Fred D. Lublin, MD: It’s exciting that we have a start in progressive disease. But, as you say, we need to do better. What do you see coming along for progressive disease?
Suhayl S. Dhib-Jalbut, MD: Separate from immunomodulation and B-cell depletion, I think there are some new data suggesting that B-cell depleting drugs not only deplete B cells, but play a role in the results of the depletion of T cells that express CD20. CD20-positive T cells may be involved in progressive disease because they are proinflammatory. They do correlate with disease progression. There has been a recent paper or 2 showing that ocrelizumab not only depletes B cells but it depletes the CD20-positive T cells. I think that would help explain a number of things in the context of this form of treatment, including progressive disease. So it really raises the question, could those CD20-positive T cells be involved in progressive disease?
The other thing is, of course, neuroprotective drugs, channel blockers, although we have not seen remarkable results with those yet. Biotin is another thing that’s being looked at, and it would be interesting to see if the original study that showed some marginal effect would be replicated in the larger population of patients. And finally, in addition to that I would like to add that prostaglandin inhibitors may be promising in terms of treating progressive disease. There are studies going on with at least 1 drug in that context. And diet, I think, and vitamin D potentially could be important in slowing progression.
Fred D. Lublin, MD: Other thoughts?
Patricia K. Coyle, MD: Well, ibudilast had a positive phase 2 trial—a phosphodiesterase inhibitor. So we’ll see if that was pushed further.
Clyde E. Markowitz, MD: Alpha-lipoic acid has also been shown in brain atrophy studies, and may be another option.
Fred D. Lublin, MD: Another small study, yes.
Clyde E. Markowitz, MD: Statins.
Fred D. Lublin, MD: Statins, yes. So for ibudilast, I don’t think there’s a follow-on study yet.
Patricia K. Coyle, MD: No.
Fred D. Lublin, MD: Statins—Jeremy Chataway, MA, PhD, FRCP, has another statin study that’s, I think, fully enrolled now. High-dose biotin—we’ll have data around this time next year. I thought it was going to be earlier, but it’s not. It’s going to be into 2020. I’m trying to think of what else is out there.
Patricia K. Coyle, MD: Masitinib is being looked at.
Fred D. Lublin, MD: Which?
Patricia K. Coyle, MD: It’s an anti-mast cell agent. It’s an oral agent.
Fred D. Lublin, MD: OK. So that gets into this issue that folks at your center have talked about a lot. Do we need to start looking at more innate molecules? Something working within the central nervous system, which you had stressed. Because I think that would make a lot of sense in dealing with progressive disease—if the inflammation, however much is there, and the pathologists say inflammation is there through the entire course of the illness, shifts to be more localized and compartmentalized within the central nervous system.
Clyde E. Markowitz, MD: I think one of the things we are left challenged by is the fact that we use and rely on MRI [magnetic resonance imaging] as much as we do, particularly in the progressive phase of the disease where you do not see significant changes with inflammation, or new lesions on T2 or flare. And there’s probably some low-level inflammation happening that we’re not able to visualize easily on the imaging. So when we come up with a better biomarker for that phase, we might be able to come up with better treatments.