Dose and frequency of interferon treatment matter--INCOMIN and OPTIMS.

Three different interferon beta (IFN beta) products are currently approved for the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). However, the recommended method of administration, the dosage and the frequency of administration differ widely between each of the three products. Although controlled clinical trials have demonstrated the efficacy of both alternate-day IFN beta-1b (Betaferon/Betaseron) and once-weekly IFN beta-1a (Avonex) compared with placebo, it is likely that patient compliance, efficacy and tolerability are affected by the dosage regimen used. There are several issues to consider. Once-weekly administration may be associated with fewer adverse events and greater convenience, and it has been suggested that this may increase compliance. Conversely, frequent administration may be associated with increased overall efficacy. There is a convincing pharmacological rationale indicating that frequent dosing, with an interval of less than 72 h, is necessary to sustain the activity of intracellular molecular signalling pathways responsible for regulating IFN beta-induced gene expression. However, there was a need to explore the overall effectiveness of the two administration protocols in a comparative trial. The INCOMIN (Independent Comparison of Interferon) study compared clinical and magnetic resonance imaging (MRI) efficacy of IFN beta-1b 250 microg (8 MIU) subcutaneously (s.c.) on alternate days and IFN beta-1a 30 microg (6 MIU) intramuscularly (i.m.) once weekly in patients with RRMS. INCOMIN demonstrated convincingly that clinical and MRI outcome measures were significantly better in the IFN beta-1b-treated group. Blinded MRI evaluation confirmed the clinical results. Despite some limitations of the study design, imposed by the ethical and practical challenges of conducting comparative trials of injectable therapies, the concordance of the clinical and MRI findings indicate that frequently administered IFN beta-1b reduced evidence of disease activity more effectively than once-weekly administered IFN beta-1a, with the clinical benefits for patients becoming more pronounced over time. Given that the response to IFN beta appears to be dose dependent, the question that might be asked is whether greater efficacy can be obtained by increasing doses beyond those currently approved. OPTIMS (Optimization of Interferon dose for MS) is currently examining the safety and efficacy of a dose of IFN beta-1b that is higher than any currently marketed IFN beta. While OPTIMS is still underway, preliminary safety analyses indicate that higher doses are well tolerated.