Smoking affects the interferon beta treatment response in multiple sclerosis

Neurology. 2018 Feb 13;90(7):e593-e600. doi: 10.1212/WNL.0000000000004949. Epub 2018 Jan 17.

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.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Arylamine N-Acetyltransferase / genetics
  • Cohort Studies
  • Female
  • Genetic Association Studies
  • HLA-A2 Antigen / genetics
  • HLA-DRB1 Chains / genetics
  • Humans
  • Immunologic Factors / therapeutic use*
  • Incidence
  • Interferon-beta / therapeutic use*
  • Isoenzymes / genetics
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / complications*
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / epidemiology
  • Multiple Sclerosis, Relapsing-Remitting / genetics
  • Polymorphism, Single Nucleotide
  • Recurrence
  • Smoking* / epidemiology
  • Smoking* / genetics
  • Smoking* / immunology
  • Treatment Outcome
  • Young Adult

Substances

  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • HLA-DRB1 Chains
  • HLA-DRB1*15:01 antigen
  • Immunologic Factors
  • Isoenzymes
  • Interferon-beta
  • Arylamine N-Acetyltransferase
  • N-acetyltransferase 1