Natalizumab plus interferon beta-1a for relapsing multiple sclerosis
Natalizumab plus interferon beta-1a for relapsing multiple sclerosis
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DOI：
10.1056/nejmoa044396
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发表时间：
2006-03-02
影响因子：
158.5
通讯作者：
Babu, A
中科院分区：
文献类型：
--
作者：
Rudick, RA;Stuart, WH;Babu, A
背景：干扰素β用于改变复发性多发性硬化症的病程。尽管进行了干扰素β治疗，许多患者仍出现病情复发。那他珠单抗是一种 (α)(sub 4) 整合素拮抗剂，在初步研究中，单独使用以及与干扰素 β-1a 联合使用似乎都是安全有效的。方法：我们随机分配了 1171 名患者，这些患者尽管接受了干扰素 β-1a 治疗，但在随机分组前的 12 个月内至少有一次复发，接受持续的干扰素 β-1a 联合 300 mg 那他珠单抗治疗 （589 名患者）或安慰剂（582 名患者）每 4 周静脉注射一次，持续长达 116 周。主要终点是 1 年时的临床复发率和 2 年时通过扩展残疾状态量表测量的持续 12 周残疾进展的累积概率。 结果：联合治疗使持续残疾进展的相对风险降低了 24%（风险比，0.76；95% 置信区间，0.61 至 0.96；P=0.02）。 Kaplan-Meier 估计，联合治疗两年内疾病进展的累积概率为 23%，单独使用干扰素 β-1a 时为 29%。与单独使用干扰素 β-1a 相比，联合治疗在两年内的年复发率较低（0.34 vs. 0.75，P
Background: Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an (alpha)(sub 4) integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies.Methods: We randomly assigned 1171 patients who, despite interferon beta-1a therapy, had had at least one relapse during the 12-month period before randomization to receive continued interferon beta-1a in combination with 300 mg of natalizumab (589 patients) or placebo (582 patients) intravenously every 4 weeks for up to 116 weeks. The primary end points were the rate of clinical relapse at 1 year and the cumulative probability of disability progression sustained for 12 weeks, as measured by the Expanded Disability Status Scale, at 2 years.Results: Combination therapy resulted in a 24 percent reduction in the relative risk of sustained disability progression (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P=0.02). Kaplan-Meier estimates of the cumulative probability of progression at two years were 23 percent with combination therapy and 29 percent with interferon beta-1a alone. Combination therapy was associated with a lower annualized rate of relapse over a two-year period than was interferon beta-1a alone (0.34 vs. 0.75, P