129 Association Between Colitis and Immune Checkpoint Inhibitor Use: Analysis of the FDA Adverse Event Reporting System (FAERS)

Abstract

INTRODUCTION: Immune checkpoint inhibitors (ICI) are increasingly being used for management of malignancies, but they are associated with serious immune-related adverse events (irAE) due to overactivation of the immune system. Gastrointestinal tract is commonly affected by the ICI and have been frequently reported in literature. The purpose of this study is to evaluate the epidemiology of colitis associated with ICI use reported to the FDA. METHODS: We used the Food and Drug Administration Adverse Event Reporting System (FAERS), a database that contains adverse events reports, medication error reports and product quality complains reported to the FDA. It is a voluntary post-marketing pharmacosurveillance database maintained by the FDA. We identified all adverse events (AEs) associated with 5 FDA-approved ICIs (Nivolumab, Ipilimumab, Pembrolizumab, Atezolizumb, Durvalumab) between April 2011 and December 2018. We investigated the number of colitis cases associated with these ICI reported to the FDA. RESULTS: We identified 53,899 adverse events related to ICI that were reported to FDA, out of which 1908 (3.54%) were reported as colitis. The highest number of colitis was reported to be associated with Ipilimumab 1278 (53.9%), followed by Nivolumab 784 (33.1%). Given that these ICI were approved during different years ranging from 2011–2017, we identified total number of colitis cases in the year 2018 and determined that 12.01% of colitis-deaths were associated with Nivolumab, followed by Ipilimumab (7.48%). The number of colitis cases reported increased from 236 in 2011–2013, to 665 in 2014–2016, and 1007 in 2017–2018 (Figure 2). Moreover, of the total 1908 colitis cases, 1849 cases were noted to be serious cases out of which 336 (17.6%) died due to colitis. CONCLUSION: In the FAERS database we described the prevalence of colitis as an immune related adverse event associated with the use of immune checkpoint inhibitors. Colitis accounted for 3.5% of the total adverse events reported with ICI between 2011 and 2018. Moreover, our study showed high mortality rate (17.6% of the cases) associated with ICI-Colitis.