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

Multiple effects of fingolimod have already been described. Here we investigated the acute effects on immune cell subsets and identified correlations with autonomic first dose phenomena and long-term immunological effects. Blood samples of 20 MS patients were analyzed using FACS. Immune cell frequencies before and at defined prospective time points beginning 6 h after first fingolimod administration were evaluated in parallel to cardiovascular autonomic and clinical parameters. A significant decrease of absolute lymphocyte count (1.81GPt/l to 1.42GPt/l), CD3+ (1.34GPt/l to 1.06GPt/l), CD3+CD4+ (0.94GPt/l to 0.73GPt/l), and CD19+ (0.26GPt/l to 0.19GPt/l) cells could be already demonstrated within 6 hours after first dose which correspond to a relative reduction by 28, 23, 23% resp. 29% in relation to the longterm steady state cell frequency level. Short- and long-term effects were significantly correlated for lymphocytes, CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD14+, and NK cells as well as for neutrophil granulocytes. In addition, correlations could be found between reduced heart rate (68.95-60.05 bpm) and the decrease in CD3+, CD3+CD4+, and CD19+ cells after 6 h. Early immunological changes could already be detected 6 h after fingolimod first dose. Most of the acute changes correlate with long-term modulation. A link between the acute immunological and cardiological effects was found.