The impact of accessibility to non-calcium-based phosphate binders and calcimimetics on mineral outcomes in patients receiving maintenance hemodialysis: A 10-year retrospective analysis of real-world data.

INTRODUCTION: Hyperphosphatemia and hyperparathyroidism are common in end-stage kidney disease and are associated with poor outcomes. In addition to adequate dialysis, medications are usually required for optimum control of serum phosphate and parathyroid hormone (PTH) levels. The use of calcium-based phosphate binders (CBPBs) and active vitamin D is associated with an increase in serum calcium and worsening vascular calcification. To overcome these limitations, non-calcium-based phosphate binders (NCBPBs) and calcimimetics have been developed. However, the coverage for these new medications remains limited in several parts of the world due to the lack of patient-level outcome data and cost. The present study examined the differences in mineral outcomes between two main categories of healthcare programs that provided different coverage for medications used to control mineral and bone disorders (MBD). The Social Security/Universal Coverage (SS/UC) program covered only CBPBs and active vitamin D, whereas the Civil Servant/State Enterprise (CS/SE) program provided coverage of CBPBs, active vitamin D, NCBPBs, and calcimimetics. METHODS: This 10-year retrospective cohort study examined the differences in mineral outcomes between two healthcare programs in maintenance hemodialysis patients. The differences in serum calcium, phosphate, and PTH levels, as well as the aortic arch calcification score, were analyzed according to dialysis vintage by linear mixed-effects regression analyses. The difference in the composite outcome of severe hyperparathyroidism and parathyroidectomy was analyzed by the Cox-proportional hazard regression model. RESULTS: 714 patients were included in the analyses (full cohort). Of these patients, 563 required at least one type of medication to control MBD (MBD medication subgroup). Serum calcium, phosphate, and the proportions of patients with hypercalcemia and hyperphosphatemia were substantially higher in the SS/UC group compared with the CS/SE group after appropriate adjustments for confounders in both the full cohort and the MBD medication subgroup. These findings were confirmed in propensity-score matched analyses. Higher parathyroid hormone levels and a higher rate of the composite endpoint of severe hyperparathyroidism and parathyroidectomy were also observed in the SS/UC group. A more rapid progression of aortic arch calcification was suggested in the SS/UC group, but between-group changes were not significant. CONCLUSION: Patients under the healthcare program that did not cover the use of NCBPBs and calcimimetics showed higher serum calcium and phosphate levels and a more rapid progression of hyperparathyroidism. The difference in the progression of vascular calcification could not be confirmed in the present study.

Health Economic Benefits of Introducing Sucroferric Oxyhydroxide in the Treatment of Patients with Chronic Kidney Disease under Dialysis in the Kingdom of Saudi Arabia.

Hyperphosphatemia is an electrolyte disorder highly prevalent in patients with chronic kidney disease undergoing hemodialysis (HD) that usually requires treatment with oral phosphate binders (PBs). Sucroferric oxyhydroxide (SO) is a calcium-free, iron-based PB indicated for the control of serum phosphorus. In the real-world setting, SO has shown clinical effectiveness with a lower pill burden and has also been associated with reduced hospital admission rates. This study aims to assess the potential economic benefits resulting from the introduction of SO to the health-care setting of the Kingdom of Saudi Arabia (KSA). An economic analysis using data from a retrospective real-world study that compared HD patients with uninterrupted SO prescriptions with patients who discontinued SO and switched to other PBs (oPBs). Annual drug costs for the estimated PB-eligible population in KSA were quantified. Costs per responder were estimated for all treatments. Hospital admissions' incidence rates were converted into annual inpatient cost savings and were deducted from drug costs to estimate the annual economic effect of SO versus oPBs. Sensitivity and breakeven analyses were also conducted. The eligible population for PB therapy in KSA was estimated at n = 14,748. Treating therapy-eligible populations exclusively with SO was estimated to generate annual inpatient cost-savings of SAR 107.4-119.4 million compared to treating the population with oPBs. The estimated economic effect signified overall annual savings ranging from SAR 82.8 to SAR 94.8 million when the population is treated with SO. Sensitivity analyses showed persistent cost savings. The estimated benefit-cost ratios showed that for every SAR 1 spent on SO, the expected return on investment was SAR 4.4-4.9. SO is an effective therapy that may result in substantial cost savings from reducing hospital admission costs that are attributable to hyperphosphatemia among HD patients.

