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Meta-Analysis of Randomized Trials on First Line and Adjunctive Levetiracetam

Published online by Cambridge University Press:  02 December 2014

Benjamin W. Y. Lo ,
Hmwe H. Kyu ,
Draga Jichici ,
Adrian M. Upton ,
Elie A. Akl  and
Maureen O. Meade
Benjamin W. Y. Lo*
Affiliation:
Division of Critical Care Medicine, Department of Clinical Edpiemiology & Biostatistics, McMaster University, Hamilton Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada
Hmwe H. Kyu
Affiliation:
Division of Critical Care Medicine, Department of Clinical Edpiemiology & Biostatistics, McMaster University, Hamilton
Draga Jichici
Affiliation:
Division of Critical Care Medicine, Department of Clinical Edpiemiology & Biostatistics, McMaster University, Hamilton
Adrian M. Upton
Affiliation:
Division of Critical Care Medicine, Department of Clinical Edpiemiology & Biostatistics, McMaster University, Hamilton
Elie A. Akl
Affiliation:
Division of Critical Care Medicine, Department of Clinical Edpiemiology & Biostatistics, McMaster University, Hamilton Department of Medicine, University of Buffalo, Buffalo, NY, USA
Maureen O. Meade
Affiliation:
Division of Critical Care Medicine, Department of Clinical Edpiemiology & Biostatistics, McMaster University, Hamilton
*
Faculty of Health Sciences, McMaster University, Room 2U, 1200 Main Street West, Hamilton, Ontario, L8N 3Z5, Canada
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Abstract

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Context:

New evidence suggests that levetiracetam may be as effective as traditional agents, with better safety profile.

Objective:

To synthesize evidence regarding efficacy and tolerability of levetiracetam as first line, adjunctive or prophylactic antiepileptic agent.

Study Selection & Data Extraction:

Eligible studies were randomized controlled trials (RCTs) of levetiracetam used in adults with epilepsy. MEDLINE, EMBASE, CENTRAL, CINHAL, PAPERSFIRST, PROCEEDINGSFIRST, PROQUEST and conference proceedings identified studies (to September 30, 2010). Two investigators independently selected, appraised studies, collected and analyzed data.

Results:

Of ten eligible randomized trials, eight investigated adjunctive levetiracetam for refractory seizures, one as monotherapy for newly diagnosed seizures, one as monotherapy for prophylaxis. Eight RCTs of adjunctive levetiracetam were of moderate quality (GRADE criteria), with two showing lack of allocation concealment. Meta-analyses showed adjunctive levetiracetam was more effective than placebo in achieving at least 50% reduction of seizure frequency, when added to baseline antiepileptic regimen (pooled RR 2.15 [1.65,2.82], I2 = 45%, p value (heterogeneity) = 0.08, p value (overall effect) < 0.01). Likelihood of serious adverse events necessitating withdrawal from study was not significantly different between levetiracetam and control (pooled RR 1.37 [0.88,2.13], I2 = 0%, p value (heterogeneity) = 0.84, p value (overall effect) = 0.17). Subgroup analyses suggested similar effects across different dosages. Sensitivity analysis of studies with adequate concealment showed similar effects.

Conclusions:

Levetiracetam is an effective adjunctive agent for refractory epilepsy. More studies are needed to establish whether it is effective as monotherapy for newly diagnosed seizures, and for prophylaxis in traumatic brain injury.

Résumé:

Résumé:Contexte:

Selon des données récentes, le lévétiracétam serait aussi efficace que les agents traditionnels et bénéficierait d’un meilleur profil de sécurité.

Objectif:

Le but de cette étude était de faire la synthèse des données concernant l’efficacité et la tolérance du lévétiracétam comme traitement de première intention, comme médicament d’appoint ou comme agent antiépileptique prophylactique.

Choix des études et recueil des données:

Nous avons choisi les essais cliniques contrôlés randomisés évaluant le lévétiracétam chez des adultes épileptiques ainsi que les comptes rendus de conférences, publiés avant le 30 septembre 2010 dans les bases de données MEDLINE, EMBASE, CENTRAL, CINHAL, PAPERSFIRST, PROCEEDINGSFIRST et PROQUEST. Deux chercheurs ont choisi les essais cliniques de façon indépendante, les ont évalués et ont colligé et analysé les données.

Résultats:

Parmi les 10 essais cliniques randomisés éligibles, 8 portaient sur le lévétiracétam comme médicament d’appoint pour traiter l’épilepsie réfractaire au traitement, 1 comme médicament de première intention chez des patients au moment du diagnostic de l’épilepsie et 1 comme monothérapie en prophylaxie. Huit des essais cliniques randomisés évaluant le lévétiracétam comme médicament d’appoint étaient de qualité moyenne (critères GRADE), dont 2 où le traitement n’était pas en aveugle. Les méta-analyses ont montré que le lévétiracétam comme traitement d’appoint était plus efficace que le placebo pour diminuer d’au moins 50% la fréquence des crises quand il était ajouté au régime posologique de base (RR global 2,15 [1,65 - 2,82] ; 12 = 45%, p (hétérogénéité) = 0,08 ; p effet global < 0,01). La probabilité que des incidents thérapeutiques sérieux entraînent le retrait du patient de l’étude n’était pas significativement différente entre le groupe recevant le lévétiracétam et le groupe témoin (RR global 1,37 [0,88 - 2,13] ; 12 = 0% ; p (hétérogénéité) = 0,84 ; p effet global = 0,17). Selon les analyses de sous-groupes, les effets seraient les mêmes, quelle que soit la posologie. Les analyses de sensibilité des études bien menées à l’insu ont montré des effets similaires.

Conclusions:

Le lévétiracétam est un médicament d’appoint efficace dans l’épilepsie réfractaire au traitement. Il devra faire l’objet de nouvelles études pour établir son efficacité en monothérapie chez les patients dont le diagnostic est récent et en prophylaxie chez les patients qui ont subi un traumatisme crânien.

Type
Original Article
Information
Canadian Journal of Neurological Sciences , Volume 38 , Issue 3 , May 2011 , pp. 475 - 486
Copyright
Copyright © The Canadian Journal of Neurological 2011

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