Professor of clinical neurology, and George A. Zimmermann Endowed Professor in Multiple Sclerosis, Department of Neurology, University of California San Francisco

Bruce Cree, MD, PhD

My last question is going to be to Joe and Fred, again in the context of looking ahead. What advice would you give to community-based neurologists who are treating patients with progressive MS [multiple sclerosis] and may not have access to the multidisciplinary teams that specialist centers have at their disposal? A lot of people live in rural areas and have a harder time accessing the MS centers that are typically in major metropolises. How do you advise the community-based practitioner?

Managing MS is complex. It’s multifaceted and time-consuming. One of the things that I always recommend is: Don’t be afraid to reach out. I practiced in a state that was predominantly rural. There were fewer neurologists for the entire state than we have in the city of Philadelphia. It was very often that I’d see patients who had MS maybe once or twice a year and then co-managed these cases with their community physicians. There was no way that they were able to get into Lexington, Kentucky, with the frequency that they would have had I been practicing closer.

The most important bit of advice is: Don’t be afraid to reach out to people who have skills in managing MS, because it’s become much more difficult these days. There was a time when we really didn’t have any therapies for multiple sclerosis. It wasn’t all that long ago. It was certainly while Fred and I were practicing. With the new drugs as they’ve come onto the market and the new ways of monitoring patients and their symptoms, it’s sometimes best to have an individual who has experience with doing so weigh in periodically. Don’t be afraid to co-treat patients. Even if it’s a phone call, it’s often worthwhile. 

 I agree with what Joe just said. It requires comprehensive care. We had that conversation already. It’s obviously not available in the community. But what we do is we partner with the guys out in the community. I have great respect for the guys doing general neurology because they have to know a lot about what I know and a lot about epilepsy, migraines, and Parkinson disease. All these areas have become more complicated as well.	

We’ll partner. We’ll see their patients about once a year, and they’ll work with them in the interim. That way they have the advantage of our comprehensive care staff, but they still could be far away, not have to travel as far, and have a local neurologist as well. Now with telehealth, we’ve expanded the range of people we can see comfortably, where they don’t have to travel into the city as often. 

That’s great. One of the teachings from the pandemic is that we are able to help patients remotely. All of us have developed a set of telehealth skills that we never had before as a consequence of not seeing patients in person and asking people not to travel. This has added to our skill set. 

This has been a fantastic discussion. I want to thank Dr Krysko, Dr Lublin, Dr Fox, and Dr Berger for their participation in today’s program. Thank you for watching this NeurologyLive® Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox.

Videos

Joseph R. Berger, MD, and Fred D. Lublin, MD, offer advice to community physicians and neurologists in managing patients with multiple sclerosis. 

Advice for Managing MS 

“The good news for patients is that as we sit here today, they have not 1 choice, but 3 choices for disease-modifying therapies that have been proven to be beneficial in NMOSD.”

Over the course of the last several years, the treatment landscape of neuromyelitis optica spectrum disorder (NMOSD) has experienced a massive growth relative to its prior state, which Bruce Cree, MD, PhD, MCR, FAAN, described as “nebulous.” Now, a trio of therapies are available for the treatment of this disorder: inebilizumab (Uplizna; Viela Bio), satralizumab (Enspryng; Genentech), and eculizumab (Soliris; Alexion).

Cree, the clinical research director of the UCSF Multiple Sclerosis Center, and professor of clinical neurology at UCSF Weill Institute for Neurosciences, presented a few posters on the Viela Bio product at the 

2021 American Academy of Neurology (AAN) Annual Meeting

, April 17-22. These posters detailed long-term data on the monoclonal antibody’s efficacy and safety in patients with NMOSD.

open-label extension (OLE) of the N-MOmentum trial

 (NCT02200770) showed that inebilizumab continued to provide benefits similar to those seen in the randomized controlled period of the trial—a welcome sign for physicians like Cree.

, he discussed the impact that these approvals have had on the care of patients and the advantages that disease-specific agents have brought to the population and shared his experience as an investigator on some of these trials. Additionally, he shared some of the takeaways for the clinical community of specialists treating patients with NMOSD.

REFERENCES
1. Cree B, Bennett J, Weinshenker B, et al. Long-term efficacy outcomes with inebilizumab treatment in NMOSD: the N-MOmentum trial. Presented at 2021 American Academy of Neurology Annual Meeting; April 17-22. Abstract P15.076
2. Cree B, Bennett J, Weinshenker B, et al. Long-term safety outcomes with inebilizumab treatment in NMOSD: the N-MOmentum trial. Presented at 2021 American Academy of Neurology Annual Meeting; April 17-22. Abstract P15.100

The clinical research director at the UCSF Multiple Sclerosis Center shared some of the takeaways from his research for the clinical community of specialists treating patients with NMOSD.

Leaving a Nebulous State of Care for Patients With NMOSD: Bruce Cree, MD, PhD

 In our last section for discussion, I want to turn our attention to looking ahead and what we think the future is going to look like for managing MS [multiple sclerosis]. I’m going to ask Kristen and Bob to comment on this. Where do we go from here? What do we do next?

We focus on progressive MS, which we’ve been talking about. As we highlighted, we need to focus on having better ways to identify progressive MS, to diagnose it early at a time where they may be more treatable, ways to monitor and capture progression, not only for clinical practice, but also to study medications and their effect on progression. We need to look at developing better tools, be they MRI measures, biosensors, laboratory measures, that can help us monitor and diagnose progression. There’s a lot of work going on in this area. In the future, we’ll have better ways to monitor that. 

As we’ve talked about, we have medications that target inflammation very well and seem to target the active part of progression if someone’s also having relapses or inflammatory activity. Developing strategies to target that progressive aspect of the disease and having a way to get that into the clinic would be a big step in the right direction.