Real-World Phosphate Binder Use among Dialysis-Dependent Patients with CKD.

INTRODUCTION: For patients with chronic kidney disease (CKD), the need for phosphate binder (PB) treatment peaks at onset of dialysis. This real-world study assessed rates of PB utilization and switching in patients with dialysis-dependent CKD (DD-CKD). METHODS: We identified patients with PB utilization among those with prevalent DD-CKD using 2018-2019 Medicare Parts A/B/D data. Patients were assigned to cohorts based on primary (most frequently used) PB among calcium acetate, ferric citrate, lanthanum carbonate, sevelamer (hydrochloride and carbonate), sucroferric oxyhydroxide. We measured proportion of patients who were adherent (proportion of days covered >80%) and persistent (patients whose last 90 days of outpatient dialysis reported PB use). Net switching rates were calculated as the difference between switches to and from the primary agent. RESULTS: We identified 136,912 patients with PB use. Proportion of patients adherent ranged from 63.8% (lanthanum carbonate) to 67.7% (sevelamer) and persistent from 85.1% (calcium acetate) to 89.5% (ferric citrate). Most patients (73%) used the same PB throughout the study. Overall, 20.5% of patients experienced one switch and 2.3% two or more. Positive net switching rates were observed for ferric citrate, sucroferric oxyhydroxide, and lanthanum carbonate (2-10%) but negative for sevelamer and calcium acetate (-2% to -7%). CONCLUSION: Adherence and persistence rates were low with slight variation across PBs. Net positive switching occurred for ferric citrate, sucroferric oxyhydroxide, and lanthanum carbonate. Further studies are needed to determine the reasons for these findings and could identify opportunities for better control of phosphate levels among patients with CKD.

[Investigation of Leftover Hyperphosphatemia Drugs in Hemodialysis Outpatients].

Currently, various hyperphosphatemia drugs are administered orally to hemodialysis patients in order to lower serum phosphorus levels. However, it is known that medication adherence is poor, possibly due to greater pill burden taken each time and their complicated schedules. Therefore, large amounts of unused hyperphosphatemia drugs are likely to be leftover. The increase in leftover prescribed drugs leads to the unnecessary elevation of medical care costs. To date, however, the available information on leftover hyperphosphatemia drugs in hemodialysis outpatients is limited. In this study, we performed an interview survey of medication adherence to hyperphosphatemia drugs among 60 hemodialysis outpatients and evaluated the cost of the leftover drugs. Thirty-four patients showed good adherence. On the other hand, 19 patients self-adjusted to take hyperphosphatemia drugs according to their daily diet. When assessing the serum phosphorus levels for these patients over the past year, the values often exceeded the targeted range (3.5-6.0 mg/mL). Furthermore, 35 patients kept hyperphosphatemia drugs at their home. When estimating the cost derived from leftover drugs using the bootstrap method, main distribution of drug cost was shown to be in the range of 2000 to 2500 yen. This drug cost seemed to in part reflect preparation for an emergency. A serious problem was that 14 patients had previous experience in discarding hyperphosphatemia drugs. This study suggested that more appropriate pharmaceutical care according to each patient's situation is essential in improving phosphorus control in hemodialysis outpatients and in reducing the waste of medical resources.

Evaluation of the cost-utility of phosphate binders as a treatment option for hyperphosphatemia in chronic kidney disease patients: a systematic review and meta-analysis of the economic evaluations.

BACKGROUND: Uncontrolled hyperphosphatemia in chronic kidney disease (CKD) patients commonly results in vascular calcification leading to increased risk of cardiovascular disease. Phosphate binders (PBs) are used for hyperphosphatemia and can be calcium-based (CBPBs) or non-calcium-based (NCBPBs), the latter being more expensive than CBPBs. In this study, we used meta-analysis approaches to assess the cost-utility of PBs for hyperphosphatemia in CKD patients. METHODS: Relevant studies published prior to June 2019 were identified from PubMed, Scopus, the Cochrane Library, the National Health Service Economic Evaluation Database, and the Cost-Effectiveness Analysis Registry. Studies were eligible if they included CKD patients with hyperphosphatemia, compared any PBs and reported economic outcomes. Meta-analysis was applied to pool incremental net benefit (INB) across studies stratified by country income. RESULTS: A total of 25 studies encompassing 32 comparisons were eligible. Lanthanum carbonate, a NCBPB, was a more cost-effective option than CBPBs in high-income countries (HICs), with a pooled INB of $3984.4 (599.5-7369.4), especially in pre-dialysis patients and used as a second-line option with INBs of $4860.2 (641.5-9078.8), $4011.0 (533.7-7488.3), respectively. Sevelamer, also a NCBPB, was not more cost-effective as a first-line option compared to CBPBs with a pooled INB of $6045.8 (- 23,453.0 to 35,522.6) and $34,168.9 (- 638.0 to 68,975.7) in HICs and upper middle-income countries, respectively. CONCLUSIONS: Lanthanum carbonate was significantly more cost-effective than CBPBs as a second-line option for hyperphosphatemia in pre-dialysis patients in HICs. However, the use of sevelamer is not more cost-effective as a first-line option compared to CBPBs.

