TY - JOUR
T1 - The International X-Linked Hypophosphatemia (XLH) Registry
T2 - first interim analysis of baseline demographic, genetic and clinical data
AU - Ariceta, Gema
AU - Beck-Nielsen, Signe Sparre
AU - Boot, Annemieke M.
AU - Brandi, Maria Luisa
AU - Briot, Karine
AU - de Lucas Collantes, Carmen
AU - Emma, Francesco
AU - Giannini, Sandro
AU - Haffner, Dieter
AU - Keen, Richard
AU - Levtchenko, Elena
AU - Mӓkitie, Outi
AU - Mughal, M. Zulf
AU - Nilsson, Ola
AU - Schnabel, Dirk
AU - Tripto-Shkolnik, Liana
AU - Liu, Jonathan
AU - Williams, Angela
AU - Wood, Sue
AU - Zillikens, M. Carola
N1 - Funding Information: GA has received honoraria for consultancy and for lecturing in educational activities from Kyowa Kirin International. SSBN has received honoraria for providing consultancy from Kyowa Kirin International; and research grants, in addition to honoraria, for providing consultancy from Inozyme Pharma. AMB has received research grants and honoraria for providing consultancy and lectures from Kyowa Kirin International. MLB has received honoraria from Amgen, Bruno Farmaceutici S.p.A., Calcilytix, Kyowa Kirin International and UCB Pharma; grants and/or speaker fees from Abiogen Pharma, Alexion, Amgen, Bruno Farmaceutici S.p.A., Echolight, Eli Lilly and Company, Kyowa Kirin International, SPA, Theramex and UCB Pharma; and consultancy fees from Alexion, Amolyt Pharma, Bruno Farmaceutici S.p.A., Calcilytix, Kyowa Kirin International and UCB Pharma. KB has received honoraria as a consultant from Amgen, Kyowa Kirin International, Theramex and UCB Pharma. CLC has received honoraria for consultancy and for lecturing in educational activities from Kyowa Kirin International. FE has received honoraria from Chiesi Farmaceutici, Kyowa Kirin International and Recordati Rare Diseases; grants and/or speaker fees from Chiesi Farmaceutici, Kyowa Kirin International and Recordati Rare Diseases; and consultant fees from Alnylam, AVROBIO, Kyowa Kirin International and Otsuka. SG has no competing interests to declare. DH has received consultancy and speaker fees from Chiesi Farmaceutici and Kyowa Kirin International; and research grants from Amgen, Chiesi Farmaceutici and Kyowa Kirin International. RK has received honoraria from Kyowa Kirin International for advisory board participation. EL has received consultancy fees from Kyowa Kirin International. OM has received honoraria as a consultant from BridgeBio, Kyowa Kirin International and Ultragenyx. MZM has received honoraria for attending advisory boards and for educational lectures/webinars from Kyowa Kirin International. ON has received consultancy honoraria and research funding from Kyowa Kirin International. DS serves as a consultant for Kyowa Kirin Germany; and has received honoraria for attending advisory boards from Kyowa Kirin International. LTS has received honoraria as a consultant from Amgen and Kyowa Kirin International. JL and AW are employees of Kyowa Kirin International. SW was an employee of Kyowa Kirin International at the time of drafting this manuscript. MCZ reports that her institution has received a research grant from Kyowa Kirin International. Funding Information: The registry was implemented by Medialis Ltd, acting as the clinical research organization across Europe for the first year. On transitioning the International XLH Registry from Medialis Ltd to a new clinical research organization in January 2019, the sponsor updated the core documents to refer to the burosumab post-authorization safety study as a sub-study and reassigned the role of data controller from the patient to the sponsor. J Tonge, A Dillon and J MacLeod, as employees of Medialis Ltd, served as study managers during the implementation of the International XLH Registry. GA, FE and EL are members of the European Reference Network for Rare Kidney Diseases (ERKNet); SG, ON and MCZ are members of the European Reference Network on Rare Bone Diseases (ERN BOND); ON, DS and MCZ are members of the European Reference Network on Rare Endocrine Conditions (Endo-ERN); OM is a member of the European Reference Network for Rare Malformation Syndromes, Intellectual and Other Neurodevelopmental Disorders (ERN-ITHACA) and the Cost Action CA18139 Genomics of Musculoskeletal Traits Translational Network (GEMSTONE). Edward Maguire, Ph.D. (90TEN Ltd) provided medical writing support for the manuscript. Publisher Copyright: © 2023, Institut National de la Santé et de la Recherche Médicale (INSERM).
