{"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":1792242362647,"version":"4.4.0"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T00:00:00Z","timestamp":1716768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006546","name":"Angelini Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006546","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to explore the impact of co\u2010antiseizure medication (co\u2010ASM) optimization on the effectiveness and tolerability of adjunctive cenobamate (CNB) in patients with drug\u2010resistant epilepsy in a real\u2010world setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This unicentric, retrospective, observational study included adults with focal\u2010onset seizures who had received \u22652 previous ASMs. The main effectiveness endpoints included responder rates and seizure frequency reduction at 3, 6, and 12\u2010month visits. The number of co\u2010ASMs and defined daily dose (DDD) were analyzed at every visit. Safety endpoints included adverse drug reactions (ADRs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirty\u2010four patients with a median epilepsy duration of 22\u2009years and a median of 15.5 seizures\/month were analyzed. The median number of prior ASMs was 12, and the mean number of co\u2010ASMs was 2.9 (SD 1). There was a reduction in seizure frequency\/month from baseline to the last visit (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Between baseline and the end of the study, the mean number of co\u2010ASMs in the per\u2010protocol (PP) population was reduced from 2.9 to 1.6 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), and DDD was reduced from 3.6 to 1.4 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Sodium channel blockers (carbamazepine and lacosamide) and GABAergic drugs (clobazam) were the agents with the most significant reductions in DDD after 12\u2009months. The percentage of patients in the PP population with \u22653 co\u2010ASMs was reduced from 61.8% at baseline to 14.3% at 12\u2009months; 1 patient was receiving CNB as monotherapy at the last visit. At the last visit, 85.7% of the PP population were \u226550% responders, and 33.3% were seizure\u2010free. The percentage of patients with ADRs in the PP population was 71.9% at 3\u2009months and 52.3% at 12\u2009months.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Following rational polytherapy, optimization of co\u2010ASM management during CNB treatment allowed high seizure freedom rates despite meaningful reductions in co\u2010medication, while also achieving both good tolerability and patient satisfaction scores in a highly drug\u2010resistant population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>Many patients with epilepsy still have seizures, even after being treated with several different epilepsy drugs. In this study of 34 patients from a Spanish clinic, we show that the epilepsy drug cenobamate can reduce the number of seizures in these patients, even after many other epilepsy drugs have failed. We also show that patients treated with cenobamate can reduce the dose or even stop taking certain other epilepsy drugs. This allows them to simplify their treatment and reduce adverse effects while still keeping control of their epilepsy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.12959","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T05:18:53Z","timestamp":1716787133000},"page":"1345-1356","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Treatment simplification to optimize cenobamate effectiveness and tolerability: A real\u2010world retrospective study in Spain"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5354-1256","authenticated-orcid":false,"given":"Juan Jes\u00fas","family":"Rodr\u00edguez\u2010Uranga","sequence":"first","affiliation":[{"name":"Centro de Neurolog\u00eda Avanzada Unidad de Epilepsia  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Mar\u00eda","family":"S\u00e1nchez\u2010Caro","sequence":"additional","affiliation":[{"name":"Centro de Neurolog\u00eda Avanzada Unidad de Epilepsia  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshan","family":"Hariramani\u00a0Ramchandani","sequence":"additional","affiliation":[{"name":"Centro de Neurolog\u00eda Avanzada Unidad de Epilepsia  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263\u2010021\u201000827\u20108"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/JAMANEUROL.2017.3949"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/J.1528\u20101167.2009.02397.X"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/EPI.13604"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2020.107261"},{"key":"e_1_2_9_7_1","unstructured":"The European Medicines Agency \u2010 EMA.Ontozry Summary of Product Characteristics. Available from:https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/ontozry\u2010epar\u2010product\u2010information_en.pdf. Accessed February 2024."},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.05.007"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173117"},{"key":"e_1_2_9_10_1","unstructured":"U.S. Food and Drug Administration.XCOPRI. Highlights of Prescribing Information\u2010SmPC. Available from:https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/212839s000lbl.pdf. 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