Detection of potential safety signals related to the use of remdesivir and tocilizumab in the COVID era during pregnancy, resorting to open data from the FDA adverse event reporting system (FAERS).

Background: The in-hospital treatment for COVID-19 may include medicines from various therapeutic classes, such as antiviral remdesivir and immunosuppressant tocilizumab. Safety data for these medicines are based on controlled clinical trials and case reports, limiting the knowledge about less frequent, rare or unique population adverse events excluded from clinical trials. Objective: This study aims at analyzing the reports of Adverse Drug Events (ADEs) related to these two medicines, focusing on events in pregnant women and foetuses. Methods: Data from the open-access FDA Adverse Event Reporting System (FAERS) from 2020 to 2022 were used to create a dashboard on the Grafana platform to ease querying and analyzing report events. Potential safety signals were generated using the ROR disproportionality measure. Results: Remdesivir was notified as the primary suspect in 7,147 reports and tocilizumab in 19,602. Three hundred and three potential safety signals were identified for remdesivir, of which six were related to pregnant women and foetuses (including abortion and foetal deaths). Tocilizumab accumulated 578 potential safety signals, and three of them were associated with this population (including neonatal death). Discussion: None of the possible signals generated for this population were found in the product labels. According to the NIH and the WHO protocols, both medicines are recommended for pregnant women hospitalized with COVID-19. Conclusion: Despite the known limitations of working with open data from spontaneous reporting systems (e.g., absence of certain clinical data, underreporting, a tendency to report severe events and recent medicines) and disproportionality analysis, the findings suggest concerning associations that need to be confirmed or rejected in subsequent clinical studies.

A real-world disproportionality analysis of cyclosporine from the FDA Adverse Event Reporting System (FAERS) database

Cyclosporine is an immunosuppressant used to prevent organ rejection in kidney, liver, and heart allogeneic transplants. This study aimed to assess the safety of cyclosporine through the analysis of adverse events (AEs) related to cyclosporine in the US Food and Drug Administration Adverse Event Reporting System (FAERS). To detect AEs associated with cyclosporine, a pharmacovigilance analysis was conducted using four algorithms on the FAERS database: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM). A statistical analysis was performed on data extracted from the FAERS database, covering 19,582 case reports spanning from 2013 to 2022. Among these cases, 3,911 AEs were identified, with 476 linked to cyclosporine as the primary suspected drug. Cyclosporin-induced AEs targeted 27 System Organ Classes (SOCs). Notably, the highest case at the SOC level included eye disorders, injury, poisoning, and procedural complications, as well as immune system disorders, all of which are listed on the cyclosporine label. Furthermore, we discovered novel potential AEs associated with hepatobiliary disorders, among others. Moreover, unexpected adverse drug reactions (ADRs), such as biliary anastomosis complication and spermatozoa progressive motility decrease, were identified. Importantly, these newly identified ADRs were not mentioned on the cyclosporine label, which were involved in injury, poisoning, and procedural complications, and investigations at the SOC level. The study used pharmacovigilance analysis of FAERS database to identify new and unexpected potential ADRs relating to cyclosporine, which can provide safety tips for the safe use of cyclosporine.

Cardiovascular toxicity following immune checkpoint inhibitors: A systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors may be associated with multiple immune-related toxicities. Cardiovascular adverse effects are underreported in clinical trials. METHODS: We conducted a systematic review and meta-analysis to evaluate cardiovascular adverse effects incidence among patients with solid tumors receiving immune checkpoint inhibitors in randomized clinical trials and the relative risk of presenting these effects compared to placebo or best supportive care. The search was conducted through MEDLINE, Embase, and Scopus databases from January 1st, 2010 until July 1st, 2020. Outcomes were reported following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS: 57 randomized clinical trials including 12,118 patients were included. All grade CV AEs incidence rate was 8.32% (95% CI = 6.35%-10.53%). When only grade 3-5 CV AEs were considered, ICIs were significantly associated with increased risk than placebo or BSC (RR = 1.36; 95% CI = 1.06-1.73; p = 0.01). CONCLUSION: This meta-analysis corroborates the hypothesis of increased CV risk related to immune checkpoint inhibitors.