Skip to main content
SpringerLink
Log in

Methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa for anemia in non-dialysis-dependent CKD: a systematic review

  • Review Article
  • Published:
International Journal of Clinical Pharmacy Aims and scope Submit manuscript

Abstract

Background Anemia management in non-dialysis-dependent chronic kidney disease (CKD) patients is associated with cardiovascular and cost benefits, slows decline in renal function, and prevents mortality. Different reviews have focused on evaluating the safety and efficacy of methoxy polyethylene glycol-epoetin beta (MPG-EPO), a continuous erythropoietin receptor activator, in CKD patients regardless of dialysis dependency and others have studied this novel agent exclusively in CKD patients receiving dialysis. Aim of the review To evaluate the efficacy and tolerability of MPG-EPO compared with other erythropoiesis stimulating agents (in particular darbepoetin alfa) for the treatment of anemia in non-dialysis-dependent CKD patients. Methods A systematic review of original studies published mainly in MEDLINE, Cochrane Database, ScienceDirect, ProQuest, clinical trials registries, and Google Scholar was carried out to identify randomized controlled trials (RCTs) comparing MPG-EPO with other erythropoiesis stimulating agents or placebo among patients with anemia of CKD who were not yet receiving dialysis. Data were independently extracted by two reviewers using standardized data abstraction tool. Results Four trials involving 1,155 patients were included in the review. The changes in hemoglobin level from the baseline reported by the reviewed studies demonstrate that MPG-EPO was clinically non-inferior to darbepoetin alfa. In addition, the studies documented that MPG-EPO-treated patients experienced a lower rate of hemoglobin level above the target range of 12–13 g/dL than darbepoetin-treated patients. The proportion of patients requiring RBC transfusion was higher among patients who received darbepoetin alfa than those who received MPG-EPO. However, the time to hemoglobin response was longer with MPG-EPO than with darbepoetin. Finally, the incidences of serious adverse events were similar between the two therapeutic agents. Conclusion There are currently only few well-designed head-to-head RCTs investigating the efficacy and safety of MPG-EPO compared with other ESAs in non-dialysis-dependent patients. MPG-EPO therapy compared with darbepoetin alfa has demonstrated favorable effects of increasing and maintaining hemoglobin concentrations to recommended target levels. This mini-review is not conclusive due to limited number of studies. Therefore, the beneficial effects and tolerability of MPG-EPO among non-dialysis-dependent CKD patients should be further investigated, given the economic and clinical benefits of managing anemia in this population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Astor BC, Muntner P, Levin A, Eustace JA, Coresh J. Association of kidney function with anemia: the Third National Health and Nutrition Examination Survey (1988–1994). Arch Intern Med. 2002;162:1401–8.

    Article  PubMed  Google Scholar 

  2. McClellan W, Aronoff SL, Bolton WK, Hood S, Lorber DL, Tang KL, et al. The prevalence of anemia in patients with chronic kidney disease. Curr Med Res Opin. 2004;20:1501–10.

    Article  PubMed  Google Scholar 

  3. National Kidney Foundation. KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 Update. AJKD. 2012;60:850–86.

    Article  Google Scholar 

  4. McCarley P. The KDOQI clinical practice guidelines and clinical practice recommendations for treating anemia in patients with chronic kidney disease: implications for nurses. Nephrol Nurs J. 2006;33:423–6.

    PubMed  Google Scholar 

  5. Silverberg DS, Wexler D, Iaina A, Steinbruch S, Wollman Y, Schwartz D. Anemia, chronic renal disease and congestive heart failure—the cardio renal anemia syndrome: the need for cooperation between cardiologists and nephrologists. Int J Nephrol Urol. 2006;38:295–310.

    Article  Google Scholar 

  6. Besarab A, Salifu MO, Lunde NM, Bansal V, Fishbane S, Dougherty FC, et al. Efficacy and tolerability of intravenous continuous erythropoietin receptor activator: a 19-week, phase II, multicenter, randomized, open-label, dose-finding study with a 12-month extension phase in patients with chronic renal disease. Clin Ther. 2007;29:626–39.

    Article  CAS  PubMed  Google Scholar 

  7. Ershler WB, Chen K, Reyes EB, Dubois R. Economic burden of patients with anemia in selected diseases. Value Heal. 2005;8:629–38.

