title: Persistence of neutralizing antibodies after discontinuation of IFNbeta therapy in patients with relapsing-remitting multiple sclerosis.
abstract: OBJECTIVE
  The main objective was to follow serum levels of neutralizing antibodies (NABs) against interferon-beta (IFNbeta) after discontinuation of IFNbeta therapy.
  
  
  BACKGROUND
  A large proportion of patients treated with recombinant IFNbeta for multiple sclerosis (MS) develop therapy-induced NABs. Knowledge of persistence of NABs after discontinuation of therapy is limited.
  
  
  METHODS
  A retrospective follow-up study of patients treated in Denmark for relapsing remitting (RR) MS with IFNbeta for at least 12 months. NAB-positive patients, who discontinued therapy, were followed up with measurements of NABs.
  
  
  METHODS
  We measured NAB-neutralizing capacity and NAB titres a.m. Kawade using a clinically validated cytopathic effect assay.
  
  
  RESULTS
  Thirty-seven patients were included. Mean follow-up time was 22 months. Of the 29 patients with a NAB titre at or above 25 prior to termination of therapy, only three patients reverted to a titre below 25. Of these, two had a titre below 200 and one patient a titre of 600 at the last examination before treatment stop. The longest post-treatment follow-up during which a patient maintained NAB positivity was 59 months.
  
  
  CONCLUSIONS
  NABs against IFNbeta, especially with high titres, tend to persist for a long time after discontinuation of IFNbeta therapy. NABs should always be measured before reinstitution of IFNbeta treatment in NAB-positive patients.
authors.affiliation: Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Bodil
authors.initials: B
authors.lastname: Petersen
authors.forename: Klaus
authors.initials: K
authors.lastname: Bendtzen
authors.forename: Nils
authors.initials: N
authors.lastname: Koch-Henriksen
authors.forename: Mads
authors.initials: M
authors.lastname: Ravnborg
authors.forename: Christian
authors.initials: C
authors.lastname: Ross
authors.forename: Per Soelberg
authors.initials: PS
authors.lastname: Sorensen
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000906:Antibodies / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology*; D009500:Neutralization Tests; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D016899:Interferon-beta