Efficacy of current therapeutic strategies for immune checkpoint inhibitor-related esophagitis

Carolina Colli Cruz; Maria Julia M.N. Santos; Sharada Wali; Rachel Mortan; Rohan Ahuja; Jarrett Rong; Tanvi Gupta; Irene Jeong-Ah Lee; Cristina Natha; Varun Vemulapalli; Sean Ngo; Kei Takigawa; Krishnavathana Varatharajalu; Lucy B. Kennedy; Aliyah Pabani; Bryan P. Schneider; Karen C. Kim; Mehnaz A. Shafi; Anusha S. Thomas; Yinghong Wang

Authors Carolina Colli Cruz, Maria Julia M.N. Santos, Sharada Wali, Rachel Mortan, Rohan Ahuja, Jarrett Rong, Tanvi Gupta, Irene Jeong-Ah Lee, Cristina Natha, Varun Vemulapalli, Sean Ngo, Kei Takigawa, Krishnavathana Varatharajalu, Lucy B. Kennedy, Aliyah Pabani, Bryan P. Schneider, Karen C. Kim, Mehnaz A. Shafi, Anusha S. Thomas, Yinghong Wang.

Abstract

Background Immune checkpoint inhibitor-related esophagitis (IME) is often managed with proton pump inhibitors (PPIs). Severe or refractory cases may require steroids and/or selective immunosuppressive therapies (SIT). However, large-scale studies assessing IME treatment strategies are lacking. This study evaluated their efficacy.

Method This retrospective study at a tertiary cancer center included patients with malignancy who received immune checkpoint inhibitor (ICIs) from 2010-2024 and developed IME, defined as new or worsening upper gastrointestinal (GI) symptoms post-ICI initiation with other causes excluded.

Results Among 148 patients, 75% received PD-1/PD-L1 inhibitors for 4.9 months; 50.7% received concurrent chemotherapy. Isolated IME was present in 27.7% of patients, while the remainder had concurrent immune-mediated GI conditions. Only 24.4% of isolated IME cases were treated with PPIs, and there was no significant difference between the PPI and non-PPI groups in steroid administration, outcomes or recurrence. Corticosteroids were used in 27.7% of cases, significantly shortening the time to symptom resolution (12 vs. 45 days; P=0.015). Nausea (87.8% vs. 57%, P<0.001) and emesis (58.5% vs. 34.6%, P=0.008) were more frequently observed in the steroid group, along with higher rates of hospitalization (73.2% vs. 36.4%, P<0.001), need for intravenous steroids (30% vs. 0%, P<0.001), and ICI discontinuation (74.4% vs. 44.6%, P=0.002). SIT were required for other concomitant GI adverse events in 41.5% of the steroid-treated patients. No significant differences in clinical improvement, ICI resumption or all-cause mortality were noted between the corticosteroid and non-corticosteroid groups.

Conclusion Our findings showed faster clinical improvement with steroids, while PPIs demonstrated no significant effectiveness.

Keywords Immune checkpoint inhibitors, proton pump inhibitors, corticosteroids, budesonide, immune checkpoint inhibitor-related esophagitis

Ann Gastroenterol 2026; 39 (2): 228-237