Treatment Approach for Active Crohn's Disease with Elevated Calprotectin Levels
For patients with active Crohn's disease and elevated calprotectin levels, a biomarker-based assessment and treatment adjustment strategy is recommended over relying on symptoms alone, with specific treatment decisions guided by symptom severity and biomarker levels.
Assessment of Disease Activity
- In patients with Crohn's disease, fecal calprotectin >150 μg/g indicates active inflammation and should guide treatment decisions 1
- For patients with moderate to severe symptoms and elevated biomarkers (fecal calprotectin >150 μg/g or CRP >5 mg/L), treatment adjustment can proceed without routine endoscopic assessment 1
- In patients with mild symptoms but elevated biomarkers, endoscopic assessment is recommended before empiric treatment adjustment 1
- Patients with normal biomarkers but persistent symptoms should undergo endoscopic assessment to determine the true inflammatory status 1, 2
Treatment Recommendations Based on Disease Severity
For Moderate to Severe Active Crohn's Disease:
- First-line therapy should consist of anti-TNF agents (infliximab, adalimumab) for rapid control of inflammation 3, 4
- The recommended dose of infliximab is 5 mg/kg given as an intravenous induction regimen at 0,2, and 6 weeks followed by maintenance dosing every 8 weeks 4
- For patients who don't respond by week 14, consider discontinuing infliximab as continued dosing is unlikely to induce response 4
- Alternative biologic options include integrin inhibitors (vedolizumab) or IL-12/23 inhibitors, especially for patients with contraindications to anti-TNF therapy 3, 5
For Mild Active Crohn's Disease:
- Endoscopic assessment is recommended before treatment adjustment, even with elevated biomarkers 1
- Treatment should be guided by endoscopic findings rather than empiric escalation 1
- If endoscopy confirms active inflammation, proceed with appropriate therapy based on disease location and extent 5
Monitoring Treatment Response
- Interval biomarker assessment should be performed every 2-4 months in patients being treated for active symptoms 1
- Normalization of fecal calprotectin within 12 months of diagnosis is associated with reduced risk of disease progression (including hospitalization and surgery) 6, 7
- After resolution of symptoms and normalization of biomarkers, endoscopic evaluation should be performed to confirm mucosal healing, typically 6-12 months after treatment initiation or adjustment 1
- A fecal calprotectin cutoff of <50 μg/g may be preferred over <150 μg/g to detect endoscopic improvement in patients who have recently achieved symptomatic remission 1
Important Considerations and Pitfalls
- Relying solely on symptoms without biomarker assessment may lead to under-treatment or over-treatment of Crohn's disease 1
- Persistently elevated biomarkers despite symptomatic improvement likely indicate ongoing active inflammation and may warrant treatment adjustment without additional endoscopic evaluation 1
- Some studies suggest that calprotectin and lactoferrin may not be useful for monitoring inflammatory activity in patients receiving biological therapy, highlighting the importance of periodic endoscopic assessment 8
- In patients with predominantly small bowel disease, fecal calprotectin may be less reliable, and additional imaging modalities should be considered 1
- Patients receiving biologic therapy require monitoring for potential adverse effects, including infections and malignancies 4, 5
By following this approach, clinicians can optimize treatment outcomes and reduce the risk of disease progression in patients with active Crohn's disease and elevated calprotectin levels.