Background Mitoxantrone (MTX) is an antineoplastic agent approved for the treatment of secondary progressive (SP), progressive relapsing (PR) and worsening relapsing remitting (RR) Multiple Sclerosis (MS). No treatment is currently approved for Primary Progressive (PP) MS.

Purpose To evaluate the safety and efficacy of mitoxantrone in Cypriot patients with progressive forms of MS.

Materials and methods Patients with progressive forms of MS who had either failed or were not candidates for treatment with immunomodulating agents were studied retrospectively for two years.

Patients received 18–20 mg of MTX every 3 months up to a cumulative dose of 140–160 mg. Relapses, Expanded Disability Status Scale (EDSS) and drug safety were assessed every 6 months. Statistical analysis was performed with SPSS v.20.

Results 145 patients were included in the study: 59 patients (40.7%) had worsening RRMS, 47 patients (32.4%) SP MS and 39 patients (26.9%) Primary Progressive (PP) MS.

62 patients (42.7%) discontinued the treatment protocol: 28 (19.3%) due to patient’s decision, 12 (8.3%) due to cardiovascular side effects, 10 (6.9%) due to psychiatric and 12 (8.3%) due to other side effects.

Overall, 16% of patients reported cardiovascular side-effects, 14% psychiatric and 12% gastrointestinal side-effects.

83 patients (57.3%) completed the treatment protocol. At time of treatment completion, a 68% reduction in EDSS progression was observed in the worsening RRMS group compared to the 2 year pre-treatment period (p < 0.001). A 46% reduction in EDSS progression was also observed in the SP without relapses group (p = 0.031). No significant reduction was observed in the EDSS progression of PPMS patients (p = 0.416) or the SP with relapses patients (p = 0.111).

Mean annual relapse rate (ARR) at the end of MTX treatment was 1.1 for the RRMS completers, demonstrating a 53% reduction from baseline (p < 0.001). The mean ARR for the SP with relapses completers was 0.2, signifying an 82% reduction from baseline (p = 0.015). 15 completers from the relapsing groups (33.3%) remained relapse-free throughout the treatment period.

Conclusions Mitoxantrone was found to be relatively safe in our population with 23.4% of our patients discontinuing treatment due to reversible adverse drug reactions. It was also proved to be effective in reducing disease progression and frequency of relapses in patients with worsening Relapsing Remitting and Secondary Progressive MS. However, MTX has failed to demonstrate any positive effects from its off-label use in patients with Primary Progressive MS.

No conflict of interest.