Nancy Foldvary-Schaefer1, Joanna S Fong2, Shannon Morrison3, Lu Wang3, James Bena3. 1. Cleveland Clinic Neurological Institute, Cleveland, OH, United States. Electronic address: foldvan@ccf.org. 2. University of Pittsburgh Department of Neurology, Pittsburgh, PA, United States. 3. Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, United States.
Abstract
OBJECTIVE: We evaluated the impact of planned dose reduction and mechanism of action of concomitant AEDs on tolerability in adults with partial-onset seizures undergoing lacosamide (LCM) titration. METHODS: Data were collected at baseline and 3-6 and 12-24 months post-LCM initiation. Subjects were categorized as having planned reduction of concomitant AEDs or not; AEDs were categorized as traditional sodium channel blockers (TSCB) or non-TSCB (NTSCB). Groups with/without planned reduction were compared on the presence and number of treatment-emergent adverse events (TEAEs) using chi-square tests or logistic regression and on time to LCM discontinuation with time-to-event methods controlling for standardized (STD) AED dose, a measure of concomitant AED load. Similar analyses were performed comparing subjects taking TSCB and NTSCB agents and used to identify relationships with ≥50% decreases in seizure frequency. RESULTS: One hundred six adults (mean age 41.4 ± 13.4; 50% male) underwent LCM titration from June 2009-2011 with complete data. Reduction of concomitant AEDs was planned at the time of LCM initiation in 59 (55.7%) subjects. Fewer subjects with planned reduction had TEAEs (49.2% vs. 68.1%; p=0.05), and these subjects had a lower risk of TEAEs (OR 0.36; p=0.019) after adjusting for STD AED dose. The hazard ratio (95% CI) for LCM discontinuation was 0.46 (0.23, 0.94) in subjects with planned reduction of concomitant AEDs vs. others (p=0.033) and 3.29 (1.01, 10.70) in subjects taking TSCB vs. NTSCB agents (p=0.048). Among all cases, those who ever had TEAEs had significantly higher STD dose at both follow-up visits (p=0.033 and p=0.023, respectively). Seizure outcomes were not significantly different between groups at the last follow-up assessment. SIGNIFICANCE: Planned reduction of concomitant AEDs during LCM initiation and the use of NTSCB agents only are associated with a reduced risk of TEAEs and LCM discontinuation in adults with partial-onset seizures. This study extends prior observations by considering total AED load in the assessment of tolerability and supports the benefits of early reduction of concomitant AEDs during LCM initiation.
OBJECTIVE: We evaluated the impact of planned dose reduction and mechanism of action of concomitant AEDs on tolerability in adults with partial-onset seizures undergoing lacosamide (LCM) titration. METHODS: Data were collected at baseline and 3-6 and 12-24 months post-LCM initiation. Subjects were categorized as having planned reduction of concomitant AEDs or not; AEDs were categorized as traditional sodium channel blockers (TSCB) or non-TSCB (NTSCB). Groups with/without planned reduction were compared on the presence and number of treatment-emergent adverse events (TEAEs) using chi-square tests or logistic regression and on time to LCM discontinuation with time-to-event methods controlling for standardized (STD) AED dose, a measure of concomitant AED load. Similar analyses were performed comparing subjects taking TSCB and NTSCB agents and used to identify relationships with ≥50% decreases in seizure frequency. RESULTS: One hundred six adults (mean age 41.4 ± 13.4; 50% male) underwent LCM titration from June 2009-2011 with complete data. Reduction of concomitant AEDs was planned at the time of LCM initiation in 59 (55.7%) subjects. Fewer subjects with planned reduction had TEAEs (49.2% vs. 68.1%; p=0.05), and these subjects had a lower risk of TEAEs (OR 0.36; p=0.019) after adjusting for STD AED dose. The hazard ratio (95% CI) for LCM discontinuation was 0.46 (0.23, 0.94) in subjects with planned reduction of concomitant AEDs vs. others (p=0.033) and 3.29 (1.01, 10.70) in subjects taking TSCB vs. NTSCB agents (p=0.048). Among all cases, those who ever had TEAEs had significantly higher STD dose at both follow-up visits (p=0.033 and p=0.023, respectively). Seizure outcomes were not significantly different between groups at the last follow-up assessment. SIGNIFICANCE: Planned reduction of concomitant AEDs during LCM initiation and the use of NTSCB agents only are associated with a reduced risk of TEAEs and LCM discontinuation in adults with partial-onset seizures. This study extends prior observations by considering total AED load in the assessment of tolerability and supports the benefits of early reduction of concomitant AEDs during LCM initiation.
Authors: Mesut Mete; Beyhan Gurcu; Fatih Collu; Ulkun Unlu Unsal; Yusuf Kurtulus Duransoy; Mehmet Ibrahim Tuglu; Mehmet Selcuki Journal: Childs Nerv Syst Date: 2016-07-29 Impact factor: 1.475
Authors: Fritjof Reinhardt; Yvonne G Weber; Thomas Mayer; Gerhard Luef; Lars Joeres; Frank Tennigkeit; Peter Dedeken; Marc De Backer; Scarlett Hellot; Thomas Lauterbach; Tanja Webers; Stephan Arnold Journal: Epilepsia Open Date: 2019-06-22
Authors: Viktor Farkas; Barbara Steinborn; J Robert Flamini; Ying Zhang; Nancy Yuen; Simon Borghs; Ali Bozorg; Tony Daniels; Paul Martin; Hannah C Carney; Svetlana Dimova; Ingrid E Scheffer Journal: Neurology Date: 2019-08-28 Impact factor: 9.910