Neutralizing antibodies in multiple sclerosis: a complex impact on interferon responses, magnetic resonance imaging findings and clinical outcomes

Abstract

Interferon beta (IFN-β) therapy reduces relapse rate, MRI lesion development, and delays the progression of disability in relapsing forms of multiple sclerosis. As with other protein therapies, some patients develop neutralizing antibodies (NAbs) that could limit the efficacy of IFN-β. The clinical impact of NAbs is hotly debated. Non-standardized NAb assays, NAb persistence and disappearance, plus a six-month lag before a clinical effect, different IFN-β species and formulations, variable trial duration, have made interpretation of the significance of NAbs a challenging task. There is a correlation between the presence of NAb and reduced efficacy of IFN-β therapy in two- to four-year trials. However, patients destined to become NAb positive do better in the first year of IFN-β therapy. Patients with clinical worsening have surprisingly low NAb frequency and titers. Understanding the true clinical implications of NAbs will require well-controlled longitudinal studies instead of simple cross-sectional analyses, plus innovative trial designs with immune biomarkers. Multiple Sclerosis 2007; 13: S53—S62. http://msj.sagepub.com