Costs Associated With Intravenous Darbepoetin Versus Epoetin Therapy in Hemodialysis Patients: A Randomized Controlled Trial

Andrea L Woodland, Sean W Murphy, Bryan M Curtis, Brendan J Barrett, Andrea L Woodland, Sean W Murphy, Bryan M Curtis, Brendan J Barrett

Abstract

Background: Anemia of chronic kidney disease is associated with adverse outcomes and a reduced quality of life. Erythropoiesis-stimulating agents (ESAs) have improved anemia management, and 2 agents are available in Canada, epoetin alfa (EPO) and darbepoetin alfa (DA). EPO and DA are considered equally effective in achieving target hemoglobin (Hb), but it is not clear whether there is a cost difference. There have been few head-to-head comparisons; most published studies are observational switch studies.

Objective: To compare the cost of DA and EPO and to determine the dose conversion ratio over a 12-month period.

Design: Randomized controlled trial.

Setting: Canadian outpatient hemodialysis center.

Patients: Eligible patients were adult hemodialysis patients requiring ESA therapy.

Measurements: The primary outcome was ESA cost (Can$) per patient over 12 months. Secondary outcomes included the dose conversion ratio, deviation from target ranges in anemia indices, iron dose and cost, and time and number of dose changes.

Methods: An open-label randomized controlled trial of intravenous (IV) DA versus EPO was conducted in 50 hemodialysis patients. Participants underwent a minimum 6-week run-in phase followed by a 12-month active study phase. ESA and iron were dosed using a study algorithm.

Results: The median cost was $4179 (interquartile range [IQR]: $2416-$5955) for EPO and $2303 (IQR: $1178-$4219) for DA with a difference of $1876 (P = .02). The dose conversion ratio was 280:1 (95% confidence interval [CI]: 197-362:1) at the end of the run-in phase, 360:1 (95% CI: 262-457:1) at the 3-month point of the active phase, and 382:1 (95% CI: 235-529:1) at the 6-month point of the active phase. There were no significant differences between the 2 groups in weekly iron dose, Hb, serum ferritin, or transferrin saturation. The number of dose changes and the time to Hb stability were similar.

Limitations: Results may not be generalizable to hemodialysis units without algorithm-based anemia management, with subcutaneous ESA administration, or to the nondialysis chronic kidney disease population. The effective conversion ratio between EPO and DA is known to increase at higher doses; the Hb targets used in the study were slightly higher than those recommended today so it is possible that the doses used were also higher. Because of this, the cost savings estimated for DA could differ somewhat from the savings realizable in current practice.

Conclusions: In this study of hemodialysis patients with comparable anemia management, IV DA cost $1876 less per year per patient than IV EPO. The dose conversion ratio was greater than 350:1 by the 3-month point.

Trial registration: ClinicalTrials.gov (NCT02817555).

Keywords: anemia; darbepoetin alfa; drugs and dialysis; epoetin alfa; erythropoiesis-stimulating agent.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Patient flow. Note. ESA = erythropoiesis-stimulating agent; EPO = epoetin alfa; DA = darbepoetin alfa; PD = peritoneal dialysis; HD = hemodialysis; PTH = parathyroid hormone.
Figure 2.
Figure 2.
Mean hemoglobin (±SD) run-in phase.
Figure 3.
Figure 3.
Mean hemoglobin (±SD) active phase.
Figure 4.
Figure 4.
Sensitivity analysis of costs with varying dose conversion ratios. Note. ESA = erythropoiesis-stimulating agent.

