Association of Vitamin D Levels With Multiple Sclerosis Activity and Progression in Patients Receiving Interferon Beta-1b

Abstract

IMPORTANCE Low serum 25-hydroxyvitamin D (25[OH]D) levels are associated with an increased risk of multiple sclerosis (MS) as well as with increased disease activity and rate of progression in clinically isolated syndromes and early MS. OBJECTIVE To assess the association between 25(OH)D and disease course and prognosis in patients with relapsing-remitting MS treated with interferon beta-1b. DESIGN, SETTING, AND PARTICIPANTS We conducted a prospective cohort study assessing 25(OH)D levels and subsequent MS disease course and progression characterized by magnetic resonance imaging (MRI) and clinical end points. The study took place between November 2003 and June 2005; data analysis was performed between June 2013 and December 2014. The study was conducted among participants in the Betaferon Efficacy Yielding Outcomes of a New Dose (BEYOND) study, a large, phase 3, prospective, multicenter, blinded, randomized clinical trial. Patients were monitored for at least 2 years. Clinic visits were scheduled every 3 months, and MRI was performed at baseline and annually thereafter. Eligible patients included 1482 participants randomized to receive 250 μg or 500 μg of interferon-1b with at least 2 measurements of 25(OH)D obtained 6 months apart. EXPOSURES Serum 25(OH)D measurements were performed at baseline, 6 months, and 12 months. MAIN OUTCOMES AND MEASURESMain outcomes included cumulative number of new active lesions (T2 lesions and gadolinium acetate-enhancing lesions), change in normalized brain volume, relapse rate, and progression determined by the Expanded Disability Status Scale (EDSS). Statistical analyses were adjusted for age, sex, randomized treatment, region, disease duration, and baseline EDSS score. RESULTS Overall, average 25(OH)D levels in 1482 patients were significantly inversely correlated with the cumulative number of new active lesions between baseline and the last MRI, with a 50.0-nmol/L increase in serum 25(OH)D levels associated with a 31% lower rate of new lesions (relative rate [RR], 0.69; 95% CI, 0.55-0.86; P = .001). The lowest rate of new lesions was observed among patients with 25(OH)D levels greater than 100.0 nmol/L (RR, 0.53; 95% CI, 0.37-0.78; P = .002). No significant associations were found between 25(OH)D levels and change in brain volume, relapse rates, or EDSS scores. Results were consistent following adjustment for HLA-DRB1*15 or vitamin D-binding protein status.CONCLUSIONS AND RELEVANCE Among patients with MS treated with interferon beta-1b, higher 25(OH)D levels were associated with lower rates of MS activity observed on MRI. Results for brain atrophy and clinical progression were more equivocal.

Illuminating vitamin D effects on B-cells - the multiple sclerosis perspective

“…80,82 Furthermore, inverse correlations between 25(OH)D levels and the level of disability have been found. 70,79 These were not observed for disability progression (Muris et al unpublished data), 70,83 except for a study including only patients with clinically isolated syndrome. 84 Here a poor vitamin D status was associated with more cerebral lesion accumulation, more brain atrophy and more disability progression over time.…”

Can vitamin D reduce inflammation in relapsing-remitting multiple sclerosis?

“…Thus, one study comprising 68 patients randomized to placebo or 20,000 IU vitamin D3 per week for 2 years were completely negative, although mean serum 25(OH)D more than doubled to 121 nmol/l in the intervention group [13]. Conversely, another study of comparable size showed a significant and pronounced effect of 14,000 IU vitamin D3 per week on new gadolinium-enhancing lesions after 1 year [14]. The first study included only clinical end points, and the pre-study relapse rate was only 0.11 [13].…”

Mapping the effects of vitamin D in multiple sclerosis

“…Although negative correlations between disability and vitamin D status have been described in MS cohorts [42,59] , an effect of vitamin D status on disability progression was not found in longitudinal [60][61] and cross-sectional data [59] . Only at the start of disease, in clinically isolated syndrome (CIS) patients, a higher vitamin D status predicts less disability progression [53] .…”

“…Furthermore, inverse correlations between 25(OH)D levels and the level of disability have been found [42,59] . The correlations were not observed for disability progression [59][60][61] , except for a study including only clinically isolated syndrome (CIS) patients [53] . Here a poor vitamin D status was associated with more cerebral lesion accumulation, more brain atrophy and more disability progression over time [53] .…”

“…relapses, MRI activity) [41,43,60,413,499] and disease progression (disability) [42,59,500] . Most associations have been found particularly in early relapsing remitting…”