Isolated immune-mediated enteritis in patients treated with immune checkpoint inhibitor therapy.

Abstract

Background: Immune checkpoint inhibitors (ICIs) commonly cause colitis, but isolated immune-mediated enteritis (IMEN) is poorly characterized. This study describes the clinical features, diagnostic findings, and outcomes of IMEN.

Method: We retrospectively identified adults with cancer who developed IMEN within one year of ICI initiation, confirmed as duodenitis, ileitis, or both.

Results: Among 20,991 ICI-treated patients, 30 (0.143%) developed isolated IMEN. Median age was 69.5 years; 73.3% were male, and 80% white. The most common malignancies were gastrointestinal/hepatobiliary (26.7%) and melanoma (23.3%). Presenting symptoms included nausea (66.7%), diarrhea (53.3%), and vomiting (46.7%); 62.5% of patients with diarrhea had grade ≥2 severity. Disease involved duodenitis plus ileitis in 50%, isolated duodenitis in 30%, and isolated ileitis in 20%. Median fecal calprotectin levels were highest in duodenitis plus ileitis (1335.5 μg/g), followed by ileitis (319 μg/g) and duodenitis (78 μg/g). Endoscopy showed nonulcerative inflammation in 60% and ulceration in 20%. Hospitalization was longest in duodenitis plus ileitis (median 13.5 days). Corticosteroids were required in 66.7% of ileitis cases; additional immunosuppression was needed in 33.3% of ileitis and 66.7% of duodenitis plus ileitis. Isolated duodenitis improved with supportive therapy alone. Remission occurred in 63.3% overall. ICI therapy was resumed in 12.5%, exclusively in patients with isolated duodenitis. Complications included fistula formation (10%); all-cause mortality was 36.7%.

Conclusions: IMEN is a rare but clinically significant ICI-related toxicity. Fecal calprotectin correlates with ileitis severity and not duodenitis, and small-bowel endoscopy facilitates diagnosis and management.