Briot Karine, Portale Anthony A, Brandi Maria Luisa, Carpenter Thomas O, Cheong Hae Ii, Cohen-Solal Martine, Crowley Rachel K, Eastell Richard, Imanishi Yasuo, Ing Steven, Insogna Karl, Ito Nobuaki, Jan de Beur Suzanne, Javaid Muhammad K, Kamenicky Peter, Keen Richard, Kubota Takuo, Lachmann Robin H, Perwad Farzana, Pitukcheewanont Pisit, Ralston Stuart H, Takeuchi Yasuhiro, Tanaka Hiroyuki, Weber Thomas J, Yoo Han-Wook, Nixon Annabel, Nixon Mark, Sun Wei, Williams Angela, Imel Erik A
Department of Rheumatology, Hôpital Cochin, Paris, France
Department of Pediatrics, Division of Nephrology, University of California, San Francisco, California, USA.
RMD Open. 2021 Sep;7(3). doi: 10.1136/rmdopen-2021-001714.
To report the impact of burosumab on patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia (XLH) through 96 weeks.
Adults diagnosed with XLH were randomised 1:1 in a double-blinded trial to receive subcutaneous burosumab 1 mg/kg or placebo every 4 weeks for 24 weeks (NCT02526160). Thereafter, all subjects received burosumab every 4 weeks until week 96. PROs were measured using the Western Ontario and the McMaster Universities Osteoarthritis Index (WOMAC), Brief Pain Inventory-Short Form (BPI-SF) and Brief Fatigue Inventory (BFI), and ambulatory function was measured with the 6 min walk test (6MWT).
Subjects (N=134) were randomised to burosumab (n=68) or placebo (n=66) for 24 weeks. At baseline, subjects experienced pain, stiffness, and impaired physical and ambulatory function. At week 24, subjects receiving burosumab achieved statistically significant improvement in some BPI-SF scores, BFI worst fatigue (average and greatest) and WOMAC stiffness. At week 48, all WOMAC and BPI-SF scores achieved statistically significant improvement, with some WOMAC and BFI scores achieving meaningful and significant change from baseline. At week 96, all WOMAC, BPI-SF and BFI achieved statistically significant improvement, with selected scores in all measures also achieving meaningful change. Improvement in 6MWT distance and percent predicted were statistically significant at all time points from 24 weeks.
Adults with XLH have substantial burden of disease as assessed by PROs and 6MWT. Burosumab treatment improved phosphate homoeostasis and was associated with a steady and consistent improvement in PROs and ambulatory function.
NCT02526160.
报告布罗索尤单抗对X连锁低磷血症（XLH）成人患者报告结局（PROs）和动态功能的影响，观察期为96周。
在一项双盲试验中，将确诊为XLH的成人患者按1:1随机分组，每4周皮下注射1 mg/kg布罗索尤单抗或安慰剂，共24周（NCT02526160）。此后，所有受试者每4周接受一次布罗索尤单抗治疗，直至第96周。使用西安大略和麦克马斯特大学骨关节炎指数（WOMAC）、简明疼痛量表简表（BPI-SF）和简明疲劳量表（BFI）测量PROs，用6分钟步行试验（6MWT）测量动态功能。
134名受试者被随机分为布罗索尤单抗组（n = 68）或安慰剂组（n = 66），治疗24周。基线时，受试者有疼痛、僵硬，身体和动态功能受损。在第24周时，接受布罗索尤单抗治疗的受试者在一些BPI-SF评分、BFI最严重疲劳（平均和最大）以及WOMAC僵硬方面有统计学意义的改善。在第48周时，所有WOMAC和BPI-SF评分均有统计学意义的改善，一些WOMAC和BFI评分与基线相比有显著且有意义的变化。在第96周时，所有WOMAC、BPI-SF和BFI均有统计学意义的改善，所有测量指标中的选定评分也有显著变化。从第24周起，6MWT距离和预测百分比的改善在所有时间点均有统计学意义。
通过PROs和6MWT评估，XLH成人患者疾病负担较重。布罗索尤单抗治疗改善了磷酸盐稳态，并与PROs和动态功能的稳定持续改善相关。
NCT02526160。
