Document Detail

Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis.
MedLine Citation:
PMID:  14568740     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Interferon beta is the first-line treatment for relapsing-remitting multiple sclerosis, but the drug can induce neutralising antibodies against itself, which might reduce effectiveness. We aimed to assess the clinical effect of neutralising antibodies. METHODS: We measured neutralising antibodies every 12 months for up to 60 months in 541 patients with multiple sclerosis, randomly selected from all patients who started treatment with interferon beta between 1996 and 1999. Patients left the study if they changed or discontinued therapy. Antibodies were measured blindly, using antiviral neutralisation bioassays with high, medium, and low sensitivity, and with different neutralising capacities as cutoff value for definition of a neutralising-antibody-positive result. FINDINGS: Patients developed neutralising antibodies independent of age, sex, disease duration, and progression index at start of treatment. Relapse rates were significantly higher during antibody-positive periods (0.64-0.70) than they were during antibody-negative periods (0.43-0.46; p<0.03). When comparing the number of relapses in the neutralising-antibody-positive and neutralising-antibody-negative periods we found odds ratios in the range 1.51 to 1.58 (p<0.03). Time to first relapse was significantly increased by 244 days in patients who were antibody-negative at 12 months (log rank test 6.83, p=0.009). During this short-term study, presence of neutralising antibodies did not affect disease progression measured with the expanded disability status scale. INTERPRETATION: Our findings suggest that the presence of neutralising antibodies against interferon beta reduces the clinical effect of the drug. In patients who are not doing well on interferon beta, the presence of such antibodies should prompt consideration about change of treatment.
Per Soelberg Sorensen; Christian Ross; Katja Maria Clemmesen; Klaus Bendtzen; Jette Lautrup Frederiksen; Kai Jensen; Ole Kristensen; Thor Petersen; Soren Rasmussen; Mads Ravnborg; Egon Stenager; Nils Koch-Henriksen;
Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Lancet     Volume:  362     ISSN:  1474-547X     ISO Abbreviation:  Lancet     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-10-21     Completed Date:  2003-12-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985213R     Medline TA:  Lancet     Country:  England    
Other Details:
Languages:  eng     Pagination:  1184-91     Citation Subset:  AIM; IM    
Department of Neurology, Institute for Inflammation Research, Rigshospitalet, Copenhagen, Denmark.
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MeSH Terms
Adjuvants, Immunologic / therapeutic use*
Antibodies / immunology*
Interferon-beta / immunology*,  therapeutic use*
Middle Aged
Multiple Sclerosis, Relapsing-Remitting / drug therapy*,  immunology*
Neutralization Tests / statistics & numerical data
Prospective Studies
Recurrence / prevention & control
Treatment Outcome
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/Antibodies; 77238-31-4/Interferon-beta
Comment In:
Lancet. 2004 Jan 10;363(9403):166-7; author reply 168-9   [PMID:  14726177 ]
Lancet. 2004 Jan 10;363(9403):167-8; author reply 168-9   [PMID:  14726179 ]
Lancet. 2004 Jan 10;363(9403):168; author reply 168-9   [PMID:  14726180 ]

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