Phosphate-Binder Use in US Dialysis Patients: Prevalence, Costs, Evidence, and Policies.

Medicare costs for phosphate binders for US dialysis patients and patients with chronic kidney disease enrolled in Medicare Part D exceeded $1.5 billion in 2015. Previous data have shown that Part D costs for mineral and bone disorder medications increased faster than costs for all Part D medications for dialysis patients. Despite extensive use of phosphate binders and escalating costs, conclusive evidence is lacking that they improve important clinical end points in dialysis patients or non-dialysis-dependent patients with chronic kidney disease. Using dialysis patient data from the US Renal Data System and laboratory information from the Centers for Medicare & Medicaid Services (CMS) CROWNWeb data, we update information on trends in phosphate-binder use, calcium and phosphorus values, and costs for Medicare-covered dialysis patients. We discuss these results in the context of evidence from clinical trials, meta-analyses, and observational studies evaluating phosphate-binder efficacy, safety, comparative effectiveness, and cost-effectiveness. Based on our analysis, we note a need for US Food and Drug Administration guidance regarding clinical evaluation of new phosphate binders, and we suggest that it would be in CMS' best interest to fund a clinical trial to assess whether lower versus higher phosphate concentrations improve hard clinical outcomes, and if so, whether particular phosphate binders are superior to placebo or other binders in improving these outcomes.

A Review of Phosphate Binders in Chronic Kidney Disease: Incremental Progress or Just Higher Costs?

As kidney disease progresses, phosphorus retention also increases, and phosphate binders are used to treat hyperphosphatemia. Clinicians prescribe phosphate binders thinking that reducing total body burden of phosphorus may decrease risks of mineral and bone disorder, fractures, cardiovascular disease, progression of kidney disease, and mortality. Recent meta-analyses suggest that sevelamer use results in lower mortality than use of calcium-containing phosphate binders. However, studies included in meta-analyses show significant heterogeneity, and exclusion or inclusion of specific studies alters results. Since no long-term studies have been conducted to determine whether treatment with any phosphate binder is better than placebo on any hard clinical endpoint (including mortality), it is unclear whether possible benefit with sevelamer represents net benefit of sevelamer, net harm with calcium-containing phosphate binders, or both. Although one meta-analysis suggested that calcium acetate may be more efficacious gram for gram than calcium carbonate as a binder, calcium acetate did not reduce hypercalcemia, and gastrointestinal intolerance was higher. Data are insufficient to determine whether calcium acetate provides lower risk of vascular calcification than calcium carbonate. Fears of lanthanum accumulation in the central nervous system or bone with long-term treatment do not appear to be warranted. Newer iron-containing phosphate binders have potential benefits, such as lower pill burden (sucroferric oxyhydroxide) and improved iron parameters (ferric citrate). The biggest challenge to phosphate binder efficacy is non-adherence. This article reviews the current knowledge regarding safety, effectiveness, and adherence with currently marketed phosphate binders and those in development.

Cost-effectiveness of phosphate binders among patients with chronic kidney disease not yet on dialysis: a long way to go.

Hyperphosphatemia management is integral to the management of patients with chronic kidney disease. This mineral abnormality is associated with greater costs, but so is its management, especially with the use novel phosphate binders. The economic evaluation of these pharmaceutical agents is increasingly needed to provide evidence for value of money spent and inform resource allocation. Recently, Nguyen et al. explored the economical attractiveness of Sevelamer relative to Calcium Carbonate among patients with chronic kidney disease not yet on dialysis and concluded that the former was cost-effective. The current commentary discusses the results of this analysis and sheds light on the methodological challenges of economic evaluations in this field.

