Burosumab Therapy in Children and Adolescents with X-linked Hypophosphatemia: The Real-Life Israeli Experience

Leonid Zeitlin ^1,2 Shelly Levi ^2,3 Shoshana Gal ^4,5 Avivit Brener ^2,6 Yael Lebenthal ^2,6 David Gillis ^7,8 David Strich ^8,9 Amnon Zung ^8,10 Roxana Cleper ^2,11 Yael Borovitz ^2,3 Miriam Davidovits ^2,3 Zvi Zadik ^8,10 Yael Levy-Shraga* ^2,12 Dov Tiosano* ^4,5

¹Pediatric Orthopedic Department, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, ישראל
²The Sackler Faculty of Medicine, Tel-Aviv University, ישראל
³Pediatric Nephrology Unit, Schneider Children’s Medical Center, ישראל
⁴Division of Pediatric Endocrinology, Ruth Rappaport Children's Hospital, Rambam Medical Center, ישראל
⁵Bruce Rappaport Faculty of Medicine, Technion, ישראל
⁶Pediatric Endocrinology and Diabetes Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, ישראל
⁷Pediatric Endocrinology, Hadassah-Hebrew University Medical Center, ישראל
⁸Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical School, ישראל
⁹Department of Pediatrics, Shaare Zedek Medical Center, ישראל
¹⁰Pediatrics Department, Kaplan Medical Center, ישראל
¹¹Pediatric Nephrology Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, ישראל
¹²Pediatric Endocrinology Unit, The Edmond and Lily Safra Children's Hospital, Chaim Sheba Medical Center, ישראל

Background: X-Linked Hypophosphatemia (XLH) is an inherited disease caused by mutations in the PHEX gene, resulting in elevated FGF23 concentrations which lead to hyperphosphaturia and decreased synthesis of 1,25-dihydroxy-vitamin D. Patients with XLH suffer from hypophosphatemia, rickets, short stature and significant morbidity, previously treated (with partial success) with multiple daily doses of oral phosphate salts and active vitamin D. Burosumab, a human monoclonal antibody against FGF23, is a novel treatment for XLH introduced in Israel in 2017. We describe the Israeli experience with this agent.

Methods: Real-life data of children with XLH followed at seven medical centers were collected from diagnosis through burosumab treatment. Outcome measures: anthropometric measurements, laboratory parameters, imaging and adverse events were retrieved from the medical charts. Skeletal changes were evaluated by radiography using the rickets-severity scale (RSS) and the radiographic global impression of change (RGI-C).

Results: Twenty-six patients with XLH (age 3-16 years) received burosumab subcutaneously every 2 weeks for 9-20 months. The initial dose was 0.4-0.8 mg/kg, titrated by serum phosphate according to recommendations. Phosphate homeostasis improved in all patients as evidenced by increased renal tubular reabsorption of phosphate, normalization of phosphate and alkaline phosphatase levels and increased 1,25-dihydroxy-vitamin D. Rickets severity score decreased and linear growth increased in most patients. No severe adverse events were reported.

Conclusions: Burosumab had a favorable effect on renal tubular reabsorption of phosphate and rickets score in patients treated under real-life circumstances. Further surveillance is needed to evaluate long-term effects on bone health and adult height.

* Equal contribution