P2921 - Chronic Constipation as an Underrecognized Gastrointestinal Adverse Event Following Immune Checkpoint Inhibitor Therapy

Siming Ma, MD, PhD¹, Thai Koo, MD², Darwin Tan, BS³, Ethan Su, BA³, Jinxiu Pan, MD³, Donovan Veccia, BA², Qi Wang, MD², Xiaoliang Wang, MD, PhD¹, Yinghong Wang, MD, PhD, MS⁴, William Tse, MD, MBA², Gengqing Song, MD, PhD⁵
1Cleveland Clinic, Cleveland, OH; 2Case Western Reserve University / MetroHealth, Cleveland, OH; 3Case Western Reserve University School of Medicine, Cleveland, OH; 4University of Texas MD Anderson Cancer Center, Houston, TX; 5Case Western Reserve University/Metro Health, Cleveland, OH

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 FDA-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 one 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 one 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).

Discussion: Our analysis confirms chronic constipation as a significantly underrecognized GI adverse event associated with ICI therapy.

Disclosures:
Siming Ma indicated no relevant financial relationships.
Thai Koo indicated no relevant financial relationships.
Darwin Tan indicated no relevant financial relationships.
Ethan Su indicated no relevant financial relationships.
Jinxiu Pan indicated no relevant financial relationships.
Donovan Veccia indicated no relevant financial relationships.
Qi Wang indicated no relevant financial relationships.
Xiaoliang Wang indicated no relevant financial relationships.
Yinghong Wang indicated no relevant financial relationships.
William Tse indicated no relevant financial relationships.
Gengqing Song indicated no relevant financial relationships.

Siming Ma, MD, PhD¹, Thai Koo, MD², Darwin Tan, BS³, Ethan Su, BA³, Jinxiu Pan, MD³, Donovan Veccia, BA², Qi Wang, MD², Xiaoliang Wang, MD, PhD¹, Yinghong Wang, MD, PhD, MS⁴, William Tse, MD, MBA², Gengqing Song, MD, PhD⁵. P2921 - Chronic Constipation as an Underrecognized Gastrointestinal Adverse Event Following Immune Checkpoint Inhibitor Therapy, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.