Switching Pharmacological Treatment in Wilson Disease: Case Report and Recommendations.

Background. Available treatments for Wilson disease (WD) prevent longterm complications of copper accumulation. Current anti-copper agents include zinc salts, penicillamine, and trientine. Patients with WD may switch between the agents for a number of reasons. Due to the different mechanisms of action between the copper chelators and zinc salts, transitioning could require a period of overlap and increased monitoring. There are no large studies that investigate the best transition strategies between agents. In this article, we review the treatments for WD and how to monitor for treatment efficacy. Case Summary. The patient had been diagnosed with WD for over 20 years prior to establishing care in our Hepatology Clinic. During his initial course, he was transitioned from penicillamine to zinc due to evidence suggesting penicillamine had greater adverse effects in the long term. Later, he was switched to trientine. His liver enzymes and 24-hour urine copper were monitored. During these years, he intermittently had some financial hardship, requiring him to be on penicillamine rather than trientine. He also had developed acute kidney injury. Overall, his liver disease remained under control and he never had signs of decompensated cirrhosis, but had fluctuations of liver enzymes over the years. Conclusion. Anti-copper treatment for WD has to be tailored to medication side effects profile, patient's chronic and emerging comorbidities, as well as costs. Transitioning regimens is often challenging, and it requires closer monitoring, with no predictors of response.

Real-world prescribing and switching patterns of non-calcium containing phosphate binders in dialysis patients in South Korea
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OBJECTIVE: Non-calcium containing phosphate binders (non-CPBs) are useful for the treatment of hyperphosphatemia without a concern of hypercalcemia in patients undergoing dialysis. However, due to their relatively high cost, prescribing non-CPBs is restricted in South Korea. This study was conducted to investigate prescribing patterns, especially switching between CPBs and non-CPBs, in dialysis patients in a real-world setting. MATERIALS AND METHODS: This is an observational study using the National Health Insurance Service claim data. The study population included patients who initiated dialysis between July 2012 and June 2013 and were prescribed phosphate binders at least once during the observation period (2012 - 2016) (n = 10,073). Medication costs and prescribing patterns including switching of phosphate binders were investigated. RESULTS: Compared with the first year of dialysis, the costs of phosphate binders more than doubled during the 4th year of dialysis (from US$ 28.4 to US$ 60.1), largely due to an increase in the cost of non-CPBs (from US$ 117.5 to US$ 237.8). Many patients continued to change drugs between CPBs and non-CPBs. The continuous prescription period of CPBs was shortened each time a drug was changed. A total of 551 patients (13.4%) changed their medication three times between CPBs and non-CPBs. CONCLUSION: Over time on dialysis, use of non-CPB increased and medication costs increased accordingly. Many patients continued to change drugs between CPBs and non-CPBs due to the restricted criteria of the health insurance. Further outcome research is necessary to evaluate the appropriateness of the clinical practice in which CPBs and non-CPBs are alternately used.

A systematic review of the economic evaluations of non-calcium-containing phosphate binders, sevelamer and Lanthanum, in end-stage renal disease patients with hyperphosphatemia.

INTRODUCTION: End-stage renal disease is associated with significant comorbidity and mortality. Among its implications, hyperphosphatemia constitutes a consistent and independent risk factor. The use of benchmark treatment, low-cost calcium-based binders declined due to a potential calcification effect on coronary arteries. AREAS COVERED: Given the increasing prevalence of end-stage renal disease and the high cost of hyperphosphatemia's new primary modality, the non-calcium based phosphate binders, we set-off to systematically assess the economic evaluations of non-calcium containing phosphate binders, sevelamer and lanthanum. The study was performed based on a systematic review of the economic evaluations of sevelamer and lanthanum. The cost-effectiveness profile of the two non-calcium-containing Phosphate Binders compared to calcium-based phosphate binders depends on several factors such as future dialysis costs, utility values, age, survival, and phosphorus levels. EXPERT OPINION: The comparison between the two agents is rather inconclusive; nevertheless, current review suggests that non-calcium-based phosphate binders may yield a positive cost-effectiveness ratio in patients with inadequate phosphorus management and patient with longer life-expectancy. It is crucial that the literature is endowed with more data, specifically on survival, future dialysis costs, and calcification.

Cost Effectiveness of Hematopoietic Stem Cell Transplantation Compared with Transfusion Chelation for Treatment of Thalassemia Major.

