Strategies in the Management of Relapsing-Remitting Multiple - Episode 7
The MD Magazine Peer Exchange “Strategies in the Management of Relapsing-Remitting Multiple Sclerosis” features a panel of physician experts discussing the importance of early therapy in multiple sclerosis treatment, factors that affect choice of management strategy, the need for ongoing monitoring, and other aspects of treating patients with multiple sclerosis.
This Peer Exchange is moderated by Fred D. Lublin, MD, FAAN, FANA, Saunders Family Professor of Neurology and director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Icahn School of Medicine at Mount Sinai, New York.
The panelists are:
Fred D. Lublin, MD, FAAN, FANA: We do not have good evidence-based decision making in terms of looking at how severe disease is when you first see them, and what you put them on. People do this, but the data, I don’t think, are very good. Nevertheless, we do it. So, how do you do it? How are you deciding on the efficacy side?
Patricia K. Coyle, MD: I think, in principle, you need to make some assessment of what the level of disease activity is for this particular patient. I know it is difficult because we’re often discussing this at the very first attack. So, you look at clinical properties. We know that attacks that involve motor, or cerebella coordination, or bladder bowel function are considered more severe. You want and expect a complete recovery from the first attack. If you have an incomplete recovery, then that would suggest it’s a more significant disease.
The clinical disease activity is accompanied by an MRI picture. You’re going to image the neuraxis, the brain, and the spinal cord. You know when the patient presents, they’ve had their MS for a period of time. It’s been silent. What exactly is their lesion mode? Do they have a lot of lesions, lesions in the spinal cord? Lesions in the brain stem seem to portend a more significant concern of poorer prognosis. Are you seeing a lot of enhancing of lesions? Are you seeing evident atrophy in a young person? Are you seeing a lot of T1 black holes that would be very unusual early on? And then, what is their prognostic profile?
I think you have to think about disease status, but then, also about their prognostic profile. There are a dozen different features. How many are in the checkmark of a good prognosis versus a bad prognosis? And this is things like gender, the age of onset, and the ethnicity of the individual. All of these are factors we would really count in. If I have a very active patient with a poor prognostic profile, then efficacy becomes more important than somebody who seems to have very mild disease.
Claire S. Riley, MD: How do you incorporate the environmental factors, though? You went through some of the immutable ones, but how about when you have somebody who’s smoking, obese, and not replete with vitamin D?
Patricia K. Coyle, MD: In the last couple of years, the data is just accumulating so steadily. The way that I present it to patients is as follows: they have to think about their CNS (central nervous system) reserve and brain reserve. As we hit mid-life, our brain is shrinking, even healthy controls. You want to maintain that reserve and help the brain, the CNS, to be able to repair itself. Living a healthy lifestyle does that, wellness, health maintenance, controlling vascular risk factors.
I’m paying attention to blood pressure now. I want to know what their hemoglobin A1C is. I want to know what their lipid profile is. I tell them, “This is the equivalent of being on a disease modifying therapy. You’re going to help your central nervous system, help your brain.”
So, they’ve got to stop smoking. They have to lose weight. They have to have good sleep. They have to do regular exercise. They have to make sure they’re mentally and socially stimulating themselves, and then control any vascular risk factors. That’s going to help their central nervous system and, I believe, enhance their response to any other disease modifying therapy.
Fred D. Lublin, MD, FAAN, FANA: I think the smoking is at the top of that list. Do you view selection any differently?
Clyde E. Markowitz, MD: No. I think that the way Pat is approaching makes the most sense. I like the idea of trying to have patients have the decision making shared in that way.
I think one of the things that we’re coming across is that we might spend all that time in the conversation with a patient, and at the end of the day we choose this and the patient says, “I cannot do that,” or “It has this risk, or this risk,” or whatever the issues are. Then, you’ve got to back down from that point of view. Or the insurance company comes in and says, “I’m sorry, we’re not going to approve what you want to do anyway.”
It’s a challenge, but I do take the approach, similar to Pat. We look at the whole prognostic features and make a determination of what we think is the best for the patient and try to convince the patient that that’s why we want to go down that pathway, but it can be very challenging.
Fred D. Lublin, MD, FAAN, FANA: What do you think of treating early on? Are you treating relapses? Are you treating degeneration?
Clyde E. Markowitz, MD: I think I’m doing both. I think that we have enough data to suggest that those relapses lead to tissue damage. That, ultimately, is what I’m trying to prevent. Getting them on therapy is always possible with something that is effective in preventing that. I think, ultimately, I’m reducing tissue damage in neurodegeneration. That’s what I think. I don’t know that absolutely, but that’s what I believe.
Claire S. Riley, MD: And, perhaps, that some control of these other risk factors and vascular health might have positive effects on limiting neurodegeneration too. There’s so much more to know about it.
Fred D. Lublin, MD, FAAN, FANA: Do you think that we’re at the stage yet where we could think about targeting specific immune functions—T-cells, B-cells, cytokines?
Clyde E. Markowitz, MD: Yes.
Claire S. Riley, MD: We are doing that. Our medications work in different ways, but I think that unfortunately, we don’t yet have the tools to say, “Oh, clearly your MS phenotype is going to respond better to a B-cell-directed therapy.”
Each of our treatments and classes works in different ways by harnessing different disruptions of the immune system. What we want is the ability to do a cheek swab, get genetic material, and say, “T-cell receptor, here we go,” or “B-cells with antigen-presenting cells.” That would be the targeted mechanism, we’re just not quite there yet.
Fred D. Lublin, MD, FAAN, FANA: Immunophenotyping.
Claire S. Riley, MD: Right.
Clyde E. Markowitz, MD: That would be good. One thing, that I think is kind of interesting, that’s evolved in the last couple of years, is the understanding of how some of these drugs work, and the cell types they target, or maybe the cytokines that they go after. But, if you then look at how the research has evolved over the last decade, thinking about B-cells for a moment, you can see that all the drugs we have approved currently, that we believe were working primarily on the T-cell side of things, actually work on the B-cell side as well. It may not be that we have to go after one particular type, but it just may be broad enough that you’re affecting both arms of that. That may be the benefit, ultimately, for these drugs.
When we deplete B-cells, are we depleting the B-cell function toward what happens to the T-cell at that point? You know, antigen presentation, etcetera? Or is it very specific to the B-cell? We don’t know that. But we know that you’re having a global effect on the disease. So, it may not necessarily require us to knock out a specific cell type, per se, and understand what I think is a moving target. We’re learning a lot.