Discontinuation of second- versus first-line disease-modifying treatment in middle-aged patients with multiple sclerosis

Background and purpose There has been scant research on the consequences of discontinuing second-line disease-modifying treatment (DMT) in middle-aged patients with multiple sclerosis (MS). The objective was therefore to examine the occurrence of focal inflammatory activity after the discontinuation of second versus first-line DMT in patients over 45 years. Methods Patients who had been treated for at least 6 months with second (natalizumab, fingolimod, anti CD20) or first-line DMT and who stopped their DMT were retrospectively included. Kaplan–Meier survival curves were used to study the occurrence of relapse and MRI activity according to the type of DMT stopped. Proportional hazard Cox models were calculated to identify factors associated with focal inflammatory activity. The annualized relapse rate was calculated under treatment and for every 3 months after DMT discontinuation. Results We included 232 patients (median age: 52.8 years), 49 of whom stopped second-line DMT. The probability of having a relapse within the year following discontinuation was 6% for first-line DMT, 9% for fingolimod and 43% for natalizumab. In multivariate analysis, the probability of relapse after DMT discontinuation was significantly increased with natalizumab compared to first-line DMT (HR = 3.24; 95% CI [1.52; 6.90]). A peak of relapse was observed at 0–3 months after stopping natalizumab or fingolimod. Conclusion Our study suggests that the risk of inflammatory activity is greater after discontinuation of natalizumab compared to other DMT even in middle-aged patients. As for younger patients, natalizumab discontinuation should only be considered if there is an adequate substitution of a different therapy . .