Adjunctive Brivaracetam in Focal Epilepsy: Real-World Evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST).

Adult Anticonvulsants / administration & dosage Chemotherapy, Adjuvant Drug Resistant Epilepsy / drug therapy Epilepsies, Partial / drug therapy Female Humans Italy Levetiracetam / administration & dosage Male Middle Aged Pyrrolidinones / administration & dosage Retrospective Studies Treatment Outcome

Journal

CNS drugs

ISSN: 1179-1934

Titre abrégé: CNS Drugs

Pays: New Zealand

ID NLM: 9431220

Informations de publication

Date de publication:
12 2021

Historique:

accepted: 09 08 2021

pubmed: 4 9 2021

medline: 18 3 2022

entrez: 3 9 2021

Statut: ppublish

Résumé

In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice. The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure-freedom, seizure response (≥ 50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed. A total of 1029 patients with a median age of 45 years (33-56) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p < 0.001); the corresponding values for ≥ 50% seizure frequency reduction were 47.9%, 29.7%, and 42.8% (p < 0.001). There were no statistically significant differences in seizure freedom and seizure response rates by use of strong EiASMs. The rates of seizure freedom (20.0% vs. 16.6%; p = 0.341) and seizure response (39.7% vs. 26.9%; p = 0.006) were higher in patients receiving SCBs than those not receiving SCBs; 265 (25.8%) patients discontinued BRV. AEs were reported by 30.1% of patients, and were less common in patients treated with BRV and concomitant SCBs than those not treated with SCBs (28.9% vs. 39.8%; p = 0.017). The BRIVAFIRST provided real-world evidence on the effectiveness of BRV in patients with focal epilepsy irrespective of LEV history and concomitant ASMs, and suggested favourable therapeutic combinations.

Sections du résumé

BACKGROUND

OBJECTIVE

This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice.

METHODS

The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure-freedom, seizure response (≥ 50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed.

RESULTS

A total of 1029 patients with a median age of 45 years (33-56) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p < 0.001); the corresponding values for ≥ 50% seizure frequency reduction were 47.9%, 29.7%, and 42.8% (p < 0.001). There were no statistically significant differences in seizure freedom and seizure response rates by use of strong EiASMs. The rates of seizure freedom (20.0% vs. 16.6%; p = 0.341) and seizure response (39.7% vs. 26.9%; p = 0.006) were higher in patients receiving SCBs than those not receiving SCBs; 265 (25.8%) patients discontinued BRV. AEs were reported by 30.1% of patients, and were less common in patients treated with BRV and concomitant SCBs than those not treated with SCBs (28.9% vs. 39.8%; p = 0.017).

CONCLUSION

The BRIVAFIRST provided real-world evidence on the effectiveness of BRV in patients with focal epilepsy irrespective of LEV history and concomitant ASMs, and suggested favourable therapeutic combinations.

Identifiants

DOI: 10.1007/s40263-021-00856-3 PMID: 34476770 PMC: PMC8642333

pubmed: 34476770

doi: 10.1007/s40263-021-00856-3

pii: 10.1007/s40263-021-00856-3

pmc: PMC8642333

doi:

Substances chimiques

Anticonvulsants 0

Pyrrolidinones 0

Levetiracetam 44YRR34555

brivaracetam U863JGG2IA

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

1289-1301

Investigateurs

Angela Alicino (A)

Michele Ascoli (M)

Giovanni Assenza (G)

Federica Avorio (F)

Valeria Badioni (V)

Paola Banfi (P)

Emanuele Bartolini (E)

Luca Manfredi Basili (LM)

Vincenzo Belcastro (V)

Simone Beretta (S)

Irene Berto (I)

Martina Biggi (M)

Giuseppe Billo (G)

Giovanni Boero (G)

Paolo Bonanni (P)

Jole Bongorno (J)

Francesco Brigo (F)

Emanuele Caggia (E)

Claudia Cagnetti (C)

Carmen Calvello (C)

Emanuele Cerulli Irelli (EC)

Edward Cesnik (E)

Gigliola Chianale (G)

Domenico Ciampanelli (D)

Roberta Ciuffini (R)

Dario Cocito (D)

Donato Colella (D)

Margerita Contento (M)

