Efficacy and safety of everolimus for patients with focal cortical dysplasia type 2
Abstract Objective This study aimed to evaluate the effectiveness and safety of everolimus in treating seizures associated with focal cortical dysplasia type 2 (FCD 2). Methods A prospective, crossover, placebo‐controlled clinical trial (ClinicalTrials.gov: NCT03198949) enrolled patients aged 4–40 y...
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Wiley
2025-02-01
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| Series: | Epilepsia Open |
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| Online Access: | https://doi.org/10.1002/epi4.13104 |
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| author | Se Hee Kim Hoon‐Chul Kang Yun Ho Roh Jongsung Hahn Kyung Lok Min Seok‐Jin Lee Donghwa Yang Han Som Choi Soyoung Park Jeong Ho Lee Sang‐Guk Lee Se Hoon Kim Min Jung Chang Heung Dong Kim |
| author_facet | Se Hee Kim Hoon‐Chul Kang Yun Ho Roh Jongsung Hahn Kyung Lok Min Seok‐Jin Lee Donghwa Yang Han Som Choi Soyoung Park Jeong Ho Lee Sang‐Guk Lee Se Hoon Kim Min Jung Chang Heung Dong Kim |
| author_sort | Se Hee Kim |
| collection | DOAJ |
| description | Abstract Objective This study aimed to evaluate the effectiveness and safety of everolimus in treating seizures associated with focal cortical dysplasia type 2 (FCD 2). Methods A prospective, crossover, placebo‐controlled clinical trial (ClinicalTrials.gov: NCT03198949) enrolled patients aged 4–40 years with pathologically confirmed FCD 2 and a history of ≥3 seizures per month for two out of the 3 months prior to screening. The trial included a 4‐week baseline phase, two 12‐week core phases, and a 29‐week extension phase. Patients received everolimus or placebo in a blinded manner during core phase I, with crossover to the alternate treatment in core phase II. Everolimus dosage started at 4.5 mg/m2/day, targeting a serum level of 5–15 ng/mL. The primary outcome was the proportion of patients achieving ≥50% seizure reduction from baseline in the last month of each core phase. Safety profiles were compared between groups. Results Between May 11, 2017, and June 19, 2020, 21 patients completed the core phases. There was no significant difference in the primary outcome between everolimus and placebo groups (24% vs. 19%, p = 0.66). The patients showed varied responses. Three patients with a pathogenic variant in the MTOR gene or no genetic abnormalities achieved seizure freedom with everolimus in the last month of the core phase, while none of the patients with variants in other genes did. Adverse events, such as mucositis or skin ulceration, were more common with everolimus (19/21 vs. 7/21, p < 0.001). All adverse events resolved without study drug withdrawal. Significance Everolimus treatment for 12 weeks did not show overall superiority in reducing seizures compared to placebo. However, it showed promise, mostly in patients with a pathogenic variant in the MTOR gene, highlighting the need for further research into patient‐specific factors influencing treatment response. The everolimus treatment was generally safe and manageable. Plain Language Summary This study tested everolimus for reducing seizures in patients with focal cortical dysplasia type 2 (FCD 2). While the drug was not more effective than a placebo for most, few patients showed better results, with some becoming seizure‐free. Side effects were common but manageable. More research is needed to understand why certain patients respond better to treatment. |
| format | Article |
| id | doaj-art-25d605650d7f4195b9046ae6e1211b0a |
| institution | Kabale University |
| issn | 2470-9239 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Epilepsia Open |
| spelling | doaj-art-25d605650d7f4195b9046ae6e1211b0a2025-02-07T09:12:45ZengWileyEpilepsia Open2470-92392025-02-0110124325710.1002/epi4.13104Efficacy and safety of everolimus for patients with focal cortical dysplasia type 2Se Hee Kim0Hoon‐Chul Kang1Yun Ho Roh2Jongsung Hahn3Kyung Lok Min4Seok‐Jin Lee5Donghwa Yang6Han Som Choi7Soyoung Park8Jeong Ho Lee9Sang‐Guk Lee10Se Hoon Kim11Min Jung Chang12Heung Dong Kim13Pediatric Neurology, Department of Pediatrics Yonsei University College of Medicine, Severance Children's Hospital, Epilepsy Research Institute Seoul Republic of KoreaPediatric Neurology, Department of Pediatrics Yonsei University College of Medicine, Severance Children's Hospital, Epilepsy Research Institute Seoul Republic of KoreaBiostatistics Collaboration Unit, Department of Biomedical Systems Informatics Yonsei University College of Medicine Seoul Republic of KoreaDepartment of Pharmacy and Yonsei Institute of Pharmaceutical Science, College of Pharmacy Yonsei University Incheon Republic of KoreaDepartment of Pharmacy and Yonsei Institute of Pharmaceutical Science, College of Pharmacy Yonsei University Incheon Republic of KoreaPediatric Neurology, Department