Robert Zivadinov, MD: The Clinical Takeaways of the TOPIC Study

Robert Zivadinov, MD, professor of neurology at the University of Buffalo: If you asked me, “Can community neurologists assess the cortical atrophy in the way we did in this clinical trial?” The simple answer is no. Because you really need a high-quality MRI and you need the high-quality analysis to produce this data.

But, what community and academic neurologists should take away as a take-home message from this study is that they should not rely just on the lesion development to lead to the clinically definite MS, but they should think that, even in those people who do not have lesions and develop new lesions, they can develop substantial neurodegeneration in the cortex. As a matter of fact, sub-analysis of this study showed that cortical atrophy developed even in those patients who did not have Gd+ enhancing lesions at baseline. So they didn't have inflammatory activity.

I would say there are 2 messages that should be for the neurologists themselves. First, that the cortical pathology is not a late-stage phenomenon of the disease, it's a very early stage phenomenon, and it’s, in a very short period of 4 years, influencing clinical outcomes like this development of multiple sclerosis. So they have to take it into account. Second, that we have disease-modifying treatments, like Aubagio, which already showed us that from the early stage of the disease we can delay this process. I think by delaying this process, probably, we can delay long-term disability.

This is certainly yet to be shown, but I would suspect that this would be one of the reasons why, in a number of studies and other phase 3 trials like TEMSO, Aubagio showed the ability to delay disability progression in patients with MS. Whether this has an effect on cognition, is also yet to be shown, but just to give you an idea, cortical atrophy in all studies that have been done throughout the years, is the best predictor of cognitive disability in patients with MS.