Neutralizing antibodies to interferon beta-1a and interferon beta-1b in MSpatients are cross-reactive

Objective: To determine whether neutralizing antibodies (NABs) to interfero n beta (IFN beta)-1a (Avonex) and IFN beta-1b (Betaseron) cross-react. Back ground: A total of 38% of MS patients treated with IFN beta-1b and 22% of t hose treated with IFN beta-1a were reported to develop NABs, which could re duce the clinical efficacy of the drug. Methods: Blood from 10 MS patients was collected before and at 3 and 6 months after initiating treatment with IFN beta-1a. ELISA was performed to detect binding antibodies to IFN beta-1 a. Sera from patients who tested positive for binding antibodies to IFN bet a-1a were then screened for NABs to IFN beta-1a in a biologic assay based o n neutralization of antiviral activity. These serum samples were subsequent ly tested for cross-reactivity with IFN beta-1b both in the ELISA and the b iologic assay. In the second part of the study, sera from patients who part icipated in the phase III IFN beta-1b trial at the University of Maryland w ere examined for cross-reactivity with IFN beta-1a in the ELISA and the bio logic assay. Results: Of the 10 patients treated with IFN beta-1a, three de veloped binding as well as NABs to IFN beta-1a 6 months after treatment, an d these antibodies cross-reacted with IFN beta-1b both in the binding and t he biologic assay. Similarly, sera from six patients with NABs to IFN beta- 1b showed cross-reactivity with IFN beta-1a in the binding assay. Three of these six serum samples tested for neutralizing activity against IFN beta-1 a demonstrated the presence of NABs to IFN beta-1a. Conclusions: NABs to IF N beta-1a (Avonex) and IFN beta-1b (Betaseron) cross-react, both in the bin ding and the biologic assays. This suggests that switching to alternate IFN beta preparation in patients who develop NABs may not be clinically benefi cial. Studies examining crossreactivity between NABs to IFN beta-1a and IFN beta-1b in a large number of patients are indicated.