Anemia occurs in approximately one-third of patients with inflammatory bowel disease (IBD). The most frequent cause of this common complication is iron deficiency (ID). Causes of ID are not limited to continuous or recurrent blood loss through ulcerations of the bowel mucosa, but also include decreased iron intake or limited absorption of iron. In chronic inflammatory disease or IBD, increased cytokine levels suppress erythropoiesis directly or through inhibition of erythropoietin (EPO) production. The resulting condition is referred to as anemia of chronic disease, which is also present in IBD and occurs with ID. Anemia-specific symptoms are associated with a decreased quality of life, reduced ability to work, and in severe cases, hospitalization or increased length of stay. IBD management includes intravenous and oral iron preparations and the addition of erythropoiesis-stimulating agents (ESAs) can normalize hemoglobin levels in patients who do not respond to intravenous iron alone. It is important to understand the frequency and timing of recurring anemia and ID after successful treatment with iron sucrose and the effect of ESA administration.

A retrospective analysis was conducted by Kulnigg et al on records of patients who had participated in one of three prospective clinical trials that had evaluated the use of iron sucrose (with and without erythropoietin) for the treatment of anemia in IBD. The risk for recurrence of anemia was also evaluated.

Eighty-eight patients were evaluated: patients received a mean iron dose of 2,500 mg and 33 patients had also received ESA treatment. Anemia recurred in a median of 10 months, while ID recurred within 19 months. Among patients with a post-treatment ferritin level <100 μg/L, ID recurred faster (but not anemia), as compared to patients with a post-treatment ferritin level 100-400 μg/L. Maintenance treatment with high target goals for ferritin may be able to delay recurrence of ID. However, recurrence of anemia cannot be delayed by this treatment.

Kulnigg S, Teischinger L, Dejaco C, Waldhör T, Gasche C. Rapid recurrence of IBD-associated anemia and iron deficiency after intravenous iron sucrose and erythropoietin treatment. Am J Gastroenterol. 2009 Jun;104(6):1460-67.

NAAC Expert Commentary
This study by Kulnigg et al attempted to gather data on short and long term outcomes of anemia treatment in patients with IBD. This involved providing intravenous iron sucrose with and without ESAs to anemic patients with Crohn’s disease and ulcerative colitis. The two most common forms of anemia in these patients are iron deficiency anemia (due to excess blood loss from the GI tract, poor absorption, and/or poor intake) and anemia of chronic disease (due to suppression of the bone marrow by pro-inflammatory agents).

The data was obtained from three separate IBD trials in the pre-infliximab era with no information regarding extent, severity, or duration of the inflammatory disease or details of concomitant medical or surgical treatment. All of these factors can greatly impact the duration and severity of anemia and more importantly the response to treatment observed in these patients. Iron/ESA dosage and timing of therapy was at the discretion of the individual physicians with no set schedule. The most useful conclusion gleaned from the data was that aiming for a post treatment ferritin level of 400 mcg/L resulted in prevention of iron deficiency within 1-5 years of treatment.

Physicians who plan to care for patients with IBD need to realize that close follow up of hemoglobin and iron levels, as well as prompt treatment with iron with or without ESA therapy can help to provide a better quality of life for these patients. The addition of infliximab and other “biologic agents” that can attenuate inflammation and bleeding and heal inflamed mucosa may also result in a lower incidence of chronic blood loss and ID in these patients, thereby reducing the need for iron replacement therapy. In the meantime, since active inflammation can falsely raise ambient ferritin levels in IBD patients, aiming for a post treatment ferritin level of 400mcg/L appears to be a reasonable and safe standard.

Last Updated: August 13, 2009