title: Randomized controlled trial of interferon-beta-1a in secondary progressive MS: MRI results.
abstract: OBJECTIVE
  To examine MRI changes resulting from treatment of secondary progressive MS (SPMS) with two doses of interferon-beta-1a (Rebif).
  
  
  BACKGROUND
  Interferon-beta (IFN-beta) reduces relapses and delays progression in relapsing-remitting MS, but there are conflicting results on its clinical benefit in SPMS.
  
  
  METHODS
  In a double-blind, randomized, multicenter, placebo-controlled study (SPECTRIMS), 618 patients received IFN-beta-1a 22 microg, 44 microg, or placebo subcutaneously three times weekly for 3 years. T2 activity and burden of disease (BOD) were measured in 617 patients by using semiannual proton density/T2-weighted (PD/T2) MRI scans. A cohort of 283 patients also had 11 monthly PD/T2 and T1-weighted gadolinium-enhanced (T1-Gd) scans at study start.
  
  
  RESULTS
  Treatment reduced median numbers of active lesions per patient per scan (semiannual T2 activity: 0.17, 0.20 and 0.67 for the high dose, low dose, and placebo, p < 0.0001; monthly combined unique activity [T1+T2]: 0.11, 0.22, and 1.00, p < 0.0001) and accumulation of BOD (percent change from baseline to month 36: -1.3, -0.5, and 10.0 for the high dose, low dose, and placebo, respectively; p = 0.0001). MRI benefit was most evident in the subgroup of patients who reported relapses in the 2 years before the study. Neutralizing antibody development was associated with reduction in treatment effect: antibody-positive patients did not show significant differences from placebo at either dose.
  
  
  CONCLUSIONS
  Interferon-beta-1a used in SPMS showed significant effects on all MRI measures, particularly in patients with relapses in the 2 years before the study.
authors.affiliation: Department of Radiology, University of British Columbia, Vancouver, Canada.
authors.forename: D K
authors.initials: DK
authors.lastname: Li
authors.forename: G J
authors.initials: GJ
authors.lastname: Zhao
authors.forename: D W
authors.initials: DW
authors.lastname: Paty
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis* / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D016899:Interferon-beta; D000068556:Interferon beta-1a