Introduction
Methods
Study Design
Participants
Treatments
Outcomes
Statistical analysis
Results
Participants and Treatment
Placebo–burosumab (n = 66) | Burosumab–burosumab (n = 68) | Total (n = 134) | |
---|---|---|---|
Age (years) | |||
Mean ± SD | 38.7 ± 12.8 | 41.3 ± 11.6 | 40.0 ± 12.2 |
Range | 18.5–65.5 | 20.0–63.4 | 18.5–65.5 |
Female, n (%) | 43 (65.2) | 44 (64.7) | 87 (64.9) |
Race, n (%) | |||
White | 53 (80.3) | 55 (80.9) | 108 (80.6) |
Asian | 9 (13.6) | 12 (17.6) | 21 (15.7) |
Black | 3 (4.5) | 0 | 3 (2.2) |
Other | 1 (1.5) | 1 (1.5) | 2 (1.5) |
Geographic region, n (%) | |||
North America/Europe | 58 (87.9) | 58 (85.3) | 116 (86.6) |
Japan | 5 (7.6) | 6 (8.8) | 11 (8.2) |
South Korea | 3 (4.5) | 4 (5.9) | 7 (5.2) |
Heighta, mean ± SD | |||
cm | 153 ± 11.8 | 152 ± 9.5 | 152 ± 10.7 |
Z-scoreb | − 2.3 ± 1.3 | − 2.3 ± 1.2 | − 2.3 ± 1.3 |
Percentile | 7.2 ± 12.1 | 6.4 ± 12.9 | 6.8 ± 12.5 |
Body mass indexa (kg/m2), mean ± SD | 30.6 ± 7.8 | 30.0 ± 7.5 | 30.3 ± 7.6 |
PHEX mutation, n (%) | |||
Pathogenic | 50 (75.8) | 45 (66.2) | 95 (70.9) |
Likely pathogenic | 7 (10.6) | 8 (11.8) | 15 (11.2) |
Variant of uncertain s ignificance | 8 (12.1) | 9 (13.2) | 17 (12.7) |
No mutation | 1 (1.5) | 6 (8.8) | 7 (5.2) |
WOMAC stiffnessc, mean ± SD | 61.4 ± 20.8 | 64.7 ± 20.3 | 63.1 ± 20.5 |
WOMAC physical functionc, mean ± SD | 43.9 ± 19.9 | 50.8 ± 19.7 | 47.4 ± 20.0 |
BPI Worst Pain, mean ± SD | 6.5 ± 1.4 | 6.8 ± 1.3 | 6.7 ± 1.4 |
BPI Worst Pain > 6.0, n (%) | 43 (65.2) | 53 (77.9) | 96 (71.6) |
Any pain medication at baseline, n (%) | 44 (66.7) | 47 (69.1) | 91 (67.9) |
Any opioid at baseline, n (%) | 13 (19.7) | 17 (25.0) | 30 (22.4) |
Medical historyd, n (%) | |||
Orthopedic surgery | 47 (71.2) | 45 (66.2) | 92 (68.7) |
Osteoarthritis | 38 (57.6) | 47 (69.1) | 85 (63.4) |
TmP/GFR (mg/dL)e, mean ± SD | 1.6 ± 0.37 | 1.7 ± 0.40 | 1.6 ± 0.39 |
Serum phosphorus (mg/dL)e, mean ± SD | 1.9 ± 0.32 | 2.0 ± 0.30 | 2.0 ± 0.31 |
Serum 1,25(OH)2D (pg/mL)e, mean ± SD | 33.5 ± 15.6 | 32.4 ± 13.0 | 33.0 ± 14.3 |
Serum calcium (mg/dL)e, mean ± SD | 9.1 ± 0.41 | 9.2 ± 0.49 | 9.2 ± 0.45 |
Plasma iPTH (pg/mL)e, mean ± SD | 95.2 ± 38.8 | 98.9 ± 60.8 | 97.0 ± 50.9 |
Enthesopathy on X-ray, n (%) | 65 (98.5) | 68 (100.0) | 133 (99.3) |
Nephrocalcinosis gradef, n (%) | |||
0 | 27 (40.9) | 34 (50.0) | 61 (45.5) |
1 | 32 (48.5) | 23 (33.8) | 55 (41.0) |
2 | 7 (10.6) | 9 (13.2) | 16 (11.9) |
3 | 0 | 2 (2.9) | 2 (1.5) |
Unhealed fracture/pseudofracture at baseline | |||
n (%) of participants | 38 (57.6) | 32 (47.1) | 70 (52.2) |
No. of fractures/pseudofractures | 91 | 65 | 156 |
Fractures | 13 | 14 | 27 |
Pseudofractures | 78 | 51 | 129 |
Pharmacodynamic Effects of Burosumab
Burosumab-Burosumab Group
Placebo–Burosumab Group
Fracture/Pseudofracture Healing
Burosumab–Burosumab Group
Placebo–Burosumab Group
Patient-Reported Outcomes and Functional Exercise Capacity
Burosumab–Burosumab Group
Placebo–Burosumab Group
Safety
n (%) [exposure-adjusted event incidence/year]a | ||||
---|---|---|---|---|
Double-blind Treatment | Any Exposure to Burosumab | |||
Placebo (n = 66) | Burosumab (n = 68) | Placebo- Burosumab (n = 66) | Burosumab- Burosumab (n = 68) | |
Weeks 0–24 | Weeks 0–24 | Weeks 24–cutoff | Weeks 0–cutoff | |
Any TEAE | 61 (92.4) [9.29] | 64 (94.1) [9.93] | 63 (95.5) [9.27] | 68 (100.0) [9.68] |
Related TEAEb | 26 (39.4) [1.65] | 30 (44.1) [2.30] | 32 (48.5) [1.60] | 42 (61.8) [1.96] |
Serious TEAE | 2 (3.0) [0.07] | 2 (2.9) [0.06] | 8 (12.1) [0.18] | 7 (10.3) [0.12] |
Grade 3 or 4 TEAE | 9 (13.6) [0.49] | 8 (11.8) [0.35] | 14 (21.2) [0.53] | 15 (22.1) [0.30] |
Related serious TEAEb | 0 | 0 | 0 | 0 |
TEAE led to study discontinuation | 0 | 0 | 0 | 0 |
TEAEs led to treatment discontinuation | 0 | 0 | 0 | 0 |
TEAEs leading to death | 0 | 0 | 0 | 0 |