title: The use of valproic acid and multiple sclerosis.
abstract: BACKGROUND
  Animal studies have suggested that drugs inhibiting the enzyme histone deacetylase might have a beneficial effect on multiple sclerosis (MS). Valproic acid (VPA), an anti-epileptic drug, is the only widely used human drug with a histone deacetylase inhibitory effect.
  
  
  OBJECTIVE
  The objective of this paper is to examine if VPA use is associated with a reduced risk of MS.
  
  
  METHODS
  We conducted a propensity score-matched cohort study in the period 1997-2011 linking nationwide register data on filled VPA prescriptions, MS cases, and several covariates. The VPA users were matched on propensity scores in a 1:4 ratio with non-users of VPA. Incidence rates of MS were compared among VPA users and non-users of VPA using Cox regression to estimate hazard ratios (HRs).
  
  
  RESULTS
  Among 16 028 ever-users of VPA and 54 172 non-users, 18 and 26 cases of MS were identified, respectively. Neither current VPA users nor recent users of VPA, who had ceased VPA treatment within the last year, were at a reduced risk of MS compared with non-users of VPA (HR = 1.30 (95% confidence interval, 0.44-3.80), n = 4, and HR = 1.22 (0.28-5.32), n = 2, respectively). Similarly, in an intention-to-treat analysis, ever-users of VPA were not at reduced risk of MS (HR = 2.41 (1.32-4.43), n = 18).
  
  
  CONCLUSIONS
  In the first human study addressing a possible beneficial effect of VPA use on the risk of MS, we found no support for a protective effect. However, given the wide confidence intervals, only large effects can be ruled out with sufficient certainty.
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Nete Munk
authors.initials: NM
authors.lastname: Nielsen
authors.forename: Henrik
authors.initials: H
authors.lastname: Svanström
authors.forename: Egon
authors.initials: E
authors.lastname: Stenager
authors.forename: Melinda
authors.initials: M
authors.lastname: Magyari
authors.forename: Nils
authors.initials: N
authors.lastname: Koch-Henriksen
authors.forename: Björn
authors.initials: B
authors.lastname: Pasternak
authors.forename: Anders
authors.initials: A
authors.lastname: Hviid
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000453:epidemiology* / Q000517:prevention & control; D057216:Propensity Score; D012042:Registries; D014635:Valproic Acid / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid
keywords: cohort study; epidemiology; histone deacetylase inhibitor; multiple sclerosis; pharmacoepidemiology; valproic acid