Simon Roger et al. have recently published a new analysis of safety data from the FIND-CKD trial. This extends the existing analysis to consider adverse event rates per 100 patient-years and the occurrence of adverse events that required hospitalisation, reporting no difference in adverse events between treatment groups.
FIND-CKD was a 1-year, randomised controlled trial of IV ferric carboxymaltose (FCM) for the treatment of iron deficiency anaemia in NDD-CKD patients not receiving ESA therapy. Patients received FCM to achieve either a high ferritin target (400-600ng/mL) or a lower ferritin target (100-200ng/mL), or were prescribed oral iron (200mg/day).
A post hoc analysis of adverse event (AE) rates per 100 patient-years (PY) of follow-up was performed to assess the safety of FCM compared with oral iron. Results were reported as both incidence (i.e. occurrence of one or more event) and as the cumulative number of events (i.e. every event, including recurrence in the same patient). The cumulative number of events was analysed in order to make the results of the FIND-CKD study comparable to the results of a recent other study in patients with NDD-CKD, the REVOKE study. AEs, serious AEs (SAEs) and hospitalisations related to AEs were recorded up to the point at which another anaemia therapy was initiated and/or the randomised study drug was stopped.
Data were available for 616 patients, with no marked differences in baseline characteristics.
The incidence of AEs or SAEs per 100 PY was similar across treatment groups (Table 1), as was the cumulative number of AEs per 100 PY (Table 2).
Table 1: Incidence of AEs and SAEs per 100 PY
|High ferritin FCM||Low ferritin FCM||Oral iron|
|Any AE per 100 PY||91.0||100.0||105.0|
|Any SAE per 100 PY||28.2||27.9||24.3|
Table 2: Cumulative AEs and SAEs per 100 PY
|High ferritin FCM||Low ferritin FCM||Oral iron|
|No. of AE per 100 PY||438.3||428.7||440.3|
|No. of SAE per 100 PY||43.3||39.5||40.8|
However, patients receiving oral iron were more than twice as likely to experience a treatment-related AE, compared to those in either FCM trial arm, mainly due to gastrointestinal effects associated with oral iron. Patients took an average of 524 oral iron tablets over the 12-month study.
In high ferritin target FCM patients whose serum ferritin exceeded 800ng/mL at least once (n=41), the incidence of any AE (80.5%) was not higher than the overall cohort (81.8%) or the safety population as a whole, and similar to those patients whose ferritin remained <200ng/mL (86% and 81.7%, respectively). Higher doses of FCM also showed no association with an increased frequency of AEs.
Hospitalisation for any AEs and the cumulative number of hospitalisation events were similar between groups during the safety period. During the total follow-up period, the cumulative number of hospitalisations for AEs was 42.5, 42.2 and 62.1 events per 100 PY for the high ferritin, low ferritin and oral iron groups, respectively.
Safety analysis by type of event
Safety analysis did not reveal any safety signals for IV FCM by type of event.
- The incidence of one or more infection AE per 100 PY was similar across treatment groups, with infections reported as SAEs considered rare.
- Major adverse cardiac events (MACE) were similar between groups, with 3.6, 2.3 and 3.3 SAEs per 100 PY for the high ferritin, low ferritin and oral iron groups, respectively.
- eGFR remained stable across all three groups compared to baseline.
- No patient with ferritin ≥800ng/mL discontinued the study drug due to AEs.
- Twelve patients died during the safety period: 5 in the high ferritin FCM group, 1 in the low ferritin FCM group and 6 in the oral iron group. None of the deaths were considered to be related to study drug.
The REVOKE study published in 2015 raised concerns regarding the safety of IV FCM in NDD-CKD patients, suggesting a higher rate of cardiovascular events and infections with IV iron sucrose vs oral iron. The REVOKE study reported cumulative safety data in contrast to the more commonly used incidence reporting. It was this recording of repeated events in the same patient that was largely responsible for the reported differences in SAEs. Analysis of the data from the FIND-CKD trial using both reporting methods has shown no difference in the AEs between groups.
The authors recognise the need for longer follow-up studies in larger populations in this field, but conclude that the detailed analysis of safety events from the longest completed trial to date supports the safety of using IV FCM to correct IDA in NDD-CKD patients.
- Roger SD, Gaillard CA, Bock AH, et al. Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD : an analysis of the 1-year FIND-CKD trial. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc – Eur Ren Assoc. 2016:1-10. doi:10.1093/ndt/gfw264.
- Agarwal R, Kusek JW, Pappas MK. A randomized trial of intravenous and oral iron in chronic kidney disease. Kidney Int. June 2015.