Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: Subgroup analysis of the randomized, unblinded KOMET study

Bernd Pohlmann-Eden; Anthony G. Marson; Matthias Noack-Rink; Francisco Ramirez; Azita Tofighy; Konrad J. Werhahn; Imane Wild; Eugen Trinka

doi:10.1186/s12883-016-0663-7

Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: Subgroup analysis of the randomized, unblinded KOMET study

Bernd Pohlmann-Eden, Anthony G. Marson, Matthias Noack-Rink, Francisco Ramirez, Azita Tofighy, Konrad J. Werhahn, Imane Wild, Eugen Trinka

Medicine

Research output: Contribution to journal › Article › peer-review

56 Citations (Scopus)

Abstract

Background: Few clinical trials have evaluated the efficacy and tolerability of antiepileptic drugs (AEDs) as initial monotherapy for elderly patients. Methods: This post-hoc subgroup analysis of data from an unblinded, randomized, 52-week superiority study (KOMET) compared the effectiveness of levetiracetam (LEV) with extended-release sodium valproate (VPA-ER) and controlled-release carbamazepine (CBZ-CR) as monotherapy in patients aged≥60 years with newly diagnosed epilepsy. The physician chose VPA or CBZ as preferred standard treatment; patients were randomized to standard AEDs or LEV. The primary endpoint was time to treatment withdrawal. Results are exploratory, since KOMET was not powered for a subgroup analysis by age. Results: Patients (n=308) were randomized to LEV (n=48) or VPA-ER (n=53) in the VPE-ER stratum or to LEV (n=104) or CBZ-CR (n=103) in the CBZ-CR stratum. Mean age was 69.6 years, range 60.2-89.9 years (intention-to-treat population n=307). Time to treatment withdrawal hazard ratio [HR] (95 % confidence interval [CI]) for LEV vs. standard AEDs was 0.44 (0.28-0.67); LEV vs. VPA-ER: 0.46 (0.16-1.33); LEV vs. CBZ-CR: 0.45 (0.28-0.72). Twelve-month withdrawal rates were: LEV vs. standard AEDs, 20.4 vs. 38.7 %; LEV vs. VPA-ER, 10.4 vs. 23.1 %; LEV vs. CBZ-CR, 25.0 vs. 46.6 %. Time to first seizure was similar between LEV and standard AEDs (HR: 0.92, 95 % CI: 0.63-1.35), LEV and VPA-ER (0.77, 0.38-1.56), and LEV and CBZ-CR (1.02, 0.64-1.63). Adverse events were reported by 76.2, 67.3, and 82.5 % of patients for LEV, VPA-ER, and CBZ-CR, respectively. Discontinuation rates due to AEs were 11.3, 10.2, and 35.0 % for LEV, VPA-ER, and CBZ-CR, respectively. Conclusions: Time to treatment withdrawal was longer with LEV compared with standard AEDs. This finding was driven primarly by the result in the CBZ-CR stratum, which in turn was likely due to the more favorable tolerability profile of LEV. Results of this post-hoc analysis suggest that LEV may be a suitable option for initial monotherapy for patients aged≥60 years with newly diagnosed epilepsy. Trial registration: ClinicalTrials.gov: NCT00175903 ; September 9, 2005.

Original language	English
Article number	149
Journal	BMC Neurology
Volume	16
Issue number	1
DOIs	https://doi.org/10.1186/s12883-016-0663-7
Publication status	Published - Aug 23 2016

Bibliographical note

Funding Information:
The authors thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. The authors acknowledge Jennifer Stewart, MSc (QXV Communications, an Ashfield business, Macclesfield, UK) for writing support which was funded by UCB Pharma. The authors acknowledge Barbara Pelgrims, PhD (UCB Pharma, Brussels, Belgium) for manuscript coordination.

Funding Information:
BP-E has received consulting fees from UCB Pharma, Eisai, Sunovion, SAGE and Sanofi-Aventis; research funding from UCB Pharma and Eisai; and speaker honoraria from UCB Pharma, Eisai, and Desitin Pharma. AGM has received research funding to his organization from UCB Pharma, GlaxoSmithKline and Eisai; and has received speaker honoraria from UCB Pharma and Sanofi. MN-R and KJW are employees of UCB Pharma. IW is an employee of UCB Biopharma. AT and FR were employees of UCB Pharma at the time that the analysis was conducted. ET has received consulting fees from UCB Pharma, Eisai, Bial, Ever Neuropharma, Sanofi-Aventis, Medtronics, Takeda, SAGE, Biogen Idec, and Genzyme; research funding from UCB Pharma, Biogen Idec, Sanofi-Aventis, FWF Austrian Science Fund, Jubiläumsfond der Österreichischen Nationalbank, and Red Bull; speaker honoraria from UCB Pharma, Eisai, Bial, Gerot Lannach, GlaxoSmithKline, Boehringer Ingelheim, ViroPharma, Actavis, Ever Neuropharma, Sanofi, Biogen, and Genzyme; and is Chief Executive Officer of Neuroconsult GmbH.

