, Volume 23, Issue 5, pp 379-396
Date: 29 Aug 2012

Neutralizing Antibodies to Interferon-β and other Immunological Treatments for Multiple Sclerosis

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Abstract

Biopharmaceuticals can induce antibodies, which interact with and neutralize the therapeutic effect of such drugs and are therefore termed neutralizing antibodies (NAbs). In the treatment of multiple sclerosis, NAbs against interferon (IFN)-β and natalizumab have been recognized. The prevalence of NAbs against different IFNβ preparations varies widely, mainly depending on the product but also on other factors such as amino acid sequence variations, glycosylation, formulation, route and frequency of application, dose, duration of treatment and patient characteristics (human leukocyte antigen [HLA] status). IFNβ-1a given intramuscularly induces significantly less NAbs than any other IFNβ formulation. The longitudinal development of NAbs also differs between IFNβ preparations, with higher reversion rates in IFNβ-1b-treated compared with IFNβ-1a-treated patients. The negative effect of NAbs on various outcome measures is very consistent across many studies, specifically when observation periods are longer than 2 years. NAbs against natalizumab occur less frequently (6%) and, like NAbs against IFNβ, they are associated with a loss of clinical and radiological efficacy of the drug.