title: Neutralizing anti-interferon beta antibodies are associated with reduced side effects and delayed impact on efficacy of Interferon-beta.
abstract: Interferon-beta (IFNbeta) is a biological therapy which is immunogenic, inducing anti-IFN-beta neutralizing antibodies (Nabs) in some subjects. The frequency of Nabs varies depending on IFN-beta product and the Nab assay used.
  
  
  OBJECTIVE
  Assess frequency of Nabs using novel Luciferase assay, evaluate association with relapses, frequency of side effects and to compare results with published data.
  
  
  METHODS
  Serum samples at 12 and 24 months and a follow up sample were tested for binding and Nabs. Titre >20 NU was considered positive. Charts were reviewed retrospectively for clinical data.
  
  
  RESULTS
  Out of 327 subjects included, 130 subjects (40%) were binding antibody positive, 89 (27%) were Nab +ve at anytime. Risk at 12 months for being Nab +ve: Avonex 8%, Betaferon 39%, Rebif 33%, P < 10(-5); at 24 months 8, 31 and 27% respectively, P = 0.002. Nab titres were highest in Rebif Nab +ve subjects - 50% >320 NU. Annualized relapse rate was 1.53 pre-treatment, after treatment relapse rate was higher in Nab +ve group 0.67 (95% CI 0.38-0.97) versus 0.5 (0.38-0.61) Nab -ve P = 0.04. Nab status at 12 and 24 months was significantly associated with risk of subsequent relapse, risk being greatest in those with highest titres. Side effects were also significantly associated with Nab -ve status.
authors.affiliation: National Hospital for Neurology and Neurosurgery, Institute of Neurology, Queen Square, London, UK. r.farrell@ion.ucl.ac.uk
authors.forename: R
authors.initials: R
authors.lastname: Farrell
authors.forename: R
authors.initials: R
authors.lastname: Kapoor
authors.forename: S
authors.initials: S
authors.lastname: Leary
authors.forename: P
authors.initials: P
authors.lastname: Rudge
authors.forename: Aj
authors.initials: A
authors.lastname: Thompson
authors.forename: Dh
authors.initials: D
authors.lastname: Miller
authors.forename: G
authors.initials: G
authors.lastname: Giovannoni
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood*; D000918:Antibody Specificity; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D008156:Luciferases; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D007155:Immunologic Factors; D000068576:Interferon beta-1b; D016899:Interferon-beta; D008156:Luciferases; D000068556:Interferon beta-1a