Contributions
Abstract: EP1526
Type: ePoster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: Bradycardia was shown to occur within 6h after Fingolimod intake, normalizing within 3 months (Kappos 2006). However, it remained yet to be assessed, whether, for how long and to what extent heart rate reductions occur under physical exercise, and whether this affects the patient"s objective and subjective exercise tolerance.
Objective: ...prospectively and longitudinally assessing objective and subjective physical exertion, oxygen-uptake, lactate-levels, resting- and exercise-heart-rate, blood-pressure, cardiac output and MSFC in RRMS-patients taking Fingolimod 0,5mg/d.
Methods: For 160days, 12patients (6F, 6M), aged 20-53 years, athletic/nonathletic, median EDSS: 2.0, were examined using impedance cardiography, Holter EKG, serum-lactate measurements, spiroergometry 24h-RR and RPR-scale. Visits V1+V2 took place predose, V3-7 postdose at days 3,10,28,70,150.
Results: Heartrate reduction of 16%, and compensatory rise in cardiac ejection volume of 13%, resulting in a significantly reduced cardiac output of 5% at V3 with a significant downward trend in cardiac output at rest till V7was found.
Lactate levels showed significant reduction till V3 (p=0,022), V5 (0,029) and V7 (p=0,016). Ergometer-performance in watts was significantly reduced till V3 (p=0,004), and V7( p = 0,011). We found a downward trend (p=0,000).
Maximal exercise heartrate was significantly reduced (p=0,000). Down trends were significant for the AUC under heart rate- and maximum heart rate curves (p=0,000).
Minimal exercise heartrate was significantly reduced (p=0,000) between V1 and V3, V4, between V3 and V5, V7. A downward trend was nonsignificant.
The AUC for heart rate, measuring adrenergic response to physical exercise, was reduced (p=0,000) between V1 and V3, V5, V6, V7.
Resting systolic and diastolic blood pressure showed a significant upward trend (p=0,035, 0,010 resp.)
RPE-Data and oxygen consumption remained unchanged.
Fingolimod significantly reduced exercise heart rate up to 5months after firstdose, compared to predose baseline. Another new finding is a constant and significant increase of minimum Holter heartrate throughout study duration. During exercise and bradycardia, physical performance and maximum lactate decreased.
Conclusion: Fingolimod objectively reduces physical performance, but patients subjectively feel unaffected. Bradycardia seems to occur preferentially in physically active patients.
Disclosure:
UZ has received honoraria from Biogen Idec Deutschland GmbH, Bayer Vital GmbH, CorTec GmbH, Medtronic and Servier for advisory work, and a grant from Biogen Idec for supporting an investigator initiated trial.
HS has nothing to disclose
CS has nothing to disclose
CM received travel grants from NOVARTIS pharma, Biogen Idec and a research grant from NOVARTIS pharma
Abstract: EP1526
Type: ePoster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: Bradycardia was shown to occur within 6h after Fingolimod intake, normalizing within 3 months (Kappos 2006). However, it remained yet to be assessed, whether, for how long and to what extent heart rate reductions occur under physical exercise, and whether this affects the patient"s objective and subjective exercise tolerance.
Objective: ...prospectively and longitudinally assessing objective and subjective physical exertion, oxygen-uptake, lactate-levels, resting- and exercise-heart-rate, blood-pressure, cardiac output and MSFC in RRMS-patients taking Fingolimod 0,5mg/d.
Methods: For 160days, 12patients (6F, 6M), aged 20-53 years, athletic/nonathletic, median EDSS: 2.0, were examined using impedance cardiography, Holter EKG, serum-lactate measurements, spiroergometry 24h-RR and RPR-scale. Visits V1+V2 took place predose, V3-7 postdose at days 3,10,28,70,150.
Results: Heartrate reduction of 16%, and compensatory rise in cardiac ejection volume of 13%, resulting in a significantly reduced cardiac output of 5% at V3 with a significant downward trend in cardiac output at rest till V7was found.
Lactate levels showed significant reduction till V3 (p=0,022), V5 (0,029) and V7 (p=0,016). Ergometer-performance in watts was significantly reduced till V3 (p=0,004), and V7( p = 0,011). We found a downward trend (p=0,000).
Maximal exercise heartrate was significantly reduced (p=0,000). Down trends were significant for the AUC under heart rate- and maximum heart rate curves (p=0,000).
Minimal exercise heartrate was significantly reduced (p=0,000) between V1 and V3, V4, between V3 and V5, V7. A downward trend was nonsignificant.
The AUC for heart rate, measuring adrenergic response to physical exercise, was reduced (p=0,000) between V1 and V3, V5, V6, V7.
Resting systolic and diastolic blood pressure showed a significant upward trend (p=0,035, 0,010 resp.)
RPE-Data and oxygen consumption remained unchanged.
Fingolimod significantly reduced exercise heart rate up to 5months after firstdose, compared to predose baseline. Another new finding is a constant and significant increase of minimum Holter heartrate throughout study duration. During exercise and bradycardia, physical performance and maximum lactate decreased.
Conclusion: Fingolimod objectively reduces physical performance, but patients subjectively feel unaffected. Bradycardia seems to occur preferentially in physically active patients.
Disclosure:
UZ has received honoraria from Biogen Idec Deutschland GmbH, Bayer Vital GmbH, CorTec GmbH, Medtronic and Servier for advisory work, and a grant from Biogen Idec for supporting an investigator initiated trial.
HS has nothing to disclose
CS has nothing to disclose
CM received travel grants from NOVARTIS pharma, Biogen Idec and a research grant from NOVARTIS pharma