Antibodies to interferon beta in patients with multiple sclerosis receiving CinnoVex, rebif, and betaferon

Abstract

Treatment with interferon beta (IFN-β) induces the production of binding antibodies (BAbs) and neutralizing antibodies (NAbs) in patients with multiple sclerosis (MS). NAbs against IFN-β are associated with a loss of IFN-β bioactivity and decreased clinical efficacy of the drug. The objective of this study was to evaluate the incidence and the prevalence of binding antibodies (BAbs) and neutralizing antibodies (NAbs) to IFN-β in MS patients receiving CinnoVex, Rebif, or Betaferon. The presence of BAbs was studied in serum samples from 124 MS patients using one of these IFN-β medications by ELISA. The NAbs against IFN-β were measured in BAb-positive MS patients receiving IFN-β using an MxA gene expression assay (real-time RT-PCR). Of the 124 patients, 36 (29.03%) had BAbs after at least 12 months of IFN-β treatment. The proportion of BAb+ was 38.1% for Betaferon, 21.9% for Rebif, and 26.8% for CinnoVex. Five BAb-positive MS patients were lost to follow-up; thus 31 BAb-positive MS patients were studied for NAbs. NAbs were present in 25 (80.6%) of BAb-positive MS patients receiving IFN-β. In conclusion, the three IFN-β preparations have different degrees of immunogenicity.

Keywords: Antibodies, Neutralizing; Binding Antibodies; Bioactivity; Interferon-beta; Multiple Sclerosis; Myxovirus Resistance Rrotein A (MxA).

Fig. 1

The mean optical density (OD) in the three groups. The mean absorbance values are 1.19, 1.03, and 0.98 for Betaferon, CinnoVex, and Rebif, respectively. Betaferon has shown the highest mean OD values for BAbs. The mean OD value in CinnoVex was between the Betaferon and Rebif groups. Error bars indicate (+/-2) standard error.