title: Impact of fingolimod therapy on magnetic resonance imaging outcomes in patients with multiple sclerosis.
abstract: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  Worldwide, multicenter clinical trial.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  These results, coupled with the significant reductions in relapse rates and disability progression reported previously, support the positive impact on long-term disease evolution.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00289978
authors: Medical Image Analysis Center, University Hospital, Basel, Switzerland. eradue@uhbs.ch
authors: Ernst-Wilhelm
authors: EW
authors: Radue
authors: Paul
authors: P
authors: O'Connor
authors: Chris H
authors: CH
authors: Polman
authors: Reinhard
authors: R
authors: Hohlfeld
authors: Peter
authors: P
authors: Calabresi
authors: Krystof
authors: K
authors: Selmaj
authors: Nicole
authors: N
authors: Mueller-Lenke
authors: Catherine
authors: C
authors: Agoropoulou
authors: Frederick
authors: F
authors: Holdbrook
authors: Ana
authors: A
authors: de Vera
authors: Lixin
authors: L
authors: Zhang-Auberson
authors: Gordon
authors: G
authors: Francis
authors: Pascale
authors: P
authors: Burtin
authors: Ludwig
authors: L
authors: Kappos
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004660:Encephalitis / Q000188:drug therapy / Q000209:etiology; D005260:Female; D000068876:Fingolimod Hydrochloride; D005682:Gadolinium; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007391:International Cooperation; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D017063:Outcome Assessment, Health Care; D011409:Propylene Glycols / Q000627:therapeutic use*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D005682:Gadolinium; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine