Original Investigation
Pathogenesis and Treatment of Kidney Disease
An Economic Evaluation of Erythropoiesis-Stimulating Agents in CKD

https://doi.org/10.1053/j.ajkd.2010.07.015Get rights and content

Background

The objective was to determine the cost-effectiveness of treating anemic patients with chronic kidney disease (CKD) with erythropoiesis-stimulating agents (ESAs) to a low (9-10.9 g/dL), intermediate (11-12 g/dL), or high (>12 g/dL) hemoglobin level target compared with a strategy of managing anemia without ESAs.

Study Design

Cost-utility analysis.

Setting & Participants

Publicly funded health care system. Anemic patients with CKD, overall and stratified into dialysis-/non–dialysis-dependent subgroups.

Model, Perspective, & Timeframe

Decision analysis, health care payer, patient's lifetime.

Main Outcome

Cost per quality-adjusted life-year (QALY) gained.

Results

For dialysis patients, compared with anemia management without ESAs, using ESAs to target a low hemoglobin level is associated with a cost per QALY of $96,270. Given a lack of direct trials comparing low and intermediate targets, significant uncertainty exists between these strategies. Treatment to a high hemoglobin target was always associated with worse clinical outcomes and higher costs compared with a low hemoglobin target. Results were similar in non–dialysis-dependent patients with CKD, with a cost per QALY for a low target compared with no ESA of $147,980.

Limitations

Given limitations in the available randomized controlled trials, we were able to model only 4 treatment strategies, balancing the need to consider relevant targets with the requirement for accurate estimates of clinical effect. We assumed that the efficacy of the different strategies would continue over a patient's lifetime.

Conclusions

Using ESAs to target a hemoglobin level >12 g/dL is associated with worse clinical outcomes and significant additional cost compared with using ESAs to target lower hemoglobin levels (9-12 g/dL). Given a lack of studies comparing low (9-10.9 g/dL) and intermediate (11-12 g/dL) hemoglobin targets for clinical outcomes, including quality of life, the most cost-effective hemoglobin level target within the range of 9-12 g/dL is uncertain, although aiming for higher targets within this range will lead to higher costs.

Section snippets

Study Design

We estimated the cost per quality-adjusted life-year (QALY) gained with treatment using ESAs to target different hemoglobin level targets compared with a strategy of managing anemia without ESAs. A Markov process was used to model the cost and clinical outcomes for patients in 1-year intervals. We modeled cohorts of non–dialysis-dependent patients with CKD and dialysis patients separately. Fig 1 shows the model structure, with differences between the dialysis- and non–dialysis-dependent models

Patient Cohort Characteristics

Table 1 lists baseline characteristics of the dialysis and nondialysis patient cohorts used in base-case analyses. The dialysis cohort is substantially younger than the nondialysis cohort, with 50.2% older than 65 years compared with 83.1% of the nondialysis cohort older than 65 years.

Baseline Estimates

Baseline clinical estimates are listed in Table 2. Of note, clinical outcomes and costs associated with caring for non–dialysis-dependent patients with CKD are novel contributions to the published literature.

Discussion

This analysis shows that targeting ESA treatment to hemoglobin levels >12 g/dL is not associated with overall clinical benefit and results in significant additional cost, consistent with RCT data used to inform the analysis. Targeting treatment to hemoglobin levels in the range of 9-12 g/dL is preferred to high hemoglobin level targets, although the cost per QALY to achieve low and intermediate hemoglobin level targets compared with management without ESAs was at least $100,000 in virtually all

Acknowledgements

Support: This work was funded by the Canadian Agency for Drugs and Technologies in Health. Dr Clement is supported by a postdoctoral fellowship award from the Canadian Health Services Research Foundation and from Alberta Innovates–Health Solutions (AI-HS), formerly the Alberta Heritage Foundation for Medical Research. Drs Manns and Tonelli are supported by AI-HS Health Scholar Awards, and Drs Hemmelgarn and Klarenbach are supported by AI-HS Population Health Investigator awards. Drs Manns,

References (61)

  • G.W. Torrance

    Utility approach to measuring health related quality of life

    J Chronic Dis

    (1987)
  • A. Laupacis et al.

    A study of the quality of life and cost-utility of renal transplantation

    Kidney Int

    (1996)
  • E. Ritz et al.

    Target level for hemoglobin correction in patients with diabetes and CKD: primary results of the Anemia Correction in Diabetes (ACORD) Study

    Am J Kidney Dis

    (2007)
  • H. Lee et al.

    Cost analysis of ongoing care of patients with end-stage renal disease: the impact of dialysis modality and dialysis access

    Am J Kidney Dis

    (2002)
  • K.W. Wyrwich et al.

    Heart Disease Expert PanelClinically important differences in health status for patients with heart disease: an expert consensus panel report

    Am Heart J

    (2004)
  • A. Besarab et al.

    The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin

    N Engl J Med

    (1998)
  • T.B. Drueke et al.

    Normalization of hemoglobin level in patients with chronic kidney disease and anemia

    N Engl J Med

    (2006)
  • A.K. Singh et al.

    Correction of anemia with epoetin alfa in chronic kidney disease

    N Engl J Med

    (2006)

  • KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease: 2007 update of hemoglobin target

    Am J Kidney Dis

    (2007)
  • A. Piccoli et al.

    A decision analysis comparing three dosage regimens of subcutaneous epoetin in continuous ambulatory peritoneal dialysis

    Pharmacoeconomics

    (1995)

  • Guidelines for the Economic Evaluation of Health Technologies

    (2006)

  • Treatment of End-Stage Organ Failure in Canada, 1995-20042006 Annual Report

    (2006)
  • D. Cournoyer et al.

    Anti-erythropoietin antibody-mediated pure red cell aplasia after treatment with recombinant erythropoietin products: recommendations for minimization of risk

    J Am Soc Nephrol

    (2004)
  • J. Bahlmann et al.

    Morbidity and mortality in hemodialysis patients with and without erythropoietin treatment: a controlled study

    Contrib Nephrol

    (1991)
  • W.M. Bennett

    A multicenter clinical trial of epoetin beta for anemia of end-stage renal disease

    J Am Soc Nephrol

    (1991)

  • Effect of recombinant human erythropoietin therapy on blood pressure in hemodialysis patients

    BMJ

    (1990)
  • H. Furuland et al.

    A randomized controlled trial of haemoglobin normalization with epoetin alfa in pre-dialysis and dialysis patients

    Nephrol Dial Transplant

    (2003)
  • J.S. Kaufman et al.

    Subcutaneous compared with intravenous epoetin in patients receiving hemodialysisDepartment of Veterans Affairs Cooperative Study Group on Erythropoietin in Hemodialysis Patients

    N Engl J Med

    (1998)
  • H. Klinkmann et al.

    Adverse events of subcutaneous recombinant human erythropoietin therapy: results of a controlled multicenter European study

    Artif Organs

    (1993)
  • S. Kuriyama et al.

    Reversal of anemia by erythropoietin therapy retards the progression of chronic renal failure, especially in nondiabetic patients

    Nephron

    (1997)

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    Originally published online as doi:10.1053/j.ajkd.2010.07.015 on October 8, 2010.

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    Copyright © 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.