Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: subgroup analysis of the randomized, unblinded KOMET studyReportar como inadecuado




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BMC Neurology

, 16:149

Epilepsy

Abstract

BackgroundFew clinical trials have evaluated the efficacy and tolerability of antiepileptic drugs AEDs as initial monotherapy for elderly patients.

MethodsThis 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.

ResultsPatients 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.

ConclusionsTime 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 registrationClinicalTrials.gov: NCT00175903; September 9, 2005.

KeywordsEpilepsy Elderly Antiepileptic drug Monotherapy Levetiracetam AbbreviationsAEAdverse event

AEDAntiepileptic drug

CBZCarbamazepine

CBZ-CRControlled-release carbamazepine

CIConfidence interval

EEEpilepsy in the Elderly

EEGElectroencephalogram

HRHazard ratio

ITTIntention-to-treat

KOMETKeppra vs. Older Monotherapy in Epilepsy Trial

LEVLevetiracetam

LTGLamotrigine

SANADStandard and New Antiepileptic Drugs

STEP-ONEStudy on the Treatment of Elderly Patients with Older and Newer antiEpileptic Drugs

TEAETreatment-emergent adverse event

VPASodium valproate

VPA-ERExtended-release sodium valproate

Francisco Ramirez and Azita Tofighy were employees of UCB Pharma at the time that the analysis was conducted.

Electronic supplementary materialThe online version of this article doi:10.1186-s12883-016-0663-7 contains supplementary material, which is available to authorized users.

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Autor: Bernd Pohlmann-Eden - Anthony G. Marson - Matthias Noack-Rink - Francisco Ramirez - Azita Tofighy - Konrad J. Werhahn - Im

Fuente: https://link.springer.com/







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