Clinical guidelines for burosumab in the treatment of XLH in children and adolescents: British paediatric and adolescent bone group recommendations

Endocr Connect. 2020 Oct;9(10):1051-1056. doi: 10.1530/EC-20-0291.

PMID: 33112809

Raja Padidela, Moira S Cheung, Vrinda Saraff, Poonam Dharmaraj

Summary: Burosumab, a recombinant human IgG1 monoclonal antibody, has been shown to improve phosphate homeostasis, which resolves the skeletal and non-skeletal manifestations of X-linked hypophosphataemia (XLH), in clinical trials (phases 2 and 3).

Abstract

Background: X-linked hypophosphataemia (XLH) is caused by a pathogenic variant in the PHEX gene, which results in elevated circulating FGF23. High FGF23 levels induce hypophosphatemia and low active vitamin D levels, which manifest clinically as rickets in children and osteomalacia in children and adults.

Objective: Oral phosphate and active vitamin D analogues are the conventional treatments for XLH, but they do not address the underlying pathophysiology of elevated FGF23-induced hypophosphataemia. Furthermore, frequent daily dosing and side effects such as gastrointestinal symptoms, secondary hyperparathyroidism, and nephrocalcinosis limit adherence to conventional therapy.

Conclusion: Burosumab, a recombinant human IgG1 monoclonal antibody that binds to and inhibits the activity of FGF23, is administered subcutaneously every 2 weeks. Burosumab has been shown to improve phosphate homeostasis, which resolves the skeletal and non-skeletal manifestations of XLH, in clinical trials (phases 2 and 3). Burosumab was approved in Europe in February 2018, with the National Institute for Health and Care Excellence in the United Kingdom approving it in October 2018. In this study, The British Paediatric and Adolescent Bone Group (BPABG) reviewed existing evidence and provide expert recommendations for the management of XLH with burosumab.

Keywords: BPABG; NICE; XLH; burosumab; hypophosphataemia.