Iron-related parameters in dialysis patients treated with sucroferric oxyhydroxide

Abstract

Background: Sucroferric oxyhydroxide is a non-calcium, iron-based phosphate binder indicated for the treatment of hyperphosphataemia in adult dialysis patients. This post hoc analysis of a randomized, 24-week Phase 3 study and its 28-week extension was performed to evaluate the long-term effect of sucroferric oxyhydroxide on iron parameters.

Methods: A total of 1059 patients were randomized to sucroferric oxyhydroxide 1.0-3.0 g/day (n = 710) or sevelamer carbonate ('sevelamer') 2.4-14.4 g/day (n = 349) for up to 52 weeks. The current analysis only included patients who completed 52 weeks of continuous treatment (n = 549). Changes in iron-related parameters and anti-anaemic product use during the study were measured.

Results: Some changes in iron-related parameters across both treatment groups were observed during the first 24 weeks of the study, and to a lesser extent with longer-term treatment. There were small, but significantly greater increases in mean transferrin saturation (TSAT) and haemoglobin levels with sucroferric oxyhydroxide versus sevelamer during the first 24 weeks (change in TSAT: +4.6% versus +0.6%, P = 0.003; change in haemoglobin: +1.6 g/L versus -1.1 g/L, P = 0.037). Mean serum ferritin concentrations also increased from Weeks 0 to 24 with sucroferric oxyhydroxide and sevelamer (+119 ng/mL and +56.2 ng/mL respectively; no statistically significant difference between groups). In both treatment groups, ferritin concentrations increased to a greater extent in the overall study population [>70% of whom received concomitant intravenous (IV) iron], compared with the subset of patients who did not receive IV iron therapy during the study. The pattern of anti-anaemic product use was similar in both treatment groups, with a trend towards higher use of IV iron and erythropoiesis-stimulating agents with sevelamer.

Conclusions: Initial increases in some iron-related parameters were observed in both treatment groups but were more pronounced with sucroferric oxyhydroxide. These differences between treatment groups with respect to changes in iron parameters are likely due to minimal iron absorption from sucroferric oxyhydroxide.

Keywords: chronic kidney disease; dialysis; iron; phosphate binder; sucroferric oxyhydroxide.

FIGURE 1

Mean (SEM) iron parameters—ferritin (A), TSAT (B) and haemoglobin (C)—over 1 year (completer set; n = 549). Only statistically significant differences are shown (P < 0.05). ^‡Last observation carried forward, Week 24 is the Week 24 result or the latest evaluable measurement after baseline (Week 0) in the primary study when Week 24 is missing; Week 52 Endpoint is Week 52 result or the latest available measurement after extension baseline when Week 52 is missing; SEM, standard error of the mean; TSAT, transferrin saturation.

FIGURE 2

Proportion of patients receiving concomitant anti-anaemic products—IV iron (A) and ESAs (B)—at different time periods over 1 year (completer set; n = 549). *P = 0.0252 for sucroferric oxyhydroxide versus sevelamer carbonate. Week 0 is baseline of initial Phase 3 study. ESAs, erythropoiesis stimulating agents; IV, intravenous.

FIGURE 3

Mean (SD) values at baseline and changes in iron indices by baseline ferritin levels in the initial Phase 3 study (Weeks 0–24) (completer set; n = 549). (A) Ferritin, (B) TSAT and (C) haemoglobin. Only P-values <0.05 are shown on the graphs; all other differences were not statistically significant. SD, standard deviation; TSAT, transferrin saturation. Ferritin quartiles were defined as follows: Q1, ≤310 ng/mL; Q2, ≤604 ng/mL (median for total population at baseline); Q3, ≤920 ng/mL; Q4, >920 ng/mL.

FIGURE 4

Mean (SEM) iron parameters—ferritin (A), TSAT (B) and haemoglobin (C)—in patients who did not receive concomitant IV iron over 1 year (non-IV iron completer set; n = 129). Only statistically significant differences are shown (P < 0.05). ^‡Last observation carried forward, Week 24 is the Week 24 result or the latest evaluable measurement after baseline (Week 0) in the primary study when Week 24 is missing; Week 52 Endpoint is Week 52 result or the latest available measurement after extension baseline when Week 52 is missing. IV, intravenous; SD, standard deviation; SEM, standard error of the mean; TSAT, transferrin saturation.