Effectiveness of switching to rituximab over fingolimod or dimethyl fumarate after natalizumab in preventing disease activity in multiple sclerosis

OBJECTIVE: To compare efficacy and discontinuation rates after switching from natalizumab for multiple sclerosis (MS) to rituximab, fingolimod, or dimethyl fumarate (DMF). BACKGROUND: Natalizumab discontinuation has been associated with rebound/return of disease activity. Studies have highlighted the importance of minimizing washouts after natalizumab when switching to fingolimod. Little evidence exists on switching to DMF or rituximab. DESIGN/METHODS: MS patients at Rocky Mountain MS Center at Anschutz Medical Campus (University of Colorado) were identified who received natalizumab (>=12 months) and switched to rituximab, fingolimod or DMF prior to November 2013 with maximum 6 month washout. A retrospective chart review collected demographic information, medication reactions, clinical relapses, MRI lesions, and laboratory data. RESULTS: 118, 50, and 110 patients were identified who received natalizumab for >=12 months and switched within 6 months to rituximab, fingolimod, or DMF, respectively, with >=12 months potential treatment. Of 118 patients treated subsequently with rituximab, 1 (0.8%) patient had 2 clinical relapses and none had enhancing lesions. Of the 110 patients switching to fingolimod, 2 (1.8%) had a clinical relapse and 10 (9.1%) had enhancing lesions with a mean of 4.0 enhancing lesions while on fingolimod. Of 50 patients switching to DMF, 2 (4.0%) had a clinical relapse and 3 (6.0%) had enhancing lesions with a mean of 4.7 enhancing lesions while on DMF. Switching to rituximab was associated with fewer enhancing lesions than to fingolimod (p=0.001) or DMF (p=0.007). 8 (6.8%), 19 (17.3%), and 12 (24.0%) respectively on rituximab, fingolimod, and DMF discontinued treatment before achieving 12 months (p<0.001 rituximab versus fingolimod or DMF). The median transition periods were 1 month for rituximab and fingolimod and 0 months for DMF. Factors that led to discontinuation were examined. CONCLUSION: Minimizing transition times from natalizumab to rituximab, fingolimod, or DMF was associated with little disease activity. Switching to rituximab led to fewer enhancing lesions and discontinuation of treatment than fingolimod or DMF.