title: Randomized study of once-weekly interferon beta-1la therapy in relapsing multiple sclerosis: three-year data from the OWIMS study.
abstract: BACKGROUND
  Once weekly interferon beta-1a for multiple sclerosis (OWIMS) demonstrated modest, but significant, magnetic resonance imaging (MRI) benefit of once-weekly (qw) interferon (IFN) beta-1a at 48 weeks, but no significant effect on relapses.
  
  
  OBJECTIVE
  An OWIMS extension permitted assessment of longer-term efficacy/safety of qw IFN beta-1a in relapsing-remitting multiple sclerosis (RRMS).
  
  
  METHODS
  Placebo patients were rerandomized to IFN beta-1a, 22 or 44 mcg qw, for two additional 48-week intervals. Primary outcome was MRI lesion activity. Relapse rate and other MRI measures were secondary outcomes.
  
  
  RESULTS
  After three years, median (mean) T2 lesion count/patient/scan was 1.3 (2.6) for 44 mcg, 1.7 (3.3) for 22 mcg, 1.7 (3.4) for placebo/22 mcg, 2.0 (3.6) for placebo/44 mcg (all differences not significant). Annualized relapse rates were lowest for 44 mcg (0.77) versus other groups (0.83-0.86, not significant). Persistent neutralizing antibodies did not affect relapse rates, but MRI active lesions were increased in antibody-positive patients receiving 44 mcg compared to antibody negative patients.
  
  
  CONCLUSIONS
  In RRMS, once weekly IFN beta-1a, particularly 44 mcg, can induce a significant MRI, but not relapse, effect, compared with placebo. No significant dose effect was seen. In contrast to the significant effect observed with three-times-weekly dosing of subcutaneous IFN beta-1a compared with placebo, this study confirms the lack of meaningful clinical benefit with once-weekly dosing.
authors.affiliation: Ottawa Hospital - General Campus, Ottawa, Ontario, Canada. mfreedman@ottawahospital.on.ca
authors.forename: M S
authors.initials: MS
authors.lastname: Freedman
authors.forename: G S
authors.initials: GS
authors.lastname: Francis
authors.forename: E A C M
authors.initials: EA
authors.lastname: Sanders
authors.forename: G P A
authors.initials: GP
authors.lastname: Rice
authors.forename: P
authors.initials: P
authors.lastname: O'Connor
authors.forename: G
authors.initials: G
authors.lastname: Comi
authors.forename: P
authors.initials: P
authors.lastname: Duquette
authors.forename: L
authors.initials: L
authors.lastname: Metz
authors.forename: T J
authors.initials: TJ
authors.lastname: Murray
authors.forename: J-P
authors.initials: JP
authors.lastname: Bouchard
authors.forename: O
authors.initials: O
authors.lastname: Abramsky
authors.forename: J
authors.initials: J
authors.lastname: Pelletier
authors.forename: F
authors.initials: F
authors.lastname: O'Brien
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000906:Antibodies / Q000097:blood; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D016899:Interferon-beta; D000068556:Interferon beta-1a