title: Neutralizing and binding anti-interferon-beta (IFN-beta) antibodies. A comparison between IFN-beta-1a and IFN-beta-1b treatment in multiple sclerosis.
abstract: Interferon-beta (IFN-beta) is currently the most commonly used treatment of relapsing-remitting multiple sclerosis (MS). At the time of this study, two preparations of IFN-beta were available, IFN-beta-1a (Avonextrade mark) and IFN-beta-1b (Betaferon(R)), which both can elicit an immune response with the development of anti-IFN-beta antibodies. Direct comparisons between these two preparations regarding antibody frequencies have, however, been difficult to perform, because two different analysis methods measuring partly different biological effects of IFN-beta have been employed. In the present study, binding and neutralizing anti-IFN-beta-1a and -1b antibodies were detected in parallel by an independent, well-acknowledged, interferon research laboratory using an immunoassay and a cytopathic virus inhibition assay. Five per cent of patients treated with IFN-beta-1a intramuscularly (n = 20) had neutralizing antibodies (NABs) compared with 44% of patients treated with IFN-beta-1b subcutaneously (n = 48). A high degree of cross-reactivity between neutralizing anti-IFN-beta-1a and -1b antibodies was observed. No effect of NABs on clinical outcome could be detected in this limited material. Binding anti-IFN-beta antibodies were observed in 20% of IFN-beta-1a treated patients compared with 81% of patients treated with IFN-beta-1b. Only one of 17 patients examined (6%) had detectable titres of binding anti-IFN-beta-1b antibodies in the cerebrospinal fluid (CSF). These data are the first using identical methodology to show that IFN-beta-1a gives rise to fewer NABs than IFN-beta-1b at recommended treatment schedules.
authors.affiliation: Division of Neurology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden. Pia.Kivisakk@neurotec.ki.se
authors.forename: P
authors.initials: P
authors.lastname: Kivisäkk
authors.forename: G V
authors.initials: GV
authors.lastname: Alm
authors.forename: S
authors.initials: S
authors.lastname: Fredrikson
authors.forename: H
authors.initials: H
authors.lastname: Link
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D019138:Antibodies, Blocking / Q000097:blood* / Q000134:cerebrospinal fluid; D000918:Antibody Specificity / Q000276:immunology; D001681:Biological Assay; D005260:Female; D006801:Humans; D007118:Immunoassay; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D011994:Recombinant Proteins / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D019138:Antibodies, Blocking; D011994:Recombinant Proteins; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a