Real-world data of Brazilian adults with X-linked hypophosphatemia (XLH) treated with burosumab and comparison with other worldwide cohorts

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article
Data de publicação
2024
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Scopus
Web of Science
PubMed
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Editora
WILEY
Autores
CILLO, Antonio Cesar Paulillo de
SILVA, Barbara Campolina C.
DALVA, Catarina Brasil
CARVALHO, Erico Higino de
ALMEIDA, Juliana M. C. M. de
MARQUES, Larissa L. M.
RIBEIRO, Marcia
SILVA, Mauro Borghi M. da
MEDEIROS, Paula Frassinetti V. de
Citação
MOLECULAR GENETICS & GENOMIC MEDICINE, v.12, n.2, article ID e2387, 27p, 2024
Projetos de Pesquisa
Unidades Organizacionais
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Resumo
Background: 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)(2) 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. Methods: The current real-world collaborative study evaluated genetic, clinical and laboratory data of XLH Brazilian adult patients treated with burosumab. Results: 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)(2) 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). Conclusions: 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.
Palavras-chave
adulthood, burosumab, FGF23, hyperparathyroidism, PHEX variants, X-linked hypophosphatemia
URI
https://observatorio.fm.usp.br/handle/OPI/59215
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Coleções
Artigos e Materiais de Revistas Científicas - HC/ICr