PT - JOURNAL ARTICLE AU - Karine Briot AU - Anthony A Portale AU - Maria Luisa Brandi AU - Thomas O Carpenter AU - Hae Ii Cheong AU - Martine Cohen-Solal AU - Rachel K Crowley AU - Richard Eastell AU - Yasuo Imanishi AU - Steven Ing AU - Karl Insogna AU - Nobuaki Ito AU - Suzanne Jan de Beur AU - Muhammad K Javaid AU - Peter Kamenicky AU - Richard Keen AU - Takuo Kubota AU - Robin H Lachmann AU - Farzana Perwad AU - Pisit Pitukcheewanont AU - Stuart H Ralston AU - Yasuhiro Takeuchi AU - Hiroyuki Tanaka AU - Thomas J Weber AU - Han-Wook Yoo AU - Annabel Nixon AU - Mark Nixon AU - Wei Sun AU - Angela Williams AU - Erik A Imel TI - Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension AID - 10.1136/rmdopen-2021-001714 DP - 2021 Sep 01 TA - RMD Open PG - e001714 VI - 7 IP - 3 4099 - http://rmdopen.bmj.com/content/7/3/e001714.short 4100 - http://rmdopen.bmj.com/content/7/3/e001714.full SO - RMD Open2021 Sep 01; 7 AB - Objectives To report the impact of burosumab on patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia (XLH) through 96 weeks.Methods 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).Results 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.Conclusions 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.Trial registration number NCT02526160.Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information. Requests for individual deidentified participant data and the clinical study report from this study will be available after product approval to researchers providing a methodologically sound proposal that is in accordance with the Ultragenyx data sharing commitment (www.ultragenyx.com/pipeline/clinical-trial-transparency). To gain access, data requestors will need to sign a data access and use agreement. Data will be shared via secured portal. The study protocol and statistical analysis plan for this study will be available on the relevant clinical trial registry websites with the tabulated results.