University of São Paulo School of Medicine, Sao Paulo, Brazil.
Pontifícia Universidade Católica, Campinas, Brazil.
Mol Genet Genomic Med. 2024 Feb;12(2):e2387. doi: 10.1002/mgg3.2387.
Disease-related variants in PHEX cause XLH by an increase of fibroblast growth factor 23 (FGF23) circulating levels, resulting in hypophosphatemia and 1,25(OH) vitamin D deficiency. XLH manifests in early life with rickets and persists in adulthood with osseous and extraosseous manifestations. Conventional therapy (oral phosphate and calcitriol) improves some symptoms, but evidence show that it is not completely effective, and it can lead to nephrocalcinosis (NC) and hyperparathyroidism (HPT). Burosumab (anti-FGF23 antibody) has shown to be effective and safety in the clinical trials.
The current real-world collaborative study evaluated genetic, clinical and laboratory data of XLH Brazilian adult patients treated with burosumab.
Nineteen unrelated patients were studied. Patients reported pain, limb deformities and claudication, before burosumab initiation. 78% of them were previously treated with conventional therapy. The severity of the disease was moderate to severe (15 patients with score >5). At the baseline, 3 patients presented NC (16.7%) and 12 HPT (63%). After 16 ± 8.4 months under burosumab, we observed a significant: increase in stature (p = 0.02), in serum phosphate from 1.90 ± 0.43 to 2.67 ± 0.52 mg/dL (p = 0.02); in TmP/GFR from 1.30 ± 0.46 to 2.27 ± 0.64 mg/dL (p = 0.0001), in 1,25 (OH) D from 50.5 ± 23.3 to 71.1 ± 19.1 pg/mL (p = 0.03), and a decrease in iPTH from 86.8 ± 37.4 pg/mL to 66.5 ± 31.1 (p = 0.002). Nineteen variants were found (10 novel). HPT tended to develop in patients with truncated PHEX variants (p = 0.06).
This study confirms the efficacy and safety of burosumab on XLH adult patients observed in clinical trials. Additionally, we observed a decrease in iPTH levels in patients with moderate to severe HPT at the baseline.
PHEX 中的疾病相关变异通过增加成纤维细胞生长因子 23（FGF23）的循环水平导致 XLH，导致低磷血症和 1,25（OH）维生素 D 缺乏。XLH 在生命早期表现为佝偻病，并在成年期持续存在骨骼和骨骼外表现。常规治疗（口服磷酸盐和骨化三醇）可改善一些症状，但证据表明其并非完全有效，且可能导致肾钙质沉着症（NC）和甲状旁腺功能亢进症（HPT）。Burosumab（抗 FGF23 抗体）在临床试验中已被证明是有效且安全的。
本项真实世界合作研究评估了接受 Burosumab 治疗的巴西成年 XLH 患者的遗传、临床和实验室数据。
共研究了 19 名无血缘关系的患者。在开始使用 Burosumab 之前，患者报告了疼痛、肢体畸形和跛行。其中 78%的患者曾接受过常规治疗。疾病严重程度为中度至重度（15 名患者评分>5）。在基线时，有 3 名患者出现 NC（16.7%）和 12 名 HPT（63%）。在接受 Burosumab 治疗 16±8.4 个月后，我们观察到以下显著变化：身高增加（p=0.02），血清磷酸盐从 1.90±0.43 升至 2.67±0.52mg/dL（p=0.02）；TmP/GFR 从 1.30±0.46 升至 2.27±0.64mg/dL（p=0.0001），1,25（OH）D 从 50.5±23.3 升至 71.1±19.1pg/mL（p=0.03），iPTH 从 86.8±37.4pg/mL 降至 66.5±31.1pg/mL（p=0.002）。共发现 19 种变异（10 种为新变异）。在基线时 HPT 趋于在截断型 PHEX 变异患者中发生（p=0.06）。
本研究证实了临床试验中观察到的 Burosumab 治疗 XLH 成年患者的疗效和安全性。此外，我们观察到基线时中重度 HPT 患者的 iPTH 水平降低。
