The presumed but as yet unspecified autoimmune-mediated basis for the pathogenesis of
multiple sclerosis has led to attempts to modify the immune system of patients with this disease based on general and selective approaches. The rationale for using
interferon-beta for the treatment of
multiple sclerosis is based on its
antiviral and complex immunoregulatory activities. Interferon-beta-1a (
Avonex(R)) is a recombinant molecule which is indistinguishable from natural
interferon-beta derived from human fibroblasts. Its precise mechanism of action is unknown, although effects on immune system processes which have been implicated in the pathogenesis of
multiple sclerosis have been documented. T cell activation and migration into the CNS is a primary process in the pathogenesis of
multiple sclerosis. In vitro and in vivo, interferon-beta-1a, compared with placebo or no treatment, significantly reduced expression of T cell surface activation markers, and significantly increased CNS levels of
interleukin-10 - a potent inhibitor of cell-mediated immune responses. Pharmacokinetic studies indicate that
intramuscular injection is the optimal route of administration for this formulation of interferon-beta-1a. In patients with
relapsing-remitting multiple sclerosis who participated in a randomised double-blind trial, interferon-beta-1a 30mug (6 MIU) administered by
intramuscular injection once weekly for 2 years (n = 158), compared with placebo (n = 143), significantly extended the time to onset of sustained neurological disability. Interferon-beta-1a also reduced the rate of disease relapse by approximately one-third compared with placebo, a finding which was supported by cranial magnetic resonance imaging (MRI) data showing significant reductions in lesion number and volume. Interferon-beta-1a was well tolerated, with
influenza-like symptoms making up the majority of adverse reactions. The clinical significance of the beneficial effect of interferon-beta-1a on
disease progression has been endorsed by the findings of a retrospective statistical analysis of the disability outcomes data obtained in the double-blind trial. In patients with relapsing
multiple sclerosis, interferon-beta-1a is the only
drug that has been demonstrated to significantly slow
disease progression without excessive toxicity, in addition to significantly reducing the rate of relapse - measured clinically and by MRI. Notwithstanding the absence of long term tolerability data, and data from comparative trials with other agents, interferon-beta-1a represents a promising advance in
drug therapy for relapsing
multiple sclerosis.