Sevelamer hydrochloride oral capsule.
Patients with end-stage renal disease (ESRD) and hyperphosphatemia
Traditional (calcium-based) phosphate binders may not be perceived as suitable for controlling hyperphosphatemia in all patients because of theoretical concerns about their use, and dose-limiting hypercalcemia. Sevelamer is the first non-calcium-based phosphate binder to receive Health Canada approval. Given a large differential cost between this new agent and traditional therapies, the appropriate use of this new therapy requires examination.
Methods and Results
We did a systematic review to identify relevant literature, by searching multiple databases using a defined strategy, and by hand searching relevant journals. Evidence of efficacy was determined from randomized controlled trials (RCTs). Evidence of harm was determined from trials or registries where data was gathered prospectively. Ten RCTs with a total of 3,025 participants were included in the efficacy analysis; 28 prospective trials with a total of 3,983 participants were identified and eligible for the review of harm. One unpublished, randomized, unblinded study of 2,103 dialysis patients was designed to measure overall survival and cardiovascular mortality.
Implications for Decision Making
- Sevelamer has no demonstrated effect on health outcomes compared with calcium-based phosphate binders. There was no convincing evidence that substituting sevelamer for calcium-based binders reduced all-cause mortality, cardiovascular mortality, hospitalization, or the frequency of symptomatic bone disease, and no evidence that sevelamer improved quality of life. Sevelamer therapy results in a smaller decrease in phosphate levels, and fewer episodes of hypercalcemia of unknown clinical significance, compared with calcium-based phosphate binders.
- There is uncertainty regarding the cost effectiveness of sevelamer. Even if sevelamer is assumed to be more effective than calcium-based phosphate binders, it is associated with a cost per quality-adjusted life year gained ranging from $127,000 to $278,100. It is possible that sevelamer use, restricted to patients ≥65 years old, might be more economically efficient, but improved effectiveness in this group requires confirmation from future studies.
- Funding sevelamer will require additional resources. The difference in cost per patient between calcium carbonate and sevelamer at usual daily doses is $4,127 annually. Substituting sevelamer for calcium carbonate for all patients with ESRD in Canada would increase expenditures by $70,620,616 annually. Restricting access to those ≥65 years old, or based on biochemical criteria, results in increased expenditures between $14,712,628 and $36,016,514.
This summary is based on a comprehensive health technology assessment available from CADTH’s web site (www.cadth.ca): Manns B, Tonelli M, Shrive F, Wiebe N, Klarenbach S, Lee H, Culleton B. Sevelamer in patients with end-stage renal disease: a systematic review and economic evaluation.