Ilya Kister, MD, on the MS Severity Score

In this podcast, Ilya Kister, MD, discusses an article he wrote about the concept and applications of the multiple sclerosis (MS) disease severity score, introducing Herbert's Classification, and more.

Additional Resources:

• Kister I, Kantarci OH. Multiple sclerosis severity score: concept and applications [published online January 22, 2020]. Mult Scler. https://doi.org/10.1177/1352458519880125. 
• Roxburgh RHSR, Seaman SR, Masterman T, et al. Multiple sclerosis severity score: using disability and disease duration to rate disease severity. Neurology. 2005;64(7):1144-1151. https://doi.org/10.1212/01.wnl.0000156155.19270.f8. 
• Kister I, Chamot E, Salter AR, Cutter GR, Bacon TE, Herbert J. Diability in multiple sclerosis: a reference for patients and clinicians. Neurology. 2013;80(11):1018-1024. https://dx.doi.org/10.1212%2FWNL.0b013e3182872855. 

Ilya Kister, MD, is the director of the Neuromyelitis Optica Treatment and Research Program and an associate professor in the Department of Neurology at NYU Langone Health in New York, New York.

TRANSCRIPT:

Amanda Balbi: Hello, everyone, and welcome to another installment of Podcasts360, your go‑to resource for medical news and clinical updates. I'm your moderator, Amanda Balbi with Consultant360 Specialty Network.

Severity score characterizes the level of disability among patients with multiple sclerosis (or MS) and can be used to compare disease progression among different subgroups of patients with MS. A new article published in the Multiple Sclerosis Journal discusses the MS Severity Score’s concept and applications.

Today, I'm speaking with the lead author on the paper, Dr Ilya Kister, MD, who is the director of the Neuromyelitis Optica Treatment and Research Program and an associate professor in the Department of Neurology at NYU Langone Health in New York, New York.

Thank you for joining me today Dr Kister. Let's talk about your paper.

What are some other applications of the severity score in MS research and, ultimately, for improving patient care?

Ilya Kister: I'll give a little background on the severity score to explain this concept and where it came from. Originally, it comes from genetics research in MS when researchers were trying to understand whether certain genetic variance correlate with either mild or more severe disease. To answer this question, they had to have a metric called disease severity.

It's a relative disease severity. Basically, you're trying to compare how a given patient's disease disability compares to other patients with similar disease duration. So that's the underlying concept of the severity score.

Therein lies the difference between severity score and disability score such as Extended Disability Severity Scale, EDSS. EDSS is a "objective" measure of disability, where severity score is a measure of how a person compares to other patients with similar disease duration.

By analogy, we can say that, for example, SAT admission scores do not necessarily measure level of knowledge of the student but measure the relevant competency of the student relative to other students in the same cohort. A concept was developed over the years and proved to be very versatile and very popular.

The original paper has been cited more than 700 times in the publication because primarily it was interesting not only to compare the genetic variants, the disease severity, but also compare different populations, compare different radiologic markers, and predictors of disease progression, demographic markers, immunologic markers as they have proved to be very versatile concept that used in many different areas of MS research.

Amanda Balbi: What are the limitations of the scale?

Ilya Kister: Number one, the severity score should not be calculated at the time if somebody has a relapse of MS or recovering from a relapse, because it would give an exaggerated score. Comminution should wait for about 6 months or so after the relapse to calculate more of a baseline score.

The second limitation has to do with disease duration. If a patient is not sure how long they had the disease, it can introduce a great degree of uncertainty in calculating severity score. Sometimes it's not so certain when the disease started. There might have been some subtle symptoms which may or may not have been the inaugural symptoms of the disease.

Since most people have disease onset in their 20s and 30s, it's usually less of an issue. If there is an important question whether it started just recently or person had it for decades, probably this score should be considered with caution or a degree of uncertainty.

Amanda Balbi: How may the severity score help to develop prognostic tools for patients with MS?

Ilya Kister: MS is a disease with very variable course. Severity varies widely across patients. There are people with MS for many years and decades who hardly have with any disability. There are people who are fairly rapidly disabled.

One of the important questions in clinical research of MS is to try to identify predictors of what an individual patient's course will be like. It has proven to be a very challenging, a very difficult problem. There are no great demographic and clinical predictors of disease severity, or genetic predictors, or radiologic predictors of disease severity that would be helpful for an individual patient.

