Smokers run increased risk of developing anti-natalizumab antibodies

2013 ◽  
Vol 20 (8) ◽  
pp. 1081-1085 ◽  
Author(s):  
AK Hedström ◽  
L Alfredsson ◽  
M Lundkvist Ryner ◽  
A Fogdell-Hahn ◽  
Jan Hillert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Odds Ratio ◽  
Neutralizing Antibodies ◽  
Case Control ◽  
Smoking Habits ◽  
Interferon Β ◽  
Case Control Studies ◽  
Biological Drug ◽  
Increased Risk ◽  
Multiple Sclerosis Patients

Background: Smoking may contribute to the induction of neutralizing antibodies to interferon β-1a. Objective: In this study, we aimed to investigate the influence of smoking on the risk of developing antibodies to natalizumab, another biological drug in the treatment of multiple sclerosis. Methods: This report is based on 1338 natalizumab-treated multiple sclerosis patients included in either of two Swedish case-control studies in which information on smoking habits was collected. Using logistic regression, patients with different smoking habits were compared regarding risk of developing anti-natalizumab antibodies, by calculating odds ratios with 95% confidence intervals. Results: Compared with nonsmokers, the odds ratio of developing anti-natalizumab antibodies was 2.4 (95% CI 1.2–4.4) for patients who smoked at the time of screening, and a significant trend showed higher risk of developing antibodies with higher intensity of smoking. When smoking within two years prior to screening was considered, the odds ratio of developing anti-natalizumab antibodies was 2.7 (1.5–5.1). Interpretations: The finding strengthens our hypothesis of the lungs as immune-reactive organs on irritation in relation to autoimmune responses, and may also be of clinical relevance since antibodies against natalizumab abrogate the therapeutic effect of the treatment.

Smoking and risk of treatment-induced neutralizing antibodies to interferon β-1a

2013 ◽  
Vol 20 (4) ◽  
pp. 445-450 ◽  
Author(s):  
Anna Karin Hedström ◽  
Malin Ryner ◽  
Katarina Fink ◽  
Anna Fogdell-Hahn ◽  
Lars Alfredsson ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gender Differences ◽  
Odds Ratio ◽  
Neutralizing Antibodies ◽  
Case Control ◽  
Smoking Habits ◽  
Interferon Β ◽  
Case Control Studies ◽  
Increased Risk ◽  
Risk Of Treatment

Background: Neutralizing antibodies (NAbs) to interferon β (IFNβ) products that develop during treatment are associated with a loss of clinical efficacy. Objectives: The aim of this study was to investigate the influence of smoking habits on the risk of developing NAbs to IFNβ, in the treatment of multiple sclerosis (MS). Methods: This report is based on 695 MS patients treated with IFNβ-1a, included in two Swedish case-control studies that collected information on smoking habits. Using logistic regression, the development of NAbs to IFNβ-1a among current smokers was compared with that of non-smokers, by calculating the odds ratio (OR) with a 95% confidence interval (CI). Results: Current smokers showed an increased risk of developing NAbs to IFNβ-1a, compared with non-smokers (OR 1.9; 95% CI 1.3–2.8; p = 0.002). There were no gender differences. We observed no association between past smoking and the risk of developing NAbs to IFNβ-1a. Conclusions: The finding that current smokers have an increased risk of developing NAbs to IFNβ-1a has implications, both for the practical care and the treatment of MS; it also provides an interesting perspective of the lungs as an immune-reactive organ, reacting upon irritation.

scholarly journals Traumatic Injury and Multiple Sclerosis: A Systematic Review and Meta-Analysis

2013 ◽  
Vol 40 (2) ◽  
pp. 168-176 ◽  
Author(s):  
Sharon A. Warren ◽  
Susan Armijo Olivo ◽  
Jorge Fuentes Contreras ◽  
Karen V. L. Turpin ◽  
Douglas P. Gross ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Confidence Interval ◽  
Cohort Studies ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Traumatic Injury ◽  
Case Control ◽  
Case Control Studies ◽  
Newcastle Ottawa Scale

A systematic review/meta-analysis of literature addressing a possible association between traumatic injury and onset of multiple sclerosis was conducted. Medline, Embase, Cochrane DSR, Ovid HealthStar, CINAHL, ISI Web of Science and Scopus were searched for analytical studies from 1950 to 2011. Two investigators independently reviewed articles for inclusion, assessing their quality using the Newcastle-Ottawa Scale. Of the 13 case-control studies included, 8 were moderate quality and 5 low; of the 3 cohort studies 2 were high and 1 moderate. Meta-analysis including moderate and low quality case-control studies produced a modest but significant odds ratio: 1.41 (95% confidence interval: 1.03, 1.93). However, when low quality studies were excluded, the resulting odds ratio was non-significant. Cohort studies produced a non-significant standardized incidence ratio of 1.00 (95% confidence interval: 0.86, 1.16). These findings support the conclusion that there is no association between traumatic injury and multiple sclerosis onset; more high quality cohort studies would help to confirm this observation.

scholarly journals Effect of HLA-DRB1 alleles and genetic variants on the development of neutralizing antibodies to interferon beta in the BEYOND and BENEFIT trials

2018 ◽  
Vol 25 (4) ◽  
pp. 565-573 ◽  
Author(s):  
Dorothea Buck ◽  
Till FM Andlauer ◽  
Wilmar Igl ◽  
Eva-Maria Wicklein ◽  
Mark Mühlau ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Genetic Variants ◽  
Neutralizing Antibodies ◽  
Genome Wide Association Study ◽  
Phase Iii ◽  
Interferon Β ◽  
Hla Alleles ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk

