Document Detail


Eight-year immunogenicity and safety of interferon beta-1a-Avonex treatment in patients with multiple sclerosis.
MedLine Citation:
PMID:  16042223     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
An open-label extension study of the phase III trial of intramuscular interferon beta-1a (IFNbeta-1a-Avonex) was conducted to evaluate the immunogenicity and safety of IFNbeta-1a-Avonex over six years in patients with relapsing multiple sclerosis (MS). Patients who participated in the pivotal phase III study were offered enrolment; entry was also open to patients who had not participated. All patients received IFNbeta-1a-Avonex 30 microg intramuscularly once weekly for six years, for a treatment duration of up to eight years in patients who received IFNbeta-1a-Avonex in the phase III trial. Serum levels of IFNbeta antibodies were measured every six months using a screening enzyme-linked immunosorbent assay (ELISA) followed by an antiviral cytopathic effect assay to detect neutralizing antibodies (NAbs) in serum samples positive on ELISA. The incidence of adverse events and laboratory test results assessed safety. Of 382 total patients, 218 had participated in the phase III study (103 placebo, 115 IFNbeta-1a-Avonex) and 164 had not participated; 24 of the 164 were IFNbeta-naïve. At baseline, 281 patients were negative for IFNbeta antibodies (NAb-). NAbs (titre > or = 20) developed at any time over six years in 5% of these patients. Of 140 patients who had been on IFNbeta-1b-Betaseron, 49 were positive for NAbs (NAb+) at baseline; 11 of 115 who had been on IFNbeta-1a-Avonex were NAb+ at baseline. Thirty-nine of 49 patients who had been on Betaseron and were NAb+ had titres < 100; 36 of these 39 seroconverted to NAb- while on IFNbeta-1a-Avonex, with a median time of approximately six months. Ten patients who had been on Betaseron had NAb titres > or = 100; five remained NAb+ during six years on IFNbeta-1a-Avonex and five seroconverted to NAb-, but only after at least two years. Five patients who had been on IFNbeta-1a-Avonex during the clinical trial were NAb+ with titres < 100 at baseline; four seroconverted to NAb-, with a median time of two to three years. Six patients who had been on IFNbeta-1a-Avonex had NAb titres > or = 100; five of these remained NAb+ at six years. No patient with a NAb titre > 1000 seroconverted to NAb-, whether initially treated with IFNbeta-1a-Avonex or -Betaseron. Adverse events were similar to those observed in the pivotal phase III trial. Results from this trial indicated that IFNbeta-1a-Avonex was associated with a low incidence of NAbs and was well tolerated for up to eight years. Further, the results indicate that persistence of NAbs is dependent on titre and IFNbeta product.
Authors:
Robert M Herndon; Richard A Rudick; Frederick E Munschauer; Michele K Mass; Andres M Salazar; Michael E Coats; Robert Labutta; John R Richert; Stanley L Cohan; Claude Genain; Donald Goodkin; Martin Toal; Katherine Riester
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Publication Detail:
Type:  Clinical Trial; Clinical Trial, Phase III; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Multiple sclerosis (Houndmills, Basingstoke, England)     Volume:  11     ISSN:  1352-4585     ISO Abbreviation:  Mult. Scler.     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-07-26     Completed Date:  2005-09-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9509185     Medline TA:  Mult Scler     Country:  England    
Other Details:
Languages:  eng     Pagination:  409-19     Citation Subset:  IM    
Affiliation:
University of Mississippi, VA Medical Center, Jackson, MS 39216, USA. rherndon@neurology.umsmed.edu
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MeSH Terms
Descriptor/Qualifier:
Activities of Daily Living
Adjuvants, Immunologic / therapeutic use*
Adolescent
Adult
Age of Onset
Autoantibodies / blood
Female
Humans
Interferon-beta / therapeutic use*
Male
Middle Aged
Multiple Sclerosis / immunology*,  therapy*
Recurrence
Safety
Treatment Outcome
Walking
Chemical
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/Autoantibodies; 145258-61-3/interferon beta 1a; 77238-31-4/Interferon-beta

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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