Should multiple sclerosis (MS) patients stop disease-modifying treatment (DMT) as they get older?
The answer depends on several factors, noted John Corboy, MD, of the Rocky Mountain MS Center at the University of Colorado in Aurora, at the 2025 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum.
"Many patients are discontinuing DMTs as they age, and there is little data to guide them as to risks or benefits," Corboy told MedPage Today.
Observational studies and two randomized controlled trials consistently suggest that, in general, disease recurrence after DMT discontinuation diminishes with age and patients may wish to consider stopping MS drugs.
"But the data always need to be in context," Corboy emphasized.
"The decision to discontinue DMTs is a balance of risks and benefits, as with all complex medical decision-making, and many who have remained on treatment may be uncomfortable with this as an option," he explained. "De-escalation to a lower risk medication, or simply remaining on present DMT, may be more agreeable to them -- which is fine, unless they are being harmed by the drug."
Aging and MS
Approximately 46% of U.S. adults with MS are 55 or older, but minimal data support DMT use in that age group, Corboy noted.
"Most people over the age of 55, which constitutes almost half of all U.S. adults with MS, have been excluded from clinical trials," he pointed out. "We really had very little safety data and very little efficacy data in individuals older than 55."
The risks of some DMTs -- including infection, cancer, and vaccination response -- might be greater in older patients. Comorbidities may limit DMT use.
Information from two databases -- the North American Research Committee on Multiple Sclerosis (NARCOMS) and the Multiple Sclerosis Surveillance Registry of the Veterans Affairs -- suggests that most MS patients over age 60 are not prescribed DMTs.
Only 12% of older patients with a mean age of 56 would consider going off their disease-modifying therapy, according to a NARCOMS survey, Corboy noted.
In Corboy's experience, patients have two major concerns about stopping treatment: accelerated progression of disability, or "the big one -- having a big attack that would alter their overall function in a substantial way," he said.
To Continue Treatment or Not?
Retrospective studies have found that MS patients stop DMTs for many reasons though most have assessed people of all ages, not just older patients. Often, these studies are not propensity-matched, Corboy said, and rarely do they include progressive forms of MS.
For patients who have stopped treatment, several factors have been tied to new MS activity, including recent disease activity, young age and shorter disease duration, and the DMT in question. For example, patients who stop fingolimod (Gilenya) or natalizumab (Tysabri) treatment are at risk of developing rebound disease activity.
Two randomized clinical trials -- DISCOMS and DOT-MS -- have reported results after stopping DMTs.
In DISCOMS, which was led by Corboy, stopping DMT was not inferior to continuing over 2 years, but the non-inferiority of stopping could not be established. "There was higher patient satisfaction in the group that was discontinuing their medication," Corboy noted. At baseline, participants were ages 55 and older with no relapses for at least 5 years and no new MRI changes for at least 3 years.
A DISCOMS extension study with a mean follow-up of 40 months showed similar results. "Notably, there was not a continued decline," Corboy pointed out. "Most of the people who were going to have any disease activity already had it by then."
In DOT-MS, led by researchers in the Netherlands, significant radiological inflammation occurred in nearly one in five patients with stable MS who stopped first-line treatment, mainly glatiramer acetate (Copaxone) or interferon. Participants were ages 18 and older at baseline and were without relapses and substantial MRI activity in the previous 5 years.
DOT-MS was stopped early because inflammatory disease activity was above predefined levels. The median time to disease activity was 12 months.
DISCOMS and DOT-MS "focused on either a couple of the moderately effective oral agents or the older injectable drugs," Corboy noted. What happens when high-efficacy drugs are stopped in older MS patients has not been tested in clinical trials.
"There's only one study that really addresses that in any controlled fashion," he said. That was a matched retrospective analysis of adults with a mean age of 55 from the French MS registry OFSEP who had been treated with natalizumab, fingolimod, rituximab (Rituxan), or ocrelizumab (Ocrevus), and had no relapse or MRI activity for at least 2 years.
"We know we have to start very early these kinds of treatments in order to prevent disability progression in patients," study author Anne Kerbrat, MD, PhD, of the University Hospital of Rennes in France, noted in a JAMA Neurology podcast. "But now we have the question of when can we stop -- or is it possible to stop -- these kinds of treatments."
The OFSEP analysis showed that relapses increased significantly after stopping natalizumab and fingolimod, two treatments that affect immune cell trafficking. However, there was no significant increase in relapse risk after stopping the anti-CD20 therapies rituximab and ocrelizumab.
Two new trials will look at the effects on stopping DMTs in MS patients. The STOP-I-SEP trial in France will compare stable secondary progressive MS patients older than 50 who continue versus discontinue treatment. The TWINS study, also in France, will compare stopping or continuing treatment in stable relapsing-remitting MS patients ages 55 and older.
"We need to know more about different mechanisms of action in older, more stable populations. We need [in] general, more data on the risks and benefits of treatment in older patients, especially in progressive patients," Corboy stated.
"We also need to understand more about the role of de-escalation," he continued. "There's a lot of people who would potentially be interested in discontinuation but are concerned about it, and maybe de-escalation would be one way to go."
Disclosures
Corboy reported relationships with PCORI, NMSS, NIH, and EMD Serono, and compensation as the associate editor of Annals of Neurology.
Kerbrat had no disclosures.