Impact of S1P Modulators on Brain Volume Measures in Multiple Sclerosis


Dr Flavia Nelson comments on the impact of S1P modulators on brain volume measures; highlighting thalamic atrophy and its correlation with brain volume loss in MS.

Stephen Krieger, MD: To think a little bit more about the research and the imaging research that relates to modern S1P [sphingosine-1-phosphate] modulators, can you tell us a little bit more about work looking at ozanimod or other S1Ps with volumetric measures, gray matter volumes, things of that nature? I think that's been a hot topic.

Flavia Nelson, MD: Yes, of course. As you all mentioned, when fingolimod was FDA [Food and Drug Administration] approved, we had data on a decrease in brain atrophy or brain volume loss over time. Then, when the second S1P came out—siponimod —we also had some data on that, but as you said, the patients were more advanced. Then, more recently, with the approval of ozanimod, we actually had data that we've never had before. Just to give a little bit of a background, we used to think of brain atrophy as the best marker of cognitive impairment. Now, we've been looking at thalamic atrophy. Thalamic atrophy seems to be better correlated with cognition as well as with disability and is also more sensitive and sometimes present early in the disease. The 1 thing that was seen in the clinical trials from ozanimod—aside from the effect of ozanimod on cortical gray matter, which was beneficial—was a decrease in thalamic volume loss, which to me is significant because I feel more comfortable prescribing it in a patient in whom I see some overall atrophy, because again, thalamic atrophy also correlates with overall or whole-brain atrophy. Even if I cannot measure whole-brain atrophy or thalamic atrophy—because, as you know, it's difficult to have those numbers in the clinic—I feel comfortable because these medications are not only effective, they have a very good safety profile, but now I know that I'm also preventing thalamic atrophy, cortical atrophy, and potentially cognitive impairment—or at least we also have some data on a decrease in scores for cognitive information processing speed using the SDMT [Symbol Digit Modalities Test]. I think that that data is significant, important to keep in mind, and I'm just happy that we have it.

Stephen Krieger, MD: I think these are great points and it all sort of speaks to the more modern and more comprehensive assessment of cognitive function; brain volume, the subcompartments of brain volume, including deep gray matter. As you said, thalamic volume is going to be more and more key. You made a nice point, which is that even if you can't measure it yourself in practice, knowing from the aggregate data that that effect is there does provide a real justification for that treatment strategy.

Transcript Edited for Clarity

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