Improving on existing therapiesFriday, September 30, 2005, 11:30 - 11:45
Mitoxantrone treatment in MS patients: a five-year clinical and MRI follow-up C. Buttinelli, A. Clemenzi, C. Pozzilli, F. Denaro, E. Sbardella, C. Fieschi (Rome, I)
Background: Mitoxantrone (MTX) is an antineoplastic agent with anti-inflammatory and immunomodulating properties approved for the treatment of MS. Potential side effects limit the use of the agent for few years before reaching a toxic dosage. We designed a longitudinal open label prospective study of consecutive patients with MS to evaluate clinical efficacy and toxicity of MTX during a two-year treatment period and the subsequent three years without any therapy.
Methods: Fifty consecutive patients (M/F 18/32; mean age 43.35, range 25-59) with definite MS (25 RR and 25 SP) were included. All had evidence of confirmed disability as measured by an EDSS increase of at least 1 point in the previous year. The mean disease duration was 7.59±5.58 years and the mean EDSS was 3.7±1.5. Patients received MTX intravenously (8 mg/m2 every 2 months for a total of 12 infusions with a cumulative dose less than 120 mg/m2). Treatment efficacy was assessed clinically and by brain MRI before MTX therapy, at the end of treatment and at the end of each year of the follow-up.
Results: All patients completed the clinical follow-up except one subject. Forty-four patients (89.8%), completed the 12 infusions with MTX, five patients (10.2%) interrupted the treatment for side effects. Fifteen (30.6%) patients showed an EDSS progression on treatment. During the follow-up, 9 (18.4 %) patients showed progression of disability (7 of them were clinically stable during the treatment). None of patients experienced new relapses under treatment and during the follow-up period. Seventeen (34.7%) patients had active lesions on enhanced T1-weigthed images at baseline, 9/49 (18.4%) patients at the end of treatment and none at the end of follow-up.
Conclusion: Using the present treatment schedule, MTX was well tolerated and had a substantial long-term beneficial effect on disease activity (i.e. relapses and enhanced MRI). As regards disability progression, we observed a worsening of EDSS in about 1/3 of the patients during the treatment and in 1/5 during the follow-up period. This evidence suggests that a delayed beneficial effect after the end of MTX treatment is observed in a substantial rate of patients (26.5%). On the other hand, a minority (14%) of patients showed disability progression once the drug was suspended.