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Introduction: Immune-related adverse events (irAE) secondary to immune checkpoint inhibitors (ICI) have gastrointestinal (GI) manifestations, including gastritis, enteritis, and/or colitis. The long-term sequelae of ICI-associated GI toxicities (GI-irAE), particularly the development of disorders of gut-brain interaction, are not well known. We characterized the incidence of persistent GI symptoms after GI-irAE., Methods: This is a retrospective study of adults with melanoma treated with ICI and diagnosed with GI-irAE at our institution from 2013 to 2021. All patients had endoscopic and histologic evidence of GI-irAE. The primary outcome was incidence of persistent GI symptoms (diarrhea, abdominal pain, bloating, constipation, fecal incontinence, nausea, vomiting) after resolution of GI-irAE. Hazard ratios evaluated the association between parameters and time to persistent GI symptoms., Results: One hundred four patients with melanoma (90% stage IV disease) and GI-irAE met inclusion criteria. Thirty-four percent received anti-cytotoxic T lymphocyte-associated protein-4 therapy, 33% anti-programmed death-1, and 34% dual therapy. Patients were treated for GI-irAE for an average of 9 ± 6 weeks. Twenty-eight (27%) patients developed persistent GI symptoms 1.6 ± 0.8 years after GI-irAE. The most common symptom was constipation (17%), followed by bloating (8%) and diarrhea (5%). Over 453 person-years, the incident rate was 6.2% per 100 person-years. Use of cytotoxic T lymphocyte-associated protein-4 single or dual therapy was associated with a 3.51× risk of persistent GI symptoms (95% confidence interval 1.20-10.23)., Discussion: In this cohort of melanoma patients who experienced GI-irAE, 26% developed persistent GI symptoms, most frequently constipation. Future studies should characterize the GI sequelae after GI-irAE, which may shed light on disorders of gut-brain interaction pathogenesis and improve the lives of cancer survivors., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background and Aims: Typical immune checkpoint inhibitor-induced colitis (T-ICI) has significant histomorphologic overlap with inflammatory bowel disease (IBD), a distinction further complicated in ICI-treated patients with pre-existing inflammatory bowel disease (P-IBD) and those with potentially "unmasked" inflammatory bowel disease (U-IBD) after ICI therapy. This study describes histopathologic findings seen in U-IBD colonic biopsies and assesses for distinguishing features from T-ICI and P-IBD biopsies., Methods: Initial colon biopsies after symptom onset from 34 patients on ICI therapy were reviewed, and histopathologic features were tabulated. U-IBD patients were identified clinically based on rapid toxicity development post-ICI treatment with multiple recurrences after immune suppression, frequently with regional colitis (versus pancolitis)., Results: The study cohort was classified into T-ICI (n = 20), P-IBD (n = 9), and U-IBD (n = 5) groups. The predominant histological patterns were diffuse active colitis (35%) in the T-ICI, and chronic active colitis in both the P-IBD (67%) and U-IBD (60%) groups (overall P  = .003, P > .05 between the two IBD groups). None of the T-ICI biopsies demonstrated chronicity features (ie, architectural distortion score 2, basal lymphoplasmacytosis, or Paneth cell metaplasia). Only U-IBD biopsies demonstrated basal lymphoplasmacytosis (60% vs 0% in T-ICI/P-IBD, P  = .002). Among available follow-up biopsies, chronicity features were present in all (4/4) U-IBD patients, including those without chronicity seen in the initial biopsy, but none (0/7) of T-ICI patients., Conclusion: These early results show that no definite features of chronicity were seen in colon biopsies from T-ICI patients, suggesting that the presence of those features may be a clue to U-IBD in patients without a known IBD diagnosis. Frequent basal lymphoplasmacytosis seen in U-IBD may support a recent onset of mucosal injury and early architectural remodeling., (© 2024 The Authors.)