Association between Myocarditis and Other Immune-Related Adverse Events Associated with Immune Checkpoint Inhibitor Use: Analysis of the FDA Adverse Events Reporting System (FAERS)

Abstract

Background Immune checkpoint inhibitors (ICI) are increasingly being used for the management of malignancies, but they are associated with immune-related adverse events (irAE). Myocarditis is a rare irAE that is associated with high mortality, and thus early diagnosis is essential. Because some myocarditis events are asymptomatic, it is important to suspect myocarditis in patients presenting with irAEs. The purpose of this study is to evaluate the association between myocarditis and other irAEs reported to the FDA, to identify high-risk patients that may benefit from screening for myocarditis. Hypothesis We hypothesized that ICI- associated myocarditis is associated with other irAEs. Methods Using the FDA Adverse Events Reporting System (FAERS), we identified all adverse events (AEs) associated with 5 ICIs (Nivolumab, Ipilimumab, Pembrolizumab, Atezolizumab, Durvalumab) between April 2011 and December 2018. We investigated the association between myocarditis and type of ICI, patient characteristics, and other concomitantly-reported irAE, using logistic regression and reporting odds ratio (ROR), adjusting for age, sex, reporting year, and combination ICIs. Results There were a total of 398 myocarditis events reported during the study period, accounting for 0.7% of all 55,642 ICI-AEs, and 3.5% of 11,480 irAE events. Mean age for myocarditis 65.7±12.4 years, and 64.5% were male. Combination ICI was associated with increased risk of myocarditis (OR 1.85, 95% CI: 1.41-2.42, P Conclusions ICI-associated myocarditis is associated with myositis, encephalitis, and hepatitis. The presence of either of this high-risk irAEs should raise suspicion for myocarditis.