A practical Approach to immunomodulatory therapy of MS

I. Introduction: In Multiple Sclerosis (MS) neither the pathogenesis of the disease nor the mechanism of an action of immunomodulating therapies (IMT " S) are fully understood [1,2,3]. Genetic predispositions, socioeconomic influences, gender (females: males = 2:1), infectious agents, and other environmental factors have been implicated [4,5]. Identifying treatment has been challenging since the discovery of a successful therapy usually begins with a solid understanding the pathogenesis of the disease. In spite of a lack of complete understanding of the pathogenesis, four immunomodulating and one immunosuppressive drug have received FDA approval for the treatment of MS since 1993. This chapter provides a current overview of the definition and pathogenesis of the disease, the different types of MS, a new diagnostic criteria, the rationale for early therapy, a review of the approved MS therapies, the strategies to evaluate ongoing treatment efficacy, the management of " sub optimal " treatment responders and the prospects for future therapies. (Table 1) The emphasis is on relapsing remitting MS (RRMS) because most of the therapeutic data deals with RRMS. No immunomodulating therapies (IMT's) have been FDA approved for primary progressive MS (PPMS) or secondary progressive MS (SPMS) without relapses. One immunosuppressive, antineoplastic agent, mitoxantrone (Novantrone), also has FDA approval for " worsening MS ". Its role as a " rescue therapy " of sub optimal responders to the IMT's will also be discussed.