The current role of mitoxantrone in the treatment of multiple sclerosis

Abstract

Mitoxantrone is an immunosuppressive drug approved for aggressive relapsing and progressive multiple sclerosis. In recent years, its use has decreased due to the risk of severe adverse events and the introduction of novel therapies, such as natalizumab or fingolimod. Mitoxantrone is effective in reducing inflammatory activity by decreasing the number of relapses and MRI lesions and simultaneously decreasing the worsening of disability. Apart from its role as a second/third-line therapy, some studies suggest its use as an induction therapy. However, mitoxantrone use is limited because of its potential risk of severe adverse events, such as cardiotoxicity and the induction of therapy-related acute leukemia. Genetic markers are on evaluation to predict side effects and therapeutic efficacy, which is consistent with the direction of personalized treatment. Considering its efficacy and the potential risks, mitoxantrone use is limited to active patients after a careful, individualized evaluation of the risk/benefit balance.

Keywords::

• cardiotoxicity
• disability
• inflammation
• leukemia
• mitoxantrone
• multiple sclerosis

Financial & competing interests disclosure

E Cocco serves on scientific advisory boards and has received honoraria for speaking from Bayer, Biogen, Merck Serono, Novartis, Sanofi-Genzyme and Teva. MG Marrosu has received honoraria for consultancy or speaking and research grants from Bayer, Biogen-Idec, Novartis, Sanofi-Genzyme, Serono and Teva. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Mitoxantrone is indicated for aggressive relapsing and progressive multiple sclerosis.

• Progressive patients should have clinical and MRI evidence of active inflammatory disease, otherwise, there is no point in treating progressive patients with mitoxantrone.

• Mitoxantrone is effective in reducing inflammatory activity and decreasing the worsening of disability. There are many evidences supporting mitoxantrone use in the induction.

• Mitoxantrone use is limited by its potential risk of severe adverse events.

• Genetic polymorphisms are under evaluation as predictive markers.

• Careful, individualized evaluation of the risk/benefit balance in mitoxantrone use.