Study on the risk signal mining related to denosumab based on the US Food and Drug Administration Adverse Event Reporting System
10.3760/cma.j.cn114015-20210813-00897
- VernacularTitle:基于美国FDA不良事件报告系统数据库的地舒单抗风险信号挖掘
- Author:
Jing PENG
1
;
Kaijie JIANG
;
Xiaolei REN
;
Mingli WU
;
Yanyan ZHAO
;
Meixia WANG
;
Luhua MENG
;
Zhen LIU
;
Li WANG
Author Information
1. 济宁医学院附属医院药学部，济宁 272029
- Publication Type:Journal Article
- Keywords:
RANK ligand;
Osteonecrosis;
Adverse drug reaction reporting systems;
United States Food and Drug Administration;
Signal processing, computer-assisted;
Deno
- From:
Adverse Drug Reactions Journal
2022;24(2):67-73
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To understand the main adverse event (AE) related to denosumab and the risks and provide reference for the safe use of the drug in clinic.Methods:The AE reports on denosumab included in the US FDA Adverse Event Reporting System from the second quarter of 2010 to the first quarter of 2021 were collected, and the AE risk signals was explored using proportional reporting odds ratio ( PRR) method. AEs with ≥3 reports, PRR value ≥2, and χ2≥4 were defined as positive risk signals. AEs were counted and classified using the preferred system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities 24.0. The PTs of top 50 adverse event reports and signal intensity were selected and analyzed. Results:A total of 132 764 AE reports with denosumab as the primary suspected drug were collected, involving 5 571 PTs, and 641 positive risk signals were selected. After the second screening, the top 50 PTs in the number of AE reports and the top 50 PTs with great PRR values were obtained, and 93 PTs were included in the analysis after sifting out the repeated, involving 114 617 AE reports. The top 5 PTs in the number of AE reports were off-label use (28.7%, 32 863/114 617), death (14.2%, 16 230/114 617), osteonecrosis of the jaw (6.0%, 6 861/114 617), arthralgia (4.7%, 5 420/114 617), and limb pain (4.1%, 4 727/114 617). The top 5 PTs with the high signal intensity were giant-cell tumour of bone ( PRR=402.7), malignant giant-cell tumour of bone ( PRR=325.2), C-telopeptide increase ( PRR=169.4), exostosis of jaw ( PRR=163.2), and ionised calcium abnormal ( PRR=158.1). The top 5 SOC involving AE reports were injury, poisoning and procedural complications (35.9%, 41 757/114 617), musculoskeletal and connective tissue disorders (32.7%, 37 455/114 617), general disorders and administration site conditions (18.2%, 20 814/114 617), surgical and medical procedures (4.1%, 4 744/114 617), and investigations (2.9%, 3 290/114 617). Forty-four PTs were not included in the drug instructions, of which 23 were related to the oral cavity. Conclusions:Denosumab AE with the most reports were off-label use and osteonecrosis of the jaw. The risk signals of osteonecrosis of the jaw and recurrence or deterioration of giant-cell tumor of bone was strong. Most of the AE risk signals that were not included in the instructions are oral problems.
