The clinical effect of neutralizing antibodies against interferon-beta is independent of the type of interferon-beta used for patients with relapsing-remitting multiple sclerosis.
OBJECTIVE
To establish whether the clinical effect of neutralizing antibodies (NAbs) against interferon-beta (IFN beta) depends on the type of IFNbeta (1a or 1b) used for treatment of patients with relapsing-remitting multiple sclerosis (MS).


BACKGROUND
NAbs against IFN beta-1b appear faster and may be more evenly distributed on IgG subclasses, whereas NAbs against IFN beta-1a develop more slowly and may be devoid of IgG3. This might cause different clinical responses to NAbs.


METHODS
All Danish MS-patients who had started first-time treatment with IFNbeta-1a 22 microg s.c tiw (Rebif22) or IFN beta-1b 250 microg s.c. qod (Betaferon) before January 1st 2003 were included. Relapses were recorded at bi-annual visit.


METHODS
We measured NAbs every 12 months using a clinically validated cytopathic effect assay. A blood sample with a neutralizing capacity of 20% or more was considered as NAb-positive. We used a mixed logistic regression analysis in which NAb-status (three levels), IFN beta-preparation, and time since treatment started were included as explanatory variables, and relapse rate as response variable.


RESULTS
In 1,309 patients, who were observed for 21,958 months, 32.3% were classified as NAb-positive. The odds-ratio (OR) for relapses in NAb-positive months compared with NAb-negative months was 1.25; P = 0.02. The risk of relapses was higher with Betaferon than with Rebif22 (OR 1.26; P < 0.01). The effect of NAb-level on relapses was independent of whether the patients were treated with Betaferon or Rebif22 (P = 0.89) and of time (P = 0.80).


CONCLUSIONS
NAbs caused by IFNbeta-1a s.c. do not differ from NAbs caused by IFNbeta-1b in their detrimental clinical effect.
Koch-Henriksen
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Department of Neurology, Aarhus University Hospital in Aalborg, Denmark and The Danish MS Treatment Register, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. koch-henriksen@stofanet.dk
Sorensen
P S
PS
Bendtzen
K
K
Flachs
E M
EM
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D004351:Drug Resistance / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology*; D012042:Registries; D055502:Secondary Prevention; D055815:Young Adult
D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a