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Fingolimod withdrawal may trigger the return of pretreatment disease activity. It is difficult to identify patients at risk of disease reactivation. We compared the demographic and clinical features of patients experiencing severe disease reactivation (SDR) after fingolimod cessation with those of patients who did not.All patients who commenced fingolimod and who continued therapy for at least 6 months were included. The demographic and clinical features of the 2 groups (SDR vs. no SDR) were assessed.Forty-four of 303 patients discontinued fingolimod for various reasons. Among these, 31 fulfilled our inclusion criteria and 8 (25.8%) exhibited SDR after drug cessation. The mean time for SDR was 2.6 months (range, 2 to 3 mo). The annualized relapse rate before fingolimod therapy was higher in the SDR than in the non-SDR group (1.59 vs. 0.81) (P=0.018). Although statistical significance was not attained, the mean Expanded Disability Status Scale score at the time of fingolimod cessation was higher in the non-SDR than in the SDR group (2.5 vs. 1.12) (P=0.074).SDR may develop within the first 3 months after cessation of fingolimod. Patients with higher annualized relapse rates and lower Expanded Disability Status Scale scores before commencing fingolimod treatment were more likely to exhibit SDR.