Treatment Effect on Brain Atrophy Correlates with Treatment Effect on Disability in Multiple Sclerosis
Treatment Effect on Brain Atrophy Correlates with Treatment Effect on Disability in Multiple Sclerosis
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DOI：
10.1002/ana.24018
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发表时间：
2014-01-01
影响因子：
11.2
通讯作者：
De Stefano, Nicola
中科院分区：
文献类型：
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作者：
Sormani, Maria Pia;Arnold, Douglas L.;De Stefano, Nicola
目的：评估在试验水平上，对脑萎缩的治疗效果能够在多大程度上介导复发缓解型多发性硬化症（RRMS）残疾进展的治疗效果。方法：我们收集了所有已发表的RRMS随机临床试验，持续至少2年，并将残疾进展作为终点（定义为6或3个月时扩展残疾状态量表确认增加1分），活动性磁共振成像（MRI）病变（定义为新的/扩大的T2病变）和脑萎缩（定义为第24个月和第6-12个月之间脑体积的变化）。治疗效果表示为相对减少。线性回归，加权试验规模和持续时间，被用来评估MRI标记物和残疾progress.Results的治疗效果之间的关系：13个试验，包括>13,500 RRMS患者被纳入荟萃分析。对残疾进展的治疗效果与对脑萎缩（R-2 = 0.48，p = 0.001）和活动性MRI病变（R-2 = 0.61，p < 0.001）的治疗效果相关。当对两个MRI终点的影响被包括在多变量模型中时，相关性更高（R-2 = 0.75，p < 0.001），并且两个变量被保留为与对残疾进展的治疗效果独立相关。这种影响与活动性MRI病变对残疾的影响无关;当联合使用时，2种MRI指标可更密切地预测对残疾的治疗效果。
Objective: To evaluate the extent to which treatment effect on brain atrophy is able to mediate, at the trial level, the treatment effect on disability progression in relapsing-remitting multiple sclerosis (RRMS).Methods: We collected all published randomized clinical trials in RRMS lasting at least 2 years and including as endpoints disability progression (defined as 6 or 3 months confirmed 1-point increase on the Expanded Disability Status Scale), active magnetic resonance imaging (MRI) lesions (defined as new/enlarging T2 lesions), and brain atrophy (defined as change in brain volume between month 24 and month 6-12). Treatment effects were expressed as relative reductions. A linear regression, weighted for trial size and duration, was used to assess the relationship between the treatment effects on MRI markers and on disability progression.Results: Thirteen trials including >13,500 RRMS patients were included in the meta-analysis. Treatment effects on disability progression were correlated with treatment effects both on brain atrophy (R-2 = 0.48, p = 0.001) and on active MRI lesions (R-2 = 0.61, p < 0.001). When the effects on both MRI endpoints were included in a multivariate model, the correlation was higher (R-2 = 0.75, p < 0.001), and both variables were retained as independently related to the treatment effect on disability progression.Interpretation: In RRMS, the treatment effect on brain atrophy is correlated with the effect on disability progression over 2 years. This effect is independent of the effect of active MRI lesions on disability; the 2 MRI measures predict the treatment effect on disability more closely when used in combination.