P485. Fecal lactoferrin, calprotectin, PMN-elastase, CRP and white blood count as indicator for clinical course of disease and mucosal healing in patients with ulcerative colitis: A prospective 12-month monitoring study
J. Langhorst1, J.H. Boone2, R. Lauche3, A. Rüffer4, G.J. Dobos3, 1University Duisburg-Essen, Kliniken Essen-Mitte, Integrative Gastroenterology, Essen, Germany, 2TechLab Inc., Virginia, Blacksburg, United States, 3University Duisburg-Essen, Kliniken Essen-Mitte, Internal and Integrative Medicine, Essen, Germany, 4Labor L+S, Enterosan, Bad Bocklet-Großenbrach, Germany
Ulcerative colitis (UC), characterized by periods of active disease and remission, is challenging to manage. Recent studies have identified mucosal healing as optimal patient outcome. This study aimed to investigate whether fecal Lactoferrin (FLA; cut-off: ≥7.25 µg/g), Calprotectin (CAL; >50 µg/g) and PMN-Elastase (PMN-e; >0.062 µg/g), serum CRP (≥0.5 mg/dl) and white blood count (WBC >8.5/nl) were able to distinguish between patients with intestinal inflammation and mucosal healing defined by endoscopy and to distinguish between acute clinical flare, clinical remission or sustained clinical remission. Furthermore, correlation of the investigated markers to endoscopy and if elevated levels at baseline would predict relapse was investigated.
Data were gathered alongside a clinical trial in patients with clinical inactive UC at baseline. Endoscopy (Index; EI-Rachmilewitz - baseline, 12 month) as well as a clinical activity index (CAI-Rachmilewitz), fecal biomarkers, CRP and WBC (baseline, 1, 3, 6, 9, 12 month) were determined repeatedly and in the event of an acute flare.
In 91patients (45female, mean age 52±13.4years) 620 CAI and 180 endoscopies were performed. 42 (46%) patients developed a clinical flare.
Median levels for acute clinical flare/intestinal inflammation (n = 35) vs clinical remission/intestinal inflammation (n = 37) vs mucosal healing (n = 107) for FLA were 43.7 vs 36.7 vs 4.4 µg/g, CAL 25.0 vs 19.8 vs 10.4 µg/g (both p < 0.0001), PMN-e 0.06 vs 0.03 vs 0.02 µg/g, CRP 0.7 vs 0.2 vs 0.2 mg/dl (both p < 0.001) and WBC 7.0 vs 6.5vs 6.4/nl (p = 0.1). Median levels for acute clinical flare (CAI >4; n = 52) vs clinical remission (CAI <5; n = 119) vs sustained clinical remission (CAI <3; n = 358) for FLA were 33.1 vs 20 vs 3.6 µg/g, CAL 25.0 vs 19.2 vs 9.2 µg/g, PMN-e levels 0.06 vs 0.04 vs 0.02 µg/g, CRP 0.5 vs 0.2 vs 0.2 mg/dl (all p < 0. 0001) and WBC 7.3 vs 6.6vs 6.3/nl (p = 0.005). EI was significantly correlated to FLA (r = 0.39), CAL (r = 0.37), PMN-e (r = 0.37), CRP (r = 0.30), (all p < 0.000) and WBC (r = 0.20, p < 0.007). Using pre-defined cut-offs, only in FLA increased levels at baseline were associated with a significant higher risk of flaring (RR 1.69, p = 0.018).
Optimized cut-offs for FLA were 11.9 µg/g, CAL 13.9 µg/g, PME-e 0.035 µg/g and CRP 0.25 mg/dl.
Using these, patients with elevated FLA at baseline had a RR of 1.99 (95% CI 1.47–2.71, p < 0.000) to develop a flare. CAL RR = 1.58 (1.20–2.09, p < 0.000) PMN-e RR = 1.67 (1.21–2.29, p < 0.000), CRP RR = 1.52 (1.15–2.0, p < 0.001) and WBC: n.s.
Fecal biomarkers showed moderate, CRP or WBC small correlation to endoscopy in UC. Only FLA had predictive value and a median level above the pre-defined cut-off for active inflammation. Using optimized cut-offs, FLA, Cal, PMN-e and CRP had predictive value.