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The Real-World Dose-Relativity of Sevelamer Hydrochloride and Lanthanum Carbonate Monotherapy in Patients with End-Stage Renal Disease

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Abstract

Introduction

Sevelamer hydrochloride (SH) and lanthanum carbonate (LC) are calcium-free phosphate binders used for the management of hyperphosphatemia in patients with end-stage renal disease (ESRD). The objective of this analysis was to evaluate the real-world dose-relativity between SH and LC monotherapy in US patients with ESRD.

Methods

This was a post hoc analysis of a 16-week, real-world study (Vemuri et al. in BMC Nephrol 12:49, 2011) of the efficacy of conversion to LC monotherapy from other phosphate binders. The SH:LC dose-relativity ratio, based on the mean daily dose, was calculated in the subset of patients from the Vemuri study who converted from SH to LC monotherapy and had available SH and LC dose data.

Results

A total of 950 patients converted from SH to LC monotherapy and had recorded dose data. The post hoc analysis population comprised 691 patients with available dose data for both SH at baseline and LC at week 16. The mean (SD) serum phosphate level at baseline was 5.91 (1.66) mg/dL. After conversion to LC monotherapy for 16 weeks, the mean (SD) serum phosphate level was 5.93 (1.85) mg/dL. The mean (SD) daily baseline SH dose was 7,703 (3,642) mg and the mean (SD) daily LC dose at week 16 was 2,800 (939) mg (9.6 versus 2.8 tablets, respectively; P < 0.0001), resulting in a SH:LC dose-relativity ratio of 2.8. The median individual patient SH:LC dose-relativity ratio was 2.6 (95% CI 2.6–2.8). Across baseline SH dose subgroups (2,400–4,800, >4,800–7,200, >7,200–9,600, and >9,600 mg/day), the mean daily SH dose was 4,051, 7,047, 9,253, and 13,150 mg, respectively. In comparison, the mean daily LC dose was 2,445–3,156 mg. Thus, patients requiring baseline SH doses >7,200 mg/day (41% of the analysis population) had higher SH:LC dose-relativity ratios of 3.1–4.2 (median individual patient ratios 3.1–4.0).

Conclusion

In this post hoc analysis of real-world dose-relativity, the overall SH:LC dose-relativity ratio was 2.8 (median individual patient ratio 2.6 (95% CI 2.6–2.8). These findings are consistent with the World Health Organization-defined daily dose and previous studies of the relative phosphate binding capacity of the two drugs. Patients requiring SH doses >7,200 mg/day had higher SH:LC dose-relativities of 3.1–4.2 (median individual patient ratios 3.1–4.0). These findings have implications for the tablet burden and cost-effectiveness of SH and LC in the treatment of hyperphosphatemia.

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Acknowledgments

Funding for study design, analysis, and article-processing charges was provided by Shire Development LLC. Writing and editorial support was provided by Fernando Gibson, an employee of PharmaGenesis™ London, with funding from Shire Development LLC. All authors meet the ICMJE criteria for authorship and no deserving authors have been omitted. Rosamund J. Wilson is the guarantor for this article and takes responsibility for the integrity of the work as a whole.

Conflict of interest

Rosamund J. Wilson is a consultant to Shire.

Michael S. Keith is an employee of Shire.

Peter Preston is a consultant to Shire.

J. Brian Copley is an employee of Shire.

Compliance with ethics guidelines

The study (ClinicalTrials.gov Identifier: NCT00160121) was performed in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 and 2008. All patients provided written, informed consent before being included in the study. The study protocol was approved by an Institutional Review Board at each center.

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Authors and Affiliations

  1. Spica Consultants, Marlborough, UK

    Rosamund J. Wilson

  2. Shire, Wayne, PA, USA

    Michael S. Keith, Peter Preston & J. Brian Copley

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  1. Rosamund J. Wilson
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Correspondence to Rosamund J. Wilson.

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Wilson, R.J., Keith, M.S., Preston, P. et al. The Real-World Dose-Relativity of Sevelamer Hydrochloride and Lanthanum Carbonate Monotherapy in Patients with End-Stage Renal Disease. Adv Ther 30, 1100–1110 (2013). https://doi.org/10.1007/s12325-013-0077-5

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