A Novel Intravenous Iron Formulation For Treatment Of Anemia In Ibd: The Ferinject Randomized, Controlled Trial

Background: Anemia is a common complication in IBD caused by various degrees of iron deficiency and anemia of chronic disease. Recently, a new parenteral iron preparation, iron carboxymaltose (FeCarb; Ferinject, Vifor Int.) was developed that can be administered iv at single and repeated high doses up to 1000mg within 15min. Aims: This study compared the efficacy (non-inferiority) and safety of FeCarb with oral ferrous sulfate (FeSulf) in reducing iron deficiency anemia in IBD. Methods: This randomized, controlled, multi-center, phase-III trial was performed in IBD patients with a hemoglobin (Hb) ≤11g/dl and a transferrin-saturation (TfS) <20% or ferritin <100µg/l. Patients were randomized at a 2:1 ratio (FeCarb:FeSulf) to receive either an iv infusion of FeCarb at a maximum dose of 1000mg iron (or 15mg/kg) at 1-week (wk) intervals until the patient's calculated total iron requirement was reached, or FeSulf (100mg BID) for 12 wks. The primary endpoint was the change in Hb from baseline to wk 12. Secondary objectives were the assessment of safety and the quality of life (by SF-36). Results: 200 patients were randomized at 36 centers (57 CD, 143 UC), 137 into the FeCarb group, 63 into the FeSulf group. The mean calculated iron deficit was 1449mg (range 937 to 2102mg). The Hb improved from 8.6±1.5g/dl to 12.4±1.6 by FeCarb (p<0.001) and from 8.8±1.5 to 12.5±1.9g/dl by FeSulf (p<0.001). A faster response (defined as proportion of patients with a Hb increase >2.0g/dl) was observed for FeCarb at wk 2 (p=0.0065) and 4 (p=0.0257), and non-significant also at wk 8 (p=0.0763). The mean serum ferritin level of patients in the FeCarb group increased from 9.9µg/L at baseline to 424.6µg/L at wk 2, followed by a constant decrease (178µg/L at wk 4, 97.4µg/L at wk 8 and 82.3µg/L at wk 12). Patients on FeSulf who had a mean baseline ferritin of 21.7µg/L showed a modest increase (35.2µg/L at wk 2, 44.8µg/L at wk 4, 37.4µg/L at wk 8 and 42.1µg/L at wk 12). TfS increased (7% to 24% FeCarb, 10% to 31% FeSulf) and changes were not different between the two groups. Quality of life (93 to 108 FeCarb, 92 to 104 FeSulf) and disease activity improved to a similar extent. Drug related adverse events (AE) occurred in 28.5% in the FeCarb group and 22.2% in the FeSulf group (p=0.4). Study drug discontinuation due to AE occurred in 1.5% in the FeCarb group vs. 7.9% in the FeSulf group (p=0.057). There was no serious AE related to the study drug. Conclusion: Ferinject (FeCarb) is effective and safe in IBD-associated anemia. As it provides a faster Hb response, a higher increase in iron stores, and a better patient tolerance, it is superior to FeSulf.