Smoking affects the interferon beta treatment response in multiple sclerosis

ObjectiveTo 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.MethodsDNA 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.ResultsWe 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.ConclusionIn 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.

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Response to interferon-beta therapy in relapsing-remitting multiple sclerosis: a comparison of different clinical criteria

Multiple Sclerosis Journal ◽

10.1191/135248506ms1278oa ◽

2006 ◽

Vol 12 (3) ◽

pp. 281-286 ◽

Cited By ~ 26

Author(s):

E Portaccio ◽

V Zipoli ◽

G Siracusa ◽

S Sorbi ◽

M P Amato

Keyword(s):

Multiple Sclerosis ◽

Relapse Rate ◽

Interferon Beta ◽

Clinical Criteria ◽

Predictors Of Response ◽

Lower Baseline ◽

Disability Status ◽

Relapsing Remitting ◽

One Year ◽

Relapsing Remitting Multiple Sclerosis

We assessed the proportion and potential predictors of response to interferon-beta (IFNβ) therapy in relapsing-remitting (RR) multiple sclerosis (MS) patients, comparing different definitions of response: a) lower relapse rate during therapy compared to the year and the two years before therapy, b) reduction of relapse rate during therapy of at least 30% compared to the two years before therapy, c) no relapse during treatment, d) no progression on the Expanded Disability Status Scale (EDSS). Among 147 RR patients treated for at least one year, 33 received IFNβ-1b subcutaneously (SC) (Betaferon), 59 IFNβ-1a intramuscularly (Avonex) and 55 IFNβ-1a SC (Rebif). Using definitions a), b) and d), 72%, 73% and 73% patients, respectively, were considered responders. Forty-four per cent of our patients were completely relapse free. In the logistic regression model, using definitions a) and b), a higher relapse rate in the two years preceding the therapy turned out to be a significant predictor of response. Considering definition c), lower baseline relapse rate was associated with a more favourable response.

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Mitoxantrone treatment in patients with early relapsing-remitting multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458507077621 ◽

2007 ◽

Vol 13 (8) ◽

pp. 975-980 ◽

Cited By ~ 19

Author(s):

E. Cocco ◽

P. Marchi ◽

C. Sardu ◽

P. Russo ◽

A. Paolillo ◽

...

Keyword(s):

Multiple Sclerosis ◽

Adverse Events ◽

Relapse Rate ◽

Serious Adverse Events ◽

T2 Lesions ◽

End Of Treatment ◽

Relapsing Remitting ◽

Annualized Relapse Rate ◽

Relapsing Remitting Multiple Sclerosis

We investigated the clinical and MRI effects of mitoxantrone (MITOX) administered to 45 patients during the first five years of highly active relapsing-remitting multiple sclerosis. Differences occurring between the end of treatment and follow-up (clinical mean: 3.6 years; brain MR: 1.8 years) with respect to baseline variables (EDSS, annualized relapse rate, active T2 lesions, new T1 lesions and number of Gd-enhancing lesions) were analysed using parametric and non-parametric tests. One patient developed leukemia four months after the end of the treatment; no other serious adverse events occurred during treatment and the follow-up period. A clinically relevant reduction in the annualized relapse rate ( P < 0.0001 at end of treatment and P < 0.0001 at follow-up) and improvement in the EDSS ( P < 0.0001 at end of treatment and P = 0.0005 at follow-up) was found. At the end of treatment, 53% of patients experienced no increase in active T2 lesions, while 73% showed no increase in the number of new T1 lesions. At follow-up, 41 out of 45 (91%) patients showed a stable MRI pattern and were active-scan free. Despite potential serious adverse events, MITOX may be considered an option in selected patients with very active early MS. Multiple Sclerosis 2007; 13: 975—980. http://msj.sagepub.com

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The Danish National Project of interferon-beta treatment in relapsing-remitting multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/135245850000600306 ◽

2000 ◽

Vol 6 (3) ◽

pp. 172-175 ◽

Cited By ~ 21

Author(s):

Nils Koch-Henriksen ◽

Per Soelberg Sùrensen ◽

Keyword(s):

Multiple Sclerosis ◽

Relapse Rate ◽

Interferon Beta ◽

Randomised Trial ◽

Neutralizing Antibody ◽

The European Union ◽

Relapsing Remitting ◽

First Relapse ◽

Remitting Multiple Sclerosis ◽

Relapsing Remitting Multiple Sclerosis

After approval by the European Union in 1996 of interferon-beta for treatment of relapsing-remitting multiple sclerosis (RRMS), 862 patients in Denmark have received treatment (by April 1999), and 304 of those were enrolled into an open labelled randomised trial to compare the efficacy and tolerability of treatment with interferon-beta-1b (Betaferon) 8 MIU subcutaneous every other day and interferon-beta-1a (Rebif) 6 MIU subcutaneous once a week. Primary and secondary end-points included: (1) the relapse rate, (2) tolerability, (3) neutralizing antibody formation using the same specialised laboratory and validated assay, (4) time to first relapse, (5) time to sustained progression, and (6) number of gadolinium-enhancing lesions in T1-weighted MRI and the total lesion load in T2-weighted MRI. All the records are kept in a nationwide clinical database connected with the Danish Multiple Sclerosis Registry. The randomised trial will be completed by the end of 1999, and the results are not yet available. The annual relapse rate in all treated patients until April 1999 was 0.73, the annual rate of steroid treated relapses was 0.21. By 1 April 1999 8.8% of the patients had discontinued treatment and 10.4% had changed to another interferon-beta preparation. It has been planned to extend the follow-up of all patients treated according to the Danish National Protocol for a period of several years. The continuous and nation-wide registration of the course of the disease in interferon-beta treated RRMS patients may provide valuable knowledge of the treatment-modified long-term course of the disease in a cohort of patients, selected on the basis of well-defined criteria.

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