推进XLH （APEX）患者证据：全球数据统一计划的基线分析。

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone Pub Date : 2025-09-15 DOI:10.1016/j.bone.2025.117649

Thomas O. Carpenter , Seiji Fukumoto , Dieter Haffner , Erik A. Imel , Keiichi Ozono , Haruka Ishii , Zhiyi Li , Kerry Sandilands , Paul Joos-Vandewalle , Cheuk Lee , Masanori Kanematsu , Keith P. McCullough , Maria Luisa Brandi

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引用次数: 0

摘要

目的：x连锁低磷血症（XLH）是一种罕见的遗传性进行性终身疾病，由PHEX基因的致病性变异引起，导致成纤维细胞生长因子23 （FGF23）过量和肾磷酸盐消耗。推进XLH患者证据（APEX）是一项为期10年的全球数据统一项目，结合了3个区域观察性研究（XLH疾病监测计划[DMP]，国际XLH登记处[IXLHR]和向日葵）。APEX旨在描述XLH的负担和终身进展，收集有关治疗有效性和安全性的真实数据，并调查治疗结果的地区差异。方法：这是对全球一组XLH患者的特征和疾病负担的基线分析。结果:分析包括1556名参与者(XLH DMP n = 598;IXLHR n = 736;向日葵n = 222),590岁的参与者经历 年,193 13 - 17 岁和773年龄≥18 年。总体而言，66%（ %）的参与者是女性。分别有55% %和47% %的参与者报告有XLH和PHEX变异的家族史；71% %的参与者确认患有PHEX变异。与参考人群相比，参与者身高降低，体重正常，身体质量指数升高。临床病史表明，随着年龄的增长，牙齿并发症、骨折和骨关节炎的患病率增加。磷酸盐、肾小管最大磷酸盐重吸收到肾小球滤过率和尿钙/肌酐比值的中位数z得分低于参考人群的得分。结论：该基线分析提供了APEX项目中XLH患者的总体特征和自然史的大量信息。注册：ClinicalTrials.govNCT03651505（注册于2018年8月24日），NCT03193476（注册于2017年6月13日），NCT03745521（注册于2018年11月6日）。

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

Purpose

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.

Methods

This was a baseline analysis of the characteristics and disease burden of a global group of patients with XLH.

Results

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.

Conclusion

This baseline analysis provides substantial information on the global characteristics and natural history of patients with XLH in the APEX program.

Registration

ClinicalTrials.gov NCT03651505 (registered August 24, 2018), NCT03193476 (registered June 13, 2017), NCT03745521 (registered November 6, 2018).

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来源期刊

Bone 医学-内分泌学与代谢

CiteScore

8.90

自引率

4.90%

发文量

264

审稿时长

30 days

期刊介绍： BONE is an interdisciplinary forum for the rapid publication of original articles and reviews on basic, translational, and clinical aspects of bone and mineral metabolism. The Journal also encourages submissions related to interactions of bone with other organ systems, including cartilage, endocrine, muscle, fat, neural, vascular, gastrointestinal, hematopoietic, and immune systems. Particular attention is placed on the application of experimental studies to clinical practice.