Fecal Calprotectin Levels Predict Histological Healing in Ulcerative Colitis

Abstract

Introduction: Endoscopic healing (EH) is the therapeutic target for ulcerative colitis (UC). Recent data has suggested that patients who achieve histological healing (HH) may have even better outcomes. It has been shown that fecal calprotectin (FC) levels may be utilized as a proxy for assessment of endoscopic and histological remission. Our aim was to assess the clinical utility of FC levels to predict depth of remission in UC in a real-world military population. Methods: We performed a retrospective cohort study of UC patients who underwent a full colonoscopy and had FC measured within 6 weeks prior to colonoscopy at a large military treatment facility. Clinical, endoscopic, and histologic disease activity was assessed by Patient Reported Outcomes (PRO2), Mayo Endoscopic Score (0-3), and Nancy score (0-4), respectively. Outcomes of interest included 1) Deep remission (PRO2 remission and Mayo score 0) and 2) deeper remission (deep remission plus Nancy score 0 or 1). Median FC levels were expressed in μg/g. The association of FC with outcomes of interest were compared using Mann-Whitney U tests. The diagnostic ability of FC for endoscopic and mucosal healing was analyzed using receiver operating curve (ROC) analysis. Results: In 104 patients (median age 34 years), 24% had proctitis (E1), 23% left-sided (E2), and 53% pan-colitis (E3). Higher FC levels significantly correlated with Mayo score (p<0.001) and Nancy scores (p<0.001). FC levels werelower in Mayo 0 compared to Mayo 1, 2, and 3 (20 vs. 111, 362, and 915; p<0.001). FC levels were significantly lower in Nancy 0/1 compared to Nancy 2, 3, and 4 (20/68 vs. 429, 420, and 1250, respectively; p<0.001). Patients with endoscopic remission and Nancy score ≤1 (n=22) had significantly lower FC lovels compared to those with endoscopic remission and Nancy ≥2 (48 vs. 499, p<0.0001). FC levels of ≤45 predicted deep and deeper remission (AUC = 0.87, sensitivity 85%, specificity 78%). Conclusion: FC levels significantly correlated with endoscopic mucosal and histologic activity, and reflect microscopic disease activity even in the face of macroscopic healing. We validated an FC level of ≤ 45 μg/g robustly predicted depth of remission. We suggest that FC can be used instead of colonoscopy in a treat-to-target paradigm in patients with UC.