TY  - JOUR
A1  - Strzelczyk, Adam
A1  - Pringsheim, Milka
A1  - Mayer, Thomas
A1  - Polster, Tilman
A1  - Klotz, Kerstin Alexandra
A1  - Muhle, Hiltrud
A1  - Alber, Michael
A1  - Trollmann, Regina
A1  - Spors, Hartwig
A1  - Kluger, Gerhard
A1  - Kurlemann, Gerhard
A1  - Schubert-Bast, Susanne
T1  - Efficacy, tolerability, and retention of fenfluramine for the treatment of seizures in patients with Dravet syndrome: compassionate use program in Germany
T2  - Epilepsia
N2  - 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.

Key Points: Seventy-eight patients with Dravet syndrome were treated with FFA at multiple centers within the CUP in Germany; FFA had a good retention rate over a sustained period; 85% of patients remained on treatment with FFA for a median duration of 255.5 days; FFA was associated with clinically meaningful reductions in total and convulsive seizures, seizure days per month, and episodes of status epilepticus; FFA was associated with reductions in the number or dose of concomitant antiseizure medications in 68% of patients; FFA was well tolerated, with the main adverse events being somnolence (36%), decreased appetite (22%), and ataxia (8%).
KW  - Clinical Global Impression of Change
KW  - convulsive seizures
KW  - Dravet syndrome
KW  - fenfluramine
KW  - real-world
KW  - status epilepticus
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62675
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-626752
SN  - 1528-1167
N1  - Early View: Online Version before inclusion in an issue
N1  - This study was supported by a LOEWE grant to A.S. and S.S.-B. from the State of Hessen for the Center for Personalized Translational Epilepsy Research, Goethe University Frankfurt, Frankfurt am Main, Germany. K.A.K. was supported by the Berta Ottenstein Program for Clinician Scientists from the Faculty of Medicine, University of Freiburg, Germany.
N1  - A.S. reports personal fees and grants from Arvelle Therapeutics, Desitin Arzneimittel, Eisai, GW Pharmaceuticals, Marinus Pharma, Medtronic, UCB, and Zogenix. T.M. reports personal fees and grants from Arvelle. Therapeutics, Eisai, GW Pharmaceuticals, UCB, and Zogenix. T.P. reports personal fees and grants from Desitin Arzneimittel, Novartis International, UCB Pharma, and Zogenix International.
N1  - Version of Record: http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:hebis:30:3-645175
VL  - 2021
IS  - online version before inclusion in an issue
SP  - 1
EP  - 10
PB  - Wiley-Blackwell
CY  - Oxford [u.a.]
ER  -