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

doi:10.1186/s12883-016-0663-7

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

Highlights

Few clinical trials have evaluated the efficacy and tolerability of antiepileptic drugs (AEDs) as initial monotherapy for elderly patients
Time to treatment withdrawal was longer with LEV compared with standard AEDs
Sodium valproate (VPA) was deemed by the treating physicians to be standard treatment for 101 patients who were subsequently randomized to treatment with either LEV (n = 48) or VPA-ER (n = 53)

Summary

Introduction

Few clinical trials have evaluated the efficacy and tolerability of antiepileptic drugs (AEDs) as initial monotherapy for elderly patients. Given the rapidly aging population, epilepsy in the elderly is likely to become one of the most frequent forms of epilepsy encountered in clinical practice. Characteristics of epilepsy, such as etiology, clinical manifestations, and electroencephalogram (EEG) findings differ between elderly and younger populations [4,5,6,7]. New-onset seizures in the elderly are typically focal, with or without secondary generalization, reflecting their regional etiology and most often their underlying structural cause [12, 13]. The period of postictal confusion can be much prolonged [10, 12]

Methods

Results

Discussion

Conclusion