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.
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.
Summary: 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.
FRAX, Fracture reduction, Fracture risk, Romosozumab
1601-1608
McCloskey, E. V.
e968a69f-27b8-4568-987d-5d8dbbdff3fd
Johansson, H.
05aa5476-bcb9-4b97-905e-00f1dfd9d691
Harvey, Nicholas
ce487fb4-d360-4aac-9d17-9466d6cba145
Lorentzen, Mattias
72997ee0-d7ba-42b1-912e-f60414366449
Shi, Y.
88a0ad57-a5da-4dd1-93c8-a2833fdd6efb
Kanis, J.A,
52c2c5a7-a17a-49dd-9b2a-30b5a1750a5d
August 2021
McCloskey, E. V.
e968a69f-27b8-4568-987d-5d8dbbdff3fd
Johansson, H.
05aa5476-bcb9-4b97-905e-00f1dfd9d691
Harvey, Nicholas
ce487fb4-d360-4aac-9d17-9466d6cba145
Lorentzen, Mattias
72997ee0-d7ba-42b1-912e-f60414366449
Shi, Y.
88a0ad57-a5da-4dd1-93c8-a2833fdd6efb
Kanis, J.A,
52c2c5a7-a17a-49dd-9b2a-30b5a1750a5d
McCloskey, E. V., Johansson, H., Harvey, Nicholas, Lorentzen, Mattias, Shi, Y. and Kanis, J.A,
(2021)
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.
Osteoporosis International, 32 (8), .
(doi:10.1007/s00198-020-05815-0).
Abstract
Summary: 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.
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McCloskey2021_Article_RomosozumabEfficacyOnFractureO
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More information
Accepted/In Press date: 30 December 2020
e-pub ahead of print date: 3 February 2021
Published date: August 2021
Additional Information:
Funding Information:
This study was funded by Amgen, Inc., Astellas Pharma Inc., and UCB.
Funding Information:
Alexandra Stirling of BioScience Communications, New York, NY (on behalf of Amgen, Inc.), provided editorial support.
Funding Information:
Eugene V McCloskey has received consultancy/lecture fees/grant funding/honoraria from ActiveSignal, AgNovos, Amgen, AstraZeneca, Consilient Healthcare, Fresenius Kabi, Gilead, GSK, Hologic, Internis, Lilly, Medtronic, Merck, Novartis, Pfizer, Radius Health, Redx Oncology, Roche, SanofiAventis, Servier, Synexus, Tethys, UCB, Viiv, Warner Chilcott, I3 Innovus, and Unilever, all outside the presented work. Helena Johansson has no conflicts to declare. Nicholas C Harvey has received consultancy/lecture fees/honoraria/grant funding from Alliance for Better Bone Health, Amgen, MSD, Eli Lilly, Radius Health, Servier, Shire, UCB, Consilient Healthcare, and Internis Pharma, all outside the presented work. Mattias Lorentzon has received lecture fees from Amgen, Lilly, Meda, Renapharma, and UCB Pharma, and consulting fees from Amgen, Radius Health, UCB Pharma, Renapharma, and Consilient Health, all outside the presented work. Yifei Shi is an employee and stockholder of Amgen Inc. John A Kanis reports grants from Amgen, Eli Lilly, and Radius Health and consulting fees from Theramex. He led the team that developed FRAX as director of the then WHO Collaborating Centre for Metabolic Bone Diseases; he has no financial interest in FRAX. ® ®
Publisher Copyright:
© 2021, The Author(s).
Keywords:
FRAX, Fracture reduction, Fracture risk, Romosozumab
Identifiers
Local EPrints ID: 447468
URI: http://eprints.soton.ac.uk/id/eprint/447468
ISSN: 0937-941X
PURE UUID: 5af710c0-9539-4e81-9ed5-3c6b44961306
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Date deposited: 11 Mar 2021 17:38
Last modified: 17 Mar 2024 02:58
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Contributors
Author:
E. V. McCloskey
Author:
H. Johansson
Author:
Mattias Lorentzen
Author:
Y. Shi
Author:
J.A, Kanis
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