DMT Adherence and Routes of Administration in MS


Mark S. Freedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC, comments on the different modes of administration of DMTs in MS, focusing on oral DMTs.

Ahmed Zayed Obeidat, MD, PhD: We can also talk a bit about the routes of administration for medications. We have several ways of administering DMTs [disease-modifying therapies] to patients. What’s your take on them, and how do you discuss this with patients?

Mark S. Freedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: When the first drugs came out, they were injected. Before that everybody only took pills or got IV [intravenous] infusions. But this notion that you could inject yourself with something, people were very unsure and said, “I can’t do that.”

Ahmed Zayed Obeidat, MD, PhD: Definitely.

Mark S. Freedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: The first therapies were by injection, you either take this or you take nothing, so they took it. Fortunately, some of the drugs that we’ve developed are still oral, but others are not. Because most biologics break down in the acid of the stomach, you have to either inject it intramuscularly or subcutaneously, or intravenously, and it’s the only way to get them in. Compliance could be an issue with that, meaning the patients either don’t do it right, or they skip injections, and then they’re not taking the drug the way they’re meant to take it. Clearly the oral drugs leave themselves as the most convenient way of treating MS [multiple sclerosis]. But unfortunately, not all the drugs are available in oral formulations.

Ahmed Zayed Obeidat, MD, PhD: That’s correct.

Mark S. Freedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: We need to be able to convince our patients that if they need one of the drugs that’s not oral, we somehow spend a little more time trying to address this adherence and ask, “What kind of issues are you having? What can’t you do it? Are you having adverse effects? Maybe you’re not doing it right.” This is where we need a lot of ancillary help from patient support programs, nurses, or other people who can counsel the patients on how to use the therapy.

Ahmed Zayed Obeidat, MD, PhD: In your clinic when the patients come in and talk to you about their disease and how they’re doing, how do you assess adherence? If they are on an oral therapy, what do you ask them?

Mark S. Freedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: It’s funny. I remember I was sitting with my [patient] last week, and I said, “So you’re taking,” whatever it is, and I turned to them, and I go, “And you’re taking it?” I get this look.

Ahmed Zayed Obeidat, MD, PhD: Sometimes….

Mark S. Freedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: “OK, so you’re not, are you?” [The patient said,] “I was on holiday, and I forgot them at home.“ Then you find out that they’re not taking it. Now some agents allow you to do a test, so you could find out. If you think about drugs like teriflunomide, one of the adverse effects of teriflunomide because it works on pyrimidines, uridine is one of the targets. If you measured urate in your patients, it goes down. They have to have their regular blood work anyway every 6 months, so you could look and see if the uric acid, the urate is down, then they’re taking the drug.If it’s not, you go, “Are you taking the drug?” When you’re on a B-cell depletion therapy….

Ahmed Zayed Obeidat, MD, PhD: You measure the B cells.

Mark S. Freedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC If you measure and there are no B cells, you know they’re taking the drug. If the B cells are normal, it could be something else, but if the B cells are normal, maybe they’re not taking the drug. You can monitor it, but otherwise you have to ask the patients.

Ahmed Zayed Obeidat, MD, PhD: It’s real life, people can miss a few medications, days, and things like that. But then we have to make sure, counseling is very important, because these medications are as good as you take them. If you don’t take them, they are not going to work.

Mark S. Freedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: I think a big problem is the younger folks. They don’t quite get why they’re taking the drug. They think, “I had my attack, and I’m fine. I can go to the gym, I work out, I play hockey every week, I do this or that. I’m feeling good, why do I need to take that stuff?” They don’t get the sense that this is preventive. They think they don’t really need it, and then they get lax, and then they have an attack. Then you find out that it’s not that the drug didn’t work, it’s that you weren’t taking it. So it’s a very important question. If you have a patient with breakthrough disease, the first question should always be, “And you took the drug exactly the way it was supposed to be taken, yes or no?” If yes, then we have to deal with another reason for breakthrough.

Ahmed Zayed Obeidat, MD, PhD: Exactly. That then determines there is a failure of the medication if they’re taking it correctly. Since we touched on adherence and the patient’s involvement in this process, the guidelines for disease-modifying therapies…there are AAN [American Academy of Neurology] guidelines, there are other guidelines also. They focus on general concepts. They would not tell us use this first, this second, but they focus on general concepts in the treatment of MS. One of the concepts that always comes up is, we counsel patients, we say this disease-modifying therapy is used to prevent new disease activity and hopefully slow progression, but it’s not meant to help symptoms. It's that key education point when we talk to patients that, “Yes, when you take this medication you’re not going to feel different.” That’s sometimes when I see patient’s say, “I’m not feeling better, I’m not going to take this medicine.”

Mark S. Freedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: You’re right.

Ahmed Zayed Obeidat, MD, PhD: That’s where we have to really invest in the education ahead of time. They have to know that.

Mark S. Freedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: They have to have realistic expectations as to what this is going to do for them. “I’ve taken this for 3 months, and Dr Ahmed, my eye is still twitching.” Or, “I still have weakness in my leg. This stuff isn’t working.” That’s never what you promised them, that they would recover any of this stuff. You have to reinforce that each time you see them.

Ahmed Zayed Obeidat, MD, PhD: Because automatically patients think, I’m taking a medication, I should get better. But in MS, it’s a little different, where you take a medication so hopefully, you’re not going to get worse, and some people will plateau. Some people will think about it.

Mark S. Freedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: Let me jump on what you just said. Theoretically, you won’t get worse. That is not, unfortunately, what happens. Especially when you’re talking about therapies for progressive MS, that’s not what we’re talking about today, but then, the patients really don’t know if the medicine’s working. Even in the trials, the patients got worse. They just got worse a lot slower than the patients who didn’t take the drug.

Ahmed Zayed Obeidat, MD, PhD: Yes, slower.

Mark S. Freedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: We still see some of that in relapsing-remitting MS. There may be some people who get slowly worse. We don’t like seeing that. There may be an opportunity to do better for those individuals. I think when you see it early, you’re going to try to change pace.

Ahmed Zayed Obeidat, MD, PhD: Act on it, or something. Yes, this progression independent of relapse activity concept, and those kinds of things that people are looking at now.

Transcript edited for clarity

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