Interferon-β-1b: a review of its use in multiple sclerosis.

Interferon-β-1b has been used as a disease-modifying therapy in multiple sclerosis (MS) for many years. Although its mechanism of action in MS has not been fully elucidated, it appears to involve immunomodulatory effects mediated by interactions with specific receptors. Large, randomized, multicentre, clinical trials of 2-3.5 years' duration have demonstrated the efficacy of interferon-β-1b 250 μg subcutaneously every other day in patients with a first clinical event suggestive of MS (i.e. those with clinically isolated syndrome [CIS]) and in those with relapsing-remitting MS (RRMS). In terms of its efficacy on primary (or co-primary) endpoints, interferon-β-1b significantly reduced the risk of developing clinically definite MS compared with placebo in patients with CIS in the BENEFIT study. In patients with RRMS, interferon-β-1b was associated with a significantly lower annualized relapse rate and a significantly higher proportion of relapse-free patients compared with placebo in a registration trial conducted by the Interferon-β MS Study Group. The INCOMIN trial in patients with RRMS showed a significant advantage of interferon-β-1b over intramuscular interferon-β-1a in terms of the percentage of relapse- and progression-free patients and the proportion of patients without new MRI-documented lesions. Other active-comparator trials in RRMS used a variety of primary (or co-primary) endpoints and showed no significant differences between interferon-β-1b and either subcutaneous glatiramer acetate (BECOME and BEYOND trials) or subcutaneous interferon-β-1a (Danish MS Group trial) for these outcomes. In patients with secondary progressive MS (SPMS), the European Study Group showed that interferon-β-1b significantly increased the time to confirmed disease progression compared with placebo, although there was no significant between-group difference for this primary endpoint in a similar trial conducted by the North American Study Group. The studies allowed inclusion of patients with superimposed relapse, and both trials showed a significant reduction in annualized relapse rate with interferon-β-1b. The most frequently reported adverse events with interferon-β-1b are flu-like symptoms and injection-site reactions, which can usually be managed. The incidence of these adverse events generally declines markedly after the first year of treatment. Lymphopenia is the most frequently reported laboratory abnormality and occurs in the majority of patients. Depression, suicidal ideation and injection-site necrosis were the most serious adverse events reported with interferon-β-1b in clinical trials. Long-term safety data over a 16-year follow-up period showed no unexpected adverse events among patients treated with interferon-β-1b. Thus, interferon-β-1b is a well established, first-line, disease-modifying therapy that has demonstrated efficacy in newly emerging MS, RRMS and SPMS with superimposed relapse in well designed clinical trials, and has a generally manageable tolerability profile, with no unexpected adverse events after many years of follow-up.