Burden of Illness and Quality of Life in Tuberous Sclerosis Complex: Findings From the TOSCA Study

Jansen, Anna; Vanclooster, Stephanie; Vries, Petrus J. de; Fladrowski, Carla; d’Augères, Guillaume Beaure; Carter, Thomas; Belousova, Elena; Benedik, Mirjana P; Cottin, Vincent; Curatolo, Paolo; Dahlin, Maria; D’Amato, Lisa; Ferreira, José Carlos; Feucht, Martha; Hertzberg, Christoph; Jóźwiak, Sergiusz; Lawson, John A.; Macaya, Alfons; Marques, Rúben; Nabbout, Rima; O'Callaghan, Finbar; Qin, Jiong; Sander, Valentin; Sauter, Matthias; Shah, Seema; Takahashi, Yukitoshi; Touraine, Renaud; Youroukos, Sotiris; Zonnenberg, Bernard A.; Kingswood, J. Chris

doi:10.3389/fneur.2020.00904

Cited by 28 publications

(28 citation statements)

References 37 publications

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“… 5 In addition, caregivers report negative impacts on family, social and work-related dynamics. 11 TSC is associated with a high burden of illness with consequent cost and resource implications for healthcare systems. 5 , 14 , 15 …”

Section: Introductionmentioning

confidence: 99%

Review of the treatment options for epilepsy in tuberous sclerosis complex: towards precision medicine

Schubert‐Bast

Strzelczyk

2021

Ther Adv Neurol Disord

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Tuberous sclerosis complex (TSC) is a rare genetic disorder caused by mutations in the TSC1 or TSC2 genes, which encode proteins that antagonise the mammalian isoform of the target of rapamycin complex 1 (mTORC1) – a key mediator of cell growth and metabolism. TSC is characterised by the development of benign tumours in multiple organs, together with neurological manifestations including epilepsy and TSC-associated neuropsychiatric disorders (TAND). Epilepsy occurs frequently and is associated with significant morbidity and mortality; however, the management is challenging due to the intractable nature of the seizures. Preventative epilepsy treatment is a key aim, especially as patients with epilepsy may be at a higher risk of developing severe cognitive and behavioural impairment. Vigabatrin given preventatively reduces the risk and severity of epilepsy although the benefits for TAND are inconclusive. These promising results could pave the way for evaluating other treatments in a preventative capacity, especially those that may address the underlying pathophysiology of TSC, including everolimus, cannabidiol and the ketogenic diet (KD). Everolimus is an mTOR inhibitor approved for the adjunctive treatment of refractory TSC-associated seizures that has demonstrated significant reductions in seizure frequency compared with placebo, improvements that were sustained after 2 years of treatment. Highly purified cannabidiol, recently approved in the US as Epidiolex® for TSC-associated seizures in patients ⩾1 years of age, and the KD, may also participate in the regulation of the mTOR pathway. This review focusses on the pivotal clinical evidence surrounding these potential targeted therapies that may form the foundation of precision medicine for TSC-associated epilepsy, as well as other current treatments including anti-seizure drugs, vagus nerve stimulation and surgery. New future therapies are also discussed, together with the potential for preventative treatment with targeted therapies. Due to advances in understanding the molecular genetics and pathophysiology, TSC represents a prototypic clinical syndrome for studying epileptogenesis and the impact of precision medicine.

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Section: Introductionmentioning

confidence: 99%

Review of the treatment options for epilepsy in tuberous sclerosis complex: towards precision medicine

Schubert‐Bast

Strzelczyk

2021

Ther Adv Neurol Disord

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“…The burden of illness associated with TSC is considerable and can vary according to the complex and multifaceted disease manifestations [ 15 – 17 ]. Several studies published during the last two decades have examined the cost-of-illness (COI) and COI predictors in TSC.…”

Section: Introductionmentioning

confidence: 99%

Direct and indirect costs and cost-driving factors in adults with tuberous sclerosis complex: a multicenter cohort study and a review of the literature

