Fred Lublin, MD (FL): I am Fred Lublin, the Saunders Family Professor of Neurology and director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at the Icahn School of Medicine at Mount Sinai in New York City.

Aaron Miller, MD (AM): I am Aaron Miller. I am the medical director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai and professor of neurology also at the Icahn School of Medicine at Mount Sinai in New York.

Stephen Krieger, MD (SK): I am Stephen Krieger, also a professor of neurology at the Icahn School of Medicine at Mount Sinai in New York and a neurologist here at the Corinne Goldsmith Dickinson Center for Multiple Sclerosis.

Improving Adherence to Disease-Modifying Therapies (DMTs) for Multiple Sclerosis (MS): Identifying Patients Suited for Clinician-Administered Therapy

AM: Well, I think 1 category of patients for that situation is a patient who is already demonstrated difficulty adhering to a particular regimen, especially to a medication that is given either every day or multiple times a week. Those patients may be better suited to go for an infusible therapy, partly because the provider has better control or knowledge of whether the patient is actually coming for the medication, plus the frequency is diminished. So I think that is 1 kind of person who might want that.

Then when we have the discussions up front, getting a sense of the person’s lifestyle. For example, I have had patients who when they were considering the possibility of a twice-a-day medication as opposed to a once-a-day medication, told me, “I am just not going to remember that second dose. My lifestyle is different and I am going to have trouble taking that.” That is a medicine that might not work if they do not fairly consistently take both doses.

Getting a sense of the person, getting a sense of what their issues are — are they fearful of injections, are they fearful of infusions, are they going to have trouble remembering to take a medicine every day, what has been their history with other medicines — that can all be helpful.

FL: So the healthcare provider administration works best when there is a long period between administration of a therapy. That is why the infusions every 6 months work very well. If it is a medication that needs to be given more frequently, that becomes more troublesome.

Back in the early days, there were some patients who went once a week to the doctor to get an injection of interferon beta-1a, but it was not very comfortable for them or very popular, for that matter. The long duration, the 6 months, works out very nicely for people. In fact, I find that if I am going to use 1 of the anti-CD20 therapies, I find more people prefer to get it that way than, for example, in the monthly injection.

SK: Certainly, the other patient category that I think we all think about with healthcare administering medicines as being particularly beneficial are people with MS with cognitive dysfunction, poor memory, impaired executive function, the ability to make sure that they are getting their refills and their renewals, and navigating insurance hurdles themselves to get medicines shipped to their homes. Those are folks who I think are at great risk of having gaps in treatment and where having an infusion center to oversee them instead of forcing adherence or at least having monitored adherence — you know that the patient has received the medicine. That is true for infusions given monthly or infusions given every 6 months. For those patients, we can sleep a little better at night when we know that they have gotten the drug.

Adherence Challenges for Patients With Limited Venous Access: Availability of Subcutaneous Options

AM: Well, the role of subcutaneous options depends on the availability of subcutaneous options. Not all subcutaneous administrations are the same. Some are truly subcutaneous injections and now there is 1 agent that has a sort of subcutaneous infusion that almost takes a number of minutes, as opposed to a brief moment of the injection. It depends on the patient’s tolerability to those. Get past the intravenous access for sure, so it depends on the category of medication, how high in efficacy drug 1 needs to use, and what the available options are.

Ocrelizumab in Focus: Navigating Adherence and Persistence in Shared Decision-Making

FL: Anti-CD20 therapies have been a major benefit for patients. They are highly effective and they provide us with at least 2 different ways of administering: either every 6 months, primarily intravenous, because they do not have any experience with the subcutaneous, or subcutaneously once a month. So we have 2 formulations that are given intravenously every 6 months and 1 formulation subcutaneously every month, and that is pretty good flexibility for patients.

Like we discussed earlier, some patients love the idea of not having to think about their medication for 6 months at a time, coming into the infusion center for a few hours, and it happens that we have a very nice infusion center, and patients enjoy it. They read a book, they get a lunch, they get infused, they are buzzed with some steroids and less buzzed with some Benadryl, and it works out very nicely. Then there are the others that say, “Look, I am too busy to come in even every 6 months,” so they take the once-monthly. From an efficacy point of view, they have really been very helpful for relapsing forms of MS.

SK: As Dr Lublin said, the every-6-month infusions I think have maximized both efficacy and adherence in a lot of ways in our field. There are a couple of versions of this that are approved now, including 1 that is given with a faster infusion. It becomes pretty minimally burdensome for someone to come in for a relatively quick infusion twice a year and not have to give up much more time, and as I think we alluded to earlier, not having to think about taking medicine all the time, which can make someone feel that they are in a sick role. I think these medicines have not only allowed people to live much less impacted by MS, but not having to think about it nearly so often.

One of the challenges with the entire class of anti-CD20 medicines, the B-cell depleters, will be how long do we keep people on them? Do we continue them indefinitely as someone ages, knowing that the immune system does quiet down to some degree as people get further and further into adulthood? In late adulthood it may not be necessary to dose them as consistently. So we are talking here about maintaining adherence, which is important, but at the same time, I think our field is considering in what ways we can perhaps space out these infusions. Can we lower the dose? Can we dose it based on B-cell repopulation, rather than on a calendar basis? I think that is a direction our field will be moving to try to maximize the benefit and maximize the safety of these agents.

AM: I think there is no question that the B-cell depleting therapies are highly efficacious, perhaps if not more so, at least as effective as any other type of agent that we have. But I think when discussing them with a patient, not only do we have to talk about their efficacy and the various routes of administration, which can lead to their decision, but we have to be up front about the safety issues and the potential for infections and reflect our uncertainty, as Dr Krieger said, about how long we have to keep them on these drugs, which is currently unknown. We do know that the infectious rates will increase as a patient is on these drugs for longer periods of time.

There are many people in our field who think that every patient needs to be on an anti-CD20 therapy. I do not share that viewpoint. I think many, many people would be best served by being on them, but there are other patients with seemingly milder disease who may be better off starting on a less highly efficacious but perhaps safer medication.

This discussion was edited for clarity and length.