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Cognitive Health and Sphinogine-1-Phospate Receptor Modulators in Multiple Sclerosis - Episode 12

Using Neurofilaments as a Biomarker in MS

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Dr Jacqueline Nicholas hypothesizes about the utility of neurofilaments as a biomarker of disease severity in patients with multiple sclerosis.

Stephen Krieger, MD: We’ve talked about lesion monitoring, and we’ve talked about brain volume monitoring and gray matter. Dr Nicholas, another emerging topic in monitoring for disease severity is looking at things like neurofilament light chain. I haven’t begun to use that in my practice. I’m curious if you have. Do you have thoughts about its utility and how it relates to the use of S1Ps?

Jacqueline Nicholas, MD: It’s something that we’ve been talking about for a long time. We’ve all wanted other ways to be able to monitor our patients. I haven’t had the opportunity yet to use these outside clinical trials, but I welcome that because I know it’s quickly approaching. There have been a couple of really nice papers that have come out—consensus ideas as to how these might be utilized. One caveat that we all realize is we need to understand the norm for a patient of the neurofilament light chain levels within the blood based on their age. We have to understand that, obviously, anything that could impact the brain—somebody gets a hard hit to the head—could result in an elevation. Thus, every time it elevates, we shouldn’t freak out that it’s multiple sclerosis [MS] rearing its ugly head.

What we know from those data that it’s higher at baseline in patients with multiple sclerosis than in those without. When there’s inflammation, particularly new lesions on MRI or relapses, we see an elevation in those levels. I can imagine where that could be incredibly helpful where an individual is coming in. Maybe we’re having challenges differentiating whether it’s an increase of a chronic symptom in the setting of heat sensitivity. Maybe somebody is really anxious or depressed, and we worry that it could be a pseudo relapse. That may be a useful time point to check that neurofilament level. It may be also be useful to start a new treatment. Maybe we’ve made a treatment switch because 1 treatment wasn’t effective enough, and we want to get an early check-in—a couple of months after—to see, “Is this lowering levels effectively?”

One area I’m most excited about where this may be helpful for is when we get to that older population. We’re still waiting for the results of the DISCO-MS trial to understand if stopping therapy ultimately is appropriate and what may occur as a result of that in our older patients. We have patients who come in frequently and say, “I’ve had MS for 50 years, and I’ve been taking the treatment as long as I’ve been able to since they’ve been available. I haven’t had anything happen in a really long time, and I’m 70 years old. Can I come off?” We weigh that, but this might be a place where instead of monitoring them with MRIs, we might look at neurofilament and see if that’s not elevated. Maybe they’re doing well.

Stephen Krieger, MD: That’s a clever way of utilizing it. You’re right, we haven’t seen the results of the DISCO-MS study, this discontinuation trial. Although I don’t think there were many patients in it who were on S1P modulators. I’m sure there are a few, but these were all patients over 55 years old, who’ve been stable for several years on whatever disease-modifying therapy they were on. I’d be nervous about stopping an S1P cold turkey because of the risk of rebound. If that study is reassuring and things like neurofilament levels could give us an indicator of that, that could make it a much safer proposition.

Transcript Edited for Clarity