Zöllner

Grau

Rosenow

et al. 2021

Orphanet J Rare Dis

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Background Tuberous sclerosis complex (TSC) is a monogenetic, multisystem disorder characterized by benign growths due to TSC1 or TSC2 mutations. This German multicenter study estimated the costs and related cost drivers associated with organ manifestations in adults with TSC. Methods A validated, three-month, retrospective questionnaire assessed the sociodemographic and clinical characteristics, organ manifestations, direct, indirect, out-of-pocket (OOP), and nursing care-level costs among adult individuals with TSC throughout Germany from a societal perspective (costing year: 2019). Results We enrolled 192 adults with TSC (mean age: 33.4 ± 12.7 years; range: 18–78 years, 51.6% [n = 99] women). Reported TSC disease manifestations included skin (94.8%) and kidney and urinary tract (74%) disorders, epilepsy (72.9%), structural brain defects (67.2%), psychiatric disorders (50.5%), heart and circulatory system disorders (50.5%), and lymphangioleiomyomatosis (11.5%). TSC1 and TSC2 mutations were reported in 16.7% and 25% of respondents, respectively. Mean direct health care costs totaled EUR 6452 (median EUR 1920; 95% confidence interval [CI] EUR 5533–7422) per patient over three months. Medication costs represented the major direct cost category (77% of total direct costs; mean EUR 4953), and mechanistic target of rapamycin (mTOR) inhibitors represented the largest share (68%, EUR 4358). Mean antiseizure drug (ASD) costs were only EUR 415 (6%). Inpatient costs (8%, EUR 518) and outpatient treatment costs (7%; EUR 467) were important further direct cost components. The mean care grade allowance as an approximator of informal nursing care costs was EUR 929 (median EUR 0; 95% CI EUR 780–1083) over three months. Mean indirect costs totaled EUR 3174 (median EUR 0; 95% CI EUR 2503–3840) among working-age individuals (< 67 years in Germany). Multiple regression analyses revealed mTOR inhibitor use and persistent seizures as independent cost-driving factors for total direct costs. Older age and disability were independent cost-driving factors for total indirect costs, whereas epilepsy, psychiatric disease, and disability were independent cost-driving factors for nursing care costs. Conclusions This three-month study revealed substantial direct healthcare, indirect healthcare, and medication costs associated with TSC in Germany. This study highlights the spectrum of organ manifestations and their associated treatment needs in the German healthcare setting. Trial registration: DRKS, DRKS00016045. Registered 01 March 2019, http://www.drks.de/DRKS00016045.

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“…Quantitatively, generally higher HRQoL was observed in our cohort than among individuals with TSC from the TOSCA study [ 12 ]. However, the QOLIE-31 reporting among this comparator cohort was limited ( n = 24), making comparisons prone to bias.…”

Section: Discussionmentioning

confidence: 99%

Quality of life and its predictors in adults with tuberous sclerosis complex (TSC): a multicentre cohort study from Germany

Zöllner

Conradi

Sauter

et al. 2021

Neurol. Res. Pract.

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Background Tuberous sclerosis complex (TSC) is a monogenetic, multisystemic disease characterised by the formation of benign tumours that can affect almost all organs, caused by pathogenic variations in TSC1 or TSC2. In this multicentre study from Germany, we investigated the influence of sociodemographic, clinical, and therapeutic factors on quality of life (QoL) among individuals with TSC. Methods We assessed sociodemographic and clinical characteristics and QoL among adults with TSC throughout Germany using a validated, three-month, retrospective questionnaire. We examined predictors of health-related QoL (HRQoL) using multiple linear regression analysis and compared the QoL among patients with TSC with QoL among patients with other chronic neurological disorders. Results We enrolled 121 adults with TSC (mean age: 31.0 ± 10.5 years; range: 18–61 years, 45.5% [n = 55] women). Unemployment, a higher grade of disability, a higher number of organ manifestations, the presence of neuropsychiatric manifestations or active epilepsy, and a higher burden of therapy-related adverse events were associated with worse QoL, as measured by two QoL instruments (EuroQoL-5 dimensions [EQ-5D] and Quality of Life in Epilepsy Patients [QOLIE-31]). Neuropsychiatric and structural nervous system manifestations, the number of affected organs, and therapy-related adverse events were also associated with higher depression, as measured by the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). In multiple regression analysis, more severe therapy-related adverse events (large effect, p < 0.001), active epilepsy (large effect, p < 0.001), and neuropsychiatric manifestations (medium effect, p = 0.003) were independently associated with worse HRQoL, explaining 65% of the variance (p < 0.001). The HRQoL among patients with active TSC-associated epilepsy was worse than that among patients with drug-refractory mesial temporal lobe epilepsy (p < 0.001), and the generic QoL among patients with more than three TSC organ manifestations was similar to those of patients with severe migraine and uncontrolled asthma. Conclusions Active epilepsy, neuropsychiatric manifestations (such as anxiety and depression), and therapy-related adverse events are important independent predictors of worse quality of life among adults with TSC. Generic quality of life in TSC with several manifestations is similar to uncontrolled severe chronic diseases and significantly negatively correlates with TSC severity. Trial registration DRKS, DRKS00016045. Registered 01 March 2019.

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Burden of Illness and Quality of Life in Tuberous Sclerosis Complex: Findings From the TOSCA Study

Cited by 28 publications

References 37 publications

Review of the treatment options for epilepsy in tuberous sclerosis complex: towards precision medicine

Review of the treatment options for epilepsy in tuberous sclerosis complex: towards precision medicine

Direct and indirect costs and cost-driving factors in adults with tuberous sclerosis complex: a multicenter cohort study and a review of the literature

Quality of life and its predictors in adults with tuberous sclerosis complex (TSC): a multicentre cohort study from Germany

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