A randomized trial presented at the recent Consortium of Multiple Sclerosis Centers (CMSC) annual meeting evaluated the effects of discontinuing disease-modifying therapy for patients with multiple sclerosis (MS) as they age.
In this MedPage Today video, John Corboy, MD, co-director of the Rocky Mountain MS Center at the University of Colorado in Aurora, discusses the data found in the DISCOMS study.
Following is a transcript of his remarks:
The topline takeaway is that by the primary outcome measure, which we used a combination outcome measure, any new relapse, new activity clinically and/or any new brain MRI scan lesions, and the logic for why we did that was that we expected to see very little activity. We wanted to have the greatest possibility to show either inferiority or non-inferiority of discontinuing medication compared to continuing it.
And the important point statistically is that the way we did the study was not like normal studies, where you compare, say, a new drug to an old drug or to placebo and try and show it’s superior. It’s the opposite of that. We actually try and show that the new treatment — in this case going off drug — is not inferior. Statistically it’s a different question. And so there are three outcomes which are possible.
One is that you show it’s clearly inferior — that is, you set up what’s known as the non-inferiority zone. And you do this ahead of time and you say, I will accept a small amount of new activity so long as it’s not really different by “this much” more. And we used a non-inferiority margin of 8%; we expected about 2% of new activity. And so we would figure that greater than 10% would be significant enough that it would not be reasonable for someone to discontinue their medication.
So one possibility is that it’s clearly inferior; it’s outside that non-inferior zone. A second possibility is that you can show that it actually is not inferior by that definition, and you statistically show that.
The third possibility is in between that — that is, your answer is within the 10% zone in this case, or within 8% more so it looks like it’s okay. But the confidence limits, the error margin — because of course there’s also an error margin, right, it’s not just an exact number, there’s the so-called 95% confidence intervals — overlap and go outside the non-inferiority zone. And that was a possibility as well. And in fact, that’s exactly what we found.
If you look further at it, the number of lesions on the scans, one or two new dots accounted for about 68% of all the primary outcome measures. So the vast majority of people had no clinical event. But overall, if there was a new event, 68% of the time, it was just one or two new dots on your brain scan.
And then the question is, what is the significance of that? And that’s not as well known, certainly not in this population. So clinically, if you just look at relapses and look at progression of disability, not much was seen. But there probably was a small amount of increased risk of having some new MRI activity. And then people will have to judge is that small amount of activity on the scan worrisome enough to them that they want to stay on medication or would they want to consider a trial off of medication?
And this population was older — average age 63, 80% women, 90% white, average time — some since symptom onset was 22 years. So they’d had MS for quite some time. Average time since their last acute relapse was almost 14 years. So they had been stable for a long time. And over 70% were still using older injectable drugs. And what that means is that they’ve been super-stable on medications for a very long time.
And it doesn’t necessarily translate to people who perhaps have had maybe a relapse 6 years ago or 7 years ago and changed their medication, even though they could have gotten into the study. In fact, it may not translate as well to them.
This does not answer every question. It answers partially the question, is it reasonable to go off medication in this population. Overall, it was safe. There was no change in symptoms. There was no change in quality of life. No change in cognition, no change in progression of disability, no difference in relapses, but a small, perhaps increased risk of having MRI scan changes.