Monday, May 12

Mark S. Freedman, MD, MSc & Patricia K. Coyle, MD

DISCUSSION: Treating Multiple Sclerosis in 2013

Mark S. Freedman, MD, MSc: Hello. I am Dr. Mark Freedman, Professor of Neurology at the University of Ottawa and the senior scientist at the Ottawa Hospital Research Institute in Ottawa, Ontario, Canada, speaking to you from the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in beautiful Copenhagen, Denmark. I am here today with Patricia Coyle, Vice Chair of Clinical Affairs and Director of the MS Comprehensive Care Center at Stony Brook University in Stony Brook, New York. Welcome, Pat.

Patricia K. Coyle, MD: Thank you, Mark.

Dr. Freedman: It's a great meeting. There are many new developments. Could you tell us about some of the new medications that have been approved in the past few months throughout the world, and what this means for multiple sclerosis treatment?

Dr. Coyle: Itis becoming very cluttered. Alemtuzumab has just been approved in the European Union and is likely to be approved in the United States in the next couple of months. We also have 2 new oral agents that were approved within the past year in the United States: teriflunomide and dimethyl fumarate. We are learning more about these agents and thinking about how we are going to use them. They are quite different.

Dr. Freedman: Let's start with the 2 new orals. Where are you placing them in the cascade of treatments? Are these first-line agents?

Dr. Coyle: They are first-line agents but they are a little bit different. Teriflunomide has a category X pregnancy rating, so you might favor that drug in patients who are not interested in pregnancy. It is an extremely well-tolerated agent; it has the perception of not being dynamite in reducing relapses, but it is associated with some very good disability and MRI data. Dimethyl fumarate came on the market with a big bang, has good data, but is a little bit dicier with respect to the gastrointestinal side effects, which are a little more than we expected. You need to play around with it and prepare patients for that.

Dr. Freedman: And we now have fingolimod. We are looking at many congeners of fingolimod with other sphingosine 1 phosphate (S1P) receptor agonists not yet on the market. Have we learned anything more about fingolimod now that it has been out there for a year or two?

Dr. Coyle: We have refined our knowledge about the cardiac adverse events, and the manufacturer has made a label change that makes it somewhat more restrictive with respect to medical history, comorbid conditions, and awareness of how drugs can interact to cause conduction issues. We are more careful about using that drug in the small group of patients with multiple sclerosis who have significant cardiac disease.

Injectables Become More Convenient

Dr. Freedman: What about the injectables? They haven't fallen off the side of the earth yet, but some developments are changing some of the injectables. What are those?

Dr. Coyle: A couple of interesting developments should make injectables easier to use. Glatiramer acetate, for example, has been studied in a double dose of 40 mg subcutaneously 3 times weekly instead of 20 mg daily; and with interferon beta, they now have a pegylated subcutaneous form that would be given every 2 weeks, so, much less dosing. We are waiting to see whether they are going to be approved. It is highly likely that we will have them in a year or so.

Dr. Freedman: Let's return to alemtuzumab, an exciting agent. Is it a first-line drug?

Dr. Coyle: This is a real issue. I view alemtuzumab as an induction strategy. The question is, would you use it in a treatment-naive patient? Certainly in the trials it was used with very good results, but I am a bit leery of doing that. It would be easier to justify for a patient who is clearly failing other treatments, and then you might move to it very quickly.

Dr. Freedman: It is very attractive to patients, given its annual administration schedule. Patients take it only once a year, and then they don't have to take anything for the full year. Why wouldn't you want to use that first-line? What's the downside?

Dr. Coyle: First,there is up to a 30% rate of thyroid disease, a small risk for immune-mediated thrombocytopenia which must be monitored and that might need to be treated, and a risk for immune-mediated renal disease, which can be severe although extremely rare. We don't have huge numbers of patients who have been treated multiple times with alemtuzumab to have a good sense of whether there might be some long-term problems associated with it.

Sequencing the Available Drugs

Dr. Freedman: Let's think about the drugs that we do have. The injectable natalizumab has been on the market for a little while. In come these new oral agents, perhaps with some different mechanisms, and then the powerhouse alemtuzumab. Do we have to consider the order in which we use them, or if you gave an induction therapy with alemtuzumab and the patient stabilizes for a couple of years, would you want to use natalizumab after that?

Dr. Coyle: There is concern about staging. One of the risk-stratification factors for progressive multifocal leukoencephalopathy with natalizumab is previous immunosuppressive therapy. Alemtuzumab would count as immunosuppressive therapy. So if you use alemtuzumab before natalizumab, you have put patients who are JC virus-infected at higher risk.

Dr. Freedman: We are excited about new therapies. We are not certain where they are going to be positioned, and we are not sure yet, as we start to use them, what risks will evolve, but it is always nice to expand the tool chest. That is what is so exciting about coming to ECTRIMS and learning about all of these wonderful new treatments. Thank you very much for your attention.