Interferon β neutralizing antibodies in multiple sclerosis: neutralizing activity and cross-reactivity with three different preparations

Abstract

The presence and titer of neutralizing antibodies (NABs) was evaluated by an antiviral biological assay in 387 samples of 111 multiple sclerosis (MS) patients treated with one of the three commercial preparations of interferon beta (IFNβ). Fifty NAB positive samples were found in 19 patients: 11 treated with IFNβ-1b (Betaferon®) and eight with IFNβ-1a (five with Avonex® and three with Rebif®). All the 38 NABs+ samples of patients treated with IFNβ-1b cross-reacted with IFNβ-1a of both commercial types. The median level of neutralizing units (NUs) of the sera was higher when tested against IFNβ-1a than against IFNβ-1b (p=0.000 vs. Avonexr® and p=0.003 vs. Rebif®).In line with these data, the NABs+ sera of patients treated with IFNβ-1a cross-reacted with IFNβ-1b and the level of NUs were lower when tested against IFNβ-1b than against IFNβ-1a (p=0.003). The different amount of NUs against IFNβ types 1a and 1b could be due to the presence of aggregates in the IFNβ-1b preparation. The different levels of cross-reactivity of NABs could reduce the bioavailability and therapeutic efficacy of IFNβ in NABs+ patients switching from IFNβ-1b to IFNβ-1a.