Favorable skeletal benefit/risk of long-term denosumab therapy: A virtual-twin analysis of fractures prevented relative to skeletal safety events observed

被引:17
作者
Ferrari, Serge [1 ]
Lewiecki, E. Michael [2 ]
Butler, Peter W. [3 ]
Kendler, David L. [4 ]
Napoli, Nicola [5 ,8 ]
Huang, Shuang [3 ]
Crittenden, Daria B. [3 ]
Pannacciulli, Nicola [3 ]
Siris, Ethel [6 ]
Binkley, Neil [7 ]
机构
[1] Geneva Univ Hosp, CH-1211 Geneva, Switzerland
[2] New Mexico Clin Res & Osteoporosis Ctr, Albuquerque, NM USA
[3] Amgen Inc, Thousand Oaks, CA 91320 USA
[4] Univ British Columbia, Vancouver, BC, Canada
[5] Univ Campus Biomed Roma, Rome, Italy
[6] Columbia Univ, Med Ctr, New York, NY USA
[7] Univ Wisconsin, Madison, WI USA
[8] Washington Univ, Div Bone & Mineral Dis, St Louis, MO 63110 USA
关键词
Osteoporosis; Antiresorptives; Fracture prevention; QUALITY-OF-LIFE; ZOLEDRONIC ACID; HIP FRACTURE; OSTEOPOROSIS TREATMENT; AMERICAN ASSOCIATION; POSTMENOPAUSAL WOMEN; VERTEBRAL FRACTURES; CLINICAL FRACTURES; RISK; MORTALITY;
D O I
10.1016/j.bone.2020.115287
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Antiresorptive therapies reduce fracture risk; however, long-term bone turnover inhibition may raise concerns about rare, but serious, skeletal adverse events-atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ). Denosumab, a fully human monoclonal antibody against RANKL, has demonstrated sustained low vertebral and nonvertebral fracture rates with low skeletal adverse event rates in the 3-year FREEDOM trial and its 7-year Extension (in which all subjects received open-label denosumab). In this analysis, we aimed to estimate fractures prevented relative to skeletal adverse events observed with 10 years of denosumab therapy. We modeled a hypothetical placebo group using the virtual-twin method, thereby allowing calculation of fractures prevented with denosumab treatment (relative to the virtual-placebo group) in the context of AFF or ONJ events observed in the long-term denosumab group. Estimated virtual-placebo and observed long-term denosumab exposure-adjusted fracture rates per 100,000 subject-years were calculated for fractures classified as clinical (3180 and 1777, respectively), major osteoporotic (2699 and 1525), vertebral (1879 and 901), and nonvertebral (2924 and 1528), and compared with observed AFF and ONJ in the long-term denosumab group (5 and 35 per 100,000 subject-years, respectively). The skeletal benefit/risk ratio (fractures prevented per adverse event observed) for clinical fractures was 281 (AFF) and 40 (ONJ). Based on this model, denosumab treatment for up to 10 years has a favorable skeletal benefit/risk profile when comparing fractures prevented per skeletal adverse event observed.
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页数:7
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