Abstract
Erythropoiesis-stimulating agents (ESAs) are genetically engineered forms of erythropoietin that are used in the treatment of anaemia. Their successful use in the treatment of anaemia associated with renal disease, cancer and other diseases, as well as the development of multiple agents, has increased the visibility of these agents in the clinical and health economics literature. The circumstances under which the use of ESAs is cost effective, or indeed, whether it is cost effective, is of central concern for clinicians and payers who must make informed decisions regarding the management of these costly resources.
Much of the recent literature on ESAs in the treatment of anaemia associated with chronic kidney disease and cancer, the two major therapeutic areas for ESA treatment, has focused on comparisons between individual ESAs, particularly epoetin alfa and darbepoetin alfa. While there have been some studies of cost effectiveness, many studies in these treatment areas have employed a cost-minimization approach and have relied on published prices rather than actual market prices.
In general, this review of the literature suggests a cost advantage for epoetin alfa relative to darbepoetin alfa in the treatment of anaemia in renal and oncology indications. For other indications in which the literature is less developed, such as anaemia induced by antiviral therapy and blood management in surgery, small prospective studies or decision-analytic models comparing ESA therapy and standard care have been most common. Few conclusions can be drawn about the overall and relative costs or cost effectiveness of ESAs in these treatment areas.
With the recent concerns about the safety of ESAs, especially when used outside the approved product labelling, future evaluations of epoetin alfa and darbepoetin alfa should factor their safety profiles into estimates of cost effectiveness. Moreover, additional studies are needed to evaluate whether the treatment of anaemia with ESAs is cost effective compared with no treatment or minimal blood transfusions, and whether the cost effectiveness of ESAs would be improved if ESA doses and durations were reduced.
With the introduction of new longer-acting ESAs, such as the continuous erythropoietin receptor activator, the relative cost effectiveness among the different ESAs will continue to be an important question for public and private payers, policy makers and clinicians who must consider the emergence of new data and changing dosing patterns when making decisions about the use of these important but costly agents.
Similar content being viewed by others
Notes
The use of trade names is for product identification purposes only and does not imply endorsement.
References
Duh MS, Latypova A, Greenberg P. Impact and treatment of anemia in the elderly: clinical, epidemiological and economic perspectives. Expert Rev Pharmacoeconomics Outcomes Res 2006 Oct; 6 (5): 577–590
Cella D. Factors influencing quality of life in cancer patients: anemia and fatigue. Semin Oncol 1998; 25: 43–46
Deray G. Achieving therapeutic targets in renal anaemia: considering cost-efficacy. Cur Med Res Opin 2004; 20 (7): 1095–1101
Caro JJ, Salas M, Ward A, et al. Anemia as an independent prognostic factor for survival in patients with cancer: a systematic, quantitative review. Cancer 2001: 91: 2214–2221
Ebben JP, Gilbertson DT, Foley RN, et al. Hemoglobin level variability: associations with comorbidity, intercurrent events, and hospitalizations. Clin J Am Sec Nephrol 2006 Nov; 1 (6): 1205–1210
Graber SE Krantz SB. Erythropoietin: biology and clinical use. Hematol Oncol Clin North Am 1989 Sep; 3 (3): 369–400
