Long-term safety profile of mitoxantrone in a French cohort of 802 multiple sclerosis patients: a 5-year prospective study

Background: From 2001, a French multicentre study was conducted prospectively in a large cohort of MS patients and annually updated up to at least 5 years after initiation of MITOX therapy. Objective: To determine long-term safety profile of mitoxantrone (MITOX) in multiple sclerosis (MS). Methods: Eight hundred and two patients from 12 MS centres (308 relapsing-remitting, 352 secondary progressive and 142 primary progressive) received MITOX monthly for 6 months (87%) or every 3 months (13%). Patients underwent clinical and haematologic evaluations before every MITOX infusion and every 6-12 months up to 5 years after MITOX start. Echocardiograms were performed at the start and end of MITOX and up to 5 years after. Results: The cohort was followed for 5354 patient-years (mean). One out of 802 patients (0.1%) presented with acute congestive heart failure and 39 out of 794 patients (4.9%) presented with asymptomatic left ventricular ejection fraction reduction under 50% (persistent in 11 patients (28%), transient in 27 patients (69%), on the last scan at year 5 in 1 patient). Two cases of therapy-related leukaemia (0.25%) were detected 20 months after MITOX start (one death and one with 8 years confirmed remission). Of the 317 women treated before the age of 45, 17.3% developed a persistent age-dependant amenorrhea. Conclusion: This large cohort with at least 5 years of follow-up provided good insights into the long-term safety profile of MITOX in MS.