Interferon beta 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 a n antiviral biological assay in 387 samples of ill multiple sclerosis (MS) patients treated with one of the three commercial preparations of interfero n 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 w ith Avonex(R) and three with Rebif(R)). All the 38 NABs + samples of patien ts treated with IFN beta-1b cross-reacted with IFN beta-1a of both commerci al types. The median level of neutralizing units (NUs) of the sera was high er 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 test ed 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 cros s-reactivity of NABs could reduce the bioavailability and therapeutic effic acy of IFN beta in NABs + patients switching from IFN beta-1b to IFN beta-1 a, (C) 2000 Elsevier Science B.V. All rights reserved.