title: The influence of patient demographics, disease characteristics and treatment on brain volume loss in Trial Assessing Injectable Interferon vs FTY720 Oral in Relapsing-Remitting Multiple Sclerosis (TRANSFORMS), a phase 3 study of fingolimod in multiple sclerosis.
abstract: BACKGROUND
  Patients with multiple sclerosis (MS) lose brain volume (BV) faster than healthy individuals.
  
  
  OBJECTIVE
  Our purpose, within the 12-month phase 3 TRANSFORMS study, was to examine the effect of treatment on BV loss in patient subgroups, establish correlations between baseline normalized BV (NBV) and baseline disease parameters, to identify variables predictive of baseline NBV and on-study percentage BV change (PBVC), and to establish correlations between on-study PBVC and on-study efficacy outcomes.
  
  
  METHODS
  Patients received fingolimod 0.5 mg or 1.25 mg, or intramuscular (IM) interferon β-1a (IFNβ-1a) for 12 months. The effect of treatment on PBVC was examined in patient demographic, disease and magnetic resonance imaging (MRI) characteristic subgroups. Pearson's correlation analyses and a stepwise linear regression model were used to identify variables predictive of NBV and PBVC.
  
  
  RESULTS
  Fingolimod reduced BV loss over 12 months versus IFNβ-1a IM in all patient subgroups assessed, including individuals with or without gadolinium (Gd)-enhancing lesions at baseline. Baseline T1 hypointense lesion volume had the strongest correlation with baseline NBV. Baseline Gd-enhancing T1 lesion count was most predictive of change in PBVC over 12 months.
  
  
  CONCLUSIONS
  Our results improve understanding of the contributions of different baseline demographic, clinical and MRI characteristics to NBV, including factors that may be predictive of future BV loss.
authors.affiliation: Image Analysis Center, VU University Medical Center, The Netherlands f.barkhof@vumc.nl.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Image Analysis Center, VU University Medical Center, The Netherlands.
authors.forename: Remko
authors.initials: R
authors.lastname: de Jong
authors.affiliation: Novartis Pharma AG, Switzerland.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Sfikas
authors.affiliation: Novartis Pharma AG, Switzerland.
authors.forename: Ana
authors.initials: A
authors.lastname: de Vera
authors.affiliation: Novartis Pharmaceuticals Corporation, USA.
authors.forename: Gordon
authors.initials: G
authors.lastname: Francis
authors.affiliation: Neurological Institute, Cleveland Clinic Foundation, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cohen
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology*; D011409:Propylene Glycols / Q000627:therapeutic use*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D004338:Drug Combinations; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D016899:Interferon-beta; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; D000068556:Interferon beta-1a
keywords: Randomized controlled trial; Trial Assessing Injectable Interferon vs FTY720 Oral in Relapsing–Remitting Multiple Sclerosis (TRANSFORMS) study; brain atrophy; multiple sclerosis; prognosis; volumetric magnetic resonance imaging