Review of mitoxantrone in the treatment of multiple sclerosis.
Mitoxantrone is a synthetic anthracenedione recently approved by the FDA for the treatment of worsening relapsing-remitting (RR), secondary progressive (SP), and progressive relapsing (PR) multiple sclerosis (MS). In experimental allergic encephalomyelitis (EAE), mitoxantrone prevented the development of the signs and decreased the frequency of relapses in relapsing EAE. Early pilot trials using mitoxantrone were carried out using vastly different dosage regimens and patient populations, which may have resulted in conflicting results. Subsequent trials of mitroxantrone in patients with active inflammatory forms of MS suggested a profound effect in decreasing relapse rates, enhancing lesion frequency, and progression of disability. These results were later confirmed in a large, randomized, double-blind trial in patients with either worsening RRMS or SPMS. Treatment with mitoxantrone brought about statistically significant decreases in relapse rates, progression of disability, gadolinium-enhancing, and new lesions on T2-weighted MRI. Although mitoxantrone is generally well tolerated, it is associated with a variety of potential toxicities. Therefore, its use should probably be restricted to those patients with a suboptimal response to high-dose interferon therapy or those with rapidly progressive disease from onset.
Jeffery
Douglas R
DR
Wake Forest University School of Medicine, Department of Neurology, Medical Center Blvd., Winston-Salem, NC 27106, USA. djeffery@wfubmc.edu
Herndon
Robert
R
D000818:Animals; D002986:Clinical Trials as Topic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy; D008942:Mitoxantrone / Q000009:adverse effects / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000503:physiopathology; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy; D018579:Patient Selection
D007166:Immunosuppressive Agents; D008942:Mitoxantrone