Glatiramer acetate in primary progressive multiple sclerosis: Results of a multinational, multicenter, double-blind, placebo-controlled trial
Glatiramer acetate in primary progressive multiple sclerosis: Results of a multinational, multicenter, double-blind, placebo-controlled trial
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DOI：
10.1002/ana.21079
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发表时间：
2007-01-01
影响因子：
11.2
通讯作者：
Laclkani, David
中科院分区：
文献类型：
--
作者：
Wolinsky, Jerry S.;Narayana, Pormada A.;Laclkani, David
目的：确定醋酸格拉替雷 (GA) 是否可以减缓原发进展型多发性硬化症的残疾累积。方法：在这项为期 3 年的双盲试验中，共有 943 名原发进展型多发性硬化症患者被随机分配至 GA 组或安慰剂 (PBO) 组。主要终点是对持续 3 个月达到 1-（进入扩展残疾状态量表，3.0-5.0）或 0.5 点扩展残疾状态量表变化（进入扩展残疾状态量表，5.5-6.5）的时间进行意向治疗分析。独立数据安全监测委员会的中期分析表明治疗对主要结果没有明显影响后，该试验被停止。对残疾和磁共振成像终点进行了意向治疗分析。 结果：与 PBO 治疗的患者相比，GA 治疗的患者出现持续累积残疾的时间没有显着延迟（风险比，0.87 [95% 置信区间，0.71-1-07]；p = 0.1753），与 PBO 相比，第 1 年强化病灶显着减少，第 2 年和第 3 年 T2 病灶体积增加较小。事后分析显示，接受 GA 治疗的男性患者的生存曲线与接受 PBO 治疗的男性受试者的生存曲线很早就出现了分歧（风险比，0.71 [95% 置信区间，0.53-0.95]；P = 0.0193）。 解释：该试验未能证明 GA 对原发性进行性多发性硬化症的治疗效果。意外的低事件发生率和过早停止研究药物都降低了检测治疗效果的能力。事后分析表明，GA 可能会减缓男性患者的临床进展，而男性患者在未经治疗时表现出更快的进展。
Objective: To determine whether glatiramer acetate (GA) slows accumulation of disability in primary progressive multiple sclerosis.Methods: A total of 943 patients with primary progressive multiple sclerosis were randomized to GA or placebo (PBO) in this 3-year, double-blind trial. The primary end point was an intention-to-treat analysis of time to 1-(entry expanded disability status scale, 3.0-5.0) or 0.5-point expanded disability status scale change (entry expanded disability status scale, 5.5-6.5) sustained for 3 months. The trial was stopped after an interim analysis by an independent data safety monitoring board indicated no discernible treatment effect on the primary outcome. Intention-to-treat analyses of disability and magnetic resonance imaging end points were performed.Results: There was a nonsignificant delay in time to sustained accumulated disability in GA- versus PBO-treated patients (hazard ratio, 0.87 [95% confidence interval, 0.71-1-07]; p = 0.1753), with significant decreases in enhancing lesions in year 1 and smaller increases in T2 lesion volumes in years 2 and 3 versus PBO. Post hoc analysis showed that survival curves for GA-treated male patients diverged early from PBO-treated male subjects (hazard ratio, 0.71 [95% confidence interval, 0.53-0.95]; P = 0.0193).Interpretation: The trial failed to demonstrate a treatment effect of GA on primary progressive multiple sclerosis. Both the unanticipated low event rate and premature discontinuation of study medication decreased the power to detect a treatment effect. Post hoc analysis suggests GA may have slowed clinical progression in male patients who showed more rapid progression when untreated.