{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:19:09Z","timestamp":1790194749603,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014114","name":"GW Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014114","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Lennox\u2013Gastaut syndrome (LGS) is an epileptic encephalopathy that is often treatment resistant. Efficacy and safety of add\u2010on cannabidiol (CBD) to treat seizures associated with LGS was demonstrated in two randomized controlled trials (RCTs). Patients who completed the RCTs were invited to enroll in this long\u2010term open\u2010label extension (OLE) trial, GWPCARE5 (NCT02224573). We present the final analysis of safety and efficacy outcomes from GWPCARE5.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients received plant\u2010derived highly purified CBD (Epidiolex in the United States; Epidyolex in the European Union; 100\u00a0mg\/ml oral solution), titrated to a target maintenance dose of 20\u00a0mg\/kg\/day over 2\u00a0weeks. Based on response and tolerability, CBD could then be reduced or increased up to 30\u00a0mg\/kg\/day.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 368\u00a0patients with LGS who completed the RCTs, 366\u00a0(99.5%) enrolled in this OLE. Median and mean treatment duration were 1090 and 826\u00a0days (range = 3\u20131421), respectively, with a mean modal dose of 24\u00a0mg\/kg\/day. Adverse events (AEs) occurred in 96% of patients, serious AEs in 42%, and AE\u2010related discontinuations in 12%. Common AEs were convulsion (39%), diarrhea (38%), pyrexia (34%), and somnolence (29%). Fifty\u2010five (15%) patients experienced liver transaminase elevations more than three\u00a0times the upper limit of normal; 40\u00a0(73%) were taking concomitant valproic acid. Median percent reductions from baseline ranged 48%\u201371% for drop seizures and 48%\u201368% for total seizures through 156\u00a0weeks. Across all 12\u2010week visit windows, 87% or more of patients\/caregivers reported improvement in the patient's overall condition on the Subject\/Caregiver Global Impression of Change scale.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Long\u2010term add\u2010on CBD treatment had a similar safety profile as in the original RCTs. Sustained reductions in drop and total seizure frequency were observed for up to 156\u00a0weeks, demonstrating long\u2010term benefits of CBD treatment for patients with LGS.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17000","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T10:04:43Z","timestamp":1626775483000},"page":"2228-2239","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["Long\u2010term safety and efficacy of add\u2010on cannabidiol in patients with Lennox\u2013Gastaut syndrome: Results of a long\u2010term open\u2010label extension trial"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9313-1541","authenticated-orcid":false,"given":"Anup D.","family":"Patel","sequence":"first","affiliation":[{"name":"Nationwide Children\u2019s Hospital Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Mazurkiewicz\u2010Be\u0142dzi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurology Medical University of Gda\u0144sk Gda\u0144sk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard F.","family":"Chin","sequence":"additional","affiliation":[{"name":"Muir Maxwell Epilepsy Centre University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Gil\u2010Nagel","sequence":"additional","affiliation":[{"name":"Neurology Department Ruber Internacional Hospital Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boudewijn","family":"Gunning","sequence":"additional","affiliation":[{"name":"Stichting Epilepsie Instellingen Nederland Zwolle the Netherlands"}],"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":"Department of Neurology Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Keck School of Medicine University of Southern California and Children\u2019s Hospital Los Angeles Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Scott Perry","sequence":"additional","affiliation":[{"name":"Cook Children\u2019s Medical Center Fort Worth Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3431-4713","authenticated-orcid":false,"given":"Elizabeth A.","family":"Thiele","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arie","family":"Weinstock","sequence":"additional","affiliation":[{"name":"Oishei Children\u2019s Hospital Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Dunayevich","sequence":"additional","affiliation":[{"name":"Greenwich Biosciences Carlsbad California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Checketts","sequence":"additional","affiliation":[{"name":"GW Research Ltd. Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0044-4632","authenticated-orcid":false,"given":"Orrin","family":"Devinsky","sequence":"additional","affiliation":[{"name":"New York University Comprehensive Epilepsy Center New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,20]]},"reference":[{"issue":"1","key":"e_1_2_9_2_1","first-page":"S3","article-title":"All children who experience epileptic falls do not necessarily have Lennox\u2010Gastaut syndrome\u2026 but many do","volume":"13","author":"Arzimanoglou A","year":"2011","journal-title":"Epileptic Disord"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00505"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.1966.tb06263.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2016.11.003"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611618"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1714631"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30136-3"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.0073"},{"key":"e_1_2_9_10_1","unstructured":"EPIDIOLEX\u00ae USPI.Highlights of prescribing information: EPIDIOLEX\u00ae (cannabidiol) oral solution. 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