title: The effects of intramuscular interferon beta-Ia in patients at high risk for development of multiple sclerosis: a post hoc analysis of data from CHAMPS.
abstract: BACKGROUND
  In the Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS), intramuscular (IM) interferon beta-1a (IFNbeta-1a) delayed the development of clinically definite multiple sclerosis (CDMS) in patients with a single demyelinating event who had magnetic resonance imaging (MRI) evidence of previous subclinical disease activity (defined as >or=2 T2-weighted hyperintense lesions, 1 of which was periventricular or ovoid, on unenhanced MRI scans).
  
  
  OBJECTIVE
  This post hoc analysis was conducted to assess the effects of IM IFNbeta-1a on delaying the development of CDMS in a subgroup of CHAMPS patients who met a more stringent definition of high risk than was used in that trial.
  
  
  METHODS
  Patients from the overall CHAMPS population were included in the present analysis if they had >or=9 T2-weighted hyperintense lesions and >or=1 gadolinium-enhanced lesion on the baseline MRI scan. The cumulative probability of developing CDMS in each treatment group was calculated using the Kaplan-Meier product-limit method and compared using the log-rank test. The actual proportions of patients who developed CDMS in each treatment group were calculated and compared using the chi-square test.
  
  
  RESULTS
  Ninety-one patients met the more stringent definition of high risk and were included in the subgroup analysis. Fifty-one patients (56.0%) received IFNbeta-1a 30 microg IM once weekly and 40 (44.0%) received placebo. Baseline demographic and clinical characteristics were similar between the 2 groups. Seventy-four patients (81.3%) were female, 80 (87.9%) were white, and the mean age was 33.0 years. Overall, IM IFNbeta-1a reduced the rate of development of CDMS by 66% compared with the placebo group (P = 0.002, log-rank test) over the 3-year follow-up period. At 2 years, the Kaplan-Meier estimate of the cumulative probability of developing CDMS was 21% in the IM IFNbeta-1a group and 56% in the placebo group, representing a 63% reduction in risk for CDMS with IFNbeta-1a (P = 0.002, log-rank test). The results based on the actual proportions of patients developing CDMS were similar to the Kaplan-Meier estimates.
  
  
  CONCLUSIONS
  The results of this subgroup analysis are compatible with IM IFNbeta-1a reducing the risk of a second demyelinating event in patients meeting the more stringent definition of high risk. Although the treatment effect of IFNbeta-1a was significant in both the overall CHAMPS population (44% risk reduction vs placebo; P = 0.002) and in this high-risk subgroup (66%), the results of the present analysis suggest that the magnitude of treatment benefit with IFNbeta-1a may be greater in patients with more disease activity, as measured by MRI parameters.
authors.affiliation: Division of Neurology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. oconnorp@smh.toronto.on.ca
authors.forename: Paul
authors.initials: P
authors.lastname: O'Connor
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies
chemical_list: D000276:Adjuvants, Immunologic; D016899:Interferon-beta; D000068556:Interferon beta-1a