{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:42:20Z","timestamp":1788385340738,"version":"build-2803163510"},"reference-count":19,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T00:00:00Z","timestamp":1635120000000},"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":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Epilepsy is highly prevalent in patients with tuberous sclerosis complex (TSC). Everolimus showed higher efficacy than placebo for seizures in the primary analysis of the EXIST\u20103 study. Here, we present the long\u2010term outcomes of everolimus at the end of the postextension phase (PEP; data cutoff date: October 25, 2017).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>After completion of the extension phase, patients were invited to continue everolimus in the PEP with everolimus (targeted trough concentration = 5\u201315\u00a0ng\/ml, investigator\u2010judged). Efficacy assessments included changes in seizure status during the PEP collected at 12\u2010week intervals as parent\/caregiver\u2010reported data through a structured questionnaire.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 361 patients, 343 entered the extension phase and 249 entered the PEP. After 12\u00a0weeks in the PEP, 18.9% (46\/244) of patients were seizure\u2010free since the last visit of the extension phase and 64.8% (158\/244) had a stable\/improved seizure status. At 24\u00a0weeks, the corresponding percentages were 18.2% (42\/231) and 64.5% (149\/231). Among 244 patients, the response rate was 32.8% (80\/244) during the 12\u2010week maintenance period of the core phase and 63.9% (156\/244) at the end of the extension phase. Of the 149 responders at the end of the extension phase, 70.5% were seizure\u2010free or had stable\/improved seizure status. Long\u2010term efficacy data showed persistent responses were observed in 183 of 361 patients (50.7%); 63.9% of these patients had a response that lasted at least 48\u00a0weeks. The most frequent Grade 3\u20134 adverse events (\u22652% incidence) reported throughout the study were pneumonia, status epilepticus, seizure, stomatitis, neutropenia, and gastroenteritis. Four patients died during the study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>The final analysis of EXIST\u20103 demonstrated the sustained efficacy of everolimus as adjunctive therapy in patients with TSC\u2010associated treatment\u2010refractory seizures, with a tolerable safety profile.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17099","type":"journal-article","created":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T08:29:27Z","timestamp":1635150567000},"page":"3029-3041","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Adjunctive everolimus therapy for tuberous sclerosis complex\u2010associated refractory seizures: Results from the postextension phase of EXIST\u20103"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6039-1339","authenticated-orcid":false,"given":"David N.","family":"Franz","sequence":"first","affiliation":[{"name":"Department of Neurology Cincinnati Children's Hospital Medical Center Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Lawson","sequence":"additional","affiliation":[{"name":"Tuberous Sclerosis Multidisciplinary Management Clinic Sydney Children's Hospital Randwick New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuhal","family":"Yapici","sequence":"additional","affiliation":[{"name":"Division of Child Neurology Department of Neurology Istanbul Faculty of Medicine Istanbul University Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Ikeda","sequence":"additional","affiliation":[{"name":"National Epilepsy Center Shizuoka Institute of Epilepsy and Neurological Disorders Shizuoka 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J.","family":"Dlugos","sequence":"additional","affiliation":[{"name":"Department of Neurology and Pediatrics Children's Hospital of Philadelphia Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Herbst","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Severine","family":"Peyrard","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals SAS Rueil\u2010Malmaison France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Pelov","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation East Hanover New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2242-8027","authenticated-orcid":false,"given":"Jacqueline 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