{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T13:06:02Z","timestamp":1792242362387,"version":"4.4.0"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>We determined retention on open\u2010label cenobamate therapy in the clinical development program to assess the long\u2010term efficacy and tolerability of adjunctive cenobamate in individuals with uncontrolled focal seizures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from two randomized, controlled cenobamate studies and one open\u2010label safety and pharmacokinetic study were pooled. Based on the percentage of participants remaining on treatment, retention rates were estimated using Kaplan\u2010Meier survival analyses. We performed two additional analyses to assess factors contributing to retention, stratifying a robust data set (through 2\u00a0years) by cenobamate modal dose and frequently used concomitant anti\u2010seizure medications. Cenobamate discontinuations and treatment\u2010emergent adverse events were summarized.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Data from 1844 participants were pooled: 149 from a single\u2010dose randomized trial, 355 from a multi\u2010dose randomized trial, and 1340 from an open\u2010label safety and pharmacokinetic study. Most participants from randomized trials continued in open\u2010label extensions, and pooled data represent &gt;95% of participants exposed to cenobamate. Baseline characteristics and disease and treatment histories were similar across studies. Median duration of cenobamate exposure was 34\u00a0months, with a median modal dose of 200\u00a0mg\/day. Kaplan\u2010Meier estimates of cumulative cenobamate retention rates were 80% at 1\u00a0year and 72% at 2\u00a0years. Once participants reached the maintenance phase, retention rates were consistently high in participants receiving \u2265100\u00a0mg\/day cenobamate, and concomitant anti\u2010seizure medications did not affect long\u2010term retention. By 2\u00a0years, 535 (29%) had actually discontinued cenobamate; the most common reasons for discontinuation were adverse events (37.6%), withdrawal of consent (21.1%), and other (16.8%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Treatment retention rates provide a proxy measure for long\u2010term efficacy, safety, tolerability, and adherence. The consistently high retention rates we found suggest that cenobamate may be an effective and well\u2010tolerated new treatment option for people with drug\u2010resistant focal seizures.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17134","type":"journal-article","created":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:26:45Z","timestamp":1637713605000},"page":"139-149","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Long\u2010term individual retention with cenobamate in adults with focal seizures: Pooled data from the clinical development program"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6041-9661","authenticated-orcid":false,"given":"Josemir W.","family":"Sander","sequence":"first","affiliation":[{"name":"NIHR University College London Hospitals Biomedical Research Centre UCL Queen Square Institute of Neurology  London UK"},{"name":"Chalfont Centre for Epilepsy  Chalfont St. Peter UK"},{"name":"Stichting Epilepsie Instellingen Nederland (SEIN)  Heemstede The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9504-3980","authenticated-orcid":false,"given":"William E.","family":"Rosenfeld","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Care Center for Children and Adults  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1681-6744","authenticated-orcid":false,"given":"Jonathan J.","family":"Halford","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Center Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5995-5862","authenticated-orcid":false,"given":"Bernhard J.","family":"Steinhoff","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neurophysiology Kork Epilepsy Center  Kehl\u2010Kork Germany"},{"name":"Clinic for Neurology and Neurophysiology  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Biton","sequence":"additional","affiliation":[{"name":"Arkansas Epilepsy Program  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Toledo","sequence":"additional","affiliation":[{"name":"Epilepsy Unit Neurology Department Hospital Universitari Vall d'Hebron  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,23]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"Ontozry (initial authorisation)","author":"European Medicines Agency","year":"2021"},{"key":"e_1_2_10_3_1","volume-title":"XCOPRI\u00ae (cenobamate tablets), for oral use, CV [prescribing information]","author":"SK Life Science, Inc","year":"2021"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.05.007"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173117"},{"issue":"3","key":"e_1_2_10_6_1","first-page":"741","article-title":"Effect of stimulus intensity on the profile of anticonvulsant activity of phenytoin, ethosuximide and valproate","volume":"232","author":"Piredda SG","year":"1985","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1997.tb04523.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12657"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1535-7511.2007.00156.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2004.03400.x"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009530"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30399-0"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16525"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2007.01.004"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2005.064626"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.12.1772"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2010.04.001"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2005.00505.x"},{"key":"e_1_2_10_19_1","unstructured":"European Medicines Agency.Guideline on clinical investigation of medicinal products in the treatment of epileptic disorders.2018; Available at:https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/draft\u2010guideline\u2010clinical\u2010investigation\u2010medicinal\u2010products\u2010treatment\u2010epileptic\u2010disorders\u2010revision\u20103_en.pdf. 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