An open-label safety and drug interaction study of natalizumab (Antegren™) in combination with interferon-beta (Avonex®) in patients with multiple sclerosis

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Abstract
In this open-label drug-interaction trial, we studied 38 patients with relapsing-remitting multiple sclerosis (MS) who received 3.0 or 6.0 mg/kg of natalizumab as a single intravenous (IV) infusion during stable treatment with intramuscular (IM) interferon beta-1a 30 mg (IFNβ-1a; Avonex®). To assess the pharmacokinetic (PK) interaction of natalizumab and IFNβ-1a, serum concentration-time data for both agents were collected and analysed. Biologic response markers of IFNβ-1a activity, b2-microglobulin and neopterin, were also assessed to determine effects of natalizumab on IFNβ-1a pharmacodynamics (PD). Further, safety and immunogenicity were evaluated. The combination of drug therapies was well tolerated. Although natalizumab serum concentrations (and corresponding PK exposure measures) appeared to be somewhat elevated in the presence of IFNβ-1a, when compared to the same dose (6.0 mg/kg) administered alone in a concurrent comparator study, the differences were generally small and unlikely to be clinically relevant. In general, natalizumab had no apparent clinically relevant effects on the PK or PD properties of IFNβ-1a. The presence of antibodies to IFNβ-1a and natalizumab was relatively low. Overall, the study provided safety, immunogenicity, PK and PD data to support a combination strategy for the use of natalizumab and IFNβ-1a in the treatment of patients with relapsing-remitting MS. A large clinical study is currently in progress to evaluate the efficacy and long-term safety of this combination drug therapy.