Discontinuation of DMTs for MS: Stable Patients at Higher Risk for Recurrence

Discontinuation of first-line disease-modifying therapy (DMT) among patients with long-term stable multiple sclerosis (MS) can result in a recurrence of inflammatory disease activity, according to study findings published in JAMA Neurology.

With increasing numbers of patients with MS maintaining stable disease on DMT, the potential for discontinuing therapy has gained interest due to concerns over long-term costs, side effects, and patient burden. In the DOT-MS trial (ClinicalTrials.gov Identifier: NCT04260711), researchers investigated whether discontinuing first-line DMT was safe for patients who had shown no relapses or substantial magnetic resonance imaging (MRI) activity for at least 5 years.

The multicenter trial included 89 adults aged 18 years and older (mean age, 54.0 years; women, 67.4%) with relapse-onset MS from 14 Dutch centers. Participants were randomly assigned to either continue (n=44) or discontinue (n=45) their first-line DMT and were followed for a median of 15.3 months. The primary outcome was significant inflammatory disease activity, defined as clinical relapses and/or the appearance of new or enhancing lesions on MRI.

The researchers found that compared to 0% in the continuation group, 17.8% of patients in the discontinuation group experienced significant inflammatory disease activity. Disease recurrence occurred at a median of 12 months, primarily manifesting as radiological inflammation. Two participants in the discontinuation group experienced clinical relapses.

MRI findings indicated that compared to just 2.3% in the continuation group, 24.4% of those who discontinued DMT exhibited any MRI. Despite these results, over three-quarters of the discontinuation group (77.8%) remained disease-free throughout the trial.

While biomarkers such as neurofilament light chain and glial fibrillary acidic protein increased during disease activity, they did not reliably predict recurrences. The study also reported similar rates of adverse events between the continuation and discontinuation groups, with no serious adverse effects linked to treatment cessation.

Study limitations included early termination, insufficient sample size, incomplete follow-up, and the lack of routine spinal MRI scans and centralized MRI rereads.

“We believe that an attempt to discontinue first-line DMT in long-term stable patients with MS is still a viable option, but close clinical, radiological, and perhaps bio-marker-based monitoring is mandatory,” the researchers concluded.

This research was supported by Amgen Inc., UCB Pharma, and Astellas Pharma Inc. Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.