S1136 Chronic Constipation as an Underrecognized Gastrointestinal Adverse Event Following Immune Checkpoint Inhibitor Therapy

Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but are linked to immune-related adverse events (irAEs), including chronic constipation. This adverse event remains poorly understood. We evaluated the incidence, demographics, cancer associations, and clinical implications of chronic constipation among patients treated with ICIs. Methods: Using TriNetX platform, we established cohorts of adult patients who received US Food and Drug Administration-approved ICI therapies (PD-1, PD-L1, CTLA-4 inhibitors) between 2010-2025 and matched controls without ICI use. We excluded secondary constipation due to known GI comorbidities, recent surgeries/procedures, mechanical GI obstructions, colorectal cancers, and medications such as opioids and anticholinergics. Demographic and oncological profiles were analyzed, and propensity score matching (1:1) was performed to balance demographics and relevant risks. Primary outcomes included short-term (within 1 month) and chronic constipation (up to 15 years after ICI initiation), expressed as odds ratios (ORs). Secondary outcomes were constipation management strategies, cancer prevalence, and subsequent cancer therapies. Results: Among 4,275 ICI-treated patients identified (matched with 1,050,183 controls), chronic constipation (occurring up to 15 years post-ICI) incidence was 4.60%. After propensity score matching (4,229 patients/group), ICI therapy significantly increased chronic constipation risk (OR 2.06, 95% CI 1.36–3.11) and short-term constipation risk (within 1 month; OR 2.16, 95% CI 1.25–3.72). Higher chronic constipation prevalence was observed in younger adults (ages 15–24: 28.3%, ages 25–34: 13.5%), Asians (16.4%), and African Americans (15.4%) compared to White patients (3.2%). Sex differences were not significant (overall mean age 64.6 ± 12.5 years). Among constipated patients, PD-1 inhibitors (especially pembrolizumab) were most common (73.7%), followed by PD-L1 inhibitors (24.8%) and CTLA-4 inhibitor (9.8%). Metastatic cancers (55%) and primary lung carcinomas (40%) were prevalent. Constipation treatments (laxatives) were rarely utilized (5% each). Subsequent chemotherapy use was significantly higher post-ICI (OR 2.67, 95% CI 2.05–3.47; P < 0.0001), though overall cancer prevalence did not differ significantly (OR 1.11, 95% CI 1.00–1.24; P = 0.055). Conclusion: Our analysis confirms chronic constipation as a significantly underrecognized GI adverse event associated with ICI therapy.