title: Neutralizing antibodies to disease-modifying agents in the treatment of multiple sclerosis.
abstract: Protein- and peptide-based disease-modifying agents for multiple sclerosis (MS), including interferon beta (IFNbeta) and glatiramer acetate (GA), have been associated with the formation of antibodies. Neutralizing antibodies (NAbs) block or neutralize the biological effects of the protein or polypeptide, potentially decreasing the therapeutic effects of these agents. Although the clinical relevance of antibodies against GA requires further investigation; both the incidence of NAbs to the three IFNbeta products (IFNbeta1b-Betaseron, IFNbeta1a-Rebif, and IFNbeta1a-Avonex) and the clinical relevance are quite clear. Data from clinical trials of IFNbeta products show that the immunogenicity of Betaseron > Rebif > Avonex and persistent NAbs reduce the clinical efficacy of IFNbeta. Because the initial detection of NAbs in the serum of patients receiving IFNbeta usually occurs between 6 and 15 months and appears to precede any apparent reduction in clinical efficacy by approximately 6 to 12 months, trials with a duration of less than 3 years are problematic when the clinical impact of NAbs is assessed. The potential development of NAbs is an important consideration in selection and monitoring treatment of MS. Long-term prospective studies are needed to further define the clinical effects of NAbs on patients receiving disease-modifying therapies for MS.
authors.affiliation: Multiple Sclerosis Division, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA. tvartani@bidmc.harvard.edu
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Vartanian
authors.forename: Scott S
authors.initials: SS
authors.lastname: Zamvil
authors.forename: Edward
authors.initials: E
authors.lastname: Fox
authors.forename: Per Soelberg
authors.initials: PS
authors.lastname: Sorensen
mesh_terms: D000917:Antibody Formation; D004797:Enzyme-Linked Immunosorbent Assay; D000068717:Glatiramer Acetate; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology*; D009500:Neutralization Tests; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D010455:Peptides; D000068576:Interferon beta-1b; D000068717:Glatiramer Acetate; D016899:Interferon-beta; D000068556:Interferon beta-1a