Advances in Early Treatment Approaches in Multiple Sclerosis - Episode 18
Fred D. Lublin, MD: We’re getting close to wrapping up. Why don’t we first talk about unmet needs for treating MS [multiple sclerosis]. Stephen, why don’t you start?
Stephen C. Krieger, MD: Well, I’ll take the low-hanging fruit here. As you said, the biotin study is using improvement as its primary end point. That’s novel because we don’t have things that fundamentally improve function in multiple sclerosis, irrespective of phenotype. Improvement remains the great unmet need. And we can go about improvement in so many different ways, and maybe other folks will want to talk specifically about remyelination or neuronal repair. But in truth, the clinical outcome, the thing that we wish to be able to tell our patients is that here is something that they can take or do that will bring about improvement.
I would also circle back, Dr Coyle, to the wellness push that you made because I also believe very much that things that people with MS can do to foster brain health and wellness, boosts their reserve, and keeps the disease under the threshold, in essence, and can probably help them in the long term. But I wish we had better data for a lot of the individual things that we believe are helpful, all the things that you alluded to, stopping smoking, body mass index, maintaining cognitive and social engagement. I would love to have data for those things, though I think that they’re really important.
Fred D. Lublin, MD: Other issues, unmet needs?
Peter A. Calabresi, MD: I think the unmet need is progressive MS in the absence of inflammation or relapses, and we’re just now starting to understand the biology that underlies the degeneration of an axon that’s been chronically demyelinated, energy starved, and understand the pathways by which the axons degenerate. I think we’re going to start seeing the next generation of therapies designed to intervene on that biology, independent of the inflammation. And I hope that that will help us to slow or arrest progressive MS.
Fred D. Lublin, MD: So repair, and neuroprotection.
Peter A. Calabresi, MD: Yes.
Patricia K. Coyle, MD: We need some biomarkers. We need a diagnostic biomarker, prognostic biomarker, disease activity biomarkers. I think that would be very helpful to define how we approach, treat, and follow MS.
Amit Bar-Or, MD, FRCP: I would add to that, biomarkers that will guide treatment selection as well and treatment monitoring because we have so many choices, and being guided by some biological insight as to how patients differ in ways that may make them better candidates or worse candidates for particular treatments, either from the efficacy or the safety standpoint. I think that the issue of repair, which of course, as expressed already, is an important unmet need, is one that is challenged by the presence of ongoing inflammation. And is that a good thing or a bad thing, and we think probably a combination of both.
And also to make a point that when we talk about inflammation, one aspect is the waves of inflammation from outside of the CNS [central nervous system] into the CNS that we think drive relapse biology. But the other is this combination of degenerative mechanisms and maybe CNS compartmentalized inflammation. And the reason to still think of inflammation in that context as well is because it may be an important contributor to nonrelapsing progressive disease, and it allows us to keep thinking of anti-inflammatory treatments for progressive disease, although inflammation by a different flavor.
Patricia K. Coyle, MD: And maybe the gut microbiome is important in MS or it’s not important in MS. That would be a very interesting question.
Fred D. Lublin, MD: OK. Any advice for our colleagues in the community?
Patricia K. Coyle, MD: Personally, I think they should align with an MS center or an MS expert because I think MS has gotten extremely complicated. And I think if they don’t treat a lot of MS and they have any issues, you can use that MS center or MS expert to help guide doing the best thing for the patient.
Fred D. Lublin, MD: I’ll highlight something you said at the very beginning, and that is checking for aquaporin-4 and checking for MOG [myelin oligodendrocyte glycoprotein] antibodies, especially individuals who have any kind of not typical, I don’t want to say atypical, just not typical presentation because we’re learning daily, especially about MOG, and I don’t fully understand yet how much is resultant and how much is pathogenic. But we’re starting to see a spectrum of antibody-mediated disorders, and this is how we’re going to pick them up. I think we ought to pay attention to it, so I think it was a good point that you mentioned.
Peter A. Calabresi, MD: And staying vigilant with the monitoring. No matter how many times you educate a patient, people forget. They get busy and they don’t do their blood tests, and we see this over and over again. And the sooner you identify liver function abnormalities or severe lymphopenia, the more you can intervene before there’s a problem.
Stephen C. Krieger, MD: I think staying vigilant for the monitoring for both disease activity and progression on our part and on the part of the clinicians in the community, so that we don’t have complacent MS care. That’s the one thing we can agree on, I think. We could debate how aggressive to be and when to be aggressive, but I think there’s no reason that we need to be or should still be complacent in the care of MS patients, not with the options that we have, not with the data that speak to the value of keeping disease activity quiet and doing so early on.
Fred D. Lublin, MD: Great. Thank you. On behalf of our panel, we hope you found this Peer Exchange discussion to be useful and informative. Thank you very much to my colleagues.