Indication and adverse event profiles of denosumab and zoledronic acid: based on U.S. FDA adverse event reporting system (FAERS)

Si Su; Liuqing Wu; Guibao Zhou; Lingling Peng; Huanzhe Zhao; Xiao Wang; Kuan Li

doi:10.3389/fphar.2023.1225919

Indication and adverse event profiles of denosumab and zoledronic acid: based on U.S. FDA adverse event reporting system (FAERS)

Front Pharmacol. 2023 Nov 1:14:1225919. doi: 10.3389/fphar.2023.1225919. eCollection 2023.

Authors

Si Su^#^{1

2}, Liuqing Wu^#³, Guibao Zhou², Lingling Peng², Huanzhe Zhao², Xiao Wang^{1

2}, Kuan Li²

Affiliations

¹ School of Pharmacy, Guangdong Medical University, Zhanjiang, China.
² Department of Pharmacy, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China.
³ Longgang Central Hospital of Shenzhen, Shenzhen, Guangdong, China.

^# Contributed equally.

Abstract

Objective: To investigate adverse events (AEs) associated with denosumab (Dmab) and zoledronic acid (ZA), compare their association strengths, and explore potential applications to provide clinical reference. Methods: We collected data from FAERS from January 2004 to November 2022 and mined AE signals for Dmab and ZA using ROR values. We compared signal intensity for same AEs and investigated off-label use. We also examined their AEs in adjuvant therapy for breast and prostate cancer. Results: 154,735 reports of primary suspect drugs were analyzed in the FAERS database (Dmab: 117,857; ZA: 36,878). Dmab and ZA had 333 and 1,379 AE signals, with 189 overlaps. The AEs of Dmab included death (ROR:3.478), osteonecrosis of jaw (ROR:53.025), back pain (ROR:2.432), tooth disorder (ROR:16.18), bone pain (ROR:6.523). For ZA, the AEs included osteonecrosis (ROR:104.866), death (ROR: 3.645), pain (ROR:3.963), osteonecrosis of jaw (ROR: 91.744), tooth extraction (ROR: 142.143). Among overlap signals, Dmab showed higher strength in exostosis of the jaw (ROR: 182.66 vs. 5.769), atypical fractures (ROR: 55.589 vs. 9.123), and atypical femur fractures (ROR:49.824 vs. 4.968). And ZA exhibited stronger associations in abscess jaw (ROR: 84.119 vs. 11.12), gingival ulceration (ROR: 74.125 vs. 4.827), increased bone formation (ROR: 69.344 vs. 3.218). Additionally, we identified 528 off-label uses for Dmab and 206 for ZA, with Dmab mainly used in prostate cancer (1.04%), breast cancer (1.03%), and arthritis (0.42%), while ZA in breast cancer (3.21%), prostate cancer (2.48%), and neoplasm malignant (0.52%). For Dmab in breast cancer treatment, AEs included death (11.6%), disease progression (3.3%), and neutropenia (2.7%), while for ZA included death (19.8%), emotional disorder (12.9%), osteomyelitis (11.7%). For prostate cancer treatment, Dmab`s AEs were death (8.9%), prostate cancer metastatic (1.6%), renal impairment (1.7%), while ZA`s included death (34.4%), general physical health deterioration (19.9%), and hemoglobin decreased (18.9%). Conclusion: Our analysis of FAERS database provided postmarketing surveillance data and revealed different strengths of reported AE signals between Dmab and ZA in some of their common AEs. It's also worth noting that both drugs have potential off-label applications, which could introduce new AEs. This highlights the necessity for safety monitoring when using Dmab and ZA off-label.

Keywords: adverse events; denosumab; off-label use; pharmacovigilance; zoledronic acid.

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (Grant NO. 81903581), Shenzhen Science and Technology Program (Grant NOs JCYJ20190807150005699 and RCBS20200714115000009), Shenzhen Key Medical Discipline Construction Fund (Grant NO. SZXK059), Shenzhen Key Laboratory of Prevention and Treatment of Severe Infections (ZDSYS20200811142804014).