Experts discuss how they monitor response to multiple sclerosis therapies and disease progression.
Bruce Cree, MD: I want to turn our attention to a topic that was alluded to in our last group discussion, which has to do with monitoring response to treatment and some of the uncertainties there.
Kristen, how do you monitor whether a particular drug you’re using is working in a patient with progressive MS [multiple sclerosis]? What are the outcomes you look at? Do you use imaging, spinal fluid, or just clinical outcomes? How do you determine whether a particular product is helping your patient?
Kristen Krysko, MD: Yes, this alludes to what we talked about: these drugs have been shown to potentially slow disability progression, which is a hard thing to monitor in clinical practice. It’s pretty difficult to determine if someone’s trajectory of worsening disability has decreased in terms of the rate of decline. Patients sometimes have a hard time making that determination.
On the clinical examination, it’s also hard to determine. In clinical practice, we tend to use a standard neurological exam and EDSS [Expanded Disability Status Scale] scores, which may be insensitive to detect change. They are problematic, especially because they rely on measuring ambulatory function, whereas they may not capture if someone’s upper limb function, for instance, slowed in decline. It can be difficult.
In clinic, I tend to add on the timed 25-foot walk because that’s pretty easy to do and is something that we can monitor as well. If they’re not continuing to worsen on that measure, that’s a good thing. But at the same time, we don’t expect improvement, which is sometimes difficult to convey to the patient.
Ideally, we would also be monitoring cognition and upper limb function. I know some clinics are able to incorporate a CMT [Charcot-Marie-Tooth disease test] or the 9-hole peg test. Sometimes there’s not enough time to do all of this in the clinical evaluation. But if that’s translated into some sort of app or monitoring they can perform during the waiting room time, then that would be beneficial.
In terms of imaging, I still tend to order an MRI at the new baseline, about 6 months after starting disease-modifying therapy in these patients. I tend to monitor MRI annually, although we’re often not seeing inflammatory activity, and we don’t really have a good measure to determine whether progression is affected. In clinical practice, we don’t tend to use measures of atrophy at this point, but in the future, spinal cord atrophy or other whole-brain atrophy measures may be helpful to monitor that, as would biomarkers such as sensors and monitoring step count. Potentially other laboratory biomarkers could be helpful in the future, but we’re not really using that in clinical practice yet.
Bruce Cree, MD: Thanks, Kristen. That’s terrific. One of the considerations when we’re looking at some of our patients as they transition from relapsing MS to secondary progressive MS is about what to do in terms of switching treatment.
I want to have an opportunity to review that with everybody. I’m going to ask Bob to start that discussion. Let’s say you have a patient on a platform therapy, one of our ABCR [Avonex, Betaseron, Copaxone, and Rebif] drugs, or even teriflunomide. At what point do you decide to transition a patient who you think has secondary progressive MS? Is there a particular go-to drug once you’ve decided that it is appropriate to move a patient onto a progressive therapy?
Robert Fox, MD: What’s important to recognize is we have no clinical trial data to guide our decisions here. I’m not aware of any clinical trials that enrolled patients who had progression on an MS therapy and randomized them to a number of different treatment options. We just don’t know how to best treat patients.
I follow a first principle approach. If there’s evidence of active inflammation, either clinical relapses or new lesions or active lesions on MRI, along with their secondary progression, then I will shift them to a different anti-inflammatory therapy, whether it be an S1P [sphingosine-1-phosphate], an anti-CD20, or natalizumab.
If they have solely gradually progressive myelopathy from progressive MS and no evidence of active inflammation, particularly if they’re older—which to me is roughly in the mid-50s and older—then those are patients who I generally don’t move to another MS therapy. I have many colleagues who do. Again, we don’t have clinical trial data to guide us as to what is the right thing to do. But if there’s active inflammation, I will change to another anti-inflammatory therapy. If there’s not active inflammation, particularly in the older patients, then those are patients I will either take off of therapy entirely or leave on their current therapy and instead optimize their symptom management.
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Transcript Edited for Clarity