Neutralizing Antibodies to Multiple Sclerosis Treatments

OBJECTIVE: This article reviews the incidence and clinical significance of neutralizing antibodies (NAbs) in patients with multiple sclerosis (MS) undergoing treatment with interferon beta (IFNβ). Implications for practice are also discussed in light of the currently available data on the clinical consequences of NAbs in patients with MS. SUMMARY: As with other recombinant protein drugs used for the treatment of a number of diseases, antibodies commonly develop to IFNβ products during the treatment of patients with MS. Neutralizing antibodies (NAbs) are a subset of antibodies that reduce or diminish the biologic activity of IFNβ. Three formulations of IFNβ are currently available for the treatment of relapsing-remitting MS: IFNβ-1b (Betaseron), intramuscular (IM) IFNβ-1a (Avonex), and subcutaneous (SC) IFNβ-1a (Rebif). Individual phase III clinical trials and direct comparison studies have shown that NAbs develop more frequently during treatment with IFNβ-1b than IFNβ-1a and that between the 2 IFNβ-1a products, NAbs develop more frequently during treatment with SC IFNβ-1a than IM IFNβ-1a. Data from clinical trials of IFNβ products indicate that clinical efficacy of IFNβ is reduced in NAb-positive patients. CONCLUSION: In light of these data, the immunogenicity of IFNβ products should be considered prior to initiating treatment with IFNβ. Also, ongoing laboratory monitoring of patients treated with higher-dose IFNβ is recommended for early detection of NAbs.