MRI Lesions for MS Debate: Why the Answer is 'Yes'

When it comes to treating and studying multiple sclerosis, the correlation between magnetic resonance imaging (MRI) lesions and actual disease activity has been widely disputed. A new analysis says that using MRI lesions as a proxy for disease activity is a sufficient approach when determining primary endpoints in clinical trials.

Maria Pia Sormani, PhD, from the University of Geneva, spoke on this topic at the 31^st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS 2015) in Barcelona, Spain.

The original question up for debate was: “Should MRI be the primary endpoint of phase III clinical trials in MS?” However, Sormani said a better question would be: “Should MRI be the primary endpoint instead of relapses in patients participating in phase III clinical trials when evaluating anti-inflammatory drugs in MS?” If that is the question, then Sormani said the answer should be “yes!”

The two primary outcomes for MS are clinical relapses and worsening disease. Some health care providers use MRI lesions as evidence of disease activity, but others remain skeptical about the practice. Sormani referenced two studies that evaluated the topic, one of which was a phase III trial that reported a predicted 78% reduction in relapses.

Sormani asked another interesting question during her presentation: “We know how primary outcomes of MS are measured now, but what method should we use?”

To make a case for relying on MRI lesions, the first referenced trial looked at 100 to 200 patients over the course of six months. Researchers were able to identify treatment outcomes in the majority of them. Similar results showed when 700 to 1,000 patients were followed for one to two years. The findings indicated that the researchers were able to roughly estimate the effect treatment had on relapses and MRI lesions.

Sormani clarified that she was not speaking on the correlation between lesions and relapses, but rather the correlation between treatment effect on lesions and treatment effect on relapses. MRI has been confirmed as a surrogate for relapses.

Based on the researchers’ observations, the approach can be used:

1. For assessing the efficacy of biosimilar/generics of registered (anti-inflammatory) drugs

2. For assessing the efficacy of drugs in different populations those for which the drugs have been approved

The outcomes drawn from the phase III results were in line with those of earlier phase II studies. The observed effects held true for both phases, Sormani verified. She stressed that the conclusion of MRI lesions being valid markers is only for known drugs; this does not include new ones that lack long-term studies.

“MRI lesions are a validated surrogate marker for relapses to assess the efficacy of anti-inflammatory drugs in RRMS [relapsing-remitting multiple sclerosis],” Sormani concluded.

Clinical trials are typically done using adult patient; however, important information could be lacking when it comes to pediatric populations. “I think MRI could be the right application for testing the known drugs on children,” Sormani said.

Get the opposite side of the argument: MRI Lesions for MS Debate: Why the Answer is ‘No’