Impact of fingolimod therapy on magnetic resonance imaging outcomes in patients with multiple sclerosis

Arch Neurol. 2012 Oct;69(10):1259-69. doi: 10.1001/archneurol.2012.1051.


Objective: To assess the impact of fingolimod (FTY720) therapy on magnetic resonance imaging measures of inflammatory activity and tissue damage in patients participating in a 2-year, placebo-controlled, phase 3 study.

Design: Patients with active relapsing-remitting multiple sclerosis were randomized to receive fingolimod, 0.5 mg; fingolimod, 1.25 mg; or placebo for 2 years. Standardized magnetic resonance imaging scans were obtained at months 0, 6, 12, and 24 and centrally evaluated for number and volume of T1 gadolinium-enhancing, T2 hyperintense, and T1 hypointense lesions and for percentage of brain volume change. Findings were compared across subgroups by treatment and baseline characteristics.

Setting: Worldwide, multicenter clinical trial.

Patients: Patients were part of the fingolimod FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) clinical trial for relapsing-remitting multiple sclerosis (N=1272).

Main outcome measures: We measured the effect of therapy on acute inflammatory activity, burden of disease, and irreversible loss of brain volume.

Results: Fingolimod therapy resulted in rapid and sustained reductions in inflammatory lesion activity as assessed by gadolinium-enhancing and new/newly enlarged T2 lesions after 6, 12, and 24 months of therapy (P.001, all comparisons vs placebo). Changes in T2 hyperintense and T1 hypointense lesion volume also significantly favored fingolimod (P.05, all comparisons). Fingolimod, 0.5 mg (licensed dose), significantly reduced brain volume loss during months 0 to 6, 0 to 12, 12 to 24, and 0 to 24 (P.05, all comparisons) vs placebo, and subgroup analyses confirmed these effects over 2 years irrespective of the presence/absence of gadolinium-enhancing lesions, T2 lesion load, previous treatment status, or level of disability.

Conclusion: These results, coupled with the significant reductions in relapse rates and disability progression reported previously, support the positive impact on long-term disease evolution.

Trial registration: Identifier: NCT00289978

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Brain / drug effects
  • Brain / pathology*
  • Disability Evaluation
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Encephalitis / drug therapy
  • Encephalitis / etiology
  • Female
  • Fingolimod Hydrochloride
  • Gadolinium
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • International Cooperation
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis / complications
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / pathology*
  • Outcome Assessment, Health Care*
  • Propylene Glycols / therapeutic use*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / therapeutic use
  • Time Factors
  • Young Adult


  • Immunosuppressive Agents
  • Propylene Glycols
  • Gadolinium
  • Fingolimod Hydrochloride
  • Sphingosine

Associated data