Impact of neutralizing antibodies on the clinical efficacy of interferon beta in multiple sclerosis

Neutralizing antibodies (NAbs) can develop in a large proportion of patients with MS who receive treatment with interferon beta (IFNbeta). Data show that IFNbeta-1b is more immunogenic than IFNbeta-1a and that IFNbeta-1a-Rebif((R)) is more immunogenic than IFNbeta-1a-Avonex((R)). This article reviews the long-term data from large phase III clinical trials showing that NAbs can reduce the clinical efficacy of IFNbeta in patients with MS; patients who have a positive result on NAb testing have a higher relapse rate and more disease activity, as measured by brain MRI, than do patients with a negative result. The detrimental effects of NAbs were not observed until after 18 months of treatment, suggesting that short-term clinical trials cannot adequately assess the efficacy of IFNbeta products in MS. Clinicians should consider the possible development of NAbs when starting patients on treatment and in patients with disease progression while on IFNbeta treatment.