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Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events
OBJECTIVE: Osteonecrosis of the jaw (ONJ) is a recognized complication of potent antiresorptive therapies, especially at the doses indicated to prevent skeletal complications for cancer patients with bone metastases. This paper describes the rationale and methods for a prospective, post-authorizatio...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959599/ https://www.ncbi.nlm.nih.gov/pubmed/27499646 http://dx.doi.org/10.2147/CLEP.S107270 |
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author | Acquavella, John Ehrenstein, Vera Schiødt, Morten Heide-Jørgensen, Uffe Kjellman, Anders Hansen, Svein Larsson Wexell, Cecilia Herlofson, Bente Brokstad Noerholt, Sven Erik Ma, Haijun Öhrling, Katarina Hernandez, Rohini K Sørensen, Henrik Toft |
author_facet | Acquavella, John Ehrenstein, Vera Schiødt, Morten Heide-Jørgensen, Uffe Kjellman, Anders Hansen, Svein Larsson Wexell, Cecilia Herlofson, Bente Brokstad Noerholt, Sven Erik Ma, Haijun Öhrling, Katarina Hernandez, Rohini K Sørensen, Henrik Toft |
author_sort | Acquavella, John |
collection | PubMed |
description | OBJECTIVE: Osteonecrosis of the jaw (ONJ) is a recognized complication of potent antiresorptive therapies, especially at the doses indicated to prevent skeletal complications for cancer patients with bone metastases. This paper describes the rationale and methods for a prospective, post-authorization safety study of cancer patients treated with antiresorptive therapies. METHODS: As part of a comprehensive pharmacovigilance plan, developed with regulators’ input, the study will estimate incidence of ONJ and of serious infections among adult cancer patients with bone metastases treated with denosumab (120 mg subcutaneously) or zoledronic acid (4 mg intravenously, adjusted for renal function). Patients will be identified using routinely collected data combined with medical chart review in Denmark, Sweden, and Norway. Followup will extend from the first administration of antiresorptive treatment to the earliest of death, loss-to-follow-up, or 5 years after therapy initiation. Results will be reported for three treatment cohorts: denosumab-naïve patients, zoledronic acid-naïve patients, and patients who switch from bisphosphonate treatment to denosumab. ONJ cases will be identified in three newly established national ONJ databases and adjudicated by the committee that functioned during the XGEVA(®) clinical trials program. CONCLUSION: This study will provide a real world counterpart to the clinical trial-estimated risks for ONJ and serious infections for cancer patients initiating denosumab or zoledronic acid. The establishment of ONJ databases in the three Scandinavian countries will have potential benefits outside this study for the elucidation of ONJ risk factors and the evaluation of ONJ treatment strategies. |
format | Online Article Text |
id | pubmed-4959599 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-49595992016-08-05 Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events Acquavella, John Ehrenstein, Vera Schiødt, Morten Heide-Jørgensen, Uffe Kjellman, Anders Hansen, Svein Larsson Wexell, Cecilia Herlofson, Bente Brokstad Noerholt, Sven Erik Ma, Haijun Öhrling, Katarina Hernandez, Rohini K Sørensen, Henrik Toft Clin Epidemiol Study Protocol OBJECTIVE: Osteonecrosis of the jaw (ONJ) is a recognized complication of potent antiresorptive therapies, especially at the doses indicated to prevent skeletal complications for cancer patients with bone metastases. This paper describes the rationale and methods for a prospective, post-authorization safety study of cancer patients treated with antiresorptive therapies. METHODS: As part of a comprehensive pharmacovigilance plan, developed with regulators’ input, the study will estimate incidence of ONJ and of serious infections among adult cancer patients with bone metastases treated with denosumab (120 mg subcutaneously) or zoledronic acid (4 mg intravenously, adjusted for renal function). Patients will be identified using routinely collected data combined with medical chart review in Denmark, Sweden, and Norway. Followup will extend from the first administration of antiresorptive treatment to the earliest of death, loss-to-follow-up, or 5 years after therapy initiation. Results will be reported for three treatment cohorts: denosumab-naïve patients, zoledronic acid-naïve patients, and patients who switch from bisphosphonate treatment to denosumab. ONJ cases will be identified in three newly established national ONJ databases and adjudicated by the committee that functioned during the XGEVA(®) clinical trials program. CONCLUSION: This study will provide a real world counterpart to the clinical trial-estimated risks for ONJ and serious infections for cancer patients initiating denosumab or zoledronic acid. The establishment of ONJ databases in the three Scandinavian countries will have potential benefits outside this study for the elucidation of ONJ risk factors and the evaluation of ONJ treatment strategies. Dove Medical Press 2016-07-20 /pmc/articles/PMC4959599/ /pubmed/27499646 http://dx.doi.org/10.2147/CLEP.S107270 Text en © 2016 Acquavella et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Study Protocol Acquavella, John Ehrenstein, Vera Schiødt, Morten Heide-Jørgensen, Uffe Kjellman, Anders Hansen, Svein Larsson Wexell, Cecilia Herlofson, Bente Brokstad Noerholt, Sven Erik Ma, Haijun Öhrling, Katarina Hernandez, Rohini K Sørensen, Henrik Toft Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events |
title | Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events |
title_full | Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events |
title_fullStr | Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events |
title_full_unstemmed | Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events |
title_short | Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events |
title_sort | design and methods for a scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events |
topic | Study Protocol |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959599/ https://www.ncbi.nlm.nih.gov/pubmed/27499646 http://dx.doi.org/10.2147/CLEP.S107270 |
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