The Role of S1P Modulators in Multiple Sclerosis Management

EP: 1.Overview of Multiple Sclerosis

EP: 2.Cognitive Decline Presentation in Patients With Multiple Sclerosis

EP: 3.Cognitive Dysfunction Clinical Assessments for Multiple Sclerosis

EP: 4.Initiating Conversations Around Cognitive Health for Patients With MS

EP: 5.The Role of Imaging in the Assessment of Brain Health and Cognition

EP: 6.Brain Health Assessment Challenges in MS

EP: 7.Overview of Brain Atrophy Data and Cognition Research in MS

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EP: 8.The Role of S1P Modulators in Multiple Sclerosis Management

EP: 9.Efficacy and Safety of S1P Receptor Modulators in Multiple Sclerosis

EP: 10.Impact of S1P Modulators on Brain Volume Measures in Multiple Sclerosis

EP: 11.Safety Considerations and Monitoring for S1P Modulators in MS

EP: 12.Using Neurofilaments as a Biomarker in MS

EP: 13.Treatment Sequencing in Patients With Multiple Sclerosis

EP: 14.Emerging Therapies and Future Directions in MS

EP: 15.Practice Pearls for the Management of Multiple Sclerosis

Stephen Krieger, MD: Earlier, Dr Jacqueline Nicholas, you said, you think of cognition as a motivator, in a sense, to help get people to agree to be on therapy, and understand the rationale for disease-modifying therapy. I think it's a good moment to think about disease-modifying therapies, and particularly those that have good data for preventing atrophy and preventing gray matter [GM] atrophy, which we think of as being pretty closely tied to cortical function and cognitive function. Let's talk about the sphingosine-1-phosphate receptor [S1P] modulators. There is now a whole class of disease-modifying therapies for relapsing MS [multiple sclerosis], inaugurated in 2010 with fingolimod. It is incredible to think that that was a dozen years ago, but with that, it's been an expanding class of medicines that really has changed a lot of things about how we approach the disease. Let's talk a little bit about that. Dr Crayton, maybe you can give us a quick overview of the class of S1P receptor modulators. What do they have in common? What are some key differences amongst them? And then, we'll go from there.

Heidi Crayton, MD: I think that the S1P modulators coming into the market was certainly a game changer. It was the second biggest thing after we had the first monoclonal enter the marketplace. I think it was very liberating to think that we could have people switch to an oral therapy. That was life-changing for a lot of people. But it wasn't just convenience; I think that all of us were really surprised with the efficacy. The more experience I had with utilization, I was even more amazed with efficacy and lack of patient complaints. We'd been so used to telling people that our medicines were going to make them feel worse than their MS sometimes, and it was nice to not have that situation. I think that it's important that when we talk with patients about any product that we are looking to put them on, it's important to talk about MOA—mechanism of action—so I do mention a quick, little sentence about the way that S1P receptor modulators work is by sequestering them—keeping them kind of in time-out—and people that have children understand time-out. To keep them tucked away and they go to lymph nodes until they get their marching orders and S1P receptor modulators say “Stay put because we can't trust you. If we let you run around, then you're going to misbehave.”

They understand that, and I think that we have these nuances with the various products that are in the market and the class. We have different rates of elimination. They're all oral therapy once a day, some require actually having in-person monitoring for a reduction in heart rate and a little bit more to do prior to getting somebody on drugs. As we've gotten into other incarnations with the more recent ones, there's a little bit less to do, and it's just a little bit less burdensome to get people on medicine. I know that they like to differentiate themselves quite a bit but ultimately I think that the data, points us in the direction of efficacy and I think that that's really when we started to really focus on gray matter atrophy, was with S1P receptor modulators. We talked about whole-brain atrophy for quite some time. It was a difficult conversation, and it didn't make sense. Like Dr Nelson said: there was this mismatch. You saw people that had amazing degrees of atrophy who functioned just fine. Thus, I think that sometimes it was not really thought of as a legitimate concept. I think sometimes people thought of atrophy as a marketing tool. I think that now we really have come to understand that it is real, but I think that S1P receptors have really brought that to the forefront of the conversation, which is great.

Transcript Edited for Clarity