Publisher Copyright:
© 2016 The Author(s).

ASJC Scopus Subject Areas

Clinical Neurology

PubMed: MeSH publication types

Journal Article
Multicenter Study
Randomized Controlled Trial

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10.1186/s12883-016-0663-7

Cite this

Pohlmann-Eden, B., Marson, A. G., Noack-Rink, M., Ramirez, F., Tofighy, A., Werhahn, K. J., Wild, I., & Trinka, E. (2016). Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: Subgroup analysis of the randomized, unblinded KOMET study. BMC Neurology, 16(1), Article 149. https://doi.org/10.1186/s12883-016-0663-7

Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: Subgroup analysis of the randomized, unblinded KOMET study. / Pohlmann-Eden, Bernd; Marson, Anthony G.; Noack-Rink, Matthias et al.
In: BMC Neurology, Vol. 16, No. 1, 149, 23.08.2016.

Research output: Contribution to journal › Article › peer-review

Pohlmann-Eden, B, Marson, AG, Noack-Rink, M, Ramirez, F, Tofighy, A, Werhahn, KJ, Wild, I & Trinka, E 2016, 'Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: Subgroup analysis of the randomized, unblinded KOMET study', BMC Neurology, vol. 16, no. 1, 149. https://doi.org/10.1186/s12883-016-0663-7

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title = "Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: Subgroup analysis of the randomized, unblinded KOMET study",

abstract = "Background: Few clinical trials have evaluated the efficacy and tolerability of antiepileptic drugs (AEDs) as initial monotherapy for elderly patients. Methods: This post-hoc subgroup analysis of data from an unblinded, randomized, 52-week superiority study (KOMET) compared the effectiveness of levetiracetam (LEV) with extended-release sodium valproate (VPA-ER) and controlled-release carbamazepine (CBZ-CR) as monotherapy in patients aged≥60 years with newly diagnosed epilepsy. The physician chose VPA or CBZ as preferred standard treatment; patients were randomized to standard AEDs or LEV. The primary endpoint was time to treatment withdrawal. Results are exploratory, since KOMET was not powered for a subgroup analysis by age. Results: Patients (n=308) were randomized to LEV (n=48) or VPA-ER (n=53) in the VPE-ER stratum or to LEV (n=104) or CBZ-CR (n=103) in the CBZ-CR stratum. Mean age was 69.6 years, range 60.2-89.9 years (intention-to-treat population n=307). Time to treatment withdrawal hazard ratio [HR] (95 % confidence interval [CI]) for LEV vs. standard AEDs was 0.44 (0.28-0.67); LEV vs. VPA-ER: 0.46 (0.16-1.33); LEV vs. CBZ-CR: 0.45 (0.28-0.72). Twelve-month withdrawal rates were: LEV vs. standard AEDs, 20.4 vs. 38.7 %; LEV vs. VPA-ER, 10.4 vs. 23.1 %; LEV vs. CBZ-CR, 25.0 vs. 46.6 %. Time to first seizure was similar between LEV and standard AEDs (HR: 0.92, 95 % CI: 0.63-1.35), LEV and VPA-ER (0.77, 0.38-1.56), and LEV and CBZ-CR (1.02, 0.64-1.63). Adverse events were reported by 76.2, 67.3, and 82.5 % of patients for LEV, VPA-ER, and CBZ-CR, respectively. Discontinuation rates due to AEs were 11.3, 10.2, and 35.0 % for LEV, VPA-ER, and CBZ-CR, respectively. Conclusions: Time to treatment withdrawal was longer with LEV compared with standard AEDs. This finding was driven primarly by the result in the CBZ-CR stratum, which in turn was likely due to the more favorable tolerability profile of LEV. Results of this post-hoc analysis suggest that LEV may be a suitable option for initial monotherapy for patients aged≥60 years with newly diagnosed epilepsy. Trial registration: ClinicalTrials.gov: NCT00175903 ; September 9, 2005.",

author = "Bernd Pohlmann-Eden and Marson, {Anthony G.} and Matthias Noack-Rink and Francisco Ramirez and Azita Tofighy and Werhahn, {Konrad J.} and Imane Wild and Eugen Trinka",

