The effect of a combined mitoxantrone and methylprednisolone therapy in primary compared to secondary progressive multiple sclerosis – an interim analysis after five years

Background: Mitoxantrone (mitox) has been shown an effective treatment in secondary progressive (SP)- and relapsing-remitting multiple sclerosis (MS), (Hartung et al., Lancet 2002). The aim of this open trial was to evaluate the effects of a combined mitox and methylprednisolone (MP) therapy for patients with primary progressive (PP)-MS compared to SP-MS.

Methods: This prospective study included patients with either a PP-MS or SP-MS who had had an impairment of at least 0.5 EDSS (expanded disability status scale of Kurtzke, mean±SD 0.7±0.4, range 0.5–2.5) points during the preceding 12 months. The treatment protocol called for ten courses of a combined, intravenously administered, therapy with MP (500mg on 5 successive days) and mitox (10mg/sqm body surface on day 3). The intervals were systematically extended from 3 months to 1 year and finally to an entire treatment phase of nearly 5 years (57 months). The patients underwent an EDSS evaluation at entry in the study and before each course.

Results: Of the 74 patients screened, 65 patients (age 47±11 years, 39 females) met the criteria for inclusion. Twenty of the final total of 65 patients suffered from PP-MS, 45 patients from SP-MS. Three of the 65 patients were excluded during the study. The mean follow-up time was 22.1 months. All patients completed at least four courses of therapy. At the beginning of the study, the patients in the PP-MS group had a mean EDSS of 5.3±1.4 points, and the SP-MS group, a mean of 5.6±1.0 points. Overall, the EDSS remained almost unchanged in both groups after four courses (the primary endpoint of this interim analysis) and after eight courses. The patients with PP-MS had a mean EDSS of 5.1±1.5 points after four and 5.2±1.4 points after eight courses. The SP-MS group had a mean EDSS of 5.4±1.1 points after four and 5.5±1.5 points after eight courses. Patients with PP-MS seemed to profit more from therapy than SP patients, but so far this has not been significant. The good tolerance to the combination of mitox with MP was reflected by the low dropout rate.

Conclusion: This interim analysis indicates that mitox combined with MP beneficially reduces the progression of disability in patients with PP-MS and SP-MS. Therefore, this therapy regimen can also be considered a feasible treatment option for PP-MS.