Universität zu Köln

Limmroth, Volker, Ziemssen, Tjalf, Kleiter, Ingo, Wagner, Bert, Schmidt, Stephan, Lassek, Christoph, Baier-Ebert, Monika, Wendt, Guillaume, Dechend, Ralf and Haverkamp, Wilhelm (2020). A Comprehensive Monitoring Study on Electrocardiographic Assessments and Cardiac Events After Fingolimod First Dose-Possible Predictors of Cardiac Outcomes. Front. Neurol., 11. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-2295

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Abstract

Background:First dose observation for cardiac effects is required for fingolimod. Previous results in patients with relapsing remitting multiple sclerosis (RRMS) suggest that transient bradycardia and conduction abnormalities during the observation phase are rare, benign and reversible. Prior analyses corroborate these findings. The present large scale dataset allows subgroup analyses for differences in the incidence of cardiac findings depending on patient characteristics. Methods:START was an open-label, multi-center study that enrolled 6,998 RRMS patients. Primary endpoints were incidence of bradycardia (heart rate < 45 bpm) and second-/third-degree atrioventricular (AV) block during treatment initiation. Subgroup analyses were performed according to age, gender, body mass index (BMI), baseline expanded disability status scale (EDSS), and concomitant medication to determine the impact of these variables on cardiac outcomes parameters. Results:63 patients (0.9%) developed bradycardia (<45 bpm), 120 patients (1.7%) had a second-degree Mobitz I (Wenkebach) block and/or 2:1 AV block. One case of an asymptomatic third-degree AV block occurred. No Mobitz II AV block was observed. After 1 week, no second-/third-degree AV block was observed. The incidence of second- or third-degree AV blocks was significantly higher in older patients (>= 50 years;p= 0.014 vs. patients 35-49 years). Second- or third-degree AV blocks were more frequent in females (87.5% of all patients with a second- or third-degree AV block;p< 0.001), while bradycardia occurred more often in males (58.7% of all bradycardia events;p< 0.001). Furthermore, patients with a BMI below 25 had a higher incidence of second- or third-degree AV block. Conclusions:In summary, transient bradycardia and AV conduction abnormalities after the first dose of fingolimod were rare and asymptomatic. When compared to females, male patients might have a higher risk for bradycardia during treatment initiation, presumably due to a lower resting heart rate. Furthermore, a low heart rate before treatment initiation, low body weight, or low BMI possibly increases the risk for bradycardia. Second- or third-degree AV blocks were more frequent in females, older patients and patients with a low BMI. Nevertheless, these cardiac events remained rare and benign, confirming the favorable cardiac safety profile of fingolimod upon treatment initiation in MS patients without cardiovascular comorbidities.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Limmroth, Volker UNSPECIFIED UNSPECIFIED UNSPECIFIED Ziemssen, Tjalf UNSPECIFIED UNSPECIFIED UNSPECIFIED Kleiter, Ingo UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagner, Bert UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Lassek, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Baier-Ebert, Monika UNSPECIFIED UNSPECIFIED UNSPECIFIED Wendt, Guillaume UNSPECIFIED UNSPECIFIED UNSPECIFIED Dechend, Ralf UNSPECIFIED UNSPECIFIED UNSPECIFIED Haverkamp, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-323361
DOI:	10.3389/fneur.2020.00818
Journal or Publication Title:	Front. Neurol.
Volume:	11
Date:	2020
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-2295
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language REMITTING MULTIPLE-SCLEROSIS; ORAL FINGOLIMOD; RISK-FACTOR; SAFETY; FTY720; INITIATION; EFFICACY; GENDER Multiple languages Clinical Neurology; Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32336