Fecal S100A12 is associated with future hospitalization and step-up of medical treatment in patients with Crohn’s disease in clinical remission: a pilot study

BACKGROUND/AIMS: Fecal S100A12 (FS) and serum S100A12 (SS) have been reported as novel biomarkers that accurately reflect intestinal inflammation. We evaluated if FS and SS in comparison to fecal calprotectin (FC) are associated with poor future outcomes in clinically quiescent Crohn’s disease (CD) patients. METHODS: We prospectively enrolled 49 CD patients in clinical remission (Crohn’s Disease Activity Index [CDAI] < 150 for the past 6 months). Patients were followed for a median period of 4.4 years (interquartile range [IQR], 4.3–4.5). The following outcomes were evaluated: clinical relapse, CD-related hospitalization, step-up of medical treatment, and CD-related intestinal resection. Cox proportional-hazard regression model was constructed to assess the association of baseline markers with time-to-event outcomes. RESULTS: The median levels of baseline FS, FC, and SS were 0.042 mg/kg (IQR, 0.005–0.179), 486.8 mg/kg (IQR, 203.5–886.8) and 1,398.2 ng/mL (IQR, 791.8–2,759.9), respectively. FS correlated with FC (r = 0.689), erythrocyte sedimentation rate (r = 0.524), C-reactive protein (r = 0.499), and albumin (r = –0.446), but not with CDAI (r = 0.045). Interestingly, increased FS (top quartile) was associated with a 4.9-fold increased rate of future CD-related hospitalization (P= 0.009) and a 2.8-fold increased rate of step-up of medical treatment (P= 0.032), whereas increased FC and SS were not. These findings remained significant after adjusting for age, sex, disease duration, current smoking, C-reactive protein, serum albumin, CDAI, and FC, individually. CONCLUSIONS: In this pilot study, increased FS and not FC or SS, was significantly associated with increased rates of future CD-related hospitalization and step-up of medical treatment among CD patients in clinical remission.