Clinical Implications of Latest Therapeutic Data for Cognition in MS

Stephen Krieger, MD: Now that we've started to get a sense that medicines like S1P modulators and ozanimod (Zeposia; Bristol Myers Squibb) can improve cognitive function, or certainly prevent its worsening, better than our older medications, it's been interesting to look at other modern disease-modifying therapies through the same lens. At this meeting, data from the ofatumumab (Kesimpta; Novartis) trial, the ASCLEPIOS trial (NCT02792218), looking at ofatumumab versus oral teriflunomide (Aubagio; Sanofi), also showed a similar cognitive profile. More people in the ofatumumab treatment arm achieved improvement on cognitive function than those who had been randomized to teriflunomide. And again, it was consistently seen that a greater percentage of patients were improving than worsening. It speaks to the power of higher efficacy therapies against both an older oral and, of course, an older platform injectable like interferon in the ozanimod trials. I think it paints a little bit of a optimistic picture of what we can hope for with modern MS therapies in the cognitive domain.

One outcome, I think, for the field, from the idea that disease-modifying therapy can potentially stabilize or even improve cognitive function in MS is that we really need to be looking for it. One could understand in an earlier era, when the feeling was there's nothing to do about it—which was probably not true even then—but now there's really potentially something that we do about it, not just through brain health measures, but through disease-modifying therapy itself. The onus really becomes on us to take it seriously, look for it, quantify cognitive function, and use that as an outcome for what we're expecting our disease-modifying therapies to do. I also think it can be a useful motivator for our patients. How many times as a clinician have I encouraged people to change their diet and exercise and go to physical therapy or occupational therapy? I think if we wrap that into the notion of improving brain health, having both the disease-modifying therapy and these techniques to boost reserve, I think that that can be inspiring for people. It can give them a reason, again, circling back to the idea that cognitive function and cognitive ability are very closely tied to identity—people care about it. And I think that means we should care about it, and we should be careful about looking for it and trying to improve it.

I think the big takeaway for me has been to assess cognition, ideally, at baseline when someone is diagnosed with MS or joins my practice to get a snapshot of where we're starting from. That's our metric, it's our yardstick for where they're at and where we're going to try to get them to improve from there. I also think it almost doesn't matter what cognitive test someone uses, whatever they can fit into their practice. If it's as short as the SDMT, great, you capture that—it's a good starting point. If you have a lot of findings on the SDMT, that could prompt referring a patient for a more formal neuropsych evaluation, or one of the computerized batteries. For places that have neuropsychologists or a neuropsychology program, I think bringing them on board to be involved in the care of people with MS is pretty essential. And to not be nihilistic about it, to think this is something that we can do a lot about, and that if we have only better and better therapies that can help to manage this symptom and improve it, we need to have that data on hand to guide us for the future.

We all know how to take a history of with our patients and learn about them. But my favorite question to ask—this would be my advice for someone thinking about how can I incorporate assessment of cognitive function into their MS practice—is, for someone who's employed, "Have you had your performance review this year?" Have you had your performance review? It opens a little bit of a window into what someone's life is like in their abilities or outside of the office visit. I might not see evidence of cognitive dysfunction just in the routine visit. But if I find out by asking that question that the person is struggling at work, they can't meet their deadlines, they can't multitask efficiently, they're making mistakes, they're forgotten things, they've been reprimanded—that tells me something about what's happening that I might not have been able to see in my clinical exam. It gives me a reason to move forward to look in more detail at their cognitive function. If, on the other hand, someone tells me that they've been promoted, they've been given more responsibilities, things are going really well—that's great. That gives me a sense of where their baseline is now and all the more of a mandate to try to keep them functioning at that high level.