Mitoxantrone is a drug which acts to ‘damage’ rapidly dividing cells, such as those in the immune system. It is usually used, in combination with other drugs, as a type of chemotherapy to treat certain types of cancer. In recent years it has been used to treat some forms of MS. It is normally used in very active relapsing remitting or secondary progressive MS, where relapses are still a significant feature.

During the period of treatment, mitoxantrone appears to work in MS by suppressing the immune system and giving the nervous system a chance to recover from recent relapses.

What is the evidence that it works in MS?

Mitoxantrone was tested in EAE with studies demonstrating a significant suppression of the disease (1,2). In 1997, an Italian study in 51 people with relapsing remitting MS showed a positive effect of mitoxantrone on the number of relapses. It also reported a trend toward improved MRI findings, although the effect was not statistically significant (3). 

Where is it available?

Mitoxantrone has been marketed in the United States since 1989 and later got a license for the treatment of MS in October 2000 from the Food and Drug Administration (FDA).

Mitoxantrone is currently licensed in the UK for the treatment of leukaemia and lymphoma, but not MS. However, it is used as an "Off-licence" treatment for MS in many UK centres. Mitoxantrone is no longer under patent and is made as a ‘generic’ drug by several companies. As a result there is no commercial interest in obtaining a licence for its use in MS in the UK. 

Who is likely to benefit?

It is likely to benefit patients with very active MS (many relapses and accumulating disability with each relapse) and can be used as a short to medium-term (2-3 years) treatment in an attempt to stabilise MS. Most often, it is used in people who continue to have significant relapses, despite treatment with beta interferon or Copaxone, although some neurologists will offer mitoxantrone as ‘first-line’ or ‘induction’ treatment in people with very frequent, severe relapses.

Mitoxantrone was not shown to have any benefit in primary progressive MS, in a study involving 60 people recently completed in the United States.
 

What are the limitations on use and side effects?

Mitoxantrone is given by monthly or three-monthly infusions at doses of 10-20mg (6-12mg/m2) intravenously (via a vein). The total lifetime dose should not exceed 140mg/m2 as beyond this dose there is an increased risk of cardiac side effects.
 

Last Updated

Written for the MS Society by Dr Jason Ramtahal, Clinical Research Fellow at The Walton Centre for Neurology and Neurosurgery, December 2004 

References

1. Ridge SC, Sloboda AE, McReynolds RA, Levine S, Oronsky AL, Kervar SS. Suppression of experimental allergic encephalomyelitis by mitoxantrone. Clin Immunol Immunopathol 1985; 35:35-42.

2. Lublin FD, Lavasa M, Viti C, Knobler RL. Suppression of acute and relapsing experimental allergic encephalomyelitis with mitoxantrone. Clin Immunol Immunopathol 1987; 45:122-128.

3. Millefiorini E, Gasperini C, Pozzilli C, D’Andrea F, Bastianello S, Trojano M, Morino S, Morra VB, Bozzao A, Calo’ A, Bernini ML, Gambi D, Prencipe M. Randomized placebo controlled trial of Mitoxantrone in relapsing remitting multiple sclerosis: 24 month clinical and MRI outcome, J Neurol 1997; 244:153-9.

4. Edan G, Miller D, Clanet M, Confavreux C, Lyon-Caen O, Lubetzki C, et al. Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria. J Neurol Neurosurg Psychiatry 1997;62(2):112-118.

5. Hartung HP, Gonsette R, Konig N, Kwiecinski H, Guseo A, Morrissey SP, Krapf H, Zwingers T; Mitoxantrone in Multiple Sclerosis Study Group (MIMS). Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet 2002 Dec 21-28;360(9350):2018-25.