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

The presence and titer of neutralizing antibodies (NABs) was evaluated by an antiviral biological assay in 387 samples of ill multiple sclerosis (MS) patients treated with one of the three commercial preparations of interferon beta (IFN beta). Fifty NAB positive samples were found in 19 patients: 11 treated with IFN beta-1b (Betaferon(R)) and eight with IFN beta-1a (five with Avonex(R) and three with Rebif(R)). All the 38 NABs + samples of patients treated with IFN beta-1b cross-reacted with IFN beta-1a of both commercial types. The median level of neutralizing units (NUs) of the sera was higher when tested against IFN beta-1a than against IFN beta-1b (p = 0.000 vs. Avonexr(R) and p = 0.003 vs. Rebif(R)). In line with these data, the NABs + sera of patients treated with IFN beta-1a cross-reacted with IFN beta-1b and the level of NUs were lower when tested against IFN beta-1b than against TFN beta-1a (p = 0.003). The different amount of NUs against IFN beta types 1a and 1b could be due to the presence of aggregates in the IFN beta-1b preparation. The different levels of cross-reactivity of NABs could reduce the bioavailability and therapeutic efficacy of IFN beta in NABs + patients switching from IFN beta-1b to IFN beta-1a, (C) 2000 Elsevier Science B.V. All rights reserved.