Immunosuppressive agents in multiple sclerosis

Immunosuppressive agents have been used in multiple sclerosis (MS) for decades. The approval of several immunomodulatory agents against MS beginning in the 1990s, whose putative mechanisms of action appeared more MSspecific, curtailed the importance of immunosuppressants, which made them treatment options of second choice. However, with the recent approval of mitoxantrone for treatment of patients with active forms of relapsing-remitting or secondary progressive MS and with a number of oral immunosuppressive agents being assessed in phase 11 and III clinical trials, a re- naissance of this type of agents is currently occurring. This review provides an outline of the most important clinical studies and discusses relevant side effects of the major immunosuppressants (i.e., mitoxantrone, azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil, cladribine, and sirolimus/temsirolimus). The current knowledge of the putative mechanisms of action of these compounds is discussed. Key Words: Multiple sclerosis, immunosuppressive agents, mitoxantrone, azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil, cladribine, (tem)sirolimus.