Background: Mitoxantrone was approved by the French health authority (AFSAPPS) in October 2003 to treat patients with aggressive multiple sclerosis (MS).
Objective: To report long-term effectiveness and safety of Mitoxantrone as induction therapy in Aggressive Relapsing Remitting MS patients and to assess treatment response factors.
Material and methods: 100 consecutive aggressive relapsing-remitting MS patients received Mitoxantrone 20 mg monthly combined with methylprednisolone 1g for 6 months. Relapses, EDSS and drug safety were assessed every 6 months up to at least 5 years. Within 6 months after induction, 73 patients received a maintenance therapy (Mitoxantrone every 3 months: 21; Interferon beta: 25; Azathioprine: 15; Methotrexate: 7; Glatiramer acetate: 5).
Results: During the 12 months following Mitoxantrone start, the Annual Relapse Rate (ARR) was reduced by 91%, 78% of patients remained relapse-free, MRI activity was reduced by 89%, the mean EDSS decreased by 1.2 points (p<10-6) and 64% of patients improved by 1 point EDSS or more. At a longer term, the ARR reduction was sustained (0.29-0.42 up to 5 years), the median time to the first relapse was 2.8 years and disability remained improved up-to 5 years. Younger age and lower EDSS at Mitoxantrone start were predictive of better treatment response. Three patients presented an asymptomatic decrease of the left ventricular ejection fraction under 50% (1 reversible). One patient was diagnosed with acute myeloid leukaemia (remission 5 years after diagnosis).
Conclusion: Mitoxantrone monthly for 6 months as induction therapy followed by a maintenance treatment showed sustained clinical benefit up to 5 years with acceptable adverse events profile in patients with aggressive relapsing-remitting MS.
- Aggressive Relapsing remitting
- Drug safety
- Multiple sclerosis