Neutralizing antibodies to interferon-beta and other immunological treatments for multiple sclerosis: prevalence and impact on outcomes.

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)-beta and natalizumab have been recognized. The prevalence of NAbs against different IFNbeta 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). IFNbeta-1a given intramuscularly induces significantly less NAbs than any other IFNbeta formulation. The longitudinal development of NAbs also differs between IFNbeta preparations, with higher reversion rates in IFNbeta-1b-treated compared with IFNbeta-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 IFNbeta, they are associated with a loss of clinical and radiological efficacy of the drug.