WATCHING TIME: 5 minutes

For more coverage of WCSC 2022, click here. A transcript of the conversation is below.

Matt Hoffman: How do the results match your clinical experience? We talk about it a lot – there’s anecdotal evidence that we see every day in clinical practice about how things happen and how patients might react to certain things. But it’s still nice to see this experiment aligned with hard science. So again, based on your experience with DISCO-MS and then your experience in your daily life at the clinic. How are they aligned, if at all?

Robert Fox, MD: Well, the problem with daily clinical practice is that we see patients one at a time, and we don’t necessarily know why that happened. They come in with a relapse, and we don’t know if it’s because they weren’t on MS treatment. Some patients relapse even while on MS treatment. Some patients have new spots on the MRI when undergoing treatment for MS. As patients age, we see spots on the MRI that are unrelated to MS – what we call vascular disease or small vessel disease – and can look a lot like an MS spot. Even seeing new spots and MRIs, especially as patients age, we don’t necessarily know if it’s from their MS or something different.

What the trial found was that the difference between disease activity, frequency of relapses and frequency of new lesions on MRI was slightly higher – 7% higher – in those who had stopped MS treatment than among those who did not. Now the next question a lot of people ask would be, was it statistically significant? The way this study was set up was not like your typical study [question] de, is this treatment regimen better than another, but it was actually set up as a non-inferiority trial. He was asking the question, isn’t stopping therapy inferior to continuing therapy? And in that sense, you end up with three different potential answers.

The first is that there is a lot of overlap, the two therapies, and therefore they are equivalent or not inferior. You also have one that is much lower, and then it is lower. Then you have this sort of gray area. This is where the 7% fell. We have not shown it to be non-inferior. But we also didn’t show it to be inferior, so it was a bit of a middle [ground]. Rather than focusing on statistical significance, I think the best thing is to say that this study showed that patients aged 55 or older, who had been stable on their current MS treatment, had a rate of 7% higher disease activity, either new lesions on MRI or relapse, if they stop treatment than if they continue.

Now, some providers or patients would say, well, is that too much? Or again, it comes down to shared decision-making, and it goes into the [question] how much increased risk are you willing to take to stop therapy versus continuing therapy? This trial gives us a data point – a large data point that we haven’t had from a controlled trial so far – which is an estimate, a true estimate of the frequency of disease activity – relapses or new lesions on MRI – in patients who discontinued treatment versus patients who continued.

Matt Hoffman: Are there any plans to explore this further? As you said, we are interested in patients 55 and older. But is there a chance that potentially that risk will decrease for patients who are maybe 65+, 70+?
Robert Fox, MD: We look at subgroup analysis. To look at different covariances that may be important, male versus female, older versus younger, whether they have progressed or not, higher disability versus lower disability. We’re looking at that, but there don’t seem to be any stark differences.

Now someone can say, “Well, what if you were to examine patients over 45?” Well, it’s very easy. We have not examined these patients. We can only answer the questions we asked the patients we had in the trial. The majority of patients were on either the injectable therapies or some of the previously approved oral therapies. We had very few patients on infusion, monoclonal antibody therapies. So someone might say, “Well, what if we arrest the patients on these?” And the answer is that this trial doesn’t tell us because we had very few patients taking these therapies.

Transcript edited for clarity.