Interferon-beta1a for the treatment of multiple sclerosis

Abstract

At present, two types of recombinant human interferon (IFN)-beta are in clinical use. IFN-beta1a is produced in genetically engineered Chinese hamster ovary cells, and its amino acid sequence and glycosylation pattern are identical to those of endogenous human IFN-beta. The beneficial effect of IFN-beta in multiple sclerosis (MS) probably results from different mechanisms of action, such as a direct effect on plasma cells modulating IgG synthesis, an increase of interleukin (IL)-10 levels, the inhibition of IL-1beta and tumour necrosis factor alpha, the stimulation of IL-1 receptor antagonist production, the inhibition of proliferation of leukocytes, a decreased antigen presentation in microglia, a reduction of T cell migration into the brain by inhibition of the activity of T cell matrix metalloproteinases, and a downregulation of adhesion molecules. IFN-beta1a has been shown by several multicenter controlled trials to be effective in relapsing-remitting MS. It reduces relapse rate by 30-50%, magnetic resonance imaging signs of disease activity in 30-80% and disability progression by 30%. It is also effective in preventing conversion to clinically definite MS when given at the time of a first demyelinating event (i.e., at the very beginning of the clinical disease). No clear evidence of the persistence of the efficacy over the long-term has stood out from a systematic analysis of published trials. A Cochrane review concluded that, in fact, the clinical effect beyond the first year of treatment is not clear. Finally, no efficacy has been shown in secondary progressive or primary progressive MS. However, IFN-beta1a is very well tolerated and the most frequent side effects are mild (local skin reaction and flu-like symptoms) and decline in frequency or disappear after the first 3-6 months of treatment. Although the optimal frequency between once weekly or multiple weekly administrations is still controversial, all protocols require multiple monthly injections. Some patients might find it hard to cope with such a treatment regimen over the long term. Ongoing trials with new powerful immunomodulatory drugs, such as monoclonal antibodies, that require only monthly or bimonthly parenteral administrations will probably offer a better tolerated treatment option in the near future.