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Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association?

SUMMARY: Serious adverse events of infections that occurred in subjects receiving denosumab or placebo in the Fracture Reduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) study were examined in detail. Serious adverse events of infections in denosumab subjects had heterogeneou...

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Autores principales: Watts, N. B., Roux, C., Modlin, J. F., Brown, J. P., Daniels, A., Jackson, S., Smith, S., Zack, D. J., Zhou, L., Grauer, A., Ferrari, S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer-Verlag 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249159/
https://www.ncbi.nlm.nih.gov/pubmed/21892677
http://dx.doi.org/10.1007/s00198-011-1755-2
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author Watts, N. B.
Roux, C.
Modlin, J. F.
Brown, J. P.
Daniels, A.
Jackson, S.
Smith, S.
Zack, D. J.
Zhou, L.
Grauer, A.
Ferrari, S.
author_facet Watts, N. B.
Roux, C.
Modlin, J. F.
Brown, J. P.
Daniels, A.
Jackson, S.
Smith, S.
Zack, D. J.
Zhou, L.
Grauer, A.
Ferrari, S.
author_sort Watts, N. B.
collection PubMed
description SUMMARY: Serious adverse events of infections that occurred in subjects receiving denosumab or placebo in the Fracture Reduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) study were examined in detail. Serious adverse events of infections in denosumab subjects had heterogeneous etiology, with no clear clinical pattern to suggest a relationship to time or duration of exposure to denosumab. INTRODUCTION: Denosumab reduces the risk for new vertebral, hip, and nonvertebral fractures compared with placebo. In the pivotal phase 3 fracture trial (FREEDOM), the overall safety profile and incidence of adverse events including adverse events of infections were similar between groups. Serious adverse events of erysipelas and cellulitis were more frequent in denosumab-treated subjects. In this report, we further evaluate the details of infectious events in FREEDOM to better understand if RANKL inhibition with denosumab influences infection risk. METHODS: FREEDOM was an international multicenter, randomized, double-blind, placebo-controlled study in postmenopausal women with osteoporosis randomly assigned to receive placebo (n = 3,906) or denosumab 60 mg every 6 months (n = 3,902). The incidence of adverse events and serious adverse events categorized within the Medical Dictionary for Regulatory Activities system organ class, “Infections and Infestations,” was compared between the placebo and denosumab groups by body systems and preferred terms. The temporal relationship between occurrence of serious adverse events of infections of interest and administration of denosumab was explored. RESULTS: Serious adverse events of infections involving the gastrointestinal system, renal and urinary system, ear, and endocarditis were numerically higher in the denosumab group compared with placebo, but the number of events was small. No relationship was observed between serious adverse events of infections and timing of administration or duration of exposure to denosumab. CONCLUSIONS: Serious adverse events of infections that occurred with denosumab treatment had heterogeneous etiology, with no clear clinical pattern to suggest a relationship to time or duration of exposure to denosumab. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00198-011-1755-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-32491592012-01-11 Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association? Watts, N. B. Roux, C. Modlin, J. F. Brown, J. P. Daniels, A. Jackson, S. Smith, S. Zack, D. J. Zhou, L. Grauer, A. Ferrari, S. Osteoporos Int Original Article SUMMARY: Serious adverse events of infections that occurred in subjects receiving denosumab or placebo in the Fracture Reduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) study were examined in detail. Serious adverse events of infections in denosumab subjects had heterogeneous etiology, with no clear clinical pattern to suggest a relationship to time or duration of exposure to denosumab. INTRODUCTION: Denosumab reduces the risk for new vertebral, hip, and nonvertebral fractures compared with placebo. In the pivotal phase 3 fracture trial (FREEDOM), the overall safety profile and incidence of adverse events including adverse events of infections were similar between groups. Serious adverse events of erysipelas and cellulitis were more frequent in denosumab-treated subjects. In this report, we further evaluate the details of infectious events in FREEDOM to better understand if RANKL inhibition with denosumab influences infection risk. METHODS: FREEDOM was an international multicenter, randomized, double-blind, placebo-controlled study in postmenopausal women with osteoporosis randomly assigned to receive placebo (n = 3,906) or denosumab 60 mg every 6 months (n = 3,902). The incidence of adverse events and serious adverse events categorized within the Medical Dictionary for Regulatory Activities system organ class, “Infections and Infestations,” was compared between the placebo and denosumab groups by body systems and preferred terms. The temporal relationship between occurrence of serious adverse events of infections of interest and administration of denosumab was explored. RESULTS: Serious adverse events of infections involving the gastrointestinal system, renal and urinary system, ear, and endocarditis were numerically higher in the denosumab group compared with placebo, but the number of events was small. No relationship was observed between serious adverse events of infections and timing of administration or duration of exposure to denosumab. CONCLUSIONS: Serious adverse events of infections that occurred with denosumab treatment had heterogeneous etiology, with no clear clinical pattern to suggest a relationship to time or duration of exposure to denosumab. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00198-011-1755-2) contains supplementary material, which is available to authorized users. Springer-Verlag 2011-09-03 2012 /pmc/articles/PMC3249159/ /pubmed/21892677 http://dx.doi.org/10.1007/s00198-011-1755-2 Text en © The Author(s) 2011 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Original Article
Watts, N. B.
Roux, C.
Modlin, J. F.
Brown, J. P.
Daniels, A.
Jackson, S.
Smith, S.
Zack, D. J.
Zhou, L.
Grauer, A.
Ferrari, S.
Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association?
title Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association?
title_full Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association?
title_fullStr Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association?
title_full_unstemmed Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association?
title_short Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association?
title_sort infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association?
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249159/
https://www.ncbi.nlm.nih.gov/pubmed/21892677
http://dx.doi.org/10.1007/s00198-011-1755-2
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