Bruce Hughes, MD: When we were looking at the different therapies, I was looking at all of the high-efficacy therapies out there and the data on [the impact of] brain volume loss. It is striking how, when you look at it, it kind of boils down to 3 areas, and that is anti-CD20, S1P receptor modulators, and natalizumab with regard to best data on impacting the decrease in cerebral brain volume loss. That ties in with our high-efficacy [therapy], and utilizing that information, you can then, [in]s your discussionwith patients, come up with the best therapy that we think is optimal for them. I always bring up that we dont necessarily knock it out of the park with our first attempt, but what well do, the promise is not that well have an optimal outcome, but that well monitor and, if were not headed toward optimal outcome, well make a switch and well make an adjustment. Just based on that mantra of efficacy, tolerability, safety triad that needs to come together. Are there any other thingsthat we havent touched on that would be beneficial with regard to health care providers who are managing patients with multiple sclerosis?

Robert Naismith, MD: Just to recap, what weve been discussing is that you really need to shut down the acute inflammation as early as possible. You need to stop that process because, although its not perfectly correlated to chronic inflammation and neurodegeneration, there is definitely an input from acute inflammation of those processes. So stopping that acute inflammatory component is going to benefit the patient long term because nowadays we talk about expanding lesions and microglial activation, but what if we can prevent that in the first place? I feel like using these highly effective therapies to shut down the inflammatory reaction, the bloodstream break down early is going to benefit patients. Now, unfortunately, we probably dont catch patients at the very start of their disease. Were lucky with MS compared to other degenerative disorders that we do catch them quite early in the whole process, but they may have had MS for years before you even see them the first time. If you think maybe Epstein-Barr virus [EBV] is the spark that lights the fuse and they get EBV in their teens, like at the age of 17 [or] 18, there may be processes taking place with MS pathogenesis and the susceptible patient for many years before they present in their 20s, 30s, and 40s. We cant go back and reverse that, but what we can do is try to stop that inflammation and to slow down the processes that will take place from then on out.

We cant go back and stop the processes that have already taken place because we know that they already have the cognitive issues when they present. They already have changes in brain volume when they present with RIS [radiologically isolated syndrome] or their first episode. So you cant go back to the very, very beginning, but were still able to catch most patients quite early and get them on therapies. And I monitor them to make sure that were doing our best to stop the inflammation, stop new MRI lesions, and to do our best to stabilize the disease process and their symptoms.

Bruce Hughes, MD: Yes, I think that is right. Capturing the disease process before the horse is out of the barn. We talk a lot about this need for being able to impact the disease process centrally in the brain and spinal cord vs peripherally with our agents that shut down inflammation, so extremely well. But could you obviate the need for essentially acting if you treat the disease process early enough and effectively enough? To your point, we know this, right? Clinically isolated syndrome [CIS], the cognitive testing, just that theres the program, and I completely agree with that, is that you do neurocognitive testing on patients with CIS and theyre decidedly more defective than the general age-matched population. Likewise, and Ive always found this very interesting when were looking at this data for brain volume loss, we again have learned, whereas previously we thought that was a later manifestation of multiple sclerosis, that actually the brain volume loss, the speed with which the loss occurs, is most rapid in the first few years of diagnosis, not when its decades old. So I think that does encapsulate very well the importance. I think we tied in high-efficacy therapy, brain volume loss, cognitive functioning, and some tools to monitor and to help manage that in our MS patients.

Id like to thank you for sharing your expertise, Dr Naismith. Thank you for watching this Neurology Live Peers & Perspectives. If you enjoyed the content, please subscribe for our e-newsletters to receive upcoming Peers & Perspectives and other great content right in your inbox.

Transcript is AI-generated and edited for clarity and readability.

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