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DOP064. Faecal calprotectin is superior to faecal lactoferrin and S100A12

E.K. Wright1, P.P. De Cruz1, M.A. Kamm1, A.L. Hamilton1, K.J. Ritchie1, E.O. Krejany1, S.T. Leach2, J.I. Keenan2, A. Gorelik1, D. Liew1, L. Prideaux1, I.C. Lawrance1, J.M. Andrews1, P.A. Bampton1, M.P. Sparrow1, T.H. Florin1, P.R. Gibson1, H.S. Debinski1, F.A. Macrae1, R.W. Leong1, I.J. Kronborg1, G.L. Radford-Smith1, W.S. Selby1, M.J. Johnson1, R.J. Woods1, P.R. Elliott1, S.J. Bell1, S.J. Brown1, W.R. Connell1, A.S. Day2, R.B. Gearry2, P.V. Desmond1, 1St Vincent's Hospital & University of Melbourne, Gastroenterology, Melbourne, Australia, 2Christchurch Hospital, Gastroenterology, Christchurch, New Zealand

Background

70% of patients require further surgery after “curative” resection for Crohn's disease. Early endoscopic recurrence predicts later clinical recurrence. The Post-Operative Crohn's Endoscopic Recurrence (POCER) study has demonstrated that drug treatment according to clinical risk of recurrence plus colonoscopic monitoring with treatment step-up for recurrence results in the lowest endoscopic disease recurrence. However colonoscopy is invasive. We have recently demonstrated that faecal calprotectin (FC) can be used to monitor for disease recurrence with a cut-off of >100 µg/g indicating endoscopic recurrence with a sensitivity of 0.89 and negative predictive value (NPV) of 91% (AUC 0.762). FC correlates significantly with both the presence and severity of endoscopic recurrence. We assessed the relative value of the faecal biomarkers lactoferrin (FL) and S100A12 (FS), not previously investigated, for detecting recurrent disease.

Methods

318 stool samples from 136 patients were tested for FC, FL and FS pre-operatively and 6, 12, & 18 months after resection. Colonoscopy was performed at 6 and/or 18 months. Endoscopic recurrence was assessed blindly and centrally using the Rutgeerts score. CRP and CDAI were assessed longitudinally.

Results

FL and FS concentrations were elevated pre-operatively (median FL 40.9 µg/g, FS 8.4 µg/g). At 6 months, FL and FS both fell (3.0 µg/g and 0.9 µg/g respectively) and were higher in recurrent disease than remission (5.7 v 1.6 µg/g p = 0.007 and 2.0 v 0.8 µg/g p = 0.188). At combined 6 & 18 month observations the overall prevalence of endoscopic recurrence was 42%. FL >3.4 µg/g and FS >10.5 µg/g indicated endoscopic recurrence (≥i2) with a sensitivity of 0.70 and 0.91, specificity of 0.68 and 0.12, positive predictive value (PPV) of 53% and 35% and NPV of 81% and 71%, respectively. FL correlated with both endoscopic recurrence (r = 0.306, p = 0.008) and Rutgeerts score (r = 0.384, p < 0.001) but S100A12 did not (r = 0.176, p = 0.937 and r = 0.168, p = 1.000). CRP and CDAI did not correlate with FL, FS, endoscopic recurrence or endoscopic severity.

Conclusion

Faecal calprotectin is the optimal marker for endoscopic post-operative recurrence, with high sensitivity and negative predictive value, and is superior to CRP and CDAI. It identifies which patients require colonoscopy, allowing 41% of patients to avoid colonoscopy. Faecal lactoferrin offers only modest sensitivity for detecting recurrent disease. Faecal S100A12 is sensitive but has low specificity and NPV.