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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.

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
0937-941X
1-8
McCloskey, E. V.
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Johansson, H.
05aa5476-bcb9-4b97-905e-00f1dfd9d691
Harvey, Nicholas
ce487fb4-d360-4aac-9d17-9466d6cba145
Lorentzen, Mattias
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Shi, Y.
88a0ad57-a5da-4dd1-93c8-a2833fdd6efb
Kanis, J.A,
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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), 1-8. (doi:10.1007/s00198-020-05815-0).

Record type: Article

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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Accepted/In Press date: 30 December 2020
e-pub ahead of print date: 3 February 2021
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
ORCID for Nicholas Harvey: ORCID iD orcid.org/0000-0002-8194-2512

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Date deposited: 11 Mar 2021 17:38
Last modified: 26 Nov 2021 02:48

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Contributors

Author: E. V. McCloskey
Author: H. Johansson
Author: Nicholas Harvey ORCID iD
Author: Mattias Lorentzen
Author: Y. Shi
Author: J.A, Kanis

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