Clinical effectiveness and cost-utility analysis of phosphate binders for treating hyperphosphatemia in end-stage renal disease patients : a multicenter real-world study

Abstract

Uncontrolled hyperphosphatemia in end-stage renal disease (ESRD) patients increases the risk of cardiovascular disease (CVD), bone disorders, and mortality. Phosphate binders (PBs) are recommended as a treatment option. Calcium-based PBs (CBPBs) had significantly higher all-cause mortality rates compared to non-calcium-based PBs (NCBPBs). However, their effects on individuals are still controversial. The risk of CVD and bone disorders has not been sufficiently considered due to a lack of published data with short follow-up, as well as the cost-utility of individual NCBPBs compared to CBPBs in Thailand has not been sufficiently considered. This study aimed to determine the clinical effectiveness of any PBs on all-cause mortality, CVD events, and bone disorders, as well as to perform cost-utility analysis of NCBPBs as a second-line treatment compared to CBPBs in Thai ESRD patients. Data from Ramathibodi Hospital and Bhumibol Adulyadej Hospital were used to estimate clinical effectiveness and recruited adult ESRD patients with hyperphosphatemia who were receiving PBs between January 2010 and July 2020. Four treatment approaches, i.e., intention-to-treat (ITT), modified ITT, per-protocol (PP), and second-line pattern, were designed to deal with various prescription patterns in real-world practice. The treatment effect model was applied to estimate treatment effects. A cross-sectional survey and a model-based economic evaluation were conducted to determine the economic outcome. Utility data were collected using questionnaires. Incremental cost-effectiveness ratios and incremental net benefits were presented according to the societal perspective. A total of 8,005 patients were included in the analysis, of which 54.2% received PBs in initiation, comprising CBPBs (n=4,071), lanthanum (n=60), sevelamer (n=58), and aluminum hydroxide (n=80). Our primary findings indicated that initiating with CBPBs (i.e., with or without adding on/switching to NCBPBs) resulted in a longer OS and time to CVD and an increased risk of bone disorders when compared to no-PBs. Due to the small number of patients who started NCBPBs, initial estimates were less precise. In patients who had initially received CBPBs, the results indicated that patients who received the treatment pattern with CBPBs-sevelamer had the longest OS, followed by CBPBs-lanthanum, CBPBs-aluminum, and CBPBs-CBPBs, with an average OS of 15.1, 13.6, 11.0, and 10.9 years, respectively, but the differences were not statistically significant. The average time to CVD was the longest in patients who received CBPBs-lanthanum, followed by CBPBs-sevelamer, and CBPBs-CBPBs, respectively. Patients who received CBPBs-CBPBs had the longest time to develop bone disorders, followed by CBPBs-sevelamer, CBPBs-lanthanum, and CBPBs-aluminum. However, none of the findings were statistically significant. Finally, the study suggested that sevelamer and lanthanum were not cost-effective as second-line options compared with CBPBs, with an ICER of 669,080 and 1,212,317 Baht per QALY gained, respectively. Further observational cohort studies with a larger sample size in individual NCBPBs are needed to answer this research question to resolve this clinical unmet need situation. Additionally, subgroup analyses by hypercalcemia or dialysis patients would be an added advantage.