The Future of Treating Multiple Sclerosis

Fred Lublin, MD: The last segment we’re going to discuss is looking ahead to the future. First, Sven, talk a little bit about the potential for biomarkers.

Sven Meuth, MD, PhD: There are a number of new biomarkers published and evaluated in clinical trials. Some of them are quite interesting. Maybe we can discuss a bit concerning NfL [neurofilament light] because there was a huge body of evidence. NfL is interesting because it is a protein, a neurofilament light chain. It is a protein expressed in axons, so it indicates how much tissue is at risk or already degenerating. All of the data presented so far indicate that it is also an inflammation driven biomarker. This is a problem that lies in the disease because, if we have inflammation triggering neurodegeneration, maybe it will not be possible to identify a marker indicating pure degeneration. This is why we have the correlations with NfL and Gad-enhancing lesions or also number of relapses. If we have a stable patient with the clinical readouts, like relapse activity and MRI, this can give us an additional hint if this patient is stable as indicated by the classical readouts or if they have to be treated in a different direction. 

These new biomarkers might also help to develop new study designs; for instance, the INFORMS trial where fingolimod was tested in patients with primary progressive MS [multiple sclerosis]. There have been some effects that could not be detected due to the readout parameters because how much progression do we need in such a clinical trial over 2 or 3 years to make a difference with a disease-modifying therapy? However, if we would enter the field with such a study that might be biomarker driven, the responders may be indicated by a reduced amount of NfL, even in this cohort. Then, maybe we can continue a study for a longer period. There might be a reason why these biomarkers could really help in clinical practice and for study design. A second biomarker I’m interested in is OCT [optical coherence tomography] because this is available. It’s a fast measure, and it might also help to depict near degenerative aspects in our patients. This is why I picked NfL and OCT, but if you have additional markers, I’m happy to hear about them.

Fred Lublin, MD: Yes, those are good ones. Patricia, what are you seeing changing in terms of managing the disease for the future?

Patricia K. Coyle, MD: I would mention 3 areas. Number 1, there is a major focus on the neurodegenerative component of MS, progressive MS, and CNS [central nervous system] repairs. We need strategies for progressive MS, neurodegeneration, and we need strategies for CNS. Secondly, artificial intelligence, machine learning applied to neuroimaging. What we’re finding, unfortunately, is that the computer is better at reading and analysis than the human being, and we’re going to see some major breakthroughs as we apply machine learning, artificial intelligence to analyze MS. Finally, wearable devices at home that can look at activity that are picking up transition to secondary progressive MS before the patient realizes it, at-home computer type devices. COVID-19 [coronavirus disease 2019] has pushed us into telehealth: all of us. We’ll see a burgeoning and selective use of that, more computerized ways to treat MS, and more home devices to monitor this disease and get a better handle on it.

Fred Lublin, MD: Excellent. Wallace, what advice do we have for our colleagues out in the community?

Wallace Brownlee, MBChB, PhD, FRACP: Fred, one of the biggest challenges facing all neurologists treating MS at the moment is this dizzying array of treatment options that we have available. Increasingly, as we’ve heard already in this panel discussion, this concept of first, second, third line is maybe not the right way to be going. We have to try and tailor our therapies to the patient, depending on the disease profile, the number of relapses, what their MRI is looking like, what the level of disability is, their comorbidities, and desire for family planning. One unresolved question in the MS field is this: Are we better to take an escalation approach to therapy, or should we be hitting patients hard with more effective medicines early in the course of the illness?

Now, increasingly over the last couple of years, we’ve had more and more observational data. For example, from the MS base suggesting that earlier use of highly effective medications is associated with a more favorable prognosis and lower risk of developing SPMS [secondary progressive multiple sclerosis] in the future. Hopefully we’re going to get some more definitive answers to this question from the ongoing phase 3 studies DELIVER-MS and TREAT-MS with patients being randomized to either an escalation or early intensive treatment approach in a rather pragmatic way that should be quite generalizable to everyday practice.

Fred Lublin, MD: Well, thanks, all of you, for this rich informative discussion, Dr Brownlee, Dr Coyle, and Dr Meuth, and thank you again to our viewing audience. We hope you found this NeurologyLive® Peer Exchange discussion to be useful and informative.