The use of valproic acid and multiple sclerosis

Pharmacoepidemiol Drug Saf. 2015 Mar;24(3):262-8. doi: 10.1002/pds.3692. Epub 2014 Aug 11.

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).

Conclusion: 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.

Keywords: cohort study; epidemiology; histone deacetylase inhibitor; multiple sclerosis; pharmacoepidemiology; valproic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cohort Studies
  • Denmark / epidemiology
  • Female
  • Histone Deacetylase Inhibitors / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / diagnosis*
  • Multiple Sclerosis / epidemiology*
  • Multiple Sclerosis / prevention & control
  • Propensity Score*
  • Registries
  • Valproic Acid / administration & dosage*
  • Young Adult

Substances

  • Histone Deacetylase Inhibitors
  • Valproic Acid