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Clinical Trial
. 2021 Sep;7(3):e001714.
doi: 10.1136/rmdopen-2021-001714.

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

Karine Briot  1 , Anthony A Portale  2 , Maria Luisa Brandi  3 , Thomas O Carpenter  4 , Hae Ii Cheong  5 , Martine Cohen-Solal  6   7 , Rachel K Crowley  8   9 , Richard Eastell  10 , Yasuo Imanishi  11 , Steven Ing  12 , Karl Insogna  13 , Nobuaki Ito  14 , Suzanne Jan de Beur  15 , Muhammad K Javaid  16 , Peter Kamenicky  17   18 , Richard Keen  19 , Takuo Kubota  20 , Robin H Lachmann  21 , Farzana Perwad  2 , Pisit Pitukcheewanont  22 , Stuart H Ralston  23 , Yasuhiro Takeuchi  24 , Hiroyuki Tanaka  25 , Thomas J Weber  26 , Han-Wook Yoo  27 , Annabel Nixon  28 , Mark Nixon  28 , Wei Sun  29 , Angela Williams  30 , Erik A Imel  31
Affiliations
Clinical Trial

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

Karine Briot et al. RMD Open. 2021 Sep.

Abstract

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.

Keywords: healthcare; outcome assessment; patient reported outcome measures; therapeutics.

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Conflict of interest statement

Competing interests: The following authors served as clinical investigators for one or more studies, including this trial, sponsored by Ultragenyx Pharmaceutical Inc. in partnership with Kyowa Kirin International: KB, AAP, MLB, TOC, HIC, MC-S, RKC, RE, YI, EAI, SI, NI, SJdB, MKJ, PK, RK, TK, RHL, FP, PP, SHR, YT, HT, TJW, H‑WY and KI. AAP and FP have also received honoraria from Ultragenyx Pharmaceutical for serving as an advisory board member or for lectures. PP has received research funding from Ultragenyx Pharmaceutical and is currently an employee of Ascendis Pharma. SHR has received grants from Kyowa Kirin International and Ultragenyx Pharmaceutical during the conduct of the study. During the conduct of the study, TJW also reports honoraria and travel support from Ultragenyx Pharmaceutical. AW and WS are employees of Kyowa Kirin International plc. AN and MN are employees of Chilli Consultancy and have received consultancy fees from Kyowa Kirin International to support the development of this manuscript and for projects outside this submitted work.

Figures

Figure 1
Figure 1
Proportion of adults reporting (A) WOMAC, (B) BPI-SF and (C) BFI item level scores at baseline (N=134). Interference of pain on walking ability and normal work were not recorded at baseline for one participant in each group. BFI, Brief Fatigue Inventory; BPI-SF, Brief Pain Inventory-Short Form; WOMAC, Western Ontario and the McMaster Universities Osteoarthritis.
Figure 2
Figure 2
Change from baseline in WOMAC (A) total score, and (B) physical function, (C) stiffness and (D) pain scores (N=134). Data show LS mean (±SE); lower scores indicate better health. *p<0.05 for LS mean change from baseline. †Indicates the minimal clinically important differences from baseline (≥−10.0 total score, ≥−8.0 physical function, ≥−10.0 stiffness, ≥−11.0 pain, shown by the pale grey horizontal line). LS, least squares; WOMAC, Western Ontario and the McMaster Universities Osteoarthritis.
Figure 3
Figure 3
Change from baseline in BPI-SF (A) worst pain (average), (B) worst pain (greatest) and (C) pain interference scores (N=134). Data show LS mean (±SE); lower scores indicate lower pain severity and less pain interference. *p<0.05 for LS mean change from baseline. †Indicates minimal clinically important differences from baseline (≥−1.72 worst pain (average, greatest), ≥−1.0 pain interference, shown by the pale grey horizontal line). BPI-SF, Brief Pain Inventory-Short Form; LS, least squares.
Figure 4
Figure 4
Change from baseline in BFI (A) worst fatigue (average), (B) worst fatigue (greatest), (C) global fatigue and (D) fatigue interference scores (N=134). Data show LS mean (±SE); lower scores indicate lower fatigue severity and less fatigue interference. *p<0.05 for LS mean change from baseline. †Indicates the minimal clinically important difference from baseline (≥−1.5 worst fatigue (average, greatest), ≥−1.2 global fatigue, ≥−1.2 fatigue interference, shown by the pale grey horizontal line). BFI, Brief Fatigue Inventory; LS, least squares.
Figure 5
Figure 5
Change from baseline in 6MWT (A) distance walked (metres) and (B) percentage predicted (%) (n=132). Data show LS mean (±SE); higher scores indicate better ambulatory function. *p<0.05 for LS mean change from baseline. 6MWT, 6 min walk test; LS, least squares.
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