TY  - JOUR
A1  - Willems, Laurent Maximilian
A1  - Rosenow, Felix
A1  - Schubert-Bast, Susanne
A1  - Kurlemann, Gerhard
A1  - Zöllner, Johann Philipp
A1  - Bast, Thomas
A1  - Bertsche, Astrid
A1  - Bettendorf, Ulrich
A1  - Ebrahimi-Fakhari, Daniel
A1  - Grau, Janina
A1  - Hahn, Andreas
A1  - Hartmann, Hans
A1  - Hertzberg, Christoph
A1  - Hornemann, Frauke
A1  - Immisch, Ilka
A1  - Jacobs-LeVan, Julia
A1  - Klein, Karl Martin
A1  - Klotz, Kerstin Alexandra
A1  - Kluger, Gerhard
A1  - Knake, Susanne
A1  - Knuf, Markus
A1  - Marquard, Klaus
A1  - Mayer, Thomas
A1  - Meyer, Sascha
A1  - Muhle, Hiltrud
A1  - Müller-Schlüter, Karen
A1  - Podewils, Felix von
A1  - Ruf, Susanne
A1  - Sauter, Matthias
A1  - Schäfer, Hannah
A1  - Schlump, Jan-Ulrich
A1  - Syrbe, Steffen
A1  - Thiels, Charlotte
A1  - Trollmann, Regina
A1  - Wiemer-Kruel, Adelheid
A1  - Wilken, Bernd
A1  - Zukunft, Bianca
A1  - Strzelczyk, Adam
T1  - Efficacy, retention and tolerability of everolimus in patients with tuberous sclerosis complex: a survey-based study on patients’ perspectives
T2  - CNS drugs
N2  - Background: The approval of everolimus (EVE) for the treatment of angiomyolipoma (2013), subependymal giant cell astrocytoma (2013) and drug-refractory epilepsy (2017) in patients with tuberous sclerosis complex (TSC) represents the first disease-modifying treatment option available for this rare and complex genetic disorder. Objective: The objective of this study was to analyse the use, efficacy, tolerability and treatment retention of EVE in patients with TSC in Germany from the patient’s perspective. Methods: A structured cross-age survey was conducted at 26 specialised TSC centres in Germany and by the German TSC patient advocacy group between February and July 2019, enrolling children, adolescents and adult patients with TSC. Results: Of 365 participants, 36.7% (n = 134) reported the current or past intake of EVE, including 31.5% (n = 115) who were taking EVE at study entry. The mean EVE dosage was 6.1 ± 2.9 mg/m2 (median: 5.6 mg/m2, range 2.0–15.1 mg/m2) in children and adolescents and 4 ± 2.1 mg/m2 (median: 3.7 mg/m2, range 0.8–10.1 mg/m2) in adult patients. An early diagnosis of TSC, the presence of angiomyolipoma, drug-refractory epilepsy, neuropsychiatric manifestations, subependymal giant cell astrocytoma, cardiac rhabdomyoma and overall multi-organ involvement were associated with the use of EVE as a disease-modifying treatment. The reported efficacy was 64.0% for angiomyolipoma (75% in adult patients), 66.2% for drug-refractory epilepsy, and 54.4% for subependymal giant cell astrocytoma. The overall retention rate for EVE was 85.8%. The retention rates after 12 months of EVE therapy were higher among adults (93.7%) than among children and adolescents (88.7%; 90.5% vs 77.4% after 24 months; 87.3% vs 77.4% after 36 months). Tolerability was acceptable, with 70.9% of patients overall reporting adverse events, including stomatitis (47.0%), acne-like rash (7.7%), increased susceptibility to common infections and lymphoedema (each 6.0%), which were the most frequently reported symptoms. With a total score of 41.7 compared with 36.8 among patients not taking EVE, patients currently being treated with EVE showed an increased Liverpool Adverse Event Profile. Noticeable deviations in the sub-items ‘tiredness’, ‘skin problems’ and ‘mouth/gum problems’, which are likely related to EVE-typical adverse effects, were more frequently reported among patients taking EVE. Conclusions: From the patients’ perspective, EVE is an effective and relatively well-tolerated disease-modifying treatment option for children, adolescents and adults with TSC, associated with a high long-term retention rate that can be individually considered for each patient. Everolimus therapy should ideally be supervised by a centre experienced in the use of mechanistic target of rapamycin inhibitors, and adverse effects should be monitored on a regular basis.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63570
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-635705
SN  - 1179-1934
N1  - Open Access funding enabled and organized by Projekt DEAL. This work was supported by the federal state Hessen with a LOEWE grant to the Center of Personal and Translational Epilepsy Research (CePTER).
VL  - 35
SP  - 1107
EP  - 1122
PB  - Springer
CY  - Berlin [u.a.]
ER  -