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Neutralizing antibodies in MS therapy: reviewing the Rebif experience

Medical Affairs, U.S. Neurology, EMD Serono, Inc., Rockland, MA, USA, Ahmad Al-Sabbagh{at}emdserono.com

Treatment of relapsing-remitting multiple sclerosis (RRMS) with protein therapeutics such as interferon beta (IFNß) frequently results in the development of binding antibodies (BAbs) to the administered agent. Neutralizing antibodies (NAbs) are a subset of BAbs characterized by their interference with IFNß's biological target(s) and/or function(s). At the treatment group level, NAbs to IFNß have been shown to have an impact on relapse rate and MRI disease measures. However, in individual patients, the clinical significance of NAbs remains controversial because of the lack of standardized assessment procedures, the absence of widely accepted cutoff values to distinguish NAb-positive from NAb-negative patients, and the high rate of seroconversion (to NAb-negative status) observed in clinical studies. At the recommended 44 µg tiw dose of IFNß-1a subcutaneous (SC) (Rebif^®), 12—14% of patients were persistently NAb-positive at two, three, and four years of treatment, while ~25% of anytime NAb-positive patients later became seronegative. Relapse rate and MRI measures of disease were higher in NAb-positive than NAb-negative patients; however, both demonstrated significant improvement versus placebo treatment or delayed treatment patients. Pending improved assessment methodology and better characterization of the clinical impact of NAbs, treatment decisions should continue to be based on the wide range of factors that determine clinical effectiveness. Multiple Sclerosis 2007; 13: S8—S13 http://msj.sagepub.com

Key Words: interferons • multiple sclerosis • neutralizing antibodies

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