Surrogate endpoints for EDSS worsening in multiple sclerosis. A meta-analytic approach.

Summary

The aim of this study is to evaluate the effect of clinical and MRI markers to predict the effect of a new treatment in a clinical trial. The authors studied 10,009 people with multiple sclerosis (MS) involved in 19 clinical trials. They found a significant correlation between EDSS worsening and MRI lesions. They concluded supporting the use of these markers in MS clinical trials. Sormani MP, Bonzano L, Roccatagliata L, Mancardi GL, Uccelli A, Bruzzi P. Neurology. 2010 Jun 23

Details

The onjective of this work was to evaluate whether the effects on potential surrogate endpoints, such as MRI markers and relapses, observed in trials of experimental treatments are able to predict the effects of these treatments on disability progression as defined in relapsing-remitting multiple sclerosis (RRMS) trials.

A pooled analysis was employed using all the published randomized controlled clinical trials in RRMS reporting data on Expanded Disability Status Scale (EDSS) worsening and relapses or MRI lesions or both. Data was extracted on relapses, MRI lesions, and the proportion of progressing patients. A regression analysis weighted on trial size and duration was performed to study the relationship between the treatment effect observed in each trial on relapses and MRI lesions and the observed treatment effect on EDSS worsening.

A set of 19 randomized double-blind controlled trials in RRMS were identified, for a total of 44 arms, 25 contrasts, and 10,009 patients. A significant correlation was found between the effect of treatments on relapses and the effect of treatments on EDSS worsening: the adjusted R(2) value of the weighted regression was 0.71. The correlation between the treatment effect on MRI lesions and EDSS worsening was slightly weaker (R(2) = 0.57) but significant.

These findings support the use of commonly used surrogate markers of EDSS worsening as endpoints in multiple sclerosis clinical trials. Further research is warranted to validate surrogate endpoints at the individual level rather than at the trial level, to draw important conclusions in the management of the individual patient.