Cardiac Inflammation after COVID-19 mRNA Vaccines: A Global Pharmacovigilance Analysis

Background To counter the COVID-19 pandemic, mRNA vaccines, namely tozinameran and elasomeran, have been authorized in several countries. These next generation vaccines have shown high efficacy against COVID-19 and demonstrated a favorable safety profile. As widespread vaccinations efforts are taking place, incidents of myocarditis and pericarditis cases following vaccination have been reported. This safety signal has been recently confirmed by the European Medicine Agency and the U.S. Food and Drug Administration. This study aimed to investigate and analyze this safety signal using a dual pharmacovigilance database analysis. Methods This is as an observational study of reports of inflammatory heart reactions associated with mRNA COVID-19 vaccines reported in the World Health Organization's global individual case safety report database (up to June 30th 2021), and in the U.S. Vaccine Adverse Event Reporting System (VAERS, up to May 21st 2021). Cases were described, and disproportionality analyses using reporting odds-ratios (ROR) and their 95% confidence interval (95%CI) were performed to assess relative risk of reporting according to patient sex and age. Results At a global scale, the inflammatory heart reactions most frequently reported were myocarditis (1241, 55%) and pericarditis (851, 37%), the majority requiring hospitalization (n=796 (64%)). Overall, patients were young (median age 33 [21-54] years). The main age group was 18-29 years old (704, 31%), and mostly males (1555, 68%). Pericarditis onset was delayed compared to myocarditis with a median time to onset of 8 [3-21] vs. 3 [2-6] days, respectively (p=0.001). Regarding myocarditis, an important disproportionate reporting in males (ROR, 9.4 [8.3-10.6]) as well as in adolescents (ROR, 22.3 [19.2-25.9]) and 18-29 years old (ROR, 6.6 [5.9-7.5]) compared to older patients were observed. Conclusions The inflammatory heart reactions, namely myocarditis and pericarditis, have been reported world-wide shortly following COVID-19 mRNA vaccination. An important disproportionate reporting among adolescents and young adults, particularly in males, was observed especially for myocarditis. Guidelines must take this specific risk into account and to optimize vaccination protocols according to sex and age. While the substantial benefits of COVID-19 vaccination still prevail over risks, clinicians and the public should be aware of these reactions and seek appropriate medical attention.

Adverse Event Reporting with Immune Checkpoint Inhibitors in Older Patients: Age Subgroup Disproportionality Analysis in VigiBase

Older patients represent a subpopulation of concern for immune checkpoint inhibitor (ICI) toxicity because of changes in the aging immune system and the potentially relevant clinical implications for their quality of life. Current evidence on ICI safety in older patients is conflicting. This study aimed to assess whether older patient age was a risk factor for increased reporting with ICIs as compared to other antineoplastic drugs in VigiBase, the World Health Organization database of suspected adverse drug reactions. Disproportionality analyses computing the reporting odds ratios (RORs) were performed by age subgroups (<18 years, 18–64 years, 65–74 years, 75–84 years and ≥85 years). There were not signals of disproportionate reporting with ICIs specifically detected in older patient age subgroups (≥65 years), which were not present in the disproportionality analysis over the entire dataset. A signal of disproportionate reporting with ICIs emerged for eye disorders only in the age subgroup 18–64 years (ROR 1.13, 95% confidence interval 1.05–1.23). These findings showed that adverse event reporting with ICIs in older patients was comparable to that in the overall patient cohort and prompt for the further investigation of eye disorders with ICIs to elucidating risk factors and defining management strategies.

Endotoxin-Like Reactions With Intravenous Gentamicin Results From Pharmacovigilance Tools Under Investigation

Objective:To apply two data mining algorithms (DMAs) to Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) reports that involved endotoxin-like reactions with intravenous gentamicin to determine whether a signal of disproportionate reporting of these events would have been generated concurrently with surveillance based on clinical observation.Design:Multi-item gamma-Poisson shrinker (MGPS) and proportional reporting ratios (PRRs) were used. Data used for data mining consisted of an extract of the FDA AERS database. Previously published details of clusters of endotoxin-like reactions to intravenous gentamicin were used to select adverse events for data mining.Results:The first signal of disproportionate reporting with any relevant event occurred in 1998, the year in which the outbreak was identified and evaluated by the Centers for Disease Control and Prevention and the FDA. In 1997, there were only 6 reports of rigors in the AERS; this jumped to 68 in 1998. In 1998, a signal was generated for endotoxic shock with PRRs but not with MGPS, based on one case.Conclusions:The two DMAs generated signals concurrently with the influx of reports. It would have been difficult for safety reviewers to ignore an increase in rigors by traditional methods of safety surveillance; therefore, DMAs might not have had a great deal to offer in this instance. If data mining were considered as a second-line defense to diligent clinical observations under similar circumstances, simple disproportionality methods such as PRRs might be more useful than DMAs such as MGPS when commonly cited thresholds are used.