Drs Ahmed Obeidat, Hesham Abboud, and Benjamin Greenberg share their experiences with patient compliance and the route of administration of current and emerging therapies for multiple sclerosis.
Ahmed Obeidat, MD, PhD: And there's another part of this, it's interesting. If we had a recorded program on therapeutics 10 years ago, then major topic would be around, we'd be referring to routes of administration: injectable, infusible, oral because obviously as we got oral therapies that was such a huge change for a field.
Benjamin Greenberg, MD: I'm curious as we're talking about the sequencing, as we're talking about first line versus second-line therapy, the one thing we haven't addressed here is the fact that these are all oral medication aids, and we were in a huge rush as a field to get to oral medications because nobody liked taking injections. And the data was clear that compliance with injectable medication was not the best, it was not great. There's been an unexpected aspect to my practice, a surprise over the last decade between infusible and all other medications. I have found such joy, and I hate to say it that way, but joy in my ability to ensure compliance and adherence, or at least measure it with infusible drugs, and I sound like Big Brother watching over my patients in kind of a creepy way, but are you taking your medicine or not? I know for my patients taking infusibles.
Ahmed Obeidat, MD, PhD: That's right.
Benjamin Greenberg, MD: One of the things that's interesting is as we move to orals, particularly as we move to twice-a-day orals, which several of these Bruton's tyrosine kinase ACE inhibitors are, we run into compliance issues, and when I'm talking with the patients, efficacy, safety, I do bring up the compliance issue. How big would it be for you, in terms of moving it up or down in that armamentarium, the fact that these are oral and/or possibly twice a day oral?
Ahmed Obeidat, MD, PhD: These medications are only as good as if the people's taking them, that's the thing. If you prescribe and the people are not adhering to the treatment, then maybe we would have to think about ways to improve adherence. Maybe they have these apps, they have some of the other things that it can kind of give us an idea, but would there be a biomarker to follow some of the adherence? Now, for example, we have an injectable anti-CD20 that people administer at home and for me to know sometimes if the patients taking the medication, I will test their B-cells, and I know there are zero or near zero, then I know they're taking the medicine. Maybe is there another way in a BTK inhibitor that we can monitor adherence in an indirect way by doing a blood test or something like this? Maybe that's something to think about with the trials what are the main changes that we see in this class in the blood profile, and then maybe we can pick one of those to look at. I was curious.
Hesham Abboud, MD: I know they're already measuring a total lymphocyte count in immunoglobulin levels in I think all these trials. The current thinking is that this class does not result in, at least not an early hypogammaglobulinemia and this is actually one of the reasons why the whole sequencing approach is talked about. Can we treat patients with B-cell depleting and then to avoid long-term hypogammaglobulinemia that can happen with long-term therapy, a B-cell depleting therapy can we introduce BTKi? Now, the question is if we do B cell phenotyping, for example, will this give us an idea whether a patient is taking their medication? I don’t know if we know the answer to this. The first thought in my mind is probably not, it wouldn't be indicative. But the better way to do this is to read your patient. It goes back to that individualized therapy. If you are dealing with a patient who already breakthrough, because they're not compliant with their fumarate twice-daily dosing, for example, then obviously this is not a good candidate for a BTKi and maybe a better candidate for an infusion therapy, like you mentioned.
Benjamin Greenberg, MD: Yes, I agree with you, but I've had situations where I've been surprised. I remember distinctly one patient I took care of, very pleasant woman. I had known her for years, and this is many years ago. And she was on an injectable therapy. And she came in with her first relapse in probably 8 years and mild relapse, but, symptomatic, MRI change. And we had our visit after she was treated for the relapse. And I said, well, we're going to need a switch from your injectable. She said, yes. And I had done my screening around compliance as I try to do at those visits. And 2 days later, my nurse came to me and said, your patient, was on the phone sobbing. I said, what's wrong? She feels guilty and she was lying to you. She hasn't taken the drug in 2 years. She had gone off. And, that's not just non-compliance. And she thought I would be disapproving. And for the record, I'm not. If patients want to go off their medication, that's their choice. But it's amazing when we try to dig down into compliance and adherence, human beings were funny organisms, and it creates situations where we have to guide patients around treatment decisions sometimes within incomplete data. If you're not taking the fumarates are a great example twice a day medication, what do you do in a situation where somebody says, well, I'm missing a quarter of my doses and they have breakthrough disease? Is it a failure of the drug or to your point, is it a failure of the patient to take the drug, and how do you handle it? And that's where we must personalize what that next intervention is. But I agree. It'd be great if we had a measure to know, are you really taking it or not so much? There's work on this around BTKi occupancy levels where you can take a blood sample, you can look at lymphocytes and you can see how much of the enzyme has been inhibited by the molecule. And that would be revolutionary for us in MS, to have personalized biomarkers to know, is somebody fully treated or not? We give everybody the same dose of drugs. Maybe we shouldn't.
Ahmed Obeidat, MD, PhD: Maybe some people may need more, some people need less. And then that's a good way to measure if we have the occupancy. And that will probably be more with the covalent molecules, right?
Benjamin Greenberg, MD: They can do it with both, but it is an easier assay with the irreversible covalent molecules.
Ahmed Obeidat, MD, PhD: Yes. These are great points.
Transcript Edited for Clarity