Evaluation of capsule endoscopy and fecal calprotectin for risk stratification in asymptomatic Crohn’s disease: a prospective observational study

Clinical remission in Crohn’s disease (CD) does not necessarily indicate the absence of ongoing intestinal inflammation, particularly in the small bowel. Noninvasive and minimally invasive strategies for monitoring subclinical disease activity and predicting relapse remain an unmet clinical need. This study aimed to prospectively evaluate the clinical utility of small bowel capsule endoscopy (SBCE) and fecal calprotectin (FC) for risk stratification in asymptomatic CD. In this single-center prospective observational study, asymptomatic patients with CD (Crohn’s Disease Activity Index < 150 or asymptomatic stoma) underwent SBCE at baseline and week 48. FC and blood biomarkers were measured every 8 weeks until week 48. Patients were followed for clinical relapse for up to 144 weeks. SBCE findings were assessed using the Lewis Score (LS) and the Capsule Endoscopy Crohn’s Disease Activity Index (CECDAI). Clinical relapse was defined as CDAI > 150 or the need for treatment escalation. Time-to-event analyses and receiver operating characteristic analyses were performed to evaluate the association between baseline parameters and subsequent relapse. Among 35 patients, 14 experienced clinical relapse during follow-up. Higher baseline SBCE scores and FC levels were observed in patients who subsequently relapsed. CECDAI ≥ 5.5 was associated with an increased risk of long-term relapse over 144 weeks (hazard ratio [HR] 17.56), while FC ≥ 110 mg/kg showed a non-significant trend. In contrast, FC ≥ 320 mg/kg was associated with short-term relapse within 24 weeks (HR 11.0). Patients with both low CECDAI and low FC levels remained relapse-free during follow-up. Longitudinal analyses demonstrated worsening SBCE scores in patients with long-term relapse, whereas systemic inflammatory markers showed limited discriminatory value. SBCE and FC may provide complementary information for risk stratification in asymptomatic CD. FC appears to reflect short-term risk, whereas SBCE findings may be associated with longer-term outcomes. These findings suggest the potential clinical utility of combining SBCE and FC in monitoring strategies; however, they should be interpreted as hypothesis-generating and require validation in larger multicenter studies.