Multiple Sclerosis: What’s on the Horizon for 2021?

In this podcast, Patricia K. Coyle, MD, discusses anticipated developments in the field of multiple sclerosis this year, including clinical trial data, COVID-19 vaccination, wearable devices, and more. A full transcript is provided below.

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Patricia K. Coyle, MD, is a professor in the Department of Neurology at Stony Brook University in New York, and director of the Stony Brook MS Comprehensive Care Center.

Transcript:

Christina Vogt: Hello, everyone, and welcome back to another podcast. I'm Christina Vogt, managing editor of Neurology Learning Network. Today, I'm joined by Dr Patricia K. Coyle, who is a professor of neurology and director of the Stony Brook MS Comprehensive Care Center at Stony Brook University in New York.

Today, Dr Coyle will be discussing what's on the horizon for 2021 in the field of multiple sclerosis. Thank you for joining me today, D. Coyle. First, what are some key advances that are expected for 2021 in MS, and how might they affect clinical practice?

Patricia K. Coyle, MD: We're going to see the addition of one or more new disease-modifying therapies. This is a truly burgeoning field. Right now, it's been in front of the FDA for a number of months, is a new second-generation S1P receptor modulator. It's called ponesimod. It had a positive phase 3 trial versus teriflunomide in relapsing forms of MS. The expectation is that it will likely be approved.

This is an S1P receptor 1 modulator. Remember that fingolimod, the parent in the original first S1P receptor, was receptors 1, 3, 4, and 5. Then, you had siponimod and ozanimod that were S1P receptors 1 and 5 losing a cardiac-enriched receptor 3. This is S1P receptor 1. The expectation will be that patients probably won't need first-dose monitoring.

The interesting thing about this study was that they had, as one of their secondary outcomes, a patient-reported fatigue measure that turned out to be significant by the end of the study. Fatigue remained stable over the course of the 2 years or so compared to the comparator arm where it increased in oral teriflunomide.

It'll be interesting to see if they get that in the label. That may be something that they will bring up, that there may have been a positive benefit on fatigue.

There's another disease-modifying therapy that is likely to be submitted to the FDA. It is not yet, but they have reported in a press release that their phase 3 trials in relapsing forms of MS ULTIMATE I and II were both positive on the primary outcome.

Again, this was with a chimeric, glycoengineered anti-CD20 monoclonal called ublituximab, very akin to ocrelizumab and ofatumumab. It was compared to oral teriflunomide and was clearly superior on a number of outcomes. They have not submitted that yet to the FDA, but they're likely to do it. That may very well wind up being approved by the end of the year.

It's going to be interesting, because we have a number of S1P receptor modulators. We currently have 2 FDA-approved anti-CD20 monoclonal. This may likely be a third. How we'll choose between them and how you will cut up pieces of the pie, we await the case. It's going to get very interesting with regard to multiple choices within a given class.

Another important feature for 2021 is a real emphasis on SARS-CoV-2, the COVID-19 pandemic, and what are the implications for MS. We are studying that very carefully. There's new information coming in all the time.

One big question is, are there disease-modifying therapies that make MS individuals a little bit more vulnerable to having this viral infection or having a more severe infection?

Right now, what's emerging is that the anti-CD20 monoclonals seem to put MS individuals at somewhat increased risk. Not all the studies find that, but that would be a common thread, not surprising because there is a very mild increased risk of viral infections when you use an anti-CD20.

We'll see information on MS disease-modifying therapies and any increased risk of COVID-19 illness being clarified even more so in the next year.

The other important thing is we now have COVID-19 vaccines. That comes up to their use in MS individuals. Very recently, early this year, the National MS Society came out and strongly recommended that COVID-19 vaccines be used in MS individuals.

The vaccines that we have currently are not live virus vaccines. That's something that you tend to not want to use in an MS individual. I'm obviously recommending vaccination to all my patients. We do know that anti-CD20s will blunt the vaccine response. The S1P receptor modulators also somewhat blunt the vaccine response.

