Beyond Proton Pump Inhibitors: Evaluating Treatment Strategies for Immune-Mediated Gastroenteritis from Cancer Immunotherapy.

[BACKGROUND] Immune-mediated gastroenteritis (IMG) has been commonly managed with proton pump inhibitors (PPIs), though their effectiveness is unclear. Histological analysis has shown depletion of parietal cells in the gastric mucosa during IMG, which inhibits PPI action.

[OBJECTIVE] Extending on a small cohort study, we assessed the role of PPIs, and alternatives such as corticosteroids, for managing IMG.

[PATIENTS AND METHODS] This was a retrospective study at a tertiary care cancer center, including patients with malignancy who received an immune-checkpoint inhibitor (ICI) between 2010 and 2024 and developed IMG.

[RESULTS] A total of 399 patients were included, of whom 281 (70.4%) received PD-1/PD-L1 inhibitors. Of these, 190 (47.6%) had exclusive IMG, and 69 (36.3%) were treated with PPIs. PPI use did not significantly impact clinical outcomes. In contrast, 156 (39.1%) received corticosteroids, showing improved clinical outcomes (75.8% vs 65%; p = 0.027) and a trend towards faster symptom resolution (41.5 vs 53 days; p = 0.064). Endoscopic remission was achieved in 71.1% of the steroid group and 36.7% of the non-steroid group. ICI discontinuation was more frequent with steroids (73.5% vs 50.7%; p < 0.0001), as was symptom recurrence within 6 months (16.7% vs 3.6%; p < 0.0001). All-cause mortality was higher in the non-steroid group (51.5% vs 41%; p = 0.042), which had a shorter follow-up period (0.7 vs 1.1 years; p = 0.004). Binary logistic regression showed that steroid use (OR 1.7, 95% CI 1.06-2.7; p = 0.027) and ICI discontinuation (OR 1.9, 95% CI 1.1-3.0; p = 0.007) were associated with clinical improvement.

[CONCLUSION] Our findings show faster clinical improvement and higher endoscopic remission rates with steroids, while PPIs demonstrated no significant effectiveness.