We also need to improve access to multidisciplinary care. A lot of these symptoms we’ve talked about—the fatigue, exercise, nutrition—can all be helped by having a multidisciplinary team in the MS clinics where patients can meet with all many different health care disciplines to optimize their function, even if we’re not able to stop or slow the progression as much as we would like. 

I agree. Progressive MS is the big nut that is waiting to be cracked, to figure that out. A key aspect of progressive MS that is an unmet need is: What is it? What is the pathophysiology of progressive MS? What is driving that slow, insidious decline? If we knew that, we could better direct and design treatment trials to test new therapies.

We also need to better understand the 2 ends of the relapsing MS management spectrum. Early on, what is the ideal treatment? Are there biomarkers that can point us to which therapy patients will respond to better? There’s that age-old question: Do we start low and gradually escalate, or do we start with very aggressive therapy? There are 2 ongoing trials that are looking to address that. It’s an important question. Do we come out of the gate guns blazing with a highly effective therapy, or do we escalate? Is that an acceptable approach?

At the other end of the relapsing spectrum are the older patients who probably don’t need MS therapy. Can we stop the therapies? How do we stop them? What are the risks and benefits of stopping them? There are a couple of ongoing trials, from which we should get answers over the next few years. It’s an important question. We have our patient doing well, but does the patient still need therapy now that they’re 20 or 30 years into their MS?

Discontinuation of treatment is a very interesting and highly controversial topic that we’re going to have to wrestle with more and more as our patients age out of the inflammatory phase of the disease.

Thank you for watching this NeurologyLive® Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox.

Kristen Krysko, MD, and Robert Fox, MD, look to the future of multiple sclerosis management. 

Future of MS Management  

 We’ve touched upon nutrition and cognition. What about exercise? Joe, can you comment about exercise in MS [multiple sclerosis]?

 Sure. I recommend exercise for all of my patients, regardless of whether they have MS. It’s important. I do think that exercise in patients with MS is valuable for multiple reasons. These patients often become deconditioned. They also often have problems with their strength and balance. Various forms of exercise, particularly aerobic exercise, can be helpful in that regard.

There’s hardly a patient I see who, when I ask them to do a tandem gait, doesn’t tell me, “I’m better today at it than I was last time I was in the office because I’ve been practicing it.” That’s true of anything we do. If you practice it, you get better at it. In terms of strength and balance, exercise is important.

Another important factor with respect to exercise is maintaining or reducing your weight. As I believe Bob mentioned earlier, one of the things that’s important is to not be obese. Don’t smoke, take your vitamin D, and don’t be obese. Exercise also helps in maintaining the appropriate weight.

A third benefit of exercise is less fatigue. When people exercise, we find that levels of fatigue are improved. Their sleep is also improved. There are many benefits to exercise, and it should be strongly encouraged.

Is there a particular form of exercise that people should engage in? I think it’s a bit like diets. We don’t really have any evidence that there’s a particular form of exercise that is beneficial. It’s important to just get off the chair and get on the exercise bike, treadmill, do Pilates, or whatever you can. That’s what I tell my patients.

 You didn’t mention squash or racquetball, Joe. 

That’s true, I didn’t and I don’t. It’s usually a little too vigorous. 

I would also add that mood is known to improve with exercise.

With depression being as common as it is in patients who have MS, there is evidence and some trials now underway to evaluate the direct impact of routine exercise on mood. 

I tell my patients that the best exercise for MS is the one they like to do. Because that’s the one they’re more likely to do. If you tell Joe to do yoga, he’ll laugh at you. But if you tell Joe to go play racquetball or squash, he’ll be on the court this afternoon. The most important thing is the exercise that the patient likes to do. Aligning your recommendations with their preference is key. 

Exercise is important. Fred, what do you do with your patients who are combating fatigue? How do you evaluate fatigue, and then what do you do about it? 

First, try to determine whether it’s the true fatigue of MS, fatigue from being depressed, or fatigue because they’re not sleeping well enough. That’s not all that difficult to sort through. The one that’s probably the easiest to deal with first is sleep. We do a sleep hygiene assessment to try to sort that out. Then we do simple things. We ask people specifically about whether they’re having spasms at night that are waking them up. They don’t have to be painful. They could just be spasms that wake you up. So you work on sleep hygiene. 

Mood is an important one. We deal with that. If that all works, then you get a good description of fatigue, which is different from what ordinary people think of fatigue. Sometimes the patients can’t describe it, but you hear it enough from them when they say it’s different, or it’s not like when they have the flu or any of that sort of thing. 

Then we try to treat it. If it’s depression, you treat their mood. If it’s sleep, you deal with sleep problems. The problem with trying to treat fatigue pharmacologically is that the data are so bad. The TRIUMPHANT-MS study was just published, which said, “We don’t think any of these work, except for maybe sleep issues.” But when we discussed this during our ACTRIMS [Americas Committee for Treatment and Research in Multiple Sclerosis] course, most of the clinicians said, “We saw that data, but it wasn’t a responder analysis,” which is an important critique. 

I try these various agents, modafinil or amantadine, because as with any of the symptom management medications, you can determine pretty quickly whether you’re doing anything. You could try it for a couple of weeks. If it helps, there’s not much cost to it because they’re pretty well-tolerated. I do avoid stimulants because I don’t like to get into those. But I will try things like modafinil or amantadine.

Considerations regarding the role of exercise and combatting  fatigue when treating patients with multiple sclerosis.  

Bruce Cree, MD, PhD

Articles

Advice for Managing MS

Leaving a Nebulous State of Care for Patients With NMOSD: Bruce Cree, MD, PhD

Future of MS Management

Exercise and MS Fatigue