Stable MS patients free of disease activity after DMT stops: Study
Discontinuation ‘a viable option’ with monitoring, researchers say
About four in five adults with stable multiple sclerosis (MS) for at least five years remained free of disease activity after stopping first-line treatment with a disease-modifying therapy (DMT), according to a study based on data from the DOT-MS clinical trial.
Still, disease activity reemerged in roughly 20% of participants after DMT discontinuation, mainly in the form of lesions detected by MRI scans. This activity correlated with higher levels of neurofilament light chain, a biomarker of nerve damage.
“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 biomarker-based monitoring is mandatory,” researchers wrote.
The study, “Discontinuation of First-Line Disease-Modifying Therapy in Patients With Stable Multiple Sclerosis,” was published in JAMA Neurology.
DMTs are designed to target the underlying cause of MS to slow, delay, or stop its progression. Most of these therapies seek to suppress the immune system to mitigate the abnormal inflammatory response that marks MS.
Measuring disease activity with DMTs
With continuous improvements in the criteria used to diagnose MS, patients are often diagnosed in very early disease stages, and many start treatment with a DMT before they experience any symptoms.
This can help patients control the disease in its early stages, sometimes completely preventing the occurrence of disease relapses or new lesions, but its not clear if MS patients can safely discontinue treatment after several years of stable disease.
This is particularly important as long-term use of DMTs has been associated with an increased risk of infections and certain cancers. DMTs are also believed to become less effective with age, as the inflammatory response that drives MS steadily decreases.
A team led by researchers at the Multiple Sclerosis Center Amsterdam aimed to find out whether first-line DMT can safely be discontinued in patients 18 and older with long-term, stable MS.
They launched the DOT-MS clinical trial (NCT04260711) to test the impact of DMT discontinuation in adults with relapsing forms of MS who had stable MS under a first-line DMT. Stable MS meant participants were free of relapses and evidence of inflammatory activity on MRI scans for at least the past five years.
Nearly all participants (89.9%) had relapsing-remitting MS, while the remaining had secondary progressive MS. Most were women (67.4%), with a median age of 54, and the median time since the last relapse was 9.4 years.
Participants were randomly assigned to continue or discontinue their DMT and underwent repeated clinical evaluations and brain MRI scans for up to two years. The primary goal was to determine the proportion of patients who experienced significant MS activity during follow-up, defined as any relapse and/or significant MRI activity — three or more new lesions or two or more lesions with active inflammation.
Over a median of 15.3 months, 17.8% of the participants who stopped DMT had significant disease activity, compared with none of those who continued treatment. The median time between stopping the DMT and new MS activity was 12 months, and all events involved MRI lesions with or without relapses.
The number of patients in the discontinuation group who experienced disease activity exceeded the predefined limits for the trial, prompting DOT-MS’s early termination in 2023. Researchers conducted additional analyses on the available data.
Results also showed that, although participants could restart their DMT during the trial, three out of four participants (77.8%) in the discontinued group remained off treatment until the end of follow-up. Still, within six months of restarting the DMT, 10 of 12 patients with any MRI activity were clinically and MRI stable.
Biomarkers for nerve damage were similar between the continued and discontinued groups over time, but NfL levels were significantly higher among those with substantial disease activity.
No differences were noted in disability progression, walking function, dexterity, or cognition before or after the study between the DMT-continuing and discontinued groups. The results of self-reported questionnaires for disease impact, strength, and health status were also similar between the two groups.
Participants were asked, “How satisfied are you with your present DMT or lack of DMT?” By the end of the study, all participants with significant MRI activity remained satisfied with the discontinuation of their DMT.
“This study shows that first-line DMT discontinuation led to disease recurrence (mainly radiological) in a significant proportion of participants with relapse-onset MS, even in those who were inflammatory stable for 5 or more years,” the team concluded. “However, over 75% of participants had no disease recurrence after DMT discontinuation.”
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