TOSCA – first international registry to address knowledge gaps in the natural history and management of tuberous sclerosis complex

Orphanet Journal of Rare Diseases

Martha Feucht¹  Bulent Ulker⁹  Ramon Castellana^1,14  Sotirios Youroukos³  Valentin Sander^2,25  Mirjana Perkovic Benedik⁵  Alfons Macaya^1,13  José Carlos Ferreira⁴  Maria Dahlin^2,21  Vincent Cottin^1,15  Tom Carter^1,10  Elena Belousova^2,26  Guillaume Beaure d’Augères^1,16  Silvia Comis^1,14  Stefania Crippa^1,14  Bernard Zonnenberg^1,12  Finbar O’Callaghan⁷  Renaud Touraine^1,18  Matthias Sauter^2,22  Rima Nabbout^2,23  Sergiusz Jozwiak²  Anna C Jansen^2,24  Christoph Hertzberg⁶  Carla Fladrowski^1,11  Petrus J de Vries^1,19  Paolo Curatolo^1,17  Paolo Bruzzi⁸  John C Kingswood^2,20 

[1] Universitätsklinik für Kinder-und Jugendheilkunde, Vienna, Austria;The Children’s Memorial Health Institute of Warsaw, Warsaw, Poland;“St. Sophia” Children’s Hospital, Athens, Greece;Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal;SPS Pediatrična Klinika, Ljubljana, Slovenia;Vivantes-Klinikum Neukölln, Berlin, Germany;Institute of Child Health, University College London, London, UK;IRCCS AUO San Martino IST–Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy;Novartis Pharma AG, Basel, Switzerland;TSA Tuberous Sclerosis Association, Nottingham, UK;European Tuberous Sclerosis Complex Association, In den Birken, 30, Dattein, 45711, Germany;University Medical Center, Utrecht, Netherlands;Hospital Universitari Vall d’Hebron, Barcelona, Spain;Novartis Farma S.p.A., Origgio, Italy;Hôpital Louis Pradel, Claude Bernard University Lyon 1, Lyon, France;Association Sclérose Tubéreuse de Bourneville, Gradignan, France;Tor Vergata University Hospital, Rome, Italy;Hôpital Nord, Saint Etienne, France;Division of Child and Adolescent Psychiatry, University of Cape Town, Cape Town, South Africa;Sussex Kidney Unit, Royal Sussex County Hospital, Eastern Road, Brighton BN2 5BE, UK;Karolinska University Hospital, Stockholm, Sweden;Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany;Hospital Necker Enfants Malades, Paris, France;UZ Brussel VUB, Brussels, Belgium;Tallinn Children Hospital, Tallinn, Estonia;Moscow Institute of Pediatrics and Pediatric Surgery, Moscow, Russian Federation

关键词: Angiomyolipoma;    Subependymal giant cell astrocytoma;    Epilepsy;    Registry;    Tuberous sclerosis;   

Others  :  1138788
DOI  :  10.1186/s13023-014-0182-9

 received in 2014-07-25, accepted in 2014-11-04,  发布年份 2014

【 摘 要 】

Background

Tuberous sclerosis complex (TSC) is a rare, multisystem, genetic disorder with an estimated prevalence between 1/6800 and 1/15000. Although recent years have seen huge progress in understanding the pathophysiology and in the management of TSC, several questions remain unanswered. A disease registry could be an effective tool to gain more insights into TSC and thus help in the development of improved management strategies.

Methods

TuberOus SClerosis registry to increase disease Awareness (TOSCA) is a multicentre, international disease registry to assess manifestations, interventions, and outcomes in patients with TSC. Patients of any age diagnosed with TSC, having a documented visit for TSC within the preceding 12 months, or newly diagnosed individuals are eligible. Objectives include mapping the course of TSC manifestations and their effects on prognosis, identifying patients with rare symptoms and co-morbidities, recording interventions and their outcomes, contributing to creation of an evidence-base for disease assessment and therapy, informing further research on TSC, and evaluating the quality of life of patients with TSC. The registry includes a ‘core’ section and subsections or ‘petals’. The ‘core’ section is designed to record general information on patients’ background collected at baseline and updated annually. Subsections will be developed over time to record additional data related to specific disease manifestations and will be updated annually. The registry aimed to enrol approximately 2000 patients from about 250 sites in 31 countries. The initial enrolment period was of 24 months. A follow-up observation period of up to 5 years is planned.

Results

A pre-planned administrative analysis of ‘core’ data from the first 100 patients was performed to evaluate the feasibility of the registry. Results showed a high degree of accuracy of the data collection procedure. Annual interim analyses are scheduled. Results of first interim analysis will be presented subsequent to data availability in 2014.

Implications

The results of TOSCA will assist in filling the gaps in understanding the natural history of TSC and help in planning better management and surveillance strategies. This large-scale international registry to study TSC could serve as a model to encourage planning of similar registries for other rare diseases.

