Neurology 2000;54:2055-2060
© 2000 American Academy of Neurology
Articles
A comparative study of the relative bioavailability of different interferon beta preparations
F. Deisenhammer, MD,
I. Mayringer, MD,
J. Harvey, PhD,
E. Dilitz, MD,
T. Gasse, MD,
D. Stadlbauer, MD,
M. Reindl, PhD and
T. Berger, MD
From the Department of Neurology (Drs. Deisenhammer, Mayringer, Dilitz, Gasse, Stadlbauer, Reindl, and Berger), University of Innsbruck, Austria; and Bayer Diagnostics (Dr. Harvey), Emeryville, CA.
Address correspondence and reprint requests to Dr. Florian Deisenhammer, Department of Neurology, University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; e-mail: florian.deisenhammer{at}uibk.ac.at
BACKGROUND: Three different recombinant interferon beta (IFNß) preparations are currently available for the treatment of MS, two IFNß-1a products (Rebif and Avonex) and one IFNß-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 IFNß 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 IU by the manufacturers. At the single-dose level there were no significant differences between IFNß 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/105 peripheral blood leukocytes (PBL), compared with 1.00 ng/105 PBL for Rebif, 0.57 ng/105 PBL for Avonex, and 0.14 ng/105 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: IFNß-1b induces higher levels of the above markers of IFNß bioactivity than either of the two IFNß-1a preparations. Moreover, there is a less striking difference between the two IFNß-1a preparations in favor of subcutaneous IFNß-1a.
Key words: MS—Interferon beta—Bioavailability—MxA—Vascular cell adhesion molecule.
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