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.

DESIGN/PATIENTS: 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.

CONCLUSION

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.