Berenson A, Pollack A. Doctors reaping millions for use of anemia drugs. New York Times 2007 May 9; SectA: 1
Thamer M, Zhang Y, Kaufman J, et al. Dialysis facility ownership and epoetin dosing in patients receiving hemodialysis. JAMA 2007 Apr 18; 297 (15): 1667–1674
Demetri GD, Kris M, Wade J, et al. Quality-of-life benefit in chemotherapy patients treated with epoetin alfa is independent of disease response or tumor type: results from a prospective community oncology study. Procrit Study Group. J Clin Oncol 1998 Oct; 16; (10): 3412–3425
Gabrilove JL, Cleeland CS, Livingston RB, et al. Clinical evaluation of once-weekly dosing of epoetin alfa in chemotherapy patients: improvements in hemoglobin and quality of life are similar to three-times-weekly dosing. J Clin Oncol 2001 Jun 1; 19 (11): 2875–2882
Boccia R, Lillie T, Tomita D, et al. The effectiveness of darbepoetin alfa administered every 3 weeks on hematologic outcomes and quality of life in older patients with chemotherapy-induced anemia. Oncologist 2007; 12: 584–593
Procrit® prescribing information [online]. Available from URL: http://www.procritcom/procrit/shared/OBI/PI/ProcritBook-let.pdf#page=l [Accessed 2007 May 1]
Epogen® prescribing information [online]. Available from URL: http://www.epogen.com/professional/resources/prescribing_information/pi.jsp [Accessed 2007 May 1]
NeoRecormon® prescribing information. European Medicines Agency (EMEA) [online]. Available from URL: http://www.emea.europa.eu/humandocs/Humans/EPAR/neorecormon/neorecormon.htm [Accessed 2007 Sep 4]
Macdougall IC, Gray S, Elston O, et al. Pharmacokinetics of novel erythropoiesis stimulating protein compared with epoetin alfa in dialysis patients. J Am Sec Nephrol 1999; 10 (11): 2392–2395
Zarriboni WC, Stewart CE. An overview of the pharmacokinetic disposition of darbepoetin alfa. Pharmacotherapy 2002; 22 (9 Pt 2): 133S–140S
Aranesp® prescribing information [online]. Available from URL: http://www.aranesp.com/professional/prescribing_information.jsp [Accessed 2007 May 1]
Crawford J. Erythropoietin: high profile, high scrutiny [editorial]. J Clin Oncol 2007; 25 (9): 1021–1022
Morreale A, Plowman B, DeLattre M, et al. Clinical and economic comparison of epoetin alfa and darbepoetin alfa. Curr Med Res Opin 2004; 20 (3): 381–395
Papatheofanis FJ, McKenzie RS, Mody SH, et al. Dosing patterns, hematologic outcomes, and costs of erythropoietic agents in predialysis chronic kidney disease patients with anaemia. Cur Med Res Opin 2006; 22 (5): 837–842
Duh MS, Mody SH, McKenzie RS, et al. Dosing patterns and treatment costs of erythropoietic agents in elderly patients with pre-dialysis chronic kidney disease in managed care organizations. Drugs Aging 2006; 23 (12): 969–976
Duh MS, Mody SH, Scott McKenzie R, et al. Dosing patterns and costs of erythropoietic agents in patients with chronic kidney disease not on dialysis in managed care organizations. Clin Ther 2006; 28 (9): 1443–1450
Shalansky K, Jastrzebski J. Complete switch to darbepoetin in a hemodialysis unit. Clin Nephrol 2005 Jul; 64 (1): 55–63
Brophy DF, Ripley EB, Kockler DR, et al. Darbepoetin alfa therapeutic interchange protocol for anaemia in dialysis. Ann Pharmacother 2005 Nov; 39 (11): 1808–1811
Kruep EJ, Basskin LE. Cost-minimization analysis of darbepoetin alfa versus epoetin alfa in the hospital setting. Am J Health Syst Pharm 2005 Dec 15; 62: 2597–2603
Ben-Hamadi R, Duh MS, Aggarwal J, et al. The cost-effectiveness of weekly epoetin alfa relative to weekly darbepoetin alfa in patients with chemotherapy-induced anaemia. Curr Med Res Opin 2005; 21 (10): 1677–1682
Rosberg JH, Ben-Hamadi R, Cremieux PY, et al. Dose conversion and cost-effectiveness of erythropoetic therapies in chemotherapy-related anaemia: a meta-analysis. Clin Drug Invest 2005; 25 (1): 33–48
