Bruce Cree, MD, PhD: Brain Volume Loss and Disability Progression in MS

Bruce Cree, MD, PhD, an associate professor of clinical neurology at UCSF Medical School: The second part of my talk was to take a look at the data set that we've developed at UCSF in a study called EPIC. What we previously reported was that rates of progression in this cohort were lower than that compared to natural history studies, and this is an actively treated cohort of MS patients.

One of the things that were interesting is we found that active MS MRI disease activity and absence of relapses, and absence of disability progression over 2 years - what's considered to be no evident disease activity (or NIDA) - had no correlation with long-term disability. In our cohort, we went 1 step further to ask the question: Of those patients who did worse than over time - and about half of our patients with relapsing MS did, in fact, worsen over 10 years in terms of EDSS score worsening or other measures of disability progression - we wanted to know whether that was driven by relapses because you think, “they've got a relapsing patient, maybe it's relapses that are resulting in disability accumulation.” We did find the relapses over the short-term cause an increase in disability, but it's not sustained. It's not sustained over 1 year, and it's certainly not sustained over 5 years.

And so here's this idea that relapses, which correlate very well with lesion activity in MS, are not really driving disability progression over the long term. So we wanted to know what does, and what we did find was that the patients who experienced disability progression had much more brain volume loss over time and that this brain volume loss is occurring independently of relapses, independent of lesion information. So the driver of long-term disability and multiple sclerosis is diffused tissue injury.

Well, I think the message is that secondary progression is occurring probably a lot earlier than any of us realize, and so as a practitioner, being aware of that and being aware of what to look for, I think, becomes very important and I would anticipate the drugs that have the greatest impact on volumetric loss over time are the ones that are going to have the best results over the long term.