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

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Patient-Reported Outcomes from a Randomized, Active-Controlled, Open-Label, Phase 3 Trial of Burosumab Versus Conventional Therapy in Children with X-Linked Hypophosphatemia
Calcified Tissue International ( IF 4.2 ) Pub Date : 2021-01-23 , DOI: 10.1007/s00223-020-00797-x
Raja Padidela _{1,

2} , Michael P Whyte ₃ , Francis H Glorieux ₄ , Craig F Munns _{5,

6} , Leanne M Ward _{7,

8} , Ola Nilsson _{9,

10} , Anthony A Portale ₁₁ , Jill H Simmons ₁₂ , Noriyuki Namba _{13,

14} , Hae Il Cheong ₁₅ , Pisit Pitukcheewanont ₁₆ , Etienne Sochett ₁₇ , Wolfgang Högler _{18,

19} , Koji Muroya ₂₀ , Hiroyuki Tanaka ₂₁ , Gary S Gottesman ₂₂ , Andrew Biggin ₅ , Farzana Perwad ₁₁ , Angela Williams ₂₃ , Annabel Nixon ₂₄ , Wei Sun ₂₅ , Angel Chen ₂₆ , Alison Skrinar ₂₆ , Erik A Imel ₂₇

Affiliation

Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, UK.
Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
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.
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.

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

中文翻译：

Burosumab 与常规疗法治疗 X 连锁低磷血症儿童的随机、主动对照、开放标签、3 期试验的患者报告结果

在随机、开放标签、阶段，与持续口服磷酸盐和活性维生素 D（常规治疗）相比，改用靶向成纤维细胞生长因子 23 的单克隆抗体 burosumab 可显着改善磷稳态、佝偻病、下肢畸形、活动能力和生长3 项试验涉及 1-12 岁患有 X 连锁低磷血症的儿童。患者被随机（1:1）接受皮下注射burosumab或继续常规治疗。我们展示了该试验中筛查时年龄≥ 5 岁儿童的患者报告结果 (PROs) ( n = 35)，使用患者报告的结果测量信息系统 (PROMIS) 问卷和 SF-10 儿童健康调查。在第 40 周和第 64 周，burosumab 的 PROMIS 疼痛干扰、身体功能活动性和疲劳评分从基线有所改善，但在继续常规治疗后变化不大。第 40 周时，各组之间的疼痛干扰评分显着不同（- 5.02, 95% CI - 9.29 至 - 0.75；p = 0.0212）但不是在第 64 周。组间差异在任何一周的身体功能活动性或疲劳方面均不显着。在第 40 周和第 64 周，burosumab 与基线相比 PROMIS 疼痛干扰和疲劳评分的降低具有临床意义，但在常规治疗中则没有。SF-10 身体健康评分 (PHS-10) 在第 40 周（最小二乘平均值 [标准误差] + 5.98 [1.79]；p = 0.0008）和第 64 周（+ 5.93 [1.88]；p = 0.0016）但与常规治疗无关（治疗间差异不显着）。总之，改用 burosumab 改善了 PRO 测量，第 40 周的 PROMIS 疼痛干扰与继续常规治疗和第 40 周和第 64 周的 PHS-10 与基线相比具有统计学显着差异。

试验注册：ClinicalTrials.gov NCT02915705

更新日期：2021-01-24

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