背景:当使用基于钆的造影剂(GBCA)时,超敏反应(HSR)可能会意外发生并危及生命。钆沉积病(GDD)和与钆暴露相关的症状(SAGE)长期以来一直存在争议。然而,类似的研究目前还不完整或过时。因此,使用最新的上市后安全性数据比较不同GBCA在HSR和GDD/SAGE方面的安全性,应该会对安全使用GBCA产生进一步的见解.
方法:本研究使用世界卫生组织数据库VigiBase和FDA不良事件报告系统(FAERS)数据库,对所有GBCA与GDD之间的安全性差异和GBCA相关的HSR谱进行了比较和分析。还使用FAERS数据对SAGE进行了进一步分析。报告比值比(ROR)95%置信区间的下限用于信号检测。此外,HSR的频率是通过将VigiBase中的报告数量除以2008年至2022年IQVIA跨国集成数据分析系统中的总销售量(以百万为单位)来计算的。所有不良事件均使用药物监管活动医学词典(MedDRA)26.0进行标准化。
结果:这项研究表明,所有GBCA都具有诱导HSR的潜力,非离子线性GBCA表现出相对较低的信号。根据标准化MedDRA查询进行分层分析,gadobutrol对血管性水肿的ROR025更大。对于过敏性/过敏性休克条件,g二烯酸二甲胺和gadoteridol的ROR025较大。关于严重的皮肤不良反应,只有gadoverseamide和gadidiamide在FAERS和VigiBase中显示信号。地区之间的HSR频率也存在差异。关于GDD,Gadoterate葡甲胺,gadoteridol的ROR025较低。对与SAGE相关的29个首选术语的分析表明,应特别考虑与gadoverseamide相关的皮肤硬结的风险,gadopentetate二甲葡胺,gadobenatedimeglumine,gadodiamide,还有Gadoteridol.此外,与其他GBCA相比,gadodiamide和gadoteridol的皮肤紧绷风险更大。
结论:本研究使用来自多个来源的数据比较了GBCA之间的风险差异。然而,作为一种假设生成方法,明确的因果关系需要进一步研究和验证.
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 However, similar studies are currently incomplete or outdated.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 ROR025 for angioedema. The ROR025 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 ROR025. 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.