Pediatric developmental epileptic encephalopathies treated with cenobamate: Real‐world outcomes across etiologies, syndromes, and seizure types
Year: 2026
Type: article
Study design: Observational Study
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.
Source: Epilepsia
DOI: 10.1002/epi.70460
Authors: Ángel Aledo‐Serrano, Adrián Valls‐Carbó, Elena González‐Alguacil, Juan José García‐Peñas, Andrea Sariego Jamardo, Gemma Aznar‐Laín, Salvador Ibáñez‐Micó, Helena Alarcón Martínez, Raquel Buenache‐Espartosa, Saray Rekarte‐García, Manuel Lorenzo‐Dieguez, Jana Domínguez‐Carral, María López López, Ainhoa García‐Ribes, María Jesús Martínez‐González, Eva Arias, Adrián García‐Ron, Susana Boronat, Eulalia Turón Viñas, Dolors Casellas, Virginia Navarro, David Conejo, Elena Miravet, Antonio Gil‐Nagel Rein, Irene Sánchez‐Miranda Román, Nuria Lamagrande, María Muñoz Cabeza, Patricia Smeyers, Víctor Soto‐Insuga
Institutions: Hospital Blua Sanitas Valdebebas, Sanitas (Spain), Hospital Infantil Universitario Niño Jesús, Marqués de Valdecilla University Hospital, Parc de Salut, Hospital Universitario Virgen de la Arrixaca, Hospital Universitario Ramón y Cajal, Hospital Sant Joan de Déu Barcelona, Universitat de Barcelona, Santa Lucía University General Hospital, BioCruces Health research Institute, Hospital de Cruces, Hospital Clínico San Carlos, Hospital de Sant Pau, Hospital Universitari de Girona Doctor Josep Trueta, Hospital Universitario de Burgos, Hospital Universitario Son Espases, Hospital Ruber Internacional, Hospital Universitario Virgen del Rocío, Hospital Universitari i Politècnic La Fe
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: Angelini Pharma
OpenAlex ID: W7204539288