How Are Outcomes of Progressive MS Measured?

Peter L. Salgo, MD: What are the outcomes of progressive MS [multiple sclerosis], and how do you measure them?

Patricia K. Coyle, MD, FAAN, FANA: Well, the bad thing is that once somebody has entered a progressive stage, we can’t stop the gradual worsening. We can slow it, we hope, with treatment, but we can’t stop it. So what are you measuring? You’re measuring the quantitative neurological exam. And as Tom pointed out, things like the Timed 25-foot Walk can be very good, or the 9-Hole Peg Test to evaluate hand function can be very good. A symbol digit modality test just takes a few minutes and can be done in the outpatient department and is a way to monitor cognitive function. These are clinical things that we would monitor.

Peter L. Salgo, MD: All right. There’s another acronym. We are filled with them today. NEDA.

Patricia K. Coyle, MD, FAAN, FANA: NEDA.

Peter L. Salgo, MD: No Evidence of Disease Activity. What’s that?

Patricia K. Coyle, MD, FAAN, FANA: That’s really a compilation of the major clinical and MRI [magnetic resonance imaging] outcomes. It includes no clinical attack, no confirmed worsening on the EDSS [Expanded Disability Status Scale], and no new MRI lesion. And that’s an interesting measure for clinical trials. I think it’s a little too rigorous for clinical utility, because a cohort of MS patients can’t truly maintain NEDA for a long time. It’s saying that if you have a single new MRI lesion, you failed NEDA, you haven’t met it. And that’s just too rigorous. None of our treatments is said to be an absolute cure.

Thomas P. Leist, MD, PhD: You also heard clearly from Pat Coyle’s description: no MRI activity, no disability progression, and no new attack. What about the cognition? This all describes how you show up in the office. It doesn’t tell what you do when you’re in the office. And so NEDA in itself is a conflagration of different outcomes, and it needs to be used in a clinical trial environment. I don’t think it is ready for the in-practice environment.

Peter L. Salgo, MD: I don’t want to leave this topic without another term of art, which is brain preservation. My understanding of this disease is that—little by little, uncontrolled—it chips away, and your brain is not preserved. And the object here is to preserve as much neurological function as possible. Does this make anatomic sense?

Thomas P. Leist, MD, PhD: Yes, this makes anatomic sense, and it makes particular anatomic sense from the discussions that we had about how MS is no longer just a white-matter disease. As we understand, it was always not just a white-matter disease. It’s a white-matter and gray-matter disease. Another term is neurological reserve. It may very well be that different individuals have different neurological reserves, and that injury that is absorbed by 1 person more easily—I’m not saying well—is leading to significant injury in another person. But these are terms that are just emerging. I do think that brain preservation is important, but it goes essentially to the other concept: maintaining of function.
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