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Endocrine Abstracts (2019) 63 OC7.3 | DOI: 10.1530/endoabs.63.OC7.3

1APHP, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, Filiere OSCAR and Platform of expertise for rare diseases Paris-Sud, Bicêtre Paris-Sud Hospital, Le Kremlin Bicêtre, France; 2Department of Clinical Medicine and Surgery, Division of Endocrinology, University of Naples Federico II, Naples, Italy; 3APHP, Department of Endocrinology and Diabetology for children, Bicêtre Paris-Sud Hospital, Le Kremlin Bicêtre, France; 4Paris Sud – Paris Saclay University, Faculté de Médecine, Le Kremlin Bicêtre, France; 5Department of Endocrinology and Reproductive Disease, Bicêtre Paris-Sud Hospital, Le Kremlin Bicêtre, France; 6Department Pediatric Radiology, Bicêtre Paris Sud Hospital, Le Kremlin Bicêtre, France; 7APHP, Department of ORL, Bicêtre Paris Sud Hospital, Le Kremlin Bicêtre, France; 8Department of Odontology-Maladies Rares, Hospital Bretonneau Paris, Paris, France; 9Universite Paris Descartes, Paris, France; 10Department of Pediatric orthopaedic surgery, Necker - Sick Kids University Hospital, Paris, France; 11APHP, Department of Rheumatology Hospital Cochin, Paris, France; 12Pediatric Neurosurgery, Hospital Femme Mere Enfant, Hospices Civiles de Lyon and University Claude Bernard Lyon, Bron Cedex, France; 13Reference Center for Craniosynostosis, INSERM 1033, Lyon, France; 14APHP, Department of Molecular Genetics, Pharmacogenetics and Hormonology, Bicêtre Paris-Sud Hospital, Le Kremlin Bicêtre, France; 15Université Paris V, Faculté de Médecine, Paris, France; 16Hôpital Necker Enfants Malades APHP, INSERM U1151, Paris, France.

Background/aim: Burosumab is a monoclonal antibody against anti-FGF23, which has been recently approved for the treatment of X-linked hypophosphatemia (XLH). Beyond clinical trials, little is known about its efficacy/safety in clinical practice which is the aim of the present study.

Patients/methods: Thirty-nine children with XLH were switched from conventional therapy to burosumab (starting dose 0.4 mg/kg), on the basis of following indications: non-responder to conventional therapy (persistence of leg deformities, elevated levels of alkaline phosphatase, need for orthopaedic surgery, presence of neurological, dental, hearing complications, secondary hyperparathyroidism, height<-2SDS); intolerance to conventional therapy (nephrocalcinosis, hypercalciuria) or late diagnosis (>8 years). Serum phosphate level (sP) was checked before starting burosumab (M0) and monitored every 2 weeks for dose adjustment (target sP>1.2 mmol/l). Other parameters (weight, height, ALP, 1,25(OH)2D, PTH, TmP/eGFR, CaU/CrU, side effects) were checked at M0, thereafter at 3 and 6 months of treatment (M3-M6).

Results: Twenty-five girls/14 boys (mean age 9.6±3.8 years; 84.6% of subjects (n=33) with complications) were treated with conventional therapy for 7.7±3.8 years before starting burosumab. 26 patients completed 6 months of treatment. Upon burosumab, levels of sP, TmP/eGFR, 1,25(OH)2D increased significantly (sP 0.7±1.1→1.2±0.2→1.1±0.1 mmol/l; TmP/eGFR 0.6±1.1→1.1±0.2→1.0±0.2; 1,25(OH)2D 26.0±15.3→73.4±24.0→88.0±34.4 pg/ml at M0-M3-M6, respectively, p for trend=0.000) and ALP decreased (413±163→333±150 UI/l at M0-M6, respectively, P=0.3). However, PTH level and CaU/CrU ratio were not modified during the treatment. At M6, the average dose of burosumab was 1.3±0.5 mg/kg (45±23 mg); 61.5% (n=16) of patients did not achieve target sP level. At M6, 27% (n=7) of subjects received the maximal dose of burosumab (2.0 mg/kg or 90 mg), yet had low sP level. The number of complications was positively associated with the final dose of burosumab (32±13 vs 31±16 vs 57±24 mg for children with 0, ≤2 and >2 complications, respectively, P for trend=0.004). We did not observe severe adverse events during the treatment, the most frequent side effect being redness at sites of injection.

Conclusion: Treatment with burosumab restores phosphate reabsorption, increases sP and endogenous 1,25(OH)2D synthesis. The dose of burosumab needs to be increased with the severity of the disease.

Volume 63

21st European Congress of Endocrinology

Lyon, France
18 May 2019 - 21 May 2019

European Society of Endocrinology 

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