Cinzia Costa (C)

Eduardo Cumbo (E)

Alfredo D'Aniello (A)

Francesco Deleo (F)

Jacopo C DiFrancesco (JC)

Giancarlo Di Gennaro (G)

Roberta Di Giacomo (R)

Alessandra Di Liberto (A)

Elisabetta Domina (E)

Francesco Donato (F)

Fedele Dono (F)

Vania Durante (V)

Maurizio Elia (M)

Anna Estraneo (A)

Giacomo Evangelista (G)

Maria Teresa Faedda (MT)

Ylenia Failli (Y)

Elisa Fallica (E)

Jinane Fattouch (J)

Alessandra Ferrari (A)

Florinda Ferreri (F)

Davide Fonti (D)

Francesco Fortunato (F)

Nicoletta Foschi (N)

Teresa Francavilla (T)

Rosita Galli (R)

Stefano Gazzina (S)

Loretta Giuliano (L)

Francesco Habetswallner (F)

Francesca Izzi (F)

Benedetta Kassabian (B)

Angelo Labate (A)

Concetta Luisi (C)

Matteo Magliani (M)

Giulia Maira (G)

Luisa Mari (L)

Daniela Marino (D)

Addolorata Mascia (A)

Alessandra Mazzeo (A)

Stefano Meletti (S)

Alessandra Morano (A)

Annacarmen Nilo (A)

Biagio Orlando (B)

Francesco Paladin (F)

Maria Grazia Pascarella (MG)

Chiara Pastori (C)

Giada Pauletto (G)

Alessia Peretti (A)

Gabriella Perri (G)

Marianna Pezzella (M)

Marta Piccioli (M)

Pietro Pignatta (P)

Nicola Pilolli (N)

Francesco Pisani (F)

Laura Rosa Pisani (LR)

Fabio Placidi (F)

Patrizia Pollicino (P)

Vittoria Porcella (V)

Silvia Pradella (S)

Monica Puligheddu (M)

Stefano Quadri (S)

Rui Quintas (R)

Rosaria Renna (R)

Jessica Rossi (J)

Adriana Rum (A)

Enrico Michele Salamone (EM)

Ersilia Savastano (E)

Maria Sessa (M)

David Stokelj (D)

Elena Tartara (E)

Mario Tombini (M)

Gemma Tumminelli (G)

Maria Ventura (M)

Ilaria Viganò (I)

Emanuela Viglietta (E)

Aglaia Vignoli (A)

Flavio Villani (F)

Elena Zambrelli (E)

Lelia Zummo (L)

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Références

Chen Z, Brodie MJ, Liew D, Kwan P. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol. 2018;75:279–86.

doi: 10.1001/jamaneurol.2017.3949

Lattanzi S, Zaccara G, Giovannelli F, et al. Antiepileptic monotherapy in newly diagnosed focal epilepsy. A network meta-analysis. Acta Neurol Scand. 2019;139:33–41.

doi: 10.1111/ane.13025

Laxer KD, Trinka E, Hirsch LJ, et al. The consequences of refractory epilepsy and its treatment. Epilepsy Behav. 2014;37:59–70.

doi: 10.1016/j.yebeh.2014.05.031

Rogawski MA. Brivaracetam: a rational drug discovery success story. Br J Pharmacol. 2008;154:1555–7.

doi: 10.1038/bjp.2008.221

Klein P, Diaz A, Gasalla T, Whitesides J. A review of the pharmacology and clinical efficacy of brivaracetam. Clin Pharmacol. 2018;10:1–22.

pubmed: 29403319 pmcid: 5783144

Brivaracetam. Highlight of prescribing information. https://www.briviact.com/briviact-PI.pdf . Accessed Jul 2021.

