A comparative study of the relative bioavailability of different interferon beta preparations

Background: Three different recombinant interferon beta (IFN beta) preparations are currently available for the treatment of MS, two IFN beta-1a products (Rebif and Avonex) and one IFN beta-1b product (Betaferon). These products differ with respect to the recommended dose, the dosage regimen, and the injection route. This study compared the relative biologic activity of these three products in vitro and in vivo. Methods: Blood samples were collected from 237 patients with MS (170 on IFN beta therapy and 67 control subjects receiving no therapy). Samples with neutralizing antibodies were excluded. Levels of the antiviral protein MxA and soluble vascular cell adhesion molecule-1 (sVCAM) in the four groups were measured by ELISA. In the in vitro investigation, untreated blood was incubated for 24 hours with increasing concentrations of the three IFNs from a dose of 1 IU/mL to 1000 IU/mL, after which levels of MxA were measured. Results: A difference between the groups was observed in vitro, with a significant change from baseline in MxA levels being observed at 10 IU for Betaferon compared with 100 IU for Rebif and Avonex. However, this might be due to the different methods used for the determination of TU by the manufacturers. At the single-dose level there were no significant differences between IFN beta preparations. In vivo, there were significantly different levels of MxA in the four groups. In the Betaferon group, the median value for MxA was 2.29 ng/10(5) peripheral blood leukocytes (PBL), compared with 1.00 ng/10(5) PBL for Rebif, 0.57 ng/10(5) PBL for Avonex, and 0.14 ng/10(5) PBL for the control group. Some significant. differences between the groups were also apparent with respect to levels of sVCAM, which were higher with Betaferon than with Rebif. Conclusion: IFN beta-1b induces higher levels of the above markers of IFN beta bioactivity than either of the two IFN beta-1a preparations. Moreover, there is a less striking difference between the two IFN beta-1a preparations in favor of subcutaneous IFN beta-1a.