Pharmacovigilance Evaluation of Noninfectious Myocarditis and Pericarditis in Immune Checkpoint Inhibitor Recipients Using FAERS

IntroductionImmune-related adverse events (irAEs) pose considerable challenges to the clinical application of immune-checkpoint inhibitors (ICIs). Noninfectious myocarditis/pericarditis is a class of ICI-associated adverse events with a high fatality rate in real-world settings. This study aimed to comprehensively assess noninfectious myocarditis/pericarditis adverse events associated with ICIs.MethodsReports of ICI-related noninfectious myocarditis/pericarditis AEs were extracted from the FDA Adverse Event Reporting System (FAERS) database. Disproportionality analysis was performed using the reporting odds ratio (ROR). Serious and non-serious outcomes of noninfectious myocarditis/pericarditis cases were compared using the Mann-Whitney U test or chi-squared test, and clinical priority was assigned to signals by scoring five features on a 0- to 10-point scale. Factors associated with reporting were explored based on stratified analyses.ResultsReports of noninfectious myocarditis/pericarditis AEs accounted for 1.67% of all ICI AE reports during the study period in the FAERS database. The median age of the patients was 70 years (interquartile range [IQR] 62-76), and 94.66% of reports had serious outcomes. Eight categories of noninfectious myocarditis/pericarditis AEs with positive RORs were identified. Noninfectious myocarditis/pericarditis AEs treated with ICIs were more frequently reported in male and older patients. Of note, 2, 3 and 3 AEs were identified as strong, moderate, and weak clinical priorities, respectively. The median time to onset (TTO) of strong, moderate and weak AEs for ICI treatments was 25 (IQR 14-61), 56 (IQR 24.50-116.25) and 124 (IQR 29-301) days, respectively. All disproportionality signals showed early-failure patterns, with the hazard of AE reporting decreasing over time.ConclusionsThis study suggests a significant disproportionality signal between ICIs and noninfectious myocarditis/pericarditis AEs, and the findings provide supporting evidence for clinicians in managing these AEs.