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P144. Serum neutrophil gelatinase B-associated lipocalin–matrix metalloproteinase-9 (NGAL-MMP-9) complex as a surrogate marker for mucosal healing in ulcerative colitis

M. de Bruyn1, I. Arijs2, W.-J. Wollants2, K. Machiels2, K. Van Steen3, M. Ferrante2, P. Rutgeerts2, S. Vermeire2, G. Opdenakker1, 1KULeuven, Rega Institute, Immunobiology, Leuven, Belgium, 2KU Leuven, Clinical and Experimental Medicine, TARGID, Leuven, Belgium, 3University of Liège, Montefiore Institute, Systems and Modeling Unit, Liège, Belgium

Background

The current standard for assessing intestinal inflammation and mucosal healing after therapy in inflammatory bowel diseases (IBD) is endoscopy. However, frequent assessments are costly and uncomfortable for the patient. Although C-reactive protein (CRP) is widely used as a marker of inflammation, half of the patients with active ulcerative colitis (UC) do not have elevated CRP levels. Therefore, we investigated NGAL-MMP-9 as a surrogate serum marker for mucosal healing after treatment with infliximab (IFX) in UC patients.

Methods

NGAL-MMP-9 serum levels were determined with zymography analysis and sandwich ELISA before and 4–6 weeks after first IFX infusion from 66 active, IFX-naïve UC patients (median age at first IFX: 40.9 years, male/female (%): 60.6/39.3) as well as from 40 healthy controls (HC, median age: 30.4 years; male/female (%): 62.5/37.5). The response to IFX was defined as complete mucosal healing (endoscopic Mayo score 0 or 1) at control endoscopy. Data were analyzed with SPSS statistics 20 and p-values of <0.05 were considered significant.

Results

From the 66 patients with active UC, 28 patients were classified as responder and 38 as non-responder. At baseline, NGAL-MMP-9 serum levels were found to be significantly higher in UC patients versus HC (p < 0.0001). After IFX therapy, NGAL-MMP-9 serum levels were significantly decreased in UC responders (median range from 116.3 to 32.0 ng/ml; p < 0.0001). For UC non-responders, NGAL-MMP-9 levels were also significantly decreased after treatment with IFX (median range from 94.7 to 54.1 ng/ml; p = 0.0469), however, this decrease was significantly lower in comparison with responders (p = 0.0074). A strong correlation was found between results obtained from zymography analysis and sandwich ELISA (r = 0.835, p < 0.0001). NGAL-MMP-9 serum levels correlated with the amount of neutrophils (r = 0.430, p < 0.0001) and endoscopic Mayo scores (r = 0.317, p < 0.0001). Moreover, we found that NGAL-MMP-9 serum levels correlate better with endoscopic Mayo scores than CRP levels (r = 0.299, p < 0.0001). Receiver operating characteristic (ROC) analysis defined a NGAL-MMP-9 serum level cut-off value of 97.7 ng/ml corresponding to mucosal healing (AUC=0.75, 43.27% sensitivity, 92.86% specificity).

Conclusion

In the search for surrogate markers assessing mucosal healing in UC, NGAL-MMP-9 performs better than CRP. 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.