(187) Comparative Study of Osteonecrosis of The Jaw with Bisphosphonates and Denosumab in Two Pharmacovigilance Database

Friday, August 26, 2022

8:00 AM – 6:00 PM CEST

Location: Hall C

Publication Number: 518

Presenting Author(s)

Thierry Trenque, MD, PhD
– Professor, CHU de Reims, CHU Reims, Reims, Marne, France

Co-Author(s)

Laura Canneau
– Department of Pharmacovigilance and Pharmacoepidemiology, Reims University Hospital, Reims, France., Champagne-Ardenne, France
Salomé Martin
– Department of Pharmacovigilance and Pharmacoepidemiology, Reims University Hospital, Reims, France., France
Federica Tralongo
– Department of Pharmacovigilance and Pharmacoepidemiology, Reims University Hospital, Reims, France., France
Aurore Morel
– Department of Pharmacovigilance and Pharmacoepidemiology, Reims University Hospital, Reims, France., Champagne-Ardenne, France
Brahim Azzouz
– Department of Pharmacovigilance and Pharmacoepidemiology, Reims University Hospital, Reims, France., France

Background: The occurrence of osteonecrosis of the jaw (ONJ) under denosumab and/or bisphosphonates is well known, but no comparative studies using pharmacovigilance databases have been conducted to date.

Objectives: To describe and compare the profile of ONJ notifications under denosumab (Prolia, Xgeva) and/or bisphosphonates through a two-step analysis in two pharmacovigilance databases.

Methods: First, we performed a descriptive clinical analysis and a disproportionality analysis in the French pharmacovigilance database (FPVD) from January 1985 to December 2019, then a disproportionality analysis through the calculation of reporting odds ratio (ROR) in Vigibase, the WHO pharmacovigilance data base on the same period. The cases were selected using the Standardised MedDRA Queries (SMQ) “osteonecrosis” and the prefered terms (PT) “osteonecrosis” and “osteonecrosis of jaw". We have eliminated duplicates.

Results: Of the 1,398 cases obtained by the SMQ on the FNPV, 1,120 were selected as ONJ cases: 759 are attributed to bisphosphonates, 290 to the denosumab, and 71 to both. The majority of patients are women (69.73%), mean age 67 +- 12 years, treated for bone metastases (58.66%), in the context of breast cancer (57.69%). With the PT “Osteonecrosis of jaw” in the FNPV, the denosumab (XGEVA® form) has the highest ROR 1775.1 (95% CI 1473.3-2138.8) versus 369.5 (95%CI 318.4-428.9) for bisphosphonates, the highest with zoledronate (ROR 264.5, 95% CI 228.1-306.8). In VigiBase, we found a significant ROR with the denosumab forms: Xgeva (ROR 279.8, 95% CI 267.6-292.6]) and Prolia (ROR 22.7, 95% CI , 22- 24) and with bisphosphonates (ROR 342.7 95% CI 332.5-353.3).

Conclusions: The results of the descriptive analysis are consistent with the literature. The ROR obtained show a strong signal for bisphosphonates, especially zoledronate, and for denosumab (XGEVA® form). Dental examination prior to treatment should be a requirement.