Skip to main content Accessibility help
×
Home

Brivaracetam: First Canadian Experience in an Intractable Epilepsy Population

  • Jeanne Lafortune (a1), Charles Deacon (a1) and Jean-François Clément (a1)

Abstract:

Objective:

To evaluate the effectiveness and tolerability of brivaracetam (BRV) in a refractory epilepsy population in an outpatient clinical setting.

Methods:

Retrospective medical information system review and self-report questionnaire for all patients treated with BRV until the end of 2017.

Results:

Thirty-eight patients were included, 73.7% female and mean age 36.2. The mean number of antiepileptic drugs (AEDs) for previous use was 8.9, and for current use was 2.5. Mean seizure frequency in the last 3 months was 12 per month. At 3, 6, 12, and 15 months, the 50% responder rates were 36.1%, 32%, 41.2%, and 45.5%, respectively. Patients took BRV for a median duration of 8.25 months, ranging from 7 days to 60 months. Retention rate was 75.0%, 72.0%, 59.2%, and 47.9% at 3, 6, 12, and 15 months, respectively. Overall, the main reasons for discontinuation were adverse events (AEs) (52.3%), lack of efficacy (35.3%), or both (11.8%). The rate of total AEs was 60.5% according to medical records and 85.7% according to questionnaire, including mostly tiredness, psychiatric, and memory complaints. Psychiatric side effects occurred in 31.6% according to medical records and 47.4% according to questionnaire results, which is higher than previously reported and persisted throughout the study period.

Conclusions:

BRV appears to be a useful and safe add-on treatment, even in a very refractory group of patients. In this real-life clinical setting, psychiatric AEs were found at a higher rate than previously published.

RÉSUMÉ :

Première expérience canadienne avec le brivaracetam comme anticonvulsivant chez des patients avec épilepsie réfractaire. Objectif : Évaluer l’efficacité et la tolérabilité du brivaracétam (BRV) en traitement de l’épilepsie réfractaire dans un contexte de pratique clinique. Méthodes : Procéder à une analyse rétrospective de dossiers médicaux informatisés et faire remplir un questionnaire auto-administré à tous les patients traités par BRV jusqu’à la fin de 2017. Résultats : 38 patients ont été inclus, dont étaient 73.7% des femmes. La moyenne d’âge était de 36.2 ans. Le nombre moyen de médicaments anticonvulsivants (MAC) utilisés antérieurement était de 8.9 et utilisés au moment de l’étude était de 2.5. La moyenne de crise mensuelle dans les 3 derniers mois était de 12. À 3, 6, 12 et 15 mois, le taux de répondeur 50% était de 36.1%, 32%, 41.2% et 45.5%, respectivement. La durée moyenne du traitement par BRV était de 8.25 mois, avec un intervalle de 7 à 60 mois. Le taux de rétention était de 75.0%, 72.0%, 59.2% et 47.9% à 3, 6, 12 et 15 mois, respectivement. Les principales raisons d’arrêt du BRV étaient en raison d’événements indésirables (EI) (52.3%), manque d’efficacité (35.3%) ou les deux (11.8%). Le taux général d’EI a été de 60.5% selon les dossiers médicaux informatisés et de 85.7% selon le questionnaire, incluant surtout de la fatigue ainsi que des plaintes psychiatriques et cognitives. Des EI psychiatriques sont survenus chez 31.6% des patients selon les dossiers médicaux informatisés et 47.4% selon le questionnaire, ce qui est plus élevé que précédemment rapporté et a persisté pendant la période de l’étude. Conclusions : BRV apparaît être utile et sécuritaire comme traitement d’appoint, même dans un groupe de patients avec épilepsie très réfractaire. Dans ce contexte concret de pratique clinique, les EI psychiatriques ont été observé plus fréquemment que ce qui a été évoqué antérieurement dans la littérature scientifique.

Copyright

Corresponding author

Correspondence to: Jeanne Lafortune, Department of Neurology, Centre Hospitalier Universitaire de Sherbrooke (CHUS), 3001 12e Avenue N, Sherbrooke, Quebec J1H 5H3, Canada. Email: jeanne.lafortune@usherbrooke.ca

