BACKGROUND Anemia often complicates Crohn disease and affects quality of life. OBJECTIVE To evaluate the efficacy of intravenous iron alone and in combination with erythropoietin for the treatment of anemia associated with Crohn disease. DESIGN Double-blind, randomized, placebo-controlled trial with a subsequent open-label phase. SETTING University-based gastroenterology outpatient clinic. PATIENTS 40 patients with Crohn disease and a hemoglobin concentration of
10.5 g/dL or less. INTERVENTION All patients received intravenous iron saccharate for 16 weeks. During the blinded phase of the trial, they received either erythropoietin or placebo. During the open phase, the erythropoietin dose was increased in non-responders who had received erythropoietin and erythropoietin therapy was initiated in nonresponders who had received placebo. MEASUREMENTS Response was defined as an increase in hemoglobin concentration of 2 g/dL or more. RESULTS 15 of 20 patients in the placebo group (75% [95% CI, 51% to 91%]) and 18 of 19 patients in the erythropoietin group (95% [CI, 74% to 100%]) responded to intravenous iron (P = 0.20). The erythropoietin group had a higher cumulative response rate (P = 0.036) and a more pronounced mean increase in hemoglobin concentration (4.9 g/dL in the erythropoietin group compared with 3.3 g/dL in the placebo group, a difference of 1.6 g/dL [CI, 0.6 g/dL to 2.5 g/dL]; P = 0.004). In the open phase, all 6 previous nonresponders had a response. Hematologic response was associated with improved quality of life (P = 0.03). CONCLUSIONS Most patients who have anemia associated with Crohn disease respond to intravenous iron alone. Erythropoietin has additional effects on hemoglobin concentrations.