Cremieux P, Vekeman F, Lefebvre P. Dose conversion and cost-effectiveness of erythropoetic therapies in chemotherapy-related anaemia: a Canadian application. J Oncol Pharm Practice 2006; 12: 165–178
Reed SD, Radeva JI, Daniel DB, et al. Economic evaluation of weekly epoetin alpha versus biweekly darbepoetin alpha for chemotherapy-induced anaemia: evidence from a 16-week randomised trial. Pharmacoeconomics 2006; 24 (5): 479–494
Rosberg J, Koeller J, Oster E, et al. Clinical response, cost of treatment, and cost-effectiveness of three regimens of two erythropoietic agents for treating chemotherapy-induced anaemia [abstract no. 2250]. Prcc Am Soc Clin Oncol 2003; 22: 2250
Barosi G, Marchetti M, Liberate ML. Cost effectiveness of recombinant human erythropoietin in the prevention of chemotherapy-induced anemia. Br J Cancer 1998; 78: 781–787
Wilson J, Yao GL, Raftery J, et al. A systematic review and economic evaluation of epoetin alfa, epoetin beta, and darbepoetin alfa in anaemia associated with cancer, especially that attributable to cancer treatment. Health Technol Assess 2007; 11 (13): 1–220
Cersosimo RJ, Jacobson DR. Epoetin alfa versus darbepoetin alfa in chemotherapy-related anaemia. Ann Pharmacother 2006 Jan; 40 (1): 58–65
Ben-Hamadi R, Duh MS, Henckler A, et al. Cost-effectiveness of once weekly epoetin alfa and darbepoetin alfa in treating chemotherapy-induced anaemia [abstract no. 6093]. ASCO Annual Meeting Proceedings. J Clin Oncol 2005; 23 (16s): 6093
Cremieux P, Greenberg P, Piech CT. Epoetin alfa is more effective and less costly relative to darbepoetin alfa in lung cancer patients receiving treatment for chemotherapy-induced anaemia [abstract no. 2248]. Proc Am Sec Clin Oncol 2003; 22: 2248
Duh MS, Mark TL. Cost-effectiveness of epoetin alpha and darbepoetin alpha in patients with chemotherapy-related anaemia. Expert Rev Pharmacoeconomics Outcomes Res 2005; 5 (4): 383–394
Mark TL, McKenzie RS, Fastenau J, et al. Retrospective observational study of patients with chemotherapy-related anaemia receiving erythropoietic agents. Curr Med Res Opin 2005; 21 (9): 1347–1354
McKenzie RR, Mark T, Piech CT. Better early and overall hematologic outcomes and lower drug cost with epoetin alfa (EPO) compared to darbepoetin alfa (DARB) in colorectal patients [abstract no. 232]. Gastrointestinal Cancer Symposium, 2004 Jan 22–24, San Francisco (CA)
Persson U, Borg S, Jansson S, et al. Epoetin alpha and darbepoetin alpha for the treatment of chemotherapy-related anaemia in cancer patients in Sweden: comparative analysis of drug utilization, costs, and hematologic response. Adv Ther 2005; 22 (3): 208–224
Spaepen E, Demarteau N, Bracco A, et al. Health economic evaluation of anaemia treatment in patients with non-myeloid malignancies: a Belgian hospital perspective [abstract no. 630P]. 31st European Society for Medical Oncology Congress, 2006 Sep 29–Oct 3, Istanbul
Coiffier B, Schlag R, Velasco A, et al. Cost and effectiveness of darbepoetin alfa administered every 3 weeks compared with weekly epoetin alfa or epoetin beta in patients with chemotherapy induced anaemia: a retrospective study [abstract no. 1016P]. 31st European Society for Medical Oncology Congress, 2006 Sep 29–Oct 3, Istanbul
Chen E, Peake C, Buscaino E, et al. Hematologic outcomes and erythropoiesis-stimulating therapy costs in epoetin alfa (EPO)-and Darbepoetin Alfa (DARB)-treated cancer patients: results of the Dosing and Outcomes Study of Erythropoiesis-Stimulat-ing Therapies (D.O.S.E. Registry) [abstract no. 3340]. Blood 2006 Nov 18; 108 (11): 3340
