Real-world safety and effectiveness of sucroferric oxyhydroxide for treatment of hyperphosphataemia in dialysis patients: a prospective observational study

Abstract

Background: The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), is indicated to control serum phosphorus levels in patients with chronic kidney disease on dialysis.

Methods: This non-interventional, prospective, multicentre, cohort study conducted in seven European countries evaluated the safety and effectiveness of SFOH in dialysis patients with hyperphosphataemia in routine practice. Safety outcomes included adverse drug reactions (ADRs) and changes in iron-related parameters. SFOH effectiveness was evaluated by changes-from-baseline (BL) in serum phosphorus and percentage of patients achieving in-target phosphorus levels.

Results: The safety analysis set included 1365 patients (mean observation: 420.3 ± 239.3 days). Overall, 682 (50.0%) patients discontinued the study. Mean SFOH dose during the observation period was 1172.7 ± 539.9 mg (2.3 pills/day). Overall, 617 (45.2%) patients received concomitant PB(s) during SFOH treatment. ADRs and serious ADRs were observed for 531 (38.9%) and 26 (1.9%) patients. Most frequent ADRs were diarrhoea (194 patients, 14.2%) and discoloured faeces (128 patients, 9.4%). Diarrhoea generally occurred early during SFOH treatment and was mostly mild and transient. Small increases from BL in serum ferritin were observed (ranging from +12 to +75 µg/L). SFOH treatment was associated with serum phosphorus reductions (6.3 ± 1.6 mg/dL at BL versus 5.3 ± 1.8 mg/dL at Month 30; ΔBL: -1.0 mg/dL, P < 0.01). Percentage of patients achieving serum phosphorus ≤4.5 mg/dL increased from 12.0% at BL to 34.8% at Month 30, while the percentage achieving serum phosphorus ≤5.5 mg/dL increased from 29.9% to 63.0%.

Conclusions: SFOH has a favourable safety and tolerability profile in a real-world setting, consistent with results of the Phase 3 study. Moreover, SFOH improved serum phosphorus control with a low daily pill burden.

Keywords: chronic kidney disease; end-stage kidney disease; haemodialysis; peritoneal dialysis; phosphate binder.

FIGURE 1:

VERIFIE study design. (1) Enrolment option for patients with SFOH treatment initiation at the time of inclusion into the study (treatment-naïve patients): treatment-naïve patients have a prospective observation period of up to 36 months. Retrospective data covering a period of 6 months prior to SFOH treatment start are collected. (2) Enrolment option for patients with SFOH treatment start up to 6 months prior to inclusion into the study (pre-treated patients): in pre-treated patients, SFOH treatment is documented for up to 42 months (for patients pre-treated with SFOH for >3 months and up to 6 months) including retrospective documentation of SFOH treatment up to 6 months and a prospective observation period of up to 36 months. Additionally, retrospective data covering a period of 6 months prior to SFOH treatment start are collected. Asterisks indicate inclusion into the study.

FIGURE 2:

Characteristics of diarrhoea during treatment with SFOH. (A) Time from start of treatment to first onset of diarrhoea (safety analysis set, subgroup of patients with reported diarrhoea; n = 217). (B) Duration of first diarrhoea event (safety analysis set, patients with diarrhoea with outcome; n = 186), where outcome = ‘recovered/resolved’ or ‘recovered/resolved with sequelae’.

FIGURE 3:

Mean ± SD values of iron-related parameters and changes versus BL during the observation period (safety analysis set; n = 1365). (A) Serum ferritin, (B) TSAT and (C) haemoglobin. *P < 0.05, **P < 0.01 and ***P < 0.001 versus BL. ^aTo account for the effect of premature discontinuations, data for all patients at the last completed observation time point were summarized by a final follow-up: ‘last visit’. Data for Month 36 not shown due to low number of patients with follow-up data at this time point. Bars show mean values and whiskers represent SDs.

FIGURE 4:

Serum phosphorus control during the observation period (full analysis set; n = 1322). (A) Mean ± SD phosphorus concentrations and changes from BL over time. **P < 0.01, ***P < 0.001 versus BL. (B) Proportion of patients with serum phosphorus ≤5.5 and ≤4.5 mg/dL. ^aTo account for the effect of premature discontinuations, data for all patients at the last completed observation time point were summarized by a final follow-up: ‘last visit’. Data for Month 36 not shown due to low number of patients with follow-up data at this time point. In (A), bars show mean values and whiskers represent SDs.

FIGURE 5:

Drug adherence score based on Morisky questionnaire (full analysis set; subgroup of patients who fully completed the questionnaire). The drug adherence score based on Morisky adherence questionnaire is calculated as sum of ‘No’ answers if complete assessments were given for all four questions. ^aAt baseline (SFOH treatment start) information regarding previous PB use other than SFOH was collected.