PMID- 37149853 OWN - NLM STAT- MEDLINE DCOM- 20230904 LR - 20230905 IS - 2470-9239 (Electronic) IS - 2470-9239 (Linking) VI - 8 IP - 3 DP - 2023 Sep TI - Real-world safety and effectiveness of cenobamate in patients with focal onset seizures: Outcomes from an Expanded Access Program. PG - 918-929 LID - 10.1002/epi4.12757 [doi] AB - OBJECTIVE: This study investigated early, real-world outcomes with cenobamate (CNB) in a large series of patients with highly drug-resistant epilepsy within a Spanish Expanded Access Program (EAP). METHOD: This was a multicenter, retrospective, observational study in 14 hospitals. Inclusion criteria were age >/=18 years, focal seizures, and EAP authorization. Data were sourced from patient clinical records. Primary effectiveness endpoints included reductions (100%, >/=90%, >/=75%, and >/=50%) or worsening in seizure frequency at 3-, 6-, and 12-month visits and at the last visit. Safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation. RESULTS: The study included 170 patients. At baseline, median epilepsy duration was 26 years and median number of seizures/month was 11.3. The median number of prior antiseizure medications (ASMs) and concomitant ASMs were 12 and 3, respectively. Mean CNB dosages/day were 176 mg, 200 mg, and 250 mg at 3, 6, and 12 months. Retention rates were 98.2%, 94.5%, and 87% at 3, 6, and 12 months. At last available visit, the rate of seizure freedom was 13.3%; >/=90%, >/=75%, and >/=50% responder rates were 27.9%, 45.5%, and 63%, respectively. There was a significant reduction in the number of seizures per month (mean: 44.6%; median: 66.7%) between baseline and the last visit (P < 0.001). Responses were maintained regardless of the number of prior or concomitant ASMs. The number of concomitant ASMs was reduced in 44.7% of patients. The cumulative percentage of patients with AEs and AEs leading to discontinuation were 68.2% and 3.5% at 3 months, 74.1% and 4.1% at 6 months, and 74.1% and 4.1% at 12 months. The most frequent AEs were somnolence and dizziness. SIGNIFICANCE: In this highly refractory population, CNB showed a high response regardless of prior and concomitant ASMs. AEs were frequent but mostly mild-to-moderate, and few led to discontinuation. CI - (c) 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy. FAU - Villanueva, Vicente AU - Villanueva V AUID- ORCID: 0000-0003-2080-8042 AD - Hospital Universitario y Politecnico La Fe, Member of EPICARE, Valencia, Spain. FAU - Santos-Carrasco, Daniel AU - Santos-Carrasco D AD - Centro Neurologia Avanzada, Sevilla, Spain. AD - Departamento de Psicologia Experimental, Universidad de Sevilla, Sevilla, Spain. FAU - Cabezudo-Garcia, Pablo AU - Cabezudo-Garcia P AUID- ORCID: 0000-0002-6421-5348 AD - Hospital Regional Universitario Malaga, Malaga, Spain. FAU - Gomez-Ibanez, Asier AU - Gomez-Ibanez A AD - Clinica Universidad de Navarra, Madrid, Spain. FAU - Garces, Mercedes AU - Garces M AD - Hospital Universitario y Politecnico La Fe, Member of EPICARE, Valencia, Spain. FAU - Serrano-Castro, Pedro AU - Serrano-Castro P AUID- ORCID: 0000-0002-3414-2707 AD - Hospital Regional Universitario Malaga, Malaga, Spain. FAU - Castro-Vilanova, Maria D AU - Castro-Vilanova MD AD - Complejo Hospitalario Universitario Vigo, Vigo, Spain. FAU - Sayas, Debora AU - Sayas D AD - Hospital Universitario y Politecnico La Fe, Member of EPICARE, Valencia, Spain. FAU - Lopez-Gonzalez, Francisco J AU - Lopez-Gonzalez FJ AD - Complejo Hospitalario Universitario Santiago, Santiago de Compostela, Spain. FAU - Rodriguez-Osorio, Xiana AU - Rodriguez-Osorio X AD - Complejo Hospitalario Universitario Santiago, Santiago de Compostela, Spain. FAU - Torres-Gaona, Gustavo AU - Torres-Gaona G AD - Clinica Corachan, Barcelona, Spain. FAU - Saiz-Diaz, Rosa A AU - Saiz-Diaz RA AD - Hospital Universitario, Madrid, Spain. FAU - Hampel, Kevin G AU - Hampel KG AUID- ORCID: 0000-0003-3582-060X AD - Hospital Universitario y Politecnico La Fe, Member of EPICARE, Valencia, Spain. FAU - Martinez-Ferri, Meritxell AU - Martinez-Ferri M AD - Hospital Universitari Mutua Terrassa, Terrassa, Spain. FAU - Aguilar-Amat, Maria J AU - Aguilar-Amat MJ AD - Instituto de Investigacion Sanitaria del Hospital Universitario La Paz-IdiPAZ, Madrid, Spain. FAU - Mercedes-Alvarez, Blanca AU - Mercedes-Alvarez B AUID- ORCID: 0000-0003-4374-5574 AD - Hospital Universitario Gregorio Maranon, Madrid, Spain. FAU - Garcia-Morales, Vanessa AU - Garcia-Morales V AD - Hospital Universitario Alava, Alava, Spain. FAU - Del Villar-Igea, Ana AU - Del Villar-Igea A AD - Consorcio Hospitalario Provincial de Castellon, Castellon, Spain. FAU - Massot-Tarrus, Andreu AU - Massot-Tarrus A AUID- ORCID: 0000-0002-9864-8766 AD - Hospital Universitari Mutua Terrassa, Terrassa, Spain. FAU - Rodriguez-Uranga, Juan J AU - Rodriguez-Uranga JJ AD - Centro Neurologia Avanzada, Sevilla, Spain. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20230521 PL - United States TA - Epilepsia Open JT - Epilepsia open JID - 101692036 RN - P85X70RZWS (Cenobamate) RN - 0 (Anticonvulsants) SB - IM MH - Humans MH - Adolescent MH - *Anticonvulsants/adverse effects MH - Retrospective Studies MH - Treatment Outcome MH - Seizures/drug therapy MH - *Epilepsy/drug therapy PMC - PMC10472366 OTO - NOTNLM OT - antiseizure medication OT - epilepsy OT - refractory EDAT- 2023/05/07 18:41 MHDA- 2023/09/04 06:43 PMCR- 2023/05/21 CRDT- 2023/05/07 12:32 PHST- 2023/03/17 00:00 [received] PHST- 2023/05/03 00:00 [accepted] PHST- 2023/09/04 06:43 [medline] PHST- 2023/05/07 18:41 [pubmed] PHST- 2023/05/07 12:32 [entrez] PHST- 2023/05/21 00:00 [pmc-release] AID - EPI412757 [pii] AID - 10.1002/epi4.12757 [doi] PST - ppublish SO - Epilepsia Open. 2023 Sep;8(3):918-929. doi: 10.1002/epi4.12757. Epub 2023 May 21.