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

Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

Klaus Bendtzen

Institute for Inflammation Research IIR7521, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

Nils Koch-Henriksen

The Danish MS Treatment Registry, Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen and Neurological Department, Aalborg Hospital, Aalborg, Denmark

Mads Ravnborg

Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

Christian Ross

Institute for Inflammation Research IIR7521, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

Per Soelberg Sorensen

Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark, pss{at}rh.dk

The Danish Multiple Sclerosis Group

Objective The main objective was to follow serum levels of neutralizing antibodies (NABs) against interferon-beta (IFNß) after discontinuation of IFNß therapy.

Background A large proportion of patients treated with recombinant IFNß 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 IFNß 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 IFNß, especially with high titres, tend to persist for a long time after discontinuation of IFNß therapy. NABs should always be measured before reinstitution of IFNß treatment in NAB-positive patients.

Key Words: neutralizing antibodies • IFNß-1=a • IFNß-1b • IFNß therapy • relapsing-remitting multiple sclerosis

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