Ferumoxytol for Treating Iron Deficiency Anemia in CKD

Ferumoxytol for Treating Iron Deficiency Anemia in CKD
NAAC Review Published: October 1, 2008

Iron deficiency is a prevalent cause of anemia in 25-70% of chronic kidney disease (CKD) cases, and is caused by (1) a decreased intake or absorption of iron, (2) iron sequestration, (3) blood loss, and (4) increased iron use for red blood cell production due to erythropoiesis-stimulating agents (ESAs). Managing anemia in CKD requires both iron and ESA therapy. However, oral iron administration has limited, and sometimes adverse effects that may reduce patient compliance. Intravenous iron (IV) is recommended for patients with CKD, but is infrequently used before a patient initiates dialysis. Recently, a Phase III clinical trial by Spinowitz et al described the effects of the intravenous iron product, ferumoxytol, in CKD patients.

In the study, 304 patients were randomly assigned ferumoxytol (228) and oral iron (76). The ferumoxytol group received two 510-mg doses within 5 days, and the oral iron group received 200 mg of elemental iron for 21 days. At day 35, ferumoxytol treatment significantly increased hemoglobin (Hb) levels (0.82 ± 1.24 g/dL; 39% achieving ± 1g/dL increase) compared to the oral iron group (0.16 ± 1.02 g/dL; 18.4% achieving ± 1g/dL increase). Similar significant trends were found for patients both on and not on ESAs. Furthermore, in a nonrandomized readmission trial, patients who initially received ferumoxytol received a second course, while patients who initially received oral iron received a first course of ferumoxytol. The mean increase in Hb levels was 0.55 ± 0.89 g/dL in patients receiving a second course of ferumoxytol, and 0.69 ± 0.80 g/dL in patients receiving a first course.

The fact that many patients are anemic upon dialysis initiation points to suboptimal management in clinical settings. However, the results of this trial indicate that administration of IV iron is an effective and well tolerated treatment for anemic CKD patients. Few adverse events were reported during the course of the trial, and any serious complications were unrelated to ferumoxytol treatment. Also, ferumoxytol can be administered rapidly at high doses, and appears quickly in circulating red blood cells. The authors feel these factors will allow clinicians to dictate appropriate ESA therapies and to better address iron deficiency as a first step in the management of anemia.

Spinowitz BS, Kausz AT, Baptista J, Noble SD, Sothinathan R, Bernardo MV, Brenner L, Pereira BJ. Ferumoxytol for treating iron deficiency anemia in CKD. J Am Soc Nephrol. 2008 Aug;19(

:1599-605. Epub 2008 June 4.

NAAC Expert Commentary:
The provision of supplemental iron to patients with chronic kidney disease (CKD), often but not always combined with an ESA, is a universal component of the therapeutics associated with successful anemia management. Patients receiving hemodialysis are typically and conveniently administered one of two IV iron preparations during a routine dialysis session. However, patients with Stage 1-V CKD, and not yet on dialysis, are most often prescribed oral iron, a strategy that is commonly associated with the presence of iron deficiency and the failure to achieve target hemoglobin levels. Although the use of IV iron for the pre-dialysis patient can overcome many of the barriers which preclude the achievement of an iron replete state, the medication regimen must be safe, effective and practical for the patient and provider if it can realistically become routine clinical care.

This randomized study of greater than 300 adult patients with CKD provides preliminary evidence of such a regimen. The finding that only 5 weeks after study initiation, there was a significantly greater increase in hemoglobin level among patients who received just two doses of ferumoxytol, compared with oral iron, highlights the positive potential of this intravenous agent in the CKD population. Contributing to this optimism is the fact that ferumoxytol can be given by rapid infusion and that the success experienced in the short-term study occurred irrespective of the use of an ESA and with few associated adverse events. It is very likely that if this agent is approved for use in CKD, with a decision expected soon, ferumoxytol will be eagerly incorporated as part of the armamentarium of CKD anemia management. Now all that is awaited is long-term data regarding the safety and efficacy of the therapy.
View original published article at PubMed

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