Darcy A Krueger1, Angus A Wilfong2, Maxwell Mays2, Christina M Talley2, Karen Agricola2, Cindy Tudor2, Jamie Capal2, Katherine Holland-Bouley2, David Neal Franz2. 1. From the Departments of Pediatrics and Neurology (D.A.K., M.M., K.A., C.T., J.C., K.H.-B., D.N.F.), University of Cincinnati College of Medicine; Division of Child Neurology (D.A.K., M.M., K.A., C.T., J.C., K.H.-B., D.N.F.) and Pediatric Neurology (A.A.W., C.M.T.), Texas Children's Hospital, Baylor College of Medicine, Houston. krueger_darcy@cchmc.org. 2. From the Departments of Pediatrics and Neurology (D.A.K., M.M., K.A., C.T., J.C., K.H.-B., D.N.F.), University of Cincinnati College of Medicine; Division of Child Neurology (D.A.K., M.M., K.A., C.T., J.C., K.H.-B., D.N.F.) and Pediatric Neurology (A.A.W., C.M.T.), Texas Children's Hospital, Baylor College of Medicine, Houston.
Abstract
OBJECTIVE: To evaluate the long-term benefit and safety of everolimus for the treatment of medically refractory epilepsy in patients with tuberous sclerosis complex (TSC). METHODS: Everolimus was titrated over 4 weeks and continued an additional 8 weeks in a prospective, open-label, phase I/II clinical trial design. Participants demonstrating initial benefit continued treatment until study completion (48 months). The primary endpoint was percentage of patients with a ≥50% reduction in seizure frequency compared to baseline. Secondary endpoints assessed absolute seizure frequency, adverse events (AEs), behavior, and quality of life. RESULTS: Of the 20 participants who completed the initial study phase, 18 continued extended treatment. Fourteen of 18 (78%) participants completed the study, all but 1 of whom reported ≥50% reduction in seizure frequency at 48 months. All participants reported at least 1 AE, the vast majority (94%) of which were graded mild or moderate severity. Improvements in behavior and quality of life were also observed, but failed to achieve statistical significance at 48 months. CONCLUSIONS: Improved seizure control was maintained for 4 years in the majority of patients with TSC with medically refractory epilepsy treated with everolimus. Long-term treatment with everolimus is safe and well-tolerated in this population. Everolimus may be a therapeutic option for refractory epilepsy in TSC. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with TSC with medically refractory epilepsy everolimus improves seizure control.
OBJECTIVE: To evaluate the long-term benefit and safety of everolimus for the treatment of medically refractory epilepsy in patients with tuberous sclerosis complex (TSC). METHODS: Everolimus was titrated over 4 weeks and continued an additional 8 weeks in a prospective, open-label, phase I/II clinical trial design. Participants demonstrating initial benefit continued treatment until study completion (48 months). The primary endpoint was percentage of patients with a ≥50% reduction in seizure frequency compared to baseline. Secondary endpoints assessed absolute seizure frequency, adverse events (AEs), behavior, and quality of life. RESULTS: Of the 20 participants who completed the initial study phase, 18 continued extended treatment. Fourteen of 18 (78%) participants completed the study, all but 1 of whom reported ≥50% reduction in seizure frequency at 48 months. All participants reported at least 1 AE, the vast majority (94%) of which were graded mild or moderate severity. Improvements in behavior and quality of life were also observed, but failed to achieve statistical significance at 48 months. CONCLUSIONS: Improved seizure control was maintained for 4 years in the majority of patients with TSC with medically refractory epilepsy treated with everolimus. Long-term treatment with everolimus is safe and well-tolerated in this population. Everolimus may be a therapeutic option for refractory epilepsy in TSC. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with TSC with medically refractory epilepsy everolimus improves seizure control.
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