Hematopoietic stem cell transplantation (HSCT) is the only cure for thalassemia major (TM), which inflicts a significant 1-time cost. Hence, it is important to explore the cost effectiveness of HSCT versus lifelong regular transfusion-chelation (TC) therapy. This study was undertaken to estimate incremental cost per quality-adjusted life-year (QALY) gained with the intervention group HSCT, and the comparator group TC, in TM patients. A combination of decision tree and Markov model was used for analysis. A hospital database, supplemented with a review of published literature, was used to derive input parameters for the model. A lifetime study horizon was used and future costs and consequences were discounted at 3%. Results are presented using societal perspective. Incremental cost per QALY gained with use of HSCT as compared with TC was 64,096 (US$986) in case of matched related donor (MRD) and 1,67,657 (US$2579) in case of a matched unrelated donor transplantation. The probability of MRD transplant to be cost effective at the willingness to pay threshold of Indian per capita gross domestic product is 94%. HSCT is a long-term value for money intervention that is highly cost effective and its long-term clinical and economic benefits outweigh those of TC.

Cost-Effectiveness of First-Line Sevelamer and Lanthanum versus Calcium-Based Binders for Hyperphosphatemia of Chronic Kidney Disease.

BACKGROUND: Phosphate binders are used to treat hyperphosphatemia among patients with chronic kidney disease (CKD). OBJECTIVES: To conduct an economic evaluation comparing calcium-free binders sevelamer and lanthanum with calcium-based binders for patients with CKD. METHODS: Effectiveness data were obtained from a recent meta-analysis of randomized trials. Effectiveness was measured as life-years gained and translated to quality-adjusted life-years (QALYs) using utility weights from the literature. A Markov model consisting of non-dialysis-dependent (NDD)-CKD, dialysis-dependent (DD)-CKD, and death was developed to estimate the incremental costs and effects of sevelamer and lanthanum versus those of calcium-based binders. A lifetime horizon was used and both costs and effects were discounted at 1.5%. All costs are presented in 2015 Canadian dollars from the Canadian public payer perspective. Results of probabilistic sensitivity analysis were presented using cost-effectiveness acceptability curves. Sensitivity analyses were conducted for risk pooling methods, omission of dialysis costs, and persistence of drug effects on mortality. RESULTS: Sevelamer resulted in an incremental cost-effectiveness ratio of $106,522/QALY for NDD-CKD and $133,847/QALY for DD-CKD cohorts. Excluding dialysis costs, sevelamer was cost-effective in the NDD-CKD cohort ($5,847/QALY) and the DD-CKD cohort ($11,178/QALY). Lanthanum was dominated regardless of whether dialysis costs were included. CONCLUSIONS: Existing evidence does not clearly support the cost-effectiveness of non-calcium-containing phosphate binders (sevelamer and lanthanum) relative to calcium-containing phosphate binders in DD-CKD patients. Our study suggests that sevelamer may be cost-effective before dialysis onset. Because of the remaining uncertainty in several clinically relevant outcomes over time in DD-CKD and NDD-CKD patients, further research is encouraged.

A Decision-Analytic Model to Assess the Cost-Effectiveness of Etelcalcetide vs. Cinacalcet.

INTRODUCTION: Etelcalcetide is a novel intravenous calcimimetic for the treatment of secondary hyperparathyroidism (SHPT) in haemodialysis patients. The clinical efficacy and safety of etelcalcetide (in addition to phosphate binders and vitamin D and/or analogues [PB/VD]) was evaluated in three phase III studies, including two placebo-controlled trials and a head-to-head study versus the oral calcimimetic cinacalcet. OBJECTIVE: The objective of this study was to develop a decision-analytic model for economic evaluation of etelcalcetide compared with cinacalcet. METHODS: We developed a life-time Markov model including potential treatment effects on mortality, cardiovascular events, fractures, and subjects' persistence. Long-term efficacy of etelcalcetide was extrapolated from the reduction in parathyroid hormone (PTH) in the phase III trials and the available data from the outcomes study in cinacalcet (EVOLVE trial). Etelcalcetide was compared with cinacalcet, both in addition to PB/VD. We applied unit costs averaged from five European countries and a range of potential etelcalcetide pricing options assuming parity price to weekly use of cinacalcet and varying it by a 15 or 30% increase. RESULTS: Compared with cinacalcet, the incremental cost-effectiveness ratio of etelcalcetide was €1,355 per QALY, €24,521 per QALY, and €47,687 per QALY for the three prices explored. The results were robust across the probabilistic and deterministic sensitivity analyses. CONCLUSIONS: Our modelling approach enabled cost-utility assessment of the novel therapy for SHPT based on the observed and extrapolated data. This model can be used for local adaptations in the context of reimbursement assessment.

