Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis

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. We measured neutralising antibodies every 12 mo...

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Published in:The Lancet (British edition) 2003-10, Vol.362 (9391), p.1184-1191
Main Authors: Sorensen, Per Soelberg, Ross, Christian, Clemmesen, Katja Maria, Bendtzen, Klaus, Frederiksen, Jette Lautrup, Jensen, Kai, Kristensen, Ole, Petersen, Thor, Rasmussen, Soren, Ravnborg, Mads, Stenager, Egon, Koch-Henriksen, Nils
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - therapeutic use
Adolescent
Adult
Aged
Antibodies
Antibodies - immunology
Bioassays
Biological and medical sciences
Drug therapy
Female
Humans
Immunoglobulins
Immunology
Interferon
Interferon-beta - immunology
Interferon-beta - therapeutic use
Laboratories
Male
Measurement methods
Measurement techniques
Medical sciences
Middle Aged
Multiple sclerosis
Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis
Multiple Sclerosis, Relapsing-Remitting - drug therapy
Multiple Sclerosis, Relapsing-Remitting - immunology
Neurology
Neutralization Tests - statistics & numerical data
Patients
Prospective Studies
Rank tests
Secondary Prevention
Treatment Outcome
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Summary: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. 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. 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. 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.
ISSN:0140-6736
1474-547X
DOI:10.1016/S0140-6736(03)14541-2