We'll see clarity in 2021 in the dosing of anti-CD20 and what might be the best time to get a vaccine, and how long does immunity last? Quite frankly, we don't know that for any of the COVID-19 vaccines right now.

That data is going to be studied very carefully in the next year for non-MS individuals. Then, of course, for MS individuals, I could almost foresee that we would be routinely using tests, at least to look at neutralizing antibody titers and to tell when they might fall off and when MS individuals might need to be revaccinated.

Another area that we're going to continue to see great development is further MRI exploration of MS. Right now, there are 2 novel, promising MRI findings. We'll see greater clarity in the next year.

The first is the central vein sign that's being touted as a diagnostic measure. The majority of brain MRI lesions are around a small vein. You can actually detect that. You don't see that in a myriad of other disorders that cause lesions on a brain MRI. That's a misdiagnosis confusion. It could be in the next year that we might see central vein sign being brought to clinical use.

In addition, there's an investigation of chronic active, slowly expanding lesions with or without phase rims that we know don't show enhancement, but show activated macrophages and microglia and are slowly increasing in size and seem to be a sign of risk of disability and progression that can be seen in all MS, but are most common in progressive MS.

They give us a handle on the intrathecal CNS innate immune system in MS. We'll learn more about that. We continue to grapple with how we can use brain volume loss atrophy and maybe spinal cord volume loss cervical atrophy as tools to evaluate MS.

We don't have a good role for that yet in the individual patient. We're going to see further clarifications of the role of evaluating segmental atrophy, and could it possibly be useful on an individual basis to do that. We'll have clarity in the use of blood neurofilament light protein, being touted as a prognostic and treatment response biomarker but not being able to be used on an individual basis.

We'd like to have one uniform test with standardized normal ranges, understand the impact of age, which increases neurofilament light protein. We'll see further studies in 2021 that help us understand that better.

The role of machine learning and artificial intelligence, this allows many studies to be analyzed at one time. This is being applied in particular to neuroimaging of the brain. It can actually do evaluations of multiple studies way better than a human can. We're going to see increasing use of machine learning techniques and artificial intelligence to analyze the MRI scans of large numbers of MS patients to give us additional insight into this disease.

Finally, I would mention that we're entering an era of wearable devices, the ability to track patients at home, outside of the outpatient arena on a day-to-day basis, almost on a 24/7-type basis. You need to do it unobtrusively. It needs to give you valuable data.

We're going to see increasing use of this applied to MS to give us a better handle on how the MS patient is doing, not just wait for the short 30-minute visit every couple of months but being able to get a tangible objective evaluation of how patients are doing their physical activities, their steps on a daily basis.

This is going to give us increasing insight one-on-one with regard to how our individual patients are doing. We're going to see that grow leaps and bounds in the next year.

Christina Vogt: What key take-home messages would you like to leave with listeners?

Dr Coyle: MS is a very important disease. It particularly targets young adults. We know it's on the rise. It's very important to get diagnosed early. It's very important to have the input of a physician who is knowledgeable about MS, because there is so much to be learned on a regular basis with regard to this disease.

It's clear that early treatment is very important, but it's also clear that following a wellness program promotes central nervous system health. It's increasingly clear that the central issue in MS is accelerated aging of the central nervous system.

That's what we want to stop or to minimize. Following a healthy lifestyle, healthy lifestyle choices, wellness program can push that and promote healthy aging and minimize the effects of aging, and also, the identification of the importance of recognizing comorbid diagnoses such as hypertension, diabetes, depression, and making sure they're optimally managed, because the aging is going to be accelerated if they are not being optimally managed.

This is a really important take-home with increasing data that this helps the central nervous system age better in MS individuals and healthy individuals as well, quite frankly.

Christina Vogt: Thanks again for joining me today, Dr Coyle. For more podcasts like this, visit neurologylearningnetwork.com.