Psychosocial Factors That Create Barriers to Managing Serum Phosphorus Levels in Pediatric Dialysis Patients: A Retrospective Analysis.

OBJECTIVE: Abnormal phosphorus homeostasis is among the medley of metabolic disturbances commonly associated with chronic kidney disease. We sought to determine the psychosocial factors that create barriers to controlling serum phosphorus levels in children on dialysis and to evaluate the perceptions of children and caregivers on the ease or difficulty of following a dietary phosphorus restriction and taking phosphorus binder medications. DESIGN: Single center cross-sectional study. SETTING: Pediatric dialysis unit at a children's hospital. SUBJECTS: Forty-eight patients on chronic hemodialysis or peritoneal dialysis (mean age: 11.03 ± 6.88 years; 69% male). MAIN OUTCOME MEASURE: Serum phosphorus levels were recorded from electronic health records and converted to a mean phosphorus standard deviation score (SDS) for each individual. Mean phosphorus SDS values were compared to each independent categorical variable using an analysis of variance test, continuous variables were analyzed using linear regression, and logistic regression was used to determine odds ratios. RESULTS: There was a significant relationship between age and phosphorus SDS (P < .001), with patients over 13 years of age having the highest prevalence of hyperphosphatemia (88%). Patients and caregivers who identified phosphorus levels as "controlled" had lower phosphorus SDS values compared to the other subjects (P = .003). However, of the patients and caregivers who reported that serum phosphorus levels were "controlled," 46% were hyperphosphatemic. Furthermore, 73% and 87% of patients and caregivers reported that following a phosphorus-restricted diet and taking phosphorus binders were "easy"; yet, 40% and 49% of these patients were hyperphosphatemic, respectively. CONCLUSION: In the present study, elevated serum phosphorus levels were most common in adolescent dialysis patients. There also appears to be a disconnect between the perceived ease of following a phosphorus-restricted diet and taking phosphorus binders and the achievement of normal serum phosphorus levels. These data further emphasize the importance of ongoing education regarding dietary and medical management requirements.

Economic evaluations of interventions to manage hyperphosphataemia in adult haemodialysis patients: A systematic review.

Managing hyperphosphataemia in haemodialysis patients is resource-intensive. A search for cost-effective interventions in this field is needed to inform decisions on the allocation of healthcare resources. NHSEED, MEDLINE, EMBASE and CINAHL were searched for full economic evaluations of hyperphosphataemia-managing interventions in adult haemodialysis patients, published between 2004 and 2014, in English, French, Dutch or German. Incremental cost-effectiveness ratios of the interventions were up-rated to 2013US$ using Purchasing Power Parity conversion rates and Consumer Price Indices. The quality of included studies was assessed using the Extended Consensus on Health Economic Criteria List. Twelve out of the 1681 retrieved records fulfilled the inclusion criteria. They reported only on one aspect of hyperphosphataemia management, which is the use of phosphate binders (calcium-based and calcium-free, in first-line and sequential use). No economic evaluations of other phosphorus-lowering interventions were found. The included articles derived from five countries and most of them were funded by pharmaceutical companies. The incremental cost-effectiveness ratios of phosphate binders ranged between US$11 461 and US$157 760 per quality-adjusted life-year gained. Calcium-based binders (especially calcium acetate) appear to be the optimal cost-effective first- and second-line therapy in prevalent patients, while the calcium-free binder, lanthanum carbonate, might provide good value for money, as second-line therapy, in incident patients. The studies' overall quality was suboptimal. Drawing firm conclusions was not possible due to the quality heterogeneity and inconsistent results. Future high-quality economic evaluations are needed to confirm the findings of this review and to address other interventions to manage hyperphosphataemia in this population.

[Vascular Calcification - Pathological Mechanism and Clinical Application - . The effect of phosphate binders on vascular calcification].

Vascular calcification is the abnormality in chronic kidney disease-mineral bone disorder (CKD-MBD) that directly affects the prognosis in relation with cardiovascular diseases. Phosphate binders (PB) are widely used to prevent hyperphosphatemia that can lead to vascular calcification. Two types of PB are available ; calcium (Ca) -based PB and non-Ca-based PB. Non-Ca-based PB has been shown to retard the progression of vascular calcification, while there is a great concern that Ca overload can promote calcification. Moreover, the newer non-Ca-based PBs have been developed including iron and magnesium. We must pay attention to select proper types of PB with costs, pill burdens and specific circumstances observed in Japan.

