Evaluating association between faecal calprotectin and endoscopic outcomes in Ulcerative colitis using the HICKORY open-label induction cohort

Background Faecal calprotectin (FC) is used to monitor disease activity in UC, but there is no consensus on optimal cutoff values to predict endoscopic outcomes. This study aimed to evaluate the association between FC and endoscopic disease activity and to propose a meaningful cutoff FC value to predict endoscopic outcomes using data from the open-label induction (OLI) cohort of HICKORY (NCT02100696).

Methods Phase 3 HICKORY study evaluates etrolizumab in anti-TNFα-experienced patients with moderate-to-severe UC. We included patients who received ≥1 dose of etrolizumab 105 mg subcutaneously every 4 weeks during a 14-week induction period. Change in FC was calculated at week 14. Endoscopic activity was measured by Mayo Clinic Score (MCS) Endoscopic Subscore (ES) using a robust central-reading model. Endoscopic improvement was defined as ES=0/1; clinical remission as MCS ≤2 and no individual subscore >1. FC analysis was performed by Covance® (Bühlman FC ELISA assay). Receiver operator characteristic (ROC) curve analyses were used to calculate cutoff FC values.

Results 97 patients (mean age 41±13 years) were included in the analysis. Median (interquartile range) baseline duration of disease was 6.3 (3.2-12.3) years with a median MCS of 9 (8-10). Median baseline FC and ES were 1976 (1043-3452) µg/g and 3 (3-3). At week 14, median FC percentage change was −53% (−83 to 5). A numerical association between changes in FC level and ES was observed (Table). A cutoff FC value of 236 µg/g was observed to predict endoscopic improvement with >70% sensitivity and specificity; ROC area under the curve was 0.89 (Fig. not shown). Similar results were observed for clinical remission.

Conclusion In this exploratory analysis using HICKORY OLI cohort data, changes in FC appear to associate with changes in ES. A cutoff FC value of 236 µg/g predicted endoscopic improvement. In UC, FC may be a useful noninvasive biomarker for ascertaining endoscopic disease activity in clinical trials; however, further clinical studies validating FC cutoffs against centrally read endoscopy are needed.

Tab. 1 Change in Faecal Calprotectin [µg/g, median (IQR)] by Shifted ES from Baseline to Week 14

	ES at week 14
ES at baseline	0-1	2	3
2	-845 (-1957 to -436), n=5	-1401 (-2500 to 458), n=11	-82 (-3164 to 461), n=3
3	-1273 (-2779 to -70), n=11	-1083 (-4766 to 354), n=12	-450 (-1653 to 564), n=55

Publication History

Article published online:
08 September 2020