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

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.