Ferumoxytol versus placebo in iron deficiency anemia: efficacy, safety, and quality of life in patients with gastrointestinal disorders.

INTRODUCTION: Iron deficiency anemia (IDA) is common in patients with gastrointestinal (GI) disorders and can adversely affect quality of life. Oral iron is poorly tolerated in many patients with GI disorders. Ferumoxytol is approved for the intravenous treatment of IDA in patients with chronic kidney disease. This study aimed to evaluate the efficacy and safety of ferumoxytol in patients with IDA and concomitant GI disorders. PATIENTS AND METHODS: This analysis included 231 patients with IDA and GI disorders from a Phase III, randomized, double-blind, placebo-controlled trial evaluating ferumoxytol (510 mg ×2) versus placebo in patients who had failed or were intolerant of oral iron therapy. The primary study end point was the proportion of patients achieving a ≥20 g/L increase in hemoglobin (Hgb) from baseline to Week 5. Other end points included mean change in Hgb, proportion of patients achieving Hgb ≥120 g/L, mean change in transferrin saturation, and patient-reported outcomes (PROs). RESULTS: Significantly more patients with IDA receiving ferumoxytol achieved a ≥20 g/L increase in Hgb versus placebo (82.1% vs 1.7%, respectively; P<0.001). Mean increase in Hgb (28.0 g/L vs -1.0 g/L, respectively; P<0.001) significantly favored ferumoxytol treatment. Ferumoxytol-treated patients demonstrated significantly greater improvements than placebo-treated patients relative to their very poor baseline PRO scores posttreatment, including improvements in the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire and various domains of the 36-Item Short-Form Health Survey. Ferumoxytol-treated patients had a low rate of adverse events. CONCLUSION: In this study, ferumoxytol was shown to be an efficacious and generally well-tolerated treatment option for patients with IDA and underlying GI disorders who were unable to use or had a history of unsatisfactory oral iron therapy.

Role of M-CSF-dependent macrophages in colitis is driven by the nature of the inflammatory stimulus.

Although macrophages are considered a critical factor in determining the severity of acute inflammatory responses in the gut, recent evidence has indicated that macrophages may also play a counterinflammatory role. In this study, we examined the role of a macrophage subset in two models of colitis. Macrophage colony-stimulating factor (M-CSF)-deficient osteopetrotic mice (op/op) and M-CSF-expressing heterozygote (+/?) mice were studied following the induction of colitis by either dinitrobenzene sulfonic acid (DNBS) or dextran sulfate sodium (DSS). DNBS induced a severe colitis in M-CSF-deficient op/op mice compared with +/? mice. This was associated with increased mortality and more severe macroscopic and microscopic injury. Colonic tissue myeloperoxidase (MPO) activity as well as concentrations of TNF-alpha, IL-1beta, and IL-6 were higher and IL-10 lower in op/op mice with DNBS colitis. The severity of inflammation and mortality was attenuated in op/op mice that had received human recombinant M-CSF prior to the induction of colitis. In contrast, op/op mice appeared less vulnerable to colitis induced by DSS. Macroscopic damage, microscopic injury, MPO activity, and tissue concentrations of TNF-alpha, IL-1beta, and IL-6 were all lower in op/op mice compared with +/? mice with DSS colitis, and no changes were seen in IL-10. Macrophage inflammatory protein-1alpha concentrations were increased in op/op but not +/? mice following colitis induced by DNBS but not DSS. These results indicate that M-CSF-dependent macrophages may play either a pro- or counterinflammatory role in acute experimental colitis, depending on the stimulus used to induce colitis.

The incidence of irritable bowel syndrome among community subjects with previous acute enteric infection.

The purpose of this study was to determine the incidence of postinfectious irritable bowel syndrome (IBS) among community subjects with positive stool studies. This was a prospective cohort study whereby all individuals with stool-positive acute enteric infection (AEI) were recruited from 3 health regions in Ontario, Canada. Each person completed questionnaires regarding preinfectious bowel habit and their bowel habit 3 months postinfection. Manning and Rome I criteria were used to diagnose irritable bowel syndrome. Two hundred thirty-one patients participated. Forty had preexisting IBS and were excluded. Of the remaining 191 patients, 7 developed irritable bowel syndrome, for an incidence of 3.7% (95% confidence interval: 1.0-6.3%). Fever during AEI was the only identifiable risk factor for developing postinfectious IBS (odds ratio, 11.96; P = .02). The incidence of postinfectious IBS in community subjects is 3.7%. Fever during the AEI may be an important risk factor for this condition.