Adverse event risk signal mining of anti-disialoganglioside 2 monoclonal antibody based on US FDA Adverse Event Reporting System
10.3760/cma.j.cn114015-20231016-00737
- VernacularTitle:基于美国FDA不良事件报告系统数据库的GD2单抗不良事件风险信号挖掘
- Author:
Miaomiao SHAO
1
;
Ximu SUN
;
Han ZHOU
;
Ying LI
;
Yixin SUN
;
Changqing YANG
;
Xiaoling WANG
;
Wen ZHAO
Author Information
1. 首都医科大学附属北京儿童医院药学部，北京 100045
- Publication Type:Journal Article
- Keywords:
Neuroblastoma;
Antibodies, monoclonal;
Drug toxicity;
Adverse event risk signal;
Disialoganglioside;
Naxitamab;
Dinutuximab
- From:
Adverse Drug Reactions Journal
2023;25(10):592-600
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To understand the adverse event (AE) risk signals of 3 anti-disialoganglioside 2 (GD2) monoclonal antibodies, including dinutuximab, dinutuximab beta, and naxitamab, and to provide reference to clinical use.Methods:AE reports with dinutuximab, dinutuximab beta, and naxitamab as the primary and secondary suspect drug were collected from the US FDA Adverse Event Reporting System (FAERS) database during 2015 to the 2nd quarter of 2023. AEs were standardized and classified according to the preferred term (PT) and system organ classification (SOC) in the International Medical Terminology Dictionary, Version 25.0, and AE risk signals were mined using the reporting odds ratio (ROR) method and information component (IC) method. The AE reports information and AE risk signals of 3 GD2 monoclonal antibodies were descriptively analyzed.Results:A total of 630 AE reports were collected, in which the 3 GD2 monoclonal antibodies were the primary and secondary suspect drugs, including 465 reports of dinutuximab, 61 reports of dinutuximab beta, and 104 reports of naxitamab, which involved 341, 24, and 125 PTs and mapped to 19, 2, and 12 SOCs, respectively. The AEs of the 3 GD2 monoclonal antibodies were associated with the occurrence of death, life-threatening, hospitalization, or prolonged hospitalization adverse outcomes. Signal mining using ROR and IC methods detected a total of 142, 3, and 30 AE risk signals, of which 73, 0, and 6 were not documented in the corresponding drug instructions, respectively. The top PTs in report number were fever for both dinutuximab and dinutuximab beta, and hypotension and pain for naxitamab; the top PTs in signal intensity were puncture site abscess, device related bacteraemia, and wheezing for dinutuximab, dinutuximab beta, and naxitamab, respectively. The overlapping AE risk signals for the 3 drugs were fever and pain, with dinutuximab having the strongest signal intensity for fever and naxitamab having the strongest signal intensity for pain. Among the top 30 PTs in report number, naxitamab had significantly more AE risk signals than dinutuximab in respiratory, thoracic, and mediastinal disorders, skin and subcutaneous tissue disorders, immune system disorders, and vascular disorders. For naxitamab, the PTs that differed from dinutuximab′s AE risk signals and were not documented in the naxitamab drug instructions were respiration abnormal, cyanosis, and metabolic acidosis.Conclusions:Fever, pain, and hypotension are common AEs for the 3 GD2 monoclonal antibodies. Naxitamab causes significant pain; respiration abnormal, cyanosis, and metabolic acidosis are AE risk signals specific to naxitamab and not documented in the drug instruction, which warrant clinical vigilance and prompt intervention.
