The safety, tolerability and pharmacodynamic responses of interferon BETA-1A (Rebif®) versus interferon BETA-1B (Betaseron®) in healthy male volunteers

Abstract

Interferon beta-1a (IFNβ-1a) and beta-1b (IFNβ-1b) are immunomodulators used for the treatment of relapsing-remitting multiple sclerosis (RRMS). The primary objective of this study was to compare the biological effects induced by subcutaneous administrations of IFNβ-1a (Rebif®, 44 μg, three times weekly) and IFNβ-1b (Betaseron®, 250 μg, given every other day) in healthy male volunteers (n=64). The secondary objectives were to assess the local injection site tolerability and safety of both treatments. IFNβ-1a and IFNβ-1b were administered over a 4-week period and biological response markers were measured (neopterin in serum, β2-microglobulin in serum, and MxA protein in blood). Pharmacokinetic parameters of the biological markers were calculated and injection site pain and reactions were determined using numerical rating scale (NRS) and visual analogue scale (VAS). Following treatments with IFNβ-1b and IFNβ-1a, baseline-adjusted area under the concentration-time curve of neopterin (149.2 and 153.0 nmol·day/L, respectively), β2-microglobulin (12.9 and 16.2 mg·day/L, respectively), and MxA protein (9091 and 9535 ng.day/mL, respectively) were similar. Betaseron® treatment was associated with less pain and reactions at the injection site. These results support the hypothesis that the administration of Betaseron® over 4 weeks resulted in similar pharmacodynamic responses to that of Rebif®, and with an improved safety and tolerability profile. Clinical Pharmacology & Therapeutics (2004) 75, P32–P32; doi: 10.1016/j.clpt.2003.11.120