title: Effect of disease-modifying therapies on brain volume in relapsing-remitting multiple sclerosis: results of a five-year brain MRI study.
abstract: OBJECTIVE
  To compare the long-term effect of disease-modifying therapies (DMT) on brain volume loss in relapsing-remitting MS (RRMS) patients.
  
  
  METHODS
  We conducted a study to examine the effect of daily glatiramer acetate (GA), weekly low dose interferon beta (LD-IFNB), and high-dose high-frequency interferon beta disease (HD-IFNB) on brain volume loss over 5 years in RRMS patients. All patients were previously treatment naïve, had disease duration ≤5 years at the time of initiating DMT, and subsequently received the same DMT for 5 years continuously. The percentage change in brain volume (PCBV) was measured using fully automated software. MRI analysis was performed blinded to treatment allocation.
  
  
  RESULTS
  The adjusted PCBV from baseline to year 5 was -2.27% in GA, -2.62% in LD-IFNB, and -3.21% in the HD-IFNB groups (-2.27 vs -2.62, p=0.0036; -2.27 vs -3.21, p<0.0001; -2.62 vs -3.21, p<0.0001). These data remained unchanged from year 1 to year 5, after adjusting for pseudoatrophy in the first year. A group of RRMS patients that remained untreated for a period ranging from 8 to 24 months, served as controls. All treatment groups were significantly better than the rate of projected brain volume loss in the untreated group over 5 years (p<0.0001).
  
  
  CONCLUSIONS
  Global brain volume loss is a dynamic process even in relatively early RRMS patients that occurs despite intervention with therapy. However, all DMT significantly reduced the loss of brain volume compared to no treatment. The GA-treated group experienced the least reduction in brain volume over 5 years, compared to the LD-IFNB and HD-IFNB treated groups. These differences could be partly related to the immunologic consequences of GA therapy in RRMS.
authors.affiliation: MR Image Analysis Laboratory, Department of Neurology, Wayne State University School of Medicine, Detroit, MI 48201, USA. okhan@med.wayne.edu
authors.forename: Omar
authors.initials: O
authors.lastname: Khan
authors.forename: Fen
authors.initials: F
authors.lastname: Bao
authors.forename: Megha
authors.initials: M
authors.lastname: Shah
authors.forename: Christina
authors.initials: C
authors.lastname: Caon
authors.forename: Alexandros
authors.initials: A
authors.lastname: Tselis
authors.forename: Ronald
authors.initials: R
authors.lastname: Bailey
authors.forename: Bruce
authors.initials: B
authors.lastname: Silverman
authors.forename: Imad
authors.initials: I
authors.lastname: Zak
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016899:Interferon-beta / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology*; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology; D010455:Peptides / Q000008:administration & dosage; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate; D016899:Interferon-beta