ESPE Abstracts (2019) 92 FC2.3

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-Bicetre, 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-Bicetre, France. 4APHP, Department of Endocrinology and Reproductive Diseases, Bicêtre Paris-Sud Hospital, Le Kremlin-Bicetre, France. 5Paris Sud – Paris Saclay University, Faculté de Médecine, Le Kremlin-Bicetre, France. 6APHP, Department Pediatric Radiology, Bicêtre Paris-Sud Hospital, Le Kremlin-Bicetre, France. 7APHP, Department of ORL, Bicêtre Paris-Sud Hospital, Le Kremlin-Bicetre, France. 8APHP, Department of Odontology-Maladies Rares, Hospital Bretonneau Paris, Paris, France. 9Université Paris Descartes Paris, Paris, France. 10APHP, Department 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-Bicetre, France. 15APHP, Hôpital Necker Enfants Malades,15APHP, Hôpital Necker Enfants Malades, INSERM U115115APHP, Hôpital Necker Enfants Malades, INSERM U1151 INSERM U1151, Paris, France

Background/Aim: X-linked hypophosphatemia (XLH) is a rare disease caused by mutations in PHEX, leading to elevated FGF23 levels, hypophosphatemia and chronic renal phosphate wasting. Burosumab is a monoclonal antibody against anti-FGF23, which has been recently approved for treatment of XLH. Beyond clinical trials, little is known about its efficacy/safety in clinical practice which is the aim of study.

Patients/Methods: 45 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 and elevated levels of alkaline phosphatase, need for orthopaedic surgery, presence of neurological, dental, hearing complications, secondary hyperparathyroidism, height<-2SDS treated or not with rhGH); intolerance to conventional therapy (nephrocalcinosis), 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 (ALP, 1,25(OH)2D, PTH, TmP/eGFR, CaU/CrU, side effects) were checked at M0, thereafter at 3-6-9 months of treatment (M3-M6-M9). Severe and non-severe forms of XLH were defined by >2 and ≤2 complications.

Results: 45 children (29 girls/16 boys, mean age 9.7±3.7 years) were treated with conventional therapy for 7.3±3.9 years before starting burosumab. 28 patients completed 9 months of burosumab treatment. Upon burosumab, levels of sP, TmP/eGFR, 1,25(OH)2D increased significantly (sP 0.7±0.1→1.2±0.2→1.2±0.2→1.2±0.1 mmol/l; TmP/eGFR 0.6±1.1→1.1±0.2→1.1±0.2→1.1±0.1;1,25(OH)2D26.2±15.7→73.8±22.7→88.4±39.9→82.5±19.9 pg/ml, M0-M3-M6-M9, respectively, p for trend=0.000) and ALP decreased significantly(414±153→339±141→339±146→313±148UI/l, M0-M3-M6-M9, respectively, p for trend=0.036). At M9, the average dose of burosumab was 1.4±0.5 mg/kg (47±25 mg); 39% (n=9) of patients did not achieve target sP level. At M9, 32% (n=9) of subjects received the maximal dose of burosumab (2.0 mg/kg or 90 mg), yet having low sP level. Children with the severe form of XLH needed higher final dose of burosumab compared with patients having the non-severe form (1.4±0.5 vs 1.1±0.5 mg/kg, 53±27 vs 34±20 mg, respectively, P=0.068 and 0.017, respectively). No severe adverse events were noticed, the most frequent side effect being redness at sites of injection, muscular/bone/abdominal pain.

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

Volume 92

58th Annual ESPE

Vienna, Austria
19 Sep 2019 - 21 Sep 2019

European Society for Paediatric Endocrinology 

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