Patient-Reported Outcomes from a Randomized, Active-Controlled, Open-Label, Phase 3 Trial of Burosumab Versus Conventional Therapy in Children with X-Linked Hypophosphatemia.

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

Journal: Calcified tissue international 2021;108(5):622-633

PMID: 33484279

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Abstract

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.

Address: Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, UK. [email protected].; Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. [email protected].; Shriners Hospitals for Children -Washington University School of Medicine in St Louis, St Louis, MO, USA.; Shriners Hospital for Children - Canada, McGill University, Montreal, QC, Canada.; The University of Sydney Children's Hospital Westmead Clinical School, The Children's Hospital at Westmead, Westmead, NSW, Australia.; Department of Endocrinology, The Children's Hospital at Westmead, Westmead, NSW, Australia.; Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada.; Division of Endocrinology and Metabolism, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.; Division of Pediatric Endocrinology & Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.; School of Medical Sciences, Örebro University, Örebro, Sweden.; Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.; Departments of Pediatrics, Division of Endocrinology and Diabetes, Vanderbilt University School of Medicine, Vanderbilt University, Nashville, TN, USA.; Department of Pediatrics, Osaka Hospital, Japan Community Healthcare Organization, Osaka, Japan.; Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.; Seoul National University Children's Hospital, Seoul, Republic of Korea.; Center of Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles, Los Angeles, CA, USA.; Department of Paediatrics, Hospital for Sick Children, Toronto, ON, Canada.; Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Linz, Austria.; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.; Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan.; Okayama Saiseikai General Hospital Outpatient Center, Okayama, Japan.; Shriners Hospitals for Children, St Louis, MO, USA.; The University of Sydney Children's Hospital Westmead Clinical School, The Children's Hospital at Westmead, Westmead, NSW, Australia.; Kyowa Kirin International, Marlow, UK.; Chilli Consultancy, Salisbury, UK.; Kyowa Kirin Pharmaceutical Development, Princeton, NJ, USA.; Ultragenyx Pharmaceutical, Novato, CA, USA.; Department of Medicine and Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.

DOI: 10.1007/s00223-020-00797-x