Role of Biomarkers for the Management of Crohn’s Disease

Publication Date: November 15, 2023
Last Updated: August 8, 2024

Patients with CD in symptomatic remission

Recommendation 1

In patients with CD in symptomatic remission, the AGA suggests a monitoring strategy that combines biomarkers and symptoms, rather than relying on symptoms alone.

( Low , Conditional (weak) )

Comment: Patients who place a higher value on avoiding the burden of biomarker testing, over a potentially higher risk of flare and disease progression caused by missing subclinical inflammation, may reasonably choose interval symptom-based monitoring.

Implementation considerations:
Interval biomarker monitoring may be performed every 6–12 mo in patients in symptomatic remission.
Biomarker-based monitoring may be particularly useful in patients w biomarkers have historically correlated with endoscopic disease activity

612

Recommendation 2

In patients with CD in symptomatic remission with recent confirmation of endoscopic remission (without any change in clinical status, on stable therapy), the AGA suggests using fecal calprotectin <150 μg/g and/or CRP <5 mg/L (or below cutoff for normal range for the laboratory) to rule out active inflammation, and avoid routine endoscopic assessment of disease activity.

(Low to Moderate, Conditional (weak) )
612

Recommendation 3

In patients with CD in symptomatic remission without recent confirmation of endoscopic remission, the AGA suggests endoscopic evaluation to rule out active inflammation, rather than relying solely on fecal calprotectin or CRP. (Low to Moderate, Conditional (weak) )
Implementation considerations:
  • The panel considered recent confirmation of endoscopic or radiologic remission to ideally have been within 3 y.
  • Radiologic assessment of disease activity may be a reasonable alternative to endoscopic assessment for patients with predominantly small bowel involvement.
612

Recommendation 4

In patients with CD in symptomatic remission, with elevated biomarkers of inflammation (fecal calprotectin >150 μg/g, CRP >5 mg/L), the AGA suggests endoscopic assessment of disease activity rather than empiric treatment adjustment.

( Low , Conditional (weak) )

Implementation considerations:

  • In patients with CD in sustained symptomatic remission but elevated biomarkers, repeat measurement of biomarkers (in 3–6 mo) may be a reasonable alternative to endoscopic (or radiologic) assessment, especially if the latter has been performed recently.
  • Lack of normalization of biomarkers (or persistently elevated biomarkers) in patients whose symptoms recently resolved after initial treatment of symptomatically active CD, likely suggests active inflammation, and may warrant treatment adjustment, without need for endoscopic (or radiologic) evaluation.
612

Patients with symptomatically active CD

Recommendation 5

In patients with symptomatically active CD, the AGA suggests a biomarker-based assessment and treatment adjustment strategy, rather than relying on symptoms alone. ( Moderate , Conditional (weak) )
Comment: Patients who place a higher value on avoiding the burden of biomarker testing, over a potentially higher risk of over- or undertreatment if relying only on symptoms, may consider choosing interval symptom-based treatment adjustment when being treated for active symptoms.

Implementation considerations:
  • Interval biomarker assessment and treatment adjustment may be performed every 2–4 mo in patients being treated for active symptoms.
  • After resolution of symptoms (and normalization of biomarkers), endoscopic (and/or radiologic) evaluation should be performed to rule out active inflammation, typically 6–12 mo after treatment initiation or adjustment. The patient may then transition to guidance for patients in symptomatic remission.
612

Recommendation 6

In patients with CD with mild symptoms and elevated biomarkers of inflammation (fecal calprotectin >150 μg/g, CRP >5 mg/L), the AGA suggests endoscopic assessment of disease activity rather than empiric treatment adjustment. ( Very Low , Conditional (weak) )
Implementation considerations:
  • Lack of normalization of biomarkers (or persistently elevated biomarkers) in patients whose symptoms partially improve after initial treatment of active CD, likely suggests active inflammation, and may warrant treatment adjustment, without need for endoscopic (or radiologic) evaluation.
612

Recommendation 7

In patients with CD with mild symptoms and normal biomarkers of inflammation (fecal calprotectin <150 μg/g, CRP <5 mg/L), the AGA suggests endoscopic assessment of disease activity rather than empiric treatment adjustment.

( Very Low , Conditional (weak) )
612

Recommendation 8

In patients with CD with moderate to severe symptoms, the AGA suggests using fecal calprotectin >150 μg/g or CRP >5 mg/L to rule in active inflammation and inform treatment adjustment and avoid routine endoscopic assessment of disease activity. (Low to Moderate, Conditional (weak) )
612

Recommendation 9

In patients with CD with moderate to severe symptoms with normal biomarkers of inflammation (fecal calprotectin <150 μg/g, CRP <5 mg/L), the AGA suggests endoscopic assessment of disease activity rather than empiric treatment adjustment.

