Iron deficiency generates secondary thrombocytosis and platelet activation in IBD: the randomized, controlled thromboVIT trial.

BACKGROUND: Secondary thrombocytosis is a common clinical feature. In patients with cancer, it is a risk factor for venous thromboembolic events. In inflammatory bowel disease (IBD), thrombocytosis is so far considered a marker of active disease and may contribute to the increased thromboembolic risk in this population. Observed effects of iron therapy on normalization of platelet counts led us to hypothesize that iron itself may regulate megakaryopoiesis. Here, we want to test the effect of iron replacement on platelet count and activity in IBD-associated thrombocytosis. METHODS: We performed a randomized, single-blinded placebo-controlled trial testing the effect of ferric carboxymaltose (FCM) in patients with IBD with secondary thrombocytosis (platelets > 450 G/L). Changes in platelet counts, hemoglobin, iron parameters, disease activity, megakaryopoietic growth factors, erythropoietin, and platelet activity were assessed. Patients received placebo or up to 1500 mg iron as FCM. Endpoints were evaluated at week 6. RESULTS: A total of 26 patients were included in the study, 15 patients were available for the per protocol analysis. A drop in platelets >25% (primary endpoint) was observed in 4 of 8 (50%, iron group) and 1 of 7 patients (14%, placebo group, P = 0.143). Mean platelet counts dropped on FCM but not on placebo (536 G/L to 411 G/L versus 580 G/L to 559 G/L; P = 0.002). Disease activity and megakaryopoietic growth factors remained unchanged and hemoglobin and iron parameters increased on FCM. The normalization of platelet counts was associated with a decrease in platelet aggregation and P-selectin expression. CONCLUSION: FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis.

Intravenous iron sucrose versus oral iron supplementation for the treatment of iron deficiency anemia in patients with inflammatory bowel disease--a randomized, controlled, open-label, multicenter study.

OBJECTIVES: Anemia is a frequent complication in patients with inflammatory bowel disease (IBD). The optimal route for iron supplementation to replenish iron stores has not been determined so far. We therefore evaluated the efficacy and safety of intravenous iron sucrose as compared with oral iron sulfate for the treatment of iron deficiency anemia (IDA) in patients with IBD. METHODS: A randomized, prospective, open-label, multicenter study was performed in 46 patients with anemia and transferrin saturation

Fecal leukocyte proteins in inflammatory bowel disease and irritable bowel syndrome.

UNLABELLED: The aim of this prospective study was to compare five different leukocyte proteins in feces of patients with chronic inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and healthy persons who underwent prophylactic colonoscopy. METHODS: The leukocyte proteins calprotectin, lactoferrin, lysozyme, myeloperoxidase, and PMN-elastase were determined with immunoassays in fecal samples of three consecutive feces (e.g. three days) in 40 healthy persons, 39 patients with chronic IBD (of these 21 with Crohn's disease and 18 with ulcerative colitis), and 40 patients with IBS. RESULTS: ROC curves calculated for healthy persons and patients with IBD yielded the following areas under the curves (AUCs): PMN-elastase 0.916, calprotectin 0.872, myeloperoxidase 0.750, lysozyme 0.726, and lactoferrin 0.693. The AUCs of PMN-elastase and calprotectin were not significantly different (p = 0.327), whereas PMN-elastase or calprotectin vs. the other proteins were significantly different (p < 0.001). PMN-elastase and calprotectin correlated with the endoscopically classified severity of inflammation. All fecal leukocyte markers in IBS were found in the range of the healthy persons. Data on storage stability of leukocyte proteins in fecal supernatants are given. CONCLUSION: Fecal PMN-elastase and calprotectin support the differentiation of chronic IBD from IBS and correlate with the severity of inflammation.

Budesonide foam vs. hydrocortisone acetate foam in the treatment of active ulcerative proctosigmoiditis.

INTRODUCTION: Rectal administration of corticosteroids is advocated in patients with proctosigmoiditis who have failed therapy with mesalamine enema. Foam offers patients better tolerability than an enema. In this study the efficacy and adverse effects of a new budesonide foam are compared with the presently available hydrocortisone foam. METHODS: Two hundred fifty-one patients with proctosigmoiditis were randomly assigned to receive either budesonide foam or hydrocortisone foam for eight weeks. RESULTS: Remission rates were comparable in the budesonide and hydrocortisone groups, 53 and 52 percent, respectively. The mean disease activity index for the two groups decreased to a similar extent, from 7.2 +/- 1.9 and 7 +/- 2 to 3.6 +/- 3.1 and 3.9 +/- 3.4 in the budesonide and hydrocortisone groups, respectively. In a subgroup of patients who had not responded to rectal administration of mesalamine, 23 of 44 (52 percent) patients who received budesonide responded favorably to the foam, as compared with 14 of 38 (37 percent) patients who received hydrocortisone (P = not significant). Low plasma cortisol occurred in 3 percent of the budesonide group and in none of the hydrocortisone patients. CONCLUSIONS: This trial demonstrates a similar efficacy and safety of the two foams in patients with proctosigmoiditis.

The optimal dose of 5-aminosalicylic acid in active ulcerative colitis: a dose-finding study with newly developed mesalamine.

BACKGROUND AND AIMS: 5-Aminosalicylate is the gold standard for inducing remission in patients with mildly to moderately active ulcerative colitis. The optimal dose is as yet not defined. Despite some recent developments, the ideal formulation for 5-aminosalicylic acid is still awaited. A new pellet preparation was designed combining slow and delayed release properties. Aims of the study were to find the optimal dose and to test efficacy and safety of a new 5-aminosalicylic acid formulation. METHODS: Three hundred twenty-one patients were included in a double-blind multicenter trial. Inclusion criteria were active ulcerative colitis (Clinical Activity Index [CAI] and Endoscopic Index [EI] according to Rachmilewitz, CAI 6-12; EI >/=4). Three different doses of 5-aminosalicylic acid (0.5 g 3 times a day, 1.0 g 3 times a day, and 1.5 g 3 times a day) were studied for 8 weeks. RESULTS: Clinical remission rate (CAI