Assessment of tubular reabsorption of phosphate as a surrogate marker for phosphate regulation in chronic kidney disease.

BACKGROUND/AIMS: Fibroblast growth factor 23 (FGF23) and soluble α-Klotho are emerging potential biomarkers of phosphorus and vitamin D metabolism which change in concentration in early chronic kidney disease (CKD) in order to maintain normal phosphorus levels. Tubular reabsorption of phosphate (TRP) has been commonly used to assess renal tubular phosphate transport. The aim of this study was to evaluate the usefulness of TRP as a surrogate marker of parameters of CKD-mineral bone disease (CKD-MBD) in CKD. METHODS: A cross-sectional study was performed in 93 stable patients with predialysis CKD stage 1-5. In all patients, TRP, estimated glomerular filtration rate (eGFR), calcium, phosphate, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D, serum FGF23 and urine soluble α-Klotho levels were measured. RESULTS: As renal function declined, TRP significantly decreased (P < 0.001; r = 0.763) and both iPTH and serum FGF23 increased (P < 0.001; r = -0.598, P < 0.001; r = -0.453, respectively). The prevalence of hyperphosphatemia, secondary hyperparathyroidism, FGF23 excess and abnormal TRP increased progressively with declining eGFR. Although TRP level changed later than FGF23, abnormal levels of both TRP and FGF23 were observed earlier than changes in iPTH and serum phosphate. Decreased TRP was found to be independently associated with decreased eGFR and increased iPTH but was not associated with urine soluble α-Klotho or serum FGF23 level in multiple linear regression analysis. CONCLUSION: TRP is a simple, useful and cost-saving surrogate marker of the assessment of altered mineral metabolism in CKD patients and can be used as an alternative to serum FGF23, especially for mild to moderate renal insufficiency.

Sevelamer is cost effective versus calcium carbonate for the first-line treatment of hyperphosphatemia in new patients to hemodialysis: a patient-level economic evaluation of the INDEPENDENT-HD study.

BACKGROUND: The recent multicenter, randomized, open-label INDEPENDENT study demonstrated that sevelamer improves survival in new to hemodialysis (HD) patients compared with calcium carbonate. The objective of this study was to determine the cost-effectiveness of sevelamer versus calcium carbonate for patients new to HD, using patient-level data from the INDEPENDENT study. STUDY DESIGN: Cost-effectiveness analysis. SETTING AND POPULATION: Adult patients new to HD in Italy. MODEL, PERSPECTIVE, TIMEFRAME: A patient-level cost-effectiveness analysis was conducted from the perspective of the Servizio Sanitario Nazionale, Italy's national health service. The analysis was conducted for a 3-year time horizon. The cost of dialysis was excluded from the base case analysis. INTERVENTION: Sevelamer was compared to calcium carbonate. OUTCOMES: Total life years (LYs), total costs, and the incremental cost per LY gained were calculated. Bootstrapping was used to estimate confidence intervals around LYs, costs, and cost-effectiveness and to calculate the cost-effectiveness acceptability curve. RESULTS: Sevelamer was associated with a gain of 0.26 in LYs compared to calcium carbonate, over the 3-year time horizon. Total drug costs were €3,282 higher for sevelamer versus calcium carbonate, while total hospitalization costs were €2,020 lower for sevelamer versus calcium carbonate. The total incremental cost of sevelamer versus calcium carbonate was €1,262, resulting in a cost per LY gained of €4,897. The bootstrap analysis demonstrated that sevelamer was cost effective compared with calcium carbonate in 99.4 % of 10,000 bootstrap replicates, assuming a willingness-to-pay threshold of €20,000 per LY gained. LIMITATIONS: Data on hospitalizations was taken from a post hoc retrospective chart review of the patients included in the INDEPENDENT study. Patient quality of life or health utility was not included in the analysis. CONCLUSIONS: Sevelamer is a cost-effective alternative to calcium carbonate for the first-line treatment of hyperphosphatemia in new to HD patients in Italy.

The economic impact of improving phosphate binder therapy adherence and attainment of guideline phosphorus goals in hemodialysis patients: a Medicare cost-offset model.