of Pediatrics Yonsei University College of Medicine, Severance Children's Hospital, Epilepsy Research Institute Seoul Republic of KoreaPediatric Neurology, Department of Pediatrics Yonsei University College of Medicine, Severance Children's Hospital, Epilepsy Research Institute Seoul Republic of KoreaPediatric Neurology, Department of Pediatrics Yonsei University College of Medicine, Severance Children's Hospital, Epilepsy Research Institute Seoul Republic of KoreaPediatric Neurology, Department of Pediatrics Yonsei University College of Medicine, Severance Children's Hospital, Epilepsy Research Institute Seoul Republic of KoreaGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST) SoVarGen, Inc. Daejeon Republic of KoreaDepartment of Laboratory Medicine Severance Hospital, Yonsei University College of Medicine Seoul Republic of KoreaDepartment of Pathology Yonsei University College of Medicine Seoul Republic of KoreaDepartment of Pharmacy and Yonsei Institute of Pharmaceutical Science, College of Pharmacy Yonsei University Incheon Republic of KoreaPediatric Neurology, Department of Pediatrics Yonsei University College of Medicine, Severance Children's Hospital, Epilepsy Research Institute Seoul Republic of KoreaAbstract Objective This study aimed to evaluate the effectiveness and safety of everolimus in treating seizures associated with focal cortical dysplasia type 2 (FCD 2). Methods A prospective, crossover, placebo‐controlled clinical trial (ClinicalTrials.gov: NCT03198949) enrolled patients aged 4–40 years with pathologically confirmed FCD 2 and a history of ≥3 seizures per month for two out of the 3 months prior to screening. The trial included a 4‐week baseline phase, two 12‐week core phases, and a 29‐week extension phase. Patients received everolimus or placebo in a blinded manner during core phase I, with crossover to the alternate treatment in core phase II. Everolimus dosage started at 4.5 mg/m2/day, targeting a serum level of 5–15 ng/mL. The primary outcome was the proportion of patients achieving ≥50% seizure reduction from baseline in the last month of each core phase. Safety profiles were compared between groups. Results Between May 11, 2017, and June 19, 2020, 21 patients completed the core phases. There was no significant difference in the primary outcome between everolimus and placebo groups (24% vs. 19%, p = 0.66). The patients showed varied responses. Three patients with a pathogenic variant in the MTOR gene or no genetic abnormalities achieved seizure freedom with everolimus in the last month of the core phase, while none of the patients with variants in other genes did. Adverse events, such as mucositis or skin ulceration, were more common with everolimus (19/21 vs. 7/21, p < 0.001). All adverse events resolved without study drug withdrawal. Significance Everolimus treatment for 12 weeks did not show overall superiority in reducing seizures compared to placebo. However, it showed promise, mostly in patients with a pathogenic variant in the MTOR gene, highlighting the need for further research into patient‐specific factors influencing treatment response. The everolimus treatment was generally safe and manageable. Plain Language Summary This study tested everolimus for reducing seizures in patients with focal cortical dysplasia type 2 (FCD 2). While the drug was not more effective than a placebo for most, few patients showed better results, with some becoming seizure‐free. Side effects were common but manageable. More research is needed to understand why certain patients respond better to treatment.https://doi.org/10.1002/epi4.13104epilepsydrug‐resistant epilepsyEverolimusfocal cortical dysplasiaMTOR inhibitors |
| spellingShingle | Se Hee Kim Hoon‐Chul Kang Yun Ho Roh Jongsung Hahn Kyung Lok Min Seok‐Jin Lee Donghwa Yang Han Som Choi Soyoung Park Jeong Ho Lee Sang‐Guk Lee Se Hoon Kim Min Jung Chang Heung Dong Kim Efficacy and safety of everolimus for patients with focal cortical dysplasia type 2 Epilepsia Open epilepsy drug‐resistant epilepsy Everolimus focal cortical dysplasia MTOR inhibitors |
| title | Efficacy and safety of everolimus for patients with focal cortical dysplasia type 2 |
| title_full | Efficacy and safety of everolimus for patients with focal cortical dysplasia type 2 |
| title_fullStr | Efficacy and safety of everolimus for patients with focal cortical dysplasia type 2 |
| title_full_unstemmed | Efficacy and safety of everolimus for patients with focal cortical dysplasia type 2 |
| title_short | Efficacy and safety of everolimus for patients with focal cortical dysplasia type 2 |
| title_sort | efficacy and safety of everolimus for patients with focal cortical dysplasia type 2 |
| topic | epilepsy drug‐resistant epilepsy Everolimus focal cortical dysplasia MTOR inhibitors |
| url | https://doi.org/10.1002/epi4.13104 |
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