Neutralizing antibodies to interferon β-1a and interferon β-1b in MS patients are cross-reactive

Objective: To determine whether neutralizing antibodies (NABs) to interferon beta (IFNβ)-1α (Avonex) and IFNβ-1b (Betaseron) cross-react. Background: A total of 38% of MS patients treated with IFNβ-1b and 22% of those treated with IFNβ-1a were reported to develop NABs, which could reduce 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 IFNβ- 1a. ELISA was performed to detect binding antibodies to IFNβ-1a. Sera from patients who tested positive for binding antibodies to IFNβ-1a were then screened for NABs to IFNβ-1a in a biologic assay based on neutralization of antiviral activity. These serum samples were subsequently tested for cross- reactivity with IFNβ-1b both in the ELISA and the biologic assay. In the second part of the study, sera from patients who participated in the phase III IFNβ-1b trial at the University of Maryland were examined for cross- reactivity with IFNβ-1a in the ELISA and the biologic assay. Results: Of the 10 patients treated with IFNβ-1a, three developed binding as well as NABs to IFNβ-1a 6 months after treatment, and these antibodies cross-reacted with IFNβ-1b both in the binding and the biologic assay. Similarly, sera from six patients with NABs to IFNβ-1b showed cross-reactivity with IFNβ-1a in the binding assay. Three of these six serum samples tested for neutralizing activity against IFNβ-1a demonstrated the presence of NABs to IFNβ-1a. Conclusions: NABs to IFNβ-1a (Avonex) and IFNβ-1b (Betaseron) cross-react, both in the binding and the biologic assays. This suggests that switching to alternate IFNβ preparation in patients who develop NABs may not be clinically beneficial. Studies examining cross-reactivity between NABs to IFNβ-1a and IFNβ-1b in a large number of patients are indicated.