title: Lack of interferon-beta bioactivity is associated with the occurrence of relapses in multiple sclerosis.
abstract: BACKGROUND
  Treatment failure to Interferon-beta (IFNbeta) in multiple sclerosis (MS) can only partly be explained by anti-IFNbeta neutralising antibodies (NAb). Myxovirus resistance protein A (MxA) mRNA, reflecting IFNbeta bioactivity, is studied as an alternative biomarker for IFNbeta therapy response. Although absent IFNbeta bioactivity is associated with NAb and NAb are associated with reduced drug efficacy, the direct relationship between IFNbeta bioactivity and clinical disease activity is largely unknown.
  
  
  METHODS
  We enrolled 126 consecutive relapsing-remitting MS patients on IFNbeta treatment. MxA mRNA expression was assessed 4 h after IFNbeta injection. Biological response status was determined after 3 months, by combined measurement of MxA mRNA expression and induction (MxA mRNA expression after/before IFNbeta injection). Patients were considered biological non-responders when both MxA mRNA expression and MxA mRNA induction were negative.
  
  
  RESULTS
  Biological non-responders showed a significantly higher annualised relapse rate and smaller proportion relapse-free patients compared with biological responders (relapse rate 0.81 vs. 0.37; proportion relapse free 37% vs. 67%).
  
  
  CONCLUSIONS
  Our results suggest that a lack of IFNbeta bioactivity is associated with the occurrence of relapses and therefore can be useful as a biomarker for unresponsiveness to IFNbeta.
authors.affiliation: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands. laura.vandervoort@vumc.nl
authors.forename: L F
authors.initials: LF
authors.lastname: van der Voort
authors.forename: A
authors.initials: A
authors.lastname: Visser
authors.forename: D L
authors.initials: DL
authors.lastname: Knol
authors.forename: C B M
authors.initials: CB
authors.lastname: Oudejans
authors.forename: C H
authors.initials: CH
authors.lastname: Polman
authors.forename: J
authors.initials: J
authors.lastname: Killestein
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D019204:GTP-Binding Proteins / Q000097:blood*; D006801:Humans; D016899:Interferon-beta / Q000097:blood* / Q000627:therapeutic use; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy*; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017211:Treatment Failure
chemical_list: D015415:Biomarkers; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D016899:Interferon-beta; D019204:GTP-Binding Proteins