INTRODUCTION: Hyperphosphatemia (serum phosphorus >5.5 mg/dL) in hemodialysis patients is a key factor in mineral and bone disorders and is associated with increased hospitalization and mortality risks. Treatment with oral phosphate binders offers limited benefit in achieving target serum phosphorus concentrations due to high daily pill burden (7-10 pills/day) and associated poor medication adherence. The economic value of improving phosphate binder adherence and increasing percent time in range (PTR) for target phosphorus concentrations has not been previously assessed in dialysis patients. The current retrospective analysis was conducted to summarize health care cost savings to United States (US) payers associated with improved phosphate binder adherence and increased PTR for target phosphorus concentrations in adult end-stage renal disease (ESRD) patients receiving hemodialysis therapy. METHODS: Phosphate binder adherence and PTR were derived from hemodialysis patients who were treated at a large dialysis organization between January 2007 and December 2011. Cost model inputs were derived from US Renal Data System data between July 2007 and December 2009. A cost-offset model was constructed to estimate monthly and annual incremental health care costs (total Medicare; inpatient, outpatient, and Medicare Part B) associated with different levels of phosphate binder adherence and PTR. Model inputs included number of ESRD patients, population adherence to phosphate binders, PTR associated with adherence to phosphate binders, and per-patient per-month cost associated with PTR. A base case model estimated monthly and annual costs of phosphate binder therapy in the population using estimated model inputs. The estimated adherence rate was used to determine number of patients in compliant and noncompliant groups. Monthly costs were calculated as the sum of per-patient per-month cost times the number of patients in adherent and nonadherent groups. Annual costs were monthly costs times 12 and assumed the same level of adherence, PTR, and per-patient per-month costs over time. To study the impact of improving phosphate binder adherence and PTR on cost outcomes, we hypothetically and simultaneously increased both base phosphate binders adherence and PTR for adherent patients (adherence/PTR: 10/20%, 20/40%, 30/60%). Monthly and annual costs were derived for each scenario and compared against the results of the base case model. One-way sensitivity analysis was performed to test model robustness. RESULTS: The base case model estimated total Medicare and inpatient costs of $5,152,342 and $1,435,644, respectively (N = 1,000). When base case model costs were compared to results of each extended model scenario, overall Medicare cost savings (range 0.3-1.9%) and inpatient cost savings (range 1.2-5.7%) were observed. The one-way sensitivity analysis indicated that results were sensitive to PTR for adherent and nonadherent patients and the factor used to increase adherence rate and PTR associated with adherence in the hypothetical scenarios. However, cost savings in overall Medicare costs and inpatient costs were still noted. CONCLUSION: Increasing phosphate binder adherence and improving phosphorus control were associated with increased cost savings in total Medicare costs and inpatient costs.

Sevelamer is cost-saving vs. calcium carbonate in non-dialysis-dependent CKD patients in italy: a patient-level cost-effectiveness analysis of the INDEPENDENT study.

OBJECTIVES: To conduct a cost-effectiveness analysis of sevelamer versus calcium carbonate in patients with non-dialysis-dependent CKD (NDD-CKD) from the Italian NHS perspective using patient-level data from the INDEPENDENT-CKD study. METHODS: Patient-level data on all-cause mortality, dialysis inception and phosphate binder dose were obtained for all 107 sevelamer and 105 calcium carbonate patients from the INDEPENDENT-CKD study. Hospitalization and frequency of dialysis data were collected post hoc for all patients via a retrospective chart review. Phosphate binder, hospitalization, and dialysis costs were expressed in 2012 euros using hospital pharmacy, Italian diagnosis-related group and ambulatory tariffs, respectively. Total life years (LYs) and costs per treatment group were calculated for the 3-year period of the study. Bootstrapping was used to estimate confidence intervals around outcomes, costs, and cost-effectiveness and to calculate the cost-effectiveness acceptability curve. A subgroup analysis of patients who did not initiate dialysis during the INDEPENDENT-CKD study was also conducted. RESULTS: Sevelamer was associated with 0.06 additional LYs (95% CI -0.04 to 0.16) and cost savings of EUR -5,615 (95% CI -10,066 to -1,164) per patient compared with calcium carbonate. On the basis of the bootstrap analysis, sevelamer was dominant compared to calcium carbonate in 87.1% of 10,000 bootstrap replicates. Similar results were observed in the subgroup analysis. RESULTS were driven by a significant reduction in all-cause mortality and significantly fewer hospitalizations in the sevelamer group, which offset the higher acquisition cost for sevelamer. CONCLUSIONS: Sevelamer provides more LYs and is less costly than calcium carbonate in patients with NDD-CKD in Italy.

