状态量表评分持续至少3个月的增加）和t -2加权磁共振成像上钆增强病变和新发或扩大病变的累积数量。结果与安慰剂相比，接受拉喹莫德治疗可适度降低平均（+/- SE）年复发率（0.30 +/- 0.02 vs 0.39 +/- 0.03, P = 0.002）和确认残疾进展的风险（11.1% vs 15.7%；风险比为0.64；95%可信区间为0.45 ~ 0.91;P = 0.01）。接受拉喹莫德治疗的患者在t -2加权图像上钆增强病灶和新发或扩大病灶的平均累积数目低于接受安慰剂治疗的患者(分别为1.33 +/- 0.14 vs. 2.12 +/- 0.22和5.03 +/- 0.08 vs. 7.14 +/- 0.07
BACKGROUNDTwo proof-of-concept clinical trials have provided evidence that laquinimod reduces disease activity in patients with relapsing-remitting multiple sclerosis.METHODSWe conducted a randomized, double-blind, phase 3 study at 139 sites in 24 countries. A total of 1106 patients with relapsing-remitting multiple sclerosis were randomly assigned in a 1: 1 ratio to receive oral laquinimod at a dose of 0.6 mg once daily or placebo for 24 months. The primary end point was the annualized relapse rate during the 24-month period. Secondary end points included confirmed disability progression (defined as an increase in the score on the Expanded Disability Status Scale that was sustained for at least 3 months) and the cumulative number of gadolinium-enhancing lesions and new or enlarging lesions on T-2-weighted magnetic resonance imaging.RESULTSTreatment with laquinimod as compared with placebo was associated with a modest reduction in the mean (+/- SE) annualized relapse rate (0.30 +/- 0.02 vs. 0.39 +/- 0.03, P = 0.002) and with a reduction in the risk of confirmed disability progression (11.1% vs. 15.7%; hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.91; P = 0.01). The mean cumulative numbers of gadolinium-enhancing lesions and new or enlarging lesions on T-2-weighted images were lower for patients receiving laquinimod than for those receiving placebo (1.33 +/- 0.14 vs. 2.12 +/- 0.22 and 5.03 +/- 0.08 vs. 7.14 +/- 0.07, respectively; P