Effectiveness and safety of switching from fingolimod and natalizumab to rituximab in patients with relapsing remitting multiple sclerosis

Natalizumab and fingolimod are well-established, sequestrating disease-modifying treatments (DMTs), widely used as a second-line treatment in patients with relapse remitting multiple sclerosis (RRMS). However, there is no standard strategy for managing treatment failure on these agents. The present study aimed to evaluate the effectiveness of rituximab after natalizumab and fingolimod withdrawal.A retrospective cohort was accomplished on RRMS patients treated with natalizumab and fingolimod who were switched to rituximab.100 patients (50 cases in each group) were analyzed. After six months of follow-up, a substantial decline in clinical relapse and disability progression was observed in both groups. However, no significant change was demonstrated in the pattern of MRI activity (P = 1.000) in natalizumab pretreated patients. After adjusting for the baseline characteristics, a head-to-head comparison found a non-significant trend of lower EDSS in the pretreated fingolimod group compared to those previously treated with natalizumab(P = 0.057). However, in terms of clinical relapse and MRI activity, the clinical outcomes were comparable in both groups ((P = 0.194), (P = 0.957). Moreover, rituximab was well-tolerated, and no serious adverse events were reported.The present study revealed the effectiveness of rituximab as an appropriate alternative option for escalation therapy after fingolimod and natalizumab discontinuation.