Interferon-β and serum 25-hydroxyvitamin D interact to modulate relapse risk in MS

Neurology. 2012 Jul 17;79(3):254-60. doi: 10.1212/WNL.0b013e31825fded9. Epub 2012 Jun 13.


Objective: To determine whether interferon-β (IFN-β) medication use is associated with vitamin D levels and whether the two interact in exerting effects on relapse risk.

Methods: In a prospective cohort of 178 persons with clinically definite multiple sclerosis (MS) living in southern Tasmania in 2002-2005, serum 25-hydroxyvitamin D [25(OH)D] was measured biannually, with assessment by questionnaire for relevant factors, including IFN-β treatment.

Results: Subjects reporting IFN-β use had significantly higher mean 25(OH)D than persons who did not (p < 0.001). This was mediated by an interaction between personal sun exposure and IFN-β, with treated persons realizing nearly three times 25(OH)D per hour of sun exposure of persons not on therapy. The association between 25(OH)D and 1,25-dihydroxyvitamin D did not differ by IFN-β therapy (p = 0.82). 25(OH)D was associated with a reduced relapse risk only among persons on IFN-β (p < 0.001). Importantly, IFN-β was only protective against relapse among persons with higher 25(OH)D (hazard ratio [HR] 0.58 [95% confidence interval (CI) 0.35-0.98]), while among 25(OH)D-insufficient persons, IFN-β increased relapse risk (HR 2.01 [95% CI 1.22-3.32]).

Conclusion: In this study, we found that IFN-β therapy is associated with greater production of vitamin D from sun exposure, suggesting part of the therapeutic effects of IFN-β on relapse in MS may be through modulation of vitamin D metabolism. These findings suggest persons being treated with IFN-β should have vitamin D status monitored and maintained in the sufficiency range.

Classification of evidence: This study provided Class III evidence that IFN-β is associated with reduced risk of relapse, and this effect may be modified by a positive effect of IFN-β on serum 25(OH)D levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Body Mass Index
  • Cohort Studies
  • Evidence-Based Medicine
  • Female
  • Forecasting
  • Humans
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use
  • Interferon-beta / adverse effects*
  • Interferon-beta / therapeutic use*
  • Kaplan-Meier Estimate
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / drug therapy*
  • Proportional Hazards Models
  • Prospective Studies
  • Recurrence
  • Sunlight
  • Survival Analysis
  • Ultraviolet Rays
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Young Adult


  • Immunologic Factors
  • Vitamin D
  • 1,25-dihydroxyvitamin D
  • Interferon-beta
  • 25-hydroxyvitamin D