Systemic recombinant human interferon-β treatment of relapsing-remitting multiple sclerosis : pilot study analysis and six-year follow-up

A pilot study was undertaken to test the safety and establish the side effect profile of recombinant human interferon-beta 1b (Betaseron, Berlex Laboratories, Richmond, CA), in patients with relapsing-remitting multiple sclerosis (RRMS). During the initial dose finding period (24 weeks), five groups of 6 patients each were treated by subcutaneous injection three times each week with either 0.8, 4, 8, or 16 million units (mU) of Betaseron or placebo (WHO Standard). Although some side effects were noted in all groups, a dose-related trend in reduction of exacerbation frequency and side-effect profile was noted. Patients given 16 mU had no exacerbations during the initial dosing period, but associated side effects led to dose reduction or dropout. An 8 mU dose was selected for further study after 24 weeks, and continuous dosing at 8 mU in 15 patients has now exceeded 6 years. Side effects abated over time. Neutralizing antibody developed in most patients, but titers were variable, fluctuated independently of clinical course, and tended to fall with prolonged treatment. A dose-dependent rise in neopterin levels was observed during the initial dosing period. This pilot study has demonstrated responsiveness to Betaseron, shown a stable safety profile over time, and established guidelines for a dosing regimen to evaluate and optimize further the efficacy of Betaseron in RRMS.