Stephen Krieger, MD; Daniel Bandari, MD, MS; Bruce Hughes, MD; Mitzi Williams, MD; and Heidi Crayton, MD, discuss their approach to switching treatments for patients with multiple sclerosis and the timing between therapies.
Stephen Krieger, MD: How about changing a patient’s medicine? The difference between changing a patient’s medicine because of efficacy concerns, as you said, treating to target and trying to not let anything happen vs changing medicines because of safety concerns. I feel like we emphasize a lot the switching because of efficacy failure, but maybe we need to talk a little about switching for safety or for comorbidities. Can you talk about how you do that, switch between classes for safety reasons, trying to maximize treating the disease, but being mindful of the safety issues?
Mitzi Williams, MD: Absolutely. This is a very interesting question because in some cases I have even switched between S1Ps [sphingosine-1-phosphate receptor modulators] if there were concerns about things like lymphocyte count. There’s some latitude there, particularly if efficacy is not the issue, because if a person is on a drug with a mode of action that is effective for them, I’m going to try to keep them within that class as much as possible, while assessing the safety. In terms of switching for safety, I feel a little more comfortable doing what I call a lateral switch, maybe between moderate efficacy therapies whether they’re oral therapies, or within a certain class. But I think it’s very important that we look at the individual adverse effect profiles, and particularly with the S1Ps, because there can be some nuances or differences in those adverse effects and counts. You can sometimes feel comfortable switching within that class to maintain efficacy for the patient.
Stephen Krieger, MD: Even I would say allergy. Allergy to one medicine in a class doesn’t necessarily mean allergy to another because they are rather molecularly different even though their mode of action might be the same. It’s a really good point. You want to look at how well the drug is working, but if you can maintain that by staying within that mechanism of action, there are opportunities to do that. Dr Bandari, are there other things to add to this, in particular, if you’re going to switch therapies, do you leave a gap between them? Does that vary on the basis of which drug you’re switching from and to? Tell us a little about that.
Daniel Bandari, MD, MS: That is the million-dollar question.
Stephen Krieger, MD: That’s why I asked you.
Daniel Bandari, MD, MS: Thank you very much. How long do I need to be off of a particular medication before I can start the next medication? That which you would call a gap or a bridge between them. I don’t believe we have an exact answer for that. Most of us who treat a lot of patients with MS [multiple sclerosis] obviously have our own perception of how long it’s going to take for somebody to be washed out of a medication. It depends on its mechanism of action. But one of the probably greatest advantages of the newer generation of S1Ps especially, is that compared to most of the other oral medications that we have had in a different class, we are able to see that a drug is out of your system in a matter of a few weeks. For example, with ponesimod we’re looking at about 1 week, very short Tmax [time to maximum effect/concentration], in a sense that would allow the patients to be able to come off the medication, which from the applicability plays a lot of roles in someone who needs to come off of the medication for a variety of reasons, pregnancy being one of those, or potential for pregnancy. Also other medical issues that come up, cancer for example, if they need to go on a different medication for that. So, the reality is there is a gap between these medications that needs to take place.
Also, it’s important because even though we believe these are great drugs that need a short washout, there are some other medications that the patient is coming out of, in order to go to one of the S1Ps, that may need longer to clear out of their system, including some of the B-cell inhibitors that may need up to 3 months for the B cells to start coming back up. At the same time, you do not want to bombard all classes of immune cells at the same time. You need to leave some protection in that. And I believe that length of time we need to have, for example, to come out of the B-cell inhibitor before going to some of their other medications is a very important topic.
Stephen Krieger, MD: In essence, I like to think that the next medicine should start roughly whenever the next dose of their former medicine was due, as a good gut check. Some of the medicines that are given every day like oral agents, there probably shouldn’t be a long gap before they’re due for their next drug because they can come out rather quickly. For a medicine like natalizumab, given once a month, I usually say by the time the next natalizumab dose would have been due, they should be starting their next medicine. And similarly, Dr Bandari as you said, for a B-cell depletor that takes down B cells for many months, if that drug was due to be given in 6 months, I would say by the time that drug is due, a few months after their last dose, they should be started on their next medicine.
Daniel Bandari, MD, MS: With one exception to that, and that would be the injectable B-cell inhibitor, which that one, as you all know, there may not be that monthly element that comes into it because the effect will stay for a longer period. That’s one of the misnomers I think that at some point hopefully will be clarified, but that paradigm is absolutely correct.
Mitzi Williams, MD: Can I add that I think we learned a lot of these lessons in real life. Particularly when our first B-cell therapy became available, we had a long line of patients waiting to get on this therapy that we thought was going to happen fairly quickly, but maybe there were issues where we couldn’t get the therapy as quickly as possible, and we had taken patients off their drugs and realized we can’t let this long window go. Our patients are going to start relapsing and having trouble. So, I would agree, I don’t necessarily wait until I feel like it’s completely out of their system. But I want to make sure there’s not too much overlap, but enough to where they’re still having some type of therapy in their system so they’re not having relapses or issues during that transition.
Transcript edited for clarity