TY - JOUR
T1 - 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
AU - Acquavella, John
AU - Ehrenstein, Vera
AU - Schiødt, Morten
AU - Heide-Jørgensen, Uffe
AU - Kjellman, Anders
AU - Hansen, Svein
AU - Larsson Wexell, Cecilia
AU - Herlofson, Bente Brokstad
AU - Noerholt, Sven Erik
AU - Ma, Haijun
AU - Öhrling, Katarina
AU - Hernandez, Rohini K
AU - Sørensen, Henrik Toft
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.2147/CLEP.S107270
DO - 10.2147/CLEP.S107270
M3 - Journal article
C2 - 27499646
SN - 1179-1349
VL - 8
SP - 267
EP - 272
JO - Clinical Epidemiology
JF - Clinical Epidemiology
ER -