Dec. 30, 2002
Laurie Barclay, MD
Mitoxantrone is a well tolerated and effective therapy for the treatment of relapsing-remitting or secondary progressive multiple sclerosis (MS), based on the results of a randomized, placebo-controlled trial reported in the Dec. 21/28 issue of The Lancet.
"Mitoxantrone is an anthrecenedione used to treat various malignant disorders," write Hans-Peter Hartung and colleagues from the Mitoxantrone in MS Study Group. "Several immunosuppressant properties of this drug provide a rationale for its use in MS."
For 24 months, 194 patients with worsening relapsing-remitting or secondary progressive MS received placebo or mitoxantrone 5 mg/m2 or 12 mg/m2 intravenously every three months.
Compared with the placebo group, the mitoxantrone group had a better primary outcome, which was a multivariate analysis of five clinical measures. At 24 months, the difference in primary outcome was 0.30 (95% confidence interval, 0.17-0.44; P<.0001). Outcome was also significantly better in the mitoxantrone group for each of the five component measures including change in expanded disability status scale, change in ambulation index, adjusted total number of treated relapses, time to first treated relapse, and change in standardized neurological status.
There were no serious adverse events or clinically significant cardiac dysfunction. Because oncologists have reported drug-related congestive heart failure in 2.6% to 6.0% of patients who received cumulative doses of mitoxantrone up to 140 mg/m2, the authors recommend withholding mitoxantrone in patients with a left ventricular ejection fraction less than 50%.
"Mitoxantrone 12 mg/m2 was generally well tolerated and reduced progression of disability and clinical exacerbations," the authors write. "Further studies are needed to identify the patients with these forms of MS who are most likely to respond to therapy, the best treatment protocols, and the frequency of long-term drug-related side effects."
Wyeth-Lederle supported this study and has financial arrangements with some of its authors.
The Lancet. 2002;360:2018-2025
Reviewed by Michael W. Smith, MD
Laurie Barclay, MD is a staff writer with WebMD.
Medscape Medical News 2002.
© 2002 Medscape