Efficacy and safety of mitoxantrone in multiple sclerosis: a retrospective analysis of 105 patients

Background: Several controlled trials have shown mitoxantrone (MIX) to be effective in relapsing-remitting and secondary progressive multiple sclerosis (RRMS, SPMS). The MS therapy consensus group has recommended the use of MIX for treatment escalation in patients with progressive RRMS and SPMS refractory to immunomodulatory drugs. In clinical practice it is often difficult to decide which patients will be likely to benefit from initiating MIX therapy. Objective: To assess safety and efficacy of MIX in the Regensburg cohort of MS patients.

Methods: All consecutive 105 MS patients (age 35 + 8 years, 74 females) treated with MIX between July 1996 and May 2004 were included in this retrospective analysis.

Results: At treatment initiation 25 patients suffered from RRMS, 69 from SPMS including 14 without recent relapses and 11 from primary progressive/progressive-relapsing MS (PPMS/PRMS). Median disease duration was 6 years. Patients were treated with 12mg/qm MIX i.v. every 3 months, reaching a median cumulative dose of 72mg/qm (range 30–140) after 6 cycles (range 3–14). The mean follow-up time was 24,4 months. At treatment initiation, the mean score on the expanded disability status scale of Kurtzke (EDSS) was 5,8 with a worsening of 1 point (median, range 0–4,5) within the last 18 months. The median number of relapses in patients with relapsing disease was 1 (range 0–8) within the 12 months prior to treatment. Most patients remained clinically stable 12 to 18 months following treatment initiation (median change EDSS 0, 56/84 patients with a change < + 0,5); 48/83 patients were free of relapses during the first year after starting treatment. The MIX dosage had to be reduced in 20 patients and treatment was stopped in 4 patients because of side-effects. 1 patient developed cardiomyopathy with acute reversible left ventricular dysfunction. The influence of different therapy-independent parameters at baseline (e.g. age, gender, disease type, duration of disease, number of relapses, EDSS, prior treatment) on the outcome (EDSS, relapses) will be determined by multivariate regression methods and presented at the meeting.

Conclusion: MIX therapy was well tolerated in this cohort of patients with the majority of patients remaining clinically stable. Cardiac function has to be monitored regularly. Currently, the data are analyzed for baseline parameters predicting a therapeutic benefit.