Neutralising antibodies to interferon-β–measurement, clinical relevance, and management

Abstract

Neutralising antibodies develop in up to 40% of patients treated with interferon (IFN)-β. The frequency of detection of such antibodies depends on the sensitivity of the assay, as well as on the preparation, dose, frequency and route of administration of the IFN-β. The lowest frequency of antibody development is seen with IFN-β 1a im, whereas antibodies appear to develop faster with IFN-β 1b sc than with IFN-β 1a sc. After two to three years of continuous therapy, the proportion of neutralising antibody positive patients tends to decrease, although patients who have been seropositive for over twelve months usually remain seropositive for several years to come. The presence of neutralising antibodies diminishes, and at high titres, even abolishes the bioavailability and in vivo biological response to IFN-β. For this reason, neutralising antibodies reduce the clinical impact of treatment on relapse rate, time to first relapse, disease activity measured by magnetic resonance imaging and, in the long-term, accumulation of disability. Recent guidelines recommend regular antibody testing in all patients treated with IFN-β, discontinuation of IFN-β treatment in patients with sustained high neutralising antibodies titres, and switch to an alternative therapy if appropriate.