Antibodies to IFN-beta

A significant problem in relation to interferon-β (IFNβ) therapy is that a considerable proportion of the patients develop neutralizing anti-IFN antibodies (NAbs), which in high concentrations have been correlated to reduction of treatment response. In a previous study, we showed that binding and neutralizing antibodies appeared faster in patients receiving IFNβ-1b compared with IFNβ-1a, and fewer became positive if 22 μg IFNβ-1a was administered once weekly compared with three times weekly. IM administration induced antibodies less frequently than subcutaneous administration. Further, we demonstrated that the frequency of NAbs against IFNβ heavily depends on the sensitivity of the neutralizing assay.1 There have been considerable controversies regarding the clinical importance of these antibodies. Initially, all phase III studies found no relation between development of NAbs and clinical efficacy.2–4⇓⇓ In some studies, however, re-evaluation of the results or prolongation of the observation period disclosed that NAbs contribute to a lack of response to INFβ therapy in some patients with multiple sclerosis (MS).5–7⇓⇓ To evaluate the effect of different serum concentrations of NAbs against IFNβ on therapeutic efficacy, we measured NAbs to IFNβ in prospectively sampled sera from patients with relapsing-remitting MS who began treatment with a commercial IFNβ preparation during the years 1996 to 1999 in Denmark.8 The study comprised 541 patients, who all were treated with the same IFNβ preparation throughout the entire observation period: Betaferon (Schering, Berlin, Germany) 8 MIU every other day in 194 patients, Rebif (Serono, Geneva, Switzerland) 22 μg weekly in 103 patients, Rebif …