C-Reactive Protein in Immune Checkpoint Inhibitor-Associated Colitis: A Scoping Review of Evidence and Knowledge Gaps

Immune checkpoint inhibitors (ICIs) have transformed cancer care but frequently cause immune-mediated diarrhea and colitis (IMDC), a clinically significant immune-related adverse event. Prompt diagnosis and severity assessment are essential but often rely on invasive endoscopic procedures. C-reactive protein (CRP), a widely available biomarker of systemic inflammation, has been suggested as a potential adjunct in evaluating IMDC. However, its diagnostic utility and clinical relevance remain unclear.

We conducted a scoping review in accordance with the PRISMA-ScR guideline to map existing evidence and identify knowledge gaps regarding the association between CRP and IMDC. A comprehensive literature search was performed across PubMed, Embase, and Web of Science (January 2010-April 2025). Eligible studies included adult patients receiving ICIs who developed gastrointestinal immune-related adverse events, with reported CRP levels. Data were extracted on study design, patient population, CRP measurement, and its relationship with IMDC diagnosis, severity, or outcomes.

Of 538 records screened, five observational studies comprising 583 patients were included. Only one study specifically analyzed CRP levels in histologically confirmed IMDC, demonstrating a positive correlation with clinical and endoscopic severity but no validated diagnostic thresholds. The remaining studies assessed CRP as a general marker for immune-related adverse events without gastrointestinal-specific analyses or diagnostic accuracy metrics. No study provided sufficient data to establish sensitivity, specificity, or predictive values for CRP in IMDC.

This scoping review highlights the limited and heterogeneous evidence linking CRP to IMDC and underscores the absence of validated thresholds or diagnostic performance data. For generalist physicians, CRP may serve as a supportive marker to prompt further evaluation but cannot replace established diagnostic pathways. Future prospective studies should integrate CRP with organ-specific biomarkers and standardized endpoints to clarify its role in triage and severity assessment of IMDC.