title: Long-term experience with interferon beta-1b (Betaferon)in multiple sclerosis.
abstract: The interferon beta-1b (IFNbeta-1b, Betaferon/Betaseron) molecule was cloned some 20 years ago. In a pilot dose-finding trial involving 30 multiple sclerosis (MS) patients, the 10 MS patients receiving 250 microg (8 MIU) IFNbeta-1b every other day at 6 months showed a reduced attack frequency relative to 6 patients receiving placebo. Based on these extremely preliminary results a Phase III placebo-controlled trial was undertaken. Treatment with IFNbeta-1b was shown to reduce attack frequency and severity and to markedly reduce magnetic resonance imaging-(MRI) measured activity and disease burden. IFNbeta-1b therapy was subsequently shown to reduce MRI activity within 2 weeks of starting treatment. The benefits of treatment with IFNbeta-1b observed in the original pivotal study are maintained in the longer term, with consistent treatment effects seen after 5 years. IFNbeta-1b has subsequently been shown to reduce accumulation of disability in MS patients with early active secondary progressive disease, to increase cerebral metabolism, and to improve cognitive performance.IFNbeta-1b therapy is generally well tolerated. Classical systemic side effects related to all beta interferons can effectively be managed by dose escalation, and the use of an autoinjector minimises injection site reactions. About one-third of MS patients receiving IFNbeta-1b develop anti-interferon antibodies, typically within the first year of therapy. These antibodies have variable titres that fall with time and ultimately disappear in most patients. The clinical consequences of the presence of antibodies are presently unclear and inconsistent-some patients without antibodies respond poorly to treatment, whereas others with high-titre antibodies respond well to treatment. It is possible that immune complexes formed when anti-interferon antibodies encounter IFNbeta may enhance some of the immunomodulatory actions of the drug by improving CD8 cell-mediated suppressor function. Until the clinical relevance of antibodies is better understood, treatment decisions should be based on clinical grounds only.
authors.affiliation: University of Chicago Hospital, Department of Neurology, Chicago, Illinois 60637, USA. barnason@neurology.bsd.chicago.edu
authors.forename: Barry G W
authors.initials: BG
authors.lastname: Arnason
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy*
chemical_list: D000276:Adjuvants, Immunologic; D000068576:Interferon beta-1b; D016899:Interferon-beta