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Abstract

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.

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Supplementary Material

File (wnl203897-tables_e-1_through_e-5.doc)
File (znl02712000208.pdf)

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Information & Authors

Information

Published In

Neurology®
Volume 79Number 3July 17, 2012
Pages: 254-260
PubMed: 22700816

Publication History

Received: August 21, 2011
Accepted: November 14, 2011
Published online: June 13, 2012
Published in print: July 17, 2012

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Disclosure

The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.

Authors

Affiliations & Disclosures

Niall Stewart, PhD*
From the Menzies Research Institute Tasmania (N.S., S.S., I.v.d.M., L.B., B.V.T.) and School of Medicine (F.P.), University of Tasmania, Hobart; Murdoch Children's Research Institute (A.-L.P., T.D.), Royal Children's Hospital, Melbourne; and Queensland Brain Institute (D.E., P.K.), University of Queensland, St Lucia, Australia.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NHMRC grant 21108 Investigator 3 years
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Steve Simpson, Jr, MPH*
From the Menzies Research Institute Tasmania (N.S., S.S., I.v.d.M., L.B., B.V.T.) and School of Medicine (F.P.), University of Tasmania, Hobart; Murdoch Children's Research Institute (A.-L.P., T.D.), Royal Children's Hospital, Melbourne; and Queensland Brain Institute (D.E., P.K.), University of Queensland, St Lucia, Australia.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Ingrid van der Mei, PhD
From the Menzies Research Institute Tasmania (N.S., S.S., I.v.d.M., L.B., B.V.T.) and School of Medicine (F.P.), University of Tasmania, Hobart; Murdoch Children's Research Institute (A.-L.P., T.D.), Royal Children's Hospital, Melbourne; and Queensland Brain Institute (D.E., P.K.), University of Queensland, St Lucia, Australia.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
National Health and Medical Research Council of Australia; Multiple Sclerosis Research Australia
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Anne-Louise Ponsonby, PhD
From the Menzies Research Institute Tasmania (N.S., S.S., I.v.d.M., L.B., B.V.T.) and School of Medicine (F.P.), University of Tasmania, Hobart; Murdoch Children's Research Institute (A.-L.P., T.D.), Royal Children's Hospital, Melbourne; and Queensland Brain Institute (D.E., P.K.), University of Queensland, St Lucia, Australia.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
non-profit entity, National MS SOCIETY, USA, reimbursement of travel costs non-profit entity, Keystone Symposia, USA, reimbursement of travel costs non-profit entity, MS Canada, reimbursement of travel costs
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
National Health and Medical Research Council of Australia
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Leigh Blizzard, PhD
From the Menzies Research Institute Tasmania (N.S., S.S., I.v.d.M., L.B., B.V.T.) and School of Medicine (F.P.), University of Tasmania, Hobart; Murdoch Children's Research Institute (A.-L.P., T.D.), Royal Children's Hospital, Melbourne; and Queensland Brain Institute (D.E., P.K.), University of Queensland, St Lucia, Australia.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Terrence Dwyer, MD
From the Menzies Research Institute Tasmania (N.S., S.S., I.v.d.M., L.B., B.V.T.) and School of Medicine (F.P.), University of Tasmania, Hobart; Murdoch Children's Research Institute (A.-L.P., T.D.), Royal Children's Hospital, Melbourne; and Queensland Brain Institute (D.E., P.K.), University of Queensland, St Lucia, Australia.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
National Health and Medical Research Council of Australia
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Fotini Pittas, PhD
From the Menzies Research Institute Tasmania (N.S., S.S., I.v.d.M., L.B., B.V.T.) and School of Medicine (F.P.), University of Tasmania, Hobart; Murdoch Children's Research Institute (A.-L.P., T.D.), Royal Children's Hospital, Melbourne; and Queensland Brain Institute (D.E., P.K.), University of Queensland, St Lucia, Australia.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Darryl Eyles, PhD
From the Menzies Research Institute Tasmania (N.S., S.S., I.v.d.M., L.B., B.V.T.) and School of Medicine (F.P.), University of Tasmania, Hobart; Murdoch Children's Research Institute (A.-L.P., T.D.), Royal Children's Hospital, Melbourne; and Queensland Brain Institute (D.E., P.K.), University of Queensland, St Lucia, Australia.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
Project Grants 511066 (2008-2010), 569528 (2009-2011), and 623208
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Pauline Ko, BHons
From the Menzies Research Institute Tasmania (N.S., S.S., I.v.d.M., L.B., B.V.T.) and School of Medicine (F.P.), University of Tasmania, Hobart; Murdoch Children's Research Institute (A.-L.P., T.D.), Royal Children's Hospital, Melbourne; and Queensland Brain Institute (D.E., P.K.), University of Queensland, St Lucia, Australia.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Bruce V. Taylor, MD
From the Menzies Research Institute Tasmania (N.S., S.S., I.v.d.M., L.B., B.V.T.) and School of Medicine (F.P.), University of Tasmania, Hobart; Murdoch Children's Research Institute (A.-L.P., T.D.), Royal Children's Hospital, Melbourne; and Queensland Brain Institute (D.E., P.K.), University of Queensland, St Lucia, Australia.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Funding to travel to World Congress of MS Montreal September 2008 from Schering Bayer Schering Pharma Pty Ltd Funding for travel and accommodation from MS Society of Western Australia to speak at their 2008 scientific. meeting. Funding from Bayer Schering Pharma to present a series of lectures in South East Asia March 2008 Invited Guest speaker at Asia pacific MS forum funded by Bayer Schering Pharma Pty Ltd Invited guest speaker INDAPS meeting Melbourne Nov 2008 funded by CSL Pty Ltd Austrlaia. Funding to travel to AAN meeting Seattle 2009 from Bayer Schering Pharma. Funding to travel to ECTRIMS Gothenberg 2010 from Bayer Schering Pharma.
Editorial Boards:
1.
International MS Journal Editorial Advisary Board 2009 - 2011
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
Honoraria received from MS society of Western Australia for speaking at the 2008 Scientific meeting
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NHMRC australia project grant support.2008-9.490020, 2009 544922 2010 HRC New Zealand project grant support.2007-8 05/524 National MS Society of USA project grant support Australian research Council and MS Research Australia 2007-9 LP0776744 National MS society of US project grant funding
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Ms society of Tasmania research fellowship support 2007 - 2009
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

*
These authors contributed equally to this work.
Study funding: The MS Longitudinal Study was funded by a grant from the Australian National Health & Medical Research Council (Project 211308). Additional funding for 25(OH)D measures provided by the Trish Foundation. Additional funding for 1,25(OH)2D measures provided by a University of Tasmania Rising Star Award. I.v.d.M. is supported by a Future Fellowship from the Australian Research Council.
Correspondence & reprint requests to Dr. Taylor: [email protected]

Author Contributions

The MSL study was designed and implemented by B.T., I.v.M., F.P., A.-L.P., and T.D. The current project was initiated by N.S., and developed and implemented by N.S. and S.S.J. 1,25(OH)2D measurement was done by D.E. and P.O. Statistical analysis was done by S.S.J. under supervision by L.B. Initial drafting of manuscript was by S.S.J. and N.S. All authors participated in critical revision of manuscript and approve it for submission. S.S.J. and N.S. had access to all the data in the study and take full responsibility for the data presented and the decision to submit the article for publication.

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