Discontinuation of disease-modifying treatments (DMTs) may lead to an increased risk of inflammatory activity, especially with second-line drugs, in patients with multiple sclerosis (MS), according to a study recently published in the Journal of Neurology.

“Our study suggests that the risk of recurrence of focal inflammatory activity is greater after discontinuation of second-line versus first-line DMTs, even in patients over 45 years of age (and even after 55 years),” the authors wrote. 

This retrospective study included 232 patients previously diagnosed with MS with a median age of 52.8 years. According to the inclusion criteria, patients experienced a relapse according to the McDonald criteria and received the same DMT for 6 months or more prior to discontinuing it. Only 49 (21.12%) individuals discontinued second-line DMT. 

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Of all drugs, natalizumab, a second-line DMT, exhibited the highest relapse rate, with a 43% probability of inflammatory activity in 1 year after discontinuation. Patients previously treated with fingolimod, another second-line option, had a 9% risk of relapse. 

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The overall probability of relapse with second-line drugs was 20%, while first-line DMT exhibited the lowest values, at 6%. The multivariate analysis determined a stronger association of natalizumab with relapses when compared to first-line drugs, with a hazard ratio of 3.24.

Moreover, although the probability of relapse after discontinuing first-line DMT increased to 21% at 5 years, researchers observed that most relapses occurred during the first 3 months after abandoning second-line DMT.

Conversely, among the 9 patients that stopped rituximab at 45 years of age or older, none experienced a relapse. Considering all 92 patients that stopped this drug, with a median age of 40 years, only 3 presented with a relapse. 

“These encouraging results suggest that rituximab can be discontinued without the need for an alternative treatment in older patients, but will have to be confirmed,” the authors noted.

These findings suggest that discontinuing DMT should be carefully examined before making the decision, even in middle-aged patients and especially in those treated with second-line options. As for younger patients, stopping natalizumab may only be an option whenever the appropriate substitutional therapy is already assessed and ready to be initiated. 


Chappuis M, Rousseau C, Bajeux E, et al. Discontinuation of second- versus first-line disease-modifying treatment in middle-aged patients with multiple sclerosis. J Neurol. Published online September 16, 2022. doi:10.1007/s00415-022-11341-2