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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorRuiz-Falcó Rojas, María Luz
dc.contributor.authorFeucht, Martha
dc.contributor.authorMacaya Ruíz, Alfons
dc.contributor.authorWilken, Bernd
dc.contributor.authorHahn, Andreas
dc.contributor.authorMaamari, Ricardo
dc.date.accessioned2022-09-09T14:48:36Z
dc.date.available2022-09-09T14:48:36Z
dc.date.issued2022-04-08
dc.identifier.citationRuiz-Falcó Rojas ML, Feucht M, Macaya A, Wilken B, Hahn A, Maamari R, et al. Real-World Evidence Study on the Long-Term Safety of Everolimus in Patients With Tuberous Sclerosis Complex: Final Analysis Results. Front Pharmacol. 2022 Apr 8;13:802334.
dc.identifier.issn1663-9812
dc.identifier.urihttp://hdl.handle.net/11351/8131
dc.descriptionEverolimus; Post-authorization safety study; Tuberous sclerosis complex
dc.description.abstractThe TuberOus SClerosis registry to increase disease Awareness (TOSCA) Post-Authorization Safety Study (PASS) was a non-interventional, multicenter, safety substudy that assessed the long-term safety of everolimus in patients with tuberous sclerosis complex (TSC) receiving everolimus for its licensed indications in the European Union (EU). This substudy also aimed to address TSC-associated neuropsychiatric disorders (TAND), sexual development, and male infertility. Eligible patients were enrolled from 39 sites across 11 countries in the EU. Outcomes of interest included the incidence of adverse events (AEs), serious adverse events (SAEs), treatment-related AEs (TRAEs), AEs leading to everolimus discontinuation, AEs of special interest (AESIs), the observed relationship between everolimus blood levels and incidence of AESIs, TAND, and reproductive clinical features. Herein, we present the final analysis results from this substudy (data cutoff date: 22 January 2020). At data cutoff, 179 patients were enrolled (female, 59.2%; age ≥18 years, 65.9%), of which the majority completed the study (76%). Overall, 121 patients (67.6%) had AEs regardless of causality. The most frequent TRAEs (≥5%) were stomatitis (7.8%), aphthous ulcer (6.7%), and hypercholesterolemia (6.1%). The most common treatment-related SAEs (>1%) were pneumonia (3.4%), influenza, pyelonephritis, aphthous ulcer, stomatitis, dyslipidemia, and hypercholesterolemia (1.1% each). Ten patients (5.6%) reported AEs leading to everolimus discontinuation. The common psychiatric disorders (N = 179) were autism spectrum disorder (21.8%), anxiety disorder (12.8%), “other” psychiatric disorders (8.9%), attention-deficit hyperactivity disorder, and depressive disorder (7.8% each). Of 179 patients, 88 (49.2%) had ≥1 behavioral problem. Of these (n = 88), the most common (>20%) were sleep difficulties (47.7%), anxiety (43.2%), mood swings (37.5%), depression mood (35.2%), impulsivity (30.7%), severe aggression (23.9%), and overactivity (22.7%). Of 179 patients, four (2.2%) reported abnormal puberty onset, and three (1.7%) reported other reproductive disorders. Of 106 females, 23 (21.7%) reported menstrual cycle disorders and 10 (9.4%) reported amenorrhea. Available data did not show delays in sexual maturation or an association between sexual development and infertility. The results demonstrate that everolimus has a manageable long-term safety profile in the TSC treatment setting. No new safety signals emerged. This substudy also contributed to the mapping of TAND and reproductive clinical features in patients with TSC.
dc.language.isoeng
dc.publisherFrontiers Media
dc.relation.ispartofseriesFrontiers in Pharmacology;13
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectAvaluació de resultats (Assistència sanitària)
dc.subjectEsclerosi tuberosa - Tractament
dc.subject.meshTuberous Sclerosis
dc.subject.mesh/drug therapy
dc.subject.meshTreatment Outcome
dc.titleReal-World Evidence Study on the Long-Term Safety of Everolimus in Patients With Tuberous Sclerosis Complex: Final Analysis Results
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.3389/fphar.2022.802334
dc.subject.decsesclerosis tuberosa
dc.subject.decs/farmacoterapia
dc.subject.decsresultado del tratamiento
dc.relation.publishversionhttps://doi.org/10.3389/fphar.2022.802334
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Ruiz-Falcó Rojas ML] Hospital Infantil Universitario Nino Jesus, Madrid, Spain. [Feucht M] Universitäts-Klinik für Kinder-und Jugendheilkunde Wien, Vienna, Austria. [Macaya A] Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Wilken B] Klinikum Kassel GmbH, Kassel, Germany. [Hahn A] Abteilung Kinderneurologie, Universitätsklinikum Giessen und Marburg GmbH, Giessen, Germany. [Maamari R] Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States
dc.identifier.pmid35462939
dc.identifier.wos000790985200001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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