Comparative Study of the Pharmacodynamic and Pharmacologic Effects of Betaseron ® and AVONEX ™

The aim of this 1 week study was to compare the biologic effects induced by Betaseron^® and AVONEX^™ using their approved dose, route, and schedule. Sixteen healthy volunteers were randomly assigned to receive either a single i.m. dose of AVONEX^™ (6 million International Units [MIU]) or, every other day s.c. doses of Betaseron^® (8 MIU). Common side effects associated with interferon-β (IFN-β) treatment and biologic response parameters (neopterin, β₂-microglobulin, interleukin-10 [IL-10], and MxA protein levels in blood) were measured. Ibuprofen was administered to all subjects throughout the study. Fever, chills, and myalgia occurred most frequently and with the greatest severity between 6 and 12 h after the first dose of either IFN-β. Despite the additional dosing of subjects in the Betaseron^® group, the incidence, duration, and severity of the side effects were not significantly different from those in the AVONEX^™ group. Biologic response parameters reached similar maximum concentrations in both treatment groups. In the Betaseron^® group, neopterin and β₂-microglobulin levels remained significantly greater than baseline throughout the 7 day study, whereas those in the AVONEX™ group were elevated only through day 5. Betaseron^® treatment significantly increased IL-10 levels above baseline, but AVONEX^™ treatment did not. The overall induction of neopterin, β₂-microglobulin, and IL-10 (as measured by area under the concentration-time curve) was significantly greater in the Betaseron^® group than the AVONEX^™ group (p = 0.031). The results of this study demonstrate that the approved Betaseron^® dosing regimen, in combination with ibuprofen use, provided a significantly greater and more consistently elevated biologic response compared with that of AVONEX^™ and did so with a side effects profile comparable to that of once a week AVONEX^™ dosing.