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


RESULTS
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.


CONCLUSIONS
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.
Department of Neurology, Institute for Inflammation Research, Rigshospitalet, Copenhagen, Denmark. pss@rh.dk
Per Soelberg
PS
Sorensen
Christian
C
Ross
Katja Maria
KM
Clemmesen
Klaus
K
Bendtzen
Jette Lautrup
JL
Frederiksen
Kai
K
Jensen
Ole
O
Kristensen
Thor
T
Petersen
Soren
S
Rasmussen
Mads
M
Ravnborg
Egon
E
Stenager
Nils
N
Koch-Henriksen
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology*; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology*; D009500:Neutralization Tests / Q000706:statistics & numerical data; D011446:Prospective Studies; D055502:Secondary Prevention; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D000906:Antibodies; D016899:Interferon-beta