Association of Vitamin D levels with multiple sclerosis activity and progression in patients receiving interferon Beta-1b

Kathryn Fitzgerald, Kassandra L. Munger, Karl Köchert, Barry G.W. Arnason, Giancarlo Comi, Stuart Cook, Douglas S. Goodin, Massimo Filippi, Hans Peter Hartung, Douglas R. Jeffery, Paul O'Connor, Gustavo Suarez, Rupert Sandbrink, Ludwig Kappos, Christoph Pohl, Alberto Ascherio

Research output: Contribution to journalArticle

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 μgor 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 MEASURES: Main 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.

Original languageEnglish (US)
Pages (from-to)1458-1465
Number of pages8
JournalJAMA Neurology
Volume72
Issue number12
DOIs
StatePublished - Dec 1 2015
Externally publishedYes

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Vitamin D
Multiple Sclerosis
Magnetic Resonance Imaging
Brain
Serum
Vitamin D-Binding Protein
HLA-DRB1 Chains
Recurrence
Relapsing-Remitting Multiple Sclerosis
Ambulatory Care
Interferons
Atrophy
Disease Progression
Interferon beta-1b
Cohort Studies
Randomized Controlled Trials
Prospective Studies

ASJC Scopus subject areas

  • Clinical Neurology

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Association of Vitamin D levels with multiple sclerosis activity and progression in patients receiving interferon Beta-1b. / Fitzgerald, Kathryn; Munger, Kassandra L.; Köchert, Karl; Arnason, Barry G.W.; Comi, Giancarlo; Cook, Stuart; Goodin, Douglas S.; Filippi, Massimo; Hartung, Hans Peter; Jeffery, Douglas R.; O'Connor, Paul; Suarez, Gustavo; Sandbrink, Rupert; Kappos, Ludwig; Pohl, Christoph; Ascherio, Alberto.

In: JAMA Neurology, Vol. 72, No. 12, 01.12.2015, p. 1458-1465.

Research output: Contribution to journalArticle

Fitzgerald, K, Munger, KL, Köchert, K, Arnason, BGW, Comi, G, Cook, S, Goodin, DS, Filippi, M, Hartung, HP, Jeffery, DR, O'Connor, P, Suarez, G, Sandbrink, R, Kappos, L, Pohl, C & Ascherio, A 2015, 'Association of Vitamin D levels with multiple sclerosis activity and progression in patients receiving interferon Beta-1b', JAMA Neurology, vol. 72, no. 12, pp. 1458-1465. https://doi.org/10.1001/jamaneurol.2015.2742
Fitzgerald, Kathryn ; Munger, Kassandra L. ; Köchert, Karl ; Arnason, Barry G.W. ; Comi, Giancarlo ; Cook, Stuart ; Goodin, Douglas S. ; Filippi, Massimo ; Hartung, Hans Peter ; Jeffery, Douglas R. ; O'Connor, Paul ; Suarez, Gustavo ; Sandbrink, Rupert ; Kappos, Ludwig ; Pohl, Christoph ; Ascherio, Alberto. / Association of Vitamin D levels with multiple sclerosis activity and progression in patients receiving interferon Beta-1b. In: JAMA Neurology. 2015 ; Vol. 72, No. 12. pp. 1458-1465.
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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 μgor 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 MEASURES: Main 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.",
author = "Kathryn Fitzgerald and Munger, {Kassandra L.} and Karl K{\"o}chert and Arnason, {Barry G.W.} and Giancarlo Comi and Stuart Cook and Goodin, {Douglas S.} and Massimo Filippi and Hartung, {Hans Peter} and Jeffery, {Douglas R.} and Paul O'Connor and Gustavo Suarez and Rupert Sandbrink and Ludwig Kappos and Christoph Pohl and Alberto Ascherio",
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TY - JOUR

T1 - Association of Vitamin D levels with multiple sclerosis activity and progression in patients receiving interferon Beta-1b

AU - Fitzgerald, Kathryn

AU - Munger, Kassandra L.

AU - Köchert, Karl

AU - Arnason, Barry G.W.

AU - Comi, Giancarlo

AU - Cook, Stuart

AU - Goodin, Douglas S.

AU - Filippi, Massimo

AU - Hartung, Hans Peter

AU - Jeffery, Douglas R.

AU - O'Connor, Paul

AU - Suarez, Gustavo

AU - Sandbrink, Rupert

AU - Kappos, Ludwig

AU - Pohl, Christoph

AU - Ascherio, Alberto

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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 μgor 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 MEASURES: Main 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.

AB - 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 μgor 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 MEASURES: Main 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.

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