Immune-Mediated Upper Gastrointestinal System Toxicities in Patients Receiving Immune Checkpoint Inhibitors: An Analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS)

Background: Immune-mediated (im) upper gastrointestinal (GI) toxicities refer to inflammatory damage of oesophagus, stomach and duodenum following immune checkpoint inhibitors (ICIs) use. Given its rarity and vague symptoms, diagnosis is often challenging for physicians and management strategies are mainly extrapolated from im-colitis. Therefore, we aim to assess demographic characteristics of patients with im-upper GI toxicity reported in the FAERS system. Methods We retrospectively searched the data of patients receiving ICIs. We included a total of 132 patients with im-upper GI toxicity by using keywords “immune-mediated gastritis” and “immune-mediated oesophagitis”. We evaluated the associations between im-upper GI toxicities and variables including age, gender, treatment regimens used, and concurrent im-adverse events. Serious adverse events were considered as requiring hospitalization or deemed life-threatening. Categorical variables were compared using either the chi-square test or Fisher’s exact test, depending on the sample size and the distribution of expected values within the contingency tables. To evaluate the potential association between ICIs and specific upper GI toxicity events of interest, a disproportionality analysis was conducted using the Reporting Odds Ratio (ROR) method. ROR values were calculated from 2×2 contingency tables by comparing the reporting frequency of im-toxicities for each ICI to that of all other drugs in the FAERS database. A signal was considered statistically significant when the lower bound of the 95% confidence interval (CI) for the ROR exceeded 1.0, indicating a potential increased risk. Results: Im-upper GI toxicities were observed in 132 patients. Twenty-six patients developed im-esophagitis, 100 patients developed im-gastritis, and six had both. Anti-PD-1 agents were associated with higher incidence of im-upper GI toxicities compared to anti-PD-L1 agents (p = 0.001, ROR = 3.83) Hospitalization rates were higher in patients receiving anti-PD-1 therapy compared to those treated with anti-PD-L1 (p = 0.007). A higher incidence of hospitalization rate was observed in patients receiving concurrent chemotherapy (71.4%) than in those did not receive (36.1%) (p = 0.006, ROR = 3.41) Conclusion: Anti-PD-1 use may be associated with higher incidence of im-upper GI toxicity and addition of chemotherapy may lead to more serious toxicities.