Cardiac Safety Profile of First Dose of Fingolimod for Chinese Relapsing-Remitting Multiple Sclerosis patients in Real-World Settings

Abstract Background and objective: Fingolimod was the first oral therapy approved to treat relapsing-remitting multiple sclerosis (RRMS). Due to its mechanism on sphingosine 1-phosphate receptors, fingolimod can cause a transient decrease in heart rate (HR) and the occurrence of self-limited atrioventricular blocks（AVB）. We aimed to assess the cardiac safety profile in Chinese RRMS patients at least 6 hours after the initial treatment of fingolimod in real-world settings. Methods: According to the analysis of first dose observation (FDO) data of 14 RRMS patients treated with fingolimod from Jan.2020 to Jun.2020 in the neurology department of Huashan Hospital affiliated to Fudan University, the patients all met the 2017 McDonald diagnostic criteria and without a history of heart disease. Each patient performed an electrocardiogram (ECG) before taking medicine to confirm that there was no conduction block or QTc interval significantly prolonged. The blood pressure(BP) and HR were measured every hour and observed for a total of 6 hours’ period. At last hour, another ECG was performed to confirm the corresponding cardiac abnormalities. Recorded the data for statistical analysis. Results: A total of 14 patients underwent the first fingolimod monitoring. There was no patient with a history of cardiovascular disease or taking cardiovascular-related medications. 13 of the 14 patients passed the 6-hour medication monitoring without any abnormality. One patient extended the monitoring because the HR at the 6th hour was the lowest value after administration. The patient passed the monitoring at the 8th hour. No patient had a HR lower than the standard for bradycardia; no patient had symptomatic bradycardia; no patient needed overnight monitoring or required medication. No patients stopped fingolimod due to the first-dose effect of the heart. During the monitoring period, no new-onset I, II, III atrioventricular block was seen or QTc interval was prolonged than 500ms. Collected the HR and BP records of 10 patients. The baseline average HR is 88.3±7bpm, and the average HR reaches the lowest value at the 4th hour (75.7±7bpm), compared with the baseline average HR after a drop of 12.6bpm, the average HR began to recover at the 5th hour. At the same time, the BP of 10 patients was stable throughout the testing period. Conclusion: Oral fingolimod was safe for the initial treatment of multiple sclerosis populations in China. Neurologists needed to formulate FDO observation procedures and strictly implement them. More safety data and efficacy data will need to be collected and summarized so that more Chinese MS patients can receive standard treatment safely.