Improving relapse prediction in inflammatory bowel disease by neutrophil-derived S100A12.

BACKGROUND: Prediction of inflammatory bowel disease relapse has important implications for therapeutic strategies. Fecal S100A12 has been reported as a novel marker of intestinal inflammation. The objective was to investigate the utility of S100A12 as a marker for the confirmation of stable remission and prediction of relapses. METHODS: We consecutively included 147 adults and 34 children with Crohn's disease (n = 61) or ulcerative colitis (n = 120). Over a 3-year period, we collected 686 stool samples and 861 serum samples during regular follow-up visits. S100A12 and calprotectin levels were measured by an enzyme-linked immunoassay. RESULTS: Fecal S100A12 correlated with S100A12 serum levels, other laboratory markers, as well as disease activity, location, and behavior. Fecal S100A12 levels in the relapse group differed significantly from those of the nonrelapse group. A baseline fecal S100A12 level of >0.5 mg/kg was significantly associated with disease relapse within 18 months. Time course analysis of fecal S100A12 before and after relapse showed a clear increase of S100A12 concentrations up to 6 months before clinical relapse. At 0.43 mg/kg, the sensitivity and specificity of S100A12 for predicting relapse already 8 to 12 weeks earlier were 70% and 83%, respectively. CONCLUSIONS: Regular measurements of fecal S100A12 levels reliably detect inflammatory bowel disease relapse at an early stage, which makes the test a promising noninvasive tool for monitoring and optimizing therapy, and may reduce the need for invasive investigations during disease follow-up.

Clinical trial: probiotic treatment of acute distal ulcerative colitis with rectally administered Escherichia coli Nissle 1917 (EcN).

BACKGROUND: Probiotics are effective in inflammatory bowel diseases. Clinical effectiveness and dose dependency of E. coli Nissle (EcN) enemas were investigated in ulcerative colitis (UC). METHODS: In a double-blind study, 90 patients with moderate distal activity in UC were randomly assigned to treatment with either 40, 20, or 10 ml enemas (N = 24, 23, 23) containing 10E8 EcN/ml or placebo (N = 20). The study medication was taken once daily for at least 2 weeks. After 2, 4 and/or 8 weeks the clinical DAI was assessed together with tolerance to treatment. Patients who reached clinical DAI

Randomized, double blind controlled trial of subcutaneous recombinant human interleukin-11 versus prednisolone in active Crohn's disease.

BACKGROUND: Interleukin-11 has shown benefit in animal inflammatory bowel disease models. Recently, recombinant human interleukin-11 (rhIL-11) has been observed to induce remission in a subset of patients with mild to moderate Crohn's disease (CD). The present study compared the efficacy of rhIL-11 versus prednisolone in remission induction in CD. METHODS: Patients with active CD were randomly assigned to receive either subcutaneous rhIL-11 (1 mg once weekly) and prednisolone placebo tablets, or active prednisolone (60 mg/day) and rhIL-11 placebo, for 12 weeks. Prednisolone/placebo was tapered after week 1, and patients were assessed every second week. RESULTS: Fifty-one patients received medication: 13/27 (rhIL-11) and 17/24 (prednisolone) completed 12 weeks of treatment. Remission rates (intent to treat) for rhIL-11 versus prednisolone were 4% versus 46% at week 4 (p < 0.001) and 19% versus 50% at week 6 (p < 0.05). Response to treatment (deltaCDAI > 100) was seen in 19% (rhIL-11) versus 63% (prednisolone) after 4 weeks (p < 0.002) and 37% versus 63% after 6 weeks (p = 0.1). After 12 weeks of treatment, it was observed that 22% (rhIL-11) versus 21% (prednisolone) had remained in remission. Frequent side effects of rhIL-11 included fever (n = 3), rash (4), arthralgia/arthritis (3), nausea/vomiting (3), and headache (6). CONCLUSION: rhIL-11 is well tolerated but significantly inferior when compared to prednisolone in short-term remission induction in patients with active CD. In this patient cohort, both treatments appeared to be poor in maintaining remission over a period of 3 months.