A controlled trial of natalizumab for relapsing multiple sclerosis.
A controlled trial of natalizumab for relapsing multiple sclerosis.
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DOI：
10.1056/nejmoa020696
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发表时间：
2003-01-02
影响因子：
158.5
通讯作者：
O'Connor, PW
中科院分区：
文献类型：
--
作者：
Miller, DH;Khan, OA;O'Connor, PW
背景资料：在多发性硬化症患者中，炎症性脑损伤似乎是由涉及活化的淋巴细胞和单核细胞的自身免疫反应引起的。糖蛋白（α）（亚4）整联蛋白在这些细胞的表面上表达，并在其粘附于血管内皮和迁移到实质中起关键作用。那他珠单抗是一种（alpha）（sub 4）整联蛋白拮抗剂，在实验模型和多发性硬化症患者的初步研究中可减少脑病变的发展。在一项随机双盲试验中，我们将213名复发缓解型或复发继发性进展型多发性硬化症患者随机分配接受每公斤体重3 mg的那他珠单抗静脉注射（68例患者），6 mg/kg（74例患者）或安慰剂（71例患者），每28天一次，持续6个月。主要终点是6个月治疗期间每月钆增强磁共振成像显示的新发脑病变数量。临床结果包括复发率和自我报告的健康状况。结果：两组患者新发病灶的平均数量均显著减少：安慰剂组为9.6个，而每公斤3 mg的那他珠单抗组为0.7个（P
Background: In patients with multiple sclerosis, inflammatory brain lesions appear to arise from autoimmune responses involving activated lymphocytes and monocytes. The glycoprotein (alpha)(sub 4) integrin is expressed on the surface of these cells and plays a critical part in their adhesion to the vascular endothelium and migration into the parenchyma. Natalizumab is an (alpha)(sub 4) integrin antagonist that reduced the development of brain lesions in experimental models and in a preliminary study of patients with multiple sclerosis.Methods: In a randomized, double-blind trial, we randomly assigned a total of 213 patients with relapsing-remitting or relapsing secondary progressive multiple sclerosis to receive 3 mg of intravenous natalizumab per kilogram of body weight (68 patients), 6 mg per kilogram (74 patients), or placebo (71 patients) every 28 days for 6 months. The primary end point was the number of new brain lesions on monthly gadolinium-enhanced magnetic resonance imaging during the six-month treatment period. Clinical outcomes included relapses and self-reported well-being.Results: There were marked reductions in the mean number of new lesions in both natalizumab groups: 9.6 per patient in the placebo group, as compared with 0.7 in the group given 3 mg of natalizumab per kilogram (P