Adam Strzelczyk1,2, Milka Pringsheim3, Thomas Mayer4, Tilman Polster5, Kerstin A Klotz6,7, Hiltrud Muhle8, Michael Alber9, Regina Trollmann10, Hartwig Spors11, Gerhard Kluger3,12, Gerhard Kurlemann13, Susanne Schubert-Bast1,2,14. 1. Epilepsy Center Frankfurt Rhine-Main, Center of Neurology and Neurosurgery, Goethe University Frankfurt, Frankfurt am Main, Germany. 2. Center for Personalized Translational Epilepsy Research, Goethe University Frankfurt, Frankfurt am Main, Germany. 3. Clinic for Neuropediatrics and Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schön Clinic Vogtareuth, Vogtareuth, Germany. 4. Epilepsy Center Kleinwachau, Dresden-Radeberg, Germany. 5. Department of Epileptology, Bethel Epilepsy Center, Mara Hospital, Bielefeld University, Bielefeld, Germany. 6. Department of Neuropediatrics and Muscle Disorders, Center for Pediatrics, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 7. Berta Ottenstein Program, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 8. Department of Neuropediatrics, Christian-Albrecht University of Kiel and University Hospital Schleswig-Holstein, Kiel, Germany. 9. Department of Neuropediatrics, University of Tübingen, Tübingen, Germany. 10. Department of Neuropediatrics, Friedrich-Alexander University Erlangen, Erlangen, Germany. 11. Department of Neuropediatrics, Justus Liebig University Giessen, Giessen, Germany. 12. Research Institute, Rehabilitation, Transition, and Palliation, Paracelsus Medical University Salzburg, Salzburg, Austria. 13. St. Bonifatius Hospital, Lingen, Germany. 14. Department of Neuropediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany.
Abstract
OBJECTIVE: Dravet syndrome (DS) is a rare but severe drug-resistant epilepsy. Before the approval of fenfluramine (FFA) for the treatment of seizures in DS, patients in Germany could receive treatment under a compassionate use program (CUP). METHODS: We conducted a multicenter, retrospective, observational study to describe the efficacy, tolerability, and retention of FFA within the CUP. Patients received add-on therapy with oral FFA gradually titrated to a target dose between .13 and .7 mg/kg/day. RESULTS: Overall, 78 patients with DS (median age = 8.0 years, range = 2.1-46.0; 53% female, median concomitant antiseizure medications [ASMs] = 3) were treated with FFA for a median duration of 255.5 days (range = 31-572). Responder rates (a ≥50% reduction; n = 78) and seizure-freedom rates at 3 months were 68% and 14% for total seizures, respectively, and 67% and 23% for generalized tonic-clonic seizures. Responder rates were consistent at 6 and 12 months (n = 66 and n = 43, respectively). Median seizure days per month significantly decreased from 10.0 (range = .5-30) to 3.0 (range = 0-30) in the 3-month period before and after FFA treatment (p < .001). Significantly fewer patients reported at least one episode of status epilepticus (28% vs. 14% patients before and after FFA initiation, p = .005). During FFA treatment, 35 (45%) patients were able to discontinue a concomitant ASM. At the last follow-up date, 66 (85%) patients remained on treatment with FFA. The most common adverse events were somnolence (36%), decreased appetite (22%), and ataxia (8%). Forty-eight (62%) patients were reported as having a meaningful global clinical improvement. SIGNIFICANCE: In a large cohort of patients, FFA demonstrated efficacy across a range of outcomes including clinically significant reductions in convulsive seizures, and was well tolerated, providing valuable information for real-world practice.
OBJECTIVE: Dravet syndrome (DS) is a rare but severe drug-resistant epilepsy. Before the approval of fenfluramine (FFA) for the treatment of seizures in DS, patients in Germany could receive treatment under a compassionate use program (CUP). METHODS: We conducted a multicenter, retrospective, observational study to describe the efficacy, tolerability, and retention of FFA within the CUP. Patients received add-on therapy with oral FFA gradually titrated to a target dose between .13 and .7 mg/kg/day. RESULTS: Overall, 78 patients with DS (median age = 8.0 years, range = 2.1-46.0; 53% female, median concomitant antiseizure medications [ASMs] = 3) were treated with FFA for a median duration of 255.5 days (range = 31-572). Responder rates (a ≥50% reduction; n = 78) and seizure-freedom rates at 3 months were 68% and 14% for total seizures, respectively, and 67% and 23% for generalized tonic-clonic seizures. Responder rates were consistent at 6 and 12 months (n = 66 and n = 43, respectively). Median seizure days per month significantly decreased from 10.0 (range = .5-30) to 3.0 (range = 0-30) in the 3-month period before and after FFA treatment (p < .001). Significantly fewer patients reported at least one episode of status epilepticus (28% vs. 14% patients before and after FFA initiation, p = .005). During FFA treatment, 35 (45%) patients were able to discontinue a concomitant ASM. At the last follow-up date, 66 (85%) patients remained on treatment with FFA. The most common adverse events were somnolence (36%), decreased appetite (22%), and ataxia (8%). Forty-eight (62%) patients were reported as having a meaningful global clinical improvement. SIGNIFICANCE: In a large cohort of patients, FFA demonstrated efficacy across a range of outcomes including clinically significant reductions in convulsive seizures, and was well tolerated, providing valuable information for real-world practice.