AGA Role of Biomarkers for the Management of Ulcerative Colitis Guideline Summary

Summary of Recommendations

In patients with UC in symptomatic remission, the AGA suggests a monitoring strategy that combines biomarkers and symptoms, rather than symptoms alone. (C, M)

Comment:

Patients who place high value on avoiding burden of biomarker testing, over a potentially higher risk of flare or overtreatment, may reasonably choose interval symptom-based monitoring.

Implementation considerations:

Interval biomarker monitoring may be performed every 6–12 mo.
Fecal biomarkers (fecal calprotectin or fecal lactoferrin) may be optimal for monitoring and may be particularly useful in patients where biomarkers have historically correlated with endoscopic disease activity.
A biomarker-based monitoring strategy, especially using stool-based tests, however, may be inconvenient and elevated biomarkers in otherwise asymptomatic individuals may lead to high patient anxiety.
It is important to think about the downstream consequences of testing and associated costs. The optimal management strategy in cases of discrepancy between symptoms and biomarkers is unclear and would generally trigger additional endoscopic testing for confirmation or repeat biomarker testing.

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Summary of Key Considerations When Using Biomarkers for Monitoring in Ulcerative Colitis

Considerations of test performance and specificity of biomarkers: CRP, fecal calprotectin, and fecal lactoferrin may be elevated because of nonintestinal sources of infection or inflammation. In patients with UC who present with elevated biomarkers and disease-related symptoms, stool testing for Clostridioides difficile and other enteric pathogens is important to help rule out other sources of gastrointestinal infections.
Role of endoscopic evaluation for other indications: Biomarkers of inflammation have no role in dysplasia detection and surveillance and ruling out cytomegalovirus colitis, and endoscopic evaluation is the main strategy for evaluating these. Endoscopic evaluation may be useful for prognostication in patients hospitalized with acute severe UC.
Association between treatment target and biomarker performance: Test performance of all biomarkers in this guideline reflect their ability to rule out moderate to severe endoscopic inflammation (MES 2 or 3 [or equivalent]). Biomarkers may be suboptimal for detecting more rigorous treatment targets such as endoscopic remission (MES 0) or histologic remission. Biomarkers may also be suboptimal in detecting the presence of mild endoscopic activity (MES 1) in patients with mild symptoms.
Influence of disease extent on biomarker performance: Biomarkers may be less accurate in detecting endoscopic inflammation in patients with ulcerative proctitis or limited segmental disease.
Interpreting biomarker performance for low-risk vs high-risk treatment adjustments: Application of all biomarkers in clinical practice should be guided by downstream implications, including risk of consequent treatment decisions (low-risk treatment adjustment vs high-risk treatment adjustment). Test performance thresholds (acceptable FP and FN rates) may vary for patient–provider teams depending on what treatment adjustment is being considered.
Inter- and intra-assay test variability: Fecal calprotectin assays may not be interchangeable and the same assay should be used for a given patient to compare results over time. Because there can be substantial within-stool and within-day variations of fecal calprotectin measurements from a single patient, confidence in any single measurement may be limited. Hence, if there is uncertainty of results (such as borderline or unexpected results), repeat fecal calprotectin testing or endoscopic evaluation for confirmation may be required.
Inter-individual heterogeneity in biomarkers responsiveness: There are inter-individual differences in biomarker elevation in patients with intestinal inflammation, and in a subset of patients, biomarkers may correlate poorly with endoscopic activity. The overall performance and confidence in the use of biomarkers for treatment decisions in a particular patient may be higher when these biomarkers have been longitudinally observed to correlate with the patient’s endoscopic disease activity (both active disease and remission).

Overview

Title

Role of Biomarkers for the Management of Ulcerative Colitis