A randomized, open-label trial of iron isomaltoside 1000 (Monofer®) compared with iron sucrose (Venofer®) as maintenance therapy in haemodialysis patients.

There is a lack of universal consensus among nephrologists and haematologists on several core issues pertaining to iron and anaemia management in chronic kidney disease (CKD). Whereas the dose and frequency of erythropoiesis-stimulating agent (ESA) treatment in CKD patients undergoing long-term haemodialysis (HD) are not frequently questioned, and although maintenance dosing of ESA therapy is considered standard of care by practicing nephrologists, there appears to be less acceptance of iron therapy administered in a similar fashion.

To date, no randomised controlled studies have been conducted to substantiate the risk of increased infection or death as a result of intravenous (IV) iron therapy in CKD-HD patients. Nevertheless, assuming that there may still be reasons to “fear” IV iron therapy, one critical question that has persisted without any clear answer relates to the safest strategy of iron administration in CKD patients [1].

The aim of this head-to-head comparative trial by Bhandari et al. was to evaluate the efficacy and short-term safety of iron isomaltoside 1000 (Monofer) administered as a single bolus injection (500 mg at Week 0) or split bolus injections (100 mg at Week 0, 200 mg at Week 2 and 200 mg at Week 4) compared with iron sucrose (Venofer) administered as split bolus injections in HD patients. Both IV iron formulations showed similar efficacy, with >82% of the subjects having Hb levels in the target range (9.5 to 12.5 g/dL) at 6 weeks (non-inferiority, P = 0.01). There was a significant increase in ferritin from baseline to Weeks 1, 2 and 4 with Monofer compared to Venofer.

In addition, this study showed 1) identical short-term safety profile between Monofer and Venofer (the established market leader in HD); 2) potential benefits of Monofer vs. Venofer relating to less labile iron (and therefore less oxidative stress and potentially better long-term safety) and the less stable nature of Venofer (which is reflected in the study data by the marked variance on TSAT 1 week after administration); 3) the high-dose advantage of Monofer, which also applies to ferric carboxymaltose (Ferinject) [2, 3] and offers the possibility to give a higher dose and thereby reduce number of administrations which could be a safety benefit as, according to EMA [4], each administration of IV iron is associated with a (small) risk of a hypersensitivity reaction.

– Manuel Muñoz

References

1. Rhee CM, Kalantar-Zadeh K. Is iron maintenance therapy better than load and hold? J Am Soc Nephrol 2013;24:1028-31.
2. Charytan C, Bernardo MV, Koch TA, Butcher A, Morris D, Bregman DB. Intravenous ferric carboxymaltose versus standard medical care in the treatment of iron deficiency anemia in patients with chronic kidney disease: a randomized, active-controlled, multi-center study. Nephrol Dial Transplant 2013;28:953-64.
3. Macdougall IC, Bock AH, Carrera F, et al. FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia. Nephrol Dial Transplant 2014;29:2075-84.
4. European Medicines Agency. New recommendations to manage risk of allergic reactions with intravenous iron-containing medicines. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/06/news_detail_001833.jsp