Moseley BD, Chanteux H, Nicolas JM, Laloyaux C, Gidal B, Stockis A. A review of the drug-drug interactions of the antiepileptic drug brivaracetam. Epilepsy Res. 2020;163:106327.

doi: 10.1016/j.eplepsyres.2020.106327

Moseley BD, Otoul C, Staelens L, Stockis A. Pharmacokinetic interaction of brivaracetam on other antiepileptic drugs in adults with focal seizures: Pooled analysis of data from randomized clinical trials. Epilepsy Res. 2019;158:106218.

doi: 10.1016/j.eplepsyres.2019.106218

Brodie MJ, Fakhoury T, McDonough B, Colson A, Stockis A, Elmoufti S, Whitesides J. Brivaracetam-induced elevation of carbamazepine epoxide levels: A post-hoc analysis from the clinical development program. Epilepsy Res. 2018;145:55–62.

doi: 10.1016/j.eplepsyres.2018.06.002

Schoemaker R, Wade JR, Stockis A. Brivaracetam population pharmacokinetics and exposure-response modeling in adult subjects with partial-onset seizures. J Clin Pharmacol. 2016;56:1591–602.

doi: 10.1002/jcph.761

Moseley BD, Nicolas JM, Yeo KR, Chanteux H, Rosa M, Watanabe S, Kervyn S, Stockis A. The effect of brivaracetam on the pharmacokinetics of phenytoin: in vivo, in vitro, and modeling studies [abstract no. 2.207]. The American Epilepsy Society Annual Meeting; 2–6 December 2016: Houston, TX.

Nicolas JM, Chanteux H, Rosa M, Watanabe S, Stockis A. Effect of gemfibrozil on the metabolism of brivaracetam in vitro and in human subjects. Drug Metab Dispos. 2012;40:1466–72.

doi: 10.1124/dmd.112.045328

Lattanzi S, Cagnetti C, Foschi N, et al. Brivaracetam add-on for refractory focal epilepsy: a systematic review and meta-analysis. Neurology. 2016;86:1344–52.

doi: 10.1212/WNL.0000000000002545

Fisher RS, Cross JH, French JA, Higurashi N, Hirsch E, Jansen FE, et al. Operational classification of seizure types by the International League Against Epilepsy: position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58:522–30.

doi: 10.1111/epi.13670

Johannessen SI, Landmark CJ. Antiepileptic drug interactions - principles and clinical implications. Curr Neuropharmacol. 2010;8:254–67.

doi: 10.2174/157015910792246254

Lattanzi S, Cagnetti C, Foschi N, Provinciali L, Silvestrini M. Eslicarbazepine acetate as adjunctive treatment in partial-onset epilepsy. Acta Neurol Scand. 2018;137:29–32.

doi: 10.1111/ane.12803

Lattanzi S, De Maria G, Rosati E, Didato G, Chiesa V, Ranzato F, et al. Brivaracetam as add-on treatment in focal epilepsy: a real-world time-based analysis. Epilepsia. 2021;62:e1–6.

doi: 10.1111/epi.16797

Lattanzi S, Cagnetti C, Foschi N, Provinciali L, Silvestrini M. Lacosamide monotherapy for partial onset seizures. Seizure. 2015;27:71–4.

doi: 10.1016/j.seizure.2015.03.003

von Elm E, Altman DG, Egger M, et al. STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med. 2007;147:573–7.

doi: 10.7326/0003-4819-147-8-200710160-00010

Walker MC, Sander JW. Difficulties in extrapolating from clinical trial data to clinical practice: the case of antiepileptic drugs. Neurology. 1997;49:333–7.

doi: 10.1212/WNL.49.2.333

Adewusi J, Burness C, Ellawela S, Emsley H, Hughes R, Lawthom C, et al. Brivaracetam efficacy and tolerability in clinical practice: a UK-based retrospective multicenter service evaluation. Epilepsy Behav. 2020;106:106967.

doi: 10.1016/j.yebeh.2020.106967

Steinhoff BJ, Christensen J, Doherty CP, Majoie M, De Backer M, Hellot S, et al. Effectiveness and tolerability of adjunctive brivaracetam in patients with focal seizures: second interim analysis of 6-month data from a prospective observational study in Europe. Epilepsy Res. 2020;165:106329.

doi: 10.1016/j.eplepsyres.2020.106329

Menzler K, Mross P, Rosenow F, Schubert-Bast S, Willems LM, Zahnert F, et al. First clinical postmarketing experiences in the treatment of epilepsies with brivaracetam: a retrospective observational multicentre study. BMJ Open. 2019;9:030746.

