Efficacy, retention and tolerability of everolimus in patients with tuberous sclerosis complex: a survey-based study on patients’ perspectives

  • 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.
Author:Laurent Maximilian WillemsORCiDGND, Felix RosenowORCiDGND, Susanne Schubert-BastORCiDGND, Gerhard KurlemannGND, Johann Philipp ZöllnerORCiDGND, Thomas BastGND, Astrid BertscheORCiDGND, Ulrich BettendorfGND, Daniel Ebrahimi-Fakhari, Janina GrauGND, Andreas Hahn, Hans Hartmann, Christoph HertzbergORCiDGND, Frauke Hornemann, Ilka ImmischGND, Julia Jacobs-LeVan, Karl Martin KleinORCiD, Kerstin Alexandra KlotzORCiDGND, Gerhard Kluger, Susanne KnakeORCiDGND, Markus KnufGND, Klaus Marquard, Thomas Mayer, Sascha Meyer, Hiltrud MuhleORCiDGND, Karen Müller-SchlüterGND, Felix von PodewilsORCiDGND, Susanne Ruf, Matthias SauterORCiDGND, Hannah Schäfer, Jan-Ulrich SchlumpGND, Steffen SyrbeORCiDGND, Charlotte ThielsORCiDGND, Regina TrollmannORCiDGND, Adelheid Wiemer-KruelORCiD, Bernd Wilken, Bianca Zukunft, Adam StrzelczykORCiDGND
Parent Title (English):CNS drugs
Place of publication:Berlin [u.a.]
Document Type:Article
Date of Publication (online):2021/07/17
Date of first Publication:2021/07/17
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/03/16
Page Number:16
First Page:1107
Last Page:1122
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).
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (English):License LogoCreative Commons - Namensnennung-Nicht kommerziell 4.0