Magnetic Resonance Imaging as a Potential Surrogate for Relapses in Multiple Sclerosis: A Meta-analytic Approach
Magnetic Resonance Imaging as a Potential Surrogate for Relapses in Multiple Sclerosis: A Meta-analytic Approach
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DOI：
10.1002/ana.21606
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发表时间：
2009-03-01
影响因子：
11.2
通讯作者：
Bruzzi, Paolo
中科院分区：
文献类型：
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作者：
Sormani, Maria Pia;Bonzano, Laura;Bruzzi, Paolo
目的：这项工作的目的是评估磁共振成像（MRI）标记物在试验水平的治疗效果是否能够预测复发缓解型多发性sclerosis.Methods复发率的治疗效果：我们使用了汇总分析所有已发表的随机，安慰剂对照的临床试验复发缓解型多发性硬化症的MRI变量和复发的报告数据。我们提取了复发和MRI“活动性”病变的数据。对试验规模和持续时间进行了回归分析，以研究复发治疗效果与MRI病变治疗效果之间的关系。我们验证了一组独立的临床试验，满足相同的纳入标准，但与安慰剂以外的对照组的估计关系。结果：一组23个随机，双盲，安慰剂对照试验复发缓解型多发性硬化症，共63个武器，40对比，和6,591例患者。在对复发的影响和对MRI活性的影响之间发现了强相关性。加权回归线的校正R-2值为0.81。使用安慰剂对照试验估计的回归方程给出了一个令人满意的预测复发的治疗效果时，适用于validationset.Interpretation：超过80%的方差在试验之间的复发的影响解释的方差在MRI的影响。基于MRI病变终点的更小和更短的II期研究也可能表明治疗对复发终点的影响。
Objective: The aim of this work was to evaluate whether the treatment effects on magnetic resonance imaging (MRI) markers at the trial level were able to predict the treatment effects on relapse rate in relapsing-remitting multiple sclerosis.Methods: We used a pooled analysis of all the published randomized, placebo-controlled clinical trials in relapsing-remitting multiple sclerosis reporting data both on MRI variables and relapses. We extracted data on relapses and on MRI "active" lesions. A regression analysis weighted on trial size and duration was performed to study the relation between the treatment effect on relapses and the treatment effect on MRI lesions. We validated the estimated relation on an independent set of clinical trials satisfying the same inclusion criteria but with a control arm other than placebo.Results: A set of 23 randomized, double-blind, placebo-con trolled trials in relapsing-remitting multiple sclerosis was identified, for a total of 63 arms, 40 contrasts, and 6,591 patients. A strong correlation was found between the effect on the relapses and the effect on MRI activity. The adjusted R-2 value of the weighted regression line was 0.81. The regression equation estimated using the placebo-controlled trials gave a satisfactory prediction of the treatment effect on relapses when applied to the validation set.Interpretation: More than 80% of the variance in the effect on relapses between trials is explained by the variance in MRI effects. Smaller and shorter phase II studies based on MRI lesion end points may give indications also on the effect of the treatment on relapse end points.