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Significant radiological inflammation emerged in nearly one in five stable multiple sclerosis (MS) patients who stopped using first-line disease-modifying therapy (DMT), the DOT-MS trial showed.

The study was terminated prematurely because inflammatory disease activity recurred above predefined limits, reported Eva Strijbis, MD, PhD, of the Amsterdam University Medical Center in the Netherlands, and colleagues.

The primary endpoint of significant inflammatory disease activity was defined as relapse, three or more new T2 lesions, or two or more contrast-enhancing lesions.

A total of 17.8% (eight of 45 participants) in the discontinue group met the primary endpoint, according to the researchers in . Six had radiological inflammation only; two also had clinical relapse. The median time to disease activity was 12 months.

In contrast, none of the 44 participants in the continue group met this endpoint. Overall, 11 participants in the discontinue group (24.4%) and one participant in the continue group (2.3%) had any MRI activity.

"First-line DMT discontinuation can lead to recurrence of inflammatory disease activity in approximately 20% of cases, even in patients with long-term stable MS," Strijbis and colleagues wrote.

"However, over 75% of participants had no disease recurrence after DMT discontinuation," they added. "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."

In 2023, the trial, led by John Corboy, MD, of the Rocky Mountain MS Center at the University of Colorado in Aurora, provided insight into whether people with stable MS should continue DMT as they age. DISCOMS could not determine noninferiority of stopping DMT in an older population with stable disease.

Unlike DISCOMS, which evaluated MS patients ages 55 and older, "DOT-MS potentially included patients as young as 18, and the median age was 9 years younger than the DISCOMS mean age -- 54 versus 63," Corboy pointed out.

"The DOT-MS trial was a well-designed study," Corboy told 名媛直播. "It strongly reinforces that age and recency of active disease are important factors related to disease recurrence after discontinuation, given twice the amount of new activity versus DISCOMS when comparing apples to apples. This information is very useful for patients and providers."

evaluated 89 participants at 14 Dutch centers who were in the study when it was terminated in 2023. About half of participants were assigned to the continue group and half to the discontinue group. All participants were at least age 18 years and had relapse-onset MS (relapsing-remitting or secondary progressive disease) with no clinical relapses or substantial radiological disease activity in the past 5 years.

The median time since the last documented relapse was 9.4 years. Most participants (65.1%) were receiving injectable MS drugs -- glatiramer acetate or interferon beta.

Participants had a median age of 54 at enrollment and two-thirds (67.4%) were female. Most participants (90%) had relapsing-remitting disease. Baseline disability scores, cognitive scores, and levels of serum neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) were similar in the continue and discontinue groups.

There were no significant differences at baseline between participants with and without any MRI activity. Within 6 months, 10 of 12 participants with any inflammatory activity were clinically and MRI stable; two had persistent disease activity on MRI.

Planned noninferiority testing could not be performed in DOT-MS due to the sample size when the trial was terminated, Strijbis and co-authors said.

"The DOT-MS trial will continue in an observational design," they wrote. "Participants who discontinued their DMT were offered to restart and will be followed-up for 2 years. Long-term consequences of DMT discontinuation and time to status of no evident disease activity will be studied."

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