The international X-linked hypophosphataemia (XLH) registry (NCT03193476): rationale for and description of an international, observational study

Orphanet Journal of Rare Diseases

Dirk Schnabel¹  Signe Beck-Nielsen²  Outi Makitie³  Gema Ariceta⁴  Ola Nilsson⁵  Michael Smyth⁶  Ravi Jandhyala⁷  Raja Padidela⁸  Zulf Mughal⁸  Elena Levtchenko⁹  Maria Luisa Brandi^1,10  Annemieke Boot^1,11 

[1] Center for Chronic Sick Children, Pediatric Endocrinology, Charité, University Medicine Berlin;Centre for Rare Diseases, Aarhus University Hospital;Children’s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital;Hospital Vall d’Hebron, Universitat Autonoma Barcelona;Karolinska Institutet;Kyowa Kirin International;Medialis Ltd;Royal Manchester Children’s Hospital and Faculty of Biology, Medicine and Health, University of Manchester;University Hospitals Leuven, KULeuven;University of Florence;University of Groningen;

关键词: X-linked hypophosphataemia (XLH);    Rare disease;    Patient registry;    Vitamin D;    Disease history;    Post-authorisation safety;   

DOI  :  10.1186/s13023-020-01434-4

来源: DOAJ

【 摘 要 】

Abstract Background X-linked hypophosphataemia (XLH) is a rare, hereditary, progressive and lifelong phosphate wasting disorder characterised by pathological elevations in fibroblast growth factor (FGF) 23 concentration and activity; XLH has an incidence of approximately 1 in 20–25,000 individuals. Excess FGF23 activity leads to increased phosphate excretion in the kidneys – mediated by downregulation of renal tubular phosphate transporters – and reduced phosphate absorption in the intestines – due to impaired vitamin D activation. This results in impaired bone growth and mineralisation, short and disproportionate stature, leg bowing, musculoskeletal pain, spontaneous dental abscesses, rickets, and osteomalacia. The spectrum of manifestations differs between paediatric and adult patients. Those involved in the treatment of this condition face many challenges, including a lack of robust natural history and demographic data. This multicentre, international, rare-disease patient registry (XLH Registry) was established to address the paucity of data in XLH and to help inform future clinical practice. Results The XLH Registry collects standard diagnostic and monitoring practice data, including (where applicable) diagnosis and disease progression history, treatment regimens and family history; the protocol does not mandate any interventions or clinical assessments. The XLH Registry aims to recruit 1200 paediatric and adult patients with XLH over 10 years, and several data analyses and peer-reviewed publications are expected to be generated throughout this period. A post-authorisation safety study for Bburosumab, for which the registry Sponsor is the marketing authorisation holder, will be nested as a sub-study within the XLH Registry via a subsequent protocol amendment. Conclusion The data collected within this rare-disease patient registry will be utilised to synthesise real-world evidence to inform the management of XLH, to improve the quality of life and standard of care of patients living with this rare debilitating disease.

【 授权许可】

Unknown