Beyond seizure control: Non–seizure‐related outcomes in focal‐onset epilepsy treated with adjunctive cenobamate. Third interim results from the BLESS study

OBJECTIVE: Cenobamate is approved for treatment of focal seizures in adults, but evidence on non-seizure outcomes remains limited. This interim statistical analysis of the cenoBamate in aduLts with focal-onsEt SeizureS (BLESS) study evaluated patient- and clinician-reported outcomes for up to 52 weeks of cenobamate treatment. METHODS: BLESS is an observational, retrospective and prospective cohort study designed to assess the real-world effectiveness and safety of adjunctive cenobamate in adults with uncontrolled focal epilepsy. Outcomes included patient-reported health-related quality of life, sleepiness, anxiety, mood, and global functioning assessed by the 31-item Quality of Life in Epilepsy Inventory (QOLIE-31), the Epworth Sleepiness Scale (ESS), the Hospital Anxiety and Depression Scale (HADS), and the Clinical Global Impression (CGI) scales. RESULTS: A total of 377 participants were included. Among subjects with an available score at 12 (n = 197), 24 (n = 363), and 52 (n = 197) weeks, the QOLIE-31 overall score remained stable. Subjects with sustained seizure freedom at 24 weeks showed a significantly higher QOLIE-31 overall score (p = 0.041) and cognitive functioning scores (p = 0.019) compared with those who did not reach sustained seizure freedom. More than 68% of participants had normal daytime sleepiness (total ESS score 0-10) and did not report anxiety or depression according to the HADS-A and HADS-D subscales at each assessment up to 52 weeks. Clinicians rated 91.3% (n/N = 179/196), 85.7% (n/N = 300/350), and 87.4% (n/N = 167/191) of subjects as improved for their overall condition from the initiation of treatment according to the CGI-Improvement or change (CGI-I) scale, at 12, 24, and 52 weeks. SIGNIFICANCE: This interim analysis provides preliminary descriptive evidence on non-seizure outcomes in subjects treated with adjunctive cenobamate. Patient-reported outcome scores remained stable from 12 weeks and up to 52 weeks, consistent with preserved overall well-being. Better quality of life and cognitive functioning emerged in sustained vs non-sustained seizure-free participants. Based on clinicians' judgment, there was signal of improvement in overall condition compared to baseline in most treated subjects throughout the observation period. STUDY REGISTRATION: NCT05859854.

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Publication Details

Journal
Epilepsia
Published
2026-10-15
DOI
https://doi.org/10.1002/epi.70501
Primary Topic
Epilepsy research and treatment
Type
article
Field-Weighted Citation Impact
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article

Beyond seizure control: Non–seizure‐related outcomes in focal‐onset epilepsy treated with adjunctive cenobamate. Third interim results from the BLESS study

Luigi Sicurella, Luciana Tramacere, Angela La Neve, Monica Puligheddu et al.
Epilepsia
Epilepsy research and treatment
article

Beyond seizure control: Non–seizure‐related outcomes in focal‐onset epilepsy treated with adjunctive cenobamate. Third interim results from the BLESS study

Luigi Sicurella, Luciana Tramacere, Angela La Neve, Monica Puligheddu, Elena Tartara, Gionata Strigaro, Patrizia Pulitano, Francesca Bisulli, Loretta Giuliano, Michela Cecconi, Stefano Luca Sensi, Daniele Andreis, Giovanni Falcicchio, Alfonso Giordano, Alessandra Di Liberto, Simona Lattanzi, Gabriele Camattari, Lucia Simoni, Simone Beretta, Massimo Gangitano, Daniela Audenino, Anna Elisabetta Vaudano, Fedele Dono, Gionathan Mazza, Tiziano Zanoni, Rosita Galli, David Stokelj, Maria Pia Pasolini, Antonio Gambardella, Alfredo D’Aniello, Roberto De Simone, Giuseppe d’Orsi, Chiara Pizzanelli, Michela Procaccini, Edoardo Ferlazzo, Pietro Penza, Catello Vollono, Giovanni Assenza, Vincenzo Andreone, Giada Pauletto, Giovanni Boero, Mariangela Panebianco, Angelo Labate, Paolo Bonanni, Andrea Novara, Carlo Di Bonaventura, Claudio Liguori, Giancarlo Di Gennaro, Maurizio Elia, Filippo Dainese, Marianna Pezzella, Stefano Quadri, Pietro Pignatta, Nicoletta Foschi, Giampaolo Vatti, Giovanni De Maria, Elisa Fallica, Federica Ranzato, Maria Teresa Di Claudio, Valentina Villano, Monica Santo Sabato, the BLESS Study Group
article en