    Article  Google Scholar 

  8. Astor BC, Coresh J, Heiss G, Pettitt D, Sarnak MJ. Kidney function and anemia as risk factors for coronary heart disease and mortality: the Atherosclerosis Risk in Communities (ARIC) Study. Am Hear J. 2006;151:492–500.

    Article  Google Scholar 

  9. US rHuEPO Predialysis Study Group. Double-blind, placebo-controlled study of the therapeutic use of recombinant human erythropoietin for anemia associated with chronic renal failure in predialysis patients The US Recombinant Human Erythropoietin Predialysis Study Group. AJKD. 1991;18:50–9.

    Article  Google Scholar 

  10. Locatelli F, Del Vecchio L. Erythropoiesis-stimulating agents in renal medicine. Oncologist. 2011;16(Suppl 3):19–24.

    Article  PubMed  Google Scholar 

  11. Macdougall IC. Novel erythropoiesis-stimulating agents: a new era in anemia management. CJASN. 2008;3:200–7.

    CAS  PubMed  Google Scholar 

  12. Halstenson CE, Macres M, Katz SA, Schnieders JR, Watanabe M, Sobota JT, et al. Comparative pharmacokinetics and pharmacodynamics of epoetin alfa and epoetin beta. Clin Pharmacol Ther. 1991;50:702–12.

    Article  CAS  PubMed  Google Scholar 

  13. Macdougall IC, Gray SJ, Elston O, Breen C, Jenkins B, Browne J, et al. Pharmacokinetics of novel erythropoiesis stimulating protein compared with epoetin alfa in dialysis patients. JASN. 1999;10:2392–5.

    CAS  PubMed  Google Scholar 

  14. Macdougall IC. Optimizing the use of erythropoietic agents—pharmacokinetic and pharmacodynamic considerations. Neph Dial Trans. 2002;17(Suppl 5):66–70.

    Article  CAS  Google Scholar 

  15. Robinson DM, Easthope SE. Darbepoetin alfa: its use in anemia associated with chronic kidney disease. BioDrugs. 2005;19:327–43.

    Article  CAS  PubMed  Google Scholar 

  16. Ohashi N, Sakao Y, Yasuda H, Kato A, Fujigaki Y. Methoxy polyethylene glycol-epoetin beta for anemia with chronic kidney disease. Int J Nephrol Renov Dis. 2012;5:53–60.

    Article  CAS  Google Scholar 

  17. Locatelli F, Aljama P, Bárány P, Canaud B, Carrera F, Eckardt K-U, et al. Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Neph Dial Trans. 2004;19(Suppl 2):ii1–47.

    Google Scholar 

  18. Carrera F, Disney A, Molina M. Extended dosing intervals with erythropoiesis-stimulating agents in chronic kidney disease: a review of clinical data. Neph Dial Trans. 2007;22(Suppl 4):iv19–30.

    CAS  Google Scholar 

  19. Macdougall IC, Roberts DE, Coles GA, Williams JD. Clinical pharmacokinetics of epoetin (recombinant human erythropoietin). Clin Pharmacokinet. 1991;20:99–113.

    Article  CAS  PubMed  Google Scholar 

  20. Macdougall IC, Padhi D, Jang G. Pharmacology of darbepoetin alfa. Neph Dial Trans. 2007;22(Suppl 4):iv2–9.

    Google Scholar 

  21. Macdougall IC, Robson R, Opatrna S, Liogier X, Pannier A, Jordan P, et al. Pharmacokinetics and pharmacodynamics of intravenous and subcutaneous continuous erythropoietin receptor activator (CERA) in patients with chronic kidney disease. Clin J Am Soc Nephrol. 2006;1:1211–5.

    Article  CAS  PubMed  Google Scholar 

  22. Topf JM. CERA: third-generation erythropoiesis-stimulating agent. Expert Opin Pharmacother. 2008;9:839–49.

    Article  CAS  PubMed  Google Scholar 

  23. Macdougall IC, Robson R, Opatrna S, Liogier X, Pannier A, Jordan P, et al. Pharmacokinetics and pharmacodynamics of intravenous and subcutaneous continuous erythropoietin receptor activator (C.E.R.A) in patients with chronic kidney disease. CJASN. 2006;1:1211–5.

