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 sympto matic therapies for some of the complications of MS. More recently, wi th 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, doub le-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 test ing, and a second recombinant interferon beta has also shown evidence of clinical efficacy in a recently completed trial. Copolymer-1 has al so reduced relapse rate in patients with replasing-remitting MS. Globa l immunosuppression with azathioprine and cyclophosphamide has been ut ilised with varying benefit in Europe and North America for several de cades. In addition, there have been recent reports of beneficial effec ts of immunosuppressive agents such as methotrexate and cladribine in patients with chronic progressive MS. Clinical trial methodology (incl uding more sensitive clinical outcome measures and the use of serial q uantitative 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 sp ecific immunotherapies will become available, and combinations of ther apy may provide greater efficacy than current single agent approaches.