Andrew N. Wilner, MD; Mark S. Freedman, MD


October 23, 2013

Editor's Note
While onsite at the European Committee for Research and Treatment in Multiple Sclerosis (ECTRIMS) 2013 annual meeting in Copenhagen, Denmark, Medscape correspondent Andrew N. Wilner, MD, spoke with Mark S. Freedman, MSc, MD, from the University of Ottawa about new Canadian recommendations for the management of multiple sclerosis (MS).

New MS Treatment Recommendations

Dr. Wilner: Dr. Freedman, I understand that there are some new guidelines for the management of MS from Canada.[1]

Dr. Freedman: We don't use the word "guidelines" because that tends to impose a notion of a standard of care that, if not met, has legal implications. So we tend to refer to them as recommendations. Everyone is doing something similar now, and the theme is that we have developed a power chest of drugs and treatments that can make a difference in patients. The old notion of just saying, "Here, pick one of these and stay on it for a few years," without knowing what to do next, has, I think, gone astray.

Instead we have a methodology -- a logical approach in an effort to try to find patients who very early on declare themselves as "poor responders" to whatever the treatment is. Unfortunately, MS is still a bit of a hit-and-miss business. We have many different drugs, but you can't tell who is going to respond best to any drug in particular. If that was possible, it would be wonderful.

We don't have that, so you choose a drug according to where the patient is in terms of his or her disease. If the patient has an aggressive-looking disease, you might want to go to a riskier drug that has the potential of greater efficacy but will work faster. Not all patients are the same. If you feel that a patient is at an early enough stage, you would initiate with what people refer to as "platform drugs" or "first-tier drugs," which are well-established and safe.

MS Drugs: Up and Down the Tier

Dr. Wilner: For example, what are the platform drugs?

Dr. Freedman: You are not going to beat the safety records of interferon and glatiramer acetate. So you initiate a drug and watch the patient with some method to evaluate response to therapy. The recommendations describe how to monitor and measure response to therapy. If the expectation is (as we have heard from a few people) to be completely disease-free, then they are dreaming. It's an attainable goal in some people at some times, but it is more important to recognize patients who are very quickly nonresponsive to the chosen medicine and then have a mechanism to move up to stronger drugs if necessary.

Dr. Wilner: Is it true that the potency of the drug tends to go along with the increased severity of side effects? If you choose the stronger drug, it's also the riskier drug. Is that the way it works?

Dr. Freedman: No; it's not that simple. In the Canadian regimen, we have acknowledged the fact that there is very little evidence to say that one drug is better than another. Despite what you hear from various marketing messages, very few studies have been done in that respect. We will never be able to tier drugs in terms of benefit, but we can tier them in terms of the risk. There are drugs that are just absolutely über safe, and those are, unfortunately, the injectables. They represent inconvenience, but they are safe, and their safety records span almost 3 decades.

The oral agents are much more convenient, but we have limited safety data in the real world. We have lots of data from the sterile world of clinical trial patients followed long-term, and that is very encouraging. But when you throw things out into the general public, new things happen. We need to take that with a grain of salt. That is why we tier them a little bit above the injectables.

Then you get into the drugs such as natalizumab that can cause death from progressive multifocal leukoencephalopathy (PML). Are you really getting that much more from natalizumab? There is a perception out there that it is stronger, but only one study has been done. People believe that natalizumab is stronger, and there is certainly a risk. More than 400 cases of PML have occurred, and 50 people have died worldwide. Those who don't die might wish they had. There are very few good outcomes from that disorder, and patients are certainly worse off than they were to begin with. So is it worth that risk?

There are more powerful drugs such as alemtuzumab, which is now coming on the market in various places. How will it be used? People have died from hemorrhage related to the use of alemtuzumab, although it is preventable. But you are not going to use alemtuzumab as first-line treatment unless you feel that the patient has absolutely massive disease that needs control immediately. It is worth it if the drug gives us an induction therapy.


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