Maintenance zinc therapy after initial penicillamine chelation to treat symptomatic hepatic Wilson's disease in resource constrained setting.

BACKGROUND: Experience with zinc in treating symptomatic hepatic Wilson's disease (WD) is limited. AIM: To study the efficacy of Penicillamine followed by zinc in treating symptomatic hepatic Wilson's disease. METHODS: We retrospectively analyzed case records of 31 symptomatic hepatic WD patients for whom disease severity scores (Child's, model for end-stage liver disease (MELD), Nazer's, and New Wilson Index (NWI) score) and 24-h urinary copper were compared at 3-time points-baseline at presentation, at transition from penicillamine to zinc and at end of follow up. RESULTS: Thirty-one patients (median age 11 [5-24] years) with symptomatic hepatic WD were studied; ten had associated neuropsychiatric manifestations of WD. Penicillamine was changed to zinc sulfate either due to financial constraints (28 patients) or due to adverse effects of penicillamine (3 patients). At presentation (baseline), six patients belonged to Child's class A, five to Child's B, and 17 to Child's C. Duration of initial penicillamine chelation therapy was 134 (2-320) weeks, and of subsequent zinc therapy was 363 (35-728) weeks. There was a significant improvement in liver function tests and disease severity scores (Child's, MELD, Nazer's, and NWI score) at the transition from penicillamine to zinc compared to baseline. This improvement was maintained until the end of study period with 90% survival at 10 (2-20) years. Fifteen of the 17 Child's C cirrhotic patients showed significant improvement in disease severity scores from baseline until end of follow up. CONCLUSIONS: Penicillamine followed by zinc may be a safe and effective treatment in resource-constrained setting for symptomatic hepatic WD patients in all grades of baseline disease severity. Some patients with decompensated cirrhosis due to WD may be managed with medical treatment, avoiding liver transplantation.

A Real-world Cost-effectiveness Analysis of Sevelamer Versus Calcium Acetate in Korean Dialysis Patients.

PURPOSE: Sevelamer, a noncalcium phosphate binder, has been shown to attenuate the progression of vascular calcification and improve survival in patients with chronic kidney disease undergoing dialysis compared with calcium-based binders. Using real-world data from a cohort study and the Health Insurance Review and Assessment Service database, we conducted a cost-effectiveness analysis comparing sevelamer with calcium acetate in dialysis patients from the perspective of the National Health Insurance Service in South Korea. METHODS: Data (demographic, diagnostic, laboratory, and survival) from 4674 patients undergoing dialysis enrolled in a multicenter prospective cohort study conducted in South Korea between September 2008 and December 2012 were linked to phosphate binder use, hospitalization, and cost data available from the Health Insurance Review and Assessment Service database. After propensity score matching, a dataset comprising comparable patients treated with either sevelamer (n = 501) or calcium acetate (n = 501) was used in the cost-effectiveness analysis. A Markov model was used to estimate costs, life years, quality-adjusted life years (QALYs), and cost-effectiveness over each patient's lifetime. Forty-month treatment-specific overall survival (OS) data available from the dataset were extrapolated to lifetime survival with the use of regression analysis. FINDINGS: Patients had a mean age of 56.3 years and were treated with dialysis for a mean duration of 67.6 months. Compared with calcium acetate, sevelamer was associated with an incremental cost of South Korean Won (₩) 12,246,911 ($10,819) and a gain of 1.758 life years and 1.108 QALYs per patient. This outcome yielded incremental cost-effectiveness ratios of ₩6,966,350 ($6154) and ₩11,057,699 ($9768) per life year and QALY gained, respectively. Conclusions regarding sevelamer's cost-effectiveness were insensitive to alternative assumptions in time horizon, discount rate, hospitalization rate, costs, and health utility estimates, and they remained consistent in 100% of the model iterations, considering a willingness-to-pay threshold of ₩31,894,720 ($28,176) per QALY gained. IMPLICATIONS: This analysis of real-world data found that sevelamer's higher cost relative to calcium acetate was adequately offset by improved survival among patients undergoing dialysis in South Korea. As such, sevelamer offers good value for money, representing a cost-effective alternative to calcium-based binders.

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.

