Back to Search
Start Over
Burosumab Therapy in Children with X-Linked Hypophosphatemia
Burosumab Therapy in Children with X-Linked Hypophosphatemia
- Source :
- New England Journal of Medicine, 378(21), 1987-1998. MASSACHUSETTS MEDICAL SOC
- Publication Year :
- 2018
-
Abstract
- X-linked hypophosphatemia is characterized by increased secretion of fibroblast growth factor 23 (FGF-23), which leads to hypophosphatemia and consequently rickets, osteomalacia, and skeletal deformities. We investigated burosumab, a monoclonal antibody that targets FGF-23, in patients with X-linked hypophosphatemia.In an open-label, phase 2 trial, we randomly assigned 52 children with X-linked hypophosphatemia, in a 1:1 ratio, to receive subcutaneous burosumab either every 2 weeks or every 4 weeks; the dose was adjusted to achieve a serum phosphorus level at the low end of the normal range. The primary end point was the change from baseline to weeks 40 and 64 in the Thacher rickets severity total score (ranging from 0 to 10, with higher scores indicating greater disease severity). In addition, the Radiographic Global Impression of Change was used to evaluate rachitic changes from baseline to week 40 and to week 64. Additional end points were changes in pharmacodynamic markers, linear growth, physical ability, and patient-reported outcomes and the incidence of adverse events.The mean Thacher rickets severity total score decreased from 1.9 at baseline to 0.8 at week 40 with every-2-week dosing and from 1.7 at baseline to 1.1 at week 40 with every-4-week dosing (P0.001 for both comparisons); these improvements persisted at week 64. The mean serum phosphorus level increased after the first dose in both groups, and more than half the patients in both groups had levels within the normal range (3.2 to 6.1 mg per deciliter [1.0 to 2.0 mmol per liter]) by week 6. Stable serum phosphorus levels were maintained through week 64 with every-2-week dosing. Renal tubular phosphate reabsorption increased from baseline in both groups, with an overall mean increase of 0.98 mg per deciliter (0.32 mmol per liter). The mean dose of burosumab at week 40 was 0.98 mg per kilogram of body weight with every-2-week dosing and 1.50 mg per kilogram with every-4-week dosing. Across both groups, the mean serum alkaline phosphatase level decreased from 459 U per liter at baseline to 369 U per liter at week 64. The mean standing-height z score increased in both groups, with greater improvement seen at all time points with every-2-week dosing (an increase from baseline of 0.19 at week 64) than with every-4-week dosing (an increase from baseline of 0.12 at week 64). Physical ability improved and pain decreased. Nearly all the adverse events were mild or moderate in severity.In children with X-linked hypophosphatemia, treatment with burosumab improved renal tubular phosphate reabsorption, serum phosphorus levels, linear growth, and physical function and reduced pain and the severity of rickets. (Funded by Ultragenyx Pharmaceutical and Kyowa Hakko Kirin; ClinicalTrials.gov number, NCT02163577 ; EudraCT number, 2014-000406-35 ).
- Subjects :
- Male
0301 basic medicine
Fibroblast growth factor 23
SYMPTOMS
Knee Joint
urologic and male genital diseases
Severity of Illness Index
0302 clinical medicine
ADOLESCENTS
Medicine
CALCITRIOL
Child
Osteomalacia
Antibodies, Monoclonal
Genetic Diseases, X-Linked
Phosphorus
General Medicine
RICKETS
X-linked hypophosphatemia
female genital diseases and pregnancy complications
PREVALENCE
Kidney Tubules
Child, Preschool
GROWTH
Female
Familial Hypophosphatemic Rickets
Hypophosphatemia
medicine.drug
musculoskeletal diseases
medicine.medical_specialty
Calcitriol
030209 endocrinology & metabolism
Rickets
Antibodies, Monoclonal, Humanized
03 medical and health sciences
Alkaline phosphatase blood
Internal medicine
Humans
Pain Management
business.industry
nutritional and metabolic diseases
ADULTS
KRN23
Alkaline Phosphatase
medicine.disease
Fibroblast Growth Factors
Radiography
Fibroblast Growth Factor-23
stomatognathic diseases
MICE
030104 developmental biology
Endocrinology
Multicenter study
business
Subjects
Details
- Language :
- English
- ISSN :
- 00284793
- Database :
- OpenAIRE
- Journal :
- New England Journal of Medicine, 378(21), 1987-1998. MASSACHUSETTS MEDICAL SOC
- Accession number :
- edsair.doi.dedup.....b7653e5471de5e851db6876497c4d37e