Measuring Outcomes in MS

Fred D. Lublin, MD: We’ve now moved to doing a cognitive assessment annually on everybody. Just like we would do an MRI [magnetic resonance imaging] on these patients, we’re doing a cognitive screening—about an hour-and-a-half cognitive screen on everyone so we can follow them, because a single assessment doesn’t help very much. But following over time certainly would be another metric, which brings us into the last topic we’ll discuss, and that is outcome metrics. What are we actually looking to handle? We’ve alluded to this a little bit as we’ve gone along, and even the idea that maybe we’re not measuring everything we can. We certainly have relapses, if you look at this, and we’ve done a really good job at dropping relapse rates. That’s been the primary outcome measure for all of our therapies, and we’re very good at it. Progressive disease—we’re just starting to open the door to having these modest effects on progression as measured by EDSS [Expanded Disability Status Scale]. But where do we go next? What do we need to monitor to get to nothing going on—no disease activity, no progression? Clyde?

Clyde E. Markowitz, MD: Well, I think if you look at all of the clinical trials we’ve done to date, they’ve all measured those particular metrics—relapses, disability progression, and MRI. I agree that we’ve done a good job in terms of being able to suppress disease activity, but you still have the problem of people progressing independent of these other metrics. They’re not having relapses anymore. They’re not having any evidence that we see of any MRI activity with Gad [gadolinium] lesions or new T2 lesions, but they continue to slowly progress. We call that the degenerative phase or progression of the disease.

I think that maybe the neurofilament light chain will help us in that arena. I’m not convinced that this will necessarily be the answer to all this. But I do think that when patients come into the office, we have to make the determination of: Do we think that somebody is on the right therapy, or should we switch them to something else? When it’s obvious, it’s obvious. They’ve had clinical relapses. They didn’t recover. Or, there’s a significant amount of new disease activity on their MRI. Then it’s easy. We just say, “We’re going to switch you to something else.”

But we have no guidelines in this arena. We don’t really know what’s the best thing to do next, and that’s why it’s important that we understand the mechanism of the drugs and know what sequence we may need to go to next. We may go up in efficacy. For us I think, as practice clinicians, and for the people who we’re talking to, it’s not an easy piece. We don’t have the metrics to really answer these questions. We have some. We’re able to act on what we have. But we’re missing a lot of the disease activity that’s happening below the surface, at least below what we can see on an MRI.

Patricia K. Coyle, MD: You mention doing cognitive function battery once a year. Certainly a Symbol Digit Modalities Test is just a few minutes. It is very easy to do on a regular basis—a minimum of once a year or maybe twice a year. It’s a 25-foot time walk. It’s easy to do. And, from the point of view of gait, you really can pick up issues there. A 9-hole peg test is not that difficult to do. We haven’t spoken at all about the visual system. Not yet ready, but optical coherence tomography holds real promise, and low-density visual testing is much more sensitive than the regular.

And then, of course, we haven’t really spoken about nonconventional imaging techniques. Let’s talk about brain volume loss. They are now commercial, and we’re beginning to see it. We’re getting volume measurements, and segmental, and cortical, and thalamic, etcetera. It’s not ready for prime time, on the individual basis, but maybe in the not-to-distant future it will be a meaningful thing to follow if we are correcting for all the factors that can influence it tremendously.

Suhayl S. Dhib-Jalbut, MD: We need to be able to detect, by imaging, those cortical lesions that are only detected pathologically. That’s really critical in predicting disability.

Thomas P. Leist, MD, PhD: I think that a very important point was made and is maybe hidden. That’s why I want to bring it out. The 9-hole peg test, 25-foot walk, and Symbol Digit Modalities Test—these are all quantifiable tests. Where I think we need to go is to move from a purely qualitative exam in multiple sclerosis [MS] to have some quantitative measures when we evaluate patients over time. This will also be very important as we determine the value of multiple sclerosis therapies, as we determine the value of multiple sclerosis care.

James M. Stankiewicz, MD: So I think a very important point was just made, and I’d like to bring something out: Devices, or wearable devices. We haven’t explicitly mentioned them, and I think we need to better learn how to interpret the data. But, it seems intuitive that some of these things can be worn at home, and over time, will give us a better measurement.

Fred D. Lublin, MD: I think that’s true. If you have a week’s worth of walking data versus just the 25-foot time walk, that’s going to be very useful.

Clyde E. Markowitz, MD: These are all outstanding points. The thing that we don’t have in this MS world that we live in is that we don’t have comparative data for these metrics. That’s what we need. We need to be able to do these in clinical trials as comparisons, because when we’re going to make a decision that somebody is not doing well on whatever therapy they’re on, we want to go to something else, just like you have relapse rate or you have MRI lesions, you have some data that say this might be better than that. We need those kind of comparison studies for these new metrics.