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]).


CONCLUSIONS
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.


METHODS
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.
Menzies Research Institute Tasmania, and School of Medicine, University of Tasmania, Hobart, TAS, Australia.
Niall
N
Stewart
Steve
S
Simpson
Ingrid
I
van der Mei
Anne-Louise
AL
Ponsonby
Leigh
L
Blizzard
Terrence
T
Dwyer
Fotini
F
Pittas
Darryl
D
Eyles
Pauline
P
Ko
Bruce V
BV
Taylor
D000328:Adult; D000368:Aged; D015992:Body Mass Index; D015331:Cohort Studies; D019317:Evidence-Based Medicine; D005260:Female; D005544:Forecasting; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use; D016899:Interferon-beta / Q000009:adverse effects* / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012008:Recurrence; D013472:Sunlight; D016019:Survival Analysis; D014466:Ultraviolet Rays; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D055815:Young Adult
D007155:Immunologic Factors; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D016899:Interferon-beta; C104450:25-hydroxyvitamin D