Is calprotectin indicated in the follow-up of ulcerative colitis?

Fecal Calprotectin Monitoring in Ulcerative Colitis Follow-Up

Yes, fecal calprotectin is indicated in the follow-up of ulcerative colitis, even if the last measurement was only 3 months ago, as it represents a useful non-invasive marker to monitor disease activity and predict relapse. 1

Role of Fecal Calprotectin in UC Monitoring

Benefits of Biomarker-Based Monitoring

• Fecal calprotectin is a sensitive marker of intestinal inflammation that correlates well with endoscopic indices and helps in the assessment of disease severity and response to treatment 1
• The American Gastroenterological Association (AGA) suggests a monitoring strategy that combines biomarkers and symptoms rather than symptoms alone for patients with UC in symptomatic remission (conditional recommendation, moderate certainty of evidence) 1
• Interval biomarker monitoring may be performed every 6–12 months, with fecal calprotectin being the optimal choice for monitoring 1

Predictive Value

• Patients with elevated fecal calprotectin (>150 μg/g) are 4.4 times more likely to experience disease relapse compared to those with normal levels 1
• With an observed median annual risk of relapse of 15% in patients with normal fecal calprotectin, the estimated annual risk of relapse in patients with elevated levels rises to 64% 1
• A fecal calprotectin cut-off value of 193 μg/g has been shown to have an accuracy of 89% in predicting clinical relapse 2

Implementation in Clinical Practice

Monitoring Frequency

• For patients in symptomatic remission, interval monitoring with fecal calprotectin every 6-12 months is recommended 1
• For patients who have had recent treatment adjustments, more frequent monitoring (every 3-6 months) may be appropriate to assess response 1
• After initiating or adjusting therapy, repeat fecal calprotectin measurement is recommended in 2-4 months to monitor response 3

Interpretation of Results

• Fecal calprotectin <150 μg/g in patients with UC in symptomatic remission reliably rules out active inflammation, avoiding the need for endoscopic assessment 1
• Fecal calprotectin >150 μg/g indicates active intestinal inflammation that may require treatment adjustment or further evaluation 1
• A cut-off value of 110 μg/g has been shown to be highly predictive (95%) of endoscopic activity 2

Clinical Decision-Making Algorithm

For Patients in Symptomatic Remission:

1. If fecal calprotectin <150 μg/g:

   • Continue current treatment
   • Schedule next calprotectin test in 6-12 months 1

2. If fecal calprotectin >150 μg/g:

   • Consider endoscopic assessment to confirm active inflammation 1
   • If endoscopic assessment confirms inflammation, adjust treatment accordingly 1
   • If unable to perform endoscopy, consider repeating calprotectin in 1-2 months before making treatment decisions 1

For Patients with Mild Symptoms:

1. Regardless of calprotectin level:
   • Endoscopic assessment is suggested before making treatment decisions 1
   • In cases where endoscopy is not feasible, fecal calprotectin can help guide management 1

For Patients with Moderate to Severe Symptoms:

1. If fecal calprotectin >150 μg/g:
   • Consider empiric treatment adjustment without requiring endoscopic assessment 1
   • Repeat calprotectin measurement 2-4 months after treatment adjustment 3

Important Considerations and Pitfalls

Potential False Positives

• Inflammatory polyps can cause elevated fecal calprotectin levels (>150 μg/g) even in the absence of active ulcerative colitis 4
• Before escalating therapy based on elevated calprotectin alone, consider endoscopic evaluation to confirm active inflammation, especially in asymptomatic patients 4

Histologic Inflammation

• Patients in clinical and endoscopic remission may still have histologic inflammation, which is associated with increased risk of relapse 5
• Fecal calprotectin can identify patients with histologic inflammation even when they appear to be in clinical and endoscopic remission 5

Alternative Biomarkers

• When fecal calprotectin testing is challenging due to patient compliance or logistical requirements, plasma calprotectin may be considered as an alternative biomarker 6
• Fecal lactoferrin is another stool biomarker that can be used, with a sensitivity of 83% and specificity of 75% for detecting endoscopic inflammation 1

In conclusion, regular monitoring with fecal calprotectin is a valuable tool in the management of ulcerative colitis, providing important information about disease activity and helping to predict clinical outcomes, even if the last measurement was only 3 months ago.