Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy.
Lancet Neurol. 2013 Jul;12(7):669-76. doi: 10.1016/S1474-4422(13)70103-0. Epub 2013 Jun 3.
A meta-analysis of randomised trials in relapsing-remitting multiple sclerosis published in 2009 showed a quantitative relation between the treatment effects detected on MRI lesions and clinical relapses. We aimed to validate that relation using data from a large and independent set of clinical trials in multiple sclerosis.
We searched Medline for clinical trials that assessed disease-modifying drugs for relapsing-remitting multiple sclerosis published from Sept 1, 2008, to Oct 31, 2012. We extracted data for the treatment effects on MRI lesions and on relapses from each trial, and the correlation of log transformed relative measures of these treatment effects was assessed with a weighted linear regression analysis. The R(2) value was estimated to quantify the strength of the correlation, and we used an interaction test to test for a difference in slope from the previously estimated equation. We also ran several sensitivity analyses.
We identified 31 eligible trials, which provided data for 18 901 patients with relapsing-remitting multiple sclerosis. The regression equation derived using data from these studies showed a relation between the concurrent treatment effects on MRI lesions and relapses (slope=0·52; R(2)=0·71), much the same as was previously estimated (pinteraction=0·45). Analysis of trials that tested the same drugs in phase 2 and phase 3 studies showed that the effects on MRI lesions over short follow-up periods (6-9 months) can also predict the effects on relapses over longer follow-up periods (12-24 months), with reported effects on relapses that were within the 95% prediction intervals in eight of nine trials.
Our findings indicate that the effect of a treatment on relapses can be accurately predicted by the effect of that therapy on MRI lesions, implying that the use of MRI markers as primary endpoints in future clinical trials of treatments for multiple sclerosis can be considered, in specific situations, such as in trials testing generics or biosimilars of drugs with a well known mechanism of action or in paediatric trials testing drugs already approved for adults.
None.
2009 年发表的一项针对复发缓解型多发性硬化症随机试验的荟萃分析显示，MRI 病变和临床复发的治疗效果之间存在定量关系。我们旨在使用多发性硬化症的大量独立临床试验数据验证该关系。
我们在 Medline 上搜索了 2008 年 9 月 1 日至 2012 年 10 月 31 日发表的评估复发缓解型多发性硬化症疾病修饰药物的临床试验。我们从每项试验中提取了 MRI 病变和复发的治疗效果数据，并使用加权线性回归分析评估了这些治疗效果的对数转换相对量的相关性。R²值用于量化相关性的强度，我们使用交互检验来检验斜率是否与之前估计的方程不同。我们还进行了几次敏感性分析。
我们确定了 31 项符合条件的试验，这些试验提供了 18901 例复发缓解型多发性硬化症患者的数据。使用这些研究的数据得出的回归方程显示，MRI 病变和复发的治疗效果之间存在关系（斜率=0.52；R²=0.71），与之前估计的结果非常相似（p 交互=0.45）。对在 2 期和 3 期研究中测试相同药物的试验进行分析表明，短期随访（6-9 个月）期间的 MRI 病变治疗效果也可以预测长期随访（12-24 个月）期间的复发效果，9 项试验中有 8 项试验报告的复发效果在 95%预测区间内。
我们的研究结果表明，治疗对复发的影响可以通过该疗法对 MRI 病变的影响准确预测，这意味着在某些情况下，例如在测试具有明确作用机制的药物的仿制药或生物类似药的临床试验中，或在测试已批准用于成人的药物的儿科试验中，可以考虑将 MRI 标志物作为治疗多发性硬化症的未来临床试验的主要终点。
无。
