Mitoxantrone and cytotoxic drugs' mechanisms of action.
Evidence has suggested that early, aggressive intervention may improve both short- and long-term outcomes in patients with multiple sclerosis (MS). Cytotoxic agents may offer advantages in this setting, particularly when used as an induction or add-on therapy with immunomodulators. Immunosuppression is the mechanism of action common to all cytotoxic drugs; individual subtleties in immunoregulatory actions are likely of minor importance. In the United States, mitoxantrone is currently the only cytotoxic agent approved for the treatment of MS (secondary-progressive, progressive-relapsing, and worsening relapsing-remitting forms). Therapies in phase III development include cyclophosphamide, mycophenolate mofetil, cladribine, and teriflunomide. All these drugs have exhibited efficacy in controlled clinical trials, although the degree of benefit with respect to MRI and clinical endpoints has varied both within and among the various agents. Further investigations are needed to determine whether cytotoxic drugs represent a substantial improvement over treatments that have a more targeted impact on the immune system.
Vollmer
Timothy
T
Department of Neurology, University of Colorado Denver, Aurora, CO 80045, USA. Timothy.Vollmer@UCD.edu
Stewart
Thomas
T
Baxter
Nancy
N
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D003603:Cytotoxins / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007155:Immunologic Factors / Q000276:immunology; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000276:immunology; D018448:Models, Immunological; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000276:Adjuvants, Immunologic; D016207:Cytokines; D003603:Cytotoxins; D007155:Immunologic Factors; D008942:Mitoxantrone