Pediatric developmental epileptic encephalopathies treated with cenobamate: Real‐world outcomes across etiologies, syndromes, and seizure types

OBJECTIVE: This study was undertaken to assess cenobamate (CNB) effectiveness, tolerability, and dosing in pediatric developmental and epileptic encephalopathies (DEEs), testing prespecified hypotheses on response by syndrome, etiology, electroencephalographic pattern, seizure type, CNB dose (mg/kg/day), and concomitant medication. METHODS: A retrospective multicenter cohort of children (≤18 years old) with DEEs were treated with CNB at 17 Spanish hospitals. Primary outcomes were retention, response (≥50% reduction), and seizure freedom at 3, 6, and 12 months. Mixed-effects logistic and ordinal models were adjusted for age, syndrome, etiology, seizure type, and concomitant medication. RESULTS: Among 152 children (median age = 12 years), 27.6% had Lennox-Gastaut syndrome (LGS) and 58.6% unspecified DEE, with a median of 9 prior antiseizure medications. Retention was 88%, 90%, and 93% and responder rates 64%, 73%, and 79% at 3, 6, and 12 months; seizure freedom was 8%, 12%, and 18% (evaluable n = 152, 105, and 57 at 3, 6, and 12 months, respectively). LGS and other DEEs reached identical 12-month responder rates (both 79%), whereas Dravet syndrome showed limited sustained benefit. By etiology, structural cases had the highest 12-month responder rate (93% vs. 68% in nonstructural, p = .04), but no etiology was independently associated with response. By seizure type, responder rates were highest for tonic (81%) and bilateral tonic-clonic (76%) and lowest for absences (54%, adjusted odds ratio [OR] = .43, p = .032). Treatment-emergent seizure worsening occurred in 10.5%. Sodium channel blockers were the main risk factor for adverse events (OR = 2.10); 10.5% discontinued CNB due to adverse events. SIGNIFICANCE: CNB was associated with sustained effectiveness and acceptable tolerability across pediatric DEEs. Slow weight-based titration and proactive simplification of sodium channel blockers and clobazam may optimize benefit-risk.

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Journal
Epilepsia
Published
2026-08-28
DOI
https://doi.org/10.1002/epi.70460
Primary Topic
Epilepsy research and treatment
Type
article
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article

Pediatric developmental epileptic encephalopathies treated with cenobamate: Real‐world outcomes across etiologies, syndromes, and seizure types

Victor Miguel Soto Insuga, Salvador Ibáñez‐Micó, Andrea Sariego-Jamardo, Elena Miravet et al.
Epilepsia
Epilepsy research and treatment
article

Pediatric developmental epileptic encephalopathies treated with cenobamate: Real‐world outcomes across etiologies, syndromes, and seizure types

Victor Miguel Soto Insuga, Salvador Ibáñez‐Micó, Andrea Sariego-Jamardo, Elena Miravet, Eva Arias, António Gil‐Nagel, Dolors Casellas Vidal, Ángel Aledo‐Serrano, Jana Domínguez‐Carral, Patricia Smeyers, Ainhoa García-Ribes, Elena González Alguacil, Eulalia Turón‐Viñas, Adrián Valls Carbó, Nuria Lamagrande‐Casanova, David Conejo, Helena Alarcón Martínez, Gemma Aznar‐Laín, Susana Boronat, Irene Sánchez‐Miranda Román, Virginia Navarro Abia, Adrián García Ron, Juan José Garcı́a-Peñas, M.Á. Cabeza, Manuel Lorenzo‐Dieguez, María López López, María Jesús Martínez-González, Saray Rekarte‐García, Raquel Buenache‐Espartosa
article en

Abstract

OBJECTIVE: This study was undertaken to assess cenobamate (CNB) effectiveness, tolerability, and dosing in pediatric developmental and epileptic encephalopathies (DEEs), testing prespecified hypotheses on response by syndrome, etiology, electroencephalographic pattern, seizure type, CNB dose (mg/kg/day), and concomitant medication. METHODS: A retrospective multicenter cohort of children (≤18 years old) with DEEs were treated with CNB at 17 Spanish hospitals. Primary outcomes were retention, response (≥50% reduction), and seizure freedom at 3, 6, and 12 months. Mixed-effects logistic and ordinal models were adjusted for age, syndrome, etiology, seizure type, and concomitant medication. RESULTS: Among 152 children (median age = 12 years), 27.6% had Lennox-Gastaut syndrome (LGS) and 58.6% unspecified DEE, with a median of 9 prior antiseizure medications. Retention was 88%, 90%, and 93% and responder rates 64%, 73%, and 79% at 3, 6, and 12 months; seizure freedom was 8%, 12%, and 18% (evaluable n = 152, 105, and 57 at 3, 6, and 12 months, respectively). LGS and other DEEs reached identical 12-month responder rates (both 79%), whereas Dravet syndrome showed limited sustained benefit. By etiology, structural cases had the highest 12-month responder rate (93% vs. 68% in nonstructural, p = .04), but no etiology was independently associated with response. By seizure type, responder rates were highest for tonic (81%) and bilateral tonic-clonic (76%) and lowest for absences (54%, adjusted odds ratio [OR] = .43, p = .032). Treatment-emergent seizure worsening occurred in 10.5%. Sodium channel blockers were the main risk factor for adverse events (OR = 2.10); 10.5% discontinued CNB due to adverse events. SIGNIFICANCE: CNB was associated with sustained effectiveness and acceptable tolerability across pediatric DEEs. Slow weight-based titration and proactive simplification of sodium channel blockers and clobazam may optimize benefit-risk.

Epilepsia
Hospital Sant Joan de Déu Barcelona (ES), Neurosciences Institute (US), Hospital de Sant Pau (ES), Hospital Clínico San Carlos (ES), Hospital Universitari i Politècnic La Fe (ES), BioCruces Health research Institute (ES), Marqués de Valdecilla University Hospital (ES), Hospital Infantil Universitario Niño Jesús (ES), Hospital Universitario de Burgos (ES), Parc de Salut (ES), Santa Lucía University General Hospital (ES), Hospital Universitario Virgen de la Arrixaca (ES), Hospital Ruber Internacional (ES), Hospital Universitario Son Espases (ES), Hospital Universitario Virgen del Rocío (ES), Fundacion Centro De Investigacion De Enfermedades Neurologicas (ES), Hospital Universitari de Girona Doctor Josep Trueta (ES), Hospital Universitario Ramón y Cajal (ES)
Angelini Pharma
Peace, Justice and strong institutions
Openalex Percentile: Top 9%
Epilepsy research and treatment
DOIOpen Access PDFOpenAlex
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