ECTRIMS 2023: More disease activity when treatment stopped

A clinical trial that was testing if treatments for multiple sclerosis (MS) could be discontinued in people with stable disease was terminated early after several patients who stopped treatment saw new disease activity.

The findings support the continued use of disease-modifying therapies (DMTs) even by those who haven’t had substantial disease activity for a long time.

Eline Coerver, a PhD student at MS Center Amsterdam in the Netherlands, discussed the results in the presentation “Discontinuation of first-line disease-modifying therapy in stable multiple sclerosis (DOT-MS): an early-terminated multicenter randomized controlled trial.” The findings were shared at this year’s joint meeting of the European European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), held Oct. 11-13 in Milan.

DMTs are medications that slow the progression of MS, decreasing the likelihood of relapses and reducing the risk of worsening disability. Nearly two dozen DMTs are approved to treat relapsing forms of MS and all work by decreasing the inflammation that drives the disease.

In the modern era of MS treatment, it’s fairly common for patients on long-term stable treatment to not have any new disease activity for years at a time.

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Since continuing these treatments is costly and can cause side effects, it’s been proposed that some patients with stable disease may benefit from stopping them, but only if doing so won’t cause substantial worsening.

To know more, Amsterdam UMC sponsored the DOT-MS (NCT04260711) clinical trial to see if DMTs could be safely discontinued in patients with stable disease.

The trial enrolled adults with relapsing-remitting MS or active secondary progressive disease who hadn’t had any relapses or substantial MRI activity — two or more new lesions — in the five years before entering the study while being treated with a first-line DMT.

First-line DMTs in the study were Tecfidera (dimethyl fumarate), glatiramer acetate (sold as Copaxone and generics), Aubagio (teriflunomide), and interferon-based medicines.

“The aim of our trial was to investigate whether first-line disease-modifying therapies can be discontinued in relapse-onset MS patients that are inflammatory stable,” Coerver said.

The participants were randomly assigned to continue using their DMT or stop treatment. To ensure their safety, those who stopped were routinely analyzed to see if they were having substantial new disease activity.

“If the number of participants with disease activity in the discontinuation group was higher than the number in the continuation group, and this number exceeded our predefined threshold, we had to discuss premature termination of the trial,” Coerver said.

Discontinued treatment leads to trial termination

The trial was terminated in March after an interim analysis showed increased disease activity in the discontinuation group that exceeded the predefined thresholds.

At the time the trial was ended, 89 participants had been randomly assigned to one treatment arm — 45 had stopped their DMT and 44 had continued it. About two-thirds of these patients were female, the average age was in the early 50s. At the trial’s termination, most patients had been followed for at least 1.5 years.

In the discontinuation group, eight (17.8%) patients saw notable new disease activity. The median time from stopping their DMT to having new disease activity after was about a year.

Two patients in this group had a relapse and seven had new signs of substantial MRI activity, defined as three or more new total lesions or two or more new lesions with active inflammation.

None of the patients who continued their DMT saw substantial disease activity, relapses, or significant MRI activity during the trial.

Four patients in the discontinuation group had mild, nonsignificant new signs of MS activity on MRI scans, compared to one patient who continued treatment.

Those who had substantial new disease activity after stopping their DMT didn’t have any clear distinctions regarding demographic features such as age and sex nor clinical features like the duration of stable disease or what DMT they’d been on.

The researchers will continue to examine data from the trial to learn how stopping treatment affected disability progression, MRI outcomes, and certain disease-related biomarkers.

The participants are being followed in an observation that will last two years and were able to restart their previous DMT. Following them may help understand the long-term effects of discontinuing treatment, even if for a short time.

Results from a similar clinical trial called DISCOMS (NCT03073603) that was testing if DMTs can be safely stopped in MS patients older than 55 were published this year. Like DOT-MS, DISCOMS showed higher levels of disease activity in those who discontinued. Another similarly designed trial in SPMS patients older than 50, called STOP-I-SEP (NCT03653273), is underway in France, Coerver said.

Note: The Multiple Sclerosis News Today team is providing in-depth coverage of the 9th joint ECTRIMS-ACTRIMS meeting Oct. 11-13. Go here to see the latest stories from the conference.