Disease Modifying Therapies for Multiple Sclerosis

Over the last few decades the treatment of multiple sclerosis (MS) has been approached from a number of different perspectives. The initial successes in MS therapy involved the use of corticosteroid treatments to induce short term improvements in neurological function, and symptomatic therapies for some of the complications of MS. More recently, with improved understanding of the immunological events occurring during progression of the disease, therapies that modify the natural history of the disease have become available. Interferon beta-1b (‘Betaseron’) is the first new treatment for MS to be licensed by the US Food and Drug Administration (FDA) in the last 30 years. In a multicentre, double-blind, placebo-controlled trial, the drug reduced the exacerbation rate and magnetic resonance imaging (MRI) evidence of disease activity. Other interferon preparations are currently undergoing clinical testing, and a second recombinant interferon beta has also shown evidence of clinical efficacy in a recently completed trial. Copolymer-1 has also reduced relapse rate in patients with replasing-remitting MS. Global immunosuppression with azathioprine and cyclophosphamide has been utilised with varying benefit in Europe and North America for several decades. In addition, there have been recent reports of beneficial effects of immunosuppressive agents such as methotrexate and cladribine in patients with chronic progressive MS. Clinical trial methodology (including more sensitive clinical outcome measures and the use of serial quantitative MRI) and serial cognitive testing have evolved to provide more convincing evidence of efficacy of MS therapies. In addition, the mechanism of action of older therapies, such as corticosteroids, has been elucidated by these advances. In the future, increasingly more specific immunotherapies will become available, and combinations of therapy may provide greater efficacy than current single agent approaches.