When Should You Switch Therapies in Multiple Sclerosis?

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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: We talked about starting individuals on therapy. How do you decide when to switch?

Claire S. Riley, MD: When deciding on a switch, I always first assess people for compliance (or adherence) and tolerability. There can be a situation where you switch based on misery of the patient—they hate the therapy or it’s ruining their lives in some way. But in terms of incomplete efficacy driving switch, I tend to—as I think is relatively common or shared in practice—re-baseline MRI at about 6 months after starting a new immunotherapy.

Sometimes, I think with glatiramer that should be pushed out a little bit later. I think a full MRI efficacy of glatiramer might come more so at the 9- to 12-month mark, but for others, about 6 months. Then, in someone who is clinically stable, I do feel moved by MRI disease activity from surveillance MRIs, which I tend to get annually if people are doing well from a clinical perspective. Would one T2 lesion do it? Maybe, maybe not. But contrast-enhancing lesions or re-accrual of several new T2 or enlarging T2 lesions can lead me to propose a switch. Certainly, in somebody who is having relapse activity after an agent is fully effective, I’m going to explore what alternatives there are for more highly effective therapy after I’m sure the patient is actually taking the therapy that’s prescribed.

I think that when we get to a situation where we’re not seeing relapses—maybe we’re not even seeing new MRI lesions but someone is having gradual worsening of the disease, suggesting perhaps secondary progressive MS—I’m not sure that escalating immunotherapy for relapsing-remitting MS indication is helpful. I might turn to either clinical trials or perhaps off-label use of other agents. I think it’s much harder not to crack at that point.

Fred D. Lublin, MD, FAAN, FANA: So, from a practical point of view, I want to say that if we could actually parse the T2 lesion load it would lead to switching, right? Because you’re going to look at a year that they’re on whatever agent you want and they’re doing fine clinically. If you saw 10 new lesions, you’d probably switch them, right?

Claire S. Riley, MD: Right.

Fred D. Lublin, MD, FAAN, FANA: One new lesion?

Claire S. Riley, MD: I’d probably look again in 6 months.

Fred D. Lublin, MD, FAAN, FANA: Okay. Two?

Claire S. Riley, MD: I’d probably switch them.

Fred D. Lublin, MD, FAAN, FANA: So, there’s not a lot of data to guide us.

Claire S. Riley, MD: Right.

Fred D. Lublin, MD, FAAN, FANA: The only data that I’m aware of is that interferon patients who have a couple of new lesions after 1 year are going to do badly. It doesn’t tell you anything about the interferon, necessarily, but it tells you they’re going to do badly. The same data did not hold up for glatiramer acetate. None of our agents have hit 50% at 2 years of stopping all activity. So, do you worry that you may be taking someone off an agent that they didn’t need to get off of?

Claire S. Riley, MD: I do. When it’s just MRI activity, I present it as an issue around which there’s equipoise. Smart people, like those at this table, disagree as to how impactful a new, or 2, or 3 new T2 lesions should be.

Fred D. Lublin, MD, FAAN, FANA: Your equipoise is agreeing to disagree.

Claire S. Riley, MD: Yes, that’s true. What do you do, Clyde?

Clyde E. Markowitz, MD: I scan everybody on a regular basis. I don’t act on everybody on a regular basis, though. I keep it within the context of what drug they’re on, how they’re doing clinically, how they’re feeling about how they’re doing as well, and I monitor them.

So, for one lesion—no. For a couple of lesions—I’m worried. I get into the conversation with the patient and say that, “I’m not sure that this is the best drug.”

It could be a blip on the radar, right? They may just have one thing that set it off for a period of time, so I rescan them in 6 months. If I see repeated events on scans that look like we’re having ongoing disease activity with inflammatory stuff, then I will make a change. I’m not so quick, because I’m not sure that I am going to get a better response with another agent, necessarily. I may just blow through all of the compounds, and be done very quickly.

Claire S. Riley, MD: And switch studies are really problematic because the regression to the mean confounds their interpretation. I think we have little to guide us on this.

Fred D. Lublin, MD, FAAN, FANA: Switch studies have been poorly done. What do you think?

Patricia K. Coyle, MD: I think there are some basic principles that you could elucidate. The DMTs (disease-modifying therapies) are not cures, and we know that 20% to 50% may have suboptimal responders—that may be because we chose the first agent.

The first 2 years are probably critical. We have evidence-based data combining all of the interferon-betas. If you have a single-contrast lesion, or two or more T2 lesions, it’s associated with a poor outcome and is probably justification to switch. Otherwise, you’re following relapses, and in the modern era trials, you would see a relapse once every 3 to 8 years. That means that any relapse on treatment needs to be evaluated as a possible suboptimal response, necessitating a switch. You’re following the neurological exam. Is there worsening? Is there development of disability as well as silent MRI breakthrough disease activity? Then, you’re also speaking to the patient, and asking how they feel, etc.

The institution of a DMT should be combined with promoting a wellness health program and making sure you optimize management of any associated symptoms. And, if you see things accompany each other—there’s a relapse and there’s been a lot of new MRI disease activity—I’m going to bail on that treatment. If the exam is worse and there’s a lot of MRI disease activity, I’m going to bail on that treatment. If there is silent MRI disease activity with the interferon-betas, I’m going to bail. I don’t change based on a single MRI scan—outside of the interferon-betas—if the patient has had no relapse or no worsening, and tells me they’re doing great. But, I will do the next MRI sooner.

I think a focus on the first 2 years on disease-modifying therapy is critically important to detect a poor response. Since we have multiple options, we need to switch—not sit on the patient as they are accumulating injury to their central nervous system.