Persistence of neutralizing antibodies after discontinuation of IFNbeta therapy in patients with relapsing-remitting multiple sclerosis.
OBJECTIVE
The main objective was to follow serum levels of neutralizing antibodies (NABs) against interferon-beta (IFNbeta) after discontinuation of IFNbeta therapy.


BACKGROUND
A large proportion of patients treated with recombinant IFNbeta for multiple sclerosis (MS) develop therapy-induced NABs. Knowledge of persistence of NABs after discontinuation of therapy is limited.


METHODS
A retrospective follow-up study of patients treated in Denmark for relapsing remitting (RR) MS with IFNbeta for at least 12 months. NAB-positive patients, who discontinued therapy, were followed up with measurements of NABs.


METHODS
We measured NAB-neutralizing capacity and NAB titres a.m. Kawade using a clinically validated cytopathic effect assay.


RESULTS
Thirty-seven patients were included. Mean follow-up time was 22 months. Of the 29 patients with a NAB titre at or above 25 prior to termination of therapy, only three patients reverted to a titre below 25. Of these, two had a titre below 200 and one patient a titre of 600 at the last examination before treatment stop. The longest post-treatment follow-up during which a patient maintained NAB positivity was 59 months.


CONCLUSIONS
NABs against IFNbeta, especially with high titres, tend to persist for a long time after discontinuation of IFNbeta therapy. NABs should always be measured before reinstitution of IFNbeta treatment in NAB-positive patients.
Petersen
Bodil
B
Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Bendtzen
Klaus
K
Koch-Henriksen
Nils
N
Ravnborg
Mads
M
Ross
Christian
C
Sorensen
Per Soelberg
PS
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000906:Antibodies / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology*; D009500:Neutralization Tests; D012189:Retrospective Studies; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000906:Antibodies; D016899:Interferon-beta