Current Series: Advances in Early Treatment Approaches in Multiple Sclerosis

Fred D. Lublin, MD: I do have a question for you guys. What do you think is the modern conversion rate to secondary progressive MS [multiple sclerosis], in the treatment era?

Patricia K. Coyle, MD: Well, I don’t think there is any question that it’s going down. If you look at the data from the EPIC study, from University of California San Francisco Medical Center, where we talked about within 10 to 15 years this high proportion converting from relapsing to SPMS [secondary progressive multiple sclerosis], it’s well less than 20%. Part of this is likely the treatment era. Part of it may be that the MS disease process is moderating with time, maybe environmental changes. But I think we’re seeing a smaller proportion of patients move from relapsing to secondary progressive disease over fixed time periods of 10 years and 20 years than what’s been reported historically.

Stephen C. Krieger, MD: One of the challenges when communicating to our patients what the goals of treatment are is that all over the internet it is still written that 80% of MS patients with relapsing disease will develop secondary progressive MS in let’s say 10 years. And that’s very old data, from the pretreatment era, but they still exist in perpetuity on the internet. And I think one of the things that I find myself trying to do is to explain what you just said, that the likelihood that someone being diagnosed with new relapsing MS in 2020 will develop secondary progressive disease in that classical way of insidious worsening of physical disability in 10 years, that certainly is not 80%. It’s much lower, and that’s progress and it’s optimistic, but I think we have to try to convey that to our patients as a goal, but also something that they can realistically expect.

Amit Bar-Or, MD, FRCP:            We nowadays refer to “the new MS,” and I think this is a very important concept for patients to hear, that being diagnosed with MS today is not the same as having been diagnosed with MS certainly 10, 15 years ago. And the hope is that we are modifying the course meaningfully. We don’t have as much data as we’d like, but I suspect it’s not just a change in the MS natural history nor just the lead-in bias of making earlier diagnoses and then a longer lag time to emerge as secondary progressive, but an actual change in the natural history of the disease with a treatment that is limiting the conversion to progressive disease.

Peter A. Calabresi, MD: I agree. I think to answer your question that we probably cut the progression rate in half is my experience in reading the literature. But I do what you do. With my clinic notes I comment whether they’re having relapses or new MRI [magnetic resonance imaging] lesions. But I think there’s too much emphasis based on these somewhat artificial categories. Patients have it in their head that they’re relapsing, and then one day they come into the office and you tell them they’re progressive, and that means now they’re untreatable or they’re going to end up in a wheelchair. I think that does a disservice to the patient. So I talk to them about inflammation and drivers of progression and try to hit a positive and optimistic note that we have a lot of treatments that actually can impact these processes, but there’s still obviously an unmet need as well.

Stephen C. Krieger, MD: I think that patients think that the categories are akin to a cancer stage, something where there’s a very specific prognostically worrisome thing that either just happened or is about to happen. I’ve worked on something called the topographical model, which animates in a sense between these categories. It shows it more of a continuum over time. And it speaks to the idea of the categories themselves being really a time-locked phenomenon. It’s making sure that we’re looking for evidence of disease activity and that we’re looking for signs of progression so that we can address those things.

But I think you’re right. I try to talk to the patients about treating MS. I haven’t used the phrase “the new MS,” I like that. But treating MS as a whole and that our aspirational goals are to prevent disease activity and forestall progression perhaps forever.

Patricia K. Coyle, MD: I think we also realize the importance of a wellness program and boosting CNS [central nervous system] reserve and identifying comorbid factors and making sure they’re treated. And I describe that as almost a separate treatment for MS. I think that’s a very important coupling of the use of a DMT [disease modifying therapy].

Peter A. Calabresi, MD: That’s a really excellent point.

Fred D. Lublin, MD: Yes, discuss that a little more, what the concept is because wellness is a very important one.

Patricia K. Coyle, MD: There are increasing data, there are lifestyle choices that can hurt MS or help MS. You don’t want to be smoking. You want to be in optimum body weight. You want to be eating healthy. You want to have good sleep. You want regular physical exercise. We’re finding that’s promoting brain health, central nervous system health. You want intellectual stimulation, social stimulation. These are really positive. These help people age better. And if you have a disease like MS that targets the CNS, this is going to promote CNS health, you’re going to weather MS better. So I’m really speaking about that as a separate treatment that they need to follow.

Fred D. Lublin, MD: I do think that, back to progressive, that’s a term that scares people. Because very often, look at people in the first attack, and they’ll say, “Do I have the progressive form?” I also want to give at least 1 caveat for these clinical courses, and that is, they’re descriptive. And our hope is, I don’t think we’re going to have it for the next time we meet to discuss these, but that we actually come up with biological bases for this. Because right now we don’t have a biomarker—either a fluid biomarker, and certainly not an MRI biomarker yet that could distinguished between CIS [clinically isolated syndrome] and primary progressive, or anything in between.