title: Immunogenicity of interferon beta: differences among products.
abstract: Protein-based therapies are useful in a variety of diseases; however, their potential for immunogenicity is a disadvantage. Neutralizing antibodies (NAbs) that develop to interferon beta (IFNbeta) products (IFNbeta-1b, IFNbeta-1a-Avonex((R)), or IFNbeta-1a-Rebif((R))), which are first-line therapies for the treatment of multiple sclerosis, are reported to reduce the clinical efficacy of these agents. In individual clinical studies of each commercially available IFNbeta product, 28% to 47% of patients develop NAbs to IFNbeta-1b, 12% to 28 % to IFNbeta-1a-Rebif, and 2% to 6% to IFNbeta-1a-Avonex. Problems exist in comparing the incidence of NAbs among IFNbeta products across studies because of differences in study methodology, including assay methods, treatment duration, and the definition of NAb positive. Results from studies that have directly compared these products are consistent with results from the respective clinical trials of IFNbetas. Both the clinical trials and the independent studies have shown that NAbs develop more frequently with IFNbeta-1b treatment than with IFNbeta-1a treatment and that, among IFNbeta-1a products, NAbs develop more frequently with IFNbeta-1a-Rebif treatment than with IFNbeta-1a-Avonex treatment. Factors that may affect the immunogenicity of IFNbetas, including the dosing regimens and the biochemical properties of the products, are discussed.
authors.affiliation: Centro Riferimento Regionale Sclerosi Multipla and Laboratori di Neurobiologia Clinica, Ospedale Universitario San Luigi, Orbassano, Italy. nsglb@tin.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertolotto
authors.forename: Florian
authors.initials: F
authors.lastname: Deisenhammer
authors.forename: Paolo
authors.initials: P
authors.lastname: Gallo
authors.forename: Per
authors.initials: P
authors.lastname: Sölberg Sørensen
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation; D000918:Antibody Specificity; D002986:Clinical Trials as Topic / Q000379:methods; D004306:Dose-Response Relationship, Immunologic; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a