Use of anti-FGF23 monoclonal antibody in the treatment of children and adolescents with X-linked hypophosphatemic rickets: Argentine experience

HAMILTON CASSINELLI; LUCIANA BRENZONI; LAURA ALCONCHER; VERÓNICA FORCLAZ; SOLANGE ROSENBROCK; IGNACIO BERGADÁ

Congreso; 10 TH INTERNACIONAL CONFERENCE ON CHILDREN S BONE HEALTH; 2022

Hamilton Cassinelli1, Luciana Brenzoni1, Laura Alconcher2, Verónica Forclaz3, Solange Rosenbrock1, Ignacio Bergadá11CEDIE, Centro de Investigaciones Endocrinológicas Dr. Cesar Bergadá. División de Endocrinología infantil, Hospital de Niños Ricardo Gutierrez, Ciudad de Buenos Aires, Argentina. 2Unidad de Nefrología Pediátrica Hospital Interzonal Dr. José Penna, Bahía Blanca, Argentina. 3Hospital Nacional Prof. A. Posadas, Buenos Aires, Argentina.IntroductionX-linked hypophosphatemia (XLH) is caused by loss-of-function mutations in the PHEX gene which results in excess of fibroblast growth factor 23 (FGF-23). This leads to a marked renal phosphate wasting and, as a consequence, chronic hypophosphatemia. In childhood, the clinical signs of XLH manifest as rickets and osteomalacia, with varum and valgum deformity of the knees, short stature, pain and impaired quality of life. Here, we report a pilot experience in children and adolescents with XLH on the effectiveness and safety of treatment with Burosumab (a human monoclonal antibody targeted to inhibit excess FGF-23 activity).Aim: to assess the effectiveness and safety of burosumab treatment in children with XLH diagnosis. Design: a cohort descriptive study.Patients:Eight children aged > 1 year old with XLH were included in the study. The diagnosis of XLH was confirmed considering the clinical characteristics (limbs deformities –genu varum or valgum- short stature), meeting laboratory test criteria (hypophosphatemia with renal phosphate wasting), radiological evidence of rickets and/or PHEX mutation (performed in patient or in a family member with XLH). Methods:Patients included withdrew conventional treatment at least 7 days before starting Burosumab. Variables analyzed: growth velocity, degree of rickets (assessed by Thacher Rickets Severity Score), serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), parathyroid hormone (PTH), urine phosphorus and creatinine were assessed at baseline, 3,6, 12, 18 and 24 months. All serum and urine samples were obtained during fasting.Clinical and auxological characteristic were assessed at each point.Categorical data were summarized using frequency and percentage; continuous data were summarized using median and range. We applied Wilcoxom test to analyze data and a P value of< 0,05 was considered significant. Table 1. Patient baseline demographic and clinical characteristics. Fig. 1. Changes in biomarkers and growth velocity from baseline and during treatment with Burosumab. (median and range). Shaded area denotes normal range. Sex F/M (%)Age at diagnosis in years* Pubertal development (Tanner)Prepubertal (%) Pubertal (%)Weight Z score* Height Z score* Family history of XLHPHEX mutation positive, n (%)a 3/5 (37,5/62,5)0,96 (0,5-2,21)655/8 (62,5)3/8 (37,5)4-0,15 (-1,48-1,45)3-1,83 (-3,87- -0,12)5/86 (100) 2 0 0 01 5 0 01 0 0 05 0 0 Biochemistry 01 0 09 08 0 03691 21 51 82 12 4M o n t h s 003691 21 51 82 12 4M o n t h s1 51 0 Radiological assessmentRSS4 (1-6) * Median (range)a Only 6 patients were tested for PHEX mutation.ALP: alkaline phosphatase. PTR: phosphate tubular reabsorption. PTH: parathyroid hormone. FGF-23: fibroblast growth factor 23.Table 2. Adverse events. 7 06 05 003691 21 51 82 12 4M o n t h s 5003691 21 51 8M o n t h 2 12 4 A.The median of serum phosphate increases from baseline to 24 month (p