Mitoxantrone as induction therapy in aggressive relapsing remitting multiple sclerosis: a descriptive analysis of 100 consecutive patients.

Introduction. On the basis of the French and British (FB) MS Trial, Mitoxantrone (MITOX) was approved by the AFSAPPS in October 2003 in patients with aggressive multiple sclerosis (MS), given as induction therapy monthly for 6 months (ELSEP(R)). We report an observational study of 100 aggressive relapsing remitting (RR) MS patients treated by induction therapy with MITOX and followed up to 5 years. Methods. One hundred patients with aggressive RR MS received an induction therapy with MITOX 20 mg monthly combined with methylprednisolone 1 g for 6 months. MRI data within 12 months before and 6 months after MITOX induction were collected (mean cumulative dose 65 mg/m(2)). Clinical evaluation was performed every 6 months and data (relapses and EDSS scores) were prospectively recorded in the EDMUS Database. After MITOX a maintenance therapy was given to 57 patients (MITOX every 3 months: 21; Interferon beta: 13; Azathioprine: 14; Methotrexate: 7; Glatiramer acetate: 2). The mean follow-up period was of 3.8 years. Results. Patients were treated at a mean age of 27 +/- 9 years after 5 +/- 3 years of MS duration. Within the 12 months preceding MITOX onset, the annual relapse rate (ARR) was 3.2, the mean EDSS increased by 2.2 +/- 1 points (to a score of 4 at MO), 87 patients worsened by 1 point EDSS or more and 85 percent of patients had Gd enhancing lesions on MRI. During the 12 months following MITOX onset, the inflammatory activity of the disease dropped dramatically with a reduction of the ARR by 91 percent whereas 76 percent of patients were free of new relapse and MRI activity was reduced by 89 percent. In addition, the mean EDSS decreased by 1.2 points (p<10(-6)) and 60 percent of patients improved by 1 point EDSS or more. At a longer term, the reduction of the ARR was confirmed (0.28-0.37 up to 5 years) and the median time to the first relapse was 2.8 years. A significant improvement of disability was maintained until 4 years and got back to the initial level at year 5. The APR was significantly lower (0.09) for patients treated with MITOX every 3 months as maintenance therapy than for patients treated by other disease modifying therapies (0.33-0.39) or not (0.43) after the induction. Three patients presented an asymptomatic decrease of the left ventricular ejection fraction under 50 percent, reversible in one case. Conclusion. MITOX as induction therapy monthly for 6 months was safe and had a rapid and strong impact on the inflammatory process and on the evolution of disability. The drug might be a good candidate as induction therapy followed by a maintenance therapy in patients with aggressive MS.