References

    1. Fishbane S, Nissenson AR. Anemia management in chronic kidney disease. Kidney Int. 2010;78(suppl 117):S3-S9.
    1. Moist LM, Foley RN, Barrett BJ, et al. Clinical practice guidelines for evidence-based use of erythropoietic-stimulating agents. Kidney Int. 2008;78(suppl 110):S12-S18.
    1. Hudson JQ, Sameri RM. Darbepoetin alfa, a new therapy for the management of anemia of chronic kidney disease. Pharmacotherapy. 2002;22(9, pt 2):141S-149S.
    1. Deicher R, Horl WH. Differentiating factors between erythropoiesis-stimulating agents: a guide to selection for anaemia of chronic kidney disease. Drugs. 2004;64(5):499-509.
    1. Joy MS. Darbepoetin alfa: a novel erythropoiesis-stimulating protein. Ann Pharmacother. 2002;36(7-8):1183-1192.
    1. Brophy DF, Ripley EB, Holdford DA. Pharmacoeconomic considerations in the health system management of anaemia in patients with chronic kidney disease and end stage renal disease. Expert Opin Pharmacother. 2003;4(9):1461-1469.
    1. Locatelli F, Olivares J, Walker R, et al. Novel erythropoiesis stimulating protein for treatment of anemia in chronic renal insufficiency. Kidney Int. 2001;60(2):741-747.
    1. Nissenson AR, Suzanne KS, Jill SL, Steven DS, Beatey R, Wang C. Randomized, controlled trial of darbepoetin alfa for the treatment of anemia in hemodialysis patients. Am J Kidney Dis. 2002;40(1):110-118.
    1. Molina M, Garcia Hernandez MA, Navarro MJ, De Gracia MC, Ortuno T. Change of EPO treatment from subcutaneous epoetin to intravenous epoetin or darbepoetin alpha. Nefrologia. 2004;24(6):564-571.
    1. Tolman C, Richardson D, Bartlett C, Will E. Structured conversion from thrice weekly to weekly erythropoietic regimens using a computerized decision-support system: a randomized clinical study. J Am Soc Nephrol. 2005;16(5):1463-1470.
    1. Besarab A, Reyes CM, Hornberger J. Meta-analysis of subcutaneous versus intravenous epoetin in maintenance treatment of anemia in hemodialysis patients. Am J Kidney Dis. 2002;40(3):439-446.
    1. Hirai T, Nakashima A, Shiraki N, Takasugi N, Yorioka N. Dose conversion ratio one year after switching from epoetin alpha to darbepoetin alpha in Japanese hemodialysis patients. Int J Artif Organs. 2010;33(5):283-289.
    1. Hirai T, Sugiya N, Nakashima A, Takasugi N, Yorioka N. Switching from epoetin alpha to darbepoetin alpha in Japanese hemodialysis patients: dose conversion ratio. Nephron Clin Pract. 2009;111(2):c81-c86.
    1. Bock HA. Darbepoetin alpha in lower-than-equimolar doses maintains haemoglobin levels in stable haemodialysis patients converting from epoetin alpha/beta. Nephrol Dial Transplant. 2008;23(1):301-308.
    1. Icardi A, Sacco P, Salvatore F, Romano U. Long-term intravenous epoetin-alpha / darbepoetin-alpha ratio in iron-replete hemodialysis patients. J Nephrol. 2007;20(1):73-79.
    1. Roger SD, Cooper B. What is the practical conversion dose when changing from epoetin alfa to darbepoetin outside of clinical trials? Nephrology (Carlton). 2004;9(4):223-228.
    1. Jordan J, Breckles J, Leung V, Hopkins M, Battistella M. Conversion from epoetin alfa to darbepoetin alfa: effects on patients’ hemoglobin and costs to Canadian dialysis centres. Can J Hosp Pharm. 2012;65(6):443-449.
    1. Sharma A, Yee J, Gandra SR, Khan I, Petersen J. Estimate of maintenance EPO to darbepoetin alfa dose conversion ratio in a hospital-based dialysis patient population. Curr Med Res Opin. 2010;26(11):2679-2687.
    1. Raymond CB, Wazny LD, Vercaigne LM, Lesperance EM, Skwarchuk DE, Bernstein KN. Conversion from epoetin alfa to darbepoetin alfa within the Manitoba Renal Program: evaluation of dose ratios. CANNT J. 2008;18(1):39-43.
