Neutralizing antibodies to interferon beta: implications for the management of multiple sclerosis

Abstract

Purpose of review 

Antibodies against interferon-β (IFN-β) can appear in a relevant number of patients. The subset of antibodies that can neutralize IFN-β activity are called neutralizing antibodies. This review focuses on their impact both on therapeutic efficacy and on bioactivity of IFN-β, and on the managment of antibody-positive patients.

Recent findings 

When IFN-βs were first used, neutralizing antibodies were not considered important. However, recent clinical, biologic, and immunologic data have demonstrated that they reduce or abolish the therapeutic efficacy of IFN-β in 10-20% of patients. Quantification of antibodies using various biologic methods make it difficult to compare among different laboratories, and hence, standardazation of assay procedures is necessary. Despite these technical difficulties, data consistently show differences in immunogenicity among the different IFN-β products and the negative effects of neutralizing antibodies on the clinical efficacy of IFN-βs. Because the therapeutic action of IFN-β depends on activation of IFN-inducible genes, new methods for the quantification of the biologic activity of IFN-β have been developed, and a good correlation has been found between the presence of neutralizing antibodies and abrogation of IFN-β bioactivity.

Summary 

Quantification of neutralizing antibodies and the in-vivo bioactivity of IFN-β through IFN-β-inducible gene products such as Myxovirus protein A, offer valuable information on IFN-β therapy. Important questions such as the optimal therapeutic strategy for managing neutralizing antibodies positive patients require further study in clinical trials.