Tuesday, 23 January 2018

Smoking a potential drug interaction in IFNB

Are you a smoker? This is an important post if you are.




Neurology. 2018 Jan 17. pii: 10.1212/WNL.0000000000004949. doi: 10.1212/WNL.0000000000004949. [Epub ahead of print]

Smoking affects the interferon beta treatment response in multiple sclerosis.

Petersen ER, Oturai AB, Koch-Henriksen N, Magyari M, Sørensen PS, Sellebjerg F, Søndergaard HB.

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.


No ifs ands or butts, cigarette smoking is a health hazard. Together with vitamin D, smoking in MS has been well documented as a risk factor for disease susceptibility. It has also been linked to genes implicated in MS risk, including human leukocyte antigen (HLA) DRB1*15:01 and A*02:01 and N-acetyltransferase-1 (NAT1, gene involved in the metabolism of tobacco smoke constituents that modifies MS risk in smokers).

Here, the authors study the influence of smoking on relapse activity in IFN-B treated RRMS, including whether treatment response was influenced by interaction between smoking and gene variants listed above. A total of 834 PwMS were examined.

They found after adjusting for confounding factors such as gender, age at start of IFN-β and the number of relapses in the 2 years prior to commencing treatment that smoking was associated with an increased relapse rate (by ~27%) during the course of treatment. IFN-β treatment efficacy has been linked to the presence of neutralizing antibodies (Nabs), which may negate its action by as much as 50%. Therefore, they excluded those with persistent Nabs in this study. Passive smoking was not examined in this study.

They did not find any association with the genetic variants tested. Previously, another study had reported that the NAT1 genetic variant (rs7388368A) interacted with smoking as a risk factor for MS (Briggs FB, Acuna B, Shen L, et al. Smoking and risk of multiple sclerosis: evidence of modification by NAT1 variants. Epidemiology 2014;25:605–614).

The question therefore, is to what extent smoking affects the efficacy of other MS therapies if at all?...

1 comment:

  1. Isn't there a relationship between worse outcomes in MS and ever smoking? Or is it just people who are smoking now? This study sort of suggests currently smoking is the problem but it is not clear about this.

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