Prevalence of anti-drug antibodies against interferon beta has decreased since routine analysis of neutralizing antibodies became clinical practice

2012 ◽  
Vol 18 (12) ◽  
pp. 1775-1781 ◽  
Author(s):  
Roger Jungedal ◽  
Malin Lundkvist ◽  
Elin Engdahl ◽  
Ryan Ramanujam ◽  
Helga Westerlind ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Practice ◽  
Neutralizing Antibodies ◽  
Interferon Beta ◽  
Protein A ◽  
Routine Data ◽  
Cross Sectional ◽  
Resistance Protein ◽  
Multiple Sclerosis Patients ◽  
Sectional Analysis

Background: Neutralizing antibodies (NAbs) against interferon beta (IFNβ) lead to loss of treatment efficacy in multiple sclerosis patients. The seroprevalence of NAbs in multiple sclerosis patients treated with IFNβ during 2003–2004 was 32% in a cross-sectional analysis of routine data. Objectives: The aim of this study was to investigate whether the seroprevalence of NAbs, the levels of NAb titres and the IFNβ preparations used for treatment of multiple sclerosis patients had changed in 2009–2010. Methods: This study included 1296 patients, analysed for NAbs with the myxovirus resistance protein A gene expression assay in 2009–2010. Results: The seroprevalence of NAbs had decreased to 19% in 2009–2010, which is significantly lower compared with the previous study in 2003–2004 ( p<0.0001). This decrease was attributed to the IFNβ-1a preparations only, not to IFNβ-1b. The frequency of patients with high positive titres decreased the most, from 16% to 7% ( p<0.0001). Conclusions: NAb seroprevalence has decreased since NAb monitoring became clinical practice in 2003, especially for patients with high NAb titres. This might be due to the stricter monitoring of NAb titres that prompt NAb positive patients to stop treatment, to preferential use of less immunogenic drugs and to alteration of drug formulations.

Real-time TaqMan assay for myxovirus resistance protein (MxA) mRNA: a robust marker of interferon beta bioactivity in patients with multiple sclerosis

2007 ◽  
Vol 13 (1_suppl) ◽  
pp. 49-52 ◽  
Author(s):  
A.R. Pachner
Keyword(s):  
Multiple Sclerosis ◽  
Real Time ◽  
Messenger Rna ◽  
Neutralizing Antibodies ◽  
Interferon Beta ◽  
Therapeutic Option ◽  
Surrogate Marker ◽  
Taqman Assay ◽  
The Real ◽  
Resistance Protein

For many patients suffering from MS, interferon beta (IFNβ) is an effective therapeutic option; however, some patients who receive long-term IFNβ therapy for relapsing-remitting MS (RRMS) develop neutralizing antibodies (NAbs) that affect IFNβ efficacy. It is therefore important to evaluate patients' therapeutic response to IFNβ over time. Myxovirus resistance protein A (MxA), a surrogate marker of individual immunologic response to IFNβ, may be a useful tool for assessing IFNβ immunogenicity. The real-time TaqMan assay for MxA messenger RNA (mRNA) has several distinct advantages, including the ability to amplify and complete quantitative analyses in one step, a high degree of quality control and prior experience and confidence in the field of quantitative viral diagnostics. The real-time TaqMan assay for MxA mRNA can be incorporated as a component of IFNβ therapy to evaluate patients during the course of treatment. Multiple Sclerosis 2007; 13: S49—S52. http://msj.sagepub.com

Neutralizing antibodies in multiple sclerosis: a complex impact on interferon responses, magnetic resonance imaging findings and clinical outcomes

2007 ◽  
Vol 13 (1_suppl) ◽  
pp. 53-62 ◽  
Author(s):  
A.T. Reder
Keyword(s):  
Multiple Sclerosis ◽  
Neutralizing Antibodies ◽  
Interferon Beta ◽  
Clinical Effect ◽  
First Year ◽  
Trial Duration ◽  
Cross Sectional ◽  
Immune Biomarkers ◽  
Interferon Responses ◽  
Clinical Worsening

Interferon beta (IFN-β) therapy reduces relapse rate, MRI lesion development, and delays the progression of disability in relapsing forms of multiple sclerosis. As with other protein therapies, some patients develop neutralizing antibodies (NAbs) that could limit the efficacy of IFN-β. The clinical impact of NAbs is hotly debated. Non-standardized NAb assays, NAb persistence and disappearance, plus a six-month lag before a clinical effect, different IFN-β species and formulations, variable trial duration, have made interpretation of the significance of NAbs a challenging task. There is a correlation between the presence of NAb and reduced efficacy of IFN-β therapy in two- to four-year trials. However, patients destined to become NAb positive do better in the first year of IFN-β therapy. Patients with clinical worsening have surprisingly low NAb frequency and titers. Understanding the true clinical implications of NAbs will require well-controlled longitudinal studies instead of simple cross-sectional analyses, plus innovative trial designs with immune biomarkers. Multiple Sclerosis 2007; 13: S53—S62. http://msj.sagepub.com