PY - 2023/12/1
Y1 - 2023/12/1
N2 - Background: X-linked hypophosphatemia (XLH) is a rare, hereditary, progressive, renal phosphate-wasting disorder characterized by a pathological increase in FGF23 concentration and activity. Due to its rarity, diagnosis may be delayed, which can adversely affect outcomes. As a chronic disease resulting in progressive accumulation of musculoskeletal manifestations, it is important to understand the natural history of XLH over the patient’s lifetime and the impact of drug treatments and other interventions. This multicentre, international patient registry (International XLH Registry) was established to address the paucity of these data. Here we present the findings of the first interim analysis of the registry. Results: The International XLH Registry was initiated in August 2017 and includes participants of all ages diagnosed with XLH, regardless of their treatment and management. At the database lock for this first interim analysis (29 March 2021), 579 participants had entered the registry before 30 November 2020 and are included in the analysis (360 children [62.2%], 217 adults [37.5%] and 2 whose ages were not recorded [0.3%]; 64.2% were female). Family history data were available for 319/345 (92.5%) children and 145/187 (77.5%) adults; 62.1% had biological parents affected by XLH. Genetic testing data were available for 341 (94.7%) children and 203 (93.5%) adults; 370/546 (67.8%) had genetic test results; 331/370 (89.5%) had a confirmed PHEX mutation. A notably longer time to diagnosis was observed in adults ≥ 50 years of age (mean [median] duration 9.4 [2.0] years) versus all adults (3.7 [0.1] years) and children (1.0 [0.2] years). Participants presented with normal weight, shorter length or height and elevated body mass index (approximately − 2 and + 2 Z-scores, respectively) versus the general population. Clinical histories were collected for 349 participants (239 children and 110 adults). General data trends for prevalence of bone, dental, renal and joint conditions in all participants were aligned with expectations for a typical population of people with XLH. Conclusion: The data collected within the International XLH Registry, the largest XLH registry to date, provide substantial information to address the paucity of natural history data, starting with demographic, family history, genetic testing, diagnosis, auxology and baseline data on clinical presentation.
AB - Background: X-linked hypophosphatemia (XLH) is a rare, hereditary, progressive, renal phosphate-wasting disorder characterized by a pathological increase in FGF23 concentration and activity. Due to its rarity, diagnosis may be delayed, which can adversely affect outcomes. As a chronic disease resulting in progressive accumulation of musculoskeletal manifestations, it is important to understand the natural history of XLH over the patient’s lifetime and the impact of drug treatments and other interventions. This multicentre, international patient registry (International XLH Registry) was established to address the paucity of these data. Here we present the findings of the first interim analysis of the registry. Results: The International XLH Registry was initiated in August 2017 and includes participants of all ages diagnosed with XLH, regardless of their treatment and management. At the database lock for this first interim analysis (29 March 2021), 579 participants had entered the registry before 30 November 2020 and are included in the analysis (360 children [62.2%], 217 adults [37.5%] and 2 whose ages were not recorded [0.3%]; 64.2% were female). Family history data were available for 319/345 (92.5%) children and 145/187 (77.5%) adults; 62.1% had biological parents affected by XLH. Genetic testing data were available for 341 (94.7%) children and 203 (93.5%) adults; 370/546 (67.8%) had genetic test results; 331/370 (89.5%) had a confirmed PHEX mutation. A notably longer time to diagnosis was observed in adults ≥ 50 years of age (mean [median] duration 9.4 [2.0] years) versus all adults (3.7 [0.1] years) and children (1.0 [0.2] years). Participants presented with normal weight, shorter length or height and elevated body mass index (approximately − 2 and + 2 Z-scores, respectively) versus the general population. Clinical histories were collected for 349 participants (239 children and 110 adults). General data trends for prevalence of bone, dental, renal and joint conditions in all participants were aligned with expectations for a typical population of people with XLH. Conclusion: The data collected within the International XLH Registry, the largest XLH registry to date, provide substantial information to address the paucity of natural history data, starting with demographic, family history, genetic testing, diagnosis, auxology and baseline data on clinical presentation.
KW - Fibroblast growth factor 23 (FGF23)
KW - Hypophosphatemic rickets
KW - International
KW - Natural history
KW - Osteomalacia
KW - PHEX mutation
KW - Patient registry
KW - Rare disease
KW - X-linked hypophosphatemia (XLH)
UR - http://www.scopus.com/inward/record.url?scp=85172908856&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s13023-023-02882-4
DO - https://doi.org/10.1186/s13023-023-02882-4
M3 - Article
C2 - 37752558
SN - 1750-1172
VL - 18
JO - Orphanet Journal of Rare Diseases
JF - Orphanet Journal of Rare Diseases
IS - 1
M1 - 304
ER -