References

Hide All
1.Programme de recherche sur la génétique des épilepsie, Statistiques, CHUM centre de recherche/université de Montréal, www.epileptogene.ca/
2.Leoscher, W, Schmidt, D. Modern antiepileptic drug development has failed to deliver: ways out of the current dilemma. Epilepsia. 2011;52:657–78.10.1111/j.1528-1167.2011.03024.x
3.Perucca, E, Meador, KJ. Adverse effects of antiepileptic drugs. Acta Neurol Scand Suppl. 2005;181:30–5.10.1111/j.1600-0404.2005.00506.x
4.Leoscher, W, Gillard, M, Sands, ZA, Kaminski, RM, Klitgaard, H. Synaptic vesicle glycoprotein 2A ligands in the treatment of epilepsy and beyond. CNS Drugs. 2016;30:1055–77.10.1007/s40263-016-0384-x
5.Hansen, C, Ljung, H, Brodtkorb, E, Reimers, A. Mechanisms underlying aggressive behavior induced by antiepileptic drugs: focus on topiramate, levetiracetam, and perampanel. Behav Neurol. 2018;2018, Article ID 2064027, 18 p.10.1155/2018/2064027
6.Helmstaedter, C, Mihov, Y, Toliat, MR, et al.Genetic variation in dopaminergic activity is associated with the risk for psychiatric side effects of levetiracetam. Epilepsia. 2013;54(1):3644.10.1111/j.1528-1167.2012.03603.x
7.Ryvlin, P, Werhahn, KJ, Blaszczyk, B, et al.Adjunctive brivaracetam in adults with uncontrolled focal epilepsy: results from a double-blind, randomized, placebo-controlled trial. Epilepsia. 2014;55:4756.10.1111/epi.12432
8.Klein, P, Schiemann, J, Sperling, M, et al.A randomized, double-blind, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of adjunctive brivaracetam in adult patients with uncontrolled partial-onset seizures. Epilepsia. 2015;56:1890–8.10.1111/epi.13212
9.Biton, V, Berkovic, S, Abou-Khalil, B, Sperling, M, Johnson, M, Lu, S. Brivaracetam as adjunctive treatment for uncontrolled partial epilepsy in adults: a phase III randomized, double-blind, placebo-controlled trial. Epilepsia. 2014;55:5766.10.1111/epi.12433
10.Kwan, P, Trinka, E, Van Paesschen, W, Rektor, I, Johnson, M, Lu, S. Adjunctive brivaracetam for uncontrolled focal and generalized epilepsies: results of a phase III, double-blind, randomized, placebo-controlled, flexible-dose trial. Epilepsia. 2014;55:3846.10.1111/epi.12391
11.Lattanzi, S, Cagnett, C, Foschi, N, Provinciali, L, Silvestrini, M. Brivaracetam add-on for refractory focal epilepsy: a systematic review and meta-analysis. Neurology. 2014;86:1344–52.10.1212/WNL.0000000000002545
12.Baker, GA, Frances, P, Middleton, E. Initial development, reliability and validity of a patient-based adverse events scale. Epilepsia. 1994; 35;80.
13.UCB Canada Inc. BrivleraTM (brivaracetam): Canadian product monograph. 2016. Available at: https://s3.pgkb.org/attachment/brivaracetam_HCSC_Aug2016.pdf; accessed 11 November 2019.
14.“Anger” and “Irritability”. Merriam-Webster.com. Merriam-Webster 2019. Web. Accessed March 5, 2019.
15.French, JA, Costantini, C, Brodsky, A, Von Rosenstiel, P, N01193 Study Group. Adjunctive Brivaracetam for refractory partial-onset seizures: a randomized, controlled trial. Neurology. 2010;75(6):519–25.10.1212/WNL.0b013e3181ec7f7f
16.Toledo, M, Whitesides, J, Schiemann, J, et al.Safety, tolerability, and seizure control during long-term treatment with adjunctive Brivaracetam for partial-onset seizures. Epilepsia. 2016; 57(7):1139–51.10.1111/epi.13416
17.Van Paesschen, W, Hirsch, E, Johnson, M, Falter, U, von Rosenstiel, P. Efficacy and tolerability of adjunctive Brivaracetam in adults with uncontrolled partial-onset seizures: a phase IIb, randomized, controlled trial. Epilepsia. 2013;54(1):8997.10.1111/j.1528-1167.2012.03598.x
18.Steinhoff, BJ, Bacher, M, Bucurenciu, I, Hillenbrand, B, Intravooth, T, Kornmeier, R, et al.Real-life experience with Brivaracetam in 101 patients with difficult-to-treat epilepsy- a monocenter survey. Seizure. 2017;48:11–4.10.1016/j.seizure.2017.03.010
19.Steinig, I, von Podewils, F, Moddel, G, et al.Postmarketing experience with Brivaracetam in the treatment of epilepsies: a multicenter cohort study from Germany. Epilepsia. 2017;58(7):1208–16.10.1111/epi.13768
20.Zahnert, F, Krause, K, Immisch, I, et al.brivaracetam in the treatment of patients with epilepsy—first clinical experiences. Front Neurol 2018;9:38.10.3389/fneur.2018.00038
21.Willems, LM, Bertsche, A, Bösebeck, F, et al.Efficacy, retention, and tolerability of brivaracetam in patients with epileptic encephalopathies: a multicenter cohort study from Germany. Front Neurol 2018;9:569.10.3389/fneur.2018.00569
22.Strzelczyk, A, Kay, L, Bauer, S, et al.Use of brivaracetam in genetic generalized epilepsies and for acute, intravenous treatment of absence status epilepticus. Epilepsia. 2018;59:1549–56.10.1111/epi.14476
23.Villanueva, V, Lopez-Gonzalez, FJ, Mauri, JA, et al.BRIVA-LIFE–A multicenter retrospective study of the long-term use of brivaracetam in clinical practice. Acta Neurol Scand. 2019;139: 360–8.10.1111/ane.13059
24.Althubaiti, A. Information bias in health research: definition, pitfalls, and adjustment methods. J Multidiscip Healthc. 2016;9:211–7.10.2147/JMDH.S104807
25.Yates, SL, Fakhoury, T, Liang, W, Eckhardt, K, Borghs, S, D’Souza, J. An open-label, prospective, exploratory study of patients with epilepsy switching from levetiracetam to brivaracetam. Epilepsy Behav. 2015;52:165–8.10.1016/j.yebeh.2015.09.005
26.Fisher, R, Blum, DE, DiVentura, B, et al.Seizure diaries for clinical research and practice: limitations and future prospects. Epilepsy Behav. 2012;24:304–10.10.1016/j.yebeh.2012.04.128

Keywords

Related content

Powered by UNSILO

Brivaracetam: First Canadian Experience in an Intractable Epilepsy Population

  • Jeanne Lafortune (a1), Charles Deacon (a1) and Jean-François Clément (a1)

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.