title: Effect of statins on clinical and molecular responses to intramuscular interferon beta-1a.
abstract: BACKGROUND
  Findings from a small clinical study suggested that statins may counteract the therapeutic effects of interferon beta (IFNbeta) in patients with relapsing-remitting multiple sclerosis (RRMS).
  
  
  METHODS
  We conducted a post hoc analysis of data from the Safety and Efficacy of Natalizumab in Combination With IFNbeta-1a in Patients With Relapsing-Remitting Multiple Sclerosis (SENTINEL) study to determine the effects of statins on efficacy of IFNbeta. SENTINEL was a prospective trial of patients with RRMS treated with natalizumab (Tysabri, Biogen Idec, Inc., Cambridge, MA) plus IM IFNbeta-1a (Avonex, Biogen Idec, Inc.) 30 microg compared with placebo plus IM IFNbeta-1a 30 microg. Clinical and MRI outcomes in patients treated with IM IFNbeta-1a only (no-statins group, n = 542) were compared with those of patients taking IM IFNbeta-1a and statins at doses used to treat hyperlipidemia (statins group, n = 40).
  
  
  RESULTS
  No significant differences were observed between treatment groups in adjusted annualized relapse rate (p = 0.937), disability progression (p = 0.438), number of gadolinium-enhancing lesions (p = 0.604), or number of new or enlarging T2-hyperintense lesions (p = 0.802) at 2 years. More patients in the statins group reported fatigue, extremity pain, muscle aches, and increases in hepatic transaminases compared with patients in the no-statins group. Statin treatment had no ex vivo or in vitro effect on induction of IFN-stimulated genes.
  
  
  CONCLUSIONS
  Statin therapy does not appear to affect clinical effects of IM interferon beta-1a in patients with relapsing-remitting multiple sclerosis or the primary molecular response to interferon beta treatment.
authors.affiliation: Mellen Center for Treatment and Research in Multiple Sclerosis, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. rudickr@ccf.org
authors.forename: R A
authors.initials: RA
authors.lastname: Rudick
authors.forename: A
authors.initials: A
authors.lastname: Pace
authors.forename: M R S
authors.initials: MR
authors.lastname: Rani
authors.forename: R
authors.initials: R
authors.lastname: Hyde
authors.forename: M
authors.initials: M
authors.lastname: Panzara
authors.forename: S
authors.initials: S
authors.lastname: Appachi
authors.forename: J
authors.initials: J
authors.lastname: Shrock
authors.forename: S L
authors.initials: SL
authors.lastname: Maurer
authors.forename: P A
authors.initials: PA
authors.lastname: Calabresi
authors.forename: C
authors.initials: C
authors.lastname: Confavreux
authors.forename: S L
authors.initials: SL
authors.lastname: Galetta
authors.forename: F D
authors.initials: FD
authors.lastname: Lublin
authors.forename: E-W
authors.initials: EW
authors.lastname: Radue
authors.forename: R M
authors.initials: RM
authors.lastname: Ransohoff
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D000328:Adult; D045744:Cell Line, Tumor; D002490:Central Nervous System / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018450:Disease Progression; D004347:Drug Interactions / Q000502:physiology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000503:physiopathology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D006949:Hyperlipidemias / Q000188:drug therapy*; D007273:Injections, Intramuscular / Q000009:adverse effects / Q000706:statistics & numerical data; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D019169:Jurkat Cells; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D011446:Prospective Studies; D055502:Secondary Prevention; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016899:Interferon-beta; D000068556:Interferon beta-1a