title: Effect of intramuscular interferon beta-1a on gray matter atrophy in relapsing-remitting multiple sclerosis: A retrospective analysis.
abstract: BACKGROUND
  Changes in gray matter (GM) volume may be a useful measure of tissue loss in multiple sclerosis (MS).
  
  
  OBJECTIVE
  To investigate the rate, patterns, and disability correlates of GM volume change in an MS treatment clinical trial.
  
  
  METHODS
  Patients (n=140) with relapsing-remitting MS were randomized to intramuscular (IM) interferon (IFN) beta-1a or placebo. Treatment effects on GM fraction (GMF) and white matter (WM) fraction (WMF) changes, differences in rates of GMF and WMF change in year one and two on treatment, and differences in atrophy rates by disease progression status were assessed retrospectively.
  
  
  RESULTS
  Significantly less GM atrophy (during year two), but not WM atrophy (at any point), was observed with IM IFN beta-1a compared with placebo. Pseudoatrophy effects were more apparent in WM than in GM; in year one, greater WM volume loss was observed with IM IFN beta-1a than with placebo, whereas GM volume loss was similar between groups. Risk of sustained disability progression was significantly associated with GM, but not WM, atrophy.
  
  
  CONCLUSIONS
  These results suggest that GMF change is more meaningful than WMF as a marker of tissue loss and may be useful to augment whole brain atrophy measurements in MS clinical trials.
authors.affiliation: Biogen Inc., Cambridge, USA Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, USA elizabeth.fisher@biogen.com.
authors.forename: E
authors.initials: E
authors.lastname: Fisher
authors.affiliation: Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, USA.
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, USA.
authors.forename: J-C
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Biogen Inc., Cambridge, USA.
authors.forename: X
authors.initials: X
authors.lastname: You
authors.affiliation: Biogen Inc., Cambridge, USA.
authors.forename: B
authors.initials: B
authors.lastname: Sperling
authors.affiliation: Biogen Inc., Cambridge, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Rudick
mesh_terms: D000328:Adult; D001284:Atrophy / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D066128:Gray Matter / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D000068556:Interferon beta-1a / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D012189:Retrospective Studies
chemical_list: D000068556:Interferon beta-1a
keywords: Brain atrophy; brain volume; gray matter atrophy; gray matter fraction; intramuscular interferon beta-1a; magnetic resonance imaging; multiple sclerosis