    1. Biggar P, Ketteler M, Hennemann H, Domling R. Switch of ESA therapy from darbepoetin-alpha to epoetin-beta in hemodialysis patients: a single-centre experience. Clin Nephrol. 2008;69(3):185-192.
    1. Sterner G, Prutz KG. Conversion from epoetin beta to darbepoetin: what is the equivalent dose? Nephrol Dial Transplant. 2008;23(12):4084-4085.
    1. Agrawal V, Mukherjee S, Kosuri R, Dumler F. Anemia management with darbepoetin-alfa in outpatient hemodialysis patients switched from epoetin-alfa: a community hospital experience. Am J Ther. 2010;17(5):469-475.
    1. Nakagawa T. Darbepoetin alpha is highly cost-effective compared with epoetin alpha in the treatment of renal anemia: a brief report from a hemodialysis clinic in Japan. Ther Apher Dial. 2008;12(6):531-532.
    1. Shalansky K, Jastrzebski J. Complete switch to darbepoetin in a hemodialysis unit. Clin Nephrol. 2005;64(1):55-63.
    1. Martinez Castelao A, Reyes A, Valdes F, et al. Multicenter study of darbepoetin alfa in the treatment of anemia secondary to chronic renal insufficiency on dialysis. Nefrologia. 2003;23(2):114-124.
    1. Locatelli F, Canaud B, Giacardy F, Martin-Malo A, Baker N, Wilson J. Treatment of anaemia in dialysis patients with unit dosing of darbepoetin alfa at a reduced dose frequency relative to recombinant human erythropoietin (rHuEpo). Nephrol Dial Transplant. 2003;18(2):362-369.
    1. Brophy DF, Ripley EB, Kockler DR, Lee S, Proeschel LA. Darbepoetin alfa therapeutic interchange protocol for anemia in dialysis. Ann Pharmacother. 2005;39(11):1808-1811.
    1. Martin-Holohan A, Curtis K, Masterson P, Goldfarb DS. Conversion of chronic hemodialysis patients from erythropoietin alfa to darbepoetin alfa. Hosp Pharm. 2004;39(4):333-337.
    1. Bonafont X, Bock A, Carter D, et al. A meta-analysis of the relative doses of erythropoiesis-stimulating agents in patients undergoing dialysis. NDT Plus. 2009;2(5):347-353.
    1. Tonelli M, Klarenbach S, Wiebe N, Shrive F, Hemmelgarn B, Manns B. Erythropoiesis-Stimulating Agents for Anemia of Chronic Kidney Disease: Systematic Review and Economic Evaluation. Vol Technology. Ottawa, Ontario: Canadian Agency for Drugs and Technologies in Health; 2008.
    1. Madore F, White CT, Foley RN, et al. Clinical practice guidelines for assessment and management of iron deficiency. Kidney Int Suppl. 2008;(110):S7-S11.
    1. Vanrenterghem Y, Barany P, Mann JF, et al. Randomized trial of darbepoetin alfa for treatment of renal anemia at a reduced dose frequency compared with rHuEPO in dialysis patients. Kidney Int. 2002;62(6):2167-2175.
    1. Scott SD. Dose conversion from recombinant human erythropoietin to darbepoetin alfa: recommendations from clinical studies. Pharmacotherapy. 2002;22(9, pt 2):160S-165S.
    1. Churchill DN, Macarios D, Attard C, Kallich J, Goeree R. Costs associated with erythropoiesis-stimulating agent administration to hemodialysis patients. Nephron Clin Pract. 2007;106(4):c193-c198.
    1. Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl. 2012;2:279-335.
    1. Moist LM, Troyanov S, White CT, et al. Canadian Society of Nephrology commentary on the 2012 KDIGO clinical practice guideline for anemia in CKD. Am J Kidney Dis. 2013;62(5):860-873.
    1. Coritsidis GN, Maglinte GA, Acharya A, et al. Anemia management trends in hospital-based dialysis centers (HBDCs), 2010 to 2013. Clin Ther. 2014;36(3):408-418.

Source: PubMed

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