Mitoxantrone for multiple sclerosis

  • Review
  • Intervention




Mitoxantrone (MX) has been shown to be moderately effective in reducing the clinical outcome measures of disease activity in multiple sclerosis (MS) patients.


The objective was to assess the efficacy and safety of MX in relapsing-remitting MS (RRMS), progressive relapsing MS (PRMS) and secondary progressive MS (SPMS).

Search methods

We searched the Cochrane MS Group Trials Register (April 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2004), MEDLINE (Pub Med) (January 1966 to April 2005), EMBASE (January 1974 to April 2005), and reference lists of articles. We also undertook hand searching and contacting trialists and pharmaceutical companies.

Selection criteria

The trials were selected if double-blinded, placebo-controlled, randomised, irrespective of eventual additive therapy (such as steroids).

Data collection and analysis

Three reviewers independently selected articles for inclusion, assessed trials' quality and extracted data.

Main results

Four trials involving 270 participants were included. MX reduced the progression of disability at 2 years follow-up (proportion of participants with 6-months confirmed progression of disability: Odds Ratios (OR) 0.3, p = 0.05). Similar figures were found regarding the reduction in annualised relapse rate, the proportion of patients free from relapses at 1 and 2 years, and the number of patients with active MRI lesions at 6 months/ 1 year only. Side effects reported in the trials were more frequent in treated patients than in controls. Caution must be exercised in drawing conclusions from such data because of the heterogeneous quality and characteristics of the included trials. Moreover, from the included trials, it was not possible to estimate the long-term efficacy and safety of MX.

Authors' conclusions

MX is moderately effective in reducing the disease progression and the frequency of relapses in patients affected by RR, PR and SP MS in the short-term follow-up (2 years), even if the results are based on trials heterogeneous in terms of drug dosage and inclusion criteria. No major neoplastic or symptomatic cardiotoxicity related to MX have been reported from the trials. However, longer follow-up studies are highly warranted to better explore the efficacy and safety of the drug, mainly as regards the long-term risk of therapy-related leukemias and cardiotoxicity which is increasingly reported in the literature.
As a conclusion, MX has a partial efficacy, but, due to its unclear long-term safety profile, it should be used to treat patients with worsening RR and SP MS with evidence of worsening disability.

Plain language summary

The use of the immunosuppressive drug Mitoxantrone (MX) in people with multiple sclerosis (MS)

MS is an immune-mediated chronic disorder of the central nervous system (CNS) characterized by multiple areas of inflammation and demyelination. MS is among the commonest causes of neurological disability in young people. Steroids, interferon and other drugs have been used to treat specific symptoms. This review determined that MX, widely used for treatment of breast cancer and leukaemia, was moderately effective in the short-term treatment of MS. The most frequent side-effects are transitory amenorrhoea, nausea and vomiting, alopecia, urinary tract infections and transitory leucopenia. However, caution must be exercised when interpreting these results, because of the heterogeneous quality and characteristics of the included trials, which are different in terms of treatment schedule and type of enrolled patients. Moreover, there are little information on the long term effects of MX, especially as regards the risk of cardiotoxicity and therapy-related acute leukemias, which is increasingly reported in the literature.