RANDOMIZED PLACEBO-CONTROLLED TRIAL OF MITOXANTRONE IN RELAPSING-REMITTING MULTIPLE-SCLEROSIS - 24-MONTH CLINICAL AND MRI OUTCOME

We designed a randomized, placebo-controlled, multicentre trial involv ing 51 relapsing-remitting multiple sclerosis patients to determine th e clinical efficacy of mitoxantrone treatment over 2 years. Patients w ere allocated either to the mitoxantrone group (27 patients receiving IV infusion of mitoxantrone every month for 1 year at the dosage of 8 mg/m(2)) or to the placebo group (24 patients, receiving IV infusion o f saline every month for 1 year) using a centralized randomization sys tem. Disability at entry and at 12-24 months was evaluated by four bli nded neurologists trained in the application of the Kurtzke Expanded D isability Scale (EDSS). In addition, the number and clinical character istics of the exacerbations over the 24 months were recorded by the lo cal investigators. MRT, at 0,12 and 24 months, was performed with a 0. 2 T permanent unit. MRI data were analysed by two blinded neuroradiolo gists. All patients underwent a clinical evaluation. A statistically s ignificant difference in the mean number of exacerbations was observed between the mitoxantrone group and placebo group both during the 1st and the 2nd year. Although there was no statistically significant bene fit in terms of mean EDSS progression over 2 years, the proportion of patients with confirmed progression of the disease, as measured by a o ne point increase on the EDSS scale, was significantly reduced at the 2nd year evaluation in the mitoxantrone group. Forty-two (23 mitoxantr one, 19 placebo) patients underwent all MRI examinations during the 24 -month period. We observed a trend towards a reduction in the number o f new lesions on T2-weighted images in the mitoxantrone group. Our stu dy suggests that mitoxantrone might be effective in reducing disease a ctivity, both by decreasing the mean number of exacerbations and by sl owing the clinical progression sustained by most patients after 1 year from the end of treatment.