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

Mult Scler. 2016 Sep;22(10):1315-26. doi: 10.1177/1352458516650736. Epub 2016 May 26.


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.

Keywords: Multiple sclerosis; comparison; fingolimod; natalizumab; second line.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Databases, Factual
  • Deprescriptions
  • Female
  • Fingolimod Hydrochloride / therapeutic use*
  • Glatiramer Acetate / therapeutic use
  • Humans
  • Immunologic Factors / therapeutic use*
  • Immunosuppressive Agents / therapeutic use*
  • Interferons / therapeutic use
  • Leukoencephalopathy, Progressive Multifocal / chemically induced
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Natalizumab / therapeutic use*
  • Recurrence
  • Retrospective Studies
  • Treatment Failure
  • Treatment Outcome
  • Young Adult


  • Immunologic Factors
  • Immunosuppressive Agents
  • Natalizumab
  • Glatiramer Acetate
  • Interferons
  • Fingolimod Hydrochloride