Epub: Sormani and Bruzzi. MRI lesions as a surrogate for relapses in multiple sclerosis: a meta-analysis of randomised trials. Lancet Neurol. 2013 Jun 3.
METHODS: They searched Medline for clinical trials that assessed disease-modifying drugs for relapsing-remitting MS published from Sept 1, 2008, to Oct 31, 2012. They 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 R2 value was estimated to quantify the strength of the correlation. They used an interaction test to test for a difference in slope from the previously estimated equation. They also ran several sensitivity analyses.
FINDINGS: They identified 31 eligible trials, which provided data for 18 901 RRMSers. 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; R2=0·71), much the same as was previously estimated (p interaction=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.
INTERPRETATION: These 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 MS 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.