Lefebvre P, Gosselin A, McKenzie RS, et al. Dosing patterns, treatment costs, and frequency of physician visits in adults with cancer receiving erythropoietic agents in managed care organizations. Curr Med Res Opin 2006; 22 (9): 1623–1631
Reichardt B. Cost comparison of epoetin alpha, epoetin beta, and darbepoetin alpha for cancer patients with anaemia in the clinical practice setting. J Clin Pharm Ther 2006; 31: 503–512
Killian AD, Gupta V, Goetz AE. Cost analysis of erythropoietic-stimulating therapy dosing in oncology inpatients. Ann Pharmacother 2006 Mar; 40 (3): 421–426
Duh MS, Lefebvre P, Fastenau J, et al. Assessing the clinical benefits of erythropoietic agents using area under the hemoglobin change curve. Oncologist 2005; 10: 438–448
Witzig TE, Silberstein PT, Loprinzi CL, et al. Phase III, randomized, double-blind study of epoetin alfa compared with placebo in anemic patients receiving chemotherapy. J Clin Oncol 2005; 23 (12): 2606–2617
KotasekD, Canon J-L, San Miguel J, et al. Correction/maintenance dosing (front loading) of darbepoetin alfa: final results from a randomized phase 3 active controlled trial [poster presentation]. American Society of Hematology; 2004 Dec 4–7; San Diego (CA)
Wright JR, Ung YC, Julian J A, et al. Randomized, double-blind, placebo-controlled trial of erythropoietin in non-small-cell lung cancer with disease-related anemia. J Clin Oncol 2007 Mar 20; 25 (9): 1027–1032
Danish Head and Neck Cancer Group. Interim analysis of DAHANCA 10. December 2006 [online]. Available from URL: http://www.dahanca.dk/get_media_file.php?.mediaid=125 [Accessed 2007 Jun 11]
Amgen. Aranesp® phase 3 study in patients with active cancer not receiving concurrent chemotherapy or radiotherapy presented at AACR Annual Meeting [press release]. 2007 Apr 16 [online]. Available from URL: http://www.amgen.com/media/media_pr_detailjsp?.year=2007&releaseID=985366 [Accessed 2007 Jun 11]
Del Rio RA, Post AB, Singer ME. Cost-effectiveness of hematologic growth factors for anaemia occurring during hepatitis C combination therapy. Hepatology 2006; 44 (6): 1598–1606
Chapko MK, Dominitz JA. Cost-effectiveness of growth factors during hepatitis C anti-viral therapy. Aliment Pharmacol Ther 2006 Oct 1; 24 (7): 1067–1077
Spiegel BM, Chen K, Chiou CF, et al. Erythropoietic growth factors for treatment-induced anaemia in hepatitis C: a cost-effectiveness analysis. Clin Gastroenterol Hepatol 2005 Oct; 3 (10): 1034–1042
Lucas C, Carrera F, Jorge C, et al. Effectiveness of weekly darbepoetin alfa in the treatment of anaemia of HIV-infected haemodialysis patients. Nephrol Dial Transplant 2006; 21: 3202–3206
Coyle D, Lee KM, Fergusson DA, et al. Cost-effectiveness of epoetin-a to augment preoperative autologous blood donation in elective surgery. Pharmacoeconomics 2000 Aug; 18 (2): 161–171
Marchetti M, Barosi G. Cost-effectiveness of epoetin and autologous blood donation in reducing allogeneic blood transfusions in coronary artery bypass graft surgery. Transfusion 2000 Jun; 40: 673–681
Nieder AM, Rosenblum N, Lepor H. Comparison of two different doses of preoperative recombinant erythropoietin in men undergoing radical retropubic prostatectomy. Urology 2001 Apr; 57 (4): 737–741
MacLaren R, Sullivan PW. Cost-effectiveness of recombinant human erythropoietin for reducing red blood cells transfusions in critically ill patients. Value Health 2005 Mar-Apr; 8 (2): 105–116
Shermock KM, Horn E, Lipsett PA, et al. Number needed to treat and cost of recombinant human erythropoietin to avoid one transfusion-related adverse event in critically ill patients. Crit Care Med 2005; 33 (3): 497–503
Yeo CL, Choo S, Ho L. Effect of recombinant erythropoietin on transfusion needs in preterm infants. J Paediatric Child Health 2001; 37: 352–358
