Patient-reported outcomes from a randomized, active-controlled, open-label, phase 3 trial of burosumab versus conventional therapy in children with x-linked hypophosphatemia

Padidela, Raja; Whyte, Michael P.; Glorieux, Francis H.; Munns, Craig F.; Ward, Leanne M.; Nilsson, Ola; Portale, Anthony A.; Simmons, Jill H.; Namba, Noriyuki; Cheong, Hae Il; Pitukcheewanont, Pisit; Sochett, Etienne; Högler, Wolfgang; Muroya, Koji; Tanaka, Hiroyuki; Gottesman, Gary S.; Biggin, Andrew; Perwad, Farzana; Williams, Angela; Nixon, Annabel; Sun, Wei; Chen, Angel; Skrinar, Alison; Imel, Erik A.

Affiliations

¹Department of Paediatric Endocrinology, Royal Manchester Children’s Hospital, Manchester, UK

²Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

³Shriners Hospitals for Children —Washington University School of Medicine in St Louis, St Louis, MO, USA

⁴Shriners Hospital for Children — Canada, McGill University, Montreal, QC, Canada

⁵The University of Sydney Children’s Hospital Westmead Clinical School, The Children’s Hospital at Westmead, Westmead, NSW, Australia

⁶Department of Endocrinology, The Children’s Hospital at Westmead, Westmead, NSW, Australia

⁷Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada

⁸Division of Endocrinology and Metabolism, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada

⁹Division of Pediatric Endocrinology & Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden

¹⁰School of Medical Sciences, Örebro University, Örebro, Sweden

¹¹Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA

¹²Departments of Pediatrics, Division of Endocrinology and Diabetes, Vanderbilt University School of Medicine, Vanderbilt University, Nashville, TN, USA

¹³Department of Pediatrics, Osaka Hospital, Japan Community Healthcare Organization, Osaka, Japan

¹⁴Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan

¹⁵Seoul National University Children’s Hospital, Seoul, Republic of Korea

¹⁶Center of Endocrinology, Diabetes and Metabolism, Children’s Hospital Los Angeles, Los Angeles, CA, USA

¹⁷Department of Paediatrics, Hospital for Sick Children, Toronto, ON, Canada

¹⁸Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Linz, Austria

¹⁹Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK

²⁰Department of Endocrinology and Metabolism, Kanagawa Children’s Medical Center, Yokohama, Japan

²¹Okayama Saiseikai General Hospital Outpatient Center, Okayama, Japan

²²Shriners Hospitals for Children, St Louis, MO, USA

²³Kyowa Kirin International, Marlow, UK

²⁴Chilli Consultancy, Salisbury, UK

²⁵Kyowa Kirin Pharmaceutical Development, Princeton, NJ, USA

²⁶Ultragenyx Pharmaceutical, Novato, CA, USA

²⁷Department of Medicine and Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA

Abstract and keywords

Changing to burosumab, a monoclonal antibody targeting fibroblast growth factor 23, significantly improved phosphorus homeostasis, rickets, lower-extremity deformities, mobility, and growth versus continuing oral phosphate and active vitamin D (conventional therapy) in a randomized, open-label, phase 3 trial involving children aged 1–12 years with X-linked hypophosphatemia. Patients were randomized (1:1) to subcutaneous burosumab or to continue conventional therapy. We present patient-reported outcomes (PROs) from this trial for children aged ≥ 5 years at screening (n = 35), using a Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire and SF-10 Health Survey for Children. PROMIS pain interference, physical function mobility, and fatigue scores improved from baseline with burosumab at weeks 40 and 64, but changed little with continued conventional therapy. Pain interference scores differed significantly between groups at week 40 (− 5.02, 95% CI − 9.29 to − 0.75; p = 0.0212) but not at week 64. Between-group differences were not significant at either week for physical function mobility or fatigue. Reductions in PROMIS pain interference and fatigue scores from baseline were clinically meaningful with burosumab at weeks 40 and 64 but not with conventional therapy. SF-10 physical health scores (PHS-10) improved significantly with burosumab at week 40 (least-squares mean [standard error] + 5.98 [1.79]; p = 0.0008) and week 64 (+ 5.93 [1.88]; p = 0.0016) but not with conventional therapy (between-treatment differences were nonsignificant). In conclusion, changing to burosumab improved PRO measures, with statistically significant differences in PROMIS pain interference at week 40 versus continuing with conventional therapy and in PHS-10 at weeks 40 and 64 versus baseline. Trial registration: ClinicalTrials.gov NCT02915705

Keywords: Burosumab; X-linked hypophosphatemia; Patient-reported outcomes; Patient-reported outcomes measurement information system

Links

DOI: 10.1007/s00223-020-00797-x

PubMed: 33484279

WoS: 000610462000001

History

Received: 2020-10-01

Accepted: 2020-12-14

Online: 2021-01-23

Cited Works (1)

Year	Entry
2011	Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KL. A clinician's guide to x-linked hypophosphatemia. J Bone Miner Res. July 2011;26(7):1381-1388.