Stopping DMTs a ‘reasonable option’ for some older MS patients

But benefits still found for MS patients with no disease activity: Study

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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Older people with multiple sclerosis (MS) who have not experienced disease activity for several years still will benefit from disease-modifying therapies (DMTs) to control the neurodegenerative disorder, a new study found.

Data from a first trial assessing whether discontinuation of DMTs among these patients is at least as effective as continuing treatment was unable to show such non-inferiority. Specifically, stopping treatment was associated with a small but still increased risk of new MRI activity.

Still, while older MS patients might be reluctant to stop treatment, the new findings overall “should reassure patients … who are considering discontinuing their therapy that, although there might be a small increased risk of new MRI activity, a trial of discontinuation is a reasonable option,” the researchers wrote.

“This study will aid decision-making when health care providers and people with multiple sclerosis discuss potential disease-modifying therapy discontinuation as patients age,” John Corboy, MD, a professor of neurology at the University of Colorado School of Medicine, and the trial’s lead researcher, said in a press release.

The study, “Risk of new disease activity in patients with multiple sclerosis who continue or discontinue disease-modifying therapies (DISCOMS): a multicentre, randomised, single-blind, phase 4, non-inferiority trial” was published in the journal The Lancet Neurology.

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Older patients excluded from clinical trials of DMTs

More than two dozen DMTs have been approved to date to reduce disease activity and slow disability progression in people with MS. Yet, most of these drugs were tested in trials that excluded people older than 55. After that age, data has shown, relapses and new lesions on MRI scans become less and less common.

The result is that it’s unclear if available DMTs are as effective in these older patients, or if individuals with well-controlled disease for several years could safely discontinue treatment.

To know more, researchers in the U.S. launched a Phase 4 trial called DISCOMS (NCT03073603) and enrolled 259 MS patients ages 55 and older. Their goal was to determine if older MS patients without disease activity for a number of years experienced increased activity after stopping treatments.

The enrolled patients had not experienced an acute MS relapse for at least five years, or new MRI activity for at least three years. All were receiving a DMT for at least five years, and were on their most recent therapy for at least two years.

Recruitment for the study, which was funded by the independent, nonprofit Patient-Centered Outcomes Research Institute and the National MS Society, an advocacy organization, occurred between May 2017 and February 2020 across 19 MS centers in the U.S.

The participants, who had a mean age of 63, were randomly assigned to a quitting group — 131 patients, or 51% — or a continuation group, consisting of 128 patients, or 49%. The majority were women and had a diagnosis of relapsing-remitting MS. In all, 89% were non-Hispanic white people.

Also, at least 8 in 10 patients (more than 85% overall) were on either interferon-beta therapies, glatiramer acetate (sold as Copaxone, among others), or Tecfidera (dimethyl fumarate).

The trial’s main goal was to determine the percentage of patients who experienced a relapse or a new or worsening brain lesion over the study’s duration. In particular, researchers aimed to determine whether quitting DMT was non-inferior to, or meaning not worse than, treatment continuation.

“Our study addresses important concerns about the risks and benefits of disease-modifying therapies as people age,” Corboy said.

“The primary objective of our study was to identify whether discontinuation is safe to consider for older patients with multiple sclerosis and no recent relapse or new MRI activity, and our goal was to provide an estimate of disease recurrence in this context,” he added.

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No difference in life quality for patients discontinuing therapy

Over the study’s two-year duration, 22 patients experienced a relapse or a new or expanding brain lesion. Among them were six individuals (4.7%) from the continuation group and 16 (12.2%) in the quitting group. This represented a 7.5% difference, which meant that discontinuation of DMTs was worse than continuation.

For the majority of patients, or 15 of the 22, their disease activity event was a new lesion without any relapse or change in disability; four patients experienced an acute relapse.

In a post-hoc exploratory analysis — one performed after a trial is complete — considering relapses alone, the results showed that quitting DMTs was not worse than continuing therapy. However, considering brain lesions alone, stopping treatment was deemed worse than continuing on it.

A further post-hoc survival analysis showed that patients in the quitting group experienced a relapse or developed a new brain lesion significantly earlier than those in the continuation group: at a mean of 16.3 months versus 17.3 months.

No differences were seen in disability progression and life quality. Also. no differences were seen regarding symptom scores and cognitive tests.

Future observational studies will further define factors that … might aid patients, their families, and health-care providers when discussing potential risks and benefits of discontinuing disease-modifying therapy.

A similar number of patients in both groups experienced adverse events and serious adverse events. In all, adverse events affected 79% in the quitting group and 85% in the continuation group, while serious adverse events were found for 14% in the quitting group and 16% in the continuation group.

There were, however, more overall adverse events in the quitting group — a mean of 422 versus 347.

A total of three patients died: two in the quitting group and one in the continuation group. No deaths were deemed related to treatment.

According to the researchers, more data are expected from two ongoing clinical trials investigating therapy discontinuation, both slated to run through January 2028. These are STOP-I-SEP Phase 3 (NCT03653273) and DOT-MS (NCT04260711).

“These trials and future observational studies will further define factors that … might aid patients, their families, and health-care providers when discussing potential risks and benefits of discontinuing disease-modifying therapy,” the researchers concluded.