SUN-345 Use of Anti-FGF23 Monoclonal Antibody in the Treatment of Children and Adolescents with X-Linked Hypophosphatemic Rickets

摘要

Background: X-linked hypophosphataemia is the most common heritable form of rickets in children, disorder caused by mutations in PHEX, leading to elevated secretion of FGF23, renal phosphate wasting with consequent hypophosphataemia, diminish synthesis of 1,25(OH)2 vitamin D, rickets/osteomalacia, and disproportionate short stature. Conventional treatment with oral phosphate supplementation and active vitamin D heals rickets, prevents progressive growth failure, but in a substantial proportion of patients treatment is unsuccessful and/or associated with adverse effects. Since 2018, burosumab, a human monoclonal antibody against FGF23, was approved for the treatment of X-linked hypophosphataemia.Aim: We report a pilot experience on the efficacy and safety of treatment with burosumab in children and adolescents with X-linked hypophosphataemia (XLH). Methods and patients: Eight XLH patients (5 males) (5 pre pubertal and 3 Tanner IV) with an age range from 2.9 to 16.2 years, were recruited, 6/8 had family history of XLH, the remaining two were confirmed with molecular study. All discontinue conventional therapy at least 7 days before treatment with Burosumab which was administered every 2 weeks SC for 6 months, at a starting dose of 0.8 mg/kg/dose. Growth velocity, Thacher Rickets Severity Score, fasting serum calcium (mg/dl), phosphorus (P)(mg/dl), alkaline phosphatase (ALP)(IU/L), PTH (pg/dl), 25OH Vitamin D (ng/ml) and tubular phosphate reabsorption (TPR) (X±SD) were evaluated at basal, 3, and 6 months of treatment. Results: All patients had normal 25OH2 Vitamin D: 35.3±8.6 ng/ml at the start of therapy and had significantly improvement of serum P: basal 2.2±0.51, 3 months: 3.24±0.43 and at 6 months 3.01±0.38 mg/dl (p<0.005). The mean serum ALP level decreased from 686.9±410.8 to 535.8±302.4 and 402.5±106.7 IU/L (p<0.05) respectively. TPR normalized during treatment: 67.3±9, 86±3.1, and 86.9±6.1 %(p<0.001). The severity of rickets, as well, showed a significant improvement: 4.0±2.0, 2.3±1.2, and 1.0±0.8 (p<0.005), respectively. The non-pubertal children increased their growth velocity from 3.7±1.2 cm/yr to 7.0±1.4, and 7.9±2.0 cm/yr (p<0.05) respectively. Serum calcium and PTH levels did not show any significantly variation. Mild adverse events such as local reactions and headaches were observed. Conclusions: 1) Treatment with burosumab restores phosphate metabolism, 2) Growth and the Thacher Rickets Severity Score improved during treatment, 3) all patients showed a good safety profile with only minor adverse events. This is the first report of children with XLH treated with burosumab in Latin-America.