title: Effect of anti-IFN{beta} antibodies on MRI lesions of MS patients in the BECOME study.
abstract: BACKGROUND
  Interferon beta (IFNbeta) administered subcutaneously is immunogenic in some patients with multiple sclerosis (MS) and leads to the development of neutralizing antibodies (NAbs). Considerable evidence has accumulated that NAbs diminish or abolish IFNbeta bioactivity, but there is less evidence that NAbs impact clinical efficacy of the drug.
  
  
  METHODS
  Because a robust effect of IFNbeta is a decrease in enhancing lesions on brain MRI scans, the Betaseron Copaxone in Multiple Sclerosis With Triple-Dose Gadolinium and 3-Tesla MRI Endpoints (BECOME) study, a head-to-head study of IFNbeta-1b vs glatiramer acetate with a primary endpoint of enhancing lesions on MRI, provided an excellent opportunity to determine the effect of NAbs on MRI activity. We measured NAbs and IFNbeta bioactivity by myxovirus resistance protein A gene expression and identified 2 groups of patients: one labeled "bioactivity preserved," with absent NAbs and robust IFNbeta bioactivity (n = 8), and the other labeled "bioactivity lost," with high levels of NAbs and diminished bioactivity (n = 7). The development of enhancing lesions in the groups was then compared.
  
  
  RESULTS
  The incidence of NAbs and effect of NAbs on bioactivity were consistent with previous studies. We analyzed MRI outcomes in patients with NAbs at levels high enough to abolish bioactivity relative to patients without NAbs. For the preserved bioactivity group, the enhancing lesion/scan ratio decreased from 7.6 in the pretreatment period to 2.6 in the posttreatment period, a 66% decrease. For the lost bioactivity group, the decrease was 8.5 to 5.8, only a 32% decrease. Thus, lost bioactivity from high levels of NAbs resulted in reduced therapeutic efficacy of IFNbeta as manifested by diminished reductions in enhancing lesions on MRI.
  
  
  CONCLUSIONS
  High levels of anti-interferon beta (IFNbeta) antibodies, which result in diminished bioactivity, are correlated with reduced therapeutic efficacy of IFNbeta.
authors.affiliation: UMDNJ-New Jersey Medical School, 185 South Orange Ave., MSBH506, Newark, NJ 07103, USA. pachner@umdnj.edu
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Pachner
authors.forename: Diego
authors.initials: D
authors.lastname: Cadavid
authors.forename: Leo
authors.initials: L
authors.lastname: Wolansky
authors.forename: Joan
authors.initials: J
authors.lastname: Skurnick
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood* / Q000276:immunology; D003287:Contrast Media; D004361:Drug Tolerance; D005260:Female; D005682:Gadolinium; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D011446:Prospective Studies; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D003287:Contrast Media; D007155:Immunologic Factors; D016899:Interferon-beta; D005682:Gadolinium