Health-Economic Comparison of Paricalcitol, Calcitriol and Alfacalcidol for the Treatment of Secondary Hyperparathyroidism during Haemodialysis

Hubertus Rosery; Rito Bergemann; Steven E. Marx; Axel Boehnke; Joel Melnick; Raimund Sterz; Laura Williams


Clin Drug Invest. 2006;26(11):629-638. 

In This Article

Abstract and Introduction


This study evaluated the health-economic consequences of use of intravenous paricalcitol (Zemplar®), oral calcitriol or oral and intravenous alfacalcidol for the treatment of patients with secondary hyperparathyroidism, focusing on a third-party payer perspective through inclusion of medication and hospital costs, survival rates and utilities. Cost values were based on German treatment recommendations and prices. Reference values for survival rates and utilities were based on the results of a MEDLINE search. The analysis showed a clear advantage for intravenous paricalcitol with respect to costs, effectiveness and utilities compared with treatment with oral calcitriol or intravenous alfacalcidol. Since the results were very cost sensitive with respect to selected diagnosis-related groups (DRGs) for kidney disease with dialysis, a sensitivity analysis was performed. This demonstrated first-order dominance of intravenous paricalcitol for a wide range of hospitalisation costs. In conclusion, this analysis suggested a clear benefit from the perspective of a third-party payer for intravenous paricalcitol compared with oral calcitriol and intravenous alfacalcidol in the treatment of patients with secondary hyperparathyroidism.

1. Introduction

Secondary hyperparathyroidism is a common consequence of chronic kidney disease, presenting in more than half of patients with end-stage renal disease.[1,2,3] As chronic kidney disease progresses, there is decreased capacity of the kidney to produce 1,25-dihydroxycholecalciferol (the active metabolite of vitamin D, also known as calcitriol) and to excrete phosphorus, both of which may lead to decreased serum calcium. These three factors – low serum calcium, elevated serum phosphorus and reduced levels of calcitriol – independently comprise the main causes for increased synthesis and release of parathyroid hormone (PTH) in patients with chronic kidney disease. Between 40% and 80% of patients undergoing haemodialysis have PTH levels above the recommended guideline[4] target level of 150–300 pg/mL.[5,6] Application of these data to the prevalence of haemodialysis patients in Germany[7] suggests that the prevalence of secondary hyperparathyroidism in the general population is 426 patients per million or 0.042%.

Elevated PTH levels results in excessive bone turnover, which subsequently leads to renal osteo-dystrophy.[3,8] To prevent excess bone turnover, active vitamin D, calcitriol and analogues, mainly alfacalcidol, have been used in end-stage renal disease patients undergoing dialysis in Germany. These vitamin D compounds reduce PTH synthesis[9] and increase absorption of calcium in the intestines.[10] However, these treatments have been associated with hypercalcaemia, hyperphosphataemia and elevated calcium-phosphorus product (Ca × P).[11] These adverse effects are associated with soft tissue and vascular calcification,[12,13,14] leading to cardiovascular disease, which is thought to be a key factor in explaining the increased (10- to 30-fold) cardiovascular mortality among patients with chronic kidney disease relative to the general population.[15] Furthermore, cardiovascular mortality is the primary cause of death in patients on dialysis.[15]

In order to minimise these undesirable effects, vitamin D analogues with less calcaemic activity have been developed. Paricalcitol is a third-generation vitamin D analogue that lacks the exocyclic carbon at position 19 and acts as a selective vitamin D receptor activator.[16,17] Pivotal randomised controlled trials with intravenous paricalcitol conducted in haemodialysis patients have demonstrated a significant decrease in serum intact PTH (iPTH), a significant reduction in serum alkaline phosphatase (suggesting improvement in bone health), and minimal impact on serum calcium, phosphorus and Ca × P product compared with placebo.[18,19,20] Recently, Teng et al. reported a 20% survival benefit associated with use of activated vitamin D in end-stage renal disease patients on dialysis.[21] Furthermore, studies have shown improved mortality (significantly higher survival rate) and morbidity (fewer hospitalisations per year and fewer hospital days per year) in patients in whom secondary hyperparathyroidism was treated with paricalcitol compared with those treated with calcitriol.[22,23] Additionally, patients treated with paricalcitol achieved faster rates of PTH suppression compared with calcitriol.[24]

We hypothesised that use of intravenous paricalcitol in end-stage renal disease patients with secondary hyperparathyroidism would reduce healthcare-related costs from a third-payer perspective more effectively than use of calcitriol or alfacalcidol. To date, no published cost-effectiveness studies have compared intravenous paricalcitol to calcitriol or alfacalcidol; therefore, in an effort to determine the most cost-effective regimen for treating end-stage renal disease patients with secondary hyperparathyroidism on dialysis, we developed a cost-consequence analysis, supplemented by a cost-effectiveness analysis and a cost-utility analysis. In each of the three analyses, 1-year costs related to drug therapy and all-cause hospitalisations for paricalcitol, calcitriol and alfacalcidol therapy were compared.


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