Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy.
Ann Neurol. 2014 Jan;75(1):43-9. doi: 10.1002/ana.24018. Epub 2014 Jan 2.
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).
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.
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.
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.
评估在复发缓解型多发性硬化症（RRMS）中，治疗对脑萎缩的影响在多大程度上可以作为试验水平上对残疾进展的治疗效果的中介。
我们收集了所有发表的、持续时间至少为 2 年且终点为残疾进展（定义为扩展残疾状态量表（EDSS）上 6 或 3 个月确认的 1 点增加）、活跃磁共振成像（MRI）病变（定义为新/扩大的 T2 病变）和脑萎缩（定义为 24 个月至 6-12 个月之间的脑容量变化）的 RRMS 随机临床试验。治疗效果表示为相对减少。使用线性回归，根据试验大小和持续时间进行加权，评估 MRI 标志物和残疾进展治疗效果之间的关系。
纳入了 13 项包括超过 13500 例 RRMS 患者的试验进行荟萃分析。残疾进展的治疗效果与脑萎缩（R(2) = 0.48，p = 0.001）和活跃 MRI 病变（R(2) = 0.61，p < 0.001）的治疗效果相关。当将这两个 MRI 终点的效果纳入多变量模型中时，相关性更高（R(2) = 0.75，p < 0.001），并且这两个变量都被保留为与残疾进展的治疗效果独立相关。
在 RRMS 中，治疗对脑萎缩的影响与 2 年内的残疾进展治疗效果相关。这种效果独立于活跃 MRI 病变对残疾的影响；当联合使用时，这两种 MRI 测量更能准确预测治疗对残疾的效果。
