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Tytuł:
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Romosozumab efficacy on fracture outcomes is greater in patients at high baseline fracture risk: a post hoc analysis of the first year of the frame study.
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Autorzy:
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McCloskey EV; Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK. .; Centre for Integrated Research in Musculoskeletal Ageing (CIMA), Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK. .; Metabolic Bone Centre, Northern General Hospital, Herries Road, Sheffield, S5 7AU, UK. .
Johansson H; Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK.; Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.
Harvey NC; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Lorentzon M; Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.; Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.; Region Västra Götaland, Geriatric Medicine, Sahlgrenska University Hospital, Mölndal, Sweden.
Shi Y; Amgen Inc, Thousand Oaks, CA, USA.
Kanis JA; Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK.; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
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Źródło:
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Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA [Osteoporos Int] 2021 Aug; Vol. 32 (8), pp. 1601-1608. Date of Electronic Publication: 2021 Feb 03.
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Typ publikacji:
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Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial
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Język:
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English
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Imprint Name(s):
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Original Publication: London, UK : Springer International, c1990-
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MeSH Terms:
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Bone Density Conservation Agents*/therapeutic use
Osteoporosis, Postmenopausal*/complications
Osteoporosis, Postmenopausal*/drug therapy
Osteoporosis, Postmenopausal*/epidemiology
Osteoporotic Fractures*/epidemiology
Osteoporotic Fractures*/etiology
Osteoporotic Fractures*/prevention & control
Antibodies, Monoclonal ; Bone Density ; Female ; Humans ; Risk Assessment ; Risk Factors
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References:
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Contributed Indexing:
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Keywords: FRAX; Fracture reduction; Fracture risk; Romosozumab
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Molecular Sequence:
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ClinicalTrials.gov NCT01575834
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Substance Nomenclature:
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0 (Antibodies, Monoclonal)
0 (Bone Density Conservation Agents)
3VHF2ZD92J (romosozumab)
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Entry Date(s):
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Date Created: 20210204 Date Completed: 20210823 Latest Revision: 20220531
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Update Code:
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20240105
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PubMed Central ID:
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PMC8376732
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DOI:
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10.1007/s00198-020-05815-0
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PMID:
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33537844
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This study aimed to determine the interaction between baseline FRAX ® fracture probability and romosozumab efficacy. Using an ITT approach, it was determined that the efficacy of romosozumab on clinical fracture, osteoporotic fracture, and major osteoporotic fracture is significantly greater in patients at high baseline fracture risk, when compared with placebo.
Introduction: Post hoc analyses of placebo-controlled osteoporosis treatment studies have shown significantly greater reductions of fracture incidence for higher fracture risk patients. This study determined the interaction between baseline FRAX ® fracture probability and romosozumab efficacy in the placebo-controlled first year of the phase 3 FRAME study (NCT01575834).
Methods: Using an ITT approach, an extension of Poisson regression analysis studied the relationship between treatment, FRAX ® 10-year probability of major osteoporotic fracture (MOF, calculated without BMD) and risk of first incident fracture (adjusting for age and follow-up time). Treatment interactions considered outcomes of all clinical fractures, osteoporotic fractures, MOF, clinical vertebral fractures, and morphometric vertebral fractures. Two-sided p value of < 0.1 for the interaction between treatment and FRAX ® was considered significant.
Results: Compared with placebo, romosozumab reduced the incidence of all fracture outcomes in the first year (range: 32% reduction in MOF [p = 0.07] to 80% reduction in clinical vertebral fractures [p = 0.038]). Significant interactions were observed between efficacy and baseline FRAX ® probability for composite outcomes of clinical fractures, osteoporotic fractures, and MOF (p = 0.064-0.084), but not vertebral fractures (p > 0.3). For example, romosozumab decreased all clinical fractures by 22% at the 25th centile of FRAX ® probability but the reduction was 41% at the 75th centile. Exclusion of vertebral fractures from each composite fracture outcome (i.e. only nonvertebral fractures included) showed even stronger interactions with baseline FRAX ® probability (p = 0.036-0.046).
Conclusions: Efficacy of romosozumab on clinical fracture, osteoporotic fracture, and MOF is significantly greater in patients at high baseline fracture risk compared with placebo.
(© 2021. The Author(s).)
