Viatcheslav Rakov

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.

One-year efficacy and safety of the iron-based phosphate binder sucroferric oxyhydroxide in patients on peritoneal dialysis

Background Sucroferric oxyhydroxide is a noncalcium, iron-based phosphate binder that demonstrated sustained serum phosphorus control, good tolerability and lower pill burden compared with sevelamer carbonate (sevelamer) in a Phase 3 study conducted in dialysis patients. This subanalysis examines the efficacy and tolerability of sucroferric oxyhydroxide and sevelamer in the peritoneal dialysis (PD) patient population. Methods The initial study (NCT01324128) and its extension (NCT01464190) were multicenter, Phase 3, open-label, randomized (2:1), active-controlled trials comparing sucroferric oxyhydroxide (1.0-3.0 g/day) with sevelamer (2.4-14.4 g/day) in dialysis patients over 52 weeks in total. Results In the overall study, 84/1055 (8.1%) patients received PD and were eligible for efficacy analysis (sucroferric oxyhydroxide, n = 56; sevelamer, n = 28). The two groups were broadly comparable to each other and to the overall study population. Serum phosphorus concentrations decreased comparably with both phosphate binders by week 12 (mean change from baseline - 0.6 mmol/L). Over 52 weeks, sucroferric oxyhydroxide effectively reduced serum phosphorus concentrations to a similar extent as sevelamer; 62.5% and 64.3% of patients, respectively, were below the Kidney Disease Outcomes Quality Initiative target range (≤1.78 mmol/L). This was achieved with a lower pill burden (3.4 ± 1.3 versus 8.1 ± 3.7 tablets/day) with sucroferric oxyhydroxide compared with sevelamer. Treatment adherence rates were 91.2% with sucroferric oxyhydroxide and 79.3% with sevelamer. The proportion of patients reporting at least one treatment-emergent adverse event was 86.0% with sucroferric oxyhydroxide and 93.1% with sevelamer. The most common adverse events with both treatments were gastrointestinal: diarrhea and discolored feces with sucroferric oxyhydroxide and nausea, vomiting and constipation with sevelamer. Conclusions Sucroferric oxyhydroxide is noninferior to sevelamer for controlling serum phosphorus in patients undergoing PD, while providing a relatively low pill burden and a high rate of adherence.

Effects of sucroferric oxyhydroxide and sevelamer carbonate on chronic kidney disease–mineral bone disorder parameters in dialysis patients

Abstract Background Treatment of hyperphosphataemia is the primary goal of chronic kidney disease–mineral and bone disorder (CKD-MBD) management. This post hoc analysis of a randomized, Phase 3 study evaluated the effects of 1-year treatment with the phosphate binders sucroferric oxyhydroxide or sevelamer carbonate (‘sevelamer’) on CKD-MBD indices among dialysis patients with hyperphosphataemia. Methods After a 2- to 4-week washout from previous phosphate binders, 1059 patients were randomized 2:1 to sucroferric oxyhydroxide 1.0–3.0 g/day (n = 710) or sevelamer 2.4–14.4 g/day (n = 349) for up to 24 weeks. Eligible patients enrolled in a 28-week extension. This post hoc analysis was performed for patients who completed ≥1 year of continuous treatment (n = 549). As the treatment groups showed similar CKD-MBD outcomes, the data were pooled for this analysis. Results Phosphate-binder therapy was associated with significant and sustained 30% reductions in serum phosphorus (P < 0.001). Median intact fibroblast growth factor-23 (FGF-23) also significantly decreased (P < 0.001) by 64% over 1 year. Intact parathyroid hormone decreased significantly after 24 weeks (P < 0.001), but levels returned to near baseline values by Week 52; minimal changes in serum calcium were observed. Of the bone resorption markers evaluated, tartrate-resistant acid phosphatase 5b (TRAP5b) decreased significantly (P < 0.001), whereas CTx increased transiently but returned to baseline levels by Week 52. The bone formation markers bone-specific alkaline phosphatase and osteocalcin both increased over 1 year of treatment. Conclusions Overall, 1 year of sucroferric oxyhydroxide or sevelamer treatment significantly reduced serum FGF-23, which has been associated with clinical benefit in patients with CKD. The trend towards increased bone formation marker levels indicates a beneficial effect on bone metabolism.

Long-term efficacy and safety of sucroferric oxyhydroxide in African American dialysis patients: Sucroferric oxyhydroxide in AA patients

Introduction: Sucroferric oxyhydroxide (SFOH) is a non‐calcium, iron‐based phosphate binder that demonstrated sustained serum phosphorus (sP) control, good tolerability, and lower pill burden, vs. sevelamer carbonate (“sevelamer”), in a Phase 3 study conducted in dialysis patients with hyperphosphatemia. This analysis evaluates the efficacy and safety of SFOH and sevelamer among African American (AA) patients participating in the trial.