New Treatment Landscape in MS — Preventing Long Term Disability Through High Efficacy Treatments in Early MS - Episode 4

Selecting First-Line Therapy in MS

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Thomas Leist, MD and Darin Okuda, MD provide insight into first-line treatment selection for MS and the patient factors involved.

Neil Minkoff, MD: When you’re evaluating a patient, how do you start to make those determinations? There have been things that have come up about undertreatment vs overtreatment, hitting aggressively, dealing with insurance issues. Some of these factors are important to you as a clinician and some are less important. When you see a patient, how do you determine what you think should be their first- or second-line therapies?

Thomas Leist, MD: The first thing that is very important is that I don’t think about individual products or brands. I think of modes of action. I keep a mode of action, or a class of a treatment. That becomes very important because formularies change from year to year, and if a patient has already stepped through a third mode of action, particularly if they chose to move on because of ineffectiveness, that should not have to be recycled. When I’m looking at a patient, the gestalt of the patient is relevant. What factors does the patient bring to the table? Is there incomplete recovery from an attack? How does the MRI look? Where are the lesions? Is there a family history of autoimmunity? Is there a family history of MS [multiple sclerosis] in this particular individual? In a way, it’s a 360-degree view of the patient.

I mentioned that about 75% of patients are women. At initial diagnosis, family issues are on the table. We may choose a medication at that point that allows itself insertion while the family planning issues are ongoing. I have taken a bit of issue with the term aggressive. When natalizumab first came out, it was a well-tolerated medication. Problems arose afterward that it had the PML [progressive multifocal leukoencephalopathy] risk associated with it. From then on in the field, we were thinking of it as high efficacy with a lot of potential safety baggage. We have since learned there is a group of patients on natalizumab who are not at the same level of risk for PML as others. Our newer entrants in the higher efficacy group are quite safe medications overall, which haven’t had this baggage of additional safety risks that manifested shortly after introduction into the market.

If I were to propose to somebody, “Listen, we’re going to effectively treat your heart attack the next time you have an MI [myocardial infarction],” most people would probably look at me and think I’m of a quackish persuasion. That’s not necessarily a good thing. In a certain way, as a neurologist, I can try to prevent injury, but I can’t really fix [the disease]. I would like to transition to where we look at MS as a manageable disease with the tools we have. Many times, if a patient come to me with more than 10 lesions or with lesions in the spinal cord, this patient is already stigmatized to having a higher risk of disability progression over time. The best time to intervene in that disease is now, when I see this particular patient. I understand what Dr Ross said regarding persisting with insurance companies. Naturally, formularies have become stiffer, so we sometimes need to transition. We are also working outside of the formularies with our legislators in the states to perhaps educate that if the plans are too rigid, they might find some legislative inducements that will help them to understand that conditions like MS need to be treated from the beginning in an effective way. As an MS physician, I operate on the biases with the plans, I operate with the patient, the nongovernmental groups, and I also engage with my friends from the legislative side within the jurisdictions that we cover.

Neil Minkoff, MD: Your heart attack analogy might be appropriate now. Maybe 20 or 30 years ago, we actually did say things like, “We’re going to treat your second heart attack much more aggressively.” Maybe we’re just playing a little catch-up. Dr Okuda, do you agree, more specifically about some of the things, the lesions, spinal cord lesions, and the degree of disease present that make you want to—I’ll use a car analogy because of our background—turbocharge your response?

Darin Okuda, MD: It would be great if payers were to stratify groups when it comes to making decisions about authorizing a given treatment. What I mean by that is identifying key clinical, paraclinical, and even baseline demographic factors. Race and ethnicity are massive. We know that those who are non-White, Asian, African American, Black, or Hispanic have different trajectories. There are a wealth of pediatric MS experiences in which these young kids and teens are Hispanic. The incidence and prevalence of multiple sclerosis in people who are Black or African American may be higher than those who are White. We know they recover less well from relapses, their relapses are more severe, and they accrue more neurologic disability over time compared to their White counterparts. It would be nice to start with that.

Other key factors, young age is a big because we know our condition of interest is one that’s dependent upon the age of the individual. The decade of greatest risk is likely age 20 to 30. Of course, it’s not age 50 to 60, and 60 and beyond. By then, we start to get into this realm of immunosenescence. And race and ethnicity are massive.

Moving beyond that, historically in our field, we’ve used a super old term, burden of disease, which really means the volume or lesion number in your brain or spinal cord. That still has meaning because we know that disease occurs well before people present to us for the first time. We don’t know whether we can change their outcome at age 45 when we’re seeing them at age 26 because of the amount of damage that may have already occurred prior to them seeing us. The amount of lesions is important. Where the lesions are is super important as well. Does it involve the optic nerve? Does it involve the brain stem, the cerebellum, the connections there, or the spinal cord? Involvement there will automatically place people in a higher category of neurological impairment. They’re also at risk for subsequent disability accumulation over time.

As you’re caring for someone, in terms of surveillance, you can also look at their relapse history. We know that’s a high correlate to markers of aggressive or highly active MS, along with collecting new lesions on repeat MRI scans. We’re not at the point where we can use neurofilament light. All of us may be of the belief that it’s a super valuable tool, but we don’t have another biomarker that’s exceptionally valuable in our field beyond the MRI scan and what we see clinically in front of us.

Transcript edited for clarity.