The use of oral iron to correct iron deficiency and treat anaemia is associated with issues of compliance, gastrointestinal side-effects, non-response and variations in bioavailability between patients.1,2 However, as a simple and inexpensive option, it enjoys widespread use in non-dialysis dependent chronic kidney disease patients (ND-CKD).
In an open-access paper, published in Clinical Nephrology, Professor Iain Macdougall, UK, and colleagues have analysed data from the FIND-CKD trial to assess comparative response rates to oral and IV iron over 52 weeks.1
Details of the FIND-CKD study design can be found in a previous COMPACT RENAL article, along with a summary of the main results. The recent paper focuses on a post-hoc analysis of 308 patients in the FIND-CKD intent-to-treat (ITT) oral iron group, 292 of whom had baseline and week 4 Hb values available and had not received alternative anaemia management.
Short-term response rates to oral iron
Only 21.6% of 292 patients had responded to oral iron after four weeks of continuous treatment.
For comparison, the response rates at week 4 among patients receiving IV iron (ferric carboxymaltose, FCM) to a high-ferritin (400-600 µg/L) and low-ferritin target (100-200 µg/L) were 40.9% and 13.9%, respectively.
Long-term response rates to oral iron
More than half of the patients (51.2%) who had not responded to oral iron at week 4 failed to achieve an Hb increase of at least 1g d/L at any point after that.
More patients in the high-ferritin IV iron group experienced a Hb response than those in the oral iron group, although there was little difference between the low-ferritin IV iron and oral iron cohorts. Even with responders included in the analysis, the cumulative response rate for oral iron at 52 weeks was 61.7%, vs. 83% in the high-ferritin FCM group and 61.5% in the low-ferritin FCM group.
It is also worth noting that patients who were known to be intolerant of oral iron were excluded from this study. As a result, the response rates in the trial may reflect a higher level of adherence than normally found in clinical practice.
Potential implications for clinical practice
The investigators compared the baseline characteristics of patients who did, and did not, respond to oral iron by week 4, in order to see if response could be predicted. Responders were found to have lower baseline levels of haemoglobin, serum ferritin and transferrin saturation (TSAT), confirming previous studies and expectations. Macdougall et al. concluded that low levels of haemoglobin and poor iron parameters may be useful clinical indicators for response to oral iron. However further research is needed to develop more “sophisticated predictive models” of response.
When faced with early non-response to oral iron in ND-CKD patients, clinicians may consider a switch to alternative therapy, although the best timing for such a switch is not clear. While the FIND-CKD study was not designed to look at the effect of a switch to IV iron in non-responders to oral iron, the authors mention a pooled analysis of five studies in anaemic patients who had not responded after two weeks of oral iron therapy. In this study, of the patients who switched to IV iron, 38.8% achieved a response compared to only 10.2% who continued with oral therapy.3 The “strikingly higher” rates of response seen in the high-ferritin FCM group in the FIND-CKD trial also highlight the potential benefit of switching to IV iron therapy when faced with non-response to oral iron.1
- Macdougall IC, Bock AH, Carrera F, et al. Erythropoietic response to oral iron in patients with nondialysis-dependent chronic kidney disease in the FIND-CKD trial Clin Nephrol. 2017. doi:10.5414/CN109198.
- Spinowitz BS, Kausz AT, Baptista J, et al. Ferumoxytol for treating iron deficiency anemia in CKD. J Am Soc Nephrol. 2008;19(8):1599-605. doi:10.1681/ASN.2007101156.
- Okam M, Koch T, Tran MH. Clinical Criteria for Transitioning from Oral to IV Iron Replacement Therapy in Patients with Iron Deficiency Anemia. Blood. 2014;124(21):211 LP-211.