Efficacy, tolerability, and retention of fenfluramine for the treatment of seizures in patients with Dravet syndrome: Compassionate use program in Germany

Strzelczyk A, Pringsheim M, Mayer T, Polster T, Klotz KA, Muhle H, Alber M, Trollmann R, Spors H, Kluger G, Kurlemann G, Schubert-Bast S (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Epilepsia Wiley-Blackwell

DOI: 10.1111/epi.17034

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.

Authors with CRIS profile

Regina Trollmann Professur für Kinder- u. Jugendmedizin Schwerpunkt Neuropädiatrie

Involved external institutions

Goethe-Universität Frankfurt am Main DE Germany (DE) Paracelsus Medizinische Privatuniversität AT Austria (AT) Eberhard Karls Universität Tübingen DE Germany (DE) Kleinwachau - Sächsisches Epilepsiezentrum Radeberg gGmbH DE Germany (DE) Christian-Albrechts-Universität zu Kiel DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE) St. Bonifatius Hospital DE Germany (DE) Universität Bielefeld DE Germany (DE) Justus-Liebig-Universität Gießen DE Germany (DE)

How to cite

APA:

Strzelczyk, A., Pringsheim, M., Mayer, T., Polster, T., Klotz, K.A., Muhle, H.,... Schubert-Bast, S. (2021). Efficacy, tolerability, and retention of fenfluramine for the treatment of seizures in patients with Dravet syndrome: Compassionate use program in Germany. Epilepsia. https://doi.org/10.1111/epi.17034

MLA:

Strzelczyk, Adam, et al. "Efficacy, tolerability, and retention of fenfluramine for the treatment of seizures in patients with Dravet syndrome: Compassionate use program in Germany." Epilepsia (2021).

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