Burosumab vs conventional therapy in children with X-linked hypophosphatemia: results of the open-label, phase 3 extension period

作者：Leanne M. Ward, Wolfgang Högler, Francis H. Glorieux, Anthony A. Portale, Michael P. Whyte, Craig F. Munns, Ola Nilsson, Jill H. Simmons, Raja Padidela, Noriyuki Namba, Hae Il Cheong, Etienne Sochett, Koji Muroya, Hiroyuki Tanaka, Pisit Pitukcheewanont, Gary S. Gottesman, Andrew Biggin, Farzana Perwad, Angel Chen, John L. Merritt, Erik A. Imel · 发表于：JBMR Plus · 年份：2024 · DOI：10.1093/jbmrpl/ziad001 · 被引用次数：20 · 研究领域：Parathyroid Disorders and Treatments、Hip disorders and treatments、Muscle and Compartmental Disorders

Abstract In a randomized, open-label phase 3 study of 61 children aged 1–12 years old with X-linked hypophosphatemia (XLH) previously treated with conventional therapy, changing to burosumab every 2 weeks (Q2W) for 64 weeks improved the phosphate metabolism, radiographic rickets, and growth compared with conventional therapy. In this open-label extension period (weeks 64–88), 21 children continued burosumab Q2W at the previous dose or crossed over from conventional therapy to burosumab starting at 0.8 mg/kg Q2W with continued clinical radiographic assessments through week 88. Efficacy endpoints and safety observations were summarized descriptively for both groups (burosumab continuation, n = 6; crossover, n = 15). At week 88 compared with baseline, improvements in the following outcomes were observed in the burosumab continuation and crossover groups, respectively: mean (SD) RGI-C rickets total score (primary outcome), +2.11 (0.27) and +1.89 (0.35); mean (SD) RGI-C lower limb deformity score, +1.61 (0.91) and +0.73 (0.82); and mean (SD) height Z-score + 0.41 (0.50) and +0.08 (0.34). Phosphate metabolism normalized rapidly in the crossover group and persisted in the continuation group. Mean (SD) serum alkaline phosphatase decreased from 169% (43%) of the upper limit of normal (ULN) at baseline to 126% (51%) at week 88 in the continuation group and from 157% (33%) of the ULN at baseline to 111% (23%) at week 88 in the crossover group. During the extension period, treatment-emer...