Natalizumab versus fingolimod in patients with relapsing-remitting multiple sclerosis non-responding to first-line injectable therapies.

BACKGROUND: Natalizumab and fingolimod have not been compared in controlled trials but only in observational studies, with inconclusive results.

OBJECTIVES: The objective of this study is to compare the effect of natalizumab and fingolimod in reducing disease activity in relapsing-remitting multiple sclerosis (RRMS).

METHODS: We included all consecutive RRMS patients switched from first-line agents (glatiramer acetate/interferons) to natalizumab or fingolimod, with a follow-up of 24 months. Data of relapses, Expanded Disability Status Scale score and brain magnetic resonance imaging (MRI) scans were collected. We used propensity score (PS) matching and intention-to-treat analysis.

RESULTS: We retained 102 patients in each cohort after PS matching, with similar baseline characteristics. More patients discontinued natalizumab compared to fingolimod (33% vs 11%, p < 0.001), mainly for progressive multifocal leukoencephalopathy (PML) concern. No serious adverse events occurred in the two cohorts. Compared to fingolimod, the natalizumab group presented a higher percentage of relapse-free patients (66% vs 80%, p = 0.015), a higher percentage of disability-improved patients (6% vs 15%, p = 0.033), a lower percentage of MRI-active patients (38% vs 14%, p = 0.001) and a higher percentage of patients with no evidence of disease activity (NEDA-3; 44% vs 70%, p < 0.001) after 2 years of follow-up. Disability worsening was not statistically different in the two groups.

CONCLUSION: Natalizumab is superior to fingolimod in RRMS patients non-responding to first-line agents.