It's very hard to answer an individual patient's question of how they are likely to do. That said, the severity score can be considered a predictor of future course. If a patient has a low severity score, that means to say that he is less disabled than most other patients with the same disease duration at a certain point in the disease course, it's a good prognostic marker.

It means that it is likely that 5, 10, 20 years down the line, he will also be relatively less impaired compared to other patients with the same disease duration. So I think it's good to think of severity score, not as an immutable kind of affixed rate of a disease, because there is definitely variation.

People who start out as low scores, end up with higher scores and vice versa. To think of it as one of the major predictors of what is to expect down the line, especially predictors of very mild and very severe disease course.

Amanda Balbi: Absolutely. And you also wrote about introducing Herbert’s severity‑based MS classification. What is Herbert’s classification and how might it add to a patient's clinical picture?

Ilya Kister: Dr Joseph Herbert was my mentor at the NYU MS Center. One of the ideas that he introduced me to is that when we talk about MS patients, it's not enough to just talk about their disability. You also have to consider the disease severity as well. He developed this idea of classifying MS based on disease severity.

Of course, this is not entirely novel idea of the medicine. There are many diseases that are classified according to disease severity—cancer staging or heart failure classifications. But he introduced this concept to MS. He divided the scale, which is a 0 to 10 scale, into 6 equal severity groups. The mildest group is the first one, and the most aggressive group is the sixth one.

He thought that this classification would be helpful for several reasons. First of all, to communicate among clinicians and even communicate among patients to get a sense of the disease. How does it compare to the expected course? Is the patient doing better than expected for his disease duration? Worse than expected? All this can be communicative by simply stating his disease severity.

Dr Herbert also thought that it would be important to consider disease severity when trying to pick treatment. If somebody is expected to have a very mild nondisabling severe course, it's probably not wise to start them on very heavy‑duty therapies with a high number of potential side effects.

Whereas a patient's course is expected to be aggressive, it would probably be smart to use effective therapies from the get‑go to bend the curve and achieve better outcomes in the long run. So those are the major uses of severity scale. He also thought it would be helpful to use it when selecting patients for clinical trials.

More homogeneous, more similar populations are selected for clinical trials, and the trials are more specific to patient subsets. They published his specifications posthumously—he, unfortunately, passed away—a couple years after his passing, in the International Journal of MS Care. In the recent review article, we come back to it and review some of the major uses of this classification hoping that it will be more widely accepted in the MS community.

Amanda Balbi: What else do practicing neurologists need to know about the MS Severity Score and its potential future applications?

Ilya Kister: I think neurologists already know quite a bit about the scores evidenced by the fact that there's so many papers that use this scale. One aspect that I would like to highlight here is maybe that the scale is not as widely used by clinicians. It's more widely used by clinical investigators.

Part of the reason for that is that to calculate the severity score, you need to know patients' EDSS disability. This is rarely done outside of more-specialized MS centers. Most MS patients are taken care of by their community neurologist and not in specialized centers.

To circumvent these difficulties, we created a very similar scale to Multiple Sclerosis Severity Scale called Patient‑Derived Multiple Sclerosis Severity scale. This one, instead of using the EDSS, which is a clinician calculate the disability by examining the patient, the patient themselves assess their own disability.

The scale that they use is freely available. It's called PDDS, Patient Disease Disability Steps. We rank those PDDS scores rather than ranking the EDSS scores. We created a normative table which is also freely available. This was published in the Journal of Neurology.

Any patient and any clinician, no matter where they are, can use this table and calculate patient's severity scale or PMSSS and figure out where their patient scores in the Herbert classification, whether their grade is mild or severe.

Sometimes it could be quite helpful for patients when they are trying to make treatment decisions, helpful to clinicians because they have a better understanding of how this course of the disease compares to others in similar circumstances.

That's one aspect that I think has not been emphasized and if people are interested in using the scale, they should look up this PMSSS reference in Neurology. They can just print it out and it will probably take about a minute to figure out the patient's severity score based on that.

Amanda Balbi: Great. Thank you so much for speaking with me today about your article.

Ilya Kister: You're welcome. It was very nice talking to you.