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

Mult Scler. 2011 Jul;17(7):867-75. doi: 10.1177/1352458511398371. Epub 2011 Feb 15.

Abstract

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.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Amenorrhea / chemically induced
  • Female
  • France
  • Heart Failure / chemically induced
  • Heart Failure / physiopathology
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / adverse effects*
  • Leukemia / chemically induced
  • Male
  • Middle Aged
  • Mitoxantrone / administration & dosage
  • Mitoxantrone / adverse effects*
  • Multiple Sclerosis, Chronic Progressive / diagnosis
  • Multiple Sclerosis, Chronic Progressive / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / diagnosis
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Stroke Volume / drug effects
  • Time Factors
  • Treatment Outcome
  • Ventricular Dysfunction, Left / chemically induced
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Function, Left / drug effects
  • Young Adult

Substances

  • Immunologic Factors
  • Mitoxantrone