Natalizumab: A new treatment for relapsing remitting multiple sclerosis.
Natalizumab: A new treatment for relapsing remitting multiple sclerosis.
复制标题
DOI：
10.2147/tcrm.2007.3.2.259
复制
发表时间：
2007-06-01
影响因子：
2.8
通讯作者：
Hutchinson, Michael
中科院分区：
文献类型：
--
作者：
Hutchinson, Michael
那他珠单抗是一种新的缓解复发型多发性硬化症（RRMS）的疾病缓解疗法，是一种与α（4）β（1）-整联蛋白结合的人源化单克隆抗体。在一项3期试验中，与安慰剂相比，2年的那他珠单抗单药治疗使平均年复发率（ARR）降低了68%（p < 0.001），那他珠单抗组持续残疾进展的风险降低了42%（风险比[HR] 0.58; 95%置信区间[CI] 0.43-0.77; p < 0.001）。那他珠单抗在2年内使新发或扩大的T2高信号病变的平均数量减少了83%，在2年时使Gd+病变的平均数量减少了92%（均p < 0.001）。在另一项3期试验中，与IFN β-1a单药治疗相比，那他珠单抗联合IFN β-1a治疗2年后平均ARR降低55%（p < 0.001），持续残疾进展风险降低24%（HR 0.76; 95% CI 0.61-0.96; p = 0.02）。6%的患者出现持续性抗那他珠单抗抗体，但疗效丧失。在18个月内发生进行性多灶性白质脑病（PML）的风险估计为1：1000; PML的长期风险尚不确定。那他珠单抗的获益和风险支持其作为单药治疗用于尽管接受IFN β治疗但疾病活动度较高的RRMS，以及快速进展的重度RRMS患者。
Natalizumab, a new disease-modifying therapy for relapsing remitting multiple sclerosis (RRMS), is a humanized monoclonal antibody which binds to alpha(4)beta(1)-integrin. In a Phase 3 trial, 2 years of natalizumab monotherapy reduced the mean annualized relapse rate (ARR) by 68% compared with placebo (p < 0.001) and the risk of sustained disability progression was reduced by 42% in the natalizumab group (hazard ratio [HR] 0.58; 95% confidence interval [CI] 0.43-0.77; p < 0.001). Natalizumab decreased the mean number of new or enlarging T2-hyperintense lesions by 83% over 2 years and the mean number of Gd+ lesions by 92% at 2 years (both p < 0.001). In another Phase 3 trial, natalizumab with interferon (IFN) beta-1a reduced the mean ARR by 55% at 2 years compared with IFNbeta-1a alone (p < 0.001) and risk of sustained disability progression was reduced by 24% (HR 0.76; 95% CI 0.61-0.96; p = 0.02). Six percent of patients developed persistent antinatalizumab antibodies with loss of efficacy. The risk of developing progressive multifocal leukoencephalopathy (PML) is been estimated at 1:1000 over 18 months; the longer term risk for PML is uncertain. The benefits and risks of natalizumab support its use as monotherapy for RRMS with high disease activity despite treatment with IFNbeta, and for patients with rapidly evolving severe RRMS.