The Association of Faecal Calprotectin Measurements With Endo-Histological Remission in Ulcerative Colitis: A Pooled...

Endoscopic and histologic evaluation is part of routine clinical practice to confirm the presence of active disease in ulcerative colitis. Faecal calprotectin (FCAL) levels show a positive correlation with endoscopic indices, relapse, and response to treatment. Existing studies have not clearly determined cut-off values for endoscopic and histologic remissions.

Our study aims to determine an optimal FCAL threshold for discriminating between endoscopic and histologic active disease and remission in UC, based on the Mayo Endoscopic Score (MES) and the Geboes Histologic Score.

We performed a pooled analysis of retrospective and prospective studies of patients with UC from four academic centres. Key inclusion criteria were adult UC patients undergoing colonoscopy, with FCAL measurements. Receiver operating characteristic curves were computed on 80% of the data using 5-fold cross-validation to determine the optimal FCAL threshold for predicting active UC based on specificity (spec) and sensitivity. Optimal thresholds were then tested on the remaining 20% of the data. Active endoscopic disease was assessed using MES 0-1 versus 2-3 and MES 0 versus 1-3, and active histologic disease or remission was evaluated using GHS < 3.1 versus GHS ≥ 3.1 and GHS ≤ 2.0 versus GHS > 2.0.

A total of 741 patients with UC were included in our analysis. For MES 0 versus 1-2-3, the AUC was 0.716 (95% CI: 0.701-0.731, p < 0.0001) with an optimal threshold of 154.3 μg/g (specificity: 0.69 [95% CI: 0.65-0.72], sensitivity: 0.64 [95% CI: 0.60-0.69]). For MES 0-1 versus 2-3, the AUC increased to 0.802 (95% CI: 0.797-0.807, p < 0.0001), with an optimal FCAL threshold of 234.6 μg/g (specificity: 0.74 [95% CI: 0.74-0.75], sensitivity: 0.69 [95% CI: 0.62-0.75]). For GHS ≤ 2.0 versus GHS > 2.0, the AUC was 0.656 (95% CI: 0.647-0.664, p < 0.0001), with an optimal threshold of 117.6 μg/g (specificity: 0.61 [95% CI: 0.56-0.66], sensitivity: 0.59 [95% CI: 0.56-0.63]). For GHS < 3.1 vs. GHS ≥ 3.1, the AUC was 0.752 (95% CI: 0.743-0.762, p < 0.0001), with an optimal threshold of 166.2 μg/g (specificity: 0.69 [95% CI: 0.66-0.73], sensitivity: 0.69 [95% CI: 0.63-0.76]). Given the high AUC for MES 0-1 vs. MES 2-3, we tested different FCAL thresholds from the literature and propose a threshold of 170 μg/g to maximize sensitivity (sensitivity: 0.801 [95% CI: 0.729-0.873], specificity: 0.648 [95% CI: 0.641-0.656], LR+ 2.311 [95% CI: 2.001-2.670], LR- 0.289 [95% CI: 0.196-0.427], accuracy 67.62% [95% CI: 65.95-69.30]) and limit the proportion of false negatives.

Our study demonstrates that FCAL can predict both active endoscopic and histological disease with acceptable sensitivities and specificities. The proposed cut-off values will help guide clinical practice to achieve the recommended treatment outcomes. Further studies are warranted to validate our results.