John Hopkins University School of Medicine, Baltimore, MD, USA.
Ultragenyx Pharmaceutical Inc, Novato, CA, USA.
J Bone Miner Res. 2023 Nov;38(11):1654-1664. doi: 10.1002/jbmr.4900. Epub 2023 Sep 4.
Tumor-induced osteomalacia (TIO) is an ultra-rare disease caused by tumors that secrete fibroblast growth factor 23, leading to chronic hypophosphatemia, poor skeletal health, and impaired physical function. In a phase 2 trial (UX023T-CL201; NCT02304367; n = 14), 48 weeks of burosumab treatment restored phosphate homeostasis, with improvements in skeletal health, functional mobility, and patient-reported pain, fatigue, and health-related quality of life (HRQL) (SF-36 v2). Here, we report an exploratory mixed-methods analysis of change from baseline after 144 weeks of burosumab treatment alongside qualitative data from exit interviews with 8 of 14 trial participants to evaluate meaningful treatment effects from a patient perspective. The interview subset (n = 8) reported pain and fatigue and compromised HRQL at baseline. In the interviews, participants reported that compromised HRQL and pain were the most important aspects of the disease to treat; both were considered more bothersome than fatigue and compromised physical function and activities of daily living. Improvements in pain and fatigue after treatment were reported, some of which achieved statistically and/or clinically meaningful thresholds. Furthermore, improvements in SF-36 v2 scores were most pronounced in the Physical Component Score and its Physical Function and Bodily Pain domains. Overall, the interview subset provided descriptions of symptomatic improvement and its clinical meaningfulness, including physical function, participation in activities of daily living, and mental well-being. Thus, this exploratory mixed-methods analysis provides deeper understanding of patients' perception of clinical meaningfulness beyond that articulated in validated patient-reported outcome instruments. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
肿瘤性骨软化症（TIO）是一种由分泌成纤维细胞生长因子 23 的肿瘤引起的罕见疾病，导致慢性低磷血症、骨骼健康不良和身体功能受损。在一项 2 期试验（UX023T-CL201；NCT02304367；n=14）中，48 周的布罗索尤单抗治疗恢复了磷酸盐稳态，骨骼健康、功能移动性以及患者报告的疼痛、疲劳和健康相关生活质量（SF-36 v2）均得到改善。在这里，我们报告了一项探索性的混合方法分析，评估了 144 周布罗索尤单抗治疗后的基线变化，以及对 14 名试验参与者中的 8 名进行的退出访谈的定性数据，从患者角度评估了有意义的治疗效果。访谈亚组（n=8）报告基线时存在疼痛、疲劳和受损的 HRQL。在访谈中，参与者报告说，受损的 HRQL 和疼痛是治疗疾病的最重要方面；他们认为疼痛和疲劳比疲劳、身体功能和日常生活活动受损更麻烦。报告治疗后疼痛和疲劳有所改善，其中一些改善达到了统计学和/或临床上有意义的阈值。此外，SF-36 v2 评分的改善在生理成分评分及其生理功能和躯体疼痛领域最为明显。总体而言，访谈亚组描述了症状改善及其临床意义，包括身体功能、日常生活活动参与和精神健康。因此，这项探索性的混合方法分析提供了对患者对临床意义的感知的更深入理解，超出了已验证的患者报告结局工具所表达的内容。
