medwireNews: The DOT-MS trial has found that discontinuation of first-line disease-modifying therapy (DMT) for multiple sclerosis (MS) can lead to recurrence of inflammatory disease activity in nearly 20% of patients, even in those whose disease has been stable for over 5 years.
The trial was prematurely halted after a median of 15.3 months because patients randomly assigned to discontinue DMT had a significantly higher rate of significant inflammatory disease activity recurrence than those who did not discontinue treatment, at 17.8% versus 0.0%, which was above the predefined safety limit.
However, the researchers note that over 75% of participants had no disease recurrence after DMT discontinuation, and therefore they 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.”
The benefit–risk profile of therapy for MS changes as patients get older, so “there is an increasing need to know if and when treatment can potentially be discontinued,” write Eva Strijbis (Amsterdam University Medical Center, the Netherlands) and colleagues in JAMA Neurology.
They recruited patients with relapse-onset MS, aged 18 years or older (median 54 years), who were receiving first-line DMT and had not had a relapse or substantial magnetic resonance imaging (MRI) activity in the previous 5 years.
A total of 89 patients randomly assigned to discontinue or continue DMT (n=45 and 44, respectively) were available for assessment at the time the trial was terminated. Of these, 67.4% were women.
The primary endpoint of significant inflammatory disease, defined as relapse and/or three or more T2 lesions or two or more contrast-enhancing lesions on brain MRI, occurred in eight of the participants who discontinued DMT, compared with none of participants who did not, a significant difference. The median time for patients to experience significant inflammatory disease was 12 months.
“No participants experienced clinical relapse without inflammatory MRI activity,” the researchers note. Clinical relapse occurred in two patients and significant MRI activity in seven patients. An additional 11 patients in the discontinuation group and one patient in the continuation group had any MRI activity, defined as up to two new T2 lesions, one contrast-enhancing lesion, or enlarged T2 lesion.
The rate of recurrence of inflammation in the discontinuation group was significantly higher in the MS-DOT trial than the 5.3% rate reported using the same criteria in the 2023 DISCOMS trial. However, the DISCOMS trial only included participants over the age of 55 years (median 63 years), say Strijbis et al.
They found that in their trial, patients with significant disease activity were generally younger, at a median of 46 years versus 54 years for those without, although 11.1% were 45 years or older, including some older than 55 years, the investigators add.
“This suggests that even older patients face some risk of recurrence after discontinuation,” while the level of risk in younger patients “was unknown prior to the DOT-MS trial,” they observe.
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