Introduction
Materials and methods
Study design
Study procedures
Statistical methods
Results
Long-term group
BTMs and BMD
Fractures
AEs and SAEs
FREEDOM (years 1–3) Denosumab | FREEDOM Extension (years 1–5) Long-term denosumab | ||||||||
---|---|---|---|---|---|---|---|---|---|
Denosumab exposure | Year 1 | Year 2 | Year 3 | Year 4 | Year 5 | Year 6 | Year 7 | Year 8 | |
N = | 3879 | 3682 | 3487 | 2343 | 2244 | 2067 | 1867 | 1742 | |
All adverse events | 188.5 | 154.9 | 131.6 | 134.8 | 116.9 | 114.2 | 120.8 | 106.3 | |
Infections | 37.7 | 31.9 | 31.0 | 30.3 | 26.8 | 27.5 | 28.9 | 26.9 | |
Malignancies | 1.8 | 1.5 | 2.2 | 2.0 | 2.4 | 2.0 | 2.7 | 1.7 | |
Eczema | 1.6 | 1.1 | 0.9 | 1.0 | 1.3 | 1.0 | 0.7 | 0.7 | |
Hypocalcemia | 0 | 0 | 0 | 0 | <0.1 | 0 | <0.1 | 0 | |
Pancreatitis | <0.1 | <0.1 | <0.1 | 0 | <0.1 | 0.2 | <0.1 | 0.1 | |
Serious adverse events | 11.8 | 11.2 | 12.0 | 10.8 | 13.0 | 12.3 | 15.4 | 11.3 | |
Infections | 1.5 | 1.6 | 1.6 | 1.3 | 1.2 | 1.7 | 2.4 | 1.2 | |
Cellulitis or erysipelas | 0.1 | <0.1 | 0.2 | <0.1 | <0.1 | 0.1 | 0 | 0.2 | |
Fatal adverse events | 0.6 | 0.6 | 0.7 | 0.4 | 0.8 | 0.9 | 1.3 | 0.7 | |
Osteonecrosis of the jaw | 0 | 0 | 0 | 0 | 0 | 0.2 | <0.1 | 0 | |
Atypical femoral fracture | 0 | 0 | 0 | 0 | 0 | 0 | <0.1 | 0 |
FREEDOM (years 1–3) Denosumab | FREEDOM Extension (years 1–5) Long-term denosumab | ||||||||
---|---|---|---|---|---|---|---|---|---|
Denosumab exposure | Year 1 | Year 2 | Year 3 | Year 4 | Year 5 | Year 6 | Year 7 | Year 8 | |
N = | 3879 | 3682 | 3487 | 2343 | 2244 | 2067 | 1867 | 1742 | |
Hypocalcemia | 0 | 0 | 0 | 0 | 9.2 | 0 | 5.6 | 0 | |
Pancreatitis | 5.3 | 5.6 | 8.7 | 0 | 4.6 | 15.6 | 5.6 | 12.2 | |
Serious cellulitis or erysipelas | 10.6 | 2.8 | 23.3 | 8.7 | 4.6 | 10.4 | 0 | 18.3 | |
Osteonecrosis of the jaw | 0 | 0 | 0 | 0 | 0 | 20.8 | 5.6 | 0 | |
Atypical femoral fracture | 0 | 0 | 0 | 0 | 0 | 0 | 5.6 | 0 |
Cross-over group
BTMs and BMD
Fractures
AEs and SAEs
FREEDOM (years 1–3) Placebo | FREEDOM Extension (years 1–5) Cross-over denosumaba
| ||||||||
---|---|---|---|---|---|---|---|---|---|
Denosumab exposure | – | – | – | Year 1 | Year 2 | Year 3 | Year 4 | Year 5 | |
N = | 3883 | 3687 | 3454 | 2206 | 2105 | 1965 | 1756 | 1646 | |
All adverse events | 189.5 | 156.3 | 132.8 | 132.1 | 112.3 | 109.8 | 122.5 | 100.1 | |
Infections | 38.6 | 33.9 | 31.7 | 30.8 | 27.5 | 26.0 | 27.6 | 24.7 | |
Malignancies | 1.8 | 1.6 | 1.5 | 1.9 | 1.6 | 2.1 | 2.6 | 2.1 | |
Eczema | 0.8 | 0.5 | 0.6 | 1.0 | 0.9 | 1.1 | 1.2 | 1.0 | |
Hypocalcemia | <0.1 | 0 | <0.1 | 0.2 | <0.1 | 0 | <0.1 | 0.2 | |
Pancreatitis | <0.1 | <0.1 | 0 | <0.1 | 0 | <0.1 | 0 | 0 | |
Serious adverse events | 11.7 | 11.9 | 10.8 | 12.4 | 12.2 | 12.3 | 12.3 | 12.3 | |
Infections | 1.1 | 1.4 | 1.4 | 1.6 | 1.5 | 1.1 | 1.6 | 1.3 | |
Cellulitis or erysipelas | 0 | 0 | <0.1 | 0 | <0.1 | 0 | <0.1 | 0.1 | |
Fatal adverse events | 0.8 | 0.8 | 1.0 | 0.9 | 0.6 | 0.5 | 0.7 | 0.8 | |
Osteonecrosis of the jaw | 0 | 0 | 0 | 0 | 0.1 | 0 | <0.1 | 0 | |
Atypical femoral fracture | 0 | 0 | 0 | 0 | 0 | <0.1 | 0 | 0 |
FREEDOM (years 1–3) Placebo | FREEDOM Extension (years 1–5) Cross-over denosumaba
| ||||||||
---|---|---|---|---|---|---|---|---|---|
Denosumab exposure | – | – | – | Year 1 | Year 2 | Year 3 | Year 4 | Year 5 | |
N = | 3883 | 3687 | 3454 | 2206 | 2105 | 1965 | 1756 | 1646 | |
Hypocalcemia | 5.3 | 0 | 3.0 | 23.2 | 4.9 | 0 | 5.9 | 19.1 | |
Pancreatitis | 5.3 | 2.8 | 0 | 4.6 | 0 | 5.5 | 0 | 0 | |
Serious cellulitis or erysipelas | 0 | 0 | 3.0 | 0 | 4.9 | 0 | 5.9 | 12.7 | |
Osteonecrosis of the jaw | 0 | 0 | 0 | 0 | 9.8 | 0 | 5.9 | 0 | |
Atypical femoral fracture | 0 | 0 | 0 | 0 | 0 | 5.5 | 0 | 0 |