title: Interferon β-1b-neutralizing antibodies 5 years after clinically isolated syndrome.
abstract: OBJECTIVE
  To determine the frequency and consequences of neutralizing antibodies (NAbs) in patients with a first event suggestive of multiple sclerosis (MS) treated with interferon β-1b (IFNβ-1b).
  
  
  METHODS
  In the Betaseron/Betaferon in Newly Emerging MS For Initial Treatment (BENEFIT) study, patients were randomly assigned to 250 μg IFNβ-1b (Betaferon) or placebo subcutaneously every other day for 2 years or until diagnosis of clinically definite MS (CDMS). Patients were then offered open-label IFNβ-1b for up to 5 years. NAb status was assessed every 6 months by the myxovirus protein A induction assay. A titer >20 NU/mL was considered NAb-positive, with low (≥20-100 NU/mL), medium (≥100-400 NU/mL), and high (≥400 NU/mL) titer categories. Here we examine early-treated patients, who received IFNβ-1b for up to 5 years.
  
  
  RESULTS
  NAbs were measured in 277 of 292 early-treated patients and detected at least once in 88 (31.8%) patients, with 53 (60.2%) reverting to NAb negativity by year 5. Time to CDMS, time to confirmed disability progression, and annualized relapse rate did not differ between NAb-positive and NAb-negative patients or between periods of NAb positivity vs NAb negativity within patients. Increases in newly active lesion number and T2 lesion volume and conversion to McDonald MS were associated with NAb positivity and were more pronounced with higher titers.
  
  
  CONCLUSIONS
  Although NAb positivity was associated with increased brain MRI activity, no discernible effects on clinical outcomes were found. This finding may reflect the greater power of MRI compared with clinical outcomes to detect the treatment effects of IFNβ-1b and may also result from temporal changes in NAb titers and biology.
authors.affiliation: Department of Neurology, Heinrich-Heine-Universität, Düsseldorf 40225, Germany. hans-peter.hartung@uni-duesseldorf.de
authors.forename: H-P
authors.initials: HP
authors.lastname: Hartung
authors.forename: M S
authors.initials: MS
authors.lastname: Freedman
authors.forename: C H
authors.initials: CH
authors.lastname: Polman
authors.forename: G
authors.initials: G
authors.lastname: Edan
authors.forename: L
authors.initials: L
authors.lastname: Kappos
authors.forename: D H
authors.initials: DH
authors.lastname: Miller
authors.forename: X
authors.initials: X
authors.lastname: Montalbán
authors.forename: F
authors.initials: F
authors.lastname: Barkhof
authors.forename: J
authors.initials: J
authors.lastname: Petkau
authors.forename: R
authors.initials: R
authors.lastname: White
authors.forename: V
authors.initials: V
authors.lastname: Sahajpal
authors.forename: V
authors.initials: V
authors.lastname: Knappertz
authors.forename: K
authors.initials: K
authors.lastname: Beckmann
authors.forename: V
authors.initials: V
authors.lastname: Lanius
authors.forename: R
authors.initials: R
authors.lastname: Sandbrink
authors.forename: C
authors.initials: C
authors.lastname: Pohl
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood*; D003430:Cross-Sectional Studies; D003711:Demyelinating Diseases / Q000097:blood* / Q000188:drug therapy*; D005500:Follow-Up Studies; D006801:Humans; D007279:Injections, Subcutaneous; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000008:administration & dosage* / Q000097:blood* / Q000627:therapeutic use; D008137:Longitudinal Studies; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D011446:Prospective Studies
chemical_list: D057134:Antibodies, Neutralizing; D000068576:Interferon beta-1b; D016899:Interferon-beta