Management of hyperphosphataemia in chronic kidney disease: summary of National Institute for Health and Clinical Excellence (NICE) guideline.

Bone disease and ectopic calcification are the two main consequences of hyperphosphataemia of chronic kidney disease (CKD). Observational studies have demonstrated that hyperphosphataemia in CKD is associated with increased mortality. Furthermore, the use of phosphate binders in dialysis patients is associated with significantly lower mortality. The UK Renal Registry data show significant underachievement of phosphate targets in dialysis patients. It is believed to be due to wide variation in how management interventions are used. The National Institute for Health and Clinical Excellence (NICE) has developed a guideline on the management of hyperphosphataemia in CKD. This is based on the evidence currently available using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. This review outlines the recommendations including research recommendations and discusses methodology, rationale and challenges faced in developing this guideline and the health economic model used to assess the cost-effectiveness of different phosphate binders.

Economic evaluation of sevelamer for the treatment of hyperphosphatemia in chronic kidney disease patients not on dialysis in the United Kingdom.

OBJECTIVES: To determine the cost effectiveness of sevelamer vs calcium carbonate in patients with chronic kidney disease and not on dialysis (CKD-ND) from the perspective of the National Health Service (NHS) in the UK. METHODS: A Markov decision analytic model was developed to estimate (1) total life years (LYs), quality-adjusted life years (QALYs), and costs for patients treated with sevelamer or calcium carbonate; and (2) incremental costs per LY gained (LYG) and per QALY gained for sevelamer vs calcium carbonate. Data informing probability transitions to all-cause death and dialysis inception in CKD-ND patients were taken directly from the INDEPENDENT-CKD study and were extrapolated beyond the 3-year clinical trial using Weibull regression analysis. Estimates of health utility and costs (in £2011) were derived from the published literature. RESULTS: Over a lifetime horizon, sevelamer treatment resulted in a gain of 2.05 LYs and 1.56 QALYs per patient, an increase of £37,282 in total costs per patient vs calcium carbonate (3.5% discount), and a per-patient cost of £18,193/LYG and £23,878/QALY gained. Results were robust to alternative assumptions in key parameters; results were most sensitive to alternative assumptions regarding the mean daily dose of sevelamer, impact of sevelamer on dialysis initiation, cost of dialysis, and health utility estimates. The probabilistic sensitivity analysis showed that sevelamer was cost-effective vs calcium carbonate in 93% of simulations at a willingness-to-pay threshold of £30,000/QALY gained. LIMITATIONS: While the model simulated a real-world clinical setting, this analysis was subject to limitations common to all decision analytic models, in that it used a mix of data sources and relied on several assumptions. Not all variables that impact real-world outcomes and costs were included in this model. CONCLUSIONS: Sevelamer is a cost-effective option compared to calcium carbonate for the first-line treatment of hyperphosphatemia in CKD-ND patients in the UK.

A modeled economic evaluation of sevelamer for treatment of hyperphosphatemia associated with chronic kidney disease among patients on dialysis in the United Kingdom.

OBJECTIVE: There is limited information regarding the cost-effectiveness of sevelamer for the treatment of hyperphosphatemia in chronic kidney disease (CKD) patients on dialysis in the UK. Using a UK National Health Service (NHS) perspective and final results of the Dialysis Clinical Outcomes Revisited (DCOR) study, an evaluation was performed to determine the cost-effectiveness of sevelamer compared to calcium-based phosphate binders for the first-line treatment of hyperphosphatemia in CKD patients on dialysis. METHODS: A Markov model was developed to estimate life years, quality-adjusted life years (QALYs), costs, incremental cost per life year (LY) gained, and QALY gained. Treatment-specific overall survival up to 44 months, hospitalizations, and resource utilization were derived from the DCOR study. Survival was extrapolated to a lifetime horizon using Weibull regression analysis. Unit costs and utility estimates specific to the UK were obtained from the published literature. Sub-group analyses were conducted based on data reported from the DCOR study for increasing age cut-points. Outcomes and costs were modeled for a lifetime horizon. RESULTS: In the base case analysis, the use of sevelamer resulted in a gain of ∼0.73 LYs and 0.44 QALYs per patient (discounted at 3.5% per year). Total per-patient costs were higher for sevelamer, resulting in an incremental cost of £22,157 per QALY gained and £13,427 per LY gained (in £2009). Increasingly favorable cost per QALY ratios were observed with increasing age cut-points, ranging from £15,864 for patients ≥45 to £13,296 for patients ≥65 years of age. Results were most sensitive to assumptions regarding overall survival and the inclusion of dialysis costs. Key limitations of the analysis included the use of non-UK trial data for survival and hospitalizations, and the exclusion of quality-of-life impacts associated with hospitalization. CONCLUSIONS: In CKD patients receiving dialysis, treatment of hyperphosphatemia with sevelamer offers good value for money compared with calcium-based binders.

