Adjunctive cenobamate in people with focal onset seizures: Insights from the Italian Expanded Access Program

Roberta Roberti¹, Giovanni Assenza^{2

3}, Francesca Bisulli^{4

5}, Giovanni Boero⁶, Laura Canafoglia⁷, Valentina Chiesa⁸, Carlo Di Bonaventura⁹, Giancarlo Di Gennaro¹⁰, Maurizio Elia¹¹, Edoardo Ferlazzo^{12

13}, Alfonso Giordano¹⁴, Angela La Neve¹⁵, Claudio Liguori^{16

17}, Stefano Meletti^{18

19}, Francesca Felicia Operto¹, Nicola Pietrafusa²⁰, Monica Puligheddu^{21

22}, Patrizia Pulitano⁹, Eleonora Rosati²³, Ilaria Sammarra²⁴, Elena Tartara²⁵, Giampaolo Vatti²⁶, Flavio Villani²⁷; CNB EAP Italy Study Group; Emilio Russo¹, Simona Lattanzi²⁸

Collaborators, Affiliations

Affiliations

¹ Science of Health Department, Magna Graecia University, Catanzaro, Italy.
² Department of Medicine and Surgery, Research Unit of Neurology, Università Campus Bio-Medico, Rome, Italy.
³ Operative Research Unit of Neurology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.
⁴ Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
⁵ Istituto di Ricovero e Cura a Carattere Scientifico Istituto delle Scienze Neurologiche di Bologna, full member of the European Reference Network EpiCARE, Bologna, Italy.
⁶ Complex Structure of Neurology Hospital Santissima, Annunziata, Taranto, Italy.
⁷ Epilepsy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta, Milan, Italy.
⁸ Epilepsy Center, Azienda Socio Sanitaria Territoriale Santi Paolo Carlo, Milan, Italy.
⁹ Department of Human Neurosciences, Sapienza University, Rome, Italy.
¹⁰ Istituto di Ricovero e Cura a Carattere Scientifico NEUROMED, Pozzilli, Italy.
¹¹ Unit of Neurology and Clinical Neurophysiopathology, Oasi Research Institute, Istituto di Ricovero e Cura a Carattere Scientifico, Troina, Italy.
¹² Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.
¹³ Great Metropolitan Bianchi-Melacrino-Morelli Hospital, Reggio Calabria, Italy.
¹⁴ Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
¹⁵ Dipartimento di Biomedicina Traslazionale e Neuroscienze, University Hospital of Bari "A. Moro", Bari, Italy.
¹⁶ Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
¹⁷ Neurology Unit, University Hospital of Rome Tor Vergata, Rome, Italy.
¹⁸ Neurophysiology Unit and Epilepsy Center, Azienda Ospedaliero Universitaria, Modena, Italy.
¹⁹ Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena and Reggio Emilia, Italy.
²⁰ Clinical and Experimental Neurology, full member of European Reference Network EpiCARE, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.
²¹ Epilepsy Center, Neurology Unit, Azienda Ospedaliero Universitaria, Cagliari, Italy.
²² Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
²³ Neurology 2, Careggi University Hospital, Florence, Italy.
²⁴ Institute of Neurology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.
²⁵ Istituto di Ricovero e Cura a Carattere Scientifico Mondino Foundation, Epilepsy Center, full member of European Reference Network EpiCARE, Pavia, Italy.
²⁶ Unità Operativa Complessa Neurology and Clinical Neurophysiology, University Hospital of Siena, Siena, Italy.
²⁷ Division of Clinical Neurophysiology and Epilepsy Center, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Martino, Genoa, Italy.
²⁸ Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy.

PMID: 39140704
DOI: 10.1111/epi.18091

Multicenter Study

Adjunctive cenobamate in people with focal onset seizures: Insights from the Italian Expanded Access Program

Roberta Roberti et al. Epilepsia. 2024 Oct.

. 2024 Oct;65(10):2909-2922.

doi: 10.1111/epi.18091. Epub 2024 Aug 14.

