Rituximab in Patients with Primary Progressive Multiple Sclerosis Results of a Randomized Double-Blind Placebo-Controlled Multicenter Trial
Rituximab in Patients with Primary Progressive Multiple Sclerosis Results of a Randomized Double-Blind Placebo-Controlled Multicenter Trial
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DOI：
10.1002/ana.21867
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发表时间：
2009-10-01
影响因子：
11.2
通讯作者：
Smith, Craig H.
中科院分区：
文献类型：
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作者：
Hawker, Kathleen;O'Connor, Paul;Smith, Craig H.
目的：利妥昔单抗是一种选择性清除CD 20 + B细胞的单克隆抗体，已证明在减少复发缓解型多发性硬化症（MS）的疾病活动方面具有疗效。我们评估利妥昔单抗在成人原发性进展性MS（PPMS）通过96周和安全性通过122 weeks.Methods：采用2：1随机化，439 PPMS患者接受两个1,000毫克静脉利妥昔单抗或安慰剂输注，每24周，通过96周（4个疗程）。主要终点是至确认疾病进展（CDP）的时间，即扩展残疾状态量表中预先规定的持续12周的增加。次要终点是从基线到第96周的T2病变体积和总脑体积的变化磁共振imaging scans.Results：利妥昔单抗和安慰剂之间的CDP时间差异没有达到显著性（96周率：38.5%安慰剂，30.2%利妥昔单抗; p = 0.14）。从基线到第96周，利妥昔单抗患者T2病变体积的增加较小（p < 0.001）;脑体积变化与安慰剂相似（p = 0.62）。亚组分析显示，年龄较大的利妥昔单抗治疗患者的CDP时间延迟
Objective: Rituximab, a monoclonal antibody selectively depleting CD20+ B cells, has demonstrated efficacy in reducing disease activity in relapsing-remitting multiple sclerosis (MS). We evaluated rituximab in adults with primary progressive MS (PPMS) through 96 weeks and safety through 122 weeks.Methods: Using 2:1 randomization, 439 PPMS patients received two 1,000mg intravenous rituximab or placebo infusions every 24 weeks, through 96 weeks (4 courses). The primary endpoint was time to confirmed disease progression (CDP), a prespecified increase in Expanded Disability Status Scale sustained for 12 weeks. Secondary endpoints were change from baseline to week 96 in T2 lesion volume and total brain volume on magnetic resonance imaging scans.Results: Differences in time to CDP between rituximab and placebo did not reach significance (96-week rates: 38.5% placebo, 30.2% rituximab; p = 0.14). From baseline to week 96, rituximab patients had less (p < 0.001) increase in T2 lesion volume; brain volume change was similar (p = 0.62) to placebo. Subgroup analysis showed time to CDP was delayed in rituximab-treated patients aged