Cognitive Health and Sphinogine-1-Phospate Receptor Modulators in Multiple Sclerosis - Episode 13
Experts in neurology provide insight into treatment selection and sequencing in patients with multiple sclerosis, focusing on S1P modulators.
Stephen Krieger, MD: You also spoke about sequencing medicine: when we use them, when we stop them. You spoke about transitioning from S1Ps. Dr Crayton, I’ll turn to you. What are your thoughts about where to use S1P modulators and how to sequence to and from them in your practice?
Heidi Crayton, MD: For me, because the first S1P receptor modulator entered the marketplace at a time when it was the only oral option, I transitioned the majority of my injectable patients to the first oral therapy. We’d all been waiting for that. I also didn’t start newly diagnosed patients on an injectable product. I started them on an oral therapy. That’s probably the primary function for me, with the newly diagnosed person. I don’t prescribe injectable platform therapies. Psychologically it’s better. It’s kinder to start patients on an oral therapy. That’s probably where I use the most of my S1P receptor modulator products. Also, I have no issue with transitioning from higher-efficacy therapies or lateral therapy, other oral therapies.
In terms of transitioning from monoclonal antibody therapy, those of us who’ve used alemtuzumab quite a bit are familiar with the data and maybe have learned sometimes the hard way that without a long enough duration of washout from fingolimod, we can have some rebound associated with alemtuzumab and just not destroy everything because everything is out in circulation. Other than that, segueing from other monoclonals to S1P receptor modulation is smooth and fine, and there are data to support that. We’ll see data here at this meeting to support that.
Stephen Krieger, MD: That’s true. Those are great points. Dr Nelson, are there other salient sequencing pointers that you think people ought to know about—where to place S1Ps in the treatment algorithm, if you will? And how to sequence to or from it?
Flavia Nelson, MD: Speaking from my own experience, I like these drugs as a first-line agents because they have good efficacy compared with the older drugs. But sometimes patients don’t feel comfortable. They need to start with something that they feel is safer. Some patients are very concerned about safety. In much the same way, some patients want something more aggressive to start with. Perhaps they can have induction therapy and then transition to something like an S1P. For example, let’s say someone goes on a monoclonal antibody, which is very important to monitor the JC [John Cunningham] virus for risk for PML [progressive multifocal leukoencephalopathy]. You can start a patient on that IV [intravenous] infusion. But at some point—after a year, a year and a half, a maximum of 2 years—you need to switch medications. You don’t necessarily need to go to a higher-efficacy drug. You can go down, and the patients will respond well. I use them in different ways. In the first line, de-escalating, and sometimes in second line if the patient wanted something safe to start with because they’re concerned about using medication. It depends. I recommend therapy on a case-by-case basis, trying to tailor it to the disease. The patient needs safety, risk vs benefit.
Stephen Krieger, MD: Agreed. I’ll add that the data are different for these different agents. You can try to apply the data from the trials to the person in front of you as best as we can.
Flavia Nelson, MD: Exactly.
Stephen Krieger, MD: I agree. Something like ozanimod is a first-line agent or an early agent. That’s where their patient population was studied. On the other end, siponimod was studied in a much older, sicker and more disabled population. That’s where I’m more likely to use that sort of agent, to try to match it to the data we have.
Then there’s a de-escalating, or step-down approach. The more we have high-efficacy medicines utilized, the more we’re going to need maintenance strategies after that. Not everyone is going to warrant the most powerful medicine we have at any given point in time for the duration. This is the nice thing about having a mature class of medicines in a mature disease state. We have the opportunity to personalize a lot of treatment choices.
Transcript Edited for Clarity