title: Appearance and disappearance of neutralizing antibodies during interferon-beta therapy.
abstract: BACKGROUND
  Neutralizing antibodies (NABs) occur frequently in patients receiving interferon (IFN)-beta for multiple sclerosis (MS), but it is unclear whether occurrence of NABs is predictive for the persistence of NABs during continued IFN-beta therapy.
  
  
  METHODS
  The authors used an antiviral neutralization bioassay to measure NABs blindly from 6 months up to 78 months in patients with MS who were followed for at least 24 months during treatment with IFN-beta. Patients were classified into three groups: 1) persistently NAB-negative patients, defined as patients without any positive samples at any time; 2) definitely NAB-positive patients, defined as patients who had at least two consecutive positive samples; and 3) patients with fluctuating NAB-positive and NAB-negative samples.
  
  
  RESULTS
  A total of 455 patients were included in the study. Overall, 52.3% of the patients were persistently NAB-negative, 40.9% became definitely NAB-positive, and the remaining 6.8% were fluctuating. More patients treated with IFN-beta-1a (Avonex) remained NAB-negative (p < 0.0001), whereas there was no difference between IFN-beta-1b (Betaferon) and IFN-beta-1a (Rebif). Patients who have remained NAB-negative during the first 24 months of therapy rarely developed NABs. On the contrary, the majority of patients, who had been NAB-positive from 12 through 30 months after start of therapy, remained NAB-positive.
  
  
  CONCLUSIONS
  NABs should be measured in all patients treated with IFN-beta. If patients have been persistently NAB-negative for 24 months, measurements can be discontinued. Patients who have been NAB-positive for a period of 18 months or more usually remain NAB-positive for a long time.
authors.affiliation: Copenhagen MS Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark. pss@rh.dk
authors.forename: P Soelberg
authors.initials: PS
authors.lastname: Sorensen
authors.forename: N
authors.initials: N
authors.lastname: Koch-Henriksen
authors.forename: C
authors.initials: C
authors.lastname: Ross
authors.forename: K M
authors.initials: KM
authors.lastname: Clemmesen
authors.forename: K
authors.initials: K
authors.lastname: Bendtzen
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001681:Biological Assay; D002460:Cell Line; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007118:Immunoassay / Q000592:standards; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology*; D012042:Registries / Q000706:statistics & numerical data
chemical_list: D000276:Adjuvants, Immunologic; D001323:Autoantibodies; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a