Mitoxantrone (MTX) therapy in secondary-progressive multiple sclerosis (SPMS) patients

Previous studies showed that MTX therapy is effective in reducing the progression of disability and MRI activity in patients with SPMS. The aim of this open, uncontrolled study was to evaluate the clinical efficacy, safety, and tolerability of MTX in SPMS. Forty SPMS patients (pts.) (25F, 15M; mean age 42 years; mean EDSS 6 - range 3.5-7.5), with a clinical and/or MRI active disease and a confirmed increase in disability in the previous year (EDSS progression of at least 1.0 point for a baseline EDSS<5.0 or 0.5 point for baseline EDSS≥5.5) were consecutively included in the study. Eighteen placebo SPMS pts. included in a double-blind controlled study with the same criteria, performed at the same time in our hospital, were used as control. One patient dropped out after the first administration of MTX because of a systemic allergic reaction. Thirty-nine patients were treated with repeated single administrations of Novantrone, at a dose of 10 mg/m² of body surface with a mean interval of 3 months with a mean cumulative patient dose of 52 mg/m² (range 30-70). Mean follow-up was 14 months (range 9-33). At the final evaluation, EDSS was stable in 59% of patients, improved in 13% and progressed in 28%. In the control group, at 12 months follow-up EDSS was stable in 22% and progressed in 78%. The difference between the two groups is significant (P = 0,001). The treatment was well tolerated in most of the patients. Brain MRI was performed in 23 pts. Mean MRI-enhancing lesions were 4.2 (SD 9.9) at baseline evaluation, and 0.5 (SD 0.7) at the final evaluation. A statistically significant reduction of enhancing lesions were found in all the patients with enhancing lesions at the baseline period (n = 11) (Wilcoxon signed rank test: P<0,03). Our results seems to confirm the efficacy, safety, and tolerability of MTX in reducing MRI and clinical disease progression in SPMS patients.