Robert Fox, MD, offered perspective on data from the DISCO-MS study of disease-modifying therapy discontinuation in patients with multiple sclerosis and how it compares with day-to-day clinical practice.
WATCH TIME: 5 minutes
Matt Hoffman: How have the findings lined up with your clinical experience? We talk a lot about that—there's the anecdotal evidence that we see every day in clinical practice on how things are going and how patients might respond to certain things. But it's always nice to see that experience lined up with the hard science. So based on again, your experience with DISCO-MS, and then your experience in your day-to-day life in the clinic. How have those lined up, if at all?
Robert Fox, MD: Well, the problem with everyday clinical practice is we see patients one at a time, and we don't necessarily know the why of what happened. They come in with a relapse, and we're not sure if it's because they weren't on an MS therapy. Some patients have a relapse even when they're on their MS therapy. Some patients have new spots on the MRI when they're on an MS therapy. As patients get older, we see spots on the MRI that are not related to MS—what we call vascular disease or small vessel disease—and that can look a lot like an MS spot. Even seeing new spots and MRI, particularly as patients get older, we don't necessarily know if that's from their MS or something different.
What the trial found is the difference between the disease activity, the frequency of relapses and the frequency of new lesions on MRI, was slightly higher—7% higher—in those that stopped MS therapy than in those that did not. Now the next question a lot of people ask would be, was that statistically significant? The way this study was set up was not as your typical study [question] of, is this treatment regimen better than another, but it was actually set up as a noninferiority trial. It was asking the question, is stopping therapy not inferior to continuing therapy? And in that sense, you end up with three different potential answers.
One is that it's very overlapping, the two therapies, and therefore, they are equivalent or noninferior. You also have one being much inferior, and then that is inferior. Then, you have this sort of gray zone. That's where the 7% fell. We did not show that it was noninferior. But we also didn't show that it was inferior, so it was a bit of a middle [ground]. Rather than focusing on statistical significance, I think the better thing is to say this study showed that patients 55 years or older, who had been stable on their current MS therapy, have a 7% higher rate of disease activity, either new lesions in MRI or a relapse, if they stop therapy versus if they continue.
Now, some providers or patients would say, well, is that too much? Or again, that goes back to the shared decision-making, and that goes into the [question] of how much of increased risk are you willing to take to stop therapy versus continuing therapy? This trial gives us a data point—an important data point that we haven't had from a controlled trial up to this point—which is an estimate, an actual estimate of the frequency of disease activity—relapses or new lesions on MRI—in patients who stopped therapy versus patients who continued.
Matt Hoffman: Are there any plans to dive into that further? As you said, we're looking at patients who are 55 years and older. But would is there a chance that potentially that risk drops for patients who are perhaps 65 years and older, 70 years and older?
Robert Fox, MD: We are looking at subgroup analysis. To look at different covariance that may be important, the men versus the women, older versus younger, whether they had progression or they didn't have progression, higher disability versus lower disability. We're looking into that, but there doesn't seem to be marked differences.
Now someone may say, “Well, what happens if you were to look at patients who are over age 45?” Well, that's very easy. We didn't look at those patients. We are only able to answer the questions that we've asked the patients that we had in the trial. The majority of the patients were on either the injectable therapies or some of the earlier approved oral therapies. We had very few patients on the infusion, the monoclonal antibody therapies. So, someone could say, “Well, what happens if we stop patients on those?” And the answer is this trial doesn't tell us that because we just had very few patients who were on those therapies.
Transcript edited for clarity.