AUTHOR=Kingswood J. Chris , Belousova Elena , Benedik Mirjana P. , Budde Klemens , Carter Tom , Cottin Vincent , Curatolo Paolo , Dahlin Maria , D'Amato Lisa , d'Augères Guillaume B. , de Vries Petrus J. , Ferreira José C. , Feucht Martha , Fladrowski Carla , Hertzberg Christoph , Jozwiak Sergiusz , Lawson John A. , Macaya Alfons , Marques Ruben , Nabbout Rima , O'Callaghan Finbar , Qin Jiong , Sander Valentin , Sauter Matthias , Shah Seema , Takahashi Yukitoshi , Touraine Renaud , Youroukos Sotiris , Zonnenberg Bernard , Jansen Anna C. ,  TOSCA Consortium and TOSCA Investigators 

TITLE=TuberOus SClerosis registry to increAse disease awareness (TOSCA) Post-Authorisation Safety Study of Everolimus in Patients With Tuberous Sclerosis Complex

JOURNAL=Frontiers in Neurology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.630378

DOI=10.3389/fneur.2021.630378

ISSN=1664-2295

ABSTRACT=This non-interventional post-authorization safety study (PASS) assessed the long-term safety of everolimus in patients with tuberous sclerosis 46 complex (TSC), who participated in the TOSCA clinical study and received everolimus for the licensed indications in the European Union. 47 The rate of adverse events (AEs), AEs that led to dose adjustments or treatment discontinuation, AEs of potential clinical interest, treatment-48 related AEs (TRAEs), serious AEs (SAEs), and deaths were documented. 179 patients were included in the first 5 years of observation, 118 49 of 179 patients had an AE of any grade, with the most common AEs being stomatitis (7.8%) and headache (7.3%). AEs caused dose adjustments 50 in 56 patients (31.3%) and treatment discontinuation in nine patients (5%). AEs appeared to be more frequent and severe in children. On 51 Tanner staging, all patients displayed signs of age-appropriate sexual maturation. 22 (20.8%) patients had menstrual cycle disorders. The most 52 frequent TRAEs were stomatitis (6.7%) and aphthous mouth ulcer (5.6%). SAEs were reported in 54 patients (30.2%) of the most frequent 53 SAE was pneumonia (>3% patients; grade 2, 1.1% and grade 3, 2.8%). Three deaths were reported, all in patients who had discontinued 54 everolimus for more than 28 days, and none were thought to be related to everolimus according to the treating physicians. The PASS sub-55 study reflects the safety and tolerability of everolimus in the management of TSC in real-world routine clinical practice.