MRI as an outcome in multiple sclerosis clinical trials

作者：Martin Däumer, Ain A. Neuhaus, S. Morrissey, R. Hintzen, George C. Ebers · 发表于：Neurology · 年份：2008 · DOI：10.1212/01.wnl.0000336916.38629.43 · 被引用次数：107 · 研究领域：Multiple Sclerosis Research Studies、Advanced MRI Techniques and Applications、Advanced Neuroimaging Techniques and Applications

INTRODUCTION: T2-weighted and gadolinium enhanced T1-weighted MRI scans measure plaque burden and breakdown of the blood-brain barrier, respectively, in multiple sclerosis (MS) lesions. These have become widely used outcome measures for monitoring disease activity in clinical trials and clinical practice. However, their use as surrogates or biomarkers for disability and relapses, key clinical outcome measures, has remained incompletely validated. METHODS: In a clinical trial database comprised of 31 relapsing-remitting and secondary progressive MS trial placebo groups, we assessed relationships between 1) T2 lesion load (TLL) change and disability change and 2) gadolinium enhancement of MS lesions and on-study relapses with univariate and multivariate analyses. RESULTS: In relapsing-remitting MS, TLL change (n = 223) made no independent contribution to predicting change in disability from baseline to trials' end. Similarly, inclusion of gadolinium enhancing lesions (n = 170) into multivariate models did not independently contribute to the predictive value for on-trial relapses. In secondary progressive MS, a small effect of TLL was found for disability change (n = 355) but in multivariate analysis this accounted for less than 5% of the variance in end-of-trial disability. Results were replicated in independent datasets, more than doubling effective sample sizes. CONCLUSIONS: MRI measures widely used in trials of relapsing-remitting and progressive multiple sclerosis add littl...