Real-World Long-Term Effectiveness of Sucroferric Oxyhydroxide in Managing Hyperphosphatemia

Patients with advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) often experience hyperphosphatemia. Due primarily to the progressive inability of the kidneys to appropriately excrete phosphorus, disrupted phosphorus homeostasis leads to phosphorus accumulation. There have been associations between high levels of serum phosphorus and increased risk of cardiovascular morbidity and mortality. In a previous large national study, the risk of mortality among patients with CKD receiving hemodialysis therapy increased by 6% for each 1 mg/dL increase in serum phosphate level above the Kidney Disease Outcomes Quality Initiative target of 3.5 to 5.5 mg/dL.

Oral phosphate binders are effective in lowering serum phosphate. However, those agents have high pill burdens and low adherence rates. There is an association between reduced adherence to prescribed phosphate binder therapy and increased concentrations of serum phosphorus.

Sucroferric oxyhydroxide (SO; Velphoro® [Fresenius Medical Care Renal Therapies Group, Waltham, MA]) is a noncalcium, chewable, iron-based phosphate binder indicated for treating hyperphosphatemia in patients on dialysis therapy. Previous studies have shown similar efficacy, good tolerability, and lower pill burden when compared with sevelamer carbonate.

Results of a recent 6-month retrospective analysis of pharmacy data of patients on hemodialysis prescribed SO as part of routine care showed a >50% decrease in pill burden and a 95% increase in the proportion of patients with serum phosphorus levels of <5.5 mg/dL. Jessica Kendrick, MD, MPH, and colleagues conducted historical cohort analyses of de-identified electronic medical records to examine the long-term real-world effectiveness of SO in the management of serum phosphorus levels over a 1-year period in patients receiving  hemodialysis. Results were reported online in the Journal of Renal Nutrition [doi.org/10.1053/j.jrn.2018.11.002].

The analysis included comparisons between the 91-day period prior to SO initiation (baseline) and four consecutive 91-day intervals of SO treatment (Q1-Q4). Clinical measures included achievement of target phosphorus levels (≤5.5 mg/dL) and the mean number of phosphate binder pills per day. The analysis included adult (age ≥18 years) in-center hemodialysis patients from Fresenius Kidney Care units who switched from another phosphate binder to SO therapy as part of routine care between March 2014 and March 2015.

There were 3110 patients who met the criteria during the analysis period. Of those, 2580 were excluded due to changing dialysis facilities (n=201), non-continuous SO prescription days (n=785), prescription of combination phosphate binder therapy with SO (n=1024), or switching to a new phosphate binder (n=570).

Of the 530 adults in the analytic cohort, 41.0% (n=217) were black/African American and 16.4% (n=87) were Hispanic/Latino. All patients received hemodialysis three times per week. During baseline, the patients were prescribed monotherapy with sevelamer (59.8%), calcium acetate (27.6%), lanthanum carbonate (7.9%), or magnesium carbonate (0.4%) or were switched among those agents over the 3-month period.

In the month prior to the switch to SO, 18.7% of patients had in-range serum phosphorus concentrations (≤5.5 mg/dL). During the period of SO therapy, as many as 39.8% met that criterion, for a 113% increase in patients achieving target serum phosphorus goals. In the month prior to SO therapy, mean pill burden was 8.7 pills per day. Relative to that month, there was an association between SO therapy and at least a 49% reduction in mean pill burden during each subsequent month. Over the year of SO therapy, the mean SO pill burden was uptitrated from 4.0 at months 1 and 2 to 4.4 at month 12.

At baseline, the mean serum phosphorus concentration was 6.83 and only 17.7% of the patients in the analysis cohort had attained a serum phosphorus level of ≤5.5 mg/dL on their phosphate binder. Following the switch to SO, at each follow-up quarter, there was an improvement in mean serum phosphorus level from baseline: 6.54 mg/dL at Q1, 6.37 mg/dL at Q2, 6.25 mg/dL at Q3, and 6.19 mg/dL at Q4 (P<.0001 vs baseline).

The proportion of patients who achieved target serum phosphorus levels was higher than baseline throughout the SO treatment period: 24.5% at Q1, 30.5% at Q2, 36.4% at Q3, and 36.0% at Q4 (P<.001 for each quarter vs baseline). In further analyses, the proportions of patients reaching serum phosphorus concentrations ≤4.5 mg/dl increased from 4.7% at baseline to 6.6% at Q1, 11.6% at Q2, 12.1% at Q3, and 13.7% at Q4 (P<.001 for each interval vs baseline). Overall, there was a reduction in pill burden from baseline of approximately 50% for each 91-day interval during the treatment period (Q1 through Q4:4.0-4.3; P<.001 for each interval vs baseline).

When analyzed by prespecified subgroups of interest (black/African American patients, Hispanic/Latino patients, women), findings regarding the effectiveness of SO were similar.

The researchers cited some limitations to the study, including the retrospective design and lack of a comparator group followed up during the same study period, the reasons for switching from baseline phosphate binder to SO not being available, not accounting for specific nutritional education or advice given to patients, and lack of data on the use of protein supplements.

“In conclusion, results from this study demonstrate that completion of 1 year of treatment with SO was effective in controlling hyperphosphatemia in patients on hemodialysis with fewer prescribed pills per day than other PBs,” the researchers said.

Funding for the analysis was provided by Fresenius Medical Care Renal Therapies Group.

Takeaway Points

1. Researchers conducted historical cohort analyses to examine the real-world effectiveness of sucroferric oxyhydroxide (SO), a phosphate binder with a low pill burden, in managing serum phosphorus in patients prescribed SO as part of routine care.
2. Over a 1-year period, among 530 patients in the analyzed cohort, the proportion of patients achieving target serum phosphorus levels (≤5.5 mg/dL) increased by >100% after switching to SO therapy; reductions were seen at all follow-up timepoints.
3. Baseline pill burden was 8.5 pills/day. During treatment with SO, patients experienced an average 50% reduction in pill burden (Q1 through Q4: 4.0-4.3; P<.001 for each interval vs baseline).