Journal Article

Differences in hypersensitivity reactions and gadolinium deposition disease/symptoms associated with gadolinium exposure to gadolinium-based contrast agents: new insights based on global databases VigiBase, FAERS, and IQVIA-MIDAS

Wang, Yuanyuan, Lou, Yuefen, Li, Wenjing, Li, Nianyun, Qi, Chendong, Fan, Guorong, Qu, Han, Wu, Zhenghua, Li, Xiang, Feng, Tingting, Wei, Taishan

2024

Overview

Background Hypersensitivity reactions (HSRs) can occur unexpectedly and be life-threatening when gadolinium-based contrast agents (GBCAs) are used. Gadolinium deposition disease (GDD) and symptoms associated with gadolinium exposure (SAGE) have been controversial for a long time. However, similar studies are currently incomplete or outdated. Therefore, comparing the safety of different GBCAs in terms of HSRs and GDD/SAGE using the latest post-marketing safety data should yield further insights into safely using GBCAs. Methods The safety differences between all GBCAs to GDD and the spectrum of GBCA-related HSRs were all compared and analyzed by using the World Health Organization database VigiBase and the FDA Adverse Event Reporting System (FAERS) database in this study. A further analysis of SAGE was also conducted using FAERS data. The lower limit of the reporting odds ratio (ROR) 95% confidence interval was used for signal detection. Moreover, the frequency of HSRs was calculated by dividing the number of reports in VigiBase by the total sales volume (measured in millions) from 2008 to 2022 in the IQVIA Multinational Integrated Data Analysis System. All adverse events were standardized using the Medical Dictionary for Drug Regulatory Activities (MedDRA) 26.0. Results This study shows that all GBCAs have the potential to induce HSRs, with nonionic linear GBCAs exhibiting a comparatively lower signal. According to standardized MedDRA query stratification analysis, gadobutrol had a greater ROR 025 for angioedema. The ROR 025 of gadobenate dimeglumine and gadoteridol is larger for anaphylactic/anaphylactoid shock conditions. Regarding severe cutaneous adverse reactions, only gadoversetamide and gadodiamide showed signals in FAERS and VigiBase. There were also differences in the frequency of HSRs between regions. Regarding GDD, gadoterate meglumine, and gadoteridol had a lower ROR 025 . An analysis of the 29 preferred terms linked to SAGE indicated that special consideration should be given to the risk of skin induration associated with gadoversetamide, gadopentetate dimeglumine, gadobenate dimeglumine, gadodiamide, and gadoteridol. Additionally, gadodiamide and gadoteridol pose a greater risk of skin tightness compared to other GBCAs. Conclusions The risk differences among GBCAs using data from several sources were compared in this study. However, as a hypothesis-generating method, a clear causal relationship would require further research and validation.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adverse Drug Reaction Reporting Systems / Adverse events / Allergic reaction / Allergy / Anaphylaxis / Angioedema / Biomedicine / Clinical medicine / Comparative analysis / Contrast agents / Contrast media / Contrast Media - adverse effects / Data analysis / Databases, Factual / Deposition / Drug Hypersensitivity - epidemiology / Drugs / FAERS / Gadolinium / Gadolinium - adverse effects / Gadolinium deposition disease / Gadolinium-based contrast agents / Gadopentetate dimeglumine / Health aspects / Humans / Hypersensitivity / Hypersensitivity reactions / Information management / IQVIA-MIDAS / Medical research / Medicine / Medicine & Public Health / Medicine, Experimental / Pharmacovigilance / Physiological aspects / Research Article / Safety / Signal detection / Signs and symptoms / Skin / Tightness / United States / VigiBase / World Health Organization