P040 - Good cardiac safety in patients with relapsing remitting multiple sclerosis upon first fingolimod dose

Abstract

Background/objective Fingolimod, a sphingosine 1-phosphate receptor (S1PR) modulator, is approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Following treatment initiation, fingolimod activates S1PR at the surface of cardiac myocytes, resulting in transient pulse rate reduction, and in rare cases in atrioventricular conduction blocks. The START-study characterizes the cardiac safety profile of fingolimod treatment initiation in a RRMS patient population. Design/methods The START study is a prospective, 1-week, open-label study enrolling up to 7000 RRMS patients in >250 centers in Germany, according to the EU label criteria of fingolimod. The study consists of a screening period, a baseline visit, and a final visit after one week. The procedure at baseline is as follows: prior to the first intake of fingolimod, a 12-lead ECG is recorded. After the first dose, a continuous 6 h Holter ECG is carried out, while pulse and blood pressure are measured simultaneously, every hour. A final 12-lead ECG is performed afterwards. In 200 patients, diagnostics include a 24 h ECG during screening and at baseline. All ECG recordings are centrally evaluated by cardiologists. Results In a first, interim analysis based on 599 patients, there was no Mobitz type II 2nd degree AV-block. Only 1.4% and 0.3% of patients developed a Mobitz type I 2nd degree block and a 2:1 2nd degree AV block, respectively. Additionally, data regarding QT intervals after fingolimod treatment initiation will be available. The new data set will also be analyzed with regard to the potential impact of co-medications frequently prescribed in RRMS-patients, as symptomatic treatments upon occurrence of cardiac events. Conclusion This national study confirms the good cardiac safety profile of fingolimod, which has already been documented in the previous pivotal multicenter trials, leading to approval. Additionally, the possible impact of comedication on AV-conduction, relevant for sub-groups of RRMS patients, is addressed.