Using measurements of neutralizing antibodies: the challenge of IFN-beta therapy

Although the occurrence of neutralizing antibodies (NAbs) to interferon (IFN)-beta has been acknowledged since the pivotal trials of IFN-beta in multiple sclerosis (MS), the effect of these antibodies has for several reasons been debated. The main reason for the controversies has been insufficient knowledge of the fact that clinically relevant NAbs do not appear until 12-18 months after initiation of IFN-beta therapy which make studies of 2 years or less unsuited to assess the clinical relevance of NAbs. Further, changes in NAb affinity occur and contribute to increase NAb effects by time. The present paper reviews our current knowledge of NAbs and stresses the importance of using measurements of NAbs routinely. It is concluded that NAb titres are important for the biological response to IFN-beta. Patients with low or intermediate titres may have preserved a full or partial biological response and might still benefit from IFN-beta therapy. However, persistent high titres of NAbs indicate an abrogation of the biological response and, hence, absence of therapeutic efficacy, and this observation should lead to a change of therapy. The application of the existing information about NAbs in clinical practice would lead to improved efficacy of IFN-beta treatment for the benefit of patients with MS.