mitoxantrone and MS

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Gonsette RE.

Institution

National Centre for Multiple Sclerosis, Melsbroek, Belgium.

r.gonsette@...

Title

A comparison of the benefits of mitoxantrone and other recent

therapeutic approaches in multiple sclerosis. [Review] [161 refs]

Source

Expert Opinion on Pharmacotherapy. 5(4):747-65, 2004 Apr.

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.