Authors

Affiliations

¹ Science of Health Department, Magna Graecia University, Catanzaro, Italy.
² Department of Medicine and Surgery, Research Unit of Neurology, Università Campus Bio-Medico, Rome, Italy.
³ Operative Research Unit of Neurology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.
⁴ Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
⁵ Istituto di Ricovero e Cura a Carattere Scientifico Istituto delle Scienze Neurologiche di Bologna, full member of the European Reference Network EpiCARE, Bologna, Italy.
⁶ Complex Structure of Neurology Hospital Santissima, Annunziata, Taranto, Italy.
⁷ Epilepsy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta, Milan, Italy.
⁸ Epilepsy Center, Azienda Socio Sanitaria Territoriale Santi Paolo Carlo, Milan, Italy.
⁹ Department of Human Neurosciences, Sapienza University, Rome, Italy.
¹⁰ Istituto di Ricovero e Cura a Carattere Scientifico NEUROMED, Pozzilli, Italy.
¹¹ Unit of Neurology and Clinical Neurophysiopathology, Oasi Research Institute, Istituto di Ricovero e Cura a Carattere Scientifico, Troina, Italy.
¹² Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.
¹³ Great Metropolitan Bianchi-Melacrino-Morelli Hospital, Reggio Calabria, Italy.
¹⁴ Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
¹⁵ Dipartimento di Biomedicina Traslazionale e Neuroscienze, University Hospital of Bari "A. Moro", Bari, Italy.
¹⁶ Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
¹⁷ Neurology Unit, University Hospital of Rome Tor Vergata, Rome, Italy.
¹⁸ Neurophysiology Unit and Epilepsy Center, Azienda Ospedaliero Universitaria, Modena, Italy.
¹⁹ Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena and Reggio Emilia, Italy.
²⁰ Clinical and Experimental Neurology, full member of European Reference Network EpiCARE, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.
²¹ Epilepsy Center, Neurology Unit, Azienda Ospedaliero Universitaria, Cagliari, Italy.
²² Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
²³ Neurology 2, Careggi University Hospital, Florence, Italy.
²⁴ Institute of Neurology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.
²⁵ Istituto di Ricovero e Cura a Carattere Scientifico Mondino Foundation, Epilepsy Center, full member of European Reference Network EpiCARE, Pavia, Italy.
²⁶ Unità Operativa Complessa Neurology and Clinical Neurophysiology, University Hospital of Siena, Siena, Italy.
²⁷ Division of Clinical Neurophysiology and Epilepsy Center, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Martino, Genoa, Italy.
²⁸ Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy.

PMID: 39140704
DOI: 10.1111/epi.18091

Abstract

Objective: This study was undertaken to assess the effectiveness/tolerability of adjunctive cenobamate, variations in the load of concomitant antiseizure medications (ASMs) and predictors of clinical response in people with focal epilepsy.

Methods: This was a retrospective study at 21 centers participating in the Italian Expanded Access Program. Effectiveness outcomes included retention and responder rates (≥50% and 100% reduction in baseline seizure frequency). Tolerability/safety outcomes included the rate of treatment discontinuation due to adverse events (AEs) and their incidence. Total drug load was quantified as the number of concomitant ASMs and total defined daily dose (DDD). Concomitant ASMs were also classified according to their mechanism of action and pharmacokinetic interactions to perform explorative subgroup analyses.

Results: A total of 236 subjects with a median age of 38 (Q₁-Q₃ = 27-49) years were included. At 12 months, cenobamate retention rate was 78.8% and responders were 57.5%. The seizure freedom rates during the preceding 3 months were 9.8%, 12.2%, 16.3%, and 14.0% at 3, 6, 9, and 12 months. A higher percentage of responders was observed among subjects treated with clobazam, although the difference was not statistically significant. A total of 223 AEs were recorded in 133 of 236 participants, leading to cenobamate discontinuation in 8.5% cases. At 12 months, a reduction of one or two concomitant ASMs occurred in 42.6% and 4.3% of the subjects. The median total DDD of all concomitant ASMs decreased from 3.34 (Q₁-Q₃ = 2.50-4.47) at baseline to 2.50 (Q₁-Q₃ = 1.67-3.50) at 12 months (p < .001, median percentage reduction = 22.2%). The highest rates of cotreatment withdrawal and reductions in the DDD were observed for sodium channel blockers and γ-aminobutyric acidergic modulators (above all for those linked to pharmacokinetic interactions), and perampanel.

Significance: Adjunctive cenobamate was associated with a reduction in seizure frequency and in the burden of concomitant ASMs in adults with difficult-to-treat focal epilepsy. The type of ASM associated did not influence effectiveness except for a favorable trend with clobazam.

Keywords: antiseizure medication; cenobamate; clobazam; drug daily dose; epilepsy; focal seizures.

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References

REFERENCES

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Adjunctive cenobamate in people with focal onset seizures: Insights from the Italian Expanded Access Program

Collaborators

Affiliations

Adjunctive cenobamate in people with focal onset seizures: Insights from the Italian Expanded Access Program

Authors

Collaborators

Affiliations

Abstract

References

REFERENCES

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Research Materials