[Is immunosuppression a future therapeutic strategy for multiple sclerosis?].
Although in previous studies no clear demonstration was found of the efficacy of azathioprine, cyclophosphamide and methotrexate as immunoprophylactic agents in cases of multiple sclerosis (MS), over the past five years a number of well-designed clinical trials utilizing immunosuppressive and immunomodulatory agents have shown partial efficacy regarding the drugs involved, but they have not been able to determine in what way these drugs can modify the natural course of this disease. Among the immunosuppressors, mitoxantrone is of particular interest as during the past two years three controlled trials have taken place in Europe and have demonstrated its efficacy both as regards clinical (frequency of symptoms, progression of the disease) and magnetic resonance imaging (MRI) criteria. Due to its potentially severe cardiotoxicity related to total cumulative dose, mitoxantrone is only prescribed for a limited period, and its use is limited to selected patients with a high relapse rate and incomplete remission, or to those who do not respond to beta-interferon treatment. The immunomodulatory agents have less immediate efficacy, but because they are well tolerated they can be used early in the course of the disease and over a prolonged period of time. The beta-interferons (1a or 1b) have been given market approval for use in the treatment of MS: three large, randomized, double-blind studies have demonstrated their capacity to reduce by 30% the frequency of symptoms and the appearance of disabilities associated with relapse and with the progression of the disease. Glatirameracetate or copolymer 1, which is available in France (ATU), has been found to reduce the frequency of relapse by 30%. It constitutes an alternative immunomodulatory treatment for relapsing-remitting patients without major functional disabilities and who suffer from severe side effects with beta-interferon treatment. In the future, the early use of immunomodulatory agents and therapeutic drug combinations may be introduced. Therapeutic trials are currently in progress to determine the viability of this approach.
Edan
G
G
Clinique neurologique centre hospitalier universitaire de Rennes, hôpital de Pontchaillou, France.
Coustans
M
M
D001379:Azathioprine / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003520:Cyclophosphamide / Q000627:therapeutic use; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D008942:Mitoxantrone / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000628:therapy*
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D008942:Mitoxantrone; D001379:Azathioprine; D008727:Methotrexate