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

Background: Three different recombinant interferon beta (IFN beta) preparat ions are currently available for the treatment of MS, two IFN beta-1a produ cts (Rebif and Avonex) and one IFN beta-1b product (Betaferon). These produ cts differ with respect to the recommended dose, the dosage regimen, and th e injection route. This study compared the relative biologic activity of th ese three products in vitro and in vivo. Methods: Blood samples were collec ted from 237 patients with MS (170 on IFN beta therapy and 67 control subje cts receiving no therapy). Samples with neutralizing antibodies were exclud ed. 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 vit ro investigation, untreated blood was incubated for 24 hours with increasin g concentrations of the three IFNs from a dose of 1 IU/mL to 1000 IU/mL, af ter which levels of MxA were measured. Results: A difference between the gr oups 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 t he determination of TU by the manufacturers. At the single-dose level there were no significant differences between IFN beta preparations. In vivo, th ere were significantly different levels of MxA in the four groups. In the B etaferon 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 signific ant. differences between the groups were also apparent with respect to leve ls of sVCAM, which were higher with Betaferon than with Rebif. Conclusion: IFN beta-1b induces higher levels of the above markers of IFN beta bioactiv ity than either of the two IFN beta-1a preparations. Moreover, there is a l ess striking difference between the two IFN beta-1a preparations in favor o f subcutaneous IFN beta-1a.