Compared benefit of approved and experimental immunosuppressive therapeutic approaches in multiple sclerosis.
An important amount has been learnt about the mechanisms of action, efficacy and long-term toxicities of mitoxantrone. Importantly, recent observations strongly suggest that early administration of potent immunosuppressants (mitoxantrone and alemtuzumab) is definitely more effective than approved immunomodulators to delay or even reverse disability progression. Given the cardiotoxicity of mitoxantrone, restricting exposure to the drug to 2 or 3 years, the benefits and risks of immunosuppressants previously used as off-label treatments (cyclophosphamide and cladribine) have been revisited, and the potential efficacy in multiple sclerosis of recent immunosuppressants used in other autoimmune diseases, organ transplantation and cancer therapy has received increasing attention. Those immunosuppressants comprise monoclonal antibodies targeting B cells, lymphocytes and monocytes, IL-2 receptor and alpha4 integrin, as well as new molecules (pixantrone and isoxazole derivatives) and a new generation of immunosuppressants (fingolimod), which modulate lymphocyte re-circulation. This review addresses the most recent data concerning the efficacy and safety of mitoxantrone and of new experimental therapies that are presently in progress.
Gonsette
Richard E
RE
National Centre for Multiple Sclerosis, B 1820 Melsbroek, Belgium. r.gonsette@skynet.be
D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D017338:Cladribine / Q000494:pharmacology / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007555:Isoxazoles / Q000494:pharmacology / Q000627:therapeutic use; D008024:Ligands; D008942:Mitoxantrone / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy*; D011409:Propylene Glycols / Q000494:pharmacology / Q000627:therapeutic use; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D008024:Ligands; D011409:Propylene Glycols; D017338:Cladribine; D003520:Cyclophosphamide; D008942:Mitoxantrone; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine