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February 13, 2018; 90 (7) Article

Smoking affects the interferon beta treatment response in multiple sclerosis

Eva R. Petersen, Annette B. Oturai, Nils Koch-Henriksen, Melinda Magyari, Per S. Sørensen, Finn Sellebjerg, Helle B. Søndergaard
First published January 17, 2018, DOI: https://doi.org/10.1212/WNL.0000000000004949
Eva R. Petersen
From the Danish Multiple Sclerosis Center (E.R.P., A.B.O., M.M., P.S.S., F.S., H.B.S.), Department of Neurology, and Danish Multiple Sclerosis Treatment Register (N.K.-H., M.M.), Rigshospitalet, University of Copenhagen; and Department of Clinical Epidemiology (N.K.-H), Clinical Institute, University of Aarhus, Denmark.
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Annette B. Oturai
From the Danish Multiple Sclerosis Center (E.R.P., A.B.O., M.M., P.S.S., F.S., H.B.S.), Department of Neurology, and Danish Multiple Sclerosis Treatment Register (N.K.-H., M.M.), Rigshospitalet, University of Copenhagen; and Department of Clinical Epidemiology (N.K.-H), Clinical Institute, University of Aarhus, Denmark.
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Nils Koch-Henriksen
From the Danish Multiple Sclerosis Center (E.R.P., A.B.O., M.M., P.S.S., F.S., H.B.S.), Department of Neurology, and Danish Multiple Sclerosis Treatment Register (N.K.-H., M.M.), Rigshospitalet, University of Copenhagen; and Department of Clinical Epidemiology (N.K.-H), Clinical Institute, University of Aarhus, Denmark.
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Melinda Magyari
From the Danish Multiple Sclerosis Center (E.R.P., A.B.O., M.M., P.S.S., F.S., H.B.S.), Department of Neurology, and Danish Multiple Sclerosis Treatment Register (N.K.-H., M.M.), Rigshospitalet, University of Copenhagen; and Department of Clinical Epidemiology (N.K.-H), Clinical Institute, University of Aarhus, Denmark.
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Per S. Sørensen
From the Danish Multiple Sclerosis Center (E.R.P., A.B.O., M.M., P.S.S., F.S., H.B.S.), Department of Neurology, and Danish Multiple Sclerosis Treatment Register (N.K.-H., M.M.), Rigshospitalet, University of Copenhagen; and Department of Clinical Epidemiology (N.K.-H), Clinical Institute, University of Aarhus, Denmark.
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Finn Sellebjerg
From the Danish Multiple Sclerosis Center (E.R.P., A.B.O., M.M., P.S.S., F.S., H.B.S.), Department of Neurology, and Danish Multiple Sclerosis Treatment Register (N.K.-H., M.M.), Rigshospitalet, University of Copenhagen; and Department of Clinical Epidemiology (N.K.-H), Clinical Institute, University of Aarhus, Denmark.
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Helle B. Søndergaard
From the Danish Multiple Sclerosis Center (E.R.P., A.B.O., M.M., P.S.S., F.S., H.B.S.), Department of Neurology, and Danish Multiple Sclerosis Treatment Register (N.K.-H., M.M.), Rigshospitalet, University of Copenhagen; and Department of Clinical Epidemiology (N.K.-H), Clinical Institute, University of Aarhus, Denmark.
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Citation
Smoking affects the interferon beta treatment response in multiple sclerosis
Eva R. Petersen, Annette B. Oturai, Nils Koch-Henriksen, Melinda Magyari, Per S. Sørensen, Finn Sellebjerg, Helle B. Søndergaard
Neurology Feb 2018, 90 (7) e593-e600; DOI: 10.1212/WNL.0000000000004949

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Abstract

Objective To investigate whether smoking in patients with relapsing-remitting multiple sclerosis (RRMS) treated with interferon beta (IFN-β) is associated with the relapse rate and whether there is an interaction between smoking and human leukocyte antigen (HLA)–DRB1*15:01, HLA-A*02:01, and the N-acetyltransferase-1 (NAT1) variant rs7388368A.

Methods DNA from 834 IFN-β–treated patients with RRMS from the Danish Multiple Sclerosis Biobank was extracted for genotyping. Information about relapses from 2 years before the start of treatment to either the end of treatment or the last follow-up visit was obtained from the Danish Multiple Sclerosis Treatment Register. Smoking information came from a comprehensive questionnaire.

Results We found that the relapse rate in patients with RRMS during IFN-β treatment was higher in smokers compared to nonsmokers, with an incidence rate ratio (IRR) of 1.20 (95% confidence interval [CI] 1.021–1.416, p = 0.027) and with an IRR increase of 27% per pack of cigarettes per day (IRR 1.27, 95% CI 1.056–1.537, p = 0.012). We found no association or interaction with HLA and the NAT1 variant.

Conclusion In this observational cohort study, we found that smoking is associated with increased relapse activity in patients with RRMS treated with IFN-β, but we found no association or interaction with HLA or the NAT1 variant.

Glossary

DMD=
disease-modifying drug;
HLA=
human leukocyte antigen;
IFN-β=
interferon beta;
MS=
multiple sclerosis;
NAb=
neutralizing antibody;
NAT1=
N-acetyltransferase-1;
SNP=
single nucleotide polymorphism

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received February 3, 2017.
  • Accepted in final form November 2, 2017.
  • © 2018 American Academy of Neurology
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