Abstract

OBJECTIVE: Cenobamate is approved for treatment of focal seizures in adults, but evidence on non-seizure outcomes remains limited. This interim statistical analysis of the cenoBamate in aduLts with focal-onsEt SeizureS (BLESS) study evaluated patient- and clinician-reported outcomes for up to 52 weeks of cenobamate treatment. METHODS: BLESS is an observational, retrospective and prospective cohort study designed to assess the real-world effectiveness and safety of adjunctive cenobamate in adults with uncontrolled focal epilepsy. Outcomes included patient-reported health-related quality of life, sleepiness, anxiety, mood, and global functioning assessed by the 31-item Quality of Life in Epilepsy Inventory (QOLIE-31), the Epworth Sleepiness Scale (ESS), the Hospital Anxiety and Depression Scale (HADS), and the Clinical Global Impression (CGI) scales. RESULTS: A total of 377 participants were included. Among subjects with an available score at 12 (n = 197), 24 (n = 363), and 52 (n = 197) weeks, the QOLIE-31 overall score remained stable. Subjects with sustained seizure freedom at 24 weeks showed a significantly higher QOLIE-31 overall score (p = 0.041) and cognitive functioning scores (p = 0.019) compared with those who did not reach sustained seizure freedom. More than 68% of participants had normal daytime sleepiness (total ESS score 0-10) and did not report anxiety or depression according to the HADS-A and HADS-D subscales at each assessment up to 52 weeks. Clinicians rated 91.3% (n/N = 179/196), 85.7% (n/N = 300/350), and 87.4% (n/N = 167/191) of subjects as improved for their overall condition from the initiation of treatment according to the CGI-Improvement or change (CGI-I) scale, at 12, 24, and 52 weeks. SIGNIFICANCE: This interim analysis provides preliminary descriptive evidence on non-seizure outcomes in subjects treated with adjunctive cenobamate. Patient-reported outcome scores remained stable from 12 weeks and up to 52 weeks, consistent with preserved overall well-being. Better quality of life and cognitive functioning emerged in sustained vs non-sustained seizure-free participants. Based on clinicians' judgment, there was signal of improvement in overall condition compared to baseline in most treated subjects throughout the observation period. STUDY REGISTRATION: NCT05859854.

Epilepsia
University of Pisa (IT), University of Messina (IT), University of Rome Tor Vergata (IT), University of Verona (IT), University of Modena and Reggio Emilia (IT), Marche Polytechnic University (IT), Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), University of Cagliari (IT), Università degli Studi di Enna Kore (IT), Casa Sollievo della Sofferenza (IT), Policlinico Umberto I (IT), Agostino Gemelli University Polyclinic (IT), IQVIA (United Kingdom) (GB), Istituto Neurologico Mediterraneo (IT), Ente Ospedaliero Ospedali Galliera (IT), Magna Graecia University (IT), University of Chieti-Pescara (IT), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), Ospedale Antonio Cardarelli (IT), Azienda Ospedaliera di Perugia (IT), Oasi Maria SS (IT), Azienda Unita' Sanitaria Locale Di Modena (IT), Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari (IT), Fondazione Ricerca Molinette (IT), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Nuovo Ospedale San Giovanni di Dio (IT), Ospedale Garibaldi (IT), Ospedale Papa Giovanni XXIII (IT), Azienda Ospedaliero Universitaria Ospedali Riuniti (IT), Azienda Ospedaliero-Universitaria di Modena (IT), Ospedale Humanitas Gradenigo (IT), Azienda Ospedaliero Universitaria Maggiore della Carita (IT), Istituto delle Scienze Neurologiche di Bologna (IT), Azienda Ospedaliero-Universitaria Cagliari (IT), Ospedale Santa Maria della Misericordia di Udine (IT), Arcispedale Sant'Anna (IT), Azienda Ospedaliera Universitaria Università degli Studi della Campania Luigi Vanvitelli (IT), Azienda Ospedaliero-Universitaria "Renato Dulbecco" (IT), Ospedali Riuniti San Giovanni di Dio e Ruggi d'Aragona (IT), Azienda Ospedaliera Universitaria Senese (IT), Ospedale San Donato (IT), Campus Bio Medico University Hospital (IT), Azienda Ospedaliera Ospedale Maggiore (IT), Azienda Ospedale - Università Padova (IT), Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone" di Palermo (IT), Fondazione Poliambulanza Istituto Ospedaliero (IT), Ospedale SS. Annunziata (IT), Ospedale Maggiore di Lodi (IT), Metropolitan Hospital (GR), IRCCS Eugenio Medea (IT), Ospedale San Bortolo (IT), Ospedale Vito Fazzi (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Angelini Pharma (Italy) (IT), Azienda Ospedaliero Universitaria Policlinico "G.Rodolico - San Marco" (IT), Azienda sanitaria universitaria Giuliano Isontina (IT), University of Milano-Bicocca (IT), University of Bologna (IT)
Angelini Pharma
Good health and well-being
Openalex Percentile: Top 13%
Epilepsy research and treatment
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