( Low , Conditional (weak) )
612

Patients with CD in surgically induced remission

Recommendation 10

In asymptomatic patients with CD after surgically induced remission within the past 12 months, who are at low risk of postoperative recurrence or who have 1 or more risk factors for recurrence but are on postoperative pharmacologic prophylaxis, the AGA suggests using fecal calprotectin <50 μg/g to avoid routine endoscopic assessment of disease activity. ( Moderate , Conditional (weak) )
Comment: Patients, particularly those with multiple prior surgeries, and/or with failure of multiple advanced therapies before surgery, who value more accurate assessment of endoscopic recurrence over the inconvenience and costs of colonoscopy, may reasonably choose endoscopic assessment of disease activity within 12 months after surgery.
612

Recommendation 11

In asymptomatic patients with CD after surgically induced remission within the past 12 months, who are at high baseline risk of recurrence and are not receiving postoperative pharmacologic prophylaxis, the AGA suggests endoscopic evaluation, rather than relying solely on biomarkers, for assessing endoscopic recurrence.

(Low to Moderate, Conditional (weak) )

Implementation considerations:

  • Risk stratification schemes to classify patients’ risk of endoscopic recurrence after surgically induced remission are not well-defined. Risks factors typically associated with low risk of recurrence 6–12 mo after surgically induced remission include older age at surgery (older than 50 y), nonsmoking, long-standing disease (more than 10 y), and first surgery for a short segment of fibrostenotic disease (<10–20 cm). Risk factors typically associated with high risk of recurrence 6–12 mo after surgically-induced remission include two or more prior surgeries, penetrating or perianal disease, smoking, young age at surgery, with long segment of small bowel resection. However, these risk factors may not be additive.
  • In patients at low baseline risk of recurrence, who are also receiving postoperative pharmacologic prophylaxis, fecal calprotectin <150 µg/g may also rule out endoscopic recurrence.
  • Normal CRP in patients with asymptomatic CD in surgically induced remission is not able to rule out endoscopic recurrence accurately.
  • There are limited data on ongoing biomarker monitoring alone in patients with CD in surgically induced remission. Colonoscopic evaluation may be warranted beyond 12 mo after surgery in patients when biomarker-based monitoring is being pursued.
612

Endoscopic Healing Index (EHI) (Monitr) in Patients With CD

Recommendation 12

In patients with CD, the AGA suggests neither in favor of nor against the use of EHI (Monitr) for monitoring inflammation and treatment decisions. ( Evidence Gap , No recommendation )
612

Biomarker- vs Endoscopy-based Monitoring Strategy in Patients With CD

In patients with CD, the AGA makes no recommendation in favor of, or against, a biomarker-based monitoring strategy over an endoscopy-based monitoring strategy to improve long-term outcomes. ( Evidence Gap , No recommendation )
612

Recommendation Grading

Abbreviations

  • AGA: American Gastroenterological Association
  • CD: Crohn's Disease
  • CRP: C-reactive Protein
  • EHI: Endoscopic Healing Index
  • IBD: Inflammatory Bowel Disease

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Role of Biomarkers for the Management of Crohn’s Disease

Authoring Organization

American Gastroenterological Association

Publication Month/Year

November 15, 2023

Last Updated Month/Year

October 3, 2024

Document Type

Guideline

Country of Publication

US

Document Objectives

The objective of this guideline was to inform the role of commonly used serum and fecal biomarkers as surrogates for endoscopic disease activity for both cross-sectional assessment and longitudinal monitoring of patients with an established diagnosis of CD.

Target Patient Population

Patients with Crohn's Disease (CD)

Target Provider Population

Gastroenterology health care professionals; primary care, emergency, and urgent care providers; patients; and policy makers

PICO Questions

  1. In patients with CD in symptomatic remission, is interval biomarker-based monitoring superior to symptom-based monitoring to improve long-term outcomes?

  2. In patients with CD in symptomatic remission, at what fecal calprotectin, serum CRP, and EHI cutoff can we accurately rule out active inflammation, obviating routine endoscopic assessment?

  3. In patients with symptomatically active CD, is an evaluation strategy that combines biomarkers and symptoms superior to symptom-based evaluation for making treatment adjustments?

  4. In patients with symptomatically active CD, at what fecal calprotectin, serum CRP, and EHI cutoffs can we accurately diagnose active inflammation, obviating routine endoscopic assessment?

  5. In patients with CD in surgically induced remission, at what fecal calprotectin, serum CRP, and EHI cutoffs can we accurately rule out postoperative endoscopic recurrence, obviating routine endoscopic assessment?

  6. In patients with established CD, is interval biomarker-based monitoring strategy superior to interval endoscopy-based monitoring strategy to improve long-term outcomes?

Inclusion Criteria

Male, Female, Adolescent, Adult, Child, Older adult

Health Care Settings

Ambulatory, Laboratory services

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Assessment and screening

Diseases/Conditions (MeSH)

D003424 - Crohn Disease

Keywords

biomarkers, Crohn's disease, IBD, CD, crohns disease

Supplemental Methodology Resources

Data Supplement

Methodology

Number of Source Documents
38
Literature Search Start Date
November 20, 2021
Literature Search End Date
August 31, 2022