MTX Treatment May Increase Risk of Developing Late Left Ventricular Dysfunction in Patients with MS

Patients with Multiple sclerosis (MS) treated with mitoxantrone (MTX)—an antracyclin drug used to treat chronic refractory MS—may be at an increased risk of developing early and late left ventricular (LV) dysfunction, suggesting the need for these patients to be periodically evaluated for complications, a recent study found.

The research, published in the International Journal of Preventive Medicine, aimed to assess the long-term adverse effect of MTX on cardiac function. Forty-nine patients with MS on MTX therapy were included in the study. Researchers used echocardiography to measure systolic and diastolic LV functions.

“MTX (Novantrone), a synthetic anthracenedione derivative, is an antineoplastic, immunomodulatory, and anti-inflammatory agent. Its presumed mechanism of action in patients with MS is via immunomodulatory mechanisms, although these remain to be fully elucidated,” explained the authors.

“MTX interfered with the antigen-presenting capabilities of monocyte-derived dendritic cells and induced their apoptosis at low concentrations, whereas higher concentrations caused cell lysis,” they said.

The results revealed that after MTX therapy, one patient’s ejection fraction (EF) reduced below 50%. Additionally, 2 patients who previously had normal diastolic function developed diastolic dysfunction after MTX therapy.

Researchers explained that the nonparametric binominal analysis suggested that MTX therapy increased the probability of developing systolic dysfunction, early on or later.

“In this study, left ventricular ejection fraction reduction under 50% was reported in 27 (5.3%) patients during the treatment phase (n =509) and 14 (5.6%) patients during the annual follow-up phase (n =250). Signs and symptoms of congestive heart failure were observed in 10 (2.0%) patients. Post-hoc analyses of the risk for cardiotoxicity outcomes revealed that cumulative dose exposure is the primary risk factor associated with the risk of cardiac toxicity with MTX,” the authors said.

The study concluded MTX is an appropriate drug for patients with MS who have worsening relapsing-remitting MS despite prior therapy. In addition, clinical trials demonstrate that MTX would reduce relapse, the number of new lesions visualized on magnetic resonance imaging, and stop, or reduce the progression of the disease for many patients. However, patients with MS have a heightened risk developing late left ventricular dysfunction.

Reference:

Najafian J, Nasri A, Etemadifar M, Salehzadeh F. Late Cardiotoxicity in MS Patients Treated with Mitoxantrone. Int J Prev Med. 2019;10:211. doi:10.4103/ijpvm.IJPVM_477_17.