Efficacy and Safety of S1P Receptor Modulators in Multiple Sclerosis


Experts in neurology review data surrounding the role of disease-modifying therapies in preventing grey matter brain atrophy and cognitive decline.

Stephen Krieger, MD: I think you're right. I think with fingolimod, originally, there was a recognition that that agent and its mechanism could slow down brain volume loss; it didn't always correlate with disability for the reasons we've talked about. I think it was when ozanimod was added to that conversation that in the data from those studies was the focus on gray matter as you said—kind of homing in on that a little bit. Another differentiator I think is worth mentioning is the siponimod data, which, unlike the others, was from a study performed in an older population with more progressed MS multiple sclerosis. That study was actually/ostensibly a secondary progressive MS study. I think the data was a bit different, although it's been approved for relapsing forms of MS like the others. Dr Nicholas, do you want to talk a little bit more about some of the distinctions that you have observed as this class of medicines has matured and how you're thinking about using them in practice now?

Jacqueline Nicholas, MD: I think one of the really important distinctions has been the impact on the absolute lymphocyte count [ALC]. With fingolimod in the clinical trials program, we had to stop treatment if the ALC went below 0.2. One of the challenges that I’ve found over time is that some of my patients on daily dosing with fingolimod will drop below that consistently, and in the current era, we are very concerned about potential risks for infection that may be associated with that. One of the favorable attributes, for instance, for a medicine like ozanimod is that the ALC on average is much higher, and I would say that we see it as also a bit higher with siponimod as well as ponesimod. That's been a nice characteristic that in our practice we've tended to move a bit over towards those. I think another differentiator when we look at the data is that we have a rich dataset in pediatric MS with fingolimod. I think that has moved the care of pediatric forward significantly where many neurologists understandably were a bit fearful to use something that they potentially felt was riskier in this patient population and these individuals developing MS in childhood could ultimately face a much greater level of disability over time. That data that came and showed its high impact in pediatric MS has been exciting, and it's been something that's allowed physicians in my practice to have those conversations with parents that this was studied in that population and it was incredibly effective.

Stephen Krieger, MD: I think that's a great point. Even for those of us who don't take care of pediatric patients in our own practices, the idea that S1P [sphingosine-1-phosphate] receptor modulators— fingolimod in particular, but as a class—are safe enough to use in kids, I think has kind of moved the needle a little bit towards how we understand the overall beneficial profile of the drugs and their very reasonable safety profile.

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