doi: 10.1136/bmjopen-2019-030746

Villanueva V, López-González F, Mauri J, Rodriguez-Uranga J, Olivé-Gadea M, Montoya J, et al. BRIVA-LIFE study group: a multicenter retrospective study of the long-term use of brivaracetam in clinical practice. Acta Neurol Scand. 2018;139:360–8.

doi: 10.1111/ane.13059

Hirsch M, Hintz M, Specht A, Schulze-Bonhage A. Tolerability, efficacy and retention rate of brivaracetam in patients previously treated with levetiracetam: a monocenter retrospective outcome analysis. Seizure. 2018;61:98–103.

doi: 10.1016/j.seizure.2018.07.017

Zahnert F, Krause K, Immisch I, Habermehl L, Gorny I, Chmielewska I, et al. Brivaracetam in the treatment of patients with epilepsy—first clinical experiences. Front Neurol. 2018;9:38.

doi: 10.3389/fneur.2018.00038

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.

doi: 10.1016/j.seizure.2017.03.010

Steinig I, von Podewils F, M.ddel G, Bauer S, Klein KM, Paule E, et al. Postmarketing experience with brivaracetam in the treatment of epilepsies: a multicenter cohort study from Germany. Epilepsia. 2017;58:1208–16.

doi: 10.1111/epi.13768

Villanueva V, Holtkamp M, Delanty N, et al. Euro-Esli: a European audit of real-world use of eslicarbazepine acetate as a treatment for partial-onset seizures. J Neurol. 2017;264:2232–48.

doi: 10.1007/s00415-017-8618-5

Runge U, Arnold S, Brandt C, et al. A noninterventional study valuating the effectiveness and safety of lacosamide added to monotherapy in patients with epilepsy with partial-onset seizures in daily clinical practice: the VITOBA study. Epilepsia. 2015;56:1921–30.

doi: 10.1111/epi.13224

Schiller Y, Najjar Y. Quantifying the response to antiepileptic drugs. Effect of past treatment history. Neurology. 2008;70:54–65.

doi: 10.1212/01.wnl.0000286959.22040.6e

Asadi-Pooya AA, Sperling MR, Chung S, Klein P, Diaz A, Elmoufti S, et al. Efficacy and tolerability of adjunctive brivaracetam in patients with prior antiepileptic drug exposure: a post-hoc study. Epilepsy Res. 2017;131:70–5.

doi: 10.1016/j.eplepsyres.2017.02.007

Klitgaard H, Matagne A, Nicolas JM, Gillard M, Lamberty Y, De Ryck M, et al. Brivaracetam: rationale for discovery and preclinical profile of a selective SV2A ligand for epilepsy treatment. Epilepsia. 2016;57:538–48.

doi: 10.1111/epi.13340

Lattanzi S, Cagnetti C, Foschi N, Ciuffini R, Osanni E, Chiesa V, et al. Adjunctive perampanel in older patients with epilepsy: a multicenter study of clinical practice. Drugs Aging. 2021;38:603–10.

doi: 10.1007/s40266-021-00865-3

Wehner T, Mannan S, Turaga S, et al. Retention of perampanel in adults with pharmacoresistant epilepsy at a single tertiary care center. Epilepsy Behav. 2017;73:106–10.

doi: 10.1016/j.yebeh.2017.04.006

Villanueva V, López-Gomáriz E, López-Trigo J, et al. Rational polytherapy with lacosamide in clinical practice: results of a Spanish cohort analysis RELACOVA. Epilepsy Behav. 2012;23:298–304.

doi: 10.1016/j.yebeh.2011.11.026

Zaccara G, Gangemi PF, Cincotta M. Central nervous system adverse effects of new antiepileptic drugs: a meta-analysis of placebo-controlled studies. Seizure. 2008;17:405–21.

doi: 10.1016/j.seizure.2007.12.003

Deckers CLP, Czuczwar SJ, Hekster YA, Keyser A, Kubova H, Meinardi H, et al. Selection of antiepileptic drug polytherapy based on mechanisms of action: the evidence reviewed. Epilepsia. 2000;41:1364–74.

doi: 10.1111/j.1528-1157.2000.tb00111.x

Verrotti A, Lattanzi S, Brigo F, et al. Pharmacodynamic interactions of antiepileptic drugs: From bench to clinical practice. Epilepsy Behav. 2020;104(Pt A):106939.