    CAS  PubMed  Google Scholar 

  24. Roche. Mircera (methoxy polyethylene glycol-epoetin beta)—Product Information 2011.

  25. Provenzano R, Besarab A, Macdougall IC, Ellison DH, Maxwell AP, Sulowicz W, et al. The continuous erythropoietin receptor activator (C.E.R.A.) corrects anemia at extended administration intervals in patients with chronic kidney disease not on dialysis: results of a phase II study. Clin Neph. 2007;67:306–17.

    CAS  Google Scholar 

  26. Levin NW, Fishbane S, Cañedo FV, Zeig S, Nassar GM, Moran JE, et al. Intravenous methoxy polyethylene glycol-epoetin beta for haemoglobin control in patients with chronic kidney disease who are on dialysis: a randomised non-inferiority trial (MAXIMA). Lancet. 2007;370:1415–21.

    Article  CAS  PubMed  Google Scholar 

  27. Sulowicz W, Locatelli F, Ryckelynck J-P, Balla J, Csiky B, Harris K, et al. Once-monthly subcutaneous CERA maintains stable hemoglobin control in patients with chronic kidney disease on dialysis and converted directly from epoetin one to three times weekly. CJASN. 2007;2:637–46.

    CAS  PubMed  Google Scholar 

  28. Drüeke TB, Locatelli F, Clyne N, Eckardt K-U, Macdougall IC, Tsakiris D, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. NEJM. 2006;355:2071–84.

    Article  PubMed  Google Scholar 

  29. Panchapakesan U, Sumual S, Pollock C. Nanomedicines in the treatment of anemia in renal disease: focus on CERA (Continuous Erythropoietin Receptor Activator). Int J Nanomedicine. 2007;2:33–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Taéron C. Methoxy polyethylene glycol epoetin beta. Rev Infirm. 2010;159:47–9.

  31. Schmidt RJ. Methoxy polyethylene glycol-epoetin beta: worth waiting for or a novelty worn off? Expert Opin Pharmacother. 2009;10:1509–14.

    Article  CAS  PubMed  Google Scholar 

  32. Curran MP, McCormack PL. Methoxy polyethylene glycol-epoetin beta: a review of its use in the management of anaemia associated with chronic kidney disease. Drugs. 2008;68:1139–56.

    Article  CAS  PubMed  Google Scholar 

  33. Macdougall IC. New anemia therapies: translating novel strategies from bench to bedside. AJKD. 2012;59:444–51.

    Article  PubMed  Google Scholar 

  34. Fink J, Blahut S, Reddy M, Light P. Use of erythropoietin before the initiation of dialysis and its impact on mortality. AJKD. 2001;37:348–55.

    Article  CAS  PubMed  Google Scholar 

  35. Collins AJ. Anaemia management prior to dialysis: cardiovascular and cost-benefit observations. Neph Dial Trans. 2003;18(Suppl 2):ii2–6.

    Google Scholar 

  36. Gouva C, Nikolopoulos P, Ioannidis JPA, Siamopoulos KC. Treating anemia early in renal failure patients slows the decline of renal function: a randomized controlled trial. Kid Inter. 2004;66:753–60.

    Article  Google Scholar 

  37. Aizawa K, Takeda S, Tashiro Y, Yorozu K, Hirata M, Kanada H, et al. Renoprotection by continuous erythropoietin receptor activator in puromycin aminonucleoside-induced nephrotic syndrome. Am J Nephrol. 2012;36:419–26.

    Article  CAS  PubMed  Google Scholar 

  38. Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, et al. Correction of anemia with epoetin alfa in chronic kidney disease. NEJM. 2006;355:2085–98.

    Article  CAS  PubMed  Google Scholar 

  39. Pfeffer MA, Burdmann EA, Chen C-Y, Cooper ME, de Zeeuw D, Eckardt K-U, et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. NEJM. 2009;361:2019–32.

    Article  PubMed  Google Scholar 

  40. Higgins JPT, Green S. Guide to the contents of a cochrane protocol and review. In: Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The cochrane collaboration, 2011. www.cochrane-handbook.org.

  41. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Con Clin Trials. 1996;17:1–12.

    Article  CAS  Google Scholar 

  42. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Roger SD, Locatelli F, Woitas RP, Laville M, Tobe SW, Provenzano R, et al. C.E.R.A. once every 4 weeks corrects anaemia and maintains haemoglobin in patients with chronic kidney disease not on dialysis. Neph Dial Trans. 2011;26:3980–6.

