Optimal Management of Relapsing Multiple Sclerosis: Advanced Practice Providers Perspectives - Episode 8
Bryan Walker, MHS, PA-C, describes the rationale for treating relapsing multiple sclerosis (MS) with sphingosine 1-phosphate (S1P1) receptor modulators and compares available options.
Amy Perrin Ross, APN, MSN, CNRN, MSCN: Let’s move on to a discussion of a completely different class, in terms of medications, which are the S1P1 receptor modulators for MS [multiple sclerosis]. I’ll ask Bryan to lead us off on this one.
Bryan Walker, MHS, PA-C: That transitions when we’re talking about what absolute lymphocyte counts do, what they look like, how that factors into mechanism of action of medications, efficacy, and safety. The S1P1 modulators have been around for a while now. Fingolimod was the first oral medication approved by the FDA for relapsing forms of MS here in the United States, and it was the mechanism of action that was shown to be efficacious. That subsequently spawned a few more S1P1 modulator drugs to include siponimod, ozanimod, and ponesimod. These are medications that have a unique mechanism of action. These medications are more strategic in how their effect on the immune system works. The older medication, fingolimod, based on its S1P1 receptor subtypes, had more in the way of things that we needed to do for surveillance and onboarding of that medication, looking at the subtype receptors that were, say, in the macula or in cardiac tissue, and what that looked like, making sure that a first dose observation was done in those patients onboarding on to fingolimod. We don’t need to do first dose observation with newer S1P1 drugs because they’re more selective, and which S1P1 receptor subtypes that they effect is not to say that they can’t have an effect on the receptor subtypes in the macula or in cardiac tissue. But it works differently on those receptor subtypes.
It’s important for us to think about this as an effective oral medication for our patients and what that patient population looks like. A lot of times we were using this medication as a switch when it first came out, and maybe even now as we’re getting more of these medications available to us. We’ve also grown into our prescribing habits that this might be an initial medication that we use with a patient, based on their presentation and their preference, as far as risk aversion, lifestyle, or what have you. As a class, it’s an effective group of medications. Certainly, with the study that was done regarding siponimod getting the indication for secondary progressive MS—we’ve seen this with a couple of medications that have come to market now. We can’t compare drugs to each other because the studies weren’t powered the same way, their outcomes are all different as to what they’re using for primary and secondary outcomes—they all seem to look at the same thing: Confirmed disability progression, amount of new and/or enhancing lesions on an MRI [magnetic resonance imaging] scan, other metrics regarding quality of life, things such as timed 25-ft walks, and so forth. But again, they’re all powered differently, so we can’t compare them. We can look at all these as 1 piece, as a class effect type of scenario.
Part of it is also the differences in nuances with these medications. Certainly with siponimod, we’re able to do the phenotype testing so that we’re able to target better what the individual dose would be for the patient, based on their phenotype testing. There are some small differences regarding ozanimod and the use of other concurrent medications, so we have to be more mindful about what some of those other medications might be, specifically for mood disorder or for pain, whereas some of the other ones don’t have those indications. It’s important for us to realize not only what the patient’s preference is, and that we’re comfortable with this being an efficacious medication, but also the monitoring that goes on with any of these medications. We’re going to continue to do surveillance, not only radiographic and clinical surveillance, but also serologic surveillance. We want to make sure that our absolute eosinophil count is not dropping too far down. Are the other differentials looking where they should? Or are things getting a little wonky there? We do know that they selectively inhibit the activity of those activated lymphocytes, so we’re able to see a reversal of that upon discontinuation of these medications. It’s not a sustained effect, nor have I seen that. There’s an ease of convenience. These are well-tolerated medications.
Amy Perrin Ross, APN, MSN, CNRN, MSCN: Thank you all so much. I would like to thank this wonderful panel, Christen Kutz, Stephanie Agrella, Bryan Walker, and Patricia Melville for this wonderful discussion. I’d like to thank you, as an audience, for watching NeurologyLive® Peer Exchange. If you enjoyed the content, I suggest that you subscribe to the NeurologyLive® newsletters to receive information about upcoming Peer Exchange segments and other content available to you. Thank you all so much.
Transcript edited for clarity.