MS Agents: Effects on Delaying Disease Worsening

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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:

• Patricia K. Coyle, MD, professor and vice chair (Clinical Affairs) and director of the Multiple Sclerosis Comprehensive Care Center at Stony Brook University Medical Center, New York
• Clyde E. Markowitz, MD, associate professor of neurology and director of the Multiple Sclerosis Comprehensive Care Center at Perelman School of Medicine, University of Pennsylvania, Philadelphia,
• Claire S. Riley, MD, assistant professor of neurology and director of the Columbia University Multiple Sclerosis Clinical Care and Research Center, Department of Neurology, Columbia University, New York

Fred D. Lublin, MD, FAAN, FANA: How about the effects we see on changes in worsening disability?

Clyde E. Markowitz, MD: I think that even going back to some of the earliest clinical trials in MS, there’s always been the question of, how do we measure disability, and what is that measure showing us?

I think that you can see a suppression of disability evolution, maybe by 30%, in some of our studies. And the question we’ve always asked is, is that sustained disability a function of having a relapse that did not recover as opposed to the underlying progression that we talk about that is not clear to us? What’s causing that?

At the end of the day, I think that as our clinical trials have evolved over the last couple of decades, we start to see that maybe there is a separate metric, particularly in the people who have progression without attacks. That metric is really what we’re trying to go after because that’s the piece that’s going to lead to patients having disability in wheelchairs, and walkers, etc.

So, I think that at least from some of the most recent clinical trials that are looking at progressive patients, that metric is much more useful to us than the metric of the stepwise activity that you see in the early clinical trials. I think we’re inching up a little bit with each clinical trial. Maybe the populations are different, maybe our efficacy of the medications are a little bit more impressive. We’re getting into the 40% range, now, with suppression of disability. I think that our ultimate goal is to really prevent people from losing function. That metric of how we score people on disability is so nebulous and so difficult for us to get a handle on because there’s so many things that play into that. Whether the patient comes in at the end of the day for a study, or they’re seen in the beginning of the day, or whether or not they had an infection, there are so many pieces that play into that. But I still think at the end of the day, our goal is to prevent them from evolving and having neurologic dysfunction. Our clinical trials seem to point to the idea that we’re improving a little bit in terms of our ability to suppress that.

Claire S. Riley, MD: I think one thing that’s interesting is the clinical trials that have shown sort of a mismatch between the amount of relapse suppression and impact on disability. While it doesn’t shock me that our most highly effective anti-inflammatory therapies—natalizumab, alemtuzumab—might show a slowdown in disability progression, I am intrigued by what we’ve seen. Teriflunomide and some of the emerging data with agents that are having relatively modest effects on relapse rate but are showing some slowing in disability progression are examples. I find that interesting.