Great MS Debate: How have MS management strategies evolved?

Welcome to the Great MS Debate.

DR. LUBLIN: Hello. This program will be a debate and reflective discussion with current treatment paradigms in multiple sclerosis, the potential role of the early high-efficacy therapy and how patient preferences come into the play in the shared decision-making process.

DR LUBLIN:

We recognize that we have come a long way in MS management. Patients no longer are guaranteed to be in a wheelchair because they have MS.

Given the growing treatment landscape, now we have a lot more factors to consider when we treat MS. How have management treatment strategies evolved?

So Tim Vartanian, let's hear from you. What are some of the reasons driving the different management approaches and why would a patient or a clinician prefer one approach over another?

DR. VARTANIAN:

So I think the two major treatment strategies are escalation and beginning with a high-efficacy therapy upfront.

So let's talk about escalation therapy first. I think the rationale between, the rationale about using escalation therapy is really one centered on safety, and so the idea here that people who use this strategy are thinking is that high-efficacy drugs often have more serious adverse events associated with them. Modest efficacy drugs may be safer, fewer SAEs, so start a patient on a modest therapy agent that's safe or relatively safe and wait for, you know, monitor them and wait for any signs of disease progression clinically or by MRI that would then warrant a change to a higher-efficacy therapy.

The issue with this is a couple of things. It implies that what we're seeing clinically is a true indication of disease activity and damage to the central nervous system. And that is not true. What we see clinically and what we see by MRI is a partial, a partial view of the total disease activity.

So I think the problem is that it's two-fold. One, monitoring is not catching everything; and two, by the time something happens, there has already been damage done. And that's why I don't favor this escalation approach but favor the high-efficacy therapy upfront. The idea with high-efficacy therapy upfront is to recognize that for the most part once the damage has been done to the CNS, it's irreversible, or partially reversible. And so we're trying to prevent that damage from happening at all. High-efficacy therapy upfront is our best chance of protecting the nervous system from injury, and therefore, our best chance of limiting the probability of disability in patients long term. It's something that I think most MS specialists do.

I think one of the things that limits people's use of high-efficacy therapy is they might not have infusions available in their clinic. Patients may be, you know, risk averse, and therefore, not want to go on high-efficacy therapy. But it's clearly in, you know, in my experience, high-efficacy therapy upfront has had the biggest impact on disease.

DR. LUBLIN: Okay. Thanks, Tim, for sharing that. Hey, Jamie, what are we currently seeing happening in the practice?

DR. STANKIEWICZ:

I think there is a movement in the MS field towards using higher efficacy therapies earlier. I think you can see this across the country. I think there is still a way to go, to be aligned with sort of best possible results in our patients.

But I think there is a, I mean sort of for the reasons that we discussed a little bit and that Tim has sort of talked about, there is, I think, it just makes sense. I think if the side effect profile of these drugs was materially, higher efficacy drugs was materially worse, then it's a different discussion. But I'm not really convinced of that.

I'm not sure that really is most rationally in line, although again, it's an individual choice of the patient.

DR LUBLIN: So in August 2019 of approximately 235,000 patients with MS treated, 28 percent initiate or changed to new treatments annually. Of this group, 55 percent had received a new prescription were switching the disease modifying therapy.

In a multinational market research survey, 463 qualified patients with the MS, who were currently taking prescription medication responded to the question, overall, how satisfied are you with your current disease modifying MS medications? The survey included participants from Italy, Germany, Spain, UK and the US. Among the 245 patients from the United States who responded, 22 percent were either somewhat satisfied or not at all satisfied with their current DMT, which would represent the two lowest characterizations.

So what could be driving the rates of treatment switching?

DR LUBLIN: We will seek to understand this topic further in the form of a dynamic debate analyzing the benefits of risks to both treatment approaches.

Considering the potential risks and benefits of high-efficacy options, what do you consider the right time to start a high-efficacy MS therapy and what drives this decision. Jamie?

DR. STANKIEWICZ: I guess I would pose the question differently and say, when is there not a right time for high-efficacy therapy? And, you know, I think there is, there are multiple lines of evidence to support this. You can see in this slide here, something that we've known and that's been again seen in a number of studies. This idea that when people have more attacks in the first two years, they're apt to accumulate disability more over the long term, and when there is a shorter inner attack interval, they're more apt to accumulate disability over the long term.

But of course I think that there are many different studies along these lines and I would even say that there are registry studies now suggesting that patients that are treated with higher-efficacy agents earlier do better over the long term, which I don't think is really surprising based on good quality phase 3 studies that we have over two years, that that benefit would extend over the longer term. But there are now, you know, some papers published showing this.

DR. LUBLIN: So there is this issue of what we can see and determine early on, when there may not be a lot going on. And, Tim, you alluded to this already, in terms of underlying damage that is not necessarily perceived. You want to discuss that a bit more?

DR. VARTANIAN:

So clinically, you know, there is disease activity happening, but it's clinically sometimes very difficult to see and imaging doesn't pick up everything. It picks up large lesions, contrast enhancing lesions but it does not pick up this smoldering disease of activity and we're beginning to understand that that disease activity is, you know, is driven by a number of immunologic mechanisms that we have therapies for and often what we see is that the high-efficacy therapies are impacting that immunopathology to a much greater extent than our modest efficacy therapies.

So as I think Jamie pointed out, it's really no surprise that we're seeing our best results when we start with a high-efficacy therapy, and it's also no surprise that we see better results when we start treatment earlier.

Part of the same process, limiting the path of physiology from taking hold and expanding and causing further injury to the CNS.

DR. LUBLIN: Okay. So thank you, everyone, for sharing your perspectives.