Gastrointestinal Infection Before Immune Checkpoint Inhibition Hinders Treatment Efficacy and Increases the Risk of Colitis

Abstract

ABSTRACT Background Gastrointestinal (GI) infections, which often result in or stem from intestinal dysbiosis, can affect the efficacy of immune checkpoint inhibitors (ICIs) and increase the risk of adverse effects, such as colitis. In this study, we explored the impact of GI infections before initiation of ICI therapy on the incidence and severity of immune‐mediated colitis (IMC) and survival. Methods A single‐center, retrospective review including all patients who received ICIs from January 2010 to February 2024 and subsequently developed IMC. Patients were screened for IMC and prior GI infections based on symptoms and stool tests. Patients' demographic, IMC, and GI infection–related clinical data were collected. Results Thirty‐four of the 1132 patients (3.0%) included in the analysis had GI infections before ICI therapy. GI infections were most commonly caused by Clostridioides difficile and most often treated with oral antibiotics (interquartile range [IQR], 7–14 days). The incidence of IMC was higher in patients with prior GI infections compared to patients without prior infections (8.7% vs. 5.1%, p = 0.002). IMC symptoms, severity, and outcomes were similar in both groups (p > 0.05). In multivariate Cox proportional survival analysis, prior GI infection was independently associated with an increased risk of mortality (odds ratio, 1.6 [95% CI, 1.4–1.8]; p < 0.001) for patients who received ICIs. Conclusions Our study is the first to explore the impact of GI infection before ICI therapy on IMC risk and survival. We found that prior GI infection was associated with an increased incidence of IMC and an increased risk of mortality in patients receiving ICIs.

Keywords

• gastrointestinal infections
• gut microbiome
• immune checkpoint inhibitors
• immune‐mediated colitis
• intestinal dysbiosis
• risk factors