Comparison between faecal chitinase 3-like 1, matrix metalloprotease 9, and calprotectin to assess mucosal healing in Crohn's disease: a multicentre prospective study

Mucosal healing (MH) is the best therapeutic target in Crohn’s disease (CD). While faecal calprotectin (FCal) is the most validated surrogate marker of MH, faecal chitinase 3-like 1 (CHI3L1) and matrix metalloprotease 9 (MMP-9) demonstrated recently promising performances. We aimed to compare the performances of FCal, CHI3L1 and MMP-9 to assess the different definitions of endoscopic MH (no ulcer, CDEIS or SES-CD = 0, SES-CD < 2 and CDEIS ≤ 3) in patients with CD. We included, in this prospective multicentre study (8 centres), the patients with CD requiring ileocolonoscopy. Stools collection was performed the day before endoscopy for Fcal measurement (local testing=LT) and were stored at – 80°C to assess the level of Fcal, CHI3L1 and MMP-9 (central testing (CT) using ELISA assay). Estimation of the grey-zone was used to determine the zone of uncertainty of these biomarkers.1 Overall, 71 patients were included (57.7% of female genders, 30.0% of current smokers, 19.7% with perianal lesions and 43.6% with prior intestinal resection). Mean age and mean CD duration were 37.5 ± 12.2 years and 12.5 ± 9.1 years, respectively. CD location was ileal (25.3%), colonic (9.9%) or ileocolonic (64.8%) while CD phenotype was stricturing and fistulising in respectively 28.0% and 19.1% of the patients. The medications at baseline were steroids (12.7%), immunosuppressive therapy (33.8%) and anti-TNF (32.4%). We observed a substantial correlation between endoscopic scores (CDEIS and SES-CD, respectively) and FCal-LT (ϱ=0.6 for both), Fcal-CT (ϱ=0.76 and ϱ=0.74), CHI3L1 (ϱ=0.76 and ϱ=0.74) and MMP-9 (ϱ=0.64 and ϱ=0.63). All the faecal biomarkers were significantly lower in The presence of MH (p < 0.001). The best thresholds of FCal, CHI3L1 and MMP-9 to detect endoscopic MH are detailed in Table 1. Performances of Faecal calprotectin , chitinase 3-like 1, and matrix metalloprotease to assess the available definitions of endoscopic mucosal healing in patients with CD. CHI3L1 and Fcal are two reliable biomarkers to assess MH in CD and demonstrates similar performances. IBD physicians should be aware of the existence of uncertainty zone when using faecal biomarkers in daily practice. Central testing should be preferred to assess Fcal in clinical trials. 1. Cannesson M, Le Manach Y, Hofer CK, et al. Assessing the diagnostic accuracy of pulse pressure variations for the prediction of fluid responsiveness: a “grey zone” approach. Anesthesiology, 2011;15:231–41.