Pajoumand M, Erstad BL, Camamo JM. Use of epoetin alfa in critically ill patients. Ann Pharmacother 2004 Apr; 38 (4): 641–648
Leese B, Hutton J, Maynard A. A comparison of the costs and benefits of recombinant human erythropoietin (epoetin) in the treatment of chronic renal failure in 5 European countries. Pharmacogenomics 1992 May; 1 (5): 346–356
Remák E, Hutton J, Jones M, et al. Changes in cost-effectiveness over time: the case of epoetin alfa for renal replacement therapy patients in the UK. Eur J Health Econom 2003; 4: 115–121
Cornes P, Coiffier B, Zambrowski JJ. Erythropoietin therapy for the treatment of anemia in patients with cancer: a valuable clinical and economic option. Curr Med Res Opin 2007 Feb; 23 (2): 357–368
Cremieux P, Finkelstein S, Berndt E, et al. Cost-effectiveness, quality-adjusted life-years and supportive care: recombinant human erythropoietin as a treatment of cancer-associated anaemia. Pharmacoeconomics 1999; 16: 459–472
Ross SD, Allen E, Henry D, et al. Clinical benefits and risks associated with epoetin and darbepoetin in patients with chemotherapy-induced anaemia: a systematic review of the literature. Clin Ther 2006; 28 (6): 801–831
Marchetti M, Barosi G. Clinical and economic impact of epoetins in cancer care. Pharmacoeconomics 2004; 22 (16): 1029–1045
Food and Drag Administration. FDA Public Health Advisory. Erythropoiesis-stimulating agents [online]. Available from URL: http://www.fda.gov/cder/drag/advisory/RHE2007.htm [Accessed 2007 May 1]
US Food and Drag Administration. Center for Drag Evaluation and Research. Department of Health and Human Services. Information on erythropoiesis stimulating agents [ESA] (marketed as Procrit, Epogen, and Aranesp) [online]. Available from URL: http://www.fda.gov/cder/drag/infopage/RHE/ [Accessed 2007 Apr 30]
Tonelli M, Winkelmayer WC, Jindal KK, et al. The cost-effectiveness of maintaining higher hemoglobin targets with erythropoietin in hemodialysis patients. Kidney Int 2003 Jul; 64 (1): 295–304
Centers for Medicare and Medicaid Services. Decision memo for erythropoiesis stimulating agents (ESAs) for nonrenal disease indications (CAG-00383N) [online]. Available from URL: http://www.cms.hhs.gov/mcd/viewdecisionmemo.asp?.id=203 [Accessed 2007 Sep 3]
Twachtman G. Medicare ESA coverage will not experiment with clinical trial approach. The Pink Sheet 2007 Aug; 69 (032): 21
Singh AK, Szczech L, Tang K, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 2006 Nov 16; 355: 2085–2098
Campos SM, Duh MS, Lefebvre P, et al. Benefits associated with an early hemoglobin response to epoetin alfa therapy in the treatment of chemotherapy-related anemia. J Natl Compr Cane Netw 2005; 3: 807–816
Acknowledgements
Financial support for this study was provided by Ortho Biotech Clinical Affairs, LLC. Mei Sheng Duh, Jennifer R. Weiner, Leigh Ann White, Patrick Lefebvre and Paul E. Greenberg are employees of Analysis Group, Inc., which has received research grants from Ortho Biotech Clinical Affairs, LLC. Dr Lefebvre has also acted as a consultant for attorneys during litigation regarding erythropoiesis-stimulating agents. Ortho Biotech had no involvement in the design and conduct of the study, collection, management, analysis and interpretation of the data, or preparation of the manuscript, except for providing editorial review and approval of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Duh, M.S., Weiner, J.R., White, L.A. et al. Management of Anaemia. Pharmacoeconomics 26, 99–120 (2008). https://doi.org/10.2165/00019053-200826020-00002
Published:
Issue Date:
DOI: https://doi.org/10.2165/00019053-200826020-00002