Contributions
Abstract: P1254
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: Fingolimod is an oral immunomodulator exerting its therapeutic effects in multiple sclerosis via sphingosine-1P receptors (S1PR). S1PR are also expressed in the heart, mainly in atrial myocytes, and mediate cardiovascular (CV) effects. Effects of fingolimod first dose (FFD) on heart rate (HR) and atroventricular (AV) conduction are well defined, and the recommended FFD continuous 6-hours (hrs) ECG monitoring can be extended until the day after in case given conditions occur. Understanding potential interactions of preexisting individual autonomic profile with the FFD effects may add novel safety information and help explain the cases requiring extension of the 6-hrs period
Objectives: To characterize the patient population treated with FFD according to EMA label and clinical practice, in terms of baseline demographics, clinical and neurovegetative status and probability of extension of the continuous ECG monitoring
Methods
Observational, prospective study of 6 (up to 24) hrs. ECG was recorded for 15 min before FFD administration and for 6 hrs after. Heart Rate and HR Variability (HRV) in the frequency domain were derived from the ECG traces by a specialized software
Results: 625 patients were enrolled in 59 Italian centres. Of these, 580 (92.8%) patients were discharged at the 6th hour after FFD administration, while 45 (7.2%) required monitoring extension. Ten (1.6%) patients showed an AV block (3 of 1st degree, 7 of 2nd), all benign and reversible. The mean max percentage reduction in HR was 17.6±8.4. Normalized spectral power (norm units, nu) in the Low Frequency band (LFnu; marker of sympathetic modulation) < 75.2 (OR=0.47; 95%CI: 0.23-0.94), nu power in the High Frequency band (HFnu; marker of vagal modulation) < 19.4 (OR=2.07; 95%IC: 1.04-4.12) and previous annualized relapse rate 0 vs ≥2 (OR=0.25; 95%CI: 0.08-0.75) were correlated with the probability of discharge at 6 hrs (which was not correlated with demographic or other clinical variables). With regard to HRV and the max HR reduction, coefficients indicated a weak positive correlation between the latter and LFnu and LF/HF ratio, whereas HFnu showed a weak negative correlation
Conclusions: Data confirm the well known and manageable CV profile of FFD. An individual higher vagal tone at baseline may contribute to the chances of extending CV monitoring. The potentially synergistic effects of FFD and individual inherent vagal tone were not associated with clinically significant cardiac events
Disclosure: Prof Mancardi G has received honoraria for lecturing, travel expenses for attending meetings, and financial support for research from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis and Teva Pharmaceuticals
Dr De Angelis G receives consulting fee from Novartis
Dr Nicola M received consulting fees from Novo Nordisk, Resmed and Novartis
Dr Vanoli E received consulting fees from Novartis
Dr Mirabella M has received honoraria for scientific lectures and advisory board activities from Biogen, Novartis, Teva, Sanofi Genzyme, Bayer Schering, Merck Serono, Almirall, and research support from Merck Serono, Novartis, Teva, Genzyme
Prof Bonavita S. received speaker honoraria from Biogen-Idec, Teva, Merck-Serono, Novartis
Prof Patti F served as advisor to Almirall, Bayer, Biogen, Merck, Novartis, Sanofi and TEVA and received fee for personal consultations and speaking activities by Almirall, Bayer, Biogen, Merck and Sanofi. He received research grants by MIUR (University of Catania) and FISM (Fondazione Italiana Sclerosi Multipla)
Dr Frigerio F is an employee of Novartis
Dr Bartezaghi M is an employee of Novartis
Dr Turrini R is an employee of Novartis
Abstract: P1254
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: Fingolimod is an oral immunomodulator exerting its therapeutic effects in multiple sclerosis via sphingosine-1P receptors (S1PR). S1PR are also expressed in the heart, mainly in atrial myocytes, and mediate cardiovascular (CV) effects. Effects of fingolimod first dose (FFD) on heart rate (HR) and atroventricular (AV) conduction are well defined, and the recommended FFD continuous 6-hours (hrs) ECG monitoring can be extended until the day after in case given conditions occur. Understanding potential interactions of preexisting individual autonomic profile with the FFD effects may add novel safety information and help explain the cases requiring extension of the 6-hrs period
Objectives: To characterize the patient population treated with FFD according to EMA label and clinical practice, in terms of baseline demographics, clinical and neurovegetative status and probability of extension of the continuous ECG monitoring
Methods
Observational, prospective study of 6 (up to 24) hrs. ECG was recorded for 15 min before FFD administration and for 6 hrs after. Heart Rate and HR Variability (HRV) in the frequency domain were derived from the ECG traces by a specialized software
Results: 625 patients were enrolled in 59 Italian centres. Of these, 580 (92.8%) patients were discharged at the 6th hour after FFD administration, while 45 (7.2%) required monitoring extension. Ten (1.6%) patients showed an AV block (3 of 1st degree, 7 of 2nd), all benign and reversible. The mean max percentage reduction in HR was 17.6±8.4. Normalized spectral power (norm units, nu) in the Low Frequency band (LFnu; marker of sympathetic modulation) < 75.2 (OR=0.47; 95%CI: 0.23-0.94), nu power in the High Frequency band (HFnu; marker of vagal modulation) < 19.4 (OR=2.07; 95%IC: 1.04-4.12) and previous annualized relapse rate 0 vs ≥2 (OR=0.25; 95%CI: 0.08-0.75) were correlated with the probability of discharge at 6 hrs (which was not correlated with demographic or other clinical variables). With regard to HRV and the max HR reduction, coefficients indicated a weak positive correlation between the latter and LFnu and LF/HF ratio, whereas HFnu showed a weak negative correlation
Conclusions: Data confirm the well known and manageable CV profile of FFD. An individual higher vagal tone at baseline may contribute to the chances of extending CV monitoring. The potentially synergistic effects of FFD and individual inherent vagal tone were not associated with clinically significant cardiac events
Disclosure: Prof Mancardi G has received honoraria for lecturing, travel expenses for attending meetings, and financial support for research from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis and Teva Pharmaceuticals
Dr De Angelis G receives consulting fee from Novartis
Dr Nicola M received consulting fees from Novo Nordisk, Resmed and Novartis
Dr Vanoli E received consulting fees from Novartis
Dr Mirabella M has received honoraria for scientific lectures and advisory board activities from Biogen, Novartis, Teva, Sanofi Genzyme, Bayer Schering, Merck Serono, Almirall, and research support from Merck Serono, Novartis, Teva, Genzyme
Prof Bonavita S. received speaker honoraria from Biogen-Idec, Teva, Merck-Serono, Novartis
Prof Patti F served as advisor to Almirall, Bayer, Biogen, Merck, Novartis, Sanofi and TEVA and received fee for personal consultations and speaking activities by Almirall, Bayer, Biogen, Merck and Sanofi. He received research grants by MIUR (University of Catania) and FISM (Fondazione Italiana Sclerosi Multipla)
Dr Frigerio F is an employee of Novartis
Dr Bartezaghi M is an employee of Novartis
Dr Turrini R is an employee of Novartis