The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL
The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL
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DOI：
10.1007/s00415-009-0093-1
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发表时间：
2009-03-01
影响因子：
6
通讯作者：
Panzara, Michael A.
中科院分区：
文献类型：
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作者：
Hutchinson, Michael;Kappos, Ludwig;Panzara, Michael A.
AFFIRM和SENTINEL研究表明，那他珠单抗单药治疗和与干扰素β（IFN β）-1a联合治疗复发性多发性硬化症（MS）患者均有效。对AFFIRM和SENTINEL数据进行了进一步分析，以根据基线特征确定那他珠单抗在预先指定的患者亚组中的疗效：随机化前1年的复发史（1、2、千分之一3）、扩展残疾状况量表评分（千分之一货币符号3.5，> 3.5），T2病变数量（< 9，千分之一日元9），存在钆增强（Gd+）病变（0，千分之一日元1），年龄（< 40，千分之一日元40）和性别（男性，女性）。进行事后分析以确定那他珠单抗在患有高活动性疾病（即，例如，在研究开始前一年中复发率为1/1000日元，在研究开始时复发率为1/1000日元。在AFFIRM和SENTINEL研究中，那他珠单抗在2年内降低了所有亚组（基线T2病变< 9处的小亚组除外）的年复发率。在AFFIRM中，那他珠单抗显著降低了大多数亚组中持续残疾进展的风险。在SENTINEL中，那他珠单抗显著降低了以下亚组的持续残疾进展风险：基线时每千日元9个T2病变的1部分，基线时每千日元1个Gd+病变的1部分，女性患者和< 40岁的患者。那他珠单抗使未经治疗的高活动性疾病患者的残疾进展风险降低了64%，复发率降低了81%，尽管IFN β-1a治疗，但仍使高活动性疾病患者的残疾进展风险降低了58%和76%。这些结果表明，那他珠单抗可有效减少复发性MS患者的残疾锡永和复发，特别是高度活动性疾病患者。
The AFFIRM and SENTINEL studies showed that natalizumab was effective both as monotherapy and in combination with interferon beta (IFN beta)-1a in patients with relapsing multiple sclerosis (MS). Further analyses of AFFIRM and SENTINEL data were conducted to determine the efficacy of natalizumab in prespecified patient subgroups according to baseline characteristics: relapse history 1 year before randomization (1, 2, a parts per thousand yen 3), Expanded Disability Status Scale score (a parts per thousand currency sign 3.5, > 3.5), number of T2 lesions (< 9, a parts per thousand yen 9), presence of gadolinium-enhancing (Gd+) lesions (0, a parts per thousand yen 1), age (< 40, a parts per thousand yen 40) and gender (male, female). A post hoc analysis was conducted to determine the efficacy of natalizumab in patients with highly active disease (i. e., a parts per thousand yen 2 relapses in the year before study entry and a parts per thousand yen 1 Gd+ lesion at study entry). In both AFFIRM and SENTINEL studies natalizumab reduced the annualized relapse rates across all subgroups (except the small subgroups with < 9 baseline T2 lesions) over 2 years. In AFFIRM, natalizumab significantly reduced the risk of sustained disability progression in most subgroups. In SENTINEL, natalizumab significantly reduced the risk of sustained disability progression in the following subgroups: a parts per thousand yen 9 T2 lesions at baseline, a parts per thousand yen 1 Gd+ lesions at baseline, female patients and patients < 40 years of age. Natalizumab reduced the risk of disability progression by 64 % and relapse rate by 81 % in treatment- naive patients with highly active disease and by 58 % and 76 %, respectively, in patients with highly active disease despite IFN beta-1a treatment. These results indicate that natalizumab is effective in reducing disability progres- sion and relapses in patients with relapsing MS, particularly in patients with highly active disease.