P-106 Evaluation of the Association Between Fecal Lactoferrin Status and Clinical, Serologic and Endoscopic Outcomes: Post-Hoc Analysis of the Sonic Trial

In the SONIC trial, patients with Crohn's disease (CD) treated with infliximab (IFX) alone or in combination with azathioprine achieved higher rates of mucosal healing (MH) at wk 26 than patients treated with azathioprine alone. In a post-hoc analysis of SONIC, clinical symptoms as measured by the Crohn's Disease Activity Index (CDAI) were inaccurate to detect MH1. Recently, fecal biomarkers, such as lactoferrin (LF) and calprotectin, are being increasingly used in monitoring the activity of CD. This post-hoc analysis of SONIC reports on the association of fecal LF to clinical, serologic and endoscopic outcomes, and serum IFX levels in CD patients enrolled in centers in the United States who had evaluable measurements of LF, CDAI, serum CRP, and ileocolonoscopy both at baseline and wk 26, and evaluable serum IFX levels at wk 30. LF was measured by an ELISA assay and expressed as positive (pooled +2, +3, and +4 scores) or negative (pooled negative and +1 scores). MH was defined as absence of any ulceration. Corticosteroid-Free Clinical Remission (CFCR) was defined as clinical remission (CDAI <150) and no treatment with corticosteroids for >6 weeks. Post-hoc analyses were performed using the Fisher's exact test and the Kruskal-Wallis test where appropriate. Among the 109 patients (median age 43 yrs, 54% male), 33.9% were LF+ and 19.3% were LF- at both baseline and wk26; 36.7% patients changed from LF+ to LF- from baseline at wk 26 whereas 10.1% changed from LF- to LF+ (P < 0.0001). At baseline, LF was significantly associated with CDAI (P = 0.024) and serum CRP (P = 0.01) (Table 1); in addition, LF showed a trend of association with normal levels of CRP (65.6% versus 36.4% with CRP <0.8 mg/dL for LF—and LF+, respectively, P = 0.064, Table 1). At wk 26, there was no association between LF and CDAI (P = 0.09), serum CRP (P = 0.18), CRP normalization (0.512), CFCR (P = 0.245) (Table 1). The association between LF and MH (ulceration) was evaluated in 168 patients at baseline and 110 patients at wk 26 who had both LF and MH data at these measurement points. At baseline, ulcerations were not found in 43.1% (25/58) LF- patients versus 21.8% (24/110) LF+ patients (sensitivity 0.72, specificity 0.51, P = 0.004). In contrast, at wk26, 44.3% (27/61) of LF- patients versus 30.6% (15/49) LF+ patients had MH (sensitivity 0.50, specificity 0.64, P = 0.143). In this post-hoc analysis of the SONIC trial, LF was collected as a categorical variable. The association between LF and other clinical parameters may be better estimated if LF was on a continuous scale. Semi-quantitative LF does not seem to be a good biomarker in CD. Although it was useful to identify active clinical and biological disease at baseline, it could not confirm clinical, biological, or endoscopic remission at wk26. 1. L Peyrin-Biroulet, WJ Sandborn, et al. Clinical disease activity, C-reactive protein normalization and mucosal healing in Crohn's disease in the SONIC trial. Gut. 2013;63:88–95.