【 授权许可】

   
2014 Kingswood et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Curatolo P, Bombardieri R, Jozwiak S: Tuberous sclerosis. Lancet 2008, 372:657-668.
• [2]Sampson JR, Scahill SJ, Stephenson JB, Mann L, Connor JM: Genetic aspects of tuberous sclerosis in the west of Scotland. J Med Genet 1989, 26:28-31.
• [3]O’Callaghan FJ, Shiell AW, Osborne JP, Martyn CN: Prevalence of tuberous sclerosis estimated by capture-recapture analysis. Lancet 1998, 351:1490.
• [4]Yates JR: Tuberous sclerosis. Eur J Hum Genet 2006, 14:1065-1073.
• [5]Curatolo P, Maria BL: Tuberous sclerosis. Handb Clin Neurol 2013, 111:323-331.
• [6]Józwiak S, Schwartz RA, Janniger CK, Bielicka-Cymerman J: Usefulness of diagnostic criteria of tuberous sclerosis complex in pediatric patients. J Child Neurol 2000, 15:652-659.
• [7]Franz DN, Bissler JJ, McCormack FX: Tuberous sclerosis complex: neurological, renal and pulmonary manifestations. Neuropediatrics 2010, 41:199-208.
• [8]Chu-Shore CJ, Major P, Camposano S, Muzykewicz D, Thiele EA: The natural history of epilepsy in tuberous sclerosis complex. Epilepsia 2010, 51:1236e41.
• [9]Prather P, de Vries PJ: Behavioral and cognitive aspects of tuberous sclerosis complex. J Child Neurol 2004, 19:666-674.
• [10]Crino P, Mehta R, Vinters H: Pathogenesis of TSC in the Brain. In Tuberous Sclerosis Complex: Genes, Clinical Features, and Therapeutics. Edited by Kwiatkowsi D, Whittemore V, Thiele E. Wiley-Blackwell, Weinheim; 2010:285-309.
• [11]Goh S, Butler W, Thiele EA: Subependymal giant cell tumors in tuberous sclerosis complex. Neurology 2004, 63:1457-1461.
• [12]Shepherd CW, Gomez MR, Lie JT, Crowson CS: Causes of death in patients with tuberous sclerosis. Mayo Clin Proc 1991, 66:792-796.
• [13]Mavroudi M, Zarogoulidis P, Katsikogiannis N, Tsakiridis K, Huang H, Sakkas A, Kallianos A, Rapti A, Sarika E, Karapantzos I, Zarogoulidis K: Lymphangioleiomyomatosis: current and future. J Thorac Dis 2013, 5:74-79.
• [14]Cudzilo CJ, Szczesniak RD, Brody AS, Rattan MS, Krueger DA, Bissler JJ, Franz DN, McCormack FX, Young LR: Lymphangioleiomyomatosis screening in women with tuberous sclerosis. Chest 2013, 144:578-585.
• [15]Seibert D, Hong CH, Takeuchi F, Olsen C, Hathaway O, Moss J, Darling TN: Recognition of tuberous sclerosis in adult women: delayed presentation with life-threatening consequences. Ann Intern Med 2011, 154:806-813.
• [16]Crino P, Nathanson K, Henske E: The tuberous sclerosis complex. New Engl J Med 2006, 355:1345-1356.
• [17]Jóźwiak S, Kotulska K, Kasprzyk-Obara J, Domańska-Pakieła D, Tomyn-Drabik M, Roberts P, Kwiatkowski D: Clinical and genotype studies of cardiac tumors in 154 patients with tuberous sclerosis complex. Pediatrics 2006, 118:e1146-e1151.
• [18]Roach ES, Smith M, Huttenlocher P, Bhat M, Alcorn D, Hawley L: Report of the diagnostic criteria committee of the National Tuberous Sclerosis Association. J Child Neurol 1992, 7:221-224.
• [19]Roach E, Gomez M, Northrup H: Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria. J Child Neurol 1998, 13:624-628.
• [20]Roach ES: Are diagnostic criteria for tuberous sclerosis still relevant? Pediatr Neurol 2013, 49:223-224.
• [21]Northrup H, Krueger DA: Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 international tuberous sclerosis complex consensus conference. Pediatr Neurol 2013, 49:243-254.
• [22]Krueger DA, Northrup H: Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol 2013, 49:255-265.
• [23]Huang J, Manning BD: The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochem J 2008, 412:179-190.
• [24]Krueger DA, Care MM, Holland K, Agricola K, Tudor C, Mangeshkar P, Wilson KA, Byars A, Sahmoud T, Franz DN: Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med 2010, 363:1801-1811.
• [25]Krueger DA, Care MM, Agricola K, Tudor C, Mays M, Franz DN: Everolimus long-term safety and efficacy in subependymal giant cell astrocytoma. Neurology 2013, 80:574-580.