note = "Funding Information: The authors thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. The authors acknowledge Jennifer Stewart, MSc (QXV Communications, an Ashfield business, Macclesfield, UK) for writing support which was funded by UCB Pharma. The authors acknowledge Barbara Pelgrims, PhD (UCB Pharma, Brussels, Belgium) for manuscript coordination. Funding Information: BP-E has received consulting fees from UCB Pharma, Eisai, Sunovion, SAGE and Sanofi-Aventis; research funding from UCB Pharma and Eisai; and speaker honoraria from UCB Pharma, Eisai, and Desitin Pharma. AGM has received research funding to his organization from UCB Pharma, GlaxoSmithKline and Eisai; and has received speaker honoraria from UCB Pharma and Sanofi. MN-R and KJW are employees of UCB Pharma. IW is an employee of UCB Biopharma. AT and FR were employees of UCB Pharma at the time that the analysis was conducted. ET has received consulting fees from UCB Pharma, Eisai, Bial, Ever Neuropharma, Sanofi-Aventis, Medtronics, Takeda, SAGE, Biogen Idec, and Genzyme; research funding from UCB Pharma, Biogen Idec, Sanofi-Aventis, FWF Austrian Science Fund, Jubil{\"a}umsfond der {\"O}sterreichischen Nationalbank, and Red Bull; speaker honoraria from UCB Pharma, Eisai, Bial, Gerot Lannach, GlaxoSmithKline, Boehringer Ingelheim, ViroPharma, Actavis, Ever Neuropharma, Sanofi, Biogen, and Genzyme; and is Chief Executive Officer of Neuroconsult GmbH. Publisher Copyright: {\textcopyright} 2016 The Author(s).",

year = "2016",

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doi = "10.1186/s12883-016-0663-7",

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T1 - Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy

T2 - Subgroup analysis of the randomized, unblinded KOMET study

AU - Pohlmann-Eden, Bernd

AU - Marson, Anthony G.

AU - Noack-Rink, Matthias

AU - Ramirez, Francisco

AU - Tofighy, Azita

AU - Werhahn, Konrad J.

AU - Wild, Imane

AU - Trinka, Eugen

N1 - Funding Information: The authors thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. The authors acknowledge Jennifer Stewart, MSc (QXV Communications, an Ashfield business, Macclesfield, UK) for writing support which was funded by UCB Pharma. The authors acknowledge Barbara Pelgrims, PhD (UCB Pharma, Brussels, Belgium) for manuscript coordination. Funding Information: BP-E has received consulting fees from UCB Pharma, Eisai, Sunovion, SAGE and Sanofi-Aventis; research funding from UCB Pharma and Eisai; and speaker honoraria from UCB Pharma, Eisai, and Desitin Pharma. AGM has received research funding to his organization from UCB Pharma, GlaxoSmithKline and Eisai; and has received speaker honoraria from UCB Pharma and Sanofi. MN-R and KJW are employees of UCB Pharma. IW is an employee of UCB Biopharma. AT and FR were employees of UCB Pharma at the time that the analysis was conducted. ET has received consulting fees from UCB Pharma, Eisai, Bial, Ever Neuropharma, Sanofi-Aventis, Medtronics, Takeda, SAGE, Biogen Idec, and Genzyme; research funding from UCB Pharma, Biogen Idec, Sanofi-Aventis, FWF Austrian Science Fund, Jubiläumsfond der Österreichischen Nationalbank, and Red Bull; speaker honoraria from UCB Pharma, Eisai, Bial, Gerot Lannach, GlaxoSmithKline, Boehringer Ingelheim, ViroPharma, Actavis, Ever Neuropharma, Sanofi, Biogen, and Genzyme; and is Chief Executive Officer of Neuroconsult GmbH. Publisher Copyright: © 2016 The Author(s).

