The study Discontinuation of First-Line Disease-Modifying Therapy in Patients With Stable Multiple Sclerosis has been selected by the Editor of JAMA Neurology as an Editor’s Choice: Clinical Trials of 2025.  This is a special honor for principal investigator and neurologist Eva Strijbis, PhD candidates Wing Hee Fung and Eline Coerver, and the rest of the research team at the MS Center Amsterdam.

Increasing numbers of people with multiple sclerosis (MS) use disease-modifying therapy (DMT). Long-term disease stability while taking these medications provides a rationale for considering DMT discontinuation, given the patient burden, costs, and potential adverse effects of immunomodulatory therapy. With the DOT-MS clinical trial, Eva Strijbis and her colleagues aimed to investigate whether first-line DMT can be safely discontinued in patients with long-term stable MS.

This randomized clinical trial showed that even in patients whose MS had remained stable for more than five years, discontinuation of first-line DMT can lead to a recurrence of inflammatory disease activity. Although the study cohort was relatively small, recurrence of inflammation in the discontinuation group was significantly higher than in the continuation group. As a result, it was decided early in the trial to stop enrolling new participants, and participants who had discontinued their medication were advised to resume treatment.

More than 75% of participants, however, did not experience a recurrence of disease activity after discontinuing treatment. These findings suggest that discontinuation of first-line MS medication may be a feasible option for a subset of patients with long-term stable MS, although careful individualized assessment remains essential to determine whether stopping treatment can be done safely.

The two PhD candidates who conducted the research, Eline Coerver and Wing Hee Fung, emphasize that regular clinical and radiological monitoring remains important after discontinuation. Further research is needed to better predict which patients can safely stop first-line medication in stable MS.

The DOT-MS study also provided additional data, particularly in a younger MS population and through longitudinal biomarker measurements, to support informed decision-making when treatment discontinuation is being considered.

Read more about the DOT-MS Randomized Clinical Trial at the JAMA Neurology website.  

The DOT-MS clinical trial is funded by ZonMw and Foundation MS Research.