Predicting Endoscopic Crohn's Disease Activity Before and After Induction Therapy in Children: A Comprehensive Assessment of PCDAI, CRP, and Fecal Calprotectin

BACKGROUND: Mucosal healing (MH) is a vital early endpoint in management of Crohn’s disease (CD). MH depends on endoscopic assessment and there is increasing interest in non-invasive proxies, Pediatric Crohn’s Disease activity Index (PDCAI), C-reactive protein (CRP) and fecal calprotectin (FC). These proxies must be validated against endoscopic disease activity (SES-CD) at diagnosis and after induction therapy in well characterized cohorts of children with CD. METHODS: A prospective cohort of 24 newly diagnosed children (<16 yr) with luminal CD quantifiable on complete ileo-colonoscopy had paired PCDAI, CRP, FC and SES-CD at diagnosis and after 8 weeks therapy with exclusive enteral nutrition or steroids. RESULTS: At diagnosis: PCDAI had poor correlation (r = 0.33); CRP (r = 0.54) and FC (r = 0.46) had moderate correlation with SES-CD. After induction therapy: 11/24 had inactive disease (SES-CD 0-2); PCDAI (r = 0.34) and CRP (0.28) had poor correlation with SES-CD, many children with SES-CD ≥3 having normalization of both PCDAI and CRP. FC had good correlation (r = 0.50) but many with SES-CD 0-2 had FC >200 μg/gm stool. FC<500 (positive likelihood ratio, 3.2) and FC drop >50% (positive likelihood ratio, 3.8) had greater predictive value for inactive disease. Composite PCDAI (<10), CRP (<5 mg/dl) & FC <500 μg had excellent Negative LR (0.2) predicting inactive disease. CONCLUSIONS: PCDAI is unreliable for endoscopic disease severity assessment. Only FC correlates with endoscopic activity after therapy but cut off <200 μg is too high for defining endoscopic recovery in children. Composite normalized PCDAI, CRP and FC <500 μg should be considered the non-invasive endpoint for treatment response in pediatric CD.