• [26]Franz DN, Belousova E, Sparagana S, Bebin EM, Frost M, Kuperman R, Witt O, Kohrman MH, Flamini JR, Wu JY, Curatolo P, de Vries PJ, Whittemore VH, Thiele EA, Ford JP, Shah G, Cauwel H, Lebwohl D, Sahmoud T, Jozwiak S: Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet 2013, 381:125-132.
• [27]Bissler JJ, Kingswood JC, Radzikowska E, Zonnenberg BA, Frost M, Belousova E, Sauter M, Nonomura N, Brakemeier S, de Vries PJ, Whittemore VH, Chen D, Sahmoud T, Shah G, Lincy J, Lebwohl D, Budde K: Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 2013, 381:817-824.
• [28][https://www.pharma.us.novartis.com/product/pi/pdf/afinitor.pdf] webcite Afinitor (Everolimus) Tablets for Oral Administration Prescribing Information. New Jersey, NJ: Novartis Pharmaceuticals Corporation; 2014 []
• [29][http://www.votubia.com/pdf/Votubia-SMPC%20Oct%202014.pdf] webcite Votubia (Everolimus) Summary of Product Characteristics. West Sussex, UK: Novartis Europharm Limited; 2014 [].
• [30]Curatolo P, Moavero R: mTOR inhibitors in tuberous sclerosis complex. Curr Neuropharmacol 2012, 10:404-415.
• [31]Kohrman MH: Emerging treatments in the management of tuberous sclerosis complex. Pediatr Neurol 2012, 46:267-275.
• [32]Krueger DA, Wilfong AA, Holland-Bouley K, Anderson AE, Agricola K, Tudor C, Mays M, Lopez CM, Kim MO, Franz DN: Everolimus treatment of refractory epilepsy in tuberous sclerosis complex. Ann Neurol 2013, 74:679-687.
• [33]Davies DM, de Vries PJ, Johnson SR, McCartney DL, Cox JA, Serra AL, Watson PC, Howe CJ, Doyle T, Pointon K, Cross JJ, Tattersfield AE, Kingswood JC, Sampson JR: Sirolimus therapy for angiomyolipoma in tuberous sclerosis and sporadic lymphangioleiomyomatosis: a phase 2 trial. Clin Cancer Res 2011, 17:4070-4081.
• [34]Cappellano AM, Senerchia AA, Adolfo F, Paiva PM, Pinho R, Covic A, Cavalheiro S, Saba N: Successful everolimus therapy for SEGA in pediatric patients with tuberous sclerosis complex. Childs Nerv Syst 2013, 29:2301-2305.
• [35]McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP 3rd, Goldberg HJ, Young LR, Kinder BW, Downey GP, Sullivan EJ, Colby TV, McKay RT, Cohen MM, Korbee L, Taveira-DaSilva AM, Lee HS, Krischer JP, Trapnell BC: Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med 2011, 364:1595-1606.
• [36]Dabora SL, Jozwiak S, Franz DN, Roberts PS, Nieto A, Chung J, Choy YS, Reeve MP, Thiele E, Egelhoff JC, Kasprzyk-Obara J, Domanska-Pakiela D, Kwiatkowski DJ: Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs. Am J Hum Genet 2001, 68:64-80.
• [37]Dreyer NA, Garner S: Registries for robust evidence. JAMA 2009, 302:790-791.
• [38]Gliklich RE, Dreyer NA: Patient Registries. In Registries for Evaluating Patient Outcomes: A User’s Guide. 2nd edition. Edited by Gliklich RE, Dreyer NA. Agency for Healthcare Research and Quality (US), Rockville; 2010:9-21.
• [39]Orth M, Handley OJ, Schwenke C, Dunnett SB, Craufurd D, Ho AK, Wild E, Tabrizi SJ, Landwehrmeyer GB, the European Huntington’s Disease Network: Observing huntington’s disease: the European Huntington’s Disease Network’s REGISTRY.PLoS Curr Huntington Dis 2010, (1st Edition): doi:10.1371/currents.RRN1184.
• [40]Bladen CL, Rafferty K, Straub V, Monges S, Moresco A, Dawkins H, Roy A, Chamova T, Guergueltcheva V, Korngut L, Campbell C, Dai Y, Barišić N, Kos T, Brabec P, Rahbek J, Lahdetie J, Tuffery-Giraud S, Claustres M, Leturcq F, Ben Yaou R, Walter MC, Schreiber O, Karcagi V, Herczegfalvi A, Viswanathan V, Bayat F, de la Caridad Guerrero Sarmiento I, Ambrosini A, Ceradini F, et al.: The TREAT-NMD Duchenne muscular dystrophy registries: conception, design, and utilization by industry and academia. Hum Mutat 2013, 34:1449-1457.
• [41]Gliklich RE, Dreyer NA: Data Collection and Quality Assurance. In Registries for Evaluating Patient Outcomes: A User’s Guide. 2nd edition. Edited by Gliklich RE, Dreyer NA. Agency for Healthcare Research and Quality (US), Rockville; 2010:225-252.