Advancing Patient Evidence in XLH (APEX): Baseline analysis of a global data unification program.

Abstract

X-linked hypophosphatemia (XLH) is a rare, genetic, progressive, lifelong disorder caused by pathogenic variants in the PHEX gene, leading to excess fibroblast growth factor 23 (FGF23) and renal phosphate wasting. Advancing Patient Evidence in XLH (APEX) is a 10-year global data unification project that combines 3 regional observational studies (XLH Disease Monitoring Program [DMP], International XLH Registry [IXLHR], and SUNFLOWER). APEX aims to describe the burden and lifelong progression of XLH, to collect real-world data on treatment effectiveness and safety, and to investigate regional differences in treatment outcomes. This was a baseline analysis of the characteristics and disease burden of a global group of patients with XLH. This analysis included 1556 participants (XLH DMP n = 598; IXLHR n = 736; SUNFLOWER n = 222), with 590 participants aged 0-12 years, 193 aged 13-17 years, and 773 aged ≥18 years. Overall, 66 % of participants were female. Family history of XLH and of a PHEX variant were reported for 55 % and 47 % of participants, respectively; 71 % of participants had a confirmed PHEX variant. Participants had reduced height, normal weight, and elevated body mass index compared with a reference population. Clinical histories demonstrated increasing prevalence of dental complications, fractures, and osteoarthritis with age. Median Z-scores for phosphate, tubular maximum reabsorption of phosphate to glomerular filtration rate, and urine calcium/creatinine ratio were below the scores for the reference population. This baseline analysis provides substantial information on the global characteristics and natural history of patients with XLH in the APEX program. ClinicalTrials.govNCT03651505 (registered August 24, 2018), NCT03193476 (registered June 13, 2017), NCT03745521 (registered November 6, 2018).