title: Serum IL-17F does not predict poor response to IM IFNβ-1a in relapsing-remitting MS.
abstract: OBJECTIVE
  There is a significant unmet need for serum biomarkers in relapsing-remitting multiple sclerosis (RRMS) that are predictive of therapeutic response to disease-modifying therapies. Following a recent Stanford study which reported that pretreatment levels of serum interleukin (IL)-17F could predict poor response to interferon-β (IFNβ) therapy, we sought to validate the finding using samples from a large clinical trial.
  
  
  METHODS
  The validation cohort included 54 good responders (GR) and 64 poor responders (PR) selected from 762 subjects with RRMS from the IM IFNβ-1a dose comparison study (Avonex study C94-805). Subjects were classified as GR and PR based on the number of relapses, Expanded Disability Status Scale score, and new and enlarging T2 lesions on MRI. Serum samples were assayed for IL-17F using a multiplexed Luminex assay and for IL-17F/F using an ELISA. Replicate aliquots from the Stanford study were also assayed to assure reproducibility of methods.
  
  
  RESULTS
  Median pretreatment and post-treatment serum IL-17F levels were not statistically significantly different between GR and PR, and serum IL-7/IL-17F ratios were also not predictive of response status. Replicate aliquots from the Stanford study showed good correlation to their original cohort (r = 0.77).
  
  
  CONCLUSIONS
  We were unable to validate the finding that serum IL-17F is a predictor of PR in a large independent cohort of subjects with RRMS. Differences in patient populations and methodology might explain the failure to validate the results from the Stanford study.
authors.affiliation: Biogen Idec, Cambridge, MA, USA. steven.bushnell@biogenidec.com
authors.forename: S E
authors.initials: SE
authors.lastname: Bushnell
authors.forename: Z
authors.initials: Z
authors.lastname: Zhao
authors.forename: C C
authors.initials: CC
authors.lastname: Stebbins
authors.forename: D
authors.initials: D
authors.lastname: Cadavid
authors.forename: A M
authors.initials: AM
authors.lastname: Buko
authors.forename: E T
authors.initials: ET
authors.lastname: Whalley
authors.forename: J A
authors.initials: JA
authors.lastname: Davis
authors.forename: E M
authors.initials: EM
authors.lastname: Versage
authors.forename: J R
authors.initials: JR
authors.lastname: Richert
authors.forename: R C
authors.initials: RC
authors.lastname: Axtell
authors.forename: L
authors.initials: L
authors.lastname: Steinman
authors.forename: R
authors.initials: R
authors.lastname: Medori
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage*; D020381:Interleukin-17 / Q000097:blood*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D015415:Biomarkers; C440021:IL17F protein, human; D020381:Interleukin-17; D016899:Interferon-beta; D000068556:Interferon beta-1a