title: Prediction of response to interferon therapy in multiple sclerosis.
abstract: OBJECTIVE
  Single nucleotide polymorphisms (SNPs) in the genes encoding interferon response factor (IRF)-5, IRF-8 and glypican-5 (GPC5) have been associated with disease activity in multiple sclerosis (MS) patients treated with interferon (IFN)-β. We analysed whether SNPs in the IRF5, IRF8 and GPC5 genes are associated with clinical disease activity in MS patients beginning de novo treatment with IFN-β.
  
  
  METHODS
  The SNPs rs2004640, rs3807306 and rs4728142 in IRF5, rs13333054 and rs17445836 in IRF8 and rs10492503 in GPC5 were genotyped in 575 patients with relapsing-remitting MS followed prospectively after the initiation of their first treatment with IFN-β.
  
  
  RESULTS
  62% of patients experienced relapses during the first 2 years of treatment, and 32% had disability progression during the first 5 years of treatment. Patients with a pretreatment annualized relapse rate >1 had an increased risk of relapse (hazard ratio 1.53, 95% confidence interval 1.24-1.90) and progression (hazard ratio 1.48, 95% confidence interval 1.10-1.99) on treatment and patients with breakthrough relapses in the form of relapses during the first 2 years of treatment had an increased risk of progression during the first 5 years of treatment (hazard ratio 2.04, 95% confidence interval 1.47-2.85).The gene variants in IRF5, IRF8 and GPC5 were not associated with risk of relapse or disease progression.
  
  
  CONCLUSIONS
  Pretreatment relapse rate and clinical disease activity during the first 2 years of treatment may be associated with disease progression in MS patients treated with IFN-β. Genetic analysis of the studied gene variants do not provide additional information.
authors.affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Sellebjerg
authors.forename: H B
authors.initials: HB
authors.lastname: Søndergaard
authors.forename: N
authors.initials: N
authors.lastname: Koch-Henriksen
authors.forename: P S
authors.initials: PS
authors.lastname: Sørensen
authors.forename: A B
authors.initials: AB
authors.lastname: Oturai
mesh_terms: D000328:Adult; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D053673:Glypicans / Q000235:genetics*; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D016899:Interferon-beta / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D000099185:Interferon Regulatory Factor-8
chemical_list: D053673:Glypicans; D050835:Interferon Regulatory Factors; D016899:Interferon-beta; D000099185:Interferon Regulatory Factor-8; C106228:GPC5 protein, human; C431713:IRF5 protein, human
keywords: interferon-beta; multiple sclerosis; pharmacogenetics; treatment response