Persistence of neutralizing antibodies after discontinuation of IFN beta therapy in patients with relapsing-remitting multiple sclerosis

Objective The main objective was to follow serum levels of neutralizing antibodies (NABs) against interferon-beta (IFN beta) after discontinuation of IFNb therapy. Background A large proportion of patients treated with recombinant IFNb 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 IFNb 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 IFNb, especially with high titres, tend to persist for a long time after discontinuation of IFNb therapy. NABs should always be measured before reinstitution of IFNb treatment in NAB-positive patients.