Myxovirus resistance protein A (MxA) polymorphism is associated with IFNβ response in Iranian multiple sclerosis patients

2017 ◽  
Vol 38 (6) ◽  
pp. 1093-1099 ◽  
Author(s):  
Arezou Sayad ◽  
Soudeh Ghafouri-Fard ◽  
Mir Davood Omrani ◽  
Rezvan Noroozi ◽  
Mohammad Taheri
Keyword(s):  
Multiple Sclerosis ◽  
Protein A ◽  
Resistance Protein ◽  
Multiple Sclerosis Patients

Differing immunogenic potentials of interferon beta preparations in multiple sclerosis patients

2006 ◽  
Vol 12 (6) ◽  
pp. 731-737 ◽  
Author(s):  
C Gneiss ◽  
P Tripp ◽  
F Reichartseder ◽  
R Egg ◽  
R Ehling ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neutralizing Antibodies ◽  
Interferon Beta ◽  
First Line ◽  
Positive Group ◽  
Treatment Groups ◽  
First Line Therapy ◽  
Multiple Sclerosis Patients ◽  
Patients Experience ◽  
Insight Into

Interferon beta (IFNβ) is a first-line therapy for multiple sclerosis (MS). However, some patients experience a decline in efficacy with continued therapy due to the development of anti-IFNβ neutralizing antibodies (NAb). We investigated the frequency of NAb cross-sectionally in 846 MS patients who were receiving IFNβ-1b, IFNβ-1a im, or IFNβ-1a sc. The frequency of NAb in patients receiving IFNβ-1a im was lower (5%) than in patients treated with any other form of IFNβ (22-35%) (P < 0.0001). Binding antibodies (BAb) were measured in 808 patients. The frequency differed significantly between treatment groups, ranging from 45% (IFNβ-1a im) to 88% (IFNβ-1b). The proportion of NAb-positive patients within the BAb-positive group differed significantly among treatment groups, ranging between 12% (IFNβ-1a im) and 51% (IFNβ-1a sc). The median NAb titer from all IFNβ-1a-treated patients was higher than from IFNβ-1b-treated patients (446 versus 171 NU/mL, P = 0.04). Among NAb-positive patients, the frequency of NAb titers > 100 NU/mL was 71% for IFNβ-1a compared with 58% for IFNβ-1b (P = 0.04). Except for conflicting data regarding IFNβ-1a sc, the results are generally consistent with the literature and together with the differing proportion of NAb-positive patients within the BAb-positive group, provide further insight into the immunogeni-city of the IFNβ preparations.

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 Deficient Phosphorylation of Stat1 in Leukocytes Identifies Neutralizing Antibodies in Multiple Sclerosis Patients Treated with Interferon-Beta

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e88632 ◽  
Author(s):  
Sonia Gavasso ◽  
Ellen Faergestad Mosleth ◽  
Tove Marøy ◽  
Katarina Jørgensen ◽  
Hanne-Linda Nakkestad ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neutralizing Antibodies ◽  
Interferon Beta ◽  
Multiple Sclerosis Patients

Polymorphisms of innate pattern recognition receptors, response to interferon-beta and development of neutralizing antibodies in multiple sclerosis patients

2010 ◽  
Vol 16 (8) ◽  
pp. 942-949 ◽  
Author(s):  
Christian Enevold ◽  
Annette B Oturai ◽  
Per Soelberg Sørensen ◽  
Lars P Ryder ◽  
Nils Koch-Henriksen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Pattern Recognition ◽  
Neutralizing Antibodies ◽  
Interferon Beta ◽  
Pattern Recognition Receptors ◽  
Single Nucleotide ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background: Interferon-beta therapy of patients with relapsing—remitting multiple sclerosis involves repeated ‘immunizations’ with exogenous protein solutions. Innate pattern recognition receptors play an important role in immune responses towards foreign substances and may thus be related to treatment outcome. Objective: To determine the genotypes at 42 single nucleotide polymorphism loci in selected pattern recognition receptors for 567 prospectively followed relapsing—remitting multiple sclerosis patients treated with recombinant interferon-beta, and test for relationships to several outcome parameters, including formation of interferon-beta neutralizing antibodies. Results: The results suggest an association between the rs5743810 polymorphism (Ser249Pro) of TLR6 and development of neutralizing antibodies after 24 months of therapy in males ( p = 0.00002), but not in females ( p = 0.2). This association survived crude Bonferroni correction ( pcorrected = 0.02). Additional associations were observed in carriers of the TLR2-rs5743708 and NOD2-rs3135499 SNPs (time to relapse), the TLR7-rs179008 and NOD1-rs2075820 SNPs (time to disease progression) and the TLR4-rs7873784, TLR9-rs5743836, and NOD2-rs2066842 SNPs (frequency of neutralizing antibodies development). All of these, however, failed to survive correction for multiple testing. There were no significant differences between interferon-beta responders and non-responders for any of the investigated single nucleotide polymorphisms. Conclusions: The rs5743810 polymorphism of TLR6 may be involved in development of anti-interferon-beta antibodies in males, although further studies are required to firmly establish this.

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