PY - 2016/8/23

Y1 - 2016/8/23

N2 - Background: Few clinical trials have evaluated the efficacy and tolerability of antiepileptic drugs (AEDs) as initial monotherapy for elderly patients. Methods: This post-hoc subgroup analysis of data from an unblinded, randomized, 52-week superiority study (KOMET) compared the effectiveness of levetiracetam (LEV) with extended-release sodium valproate (VPA-ER) and controlled-release carbamazepine (CBZ-CR) as monotherapy in patients aged≥60 years with newly diagnosed epilepsy. The physician chose VPA or CBZ as preferred standard treatment; patients were randomized to standard AEDs or LEV. The primary endpoint was time to treatment withdrawal. Results are exploratory, since KOMET was not powered for a subgroup analysis by age. Results: Patients (n=308) were randomized to LEV (n=48) or VPA-ER (n=53) in the VPE-ER stratum or to LEV (n=104) or CBZ-CR (n=103) in the CBZ-CR stratum. Mean age was 69.6 years, range 60.2-89.9 years (intention-to-treat population n=307). Time to treatment withdrawal hazard ratio [HR] (95 % confidence interval [CI]) for LEV vs. standard AEDs was 0.44 (0.28-0.67); LEV vs. VPA-ER: 0.46 (0.16-1.33); LEV vs. CBZ-CR: 0.45 (0.28-0.72). Twelve-month withdrawal rates were: LEV vs. standard AEDs, 20.4 vs. 38.7 %; LEV vs. VPA-ER, 10.4 vs. 23.1 %; LEV vs. CBZ-CR, 25.0 vs. 46.6 %. Time to first seizure was similar between LEV and standard AEDs (HR: 0.92, 95 % CI: 0.63-1.35), LEV and VPA-ER (0.77, 0.38-1.56), and LEV and CBZ-CR (1.02, 0.64-1.63). Adverse events were reported by 76.2, 67.3, and 82.5 % of patients for LEV, VPA-ER, and CBZ-CR, respectively. Discontinuation rates due to AEs were 11.3, 10.2, and 35.0 % for LEV, VPA-ER, and CBZ-CR, respectively. Conclusions: Time to treatment withdrawal was longer with LEV compared with standard AEDs. This finding was driven primarly by the result in the CBZ-CR stratum, which in turn was likely due to the more favorable tolerability profile of LEV. Results of this post-hoc analysis suggest that LEV may be a suitable option for initial monotherapy for patients aged≥60 years with newly diagnosed epilepsy. Trial registration: ClinicalTrials.gov: NCT00175903 ; September 9, 2005.

AB - Background: Few clinical trials have evaluated the efficacy and tolerability of antiepileptic drugs (AEDs) as initial monotherapy for elderly patients. Methods: This post-hoc subgroup analysis of data from an unblinded, randomized, 52-week superiority study (KOMET) compared the effectiveness of levetiracetam (LEV) with extended-release sodium valproate (VPA-ER) and controlled-release carbamazepine (CBZ-CR) as monotherapy in patients aged≥60 years with newly diagnosed epilepsy. The physician chose VPA or CBZ as preferred standard treatment; patients were randomized to standard AEDs or LEV. The primary endpoint was time to treatment withdrawal. Results are exploratory, since KOMET was not powered for a subgroup analysis by age. Results: Patients (n=308) were randomized to LEV (n=48) or VPA-ER (n=53) in the VPE-ER stratum or to LEV (n=104) or CBZ-CR (n=103) in the CBZ-CR stratum. Mean age was 69.6 years, range 60.2-89.9 years (intention-to-treat population n=307). Time to treatment withdrawal hazard ratio [HR] (95 % confidence interval [CI]) for LEV vs. standard AEDs was 0.44 (0.28-0.67); LEV vs. VPA-ER: 0.46 (0.16-1.33); LEV vs. CBZ-CR: 0.45 (0.28-0.72). Twelve-month withdrawal rates were: LEV vs. standard AEDs, 20.4 vs. 38.7 %; LEV vs. VPA-ER, 10.4 vs. 23.1 %; LEV vs. CBZ-CR, 25.0 vs. 46.6 %. Time to first seizure was similar between LEV and standard AEDs (HR: 0.92, 95 % CI: 0.63-1.35), LEV and VPA-ER (0.77, 0.38-1.56), and LEV and CBZ-CR (1.02, 0.64-1.63). Adverse events were reported by 76.2, 67.3, and 82.5 % of patients for LEV, VPA-ER, and CBZ-CR, respectively. Discontinuation rates due to AEs were 11.3, 10.2, and 35.0 % for LEV, VPA-ER, and CBZ-CR, respectively. Conclusions: Time to treatment withdrawal was longer with LEV compared with standard AEDs. This finding was driven primarly by the result in the CBZ-CR stratum, which in turn was likely due to the more favorable tolerability profile of LEV. Results of this post-hoc analysis suggest that LEV may be a suitable option for initial monotherapy for patients aged≥60 years with newly diagnosed epilepsy. Trial registration: ClinicalTrials.gov: NCT00175903 ; September 9, 2005.

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Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: Subgroup analysis of the randomized, unblinded KOMET study

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