Current Series: Multiple Sclerosis: A Disease of an Immune System Gone Awry

Clyde E. Markowitz, MD: As practicing clinicians, we have to come up with an idea of what the best treatment is for an individual patient. In doing so, we try to make a determination. We look at their clinical symptomatology and how they presented. We look at their MRI [magnetic resonance imaging] scans and try to make a determination: How’s this patient going to do in the long term? Is this somebody who I’m very worried about, who’s going to have a very active progressive course from the get-go? Or is this somebody who looks more typical of a mild to moderate patient with some element of disease activity, but not somebody I’m really worried about. We make those determinations right up front.

With that, we then factor in the patient's concerns or lifestyle issues: They may be thinking about a family at some point in the future. There may be issues related to their job. There may be issues with the side effect profile. What kind of day-to-day experience are they going to have to deal with? Are they going to remember to take the medications? And all of these things. You’ve got that piece of it.

You’ve got my piece, which is the piece called “I’m worried about you or I’m not.” You also have the insurance piece that comes into that conversation that says, “Well, we’re not going to let you do any of those.” But at the end of the day, we try and factor in all of that and make a determination on what’s going to be the right treatment for this individual patient, with the idea that we may have to change as we go. That’s always a possibility.

Patricia K. Coyle, MD: When I think about the disease-modifying therapies for MS, I actually put them into 3 categories. I have the needle injectables, such as interferon beta and glatiramer acetate. I have the 3 oral agents, and then I have the infused monoclonal antibodies. If we focused just on the oral agents and the monoclonal antibodies with regard to adherence and adverse event profiles, certainly the oral agents gave you the option of not needing to use a needle injection, and that’s a quality-of-life issue. It’s much easier to take a pill or a capsule than to inject yourself. Of course, this puts the onus on taking the medication at home. But certainly, you lose the need to inject, and I think that that’s a positive.

When I look at the intravenously infusible agents, the monoclonal antibodies are the high efficacy agents. Even if they’ve not been compared head-to-head, they have high efficacy. As a group, they have greater efficacy than the oral agents, but they may carry somewhat greater risks. And 2 of the 3 monoclonal antibodies certainly have an RRMS [relapsing-remitting multiple sclerosis] program in place that you need to follow. The thing about the infusible monoclonal antibodies is that you need to go to an infusion center, so you know there’s adherence. You know the patient is taking the medication. There’s absolutely no issue in that regard.

Every DMT for MS has slightly different adverse events. You need to bore it down to the individual. What are their comorbid issues? How do they view a treatment? What are they willing to tolerate or not? But I think the big differences between the oral agents and the IVs [intravenous therapies] are in the efficacy and the ease of taking it, and there’s absolutely guaranteed adherence when you need to go to an infusion room.

Fred D. Lublin, MD: All of the approved agents are efficacious. If you look at the numbers, they’ll tell you what the percentage reduction was in annualized relapse rates. It can be anywhere from the 20% range to 30%, 50%, or 60%. You can’t compare them. It’s a fundamental error to try and compare the results of one clinical trial to another clinical trial. This happens with marketing, but the only way you can say you’re a percentage better than somebody else is if you were in the same study.

Even if you design 2 different studies identically, you still can’t compare them because every study is a universe unto itself and unique. There are always factors there that you can’t control, no matter how hard you try, that can alter the results. If you want to know if one drug is better than another, look at them head-to-head. As I mentioned earlier, we don’t have those kinds of data for our most effective agents, and we almost surely never will, because they’re long, complicated studies. If they’re both very effective, then it will take a long time and a lot of patience to show a difference between them.