Do patients with multiple sclerosis who have been on disease-modifying therapies (DMTs) for decades need to keep taking them? John Corboy, MD, professor of neurology, University of Colorado Denver, School of Medicine, and co-director of the Rocky Mountain MS Center at Anschutz Medical Campus, explains what is known about this area.
Do patients with multiple sclerosis who have been on disease-modifying therapies (DMTs) for decades need to keep taking them? John R. Corboy, MD, professor of neurology, University of Colorado Denver, School of Medicine, and co-director of the Rocky Mountain MS Center at Anschutz Medical Campus, explains what is known about this area.
What do we know about when to discontinue disease-modifying therapies in multiple sclerosis?
As with any other medication, device, procedure, or anything else, choosing when in medicine—choosing when to start it, switch to an alternative, abandon it, or consider that perhaps treatment is not needed—is a very important question, because multiple sclerosis got to the party somewhat late and that we, for many years, did not have effective therapies. We're sort of reaching a point now 27 years into treatment after the first approval of Betaseron in 1993, where we have a whole generation of people who've been treated for a very prolonged period of time. And yet we've not asked nor answer this very fundamental question, do they need to be treated forever? Does the benefit that they obtained from treatment outweigh any downsides, either with risk, with costs, with side effects, or other things? And this is in the background of very little data, if any, that these medicines are beneficial in people over the age of 55, just because people over the age of 55 have been excluded from all the clinical trials that have obtained federal approval here in the United States and other countries.
And so the reality is we have very little data at all one way or the other. And in addition, there is data that things that are important, they're not the only thing, but things that are important, such as relapses with multiple sclerosis, new MRI scan changes with multiple sclerosis, diminish with age and are substantially lower in those over the age of even 45 to 50. And certainly over the age of 55 to 60. And also substantial data, that the medications that are presently available are much more effective in younger people than they are people who are older. And data that is consistent with the idea that you can potentially discontinue the therapies after no specific age, but as people age, and if they've not had recent disease activity, that is have stability. And that's primarily taken from database analyses.
So the purpose of our study was to do a randomized control trial to ask that question directly. Because all of the database studies and propensity-based models where you do matching of people stay on drug versus go off drug — they're very useful, they're very helpful, and I'm glad they've been done. They are associated with a series of potential biases about how the patients are included into the studies. And they don't ask the question in a very concrete, explicit way. They mostly just see who went off medication for whatever reason, who stayed on the medication for whatever reason. And so we and our colleagues around the United States are involved in the DISCO-MS study, the discontinuation trial. In addition, there are studies in France with Anne Kerbrat and Eva Strijbis in the Netherlands, who are also doing randomized, controlled clinical trials, looking at slightly different populations than ours.
Our population is 55 and older, have not had a relapse for at least 5 years while they've been treated, have not had a scan change within at least the last 3 years and have continuously been taking medication over that timeframe. With the most recent change, being no more recent in 2 years, that is they've been stable on that particular drug as well. And so far, we've been able to fulfill enrollment up to 260 individuals, roughly half and half, half remaining on their medication, half randomized to go off their medication. And right now the last visit will be in August of 2021. And we anticipate data being available in roughly early 2022.
We do have the preliminary demographics of the people who've been included in the study. So it's 260 people and looking at them overall, that is all them together, the average age is about 63. About 80% are women, about 90% are white. The last relapse for people is averaging 13 years prior to enrollment in the study. So they've been stable for a prolonged period of time. The average level of disability is mild-to-moderate on the EDSS scale is about three, a little over three, and on the PDDS—the Patient Determined Disease Steps—is about 2. And so these are mild-to-moderately disabled individuals, the vast majority are still referred to as relapsing MS, about 83%. And 102 so far have completed their 2-year involvement in the study. So we have a significant number, well over half, who are still in the follow-up phase, and will be completing as of August of 2021.