A comparison of the benefits of mitoxantrone and other recent therapeutic approaches in multiple sclerosis

Abstract

The approval by the FDA of four immunomodulators (three IFNs and glatiramer acetate) and one immunosuppressant (mitoxantrone; Novantrone) for the treatment of multiple sclerosis is definitely the most important progress in this field since the first description of the disease > 150 years ago. However, both types of immunotherapies raise specific problems. Immunomodulators benefit patients in the relapsing-remitting phase, or patients in the secondary-progressive phase showing clinical and/or radiological signs of active inflammatory processes. Their benefit is modest, but seems to persist with long-term administration, as their tolerance is acceptable. Mitoxantrone is a rescue therapy reserved to patients with an aggressive, rapidly progressive form of the disease. This immunosuppressant is effective on inflammatory processes and pathomechanisms responsible for disability progression. Unfortunately, its cardiotoxicity and potential leukaemogenicity prevent an administration beyond 2 or 3 years. Thus, there is a need to improve on the efficacy of immunomodulators and to reduce the toxicity of immunosuppressants. Combination therapies with immunomodulators and antioxidants or with neuroprotective drugs against excitotoxicity or Na + /Ca 2+ channellopathy are currently being investigated. With regard to immunosuppressants, the development of monoclonal antibodies with fully human protein sequences and the synthesis of a new molecule as effective as mitoxantrone but with a much lower toxicity (pixantrone) seem promising to halt or even to prevent disability progression.