Document Detail


Frequency and Magnitude of Interferon β Neutralizing Antibodies in the Evaluation of Interferon β Immunogenicity in Patients with Multiple Sclerosis.
MedLine Citation:
PMID:  21226608     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Patients with multiple sclerosis (MS) treated with interferon β (IFNβ) preparations develop varying levels of antibodies that neutralize the biological effects of IFNβ, reduce its in vivo bioavailability, and diminish its therapeutic efficacy. The aim was to determine as distinct measures of immunogenicity the occurrence (frequency) and the magnitude (level) of IFNβ neutralizing antibody (NAb) formation in a large Canadian population as a cross-sectional study of patients with MS treated in a clinical practice setting with different, equally available IFNβ products: Avonex(®) (intramuscular IFNβ-1a), Rebif(®) (subcutaneous (SC) IFNβ-1a) at 22 and 44 μg, and Betaseron(®) (SC IFNβ-1b). Over a 3-year period 3,124 serum samples from 2,711 patients with MS were submitted by neurologists in MS clinics distributed across Canada and tested for NAbs in a single independent laboratory, utilizing a quantitative, standardized NAb bioassay. NAb frequency was greatest (35%) with Rebif (SC IFNβ-1a) 44 μg and least (7.5%) with Avonex (intramuscular IFNβ-1a), whereas Betaseron (IFNβ-1b) and Rebif 22 μg were in between (22%). NAb serum levels at magnitudes considered high, ≥100 tenfold reduction units (TRU)/mL, were found in 65%-83% of patients with detectable NAbs. Nearly half (42%-47%) of NAb-positive patients given IFNβ-1a preparations had very high titers (≥1,000 TRU/mL), whereas only 22% of NAb-positive patients on Betaseron had titers >1,000 TRU/mL. Differences in patterns of NAb formation among the four IFNβ product-dose combinations became more evident in patients with MS when both NAb frequency and the full range of NAb titer magnitude were measured.
Authors:
Sidney E Grossberg; Joel Oger; Leslie D Grossberg; Adel Gehchan; John P Klein
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-1-12
Journal Detail:
Title:  Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research     Volume:  -     ISSN:  1557-7465     ISO Abbreviation:  -     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-1-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9507088     Medline TA:  J Interferon Cytokine Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1 Department of Microbiology and Molecular Genetics, Medical College of Wisconsin , Milwaukee, Wisconsin.
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