{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:21:10Z","timestamp":1790014870900,"version":"4.0.1"},"reference-count":14,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T00:00:00Z","timestamp":1629244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Add\u2010on cannabidiol (CBD) reduced seizures associated with Dravet syndrome (DS) in two randomized, double\u2010blind, placebo\u2010controlled trials: GWPCARE1\u00a0Part B (NCT02091375) and GWPCARE2 (NCT02224703). Patients who completed GWPCARE1\u00a0Part A (NCT02091206) or Part B, or GWPCARE2, were enrolled in a long\u2010term open\u2010label extension trial, GWPCARE5 (NCT02224573). We present an interim analysis of the safety, efficacy, and patient\u2010reported outcomes from GWPCARE5.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients received a pharmaceutical formulation of highly purified CBD in oral solution (100\u00a0mg\/ml), titrated from 2.5 to 20\u00a0mg\/kg\/day over a 2\u2010week period, added to their existing medications. Based on response and tolerance, CBD could be reduced or increased to 30\u00a0mg\/kg\/day.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 330 patients who completed the original randomized trials, 315 (95%) enrolled in this open\u2010label extension. Median treatment duration was 444\u00a0days (range = 18\u20131535), with a mean modal dose of 22\u00a0mg\/kg\/day; patients received a median of three\u00a0concomitant antiseizure medications. Adverse events (AEs) occurred in 97% patients (mild, 23%; moderate, 50%; severe, 25%). Commonly reported AEs were diarrhea (43%), pyrexia (39%), decreased appetite (31%), and somnolence (28%). Twenty\u2010eight (9%) patients discontinued due to AEs. Sixty\u2010nine (22%) patients had liver transaminase elevations &gt;3\u00a0\u00d7 upper limit of normal; 84% were on concomitant valproic acid. In patients from GWPCARE1\u00a0Part B and GWPCARE2, the median reduction from baseline in monthly seizure frequency assessed in 12\u2010week periods up to Week 156 was 45%\u201374% for convulsive seizures and 49%\u201384% for total seizures. Across all visit windows, \u226583% patients\/caregivers completing a Subject\/Caregiver Global Impression of Change scale reported improvement in overall condition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>We show that long\u2010term CBD treatment had an acceptable safety profile and led to sustained, clinically meaningful reductions in seizure frequency in patients with treatment\u2010resistant DS.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17036","type":"journal-article","created":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T12:34:48Z","timestamp":1629290088000},"page":"2505-2517","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["Add\u2010on cannabidiol in patients with Dravet syndrome: Results of a long\u2010term open\u2010label extension trial"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2311-2174","authenticated-orcid":false,"given":"Ingrid E.","family":"Scheffer","sequence":"first","affiliation":[{"name":"University of Melbourne, Austin Health Heidelberg Victoria Australia"}],"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":"Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0416-1015","authenticated-orcid":false,"given":"Ian","family":"Miller","sequence":"additional","affiliation":[{"name":"Nicklaus Children's Hospital Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rima","family":"Nabbout","sequence":"additional","affiliation":[{"name":"Necker Enfants Malades Hospital Imagine Institute University of Paris Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5058-0686","authenticated-orcid":false,"given":"Rocio","family":"Sanchez\u2010Carpintero","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Shiloh\u2010Malawsky","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Wong","sequence":"additional","affiliation":[{"name":"Wake Forest School of Medicine Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Zolnowska","sequence":"additional","affiliation":[{"name":"Medical Center Pleiades Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Checketts","sequence":"additional","affiliation":[{"name":"GW Research Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Dunayevich","sequence":"additional","affiliation":[{"name":"Greenwich Biosciences Carlsbad California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0044-4632","authenticated-orcid":false,"given":"Orrin","family":"Devinsky","sequence":"additional","affiliation":[{"name":"NYU Langone Comprehensive Epilepsy Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,18]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"International League Against Epilepsy.Dravet syndrome: clinical overview.2019.https:\/\/www.epilepsydiagnosis.org\/syndrome\/dravet\u2010overview.html. Accessed 22 Mar 2021."},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws151"},{"key":"e_1_2_9_4_1","first-page":"125","volume-title":"Epileptic syndromes in infancy, childhood and adolescence","author":"Dravet C","year":"2012"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2016.10.006"},{"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","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005254"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14628"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-017-0480-6"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2017.10.008"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13852"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03001.x"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.17036","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/epi.17036","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.17036","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T21:06:38Z","timestamp":1692997598000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.17036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,18]]},"references-count":14,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1111\/epi.17036"],"URL":"https:\/\/doi.org\/10.1111\/epi.17036","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,18]]},"assertion":[{"value":"2021-06-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}