title: The real-world dose-relativity of sevelamer hydrochloride and lanthanum carbonate monotherapy in patients with end-stage renal disease.
abstract: BACKGROUND
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Spica Consultants, Marlborough, UK, rosamund@spicaconsultants.com.
authors.forename: Rosamund J
authors.initials: RJ
authors.lastname: Wilson
authors.forename: Michael S
authors.initials: MS
authors.lastname: Keith
authors.forename: Peter
authors.initials: P
authors.lastname: Preston
authors.forename: J Brian
authors.initials: JB
authors.lastname: Copley
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005069:Evaluation Studies as Topic; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D054559:Hyperphosphatemia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy* / Q000628:therapy; D007811:Lanthanum / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011073:Polyamines / Q000008:administration & dosage*; D006435:Renal Dialysis / Q000009:adverse effects / Q000379:methods; D018570:Risk Assessment; D000069603:Sevelamer; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D011073:Polyamines; C119467:lanthanum carbonate; D007811:Lanthanum; D000069603:Sevelamer