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. 2025 Mar;20(2):339-347.
doi: 10.1007/s11523-025-01135-7. Epub 2025 Mar 4.

Differential Disease Behavior of Immune-Mediated Colitis Among Different Types of Immune Checkpoint Inhibition

Malek Shatila #  1 , Farzin Eshaghi #  2 , Carolina Colli Cruz  1 , Antonio Pizuorno Machado  3 , Antony Mathew  3 , Dan Zhao  4 , Bilal A Siddiqui  5 , Anusha Shirwaikar Thomas  1 , Suresh T Chari  1 , Yinghong Wang  6
Affiliations

Differential Disease Behavior of Immune-Mediated Colitis Among Different Types of Immune Checkpoint Inhibition

Malek Shatila et al. Target Oncol. 2025 Mar.

Abstract

Background: Immune-checkpoint inhibitors (ICIs) enhance the immune response against cancer but can cause immune-related adverse events, with immune-mediated colitis (IMC) being among the most common.

Objective: We investigated variations in gastrointestinal disease behavior and outcomes among patients receiving different ICI regimens.

Methods: This retrospective chart review included patients who received ICIs and developed IMC. Groups were categorized by their last ICI regimen before IMC onset into either programmed cell death protein-1/ligand-1 monotherapy or cytotoxic T-lymphocyte antigen 4 (CTLA-4) monotherapy/combination immunotherapy. Demographic and IMC-related clinical information was collected.

Results: There were 414 patients included in this study: 169 treated with programmed cell death protein-1/ligand-1 monotherapy and 245 treated with CTLA-4 mono/combination therapy. Patients treated with CTLA-4 therapy had an earlier onset of IMC (median 46 days vs 123 days, p < 0.001). They were more likely to present with fever (p = 0.02), abdominal pain (p = 0.049), or hematochezia (p < 0.001). They also had more severe colitis with 47.3% of patients in the CTLA-4 group presenting with grade ≥3 colitis versus 20.2% in the programmed cell death protein-1/ligand-1 group (p < 0.05). On endoscopy, CTLA-4 mono/combination therapy was associated with increased ulcerative findings (24.4 vs 8.4%, p = 0.002). On histology, the programmed cell death protein-1/ligand-1 group was more likely to have microscopic colitis (13.9 vs 5.8%, p < 0.045).

Conclusions: This study provides insight into the effect of ICI type on IMC disease course. Cytotoxic T-lymphocyte antigen 4 inhibition leads to an earlier and more severe IMC onset with distinct endoscopic and histologic features. Further research is needed to refine treatment algorithms and identify the mechanisms underlying the variability in IMC presentation among different ICI regimens.

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Conflict of interest statement

Declarations. Funding: No external funding was used in the preparation of this article. Conflict of interest: Malek Shatila, Farzin Eshaghi, Carolina Colli Cruz, Antonio Pizuorno Machado, Antony Mathew, Dan Zhao, Bilal A. Siddiqui, Anusha Shirwaikar Thomas, Suresh T. Chari, and Yinghong Wang have no conflicts of interest that are directly relevant to the content of this article. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval for this study was granted by the institutional review board at The University of Texas MD Anderson Cancer Center (2018-0472). Consent to participate: Patient consent was waived for this study. Consent for publication: Not applicable. Availability of data and material: The datasets used and analyzed in this study are available from the corresponding author on reasonable request. Code availability: Not applicable. Author contributions: YW was the senior author of the study; she developed the concept, designed the study, interpreted the results, ensured that data accuracy and integrity were preserved at all stages, agreed to be accountable for all aspects of the study, was in charge of the overall direction and planning of the study, and contributed to the writing of the manuscript. FE, MS, APM, and AM collected the data for the study. MS conducted and interpreted the analysis. FE wrote the manuscript. BS, DZ, AST, and SC critically revised the final version of the manuscript. All authors provided input during writing of the manuscript and read and approved the final manuscript.

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