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P269 Serum neutrophil gelatinase B-associated lipocalin and matrix metalloproteinase-9 (NGAL-MMP-9) complex as a surrogate marker for mucosal healing in patients with Crohn's disease.

M. de Bruyn*1, 2, I. Arijs2, 3, G. De Hertogh4, M. Ferrante2, G. Van Assche2, P. Rutgeerts2, S. Vermeire2, G. Opdenakker1

1Rega Institute for Medical Research - KU Leuven, Department of Microbiology and Immunology, Leuven, Belgium, 2University Hospitals Leuven - KU Leuven, Translational Research Center for Gastrointestinal Disorders (TARGID), Leuven, Belgium, 3KU Leuven, Department of Cellular and Molecular Medicine, Gene Expression Unit, Leuven, Belgium, 4KU Leuven - Translational Cell and Tissue Research, Department of Imaging and Pathology, Leuven, Belgium

Background

The current standard to assess mucosal healing in patients with Crohn's disease (CD) is endoscopy. However, frequent assessments are costly and contain a risk for complications. Earlier, we described that serum NGAL-MMP-9 is a surrogate marker for mucosal healing in patients with ulcerative colitis (UC). In this study, we wanted to investigate whether serum NGAL-MMP-9 can also be used in CD patients as a surrogate marker for mucosal healing.

Methods

Serum NGAL-MMP-9 levels were determined with sandwich ELISA before and up to 5 years after first infliximab infusion in 108 patients with active CD (median age at first infliximab 35.8 years, 57% female) and in 43 healthy controls (HC, median age 27.3 years, 60% female). Endoscopic healing was defined as complete absence of ulcerations, whereas partial healing was defined as significant endoscopic improvement, but still with ulcerations present. Histological healing was defined as an absence of epithelial damage (d'Haens score). Data were analyzed with SPSS 22 using non-parametric tests and p-values <0.05.

Results

Of the 108 patients with active CD, 72 patients showed endoscopic healing (n=38 complete, n=34 partial) whereas 36 patients showed no endoscopic healing. At baseline, median [interquartile range, IQR] NGAL-MMP-9 levels were significantly higher in active CD patients versus HC (77.6 [36.9-141.0] vs 25.5 [17.8-42.8] ng/ml; p<0.001). After treatment, NGAL-MMP-9 levels significantly decreased in healed CD patients (69.0 [32.6-135.5] to 35.2 [9.4-56.1] ng/ml; p<0.001). In non-healed CD patients, NGAL-MMP-9 serum levels also decreased after treatment (100.9 [43.4-152.6] to 43.8 [27.0-96.8] ng/ml; p=0.002), however, the decrease was significantly more profound in complete healers (p=0.020). NGAL-MMP-9 levels correlated with amount of neutrophils (Spearman's rho [r]=0.470, p<0.001), CRP levels (r=0.448, p<0.001), endoscopic activity (Kendall's tau [T]=0.296, p<0.001) and histological activity (T=0.312, p<0.001). Receiver operating characteristic (ROC) analysis defined a serum NGAL-MMP-9 cut-off level of 26.4 ng/ml corresponding to complete endoscopic healing (AUC=0.79, 58% sensitivity, 85% specificity, 56% PPV and 85% NPV) and histological healing (AUC=0.73, 63% sensitivity, 84% specificity, 50% PPV and 90% NPV). Of importance, CRP was not elevated (<5 mg/L) in 33% of active patients at start of treatment, whereas 81% of these patients did have elevated NGAL-MMP-9 levels.

Conclusion

In the search for surrogate markers to assess mucosal healing in IBD, measurement of serum NGAL-MMP-9 complex can supplement CRP in both UC and CD. We therefore propagate that the use of NGAL-MMP-9 serum levels can be implemented in clinical practice, thereby potentially overriding the need for endoscopy.