Should neutralizing antibodies be monitored during interferon-β treatment for multiple sclerosis?

2006 ◽  
Vol 2 (2) ◽  
pp. 76-77 ◽  
Author(s):  
Joel Oger ◽  
Ebrima Gibbs
Keyword(s):  
Multiple Sclerosis ◽  
Neutralizing Antibodies ◽  
Interferon Β

Treatment with azathioprine and cyclic methylprednisolone has little or no effect on bioactivity in anti-interferon beta antibody-positive patients with multiple sclerosis

2009 ◽  
Vol 15 (3) ◽  
pp. 323-328 ◽  
Author(s):  
M Ravnborg ◽  
K Bendtzen ◽  
O Christensen ◽  
PEH Jensen ◽  
D Hesse ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neutralizing Antibodies ◽  
Primary Outcome ◽  
Protein A ◽  
Control Group ◽  
Interferon Β ◽  
Gene Assay ◽  
Resistance Protein ◽  
Polymerase Chain

Background It is unknown whether immunosuppression of patients who have developed interferon-β (IFN-β) neutralizing antibodies (NAbs) hastens disappearance of NAbs in the blood. Objective We wanted to test whether immunosuppression with cyclic methylprednisolone (MP) in combination with azathioprine (AZA) for 6 months accelerates recovery of IFN-β bioactivity in patients with multiple sclerosis (MS) with abolished in-vivo myxovirus resistance protein A (MxA) mRNA response to IFN-β. Methods We included 13 patients with MS with NAbs and a low IFN-β bioavailability detected by the MxA-mRNA response in a descriptive, non-randomized trial. Another 14 NAb-positive patients with a low MxA-mRNA response served as controls. The primary outcome was the fraction of patients who regained an MxA-mRNA response to IFN-β. NAbs were measured by means of a clinically validated cytopathic effect assay and a new reporter gene assay. The in-vivo MxA-mRNA response was measured by real-time polymerase chain reaction. Results A total of 11 patients in the treatment group completed the trial. In all, two of these 11 patients regained an in-vivo MxA-mRNA response as compared to one of 14 patients in the control group. Conclusion Treatment with AZA and cyclic MP for 6 months has little or no effect on IFN-β bioactivity in NAb-positive patients with MS.

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.

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.

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.

scholarly journals Impression of Clinical Worsening Fails to Predict Interferon-β Neutralizing Antibody Status

2008 ◽  
Vol 36 (6) ◽  
pp. 1418-1425 ◽  
Author(s):  
U Rot ◽  
A Sominanda ◽  
A Fogdell-Hahn ◽  
J Hillert
Keyword(s):  
Multiple Sclerosis ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Poor Response ◽  
Clinical Impression ◽  
Interferon Β ◽  
Routine Testing ◽  
Testing Facility ◽  
Testing Group ◽  
Clinical Worsening

The development of neutralizing antibodies (NAbs) against interferon-β (IFNβ) reduces clinical efficacy and markers of bioactivity in patients with multiple sclerosis (MS), although it has also been shown that a poor response to IFNβ coincided with unexpectedly low NAb levels. To try and resolve this incoherency, this study investigated 2822 patients referred to a NAb testing facility. The reason for NAb testing was indicated for 2506 patients: routine testing (76%), worsening of disease (14%) and other reasons (10%). Overall, 31% of patients were NAb positive and 17% had titres high enough to obliterate IFNβ bioactivity. The frequency of NAbs was similar in patients in the routine testing group compared with the worsening group. Samples showing high titres failed to be associated with worsening of symptoms. The study failed to show low NAb levels in patients responding poorly to IFNβ. It is concluded that it is not possible to predict NAb status by clinical impression of treatment response. This is likely to be an effect of the partial efficacy of IFNβ. Thus routine testing for NAbs must be carried out in order to identify NAb status in patients with MS.

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