Blood or stool-based biomarkers, including C-reactive protein (CRP) and fecal calprotectin (FCP), respectively, can measure levels of inflammation in IBD, thus pointing to whether Crohn’s status is active or in remission. 

 

Importance of biomarkers

 

A large proportion of IBD patients continue to be actively inflamed even after their symptoms have resolved. According to the Gastroenterology & Endoscopy News report, this observation inspired a treat-to-target approach, where objective endpoints such as biomarkers are used to demonstrate the resolution of inflammation. 

Historically, colonoscopy was the definitive way to determine whether the patient’s inflammation had resolved. 

In the AGA’s announcement of the guideline, Ashwin Ananthakrishnan, MBBS, MPH, from Massachusetts General Hospital and lead author of the publication, described the significance of this development: “Based on this guideline, biomarkers are no longer considered experimental and should be an integral part of IBD care. This is a win for Crohn’s disease patients. Biomarkers are usually easier to obtain, less invasive, more cost-effective than frequent colonoscopies and can be assessed more frequently for tighter disease control and better long-term outcomes in Crohn’s disease.”

First comprehensive guideline on using biomarkers for monitoring Crohn’s disease. AGA. November 17, 2023.

 

 

Clinical guidance

 

The AGA made 11 conditional recommendations in their guidelines concerning the role of biomarkers for the management of Crohn’s disease. The following are the clinical implications of their findings.

Symptomatic remission

For patients in symptomatic remission, CRP and FCP should be checked every 6 to 12 months. CRP and FCP levels should be matched with disease activity noted on recent endoscopic assessment. FCP <150 μg/g and CRP <5 mg/L rules out active inflammation, and obviates the need for endoscopy. On the other hand, higher levels of biomarkers warrant confirmation before adjusting treatment empirically. 

Active symptoms

In patients with mild symptoms, neither normal nor elevated biomarkers alone are sufficient to assess endoscopic activity. CRP and FCP should be checked every 2 to 4 months when a patient experiences an increase in symptoms such as diarrhea or abdominal pain, with treatment guided by symptom history. 

In patients with moderate to severe symptoms, higher levels of FCP or serum CRP indicate active inflammation and therefore obviate the need for routine endoscopic assessment for disease activity. 

It’s important to note that before any major changes in treatment, it’s generally recommended to repeat endoscopic or radiologic assessments.

Surgically induced remission

In low-risk patients who are on pharmacologic prophylaxis following surgery, normal FCP rules out endoscopic recurrence. In all other postoperative contexts, the AGA panel recommends endoscopic assessment to establish postoperative recurrence. CRP and FCP levels should be checked every 6 to 12 months in these patients and can be useful metrics for monitoring inflammation. Once again, CRP levels should be matched with disease activity seen on a recent endoscopic examination. 

“Biomarker-based monitoring is best suited in patients who have previously demonstrated a correlation between endoscopic inflammation and biomarker elevation, and who have undergone recent endoscopic assessment,” according to the AGA.

The role of biomarkers for the management of Crohn’s disease. AGA. November 17, 2023.

 

 

 

Perspectives on biomarkers

 

The guideline panel believed there was insufficient evidence to determine whether a biomarker-based monitoring strategy vs an endoscopy-based monitoring strategy was preferable in patients with Crohn's disease in symptomatic remission. Specifically, using biomarkers alone to monitor strategy could result in insufficient assessment and suboptimal performance related to attaining more robust remission endpoints, including endoscopic or transmural remission. These deeper endpoints could predict more favorable long-term outcomes.