Background: Treatment of multiple sclerosis (MS) with interferon β can lead to the development of antibodies directed against interferon β that interfere with treatment efficacy. Several observational studies have proposed different HLA alleles and genetic variants associated with the development of antibodies against interferon β. Objective: To validate the proposed genetic markers and to identify new markers. Methods: Associations of genetic candidate markers with antibody presence and development were examined in a post hoc analysis in 941 patients treated with interferon β-1b in the Betaferon® Efficacy Yielding Outcomes of a New Dose (BEYOND) and BEtaseron®/BEtaferon® in Newly Emerging multiple sclerosis For Initial Treatment (BENEFIT) prospective phase III trials. All patients were treated with interferon β-1b for at least 6 months. In addition, a genome-wide association study was conducted to identify new genetic variants. Results: We confirmed an increased risk for carriers of HLA-DRB1*04:01 (odds ratio (OR) = 3.3, p = 6.9 × 10−4) and HLA-DRB1*07:01 (OR = 1.8, p = 3.5 × 10−3) for developing neutralizing antibodies (NAbs). Several additional, previously proposed HLA alleles and genetic variants showed nominally significant associations. In the exploratory analysis, variants in the HLA region were associated with NAb development at genome-wide significance (OR = 2.6, p = 2.30 × 10−15). Conclusion: The contribution of HLA alleles and HLA-associated single-nucleotide polymorphisms (SNPs) to the development and titer of antibodies against interferon β was confirmed in the combined analysis of two multi-national, multi-center studies.

scholarly journals Association between vitamin D receptor (VDR) polymorphisms and the risk of multiple sclerosis (MS): an updated meta-analysis

BMC Neurology ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Danyal Imani ◽  
Bahman Razi ◽  
Morteza Motallebnezhad ◽  
Ramazan Rezaei
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Gene Polymorphisms ◽  
Genetic Model ◽  
Meta Analysis ◽  
Case Control ◽  
Case Control Studies ◽  
Asian Populations ◽  
Increased Risk ◽  
Apai Polymorphism

Abstract Background The association between the Vitamin D Receptor (VDR) gene polymorphism and the risk of Multiple sclerosis (MS) has been evaluated in several researches. However, the findings were inconsistent and inconclusive. Therefore, we set out a meta-analysis of all eligible published case-control studies to obtain an exact evaluation of the association between VDR gene polymorphisms and MS. Method All relevant studies reporting the association between the VDR gene FokI (rs2228570), or/and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232) polymorphisms and susceptibility to MS published up to May, 2019 were identified by comprehensive systematic search in the electronic database of web of science, Scopus, and PubMed. After that, the strength of association between VDR gene polymorphisms and susceptibility to MS was evaluated by odds ratio (OR) and 95% confidence interval (CI). Results A total of 30 case–control studies were included in the meta-analysis. The overall results suggested a significant association between TaqI polymorphism and MS risk under heterozygote genetic model (OR = 1.27, 95%CI = 1.01–1.59, random effect). Moreover, the pooled results of subgroup analysis declined presence of significant association under all defined genetic model. In subgroup analysis, BsmI polymorphisms was associated with increased risk of MS under recessive model in Asian populations. On the other hand, ApaI polymorphism was associated with decreased risk of MS under recessive and aa vs. AA model in Asian populations. Conclusion This meta-analysis suggested a significant association between TaqI polymorphism and MS susceptibility. Furthermore, BsmI polymorphism was associated with increased risk of MS in Asian populations. In contrast, ApaI polymorphism was associated with decreased risk of MS in Asian populations. Future large-scale studies on gene–environment and gene–gene interactions are required to estimate risk factors and assist early diagnosis of patients at high risk for MS.

Neutralizing antibody (NAb) assays in multiple sclerosis patients receiving interferon-β therapy

2007 ◽  
Vol 13 (1_suppl) ◽  
pp. 44-48 ◽  
Author(s):  
Florian Deisenhammer
Keyword(s):  
Multiple Sclerosis ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Diagnostic Value ◽  
Diagnostic Methods ◽  
Type I ◽  
Interferon Β ◽  
First Line Therapy ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Interferon-β (IFN-β), a type I cytokine, is first-line therapy for relapsing-remitting multiple sclerosis (RRMS), a progressive neurological disease that can result in severe disability. As with all protein-based therapies, treatment with IFN-β can result in the development of neutralizing antibodies (NAbs), which has been shown to reduce the efficacy of the regimen. Recently, assays that evaluate patients for the presence of NAbs have received increased attention as a potentially valuable diagnostic tool in assessing the therapeutic effect of a chosen IFN-β regimen. However, despite the clinical desire to consistently monitor NAb levels in these patients, no standardized NAb assay has yet been identified. A lack of method standardization can lead to confusion when comparing NAb results over time and reduces the overall diagnostic value of assessing NAb status. This review will offer a summary of current NAb diagnostic methods and the factors that limit their consistency and practicality in the clinical setting. Alternatives to current methods for assessing NAb status will also be briefly discussed. Multiple Sclerosis 2007; 13: S44—S48. http://msj.sagepub.com

Dynamics of interferon-β modulated mRNA biomarkers in multiple sclerosis patients with anti-interferon-β neutralizing antibodies

2006 ◽  
Vol 176 (1-2) ◽  
pp. 125-133 ◽  
Author(s):  
Roseane Santos ◽  
Bianca Weinstock-Guttman ◽  
Miriam Tamaño-Blanco ◽  
Darlene Badgett ◽  
Robert Zivadinov ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neutralizing Antibodies ◽  
Interferon Β ◽  
Multiple Sclerosis Patients
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