Incremental cost-utility of sevelamer relative to calcium carbonate for treatment of hyperphosphatemia among pre-dialysis chronic kidney disease patients.

BACKGROUND: Sevelamer is an alternative to calcium carbonate for the treatment of hyperphosphatemia among non-dialysis dependent patients with chronic kidney disease (CKD). Although some studies show that it may reduce mortality and delay the onset of dialysis when compared to calcium carbonate, it is also significantly more expensive. Prior studies looking at the incremental cost-effectiveness of sevelamer versus calcium carbonate in pre-dialysis patients are based on data from a single clinical trial. The goal of our study is to use a wider range of clinical data to achieve a more contemporary and robust cost-effectiveness analysis. METHODS: We used a Markov model to estimate the lifetime costs and quality-adjusted life years (QALYs) gained for treatment with sevelamer versus calcium carbonate. The model simulated transitions among three health states (CKD not requiring dialysis, end-stage renal disease, and death). Data on transition probabilities and utilities were obtained from the published literature. Costs were calculated from a third party payer perspective and included medication, hospitalization, and dialysis. Sensitivity analyses were also run to encompass a wide range of assumptions about the dose, costs, and effectiveness of sevelamer. RESULTS: Over a lifetime, the average cost per patient treated with sevelamer is S$180,724. The estimated cost for patients treated with calcium carbonate is S$152,988. A patient treated with sevelamer gains, on average, 6.34 QALYs relative to no treatment, whereas a patient taking calcium carbonate gains 5.81 QALYs. Therefore, sevelamer produces an incremental cost-effectiveness ratio (ICER) of S$51,756 per QALY gained relative to calcium carbonate. CONCLUSION: Based on established benchmarks for cost-effectiveness, sevelamer is cost effective relative to calcium carbonate for the treatment of hyperphosphatemia among patients with chronic kidney disease initially not on dialysis.

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.

Effectiveness of activated carbon and Egyptian montmorillonite in the protection against deoxynivalenol-induced cytotoxicity and genotoxicity in rats.

This study was conducted to prepare and characterize activated carbon (AC) and to evaluate its protective effect against deoxynivalenol (DON) toxicity in rats compared to Egyptian montmorillonite (EM). AC was prepared using a single-step chemical activation with phosphoric acid (H3PO4). The resulted AC has a high surface area and a high total pore volume. Male Sprague-Dawley rats were divided into 6 groups (n = 10) and treated for 3 weeks as follow: the control group, the groups fed AC or EM-supplemented diet (0.5% w/w), the group treated orally with DON (5 mg/kg b.w.) and the groups fed AC or EM-supplemented diet and treated with DON. Blood and liver samples were collected for different analyses. Treatment with DON increased liver function enzymes, lipid peroxidation, tumor necrosis factor α, DNA fragmentation, decreased hepatic glutathione content, up regulating mRNA Fas and TNF-α genes expression and increased micronucleated polychromatic erythrocytes and normochromatic erythrocytes in bone marrow. Co-treatment of DON plus AC or EM succeeded to normalize the levels of the biochemical parameters, reduced the cytotoxicity of bone marrow and ameliorated the hepatic genotoxicity. Moreover, AC was more effective than EM and has a high affinity to adsorb DON and to reduce its cytotoxicity and genotoxicity.

The cost-effectiveness of drug therapies to treat secondary hyperparathyroidism in renal failure: a focus on evidence regarding paricalcitol and cinacalcet.

The present review aims to assess the state-of-the-art regarding cost-effectiveness of therapy for secondary hyperparathyroidism in order to identify the best treatment and review methodological issues. PubMed and the Cochrane Library were searched to identify papers performing comparative analysis of costs and effects of treatment for secondary hyperparathyroidism in adult patients. Among the 66 papers identified, only 10 were included in the analysis. Treatment strategies evaluated in the selected papers were: cinacalcet in addition to vitamin D and phosphate binders versus vitamin D and phosphate binders only (seven papers), paricalcitol versus non-selective vitamin D (two papers), early and late introduction of cinacalcet in addition to vitamin D and phosphate binders (one paper) and paricalcitol versus cinacalcet (one paper). The high degree of heterogeneity among alternative treatments and methodological limits related to cost items considered, resource valuation methods and so on, make it unfeasible to reach a definite conclusion regarding cost-effectiveness but allow for future research opportunities.

Managing oral phosphate binder medication expenditures within the Medicare bundled end-stage renal disease prospective payment system: economic implications for large U.S. dialysis organizations.

