Fingolimod-induced decrease in heart rate may predict subsequent decreasing degree of lymphocytes

Abstract

Here, we determined whether degree of decreased heart rate due to fingolimod treatment correlates with decreasing degree of lymphocytes in relapse-remitting multiple sclerosis (RRMS). In total, 30 patients with RRMS were treated with 0.5 mg fingolimod and their heart rate recorded every 30 minutes for 24 hours. Time trends of heart rate were characterised as three individual amplitudes and phase angles from three cosine curves using a mixed-effect model. Spearman’s correlation coefficient and regression analysis were used to determine the effect of heart rate information on change in lymphocyte count pre- and post-fingolimod treatment. Moreover, the degree of decreased lymphocytes induced by fingolimod treatment on heart rate was compared between low and high influence groups. Positive correlation between amplitude from the second curve and difference in lymphocyte number (p = 0.006) was observed. Regression analysis was also significant (p = 0.002). Moreover, the second curve derived from the high amplitude group exhibited a greater decrease in lymphocyte number after fingolimod treatment than the low amplitude group (p < 0.001). We suggest that the degree of decreased lymphocytes after fingolimod treatment (main effect) may be predicted by estimating the influence of degree in heart rate (side effect).

Fingolimod Leads to Immediate Immunological Changes Within 6 h After First Administration

“…Correlation analysis revealed an association between the degree of induced cardiological and immunological changes for several immune cell subsets. Ikeda et al (11) have demonstrated a link between heart rate change and immunological effects as well. The explanation for this correlation could be related to an individual, but intraindividual comparable expression and composition of S1P-receptors between heart and immune cells.…”

Thinking Outside the Ischemia Box: Advancements in the Use of Multiple Sclerosis Drugs in Ischemic Stroke

“…Regarding fingolimod, it has been shown to induce lymphopenia upon its administration, and this reduction in lymphocytes is even used to monitor its action [29]. Fingolimod is associated with cardiovascular side-effects, for example bradycardia [80] and reduced left ventricular function [81], increases the risk of infections, particularly viral, due to the lymphopenia, and may even confer susceptibility towards some malignancy types [82]. However, in the available clinical studies, no serious adverse effects were noted for the treated IS patients [28][29][30], or in a cerebral hemorrhage setting [83].…”