Assessment of phosphate binding by sevelamer carbonate powder for oral suspension mixed in foods.

This study investigated mixing sevelamer carbonate powder with foods and beverages other than water. Food samples, including applesauce, oatmeal, chicken, protein powder, scrambled eggs, ginger ale, and diet ginger ale, were subjected to an in vitro assay, and the difference in the amount of phosphate bound between samples pre-exposed to foods and samples where the drug was exposed to foods concurrently was determined Under these assay conditions, pre-exposure to sevelamer carbonate powder had no effect on the ability to bind phosphate. Clinical testing is needed to further evaluate this finding.

Cost-effectiveness of lanthanum carbonate in the treatment of hyperphosphatemia in dialysis patients: a Canadian payer perspective.

BACKGROUND: Hyperphosphatemia is a common and potentially harmful condition in patients with end-stage kidney disease. In Canada, first-line treatment of hyperphosphatemia consists primarily of calcium carbonate (CC). Lanthanum carbonate (LC) and sevelamer hydrochloride (SH) are non-calcium phosphate binders that have been used as second-line therapy in patients intolerant of or not responsive to CC. OBJECTIVES: The primary objective of the present study was to assess the costs and clinical benefits of second-line use of LC after therapy failure with CC in patients receiving dialysis, from a Canadian payer perspective. The secondary objective was to perform an economic comparison between second-line LC therapy and second-line SH therapy, from a Canadian payer perspective. Short-term outcomes were treatment response and cost per additional responder, and long-term outcomes were survival, number of all-cause hospitalizations, and quality of life. METHODS: A cost-effectiveness Markov model was populated with simulated cohorts of 1000 patients receiving incident dialysis, followed life-long. Patients not responsive to CC with a serum phosphate concentration >1.78 mmol/L (>5.5 mg/dL) received a trial regimen with LC. Patients not responsive to LC returned to CC therapy. Patient data from a randomized controlled trial of 800 patients receiving dialysis were used. Extensive (probabilistic) sensitivity analyses were performed. When available, model parameters were based on Canadian data or from a Canadian perspective. All costs are in 2010 Canadian dollars (C$). RESULTS: Results of the model estimated that in patients responsive to second-line LC therapy, survival increased, on average, 0.44 years (95% confidence interval [CI], 0.35-0.54) per patient when compared with continued CC therapy. The mean (range) costs per patient in the first year of treatment with LC was C$2600 (C$2400-C$2800). Over patients' lifetimes, the second-line LC strategy resulted in a gain of 48.8 (37.1-61.3) life-years and 29.3 (21.4-38.1) quality-adjusted life-years (QALYs). The cost-effectiveness of the second-line LC strategy was C$7900 (C$1800-C$14,600) per life-year and C$13,200 (C$3000-C$25,100) per QALY gained. Most sensitivity analyses did not change the cost-effectiveness outcomes; however, including unrelated future costs raised the incremental cost-effectiveness ratio to C$159,500 (95% confidence interval, C$133,300-C$191,600) per QALY gained. Compared with second-line SH therapy, second-line LC therapy had similar effectiveness and was 23% less expensive. CONCLUSIONS: Second-line treatment with LC is cost-effective in the treatment of end-stage kidney disease in patients with hyperphosphatemia, from a Canadian payer perspective. Second-line treatment with LC is less expensive, with similar effectiveness as second-line treatment with SH. The primary limitation of health economic evaluations of phosphate binders is the relative scarcity of clinical data on the association between phosphate concentration and long-term outcome.