Cardiotoxicity in Biological Agent-Targeted Therapy for Rheumatoid Arthritis: ADR Signal Mining and Analysis of Food and Drug Administration Adverse Event Reporting System Database

Abstract

Purpose: Biologic agent-induced cardiotoxicity is markedly concerning. Rheumatoid arthritis (RA) treated with biologic agents is known to have the potential for cardiotoxicity; however, existing clinical evidence is not adequate to explain real-world patterns of cardiotoxicity. In this study, we quantify the risk of cardiotoxicity in patients with rheumatoid arthritis treated with biological agents.Methods: Cardiotoxicity reports induced by four types of biologic agents, abatacept, adalimumab, tocilizumab, and etanercept were used to mine data from the FDA's adverse event reporting system (FAERS) database from January 1, 2004 through September 30, 2020. Reports of cardiotoxic events were analyzed using a reporting odds ratio (ROR) algorithm, the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), the multi-item gamma Poisson shrinker (MGPS), and logistic regression methods. We use the preferred term of the Medical Dictionary of Regulatory Activities to identify such events.Results: A total of 3,969 reports of cardiotoxic events were identified involving biologic agents used for RA as the suspect drugs in this study, 317 reports of abatacept, 2,137 reports of adalimumab, 273 reports of tocilizumab, and 1,242 reports of etanercept. Adalimumab was the most reported, followed by etanercept. The proportion of death and disability outcomes reported for each targeted treatment represents approximately 20–25% of the total reported severe adverse events. In addition, relatively low cardiotoxicity reporting rates were found with abatacept.Conclusion: Analysis of FAERS data offers a more precise profile on the characteristics and occurrences of cardiotoxic events. The findings are a clinical reminder to physicians that an increased vigilance concerning the cardiotoxic effects of biological agents needs to be implemented. Also, more comparative studies are required in the future to explain the mechanisms that cause these cardiac phenomena.

Analysis of COVID-19 vaccine-related adverse event reports following COVID-19 vaccine BNT162b2 mRNA-1273 and Ad.26.COV2.S based on the US vaccine adverse event reporting system

“…There is concern about the increased incidence of myocarditis following the coronavirus disease-19 (COVID-19) mRNA vaccine [19]. Abnormal menstrual cycle (delaying/increase hemorrhages or pain) was also reported in the references [20].…”

“…The coronavirus disease 2019 (COVID- 19) is caused by SARS-COV-2 (severe acute respiratory syndrome coronavirus 2). The acute respiratory infections lead to a worldwide epidemic.…”

Five years of safety profile of bevacizumab: an analysis of real-world pharmacovigilance and randomized clinical trials

“…ROR allows estimation of relative risk and focuses attention on which individuals or reports should be included or excluded from the control group, thus allowing for more effective elimination of bias. The proportional reporting rate (PRR) method was proposed by Evans et al in 1998 to generate a positive signal [ 9 ]. the PRR value is related to the proportion of spontaneous reports of a drug associated with a specific adverse outcome divided by the corresponding proportion for all or several other drugs.…”

The elucidation of the anti-inflammatory mechanism of EMO in rheumatoid arthritis through an integrative approach combining bioinformatics and experimental verification

“…In the past 20 years, the emergence of biological agents including interleukin 6 (IL-6) inhibitors, costimulatory modulators, B cell depleting drugs as well as tumor necrosis factor (TNF) inhibitors has changed the original treatment strategy and fundamentally Changed the course of rheumatoid arthritis ( Crossfield et al, 2021 ). However, the above-mentioned drugs have varying degrees of adverse reactions or clinical application restrictions, which reduce their expected clinical effects, or they may cause a serious burden on patients‘ medication due to their high price and other factors ( Harigai, 2019 ; Solomon et al, 2020 ; Tang et al, 2021 ). Therefore, it is essential to search for more effective, reliable, and cost-effective anti-RA drugs.…”