    Article  CAS  Google Scholar 

  44. Macdougall IC, Walker R, Provenzano R, de Alvaro F, Locay HR, Nader PC, et al. C.E.R.A. corrects anemia in patients with chronic kidney disease not on dialysis: results of a randomized clinical trial. CJASN. 2008;3:337–47.

    PubMed Central  PubMed  Google Scholar 

  45. Kessler M, Martínez-Castelao A, Siamopoulos KC, Villa G, Spinowitz B, Dougherty FC, et al. C.E.R.A. once every 4 weeks in patients with chronic kidney disease not on dialysis: The ARCTOS extension study. Hemodial Int. 2010;14:233–9.

    Article  PubMed  Google Scholar 

  46. Hoffmann-La Roche. A study of subcutaneous mircera in patients with chronic kidney disease, not on dialysis. 2011. http://clinicaltrials.gov/show/NCT00442702.

  47. Locatelli F, Villa G, de Francisco ALM, Albertazzi A, Adrogue HJ, Dougherty FC, et al. Effect of a continuous erythropoietin receptor activator (C.E.R.A.) on stable haemoglobin in patients with CKD on dialysis: once monthly administration. Curr Med Res Opin. 2007;23:969–79.

    Article  CAS  PubMed  Google Scholar 

  48. Carrera F, Lok CE, de Francisco A, Locatelli F, Mann JFE, Canaud B, et al. Maintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa administered monthly: a randomized comparative trial. Neph Dial Trans. 2010;25:4009–17.

    Article  CAS  Google Scholar 

  49. Seliger SL, Zhang AD, Weir MR, Walker L, Hsu VD, Parsa A, et al. Erythropoiesis-stimulating agents increase the risk of acute stroke in patients with chronic kidney disease. Kid Inter. 2011;80:288–94.

    Article  CAS  Google Scholar 

  50. Mapes DL, Lopes AA, Satayathum S, McCullough KP, Goodkin DA, Locatelli F, et al. Health-related quality of life as a predictor of mortality and hospitalization: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Kid Inter. 2003;64:339–49.

    Article  Google Scholar 

  51. Macdougall IC, Obrador GT. How important is transfusion avoidance in 2013? Neph Dial Trans. 2013;28:1092–9.

    Article  Google Scholar 

  52. Choi J-Y, Yang CW, Kim Y-H, Joo KW, Yoo T-H, Lee KW, et al. Effect of conversion from ESA with shorter half-life to CERA once monthly for maintaining Hb concentration in pre-dialysis CKD patients. Kidney Blood Press Res. 2013;37:259–68.

    Article  CAS  PubMed  Google Scholar 

  53. O’Mara NB. Anemia in patients with chronic kidney disease. Diabetes Spectr. 2008;21:12–9.

    Article  Google Scholar 

  54. Beyer-Westendorf J, Büller H. External and internal validity of open label or double-blind trials in oral anticoagulation: better, worse or just different? J Thromb Haemost. 2011;9:2153–8.

    Article  CAS  PubMed  Google Scholar 

  55. Taylor GJ, Wainwright P. Open label extension studies: research or marketing? BMJ. 2005;331:572–4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Aggarwal HK, Jain D, Verma K. Efficacy and safety of continuous erythorpoietin receptor activator (C.E.R.A) in patients of chronic renal failure with anemia. Int. J Pharm Pharm Sci. 2011;3:292–7.

    Google Scholar 

Download references

Funding

This study was self-initiated and self-supported; no funding was obtained for the conduct of the study.

Conflicts of interest

The authors have no competing interests to declare.

Author information

Authors and Affiliations

  1. Geriatrics Section, Rumailah Hospital, P.O. Box 3050, Doha, Qatar

    Noor Alsalimy

  2. College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar

    Ahmed Awaisu

Authors
  1. Noor Alsalimy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ahmed Awaisu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ahmed Awaisu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Alsalimy, N., Awaisu, A. Methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa for anemia in non-dialysis-dependent CKD: a systematic review. Int J Clin Pharm 36, 1115–1125 (2014). https://doi.org/10.1007/s11096-014-0023-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11096-014-0023-x

Keywords

Search

Navigation