BACKGROUND: From January 2016, payment for oral-only renal medications (including phosphate binders and cinacalcet) was expected to be included in the new Medicare bundled end-stage renal disease (ESRD) prospective payment system (PPS). The implementation of the ESRD PPS has generated concern within the nephrology community because of the potential for inadequate funding and the impact on patient quality of care. OBJECTIVE: To estimate the potential economic impact of the new Medicare bundled ESRD PPS reimbursement from the perspective of a large dialysis organization in the United States. METHODS: We developed an interactive budget impact model to evaluate the potential economic implications of Medicare payment changes to large dialysis organizations treating patients with ESRD who are receiving phosphate binders. In this analysis, we focused on the budget impact of the intended 2016 integration of oral renal drugs, specifically oral phosphate binders, into the PPS. We also utilized the model to explore the budgetary impact of a variety of potential shifts in phosphate binder market shares under the bundled PPS from 2013 to 2016. RESULTS: The base model predicts that phosphate binder costs will increase to $34.48 per dialysis session in 2016, with estimated U.S. total costs for phosphate binders of over $682 million. Based on these estimates, a projected Medicare PPS $33.44 reimbursement rate for coverage of all oral-only renal medications (i.e., phosphate binders and cinacalcet) would be insufficient to cover these costs. A potential renal drugs and services budget shortfall for large dialysis organizations of almost $346 million was projected. CONCLUSIONS: Our findings suggest that large dialysis organizations will be challenged to manage phosphate binder expenditures within the planned Medicare bundled rate structure. As a result, large dialysis organizations may have to make treatment choices in light of potential inadequate funding, which could have important implications for the quality of care for patients with ESRD.

[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.

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.

Cost-minimization analysis of lanthanum carbonate versus sevelamer hydrochloride in US patients with end-stage renal disease.

PURPOSE: Sevelamer hydrochloride (SH) and lanthanum carbonate (LC) are calcium-free phosphate binders used in the clinical management of hyperphosphatemia in patients with end-stage renal disease (ESRD). The objective of this analysis was to assess the cost-effectiveness of LC monotherapy compared with SH monotherapy in US patients with ESRD in a clinical practice setting. METHODS: This was a post hoc assessment of phosphate binder costs among US patients with ESRD who converted from SH to LC monotherapy in a previously published, 16-week, Phase IV, real-world study. Calculations of drug costs used both average wholesale price (AWP) and wholesale acquisition cost (WAC). FINDINGS: There were 953 patients with available baseline SH dose data; 950 also had a recorded LC dose >0 mg at baseline, and 691 had dose data available for both SH at baseline and LC at week 16 (post hoc analysis population). Baseline demographic characteristics were similar in excluded patients and the post hoc analysis population. Mean (SD) serum phosphate levels were 5.91 (1.66) mg/dL at baseline and 5.93 (1.85) mg/dL after conversion to LC monotherapy for 16 weeks. Mean AWP costs were US$35.72 (16.89) per day at baseline and US$24.69 (8.28) per day at week 16, yielding an overall mean cost change (defined as LC cost - SH cost) of -US$11.03 (16.37) per day in favor of LC. The overall mean WAC cost change was -US$9.17 (13.64) per day. Within baseline SH dose subgroups 2400 to 4800, >4800 to 7200, >7200 to 9600, and >9600 mg/d, the mean AWP cost change ranged from US$2.78 (9.26) per day in favor of SH for the 2400- to 4800-mg/d subgroup to -US$33.15 (12.58) per day in favor of LC for the >9600-mg/d subgroup. Mean WAC cost changes showed a similar trend, ranging from US$2.33 (7.72) per day to -US$27.59 (10.48) per day. Linear regression analyses revealed that the inflection SH doses corresponding to a mean cost change of zero were 4905 mg/d (AWP) and 4908 mg/d (WAC). For the 455 (66%) patients in the post hoc analysis population who had baseline SH doses at least as high (≥ 5600 mg/d) as these point estimates, the mean SH:LC tablet ratio was ≥ 3.7, indicating a mean reduction in the tablet burden after conversion to LC of ≥ 73%. IMPLICATIONS: This real-world assessment of comparative phosphate binder drug costs between SH and LC among US patients with ESRD indicates that average cost savings with LC use increased with increasing SH doses. Conversion to LC from SH ≥ 5600 mg/d reduced drug costs and tablet burden while maintaining serum phosphate levels.