The argument against the use of cyclophosphamide and mitoxantrone in the treatment of multiple sclerosis.

Mitoxantrone (MITX) and cyclophosphamide (CPM) are potent immunosuppressive agents with efficacy in the treatment of multiple sclerosis (MS). Both agents appear effective in those patients with active inflammatory disease but are probably less effective in patients with a secondary progressive (SP) course dominated by a degenerative component. Given these agents are effective patients with active inflammation the question arises as to whether they are more effective than high dose interferon therapy. Interferon beta administered at high dose and high frequency suppresses enhancing lesions by as much as 90% and brings about a 35% decrease in relapse rates in addition to decreasing the progression of disability. Interferons have an excellent safety profile even after years of administration. What then is the advantage of immunosuppressive agents such as cyclophosphamide and mitoxantrone over safer and still effective treatments? The answer lies in the magnitude of effect in those with the most active and aggressive disease states. While interferons are safe and effective in those with mild or moderate inflammatory disease states, they are probably not sufficient to bring about control in disease that is highly active and resilient. Both mitoxantrone and cyclophosphamide have the ability to suppress inflammation that may be resistant to therapy with more conservative agents. Given the safety profile of these agents their use should be restricted to those patients with aggressive disease resistant to treatment with more conservative agents.