Abstract
BackgroundMitoxantrone (MX) has been used as second line therapy for aggressive multiple sclerosis (MS). Potential cardiotoxic effects of MX limit its use; a cumulative dose of up to 100 mg/m2, has been long considered relatively safe. We calculated the frequency of cardiac side effects in MS patients treated with MX.MethodsWe performed a cohort study including all MS patients treated with MX at the Neurological Department of the University Hospital of Palermo, Italy. Two hundred-sixty-four MS patients diagnosed according to validated criteria were included and followed-up until the end of September 2010. Patients were treated with MX as a second line therapy if they had no previous heart diseases determined by clinical evaluation, electrocardiography, and echocardiography. Treatment administration was made at a monthly dose of 8 mg/m2 for the first three months and at a dose of 12 mg/m2 every three months. Echocardiography was routinely performed every six months. Treatment was stopped before reaching the final dose if signs had appeared of impaired heart function, confirmed left ventricular ejection fraction reduction lower to 50%, or a confirmed reduction of more than 10% with respect to the first examination.ResultsHeart involvement was observed in 12.4% of treated individuals, and symptomatic congestive heart failure occurred in 2.7% of the cohort. A patient had a myocardial infarction, and 3.1% showed electrocardiographic anomalies not present at baseline.ConclusionOur study confirms that cardiac adverse events associated with MX are more common than previously reported.
Highlights
Mitoxantrone (MX) has been used as second line therapy for aggressive multiple sclerosis (MS)
Differences in observed frequencies of MX related heart toxicity might be determined mostly by the methodology used to calculate the occurrence of events
In the group of individuals performing echocardiography and not affected by MS we considered for comparisons, we did not observed any difference at baseline with respect to MS patients and, as previously reported, only one had significant signs of potential heart disease at echocardiographic examination
Summary
Mitoxantrone (MX) has been used as second line therapy for aggressive multiple sclerosis (MS). Potential cardiotoxic effects of MX limit its use; a cumulative dose of up to 100 mg/m2, has been long considered relatively safe. Multiple sclerosis (MS) is a chronic disease of the central nervous system due to a damage of myelin sheaths and axons mediated by the immune system and by a neurodegenerative mechanism. Its causes are still unknown is generally accepted that MS is a complex autoimmune disorder where genetic and environmental factors both contribute to the pathogenic mechanisms directed against myelin and oligodendrocytes of the central nervous system. Among treatments used for MS, Mitoxantrone (MX) has been used as a second line therapy for multiple sclerosis (MS) [2]. Cardiotoxic effects of MX limit the cumulative lifetime dose in MS patients to 140 mg/m2.
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