What is new in the treatment of multiple sclerosis?

Multiple sclerosis (MS) is considered an autoimmune disease associated with immune activity directed against central nervous system antigens. Based on this concept, immunosuppression and immunomodualtion have been the mainsta ys of therapeutic strategies in MS. During the last decade new therapies ha ve been shown to significantly improve MS disease course. The effective the rapies have led to a better understanding of MS pathogenesis and further de velopment of even more efficient therapeutic interventions. Recombinant interferon (IFN)beta represents the first breakthrough in MS th erapy. Three large placebo-controlled, double-blind studies and several sma ller studies have demonstrated the efficacy of different forms of IFN beta administrated by either subcutaneous or intramuscular routes and at differe nt doses in patients with active relapsing-remitting multiple sclerosis (RR -MS). The three IFN beta drugs are IFN beta-1b and two IFN beta-1a preparat ions (Avonex(R) and Rebif(R)). Although each clinical trial had unique feat ures and differences that make direct comparisons difficult, the aggregate results demonstrate a clear benefit of IFN beta for decreasing relapses and probability of sustained clinical disability progression in patients with RR-MS. All forms of IFN beta therapy had beneficial effects on the disease process measured by brain magnetic resonance imaging (MRI). IFN beta-1a (Av onex(R)) also showed benefit in slowing or preventing the development of MS related brain atrophy measured by MRI after 2 years of therapy. Glatiramer acetate, the acetate salt of a mixture synthetic polypeptides th ought to mimic the myelin basic protein showed a significant positive resul ts in reducing the relapse rate in patients with RR-MS. Follow up of these patients for approximately 3 years continued to show a beneficial effect on disease relapse rate. Recent MRI data supported the beneficial clinical re sults seen with glatiramer acetate in patients with RR-MS. Recent studies using intravenous immune globulin (IVIG) suggest that IVIG c ould be effective to some degree in patients with RR-MS. However, there is not enough evidence that IVIG is equivalent to IFN beta or glatiramer aceta te in the treatment of patients with RR-MS. There have also been recent therapeutical advances in secondary progressive MS (SP-MS). A recent large phase III, placebo-controlled study with IFN be ta-1b in patients with SP-MS convincingly documented that IFN beta-1b slowe d progression of the disease independent of the degree of the clinical disa bility at the time of treatment initiation and independent of presence of s uperimposed relapses. Mitoxantrone, an anthracenedione synthetic agent, was also shown to be effe ctive as treatment for active SP-MS. It is well tolerated but the duration of treatment is limited by cumulative cardiotoxicity. There is a growing consensus that disease-modifying therapies should be ini tiated early in the course of the disease before irreversible clinical disa bility has developed. Different therapies should be considered and tailored based on patient condition. Combination therapies could be considered as a therapeutic option for patients that failed therapies with IFN beta and/or glatiramer acetate. Currently, there are new ongoing studies testing safet y and/or efficacy of different combination regimens (i.e. azathioprine with IFN beta, IFN beta with glatiramer acetate, or pulses of intravenous cyclo phosphamide with IFN beta). Determining the effect of different therapies on the course of the disease within large clinical studies appears easier than determining individual re sponsiveness. Therefore. standardised methods for evaluating individual pat ients receiving disease-modifying therapies and development of effective th erapeutic algorithms are needed.