Role of Biomarkers for the Management of Ulcerative Colitis
Summary of Recommendations
- 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.
- 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.
- In patients with UC in symptomatic remission but elevated biomarkers of inflammation, repeat measurement of biomarkers (in 3–6 mo) may be a reasonable alternative to endoscopic assessment. However, if biomarkers are elevated on repeat evaluation, then endoscopic assessment may be warranted.
- Patients, particularly those with severe symptoms, who place high value in avoiding burden of biomarker testing, over a potentially higher risk of inappropriate overtreatment, may reasonably choose symptom-informed treatment decisions.
- In patients with UC who underwent recent adjustment of treatment in response to moderate to severe symptomatic flare, and now have mild residual symptoms, elevated stool or serum markers of inflammation may be used to inform treatment adjustments (such as dose adjustments of therapy).
- In patients with UC with mild symptoms (eg, slight increase in stool frequency and/or infrequent rectal bleeding), it may be reasonable to proceed directly with endoscopic assessment rather than testing biomarkers of inflammation.
- In patients with UC with mild symptoms and normal biomarkers of inflammation who prefer to avoid endoscopic assessment or empiric treatment escalation, repeat measurement of biomarkers (in 3–6 mo) may be a reasonable alternative.
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).
Consequences of Diagnostic Test Results on Patient-Important Outcomes
- Patients correctly diagnosed as having moderate to severe endoscopic activity would be eligible to undergo treatment adjustment, which may improve symptoms and decrease risk of disease-related complications and morbidity, without being subject to risk, invasiveness, and cost of endoscopic assessment.
- Patients incorrectly labeled as having moderate to severe endoscopic activity, when actually they are in endoscopic remission or have only mild endoscopic activity, may undergo unnecessary testing (endoscopy) and/or treatment adjustment, and have avoidable anxiety, potential testing- or treatment-related complications, and increased resource utilization.
- Patients correctly diagnosed as being in endoscopic remission or having only mild endoscopic activity would be reassured and obviate the need for invasive testing with endoscopy, although they may need to undergo serial assessment of biomarker at periodic intervals.
- Patients incorrectly labeled as being in endoscopic remission or having only mild endoscopic activity, when actually they have moderate to severe endoscopic activity would be falsely reassured, may have avoidable anxiety about unexplained symptoms, and may not receive appropriate treatment adjustment, potentially leading to increased disease related complications, morbidity, and mortality.
Role of Biomarkers for the Management of Ulcerative Colitis
American Gastroenterological Association
February 21, 2023
Supplemental Implementation Tools
Country of Publication
Biomarkers are used frequently for noninvasive monitoring and treatment decision making in the management of patients with ulcerative colitis (UC). This American Gastroenterological Association (AGA) guideline is intended to support practitioners in decisions about the use of biomarkers for the management of UC.
Target Patient Population
Target Provider Population
Gastroenterologists, primary care providers and other allied healthcare professionals
Male, Female, Adolescent, Adult, Child, Older adult
Health Care Settings
Ambulatory, Laboratory services, Outpatient
Nurse, nurse practitioner, physician, physician assistant
Diagnosis, Assessment and screening
D003093 - Colitis, Ulcerative, D015415 - Biomarkers
biomarkers, inflammatory bowel disease, ulcerative colitis, IBD, fecal calprotectin, serum CRP, fecal lactoferrin
Singh S, Ananthakrishnan AN, Nguyen NH, Cohen BL, Velayos FS, Weiss JM, Sultan S, Siddique SM, Adler J, Chachu KA; AGA Clinical Guidelines Committee. Electronic address: email@example.com. AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Ulcerative Colitis. Gastroenterology. 2023 Mar;164(3):344-372. doi: 10.1053/j.gastro.2022.12.007. PMID: 36822736.