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Abstract

The most frequent treatment for relapsing-remitting multiple sclerosis (RRMS) is interferon beta (IFNβ). Development of neutralizing antibodies (NAbs) to IFN therapy is a well-documented phenomenon. Patients who have persistent NAbs of sufficient titer no longer receive clinical benefit from these therapies. In the case of intramuscular (IM) IFNβ-1a (Avonex®), approximately 22% of patients in the pivotal trial (conducted from 1990 to 1994) developed NAbs. However, improvements in the processes for the production of IFNβ-1a-Avonex resulted in a commercial product (first released in 1996) that was significantly less immunogenic; approximately 2% of patients developed NAbs with titers ≥20 neutralizing units (NU)/mL. In a large three-year Phase IV clinical trial using IFNβ-1a-Avonex, it was shown that NAb-positive patients had significantly greater annual relapse rates, greater increases in disability (compared with baseline), and more lesions detected by MRI compared with NAb-negative patients, indicating that the development of NAbs has serious consequences for patients with MS treated with IFNβ. Therefore, maintaining the low immunogenicity of IFNβ-1a-Avonex in the context of improving formulations and delivery options, has been a critical objective for Biogen Idec in the development of this important therapy for patients with MS. Multiple Sclerosis 2007; 13: S14—S20 http://msj.sagepub.com

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Development of neutralizing antibodies to intramuscular interferon beta-1a (Avonex ®)

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