Recurrence of disease activity after fingolimod discontinuation in older patients previously stable on treatment

•35.2% of patients experience RDA, clinical or radiological, after fingolimod discontinuation, which can be severe in 12.5% of patients.•Younger age at disease onset, high pre-treatment disease activity and previous natalizumab treatment correlate with RDA.•RDA is not rare in older patients despite long-standing inactive disease. Discontinuing fingolimod (FTY) in older patients is a growing concern with little evidence supporting the decision to pursue treatment and reasonable doubt for disease reactivation after withdrawal. To estimate the incidence of recurrence of disease activity (RDA) and rebound after FTY withdrawal in patients older than 50 years. Retrospective analysis of all MS patients in our clinic who discontinued FTY after at least 6 months of treatment, according to disease activity on FTY and age at discontinuation. RDA was defined as the occurrence of either clinical and/or MRI activity in the 6 months after FTY withdrawal and rebound when the levels of disease activity surpassed pretreatment activity. From the 128 patients who discontinued FTY since 2011, up to 35.2% of patients experienced evidence of disease activity and 12.5% had a rebound. The incidence of both RDA and rebound was not different among individuals who had persistent disease activity on FTY to those who stopped FTY for other reasons than inefficacy (RDA: 25.5% vs 20.5%, p = 0.353 rebound: 14.5% vs 11%, p = 0.596). Negative predictive factors for RDA were younger age at disease onset (p = 0.036), highly active disease at baseline (p = 0.003) and previous treatment with NTZ (p = 0.013). Older age at FTY discontinuation did not reduce the risk of RDA in patients previously stable on treatment (OR 0.972, 95% CI 0.871–1.085, p = 0.613), although the incidence of RDA/rebound was half less in the older patients (36.5% in the